N-methylsulfonimidoyl-substituted (2-alkenyl)titanium complexes: Application to the synthesis of β- and δ-sulfonimidoyl-substituted chiral homoallylic alcohols, x-ray crystal structure analysis, and fluxional behavior

FULL PAPER

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes: Application

to the Synthesis of β- and δ-Sulfonimidoyl-Substituted Chiral Homoallylic

Alcohols, X-ray Crystal Structure Analysis, and Fluxional Behavior

Hans-Joachim Gais,*^[a]Rüdiger Hainz,^[a]Harald Müller,^[a]Peter Richard Bruns,^[a]

Nicole Giesen,^[a]Gerhard Raabe,^[a]Jan Runsink,^[a]Sabine Nienstedt,^[a]Jürgen Decker,^[a]

Marcel Schleusner,^[a]Jochen Hachtel,^[a]Ralf Loo,^[a]Chang-Wan Woo,^[a]and

Parthasarathi Das^[a]

Keywords: Titanium / Alcohols / Fluxionality / Chirality / Sulfur / Asymmetric synthesis

Enantiopure acyclic (E)- and (Z)-configured allylic sulfoxim-

ines have been synthesized from N,S-dimethyl-S-phenylsul-

lectivities and high diastereoselectivities preferentially at the

α-position to give the corresponding syn-configured β-N-

foximine

and

aldehydes

by

the

addition− methylsulfonimidoyl-substituted homoallylic alcohols along

elimination−isomerization route through the intermediate

generation of the corresponding (E)-configured vinylic sul-

with the (Z)-anti-configured δ-N-methylsulfonimidoyl-sub-

stituted homoallylic alcohols in good yields. In this way, the

foximines. Isomerization of the vinylic sulfoximines with DBU cyclic lithiated allylic sulfoximine was converted with high

preferentially afforded the corresponding (Z)-configured al-

lylic sulfoximines, which were subsequently isomerized by

DBU to preferentially yield the (E)-isomers. Titanation of

lithiated (E)-configured allylic sulfoximines with ClTi(OiPr)₃

regio- and diastereoselectivity to the corresponding isomeric

homoallylic alcohols bearing an allylic sulfonimidoyl group.

In the case of mono(alkenyl)tris(diethylamino)titanium(IV)

complexes, the regioselectivity of their reactions with alde-

furnished the corresponding bis(2-alkenyl)diisopropyloxytit- hydes has been found to depend on the size of the substitu-

anium(IV) complexes, which reacted with aldehydes in the ent at the CC double bond and the aldehyde, as well as on

presence of ClTi(OiPr)₃with high regio- and diastereoselec- the configuration of the double bond. Reaction of racemic

tivities at the γ-position to give the corresponding (Z)-anti-

configured δ-N-methylsulfonimidoyl-substituted homoallylic

alcohols in good yields. In the absence of ClTi(OiPr)₃at low

temperatures, only one allylic moiety of the bis(alkenyl)diiso-

lithiated N-methyl-S-(3,3-diphenyl-2-propenyl)-S-phenylsul-

foximine with ClTi(OiPr)₃afforded the corresponding bis(al-

kenyl)diisopropyloxytitanium(IV) complex. X-ray structure

analysis revealed a distorted octahedral cis,cis,cis-configured

propyloxytitanium complex is transferred to the aldehyde. In bis(2-alkenyl)diisopropyloxytitanium(IV) complex, in which

this way, a cyclic lithiated allylic sulfoximine has been con- the allylic moieties are coordinated in a bidentate fashion

verted with high regio- and diastereoselectivity to the corres- through C-α and the N atom to the Ti atom, both having the

ponding homoallylic alcohols bearing a vinylic sulfonimidoyl

group. Titanation of lithiated (E)- and (Z)-configured allylic

sulfoximines with ClTi(NEt₂)₃afforded the corresponding

relative configuration R_SS_C. In solution, the titanium complex

shows fluxional behavior, which is characterized by topomer-

ization of the isopropyloxy groups and allylic moieties. The

mono(2-alkenyl)tris(diethylamino)titanium(IV)

complexes, exchange of the latter occurs with retention of the configura-

which reacted with aldehydes with moderate to high regiose-

tion at C-α.

Introduction

Having developed syntheses of enantiopure allylic N-

methylsulfoximines of type I^[6Ϫ9](Scheme 1) during the

course of the aforementioned work, we were interested to

see whether both a regio- and stereoselective hydroxyalkyl-

ation of I leading to formation of the δ- and β-N-methylsul-

fonimidoyl-substituted homoallylic alcohols II and III, re-

spectively, could be brought about. Although differently

substituted homoallylic alcohols of types II or III can be

obtained by several methods, no single method is available

whereby both can be secured in enantio- and diastereopure

form from a common substituted allylic carbanion through

adjustment of the reaction conditions.^[10Ϫ12]Selective con-

versions of the vinylic sulfoximines II and allylic sulf-

oximines III to the enantio- and diastereopure building

blocks IVϪVIII can be envisaged considering (i) the facile

lithiation of vinylic sulfoximines^[4,13Ϫ17]and allylic

sulfoximines^{[2,5,11,12,18Ϫ24]}at C-α, (ii) the ready nickel-cata-

lyzed cross-coupling reaction of vinylic sulfoximines with

Sulfoximines have emerged as highly useful starting mat-

erials and auxiliaries in stereoselective synthesis.^[1Ϫ3]Their

versatility originates mainly from the endowment of the sul-

fonimidoyl group with an almost unique combination of

the features, namely chirality, carbanion stabilization, nucle-

ofugacity, basicity, nucleophilicity, and a low redox poten-

tial. Recent examples where several of these characteristics

have been exploited are the asymmetric syntheses of prosta-

cyclin analogs,^[4,5]which utilize transition metal mediated

cross-coupling reactions of vinylic and allylic sulfoximines

with organometallics for the formation of key CC bonds.

[a]

Institut für Organische Chemie der Rheinisch-Westfälischen

Technischen Hochschule Aachen,

Professor-Pirlet-Straße 1, D-52056 Aachen, Germany

Fax: (internat.) ϩ49 (0)241/8888665

E-mail: Gais@RWTH-Aachen.de

Eur. J. Org. Chem. 2000, 3973Ϫ4009

WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000

1434Ϫ193X/00/1224Ϫ3973 $ 17.50ϩ.50/0

3973

H.-J. Gais et al.

FULL PAPER

organometallics,^[4,15,25,26](iii) the excellent Michael ac-

ceptor properties of vinylic sulfoximines and their (dial-

kylamino)sulfoxonium salts,^[27Ϫ30](iv) the facile reduction

of sulfoximines,^[31](v) the ready S_Nreaction of allylic sulf-

oximines with copper organyls,^[5Ϫ7](vi) the facile elimina-

Results and Discussion

Synthesis of Allylic Sulfoximines

The allylic sulfoximines E-4aϪd, ent-4e, rac-E-4a, Z-

tion of β-hydroxy (dialkylamino)sulfoxonium salts under 4aϪd, and rac-Z-4a were synthesized from sulfoximines 1,

formation of epoxides,^[32,33]and (vii) the ready substitution ent-1, and rac-1, respectively, and the corresponding alde-

of allylic sulfoximines.^[34]Thus, if attainable, sulfoximines II hydes by the additionϪeliminationϪisomerization route

and III would be expected to considerably expand the range (AEI route) (Scheme 2).^[4Ϫ7]The enantiopure sulfoximines

of synthetic possibilities available through the use of either 1 and ent-1 were obtained from (ϩ)- and (Ϫ)-S-methyl-S-

enantio- and diastereopure homoallylic alcohols of types II phenylsulfoximine,^[32,33]] which, in turn, are accessible in en-

and III bearing an alkyloxy group,^[35Ϫ42]a Cl atom,^[43Ϫ45]antiopure form on a molar scale through an efficient race-

a (dialkylamino)carbonyloxy group,^[10e,46Ϫ51]or a silyl mate separation with (ϩ)-10-camphorsulfonic acid^[9]fol-

group^[52Ϫ54]instead of the sulfonimidoyl group, or by utiliz- lowing the method of half-quantities. Treatment of 1 with

ing aldol-type compounds^[55,56]and vinylic epoxides as nBuLi and propanal gave Li-2a as a mixture of epimers,

starting materials.^[57]The feasibility of a synthesis of II which were not isolated but treated in situ with ClCOOMe

from I was indicated by the work of Reggelin et al.,^[11,12]and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)^[60,61]to af-

who showed that lithiumϪtitanium exchange using ford the (E)-configured vinylic sulfoximine 3a in 78% yield.

ClTi(OiPr)₃of lithiated allyl and crotyl sulfoximines bear- Reaction of 3a with DBU at 60 °C in MeCN gave a mixture

ing a chiral N-(silyloxy)alkyl group instead of the N-methyl of the allylic sulfoximines E-4a and Z-4a in a ratio of 76:24

group allowed their γ-hydroxyalkylation under the highly in 95% yield. Synthesis of the allylic sulfoximines E-4b and

regio- and diastereoselective formation of vinylic hydroxy Z-4b was accomplished in a similar manner from 1 and n-

sulfoximines of type II in medium to good yields.^[58]Thus, butanal. Thus, reaction of 1 with nBuLi and n-butanal and

we hoped that isopropyloxytitanium complexes of Li-I subsequent acidic work-up led to the isolation of a mixture

would behave similarly and react with aldehydes at the γ- of the β-hydroxy sulfoximines 2b and epi-2b in 99% yield.

position to give II. Although the allylic hydroxy sulfoxim- Conversion of 2b and epi-2b to the corresponding mesylates

ines III are accessible by the reaction of Li-I with and in situ treatment of the latter with DBU gave the (E)-

aldehydes,^[21Ϫ24]the diastereoselectivity of this transforma- configured vinylic sulfoximine 3b in 98% yield. Isomeriz-

tion is too low to be synthetically useful. It is generally be- ation of 3b with DBU at 60 °C in MeCN afforded a mixture

lieved that the regioselective hydroxyalkylation of allylic ti- of the allylic sulfoximines E-4b and Z-4b in a ratio of 75:25

tanium complexes is due to intramolecular CϪC bond in 91% yield. Synthesis of the vinylic sulfoximine 3c was

formation resulting in a cyclic six-membered transition state carried out in a similar manner. Thus, reaction of 1 with

following coordination of the aldehyde to the Ti atom.^[10e]nBuLi and 3-methylbutanal furnished a mixture of 2c and

We thus speculated that in view of the reduced electrophilic- epi-2c in 95% yield. Mesylation of 2c and epi-2c and sub-

ity of a tris(dialkylamino)titanyl group as compared to a sequent elimination as described above led to isolation of

tris(alkyloxy)titanyl group, dialkylaminotitanium com- the (E)-configured vinylic sulfoximine 3c in 89% yield. Fi-

plexes of Li-I might perhaps behave differently and react nally, isomerization of 3c with DBU furnished a mixture of

with aldehydes with high regio- and diastereoselectivity at the allylic sulfoximines E-4c and Z-4c in a ratio of 83:17 in

the α-position to furnish the allylic hydroxy sulfoximines 93% yield.

III. Admittedly, however, previous experience of such a

The synthesis of the vinylic sulfoximine 3d, starting from

change in the Ti ligands in the case of other hetero-substi- 1 and cyclohexylethanal, was carried out without isolation

tuted allylic titanium complexes^[10e]was not too encour- of the corresponding β-hydroxy sulfoximines 2d and epi-2d.

aging. Despite the accessibility of vinylic hydroxy sulfoxim- Treatment of Li-2d and Li-epi-2d with MeSO₂Cl and NEt₃

ines of type II bearing a chiral N-(silyloxy)alkyl group, our led to the isolation of the (E)-configured vinylic sulfoximine

efforts were directed towards the synthesis of the N-methyl- 3d in 95% yield. Isomerization of 3d with DBU at 60 °C in

sulfoximines II and III from I for the reasons outlined be- MeCN yielded a mixture of the allylic sulfoximines E-4d

low. A wide variety of not only cyclic but also acyclic (Z)- and Z-4d in a ratio of 90:10 in 96% yield. The (Z)- and (E)-

as well as (E)-configured allylic N-methylsulfoximines I is isomers Z-4aϪd and E-4aϪd were quantitatively separated

readily accessible by the routes we have described.^[4Ϫ9]Of by either preparative HPLC or MPLC. It was found that

no less importance for our choice was, however, the fact the yields of E-4aϪd could be increased by submitting Z-

that the chemistry required for the projected syntheses of 4aϪd to DBU treatment at 60 °C in MeCN followed by a

IVϪVIII from II and III has already been established for chromatographic separation of the isomers. Monitoring of

allylic and vinylic sulfoximines bearing an N-methyl group. the isomerization of 3aϪd with DBU at 25 °C in MeCN

We report herein on studies of the reactions of isopropyl- by GC analysis and NMR spectroscopy revealed the highly

oxy- and diethylaminotitanium(IV) complexes of Li-I with selective formation of the (Z)-configured allylic sulfoxim-

aldehydes, and on the investigation of the structure of a ines Z-4aϪd, which subsequently underwent slow isomeriz-

bis(2-alkenyl)diisopropyloxytitanium(IV) complex of Li-I ation to E-4aϪd. Only after prolonged treatment of the

in solution and in the crystal.^[59]

mixtures of (Z)- and (E)-configured allylic sulfoximines

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N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

Scheme 1. δ- and β-N-Methylsulfonimidoyl-substituted homoallylic alcohols and their potential application to the synthesis of chiral

building blocks

ation of 3aϪd by varying the temperature allows access not

only to the (E)-configured allylic sulfoximines E-4aϪd, but

also to their (Z)-isomers Z-4aϪd as the major component of

the mixtures of both. The AEI route has hitherto been found

to be best for the synthesis of (Z)-configured allylic sulfoxim-

ines.^[8,11,12]

In the aforementioned syntheses of Z-4aϪd and E-4aϪd,

the vinylic sulfoximines 3aϪd, and occasionally the hydroxy

sulfoximines 2aϪd as well, were isolated and purified in or-

der to characterize them. It should be noted, however, that

for the attainment of the allylic sulfoximines these steps are

not required. We have repeatedly prepared the allylic sulfox-

imines Z-4aϪd and E-4aϪd with the same efficiency by a

shortened route omitting the isolation of the β-hydroxy sulf-

oximines 2aϪd and the purification of the vinylic sulfoxim-

ines 3aϪd. The synthesis of acyclic monosubstituted allylic

sulfoximines by the AEI route generally requires a chroma-

Scheme 2. Synthesis of monosubstituted allylic sulfoximines

tographic separation of the (E)- and (Z)-isomers. If this

with DBU at 60 °C in MeCN did the (E)-isomers become proves difficult, the pure isomers can be obtained by an

predominant. Thus, treatment of 3a with DBU at 20 °C in alternative stereoselective route starting from the α-chloro

MeCN until the starting material had been fully consumed derivative of 1 and the corresponding (E)- or (Z)-config-

yielded a mixture of Z-4a and E-4a in a ratio of 70:30. Sub- ured vinylic lithium organyl.^[8]The phenyl-substituted al-

jecting this mixture to further treatment with DBU at 60 °C lylic sulfoximine ent-E-4e was obtained directly as the pure

in MeCN afforded a mixture of the (Z)- and (E)-isomers in (E)-isomer in a one-pot process starting from ent-1 and

a reversed ratio of 24:76. Similar results were obtained in the phenylethanal without isolation of any of the interme-

isomerizations of the other alkyl-substituted vinylic sulfoxim- diates.^[7]The disubstituted allylic sulfoximines 6a and 6b

ines 3bϪd. These results suggest that in the isomerization were prepared in a similar manner as the monosubstituted

of 3aϪd with DBU, the (Z)-isomers Z-4aϪd are the kinetic analogs starting from 1 and the corresponding aldehydes

products, while the (E)-isomers E-4a؊d are the thermodyn- (Scheme 3). The successive treatment of 1 with nBuLi, 2-

amic products. Similar results have been reported previously methylpropanal, MeSO₂Cl, and NEt₃, followed by the

for the isomerization of (E)-configured vinylic sulfones with usual work-up, furnished the vinylic sulfoximine 5a in 67%

DBU.^[62]The reason for the preferential formation of (Z)- yield. Isomerization of 5a with DBU at 60 °C in MeCN

configured allylic sulfoximines and sulfones from the corres- gave the allylic sulfoximine 6a in 75% yield. The allylic sulf-

ponding (E)-configured vinylic sulfoximines and sulfones, re- oximine 6b was prepared in 60% yield in a one-pot process

spectively, under the described conditions is not yet clear. involving treatment of 1 with nBuLi and diphenylethanal

Besides the mechanistic implications, the stepwise isomeriz- and subsequent addition of ClCOOEt followed by KOtBu.

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3975

H.-J. Gais et al.

FULL PAPER

the aforementioned hydroxyalkylations, is not capable of ef-

fecting the γ-selective transfer of both allylic moieties of the

bis(2-alkenyl)diisopropyloxytitanium complexes. Similar re-

sults were obtained when Cl₂Ti(OiPr)₂was used instead of

the monochloro reagent. Thus, treatment of Li-E-4d with

0.50 equiv. of Cl₂Ti(OiPr)₂at Ϫ78 °C in THF followed by

the addition of 2-methylpropanal gave 7l in only 10% chem-

ical yield (Table 1, entry 14). However, the use of 1.1 equiv.

of Cl₂Ti(OiPr)₂under otherwise identical conditions led to

an increase in the chemical yield of 7l to 45% (Table 1, entry

15). Finally, when in the latter experiment the reaction mix-

ture was allowed to warm to ambient temperature after the

addition of the aldehyde, the chemical yield of 7l increased

to 78% (Table 1, entry 16) and it could be isolated in 70%

yield. Again, the formation of E-10l and epi-E-10l was not

observed under these conditions. Although not all of the

described hydroxyalkylations were re-examined using 2.1

equiv. of ClTi(OiPr)₃and ambient reaction temperatures,

we are convinced that with these modifications good yields

of 7 can generally be achieved.

Scheme 3. Synthesis of disubstituted allylic sulfoximines

Isopropyloxytitanium Complexes: Synthesis of (Z)-anti-

Configured δ-N-Methylsulfonimidoyl-Substituted Chiral

Homoallylic Alcohols

Titanation^[63,64]of the lithiated (E)-configured allylic sulf-

oximines Li-E-4aϪd and ent-Li-E-4e^[7]with 1.2 equiv. of

ClTi(OiPr)₃at Ϫ78 °C to 0 °C in THF presumably gave the

corresponding bis(2-alkenyl)diisopropyloxytitanium com-

plexes, admixed with equimolar amounts of Ti(OiPr)₄(vide

infra). At Ϫ78 °C, these reacted with ethanal, propanal, 2-

methylpropanal, and benzaldehyde, as anticipated, with

high regioselectivities and generally also with high diaster-

Scheme 4. Synthesis of acyclic δ-N-methylsulfonimidoyl-substi-

tuted homoallylic alcohols

In view of the formation of bis(alkenyl)titanium com-

eoselectivities, to furnish the (Z)-anti-configured δ-N- plexes upon reaction of Li-E-4 with ClTi(OiPr)₃(vide

methylsulfonimidoyl-substituted homoallylic alcohols infra), it was of interest to see whether a difference in the

7aϪc, 7e, 7g, 7iϪl, and ent-7n, respectively (Scheme 4, selectivity of the hydroxyalkylation would be observed by

Table 1, entries 1Ϫ3, 6Ϫ17). Formation of the correspond- using racemic instead of enantiopure Li-4 as the starting

ing isomeric allylic hydroxy sulfoximines E-10 (vide infra, material. Reaction of the isopropyloxytitanium complexes

Scheme 5), derived from α-hydroxyalkylation, could either prepared from rac-Li-E-4a or rac-Li-E-4e and 1.2 equiv. of

not be detected or amounted to less than 3%. Much to our ClTi(OiPr)₃with 2-methylpropanal and benzaldehyde also

surprise, however, the chemical yields (cy) of 7 under these proceeded with high regio- and diastereoselectivities and af-

conditions were generally only in the range 37Ϫ52%, and forded the racemic (Z)-anti-configured vinylic hydroxy sul-

the yields of pure 7 were only in the range 31Ϫ45%. Ap- foximines rac-7c, rac-7d, and rac-7n, respectively, in yields

proximately half of the starting allylic sulfoximine remained similar to those obtained with the enantiopure starting mat-

unchanged and could be recovered. Deuterative work-up of erials (Table 1, entries 4, 5, and 18).

the reaction mixtures led to isolation of the (E)-configured

The reactions of the isopropyloxytitanium complexes de-

allylic sulfoximines containing one D atom at the α-posi- rived from Li-Z-4a؊d having a (Z)-configured double bond

tion. Increasing the temperature of the reaction mixture to with aldehydes were not only much slower than those of

ambient after the addition of the aldehyde did not lead to their (E)-isomers, but occurred at the γ- as well as the α-

an increase in the yield of 7. Instead, in a competing sec- position, thereby affording the corresponding hydroxy sul-

ondary reaction, the α-adducts E-10 and epi-E-10 were foximines with low stereoselectivities. The selectivity was

formed besides γ-adduct 7. After having carried out most found to depend on the size of the alkyl group of the allylic

of the hydroxyalkylations, we eventually found that the use sulfoximine and on the size of the aldehyde (Scheme 5).

of 2.1 equiv. of ClTi(OiPr)₃in the titanation of Li-E-4, in Most interestingly, the sulfoximines derived from a γ-attack

combination with ambient temperatures for the hydroxyalk- were found to have the (E)- rather than (Z)-configuration.

ylation step, led to an increase in the chemical yields of 7 In the series of isopropyloxytitanium complexes derived

to 74Ϫ82% and in the yields of pure 7 to 45Ϫ72% (Table 1, from rac-Li-Z-4a, Li-Z-4b, and Li-Z-4c, that bearing a

entries 6, 9, 11, and 13). Under these conditions, formation methyl group at the γ-position reacted most rapidly with

of E-10 and epi-E-10 was not observed. It is interesting to the aldehydes. Thus, reaction of the isopropyloxytitanium

note that Ti(OiPr)₄, which was presumably present in all complex derived from rac-Li-Z-4a and 1.2 equiv. of

3976

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N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

Table 1. Synthesis of the δ-N-methylsulfonimidoyl-substituted acyclic homoallylic alcohols 7

Entry

Starting material

Aldehyde

Product

R¹

R²

ds (%)^[a][b]

Yield (%)^[c]

1

2

3

4

5

E-4a

rac-E-4a

E-4b

؊

MeCHO

EtCHO

iPrCHO

PhCHO

MeCHO

Ϫ

7a

Me

Et

Ն98 (Ն96)

97 (96)^[e]

Ն98 (92)^[e]

Ϫ

31 (44)

32 (37)

36 (46)

32 (52)^[d]

45 (53)^[f]

44 (74)^[g,d]

Ϫ

7b

Me

7c

Me

iPr

Ph

Me

iPr

Me

Et

rac-7c

rac-7d

7e

Me

6

Et

[h]

7f

Et

7

E-4c

؊

MeCHO

؊

7g

iPr

Ն98 (Ն96)

Ϫ

32 (48)

Ϫ

[h]

7h

iPr

8

9

E-4c

E-4d

Ϫ

iPrCHO

PhCHO

EtCHO

iPrCHO

Ϫ

7i

iPr

Ph

Et

iPr

Ph

iPr

Ն98 (Ն96)

Ն98 (96)^[e]

(Ն96)

44 (48)

72 (82)^[g]

43 (48)

69 (77)^[g]

(52)

7i

iPr

10

11

12

13

14

15

7j

iPr

7k

cC₆H₁₁

Ph

7l

Ն98 (Ն96)

Ϫ

72 (82)^[g]

(10)^[i]

7l

(Ն96)

(45)^[j]

16

7l

Ն98 (Ն96)

70 (78)^[k]

Ϫ

[h]

7m

ent-7n

rac-7n

Ϫ

17

18

ent-E-4e

rac-E-4e

iPrCHO

Ն98 (Ն96)

(Ն96)

29 (40)^[d]

(42)

Ph

[a]

1

From H-NMR spectroscopic analysis. Where ds values are quoted as Ն98 % and Ն96 %, no other isomer could be detected in the

[b]

[c]

isolated and in the crude product, respectively. Ϫ

Values in parentheses refer to crude products. Ϫ Values in parentheses refer to

[d]

[e]

[f]

[i]

chemical yields (cy). Ϫ

Isolated as triethylsilyl ether.Ϫ A second (Z) diastereomer was observed in the ¹H NMR spectrum. Ϫ

[g] [h]

Isolated as tert-butyldimethylsilyl ether. Ϫ Titanation with 2.1 equiv. of ClTi(OiPr)₃at Ϫ78 °C to 25 °C. Ϫ Not investigated. Ϫ

[j]

[k]

Titanation with 0.50 equiv. of Cl₂Ti(OiPr)₂. Ϫ Titanation with 1.1 equiv. of Cl₂Ti(OiPr)₂at Ϫ78 °C. Ϫ

Titanation with 1.1 equiv.

of Cl₂Ti(OiPr)₂at Ϫ78 °C.

ClTi(OiPr)₃with benzaldehyde proceeded with high re-

gioselectivity but with low syn/anti selectivity to give the

(E)-anti-configured vinylic hydroxy sulfoximine rac-8a and

the (E)-syn-configured vinylic hydroxy sulfoximine rac-9a in

a 2:1 ratio in only 26% yield (isolated as the tert-butyldime-

thylsilyl ether). The corresponding reaction of the isopropyl-

oxytitanium complex derived from Li-Z-4b and 2.1 equiva-

lents of ClTi(OiPr)₃with ethanal furnished a mixture of the

(E)-anti-configured vinylic hydroxy sulfoximine 8b, its (E)-

syn-configured epimer 9b, and the (Z)-syn-configured allylic

hydroxy sulfoximine Z-10a (vide infra) in a ratio of 58:2:40

in 56% chemical yield. Crystallization of this mixture af-

forded pure 8b in 26% yield. The reaction of the isopropyl-

substituted isopropyloxytitanium complex of Li-Z-4c, pre-

pared using 1.2 equiv. of ClTi(OiPr)₃, with 2-methylpro-

panal occurred exclusively at the α-position to furnish a

mixture of the (Z)-anti- and the (Z)-syn-configured allylic

hydroxy sulfoximines epi-Z-10b and Z-10b (vide infra) in a

2:1 ratio in 45% chemical yield.

The reactivity differences between the isopropyloxytitan-

ium complexes of Li-E-4 and Li-Z-4 were generally suffi-

cient to allow for a selective synthesis of the corresponding

vinylic hydroxy sulfoximine 7 starting from an (E)/(Z)-mix-

ture of the allylic sulfoximine. Hence, separation of the (Z)-

and (E)-isomers of 4 was generally not required in the syn-

theses of compounds 7. An illustrative example is the syn-

thesis of the silyloxy-substituted (Z)-anti-configured vinylic

hydroxy sulfoximine 12, which was obtained in diastereop-

ure form in 32% yield starting from a 70:30 mixture of Li-

E-4a and Li-Z-4a and the aldehyde 11^[65](Scheme 6).

Formation of the corresponding (E)-anti-configured dia-

Scheme 5. Reaction of the isopropyloxytitanium complexes of Li-

Z-4 with aldehydes

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3977

H.-J. Gais et al.

FULL PAPER

stereomer of 12, as would be derived from Z-4a, was not

Finally, it is important to note that incomplete

observed. The sulfoximines E-4a and Z-4a were recovered lithiumϪtitanium exchange of Li-E-4, Li-13, and Li-15

in 53% yield in a 1:1 ratio. Treatment of this mixture with with ClTi(OiPr)₃leads to a competing and unselective

DBU in MeCN gave the two isomers in a 70:30 ratio. Since formation of the corresponding allylic hydroxy sulfoximines

in the synthesis of 12 only 1.2 equiv. of ClTi(OiPr)₃were derived from an α-attack of the aldehyde on the lithiated

used, a considerable improvement in the yield of the vinylic allylic sulfoximines.^[66]

hydroxy sulfoximine should be possible by using 2.1 equiv.

The acyclic and cyclic vinylic hydroxy sulfoximines

of the titanium reagent and pure E-4a as the starting mat- (Table 1 and 2) were purified by either crystallization, chro-

erial (vide supra).

matography, or chromatography following silylation. In

some cases, formation of N-methyl-S-phenylsulfinamide as

a minor side product was observed, which proved to be easy

to separate by crystallization but difficult by chromato-

graphy. Thus, in the latter case, the crude mixture was

treated with either ClSiEt₃or ClSitBuMe₂, which gave a

mixture of the corresponding O-silylated vinylic sulfoxim-

ine, N-silyl-N-methyl-S-phenylsulfinamide, and the allylic

sulfoximine, which could readily be separated by chromato-

graphy.

Scheme 6. Synthesis of the δ-N-methylsulfonimidoyl-substituted

homoallylic alcohol 12 starting from a mixture of E-4a and Z-4a

The (Z)-anti-configuration of the vinylic hydroxy sulfoxi-

mines 7g (Figure 1), 7j (Figure 2), 16c (Figure 3), and 16d

(Figure 4) was confirmed by X-ray structure analyses.^[67]In-

ternal correlation based on the known (S)-configuration of

1 led to the assignment of the absolute configurations of

7g, 7j, 16c, and 16d as shown in Schemes 8 and 12. Because

of the similarity of the key NMR spectroscopic data (vide

infra), we also assigned the configurations depicted in

Schemes 8, 10, and 11 to sulfoximines 7aϪe, 7g, 7iϪl, ent-

7n, 12, 14, and 16b. Interestingly, besides a pseudoaxial hy-

droxyalkyl group, in the crystal the hydroxy sulfoximines

16c and 16d feature an intramolecular hydrogen bond be-

tween the hydroxy group and the N atom belonging to an

eight-membered ring (Figure 3 and 4). As a result, α-H and

β-H^[68a]of 16c and 16d are antiperiplanar. According to the

magnitude of the coupling constant ³J(α-H,β-H) in the

NMR spectra, and in the light of the results of the NOE

experiments, the basic structure of sulfoximines 16c and 16d

seen in the crystal is retained in solution. In contrast to 16c

and 16d, sulfoximines 7g and 7j do exhibit an intermolecu-

lar hydrogen bond between the hydroxy group and the N

atom in the crystal. As a consequence, α-H and β-H of 7g

and 7j are synclinal in the crystal. However, according to

β,γ-Disubstituted allylic sulfoximines are also amenable

to selective γ-hydroxyalkylation. Thus, treatment of sulfoxi-

mine Li-13, obtained by lithiation of 13,^[7]with 1.2 equiv.

of ClTi(OiPr)₃at Ϫ78 °C in THF and subsequent addition

of benzaldehyde led to the isolation of the (Z)-anti-config-

ured vinylic hydroxy sulfoximine 14 incorporating a trisub-

stituted double bond in 41% yield with Ն98% ds

(Scheme 7).

Scheme 7. Synthesis of the δ-N-methylsulfonimidoyl-substituted

homoallylic alcohol 14

Not only isopropyloxytitanium complexes of acyclic but

also those of cyclic allylic sulfonimidoyl carbanions react

with aldehydes with high regio- and diastereoselectivity at

the γ-position to yield the corresponding vinylic sulfoxim-

ines (Scheme 8, Table 2). Thus, successive treatment of 15,

prepared from cyclohexanone and 1 in 93% overall yield by

the shortened AEI route,^[6]with nBuLi and 2.2 equiv. of

ClTi(OiPr)₃, and subsequent reaction of the thus formed

isopropyloxytitanium complex with ethanal, 2-methylpro-

panal, or benzaldehyde afforded the (Z)-anti-configured vi-

nylic hydroxy sulfoximines 16bϪd with Ն96% ds in

62Ϫ77% chemical yield. The diastereopure sulfoximines 16c

and 16d were isolated in 59% and 47% yield, respectively.

3

the magnitudes of the coupling constants J(α-H,β-H) and

³J(β-H,γ-H) in the NMR spectra of 7a؊e, 7g, 7i؊l, ent-7n,

12, and 14, and in view of the results of NOE experiments

on 7g and 7j, in solution these sulfoximines preferentially

adopt a conformation similar to that of 16c and 16d in the

crystal, with an intramolecular hydrogen bond between the

hydroxy group and the O atom or N atom of the sulfoxim-

ine group. This conformation is characterized by antiper-

iplanar positions of α-H and β-H as well as of β-H and γ-

H. In contrast, the ethers 7g-SiEt₃and 7j-SiEt₃, which can-

not form such a hydrogen bond, preferentially exist in solu-

tion in a conformation similar to that of the parent sulfoxi-

mine 7g or 7j in the crystal.

The (E)-anti-configuration of the vinylic hydroxy sulfoxi-

mine 8b was determined by the following chemical correla-

tion. Successive treatment of the (Z)-configured vinylic hy-

droxy sulfoximine 7e with nBuLi and acetic acid furnished

Scheme 8. Synthesis of cyclic δ-N-methylsulfonimidoyl-substituted

homoallylic alcohols

3978

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

Table 2. Synthesis of the δ-N-methylsulfonimidoyl-substituted cyclic homoallylic alcohols 16

Entry

Starting material

Aldehyde

Product

R

ds (%)^[a]

Yield (%)

[b]

Ϫ

16a

16b

16c

16d

Me

Et

iPr

Ph

Ϫ

1

2

3

15

EtCHO

iPrCHO

PhCHO

(Ն96)^[c]

(77)^[d]

Ն98 (Ն96)^[c]

59 (77)^[d]

47 (62)^[d]

[a]

From ¹H-NMR spectroscopic analysis. Where ds values are quoted as Ն98% and Ն96%, no other isomer could be detected in the

[b]

[c]

[d]

isolated and in the crude product, respectively. Ϫ Not investigated. Ϫ Values in parentheses refer to crude products. Ϫ Values in

parenthesis refer to chemical yields.

Figure 4. Crystal structure of sulfoximine 16d (some H atoms have

Figure 1. Crystal structure of sulfoximine 7g (some H atoms have

˚

been omitted for the sake of clarity); selected bond lengths [A]:

˚

been omitted for the sake of clarity); selected bond lengths [A]:

SϪN 1.530(3), SϪO 1.454(3), SϪC 1.744(4), SϪPh 1.788(3)

SϪN 1.542(4), SϪO 1.447(3), SϪC 1.755(5), SϪPh 1.777(5)

the (E)-isomer 8b in quantitative yield.^[34a,69]Because of the

close similarity of the NMR spectroscopic data of 8b and

rac-8a, the (E)-anti-configuration was also assigned to the

latter sulfoximine. The configurations of the vinylic sulfoxi-

mines rac-9a and 9b were provisionally assigned as depicted

1

on the basis of their H NMR spectroscopic data.

The configuration of epi-Z-10b was assigned by ¹H NMR

spectroscopy through comparison with data for an analog-

ous allylic hydroxy sulfoximine, the configuration of which

has been confirmed by X-ray structure analysis (vide infra).

(Diethylamino)titanium Complexes: Synthesis of syn-

Configured β-N-Methylsulfonimidoyl-Substituted Chiral

Homoallylic Alcohols

Figure 2. Crystal structure of sulfoximine 7j (some H atoms have

˚

been omitted for the sake of clarity); selected bond lengths [A]:

SϪN 1.548(5), SϪO 1.460(4), SϪC 1.772(5), SϪPh 1.778(5)

Titanation of Li-E-4aϪd with 1.1Ϫ1.2 equiv. of ClTi-

(NEt₂)₃at Ϫ78 °C to 0 °C in THF or diethyl ether presum-

ably afforded the corresponding mono(2-alkenyl)tris(diethy-

lamino)titanium complexes (vide infra). At Ϫ78 °C, these

reacted with ethanal, propanal, 2-methylpropanal, and

benzaldehyde to give, as hoped for, the corresponding dias-

tereopure (E)-syn-configured β-N-methylsulfonimidoyl-sub-

stituted homoallylic alcohols E-10 in moderate to good

yields (Scheme 9, Table 3, entries 1Ϫ8). However, a more

detailed study of the reactions of the diethylaminotitanium

complexes of Li-E-4aϪd bearing different alkyl groups at

the double bond with a number of aldehydes revealed in a

few cases the formation of significant amounts of the vi-

nylic hydroxy sulfoximines 7 besides the allylic sulfoximines

E-10 (Table 4, entries 1, 5, 7, and 8). The regioselectivity of

the hydroxyalkylation was found to be strongly dependent

on both the size of the aldehyde and the substituent on

Figure 3. Crystal structure of sulfoximine 16c (some H atoms have

˚

been omitted for the sake of clarity); selected bond lengths [A]:

SϪN 1.524(3), SϪO 1.452(2), SϪC 1.749(3), SϪPh 1.793(3)

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3979

H.-J. Gais et al.

FULL PAPER

the allylic sulfoximine. The α-selectivity increased markedly configured allylic sulfoximines. Only in the reaction of the

with increasing size of both reactants. From inspection of diethylaminotitanium complex derived from crotyl sulfoxi-

the data in Table 4, it would seem that the size of the alde- mine Li-Z-4a with ethanal was the formation of a mixture

hyde has a stronger effect on the α-selectivity than the size of Z-10a and the (E)-isomer of 7a observed (Table 4, entries

of the substituent on the allylic sulfoximine. It is interesting 16 and 17). In all cases investigated, the (Z)-configured al-

to note that the α-selectivity also increases at higher temper- lylic hydroxy sulfoximines were formed with high diastereo-

atures (Table 4, entries 2, 3, 7, 8, 9, and 10). In summary, a selectivity. The results in Table 4 show that most reactions

highly selective α-hydroxyalkylation can generally be of the (E)- and (Z)-configured diethylaminotitanium com-

achieved except in those cases where both reactants bear plexes with ethanal, which ought to be the most reactive

small groups. It is noteworthy that, in general, not only the aldehyde of those investigated, were only sluggish, and that

allylic hydroxy sulfoximine E-10 but also the corresponding most of the starting allylic sulfoximine was recovered. Al-

vinylic hydroxy sulfoximine 7 was formed with high diaster- though not verified experimentally, the apparent low react-

eoselectivity.

ivity of ethanal may perhaps be due to a competing transfer

of a diethylamino group^[64]from the allylic aminotitanium

complex to the aldehyde with formation of the aminal com-

plex IX (Scheme 10). Alternatively, the allylic aminotitan-

ium complex may react with the aldehyde under elimination

of diethylamine to give the enolate complex X. Such side

reactions would be expected to be more pronounced with

ethanal than with the other aldehydes used on steric

grounds.

Hydroxyalkylation of the diethylaminotitanium complex

of the γ,γ-disubstituted sulfoximine Li-6a with 2-methylpro-

panal took place exclusively at the α-position to furnish the

syn-configured allylic hydroxy sulfoximine 17a with Ն98%

ds in 75% yield (92% cy) (Scheme 11). Reaction of Li-6b

with propanal under similar conditions afforded the syn-

Scheme 9. Synthesis of acyclic β-N-methylsulfonimidoyl-substi-

tuted homoallylic alcohols

Table 3. Synthesis of the β-N-methylsulfonimidoyl-substituted acyclic homoallylic alcohols 10

Entry

Starting material

Aldehyde

Product

R¹

R²

ds (%)^[a]

Yield (%)

1

E-4a

E-4b

E-4c

E-4d

Z-4a

Z-4b

Z-4c

MeCHO

iPrCHO

EtCHO

iPrCHO

PhCHO

iPrCHO

PhCHO

MeCHO

EtCHO

MeCHO

iPrCHO

PhCHO

E-10c

E-10e

E-10f

E-10h

E-10i

E-10j

E-10l

E-10m

Z-10a

Z-10b

Z-10e

Z-10f

Z-10i

Z-10j

Me

Et

iPr

Me

iPr

Et

iPr

Ph

iPr

Ph

Me

Et

Me

iPr

Ph

Ն98

76

48

47

87

81

70

86

68

20

90

64

91

73

2

3

Et

4

iPr

5

iPr

6

iPr

7

cC₆H₁₁

Me

Et

8

9

10

11

12

13

14

Et

iPr

[a]

1

From H-NMR spectroscopic analysis, where a ds value is quoted as 98%, no other isomer could be detected in the isolated product.

Titanation of Li-Z-4aϪc with 1.1Ϫ1.2 equiv. of ClTi- configured allylic hydroxy sulfoximine 17b with 90% ds in

(NEt₂)₃at Ϫ78 °C to 0 °C in THF and reaction of the thus 87% chemical yield. Recrystallization of the crude material

formed diethylaminotitanium complexes (vide infra) with furnished 17b containing 2% of a diastereomer in 56%

ethanal, propanal, 2-methylpropanal, and benzaldehyde led yield. The apparently lower diastereoselectivity of the

to the isolation of the corresponding diastereopure (Z)-syn- formation of 17b can most probably be attributed to a com-

configured β-N-methylsulfonimidoyl-substituted homoal- peting unselective α-hydroxyalkylation of a small amount

lylic alcohols Z-10 in moderate to good yields (Scheme 9, of Li-6b,^[70]present due to incomplete lithiumϪtitanium ex-

Table 3, entries 9Ϫ14). Again, the regioselectivity of the hy- change, as was subsequently revealed by NMR spectro-

droxyalkylation was investigated by variation of the alde- scopic monitoring of the lithiumϪtitanium exchange under

hyde and of the substituent on the allylic sulfoximine similar conditions.

(Table 4, entries 16Ϫ24). Inspection of the data in Table 4

The selective α-hydroxyalkylation could also be extended

reveals that for the (Z)-configured allylic sulfoximines the to the cyclic allylic sulfoximine Li-15. Titanation of Li-15

regioselectivity, which increases with increasing temper- with ClTi(NEt₂)₃and the subsequent reactions of the re-

ature, is significantly higher than for the corresponding (E)- sulting diethylaminotitanium complex with ethanal, pro-

3980

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

Table 4. Reactions of the diethylaminotitanium complexes of the acyclic allylic N-methylsulfonimidoyl carbanions Li-4 with aldehydes

FULL PAPER

Entry

Starting material

Aldehyde

T [°C]

Conv. (%)

10/7

10, ds (%)^[a]

7, ds (%)^[a]

R¹

R²

1

2

3

E-4a

Ϫ

E-4b

E-4c

Ϫ

MeCHO

EtCHO

iPrCHO

Ϫ

MeCHO

iPrCHO

MeCHO

EtCHO

iPrCHO

PhCHO

Ϫ

Ϫ78

25

77

62

91

97

Ϫ

50

97

53

28

67

98

99

94

Ϫ

1:1.5

E-10a, Ն96

E-10b, Ն96

E-10c, Ն96

E-10d

7a, 92^[b]

7b, Ն96

7c, Ն96

7d

Me

Et

Me

Et

4.1:1

7.2:1

Et

4

Ϫ78

23:1

iPr

Ph

Me

iPr

Me

Et

[c]

Ϫ

5

Ϫ30

Ϫ78

25

1.1:1

E-10e, Ն96

E-10f, Ն96

E-10g, Ն96

E-10h, Ն96

E-10i, Ն96

E-10j, Ն96

E-10k

7e, Ն96

7f, Ն96

7g, 85^[b]

7g, 90^[b]

7h, Ϫ

7h, ؊

7i, Ϫ

6

31:1

Et

7

1:1

iPr

8

1.8:1

iPr

9

Ϫ78

25

21:1

iPr

10

11

12

21:1

iPr

Et

Ϫ78

25

Ն100:1

Ϫ

iPr

Ph

Et

7i, ؊

iPr

13

Ϫ78

7j, Ϫ

iPr

[c]

Ϫ

7k

cC₆H₁₁

Ph

14

E-4d

Ϫ

iPrCHO

PhCHO

Ϫ

Ϫ78

Ϫ

98

78

Ϫ

Ն100:1

Ϫ

2.6:1

8.5:1

Ն100:1

E-10l, Ն96

E-10m, Ն96

E-10n

7l, Ϫ

iPr

Ph

iPr

Me

Et

15

7m, Ϫ

[c]

7n

[d]

16

17

18

19

20

21

22

23

24

Z-4a

Z-4b

Z-4c

MeCHO

EtCHO

MeCHO

iPrCHO

PhCHO

Ϫ78

36

19

98

99

63

76

99

92

90

Z-10a, Ն96

Z-10b, Ն96

Z-10e, Ն96

Z-10f, Ն96

Z-10i, Ն96

Z-10j, Ն96

Me

Et

[d]

25

Ϫ78

25

Ϫ

Et

Ϫ78

Ϫ30

Ϫ78

Me

iPr

Ph

Et

iPr

^[a]From ¹H-NMR spectroscopic analysis. Where a ds value is quoted as Ն98%, no other isomer could be detected in the isolated product.

[b]

1

[c]

[d]

Ϫ

A second (Z) diastereomer was observed in the H NMR spectrum. Ϫ Not investigated. Ϫ Several diastereomers.

spection of the data in Table 5 reveals a similar dependence

of the regioselectivity on the size of the aldehyde as in the

case of the hydroxyalkylation of the diethylaminotitanium

complexes of acyclic lithiated allylic sulfoximines (vide su-

pra). The α-selectivity increases with increasing size of the

aldehyde. The diastereopure vinylic hydroxy sulfoximines

Scheme 10. Putative side products of the reaction of the diethylami-

notitanium complexes of Li-4 with ethanal

18c and 18d were isolated in 57% and 66% yield, respect-

ively, by crystallization.

Table 5. Reaction of the diethylaminotitanium complex of the cyc-

lic allylic N-methylsulfonimidoyl carbanion Li-15 with aldehydes

Entry Aldehyde T [°C] Conv. (%) 18/16

18, ds (%)^[a]16, ds (%)^[a]

1

MeCHO Ϫ78 94

EtCHO Ϫ78 98

iPrCHO Ϫ78 91

PhCHO Ϫ78 86

2.6:1

13:1

22:1

18a, 95^[b]16a, Ն96

18b, Ն96 16b, Ն96

18c, Ն96 16c, Ն96

2

3

4

Scheme 11. Synthesis of acyclic β-N-methylsulfonimidoyl-substi-

tuted homoallylic alcohols

Ն100:1 18d, 95^[b]16d, Ն96

[a]

From ¹H NMR spectroscopic analysis. Where a ds value is

panal, 2-methylpropanal, and benzaldehyde gave with mod-

erate to high α-regioselectivities and high diastereoselectivi-

ties the (Z)-syn-configured allylic hydroxy sulfoximines

18a؊d (Scheme 12, Table 5). We ascribe the slightly lower

diastereoselectivities in the case of the formation of 18a and

quoted as Ն96%, no other isomer could be detected in the crude

product. Ϫ

NMR spectrum.

A second diastereomer was observed in the ¹H

[b]

Isolation of the aforementioned acyclic and cyclic substi-

18d to incomplete lithiumϪtitanium exchange reactions. In- tuted allylic hydroxy sulfoximines was accomplished either

by crystallization or chromatography. For the latter, the sil-

ica gel had to be deactivated by the addition of triethylam-

ine to the eluent owing to the instability of some of the

allylic hydroxy sulfoximines on standard silica gel.

The syn-configuration of the allylic hydroxy sulfoximines

Z-10e (Figure 5) and E-10i (Figure 6) was confirmed by X-

ray structure analyses.^[67]Internal correlation based on the

known (S)-configuration of 1 led to the assignment of the

Scheme 12. Synthesis of cyclic β-N-methylsulfonimidoyl-substi-

tuted homoallylic alcohols

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3981

H.-J. Gais et al.

FULL PAPER

absolute configurations of Z-10e and E-10i as shown in Dynamics of Cyclohexenyl-Substituted Allylic Hydroxy

Scheme 5Ϫ7. On the basis of these results and because of Sulfoximines

the similarity of key NMR spectroscopic data (vide infra),

we assigned to sulfoximines E-10aϪc, E-10eϪj, Z-10aϪj,

Interestingly, in the ¹H NMR spectrum (500 MHz) of the

17a, 17b, and 18aϪd the configurations depicted in cyclohexenyl-substituted hydroxy sulfoximine 18c in

Schemes 5Ϫ7. In the crystal, Z-10e exhibits an intramolecu- [D₈]THF at room temperature, nearly all of the signals are

lar hydrogen bond between the hydroxy group and the N broadened. In addition, the ¹³C NMR spectrum (125 MHz)

atom incorporated in a six-membered ring. As a con- of 18c in [D₈]THF at room temperature shows very broad

sequence, α-H and β-H^[68b]are antiperiplanar, the butenyl signals due to C-α, C-β, and the ortho C atoms of the

and methyl groups are both pseudoequatorial, and β-H and phenyl group. A similar line-broadening has also been ob-

1

γ-H are antiperiplanar. Sulfoximine E-10i adopts a similar served in the NMR spectra of 18a,b,d.^[71]The H and ¹³C

conformation as Z-10e in the crystal. Although the H atom NMR spectra of 18c at Ϫ60 °C reveal the existence of two

of the hydroxy group of E-10i could not be located, the isomeric species in a ratio of 2.4:1, the signals of which were

existence of an intramolecular hydrogen bond between the assigned by two-dimensional methods. Activation barriers

hydroxy group and the N atom seems to be highly likely in of ∆G^϶₂₇₈ϭ 53.2 Ϯ 1.3 kJ/mol and 55.9 Ϯ 1.3 kJ/mol were

this case as well. The results of NOE experiments on E- estimated for the equilibration of the isomers at the coales-

10i and 17b, together with the magnitudes of the coupling cence temperature.^[72]In their ¹H NMR spectra, the isomers

3

constants J(α-H,β-H) and J(β-H,γ-H) in the NMR spec- are characterized by a coupling constant ³J(α-H,β-H) ϭ

tra, indicate that in solution both hydroxy sulfoximines 10.1 Hz and by similar chemical shifts for the hydroxy

preferentially adopt a similar hydrogen-bond stabilized con- group signals. These observations were taken as an indica-

formation as adopted by Z-10e and E-10i in the crystal. tion that both isomers form an intramolecular hydrogen

3

Since the coupling constants J(α-H,β-H) and J(β-H,γ-H) bond between the hydroxy group and the N atom incorpor-

in the NMR spectra of E-10aϪc, E-10eϪj, Z-10aϪj, 17a, ated in a six-membered ring, at which the phenyl, cyclohex-

and 17b are of the same magnitude in each case, it seems enyl, and isopropyloxy groups are pseudoequatorially ar-

reasonable to assume that in solution these sulfoximines ranged.^[73]Characteristic chemical shift differences were ob-

preferentially adopt a similar hydrogen-bond stabilized con- served for the signals of the ϭCH and CH₂groups of the

formation.

cyclohexene rings of the isomers. Whereas in the major iso-

mer the ϭCH signal is subject to a significant high-field

shift, it is the CH₂signal of the minor isomer that shows a

significant high-field shift as compared with the respective

isomers (cf. Experimental Section). In the light of these re-

sults, we assign to the two isomers of 18c observed in the

NMR spectra the structures of the conformers 18c (A) and

18c (B) (Figure 7). Rotation of the cyclohexene ring about

the CβϪCαЈ bond of 18c (A) and 18c (B) is hindered

mainly because of steric interactions with the neighboring

phenyl and isopropyloxy groups. The estimated barriers of

53.2 kJ/mol and 55.9 kJ/mol for the rotation of the cyclo-

hexene rings of 18c (A) and 18c (B), respectively, compare

favorably in magnitude with those for other substituted cyc-

lic alkenes having restricted sp²Ϫsp³bond rotation.^[74]The

differences in the chemical shifts of the ϭCH and CH₂sig-

Figure 5 Crystal structure of sulfoximine Z-10e (some H atoms

have been omitted for the sake of clarity); selected bond lengths

˚

1

[A]: SϪN 1.532(3), SϪO 1.444(3), SϪC 1.816(2), SϪPh 1.790(4)

nals in the H NMR spectra of 18c (A) and 18c (B) arise

because of the phenyl ring current, which affects mainly

the ϭCH group in the former and the CH₂group in the

latter. A final proof of the above structural assignment was

provided by ROESY^[75]experiments. The ROESY spectra

of 18c (A) and 18c (B) in [D₈]THF at Ϫ90 °C showed no

negative, off-diagonal cross-peaks. Thus, an exchange be-

tween 18c (A) and 18c (B) did not occur on the NMR time

scale at this temperature. Appropriate positive cross-peaks

indicated the close proximity of ϭCH and β-H as well as

CH₂and α-H in 18c (A), and of ϭCH and α-H as well as

CH₂and β-H in 18c (B). Thus, the notion of the observed

isomerism of 18c being due to a restricted inversion of the

chiral cyclohexene ring and, hence, of isomers having the

structures 18c (C) and 18c (D), can be dismissed. This is

consistent with the expectation that the barriers associated

Figure 6. Crystal structure of sulfoximine E-10i (some H atoms

have been omitted for the sake of clarity); selected bond lengths

˚

[A]: SϪN 1.507(3), SϪO 1.449(2), SϪC 1.810(3), SϪPh 1.774(3)

3982

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

with inversion of the cyclohexene ring in 18c (C) and ialkyloxytitanium complexes, while titanation with ClTi-

18c (D) should be much lower^[74]than that estimated for (NEt₂)₃yields the corresponding mono(alkenyl)tris(amino)-

18c (A) and 18c (B) at the coalescence temperature. Indeed, titanium complexes. Although the formation of E-20aϪc

the NMR spectra of 18c (A) and 18c (B) at Ϫ60 °C reveal rather than the corresponding mono(alkenyl)titanium com-

an averaging of the vicinal coupling constants for the H plexes was somewhat surprising, it is not totally unpreced-

atoms of the cyclohexene ring. This shows that the inversion ented. We have previously observed that the reaction of

of the cyclohexene ring of 18c (A) and 18c (B) is still fast at lithiated dialkyl sulfones Li-XI with equimolar amounts of

low temperatures relative to the NMR time scale.

ClTi(OiPr)₃proceeds in a similar fashion to give, besides

equimolar amounts of Ti(OiPr)₄, the six-coordinate dior-

ganotitanium complexes XII, which have been character-

ized by X-ray structure analysis and NMR spectroscopy

(Scheme 14).^[79,80]Titanation of Li-4a,c,d with ClTi(OiPr)₃

can be expected to initially afford the corresponding

mono(alkenyl)tris(alkyloxy)titanium complexes. These

complexes could then undergo disproportionation with

formation of E-20a؊c and Ti(OiPr)₄. A prerequisite for

such a disproportionation would be a dimerization of the

mono(alkenyl)tris(alkyloxy)titanium complex. In fact, ag-

gregation of four-coordinate alkyloxytitanium complexes is

quite common, although less pronounced for (dialkylamin-

o)titanium complexes.^[64]While the Ti atom in monomeric

E-20aϪc can be six-coordinate (vide infra), that in the cor-

responding monomeric mono(alkenyl)tris(alkyloxy)titan-

ium complexes can only be five-coordinate. Thus, a driving

force for such a disproportionation may be the formation

of a coordinatively saturated titanium complex.

Figure 7. Conformers of the cyclohexenyl-substituted hydroxy sulf-

oximine 18c

X-ray Crystal Structure, Fluxional Behavior, and Reactivity

of a Bis(2-alkenyl)diisopropyloxytitanium(IV) Complex

A prerequisite for the rationalization of the regio- and

diastereoselectivities of the reactions of the amino- and iso-

propyloxytitanium complexes of the sulfonimidoyl-substi-

tuted allylic carbanions with aldehydes is the delineation

of their structures and dynamics. Despite the considerable

importance of (2-alkenyl)titanium(IV) complexes in stereo-

selective synthesis, knowledge about their structures and dy-

namics is scarce.^[2,10Ϫ12]Only very few (allyl)- and (crotyl)ti-

tanium(IV) complexes, where the allylic moieties have been

devoid of functional groups, have been isolated and charac-

terized by NMR spectroscopy^[76]and X-ray structure ana-

lysis.^[76e]The (allyl)titanium complexes show fluxional be-

havior due to a fast [1,3-C/C]-shift of the titanyl group. For

the (crotyl)titanium complexes, where the titanyl group is

bonded to the less substituted C atom, such a shift, al-

though highly likely, has not yet been demonstrated experi-

mentally. We have previously shown by NMR spectroscopy

that reaction of Li-E-4c with 1.2 equiv. of ClTi(NEt₂)₃at

Ϫ78

°C

in

THF

gives

the

mono(2-

alkenyl)tris(amino)titanium(IV) complex E-19a, while its

reaction with 1.2 equiv. of ClTi(OiPr)₃under the same con-

ditions affords the bis(2-alkenyl)dialkyloxytitanium com-

plex E-20a along with an equimolar amount of Ti(OiPr)₄

(Scheme 13).^[59b,77]A similar study of the titanation of Li-

E-4d and Li-E-4a with ClTi(OiPr)₃and ClTi(NEt₂)₃re-

vealed the formation of the complexes E-19b,c and E-20b,c

[ϩ Ti(OiPr)₄], respectively.^[78]The bis(alkenyl)titanium

complexes could also be obtained by using 0.5 equiv. of

Cl₂Ti(OiPr)₂.^[78]In view of these results, we believe that tit-

anation of lithiated allylic N-methylsulfoximines with

Scheme 13. Titanation of lithiated allylic N-methylsulfoximines

with ClTi(NEt₂)₃and ClTi(OiPr)₃

Scheme 14. LithiumϪtitanium exchange of α-sulfonyl carbanions

ClTi(OiPr)₃generally gives the corresponding bis(alkenyl)d- Li-XI with ClTi(OiPr)₃

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3983

H.-J. Gais et al.

FULL PAPER

¹H NMR spectroscopic investigations of E-19a in torted octahedral fashion (Figure 8). Most interestingly, the

[D₈]THF and [D₈]toluene at low temperatures showed it to allylic moieties in rac-γ,γ-20a·Et₂O are each bound to the

be a mixture of three rapidly equilibrating species in a ratio Ti atom in a bidentate fashion through C-1 and the N atom,

of approximately 30:3:1.^[77,81]Similar NMR analyses of E- but not through C-3 or the O atom. The C-1, O, and N

20aϪc in [D₈]THF and [D₈]toluene revealed in each case atoms of rac-γ,γ-20a·Et₂O are each arranged in a cis-fash-

the existence of two equilibrating bis(alkenyl)titanium com- ion around the Ti atom, thus giving this complex a cis,-

plexes, the rate of equilibration of which was found to de- cis,cis-configuration. The C-1 atoms of the enantiomer of

crease in the presence of ClTi(OiPr)₃.^[77,78]The preliminary rac-γ,γ-20a·Et₂O depicted in Figure 8, which exhibits a dis-

NMR data collected for the equilibrium components of E- torted tetrahedral coordination geometry, both have the

19a would seem to be compatible with mono(alkenyl)titan- (S)-configuration, while both S atoms have the (R) config-

ium complexes having an (E)-configured double bond and uration.^[82]Interestingly, the S-phenyl group and the di-

bearing the titanyl group at C-α or the N atom, but not at phenylvinyl group are oriented trans in relation to the four-

C-γ (vide infra). Equilibration of such complexes could oc- membered ring composed of the Ti, N, S, and C atoms.

cur by a [1,3-C/N]-shift of the titanyl group. However, the While one allylic moiety (A) features a short TiϪN bond

˚

presence of minute amounts of isomers of E-19a bearing of 2.09(1) A and a rather long TiϪC1 bond of 2.45(1) A,

the titanyl group at C-γ, which may equilibrate through a the other allylic moiety (B) is coordinated to the Ti atom

fast [1,3-C/C]-shift, cannot be excluded. The preliminary through TiϪC1 and TiϪN bonds of almost equal length

˚

NMR data collected for the equilibrium components of E- [2.21(1) and 2.29(2) A]. It is of interest to note that the

20aϪc would seem to be compatible with bis(alkenyl)titan- C1ϪTi bond trans to the O atom is the longest. In the case

ium complexes having an (E)-configured double bond and of the octahedral diorganotitanium complexes XII, which

the titanyl group at C-α and differing perhaps in the config- feature a similar bidentate coordination of the Ti atom by

uration at C-α and/or the Ti atom. Recently, Reggelin et al. the O atoms and the C-α atoms of the anions, but have the

have reported that the reactions of lithiated allyl and crotyl cis,trans,cis-configuration,

the

and

TiϪC-α

TiϪO

bonds

˚

N-(silyloxy)alkylsulfoximines with ClTi(OiPr)₃furnish [2.174(4)Ϫ2.251(6)

A]

the

bonds

[79,80]

˚

mono(alkenyl)tris(isopropyloxy)titanium and not bis(alken- [2.204(4)Ϫ2.278(2) A] are of almost uniform length.

yl)diisopropyloxytitanium complexes.^[2]However, the NMR The TiϪN bond lengths in rac-γ,γ-20a compare favorably

data did not allow a conclusion as to the configuration and well with those found in, e.g., bis(benzamidinato)dialkyltit-

dynamics of these titanium complexes. While we are still anium complexes.^[83]The C1ϪC2 and C2ϪC3 bond lengths

˚

engaged in structural studies of E-19aϪc and E-20aϪc, we in rac-γ,γ-20a·Et₂O [1.47(2)/1.46(2) and 1.31(2)/1.35(2) A]

have succeeded in isolating and structurally characterizing compare well with those observed in the (crotyl)titani-

the γ,γ-diphenyl-substituted bis(2-alkenyl)diisopropyloxy- um(IV)

titanium complex rac-γ,γ-20a (Scheme 15). Reaction of rac- CHMe)₃] [1.47 and 1.34 A (average)],

complex

[{Ti(η⁵-C₅Me₅)(µ-O)}₃(σ-CH₂CHϭ

[76e]

˚

and thus fall in

Li-6b with 1.1 equiv. of ClTi(OiPr)₃in diethyl ether at Ϫ78 the ranges for single and double bonds, respectively. How-

˚

°C with subsequent warming of the reaction mixture to ever, the TiϪCα bond in the latter complex [2.13 A (aver-

room temperature quantitatively afforded a mixture of the age)] is significantly shorter. Finally, comparison of the

bis(alkenyl)titanium complex rac-γ,γ-20a, the putative com- bond lengths in rac-γ,γ-20a·Et₂O, rac-Li-6b, and rac-6b

plex rac-γ,γ-20b, and Ti(OiPr)₄in a molar ratio of 1:1:2 (Table 6) reveals that the sulfonimidoyl-substituted allylic

(Scheme 15). Crystallization of this mixture from diethyl unit of the titanated species resembles more closely that of

ether furnished complex rac-γ,γ-20a·Et₂O as orange-red the carbon acid than that of the lithium salt.

1

crystals in 25% yield based on rac-Li-6b. According to the

The H and ¹³C NMR spectra (500 MHz and 125 MHz)

relevant NMR data, the use of enantiopure Li-6b as the of the cis,cis,cis-complex rac-γ,γ-20a·Et₂O in [D₈]THF at 25

starting material in the reaction with ClTi(OiPr)₃likewise °C feature only one set of signals for each of the diastereo-

afforded a mixture of complex γ,γ-20a, complex γ,γ-20b, topic allylic moieties and each of the diastereotopic isopro-

and Ti(OiPr)₄in a molar ratio of 1:1:2.

pyloxy groups. However, several signals show signs of

broadening at room temperature, and at Ϫ70 °C almost all

the signals are split into two signals of equal intensity. Co-

alescence phenomena are observed for the signals of the

allylic moieties as well as for those of the isopropyloxy

groups, thus suggesting a fluxional behavior of the complex.

According to the pattern of the signal sets of the two allylic

moieties of rac-γ,γ-20a, both are coordinated to the Ti atom

1

through C-1 and not through C-3. The H NMR signals of

Scheme 15. Synthesis of the bis(alkenyl)diisopropyloxytitanium

complex rac-γ,γ-20a

rac-γ,γ-20a were assigned with the aid of a COSY spectrum

recorded at Ϫ90 °C. A ROESY spectrum^[75]of rac-γ,γ-20a

X-ray structure analysis of rac-γ,γ-20a·Et₂O^[67]revealed in [D₈]THF at Ϫ90 °C showed no negative, off-diagonal

an asymmetric bis(2-alkenyl)diisopropyloxytitanium(IV) cross-peaks (Figure 9). Thus, no exchange of the allylic

complex, in which the Ti atom is coordinated by the two moieties occurred on the NMR time scale at this temper-

allylic moieties and the two isopropyloxy groups in a dis- ature. The observation of positive cross-peaks between the

3984

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

change of all ligands could occur through an intramolecular

mechanism encompassing two twists about two different

imaginary C₃axes via two six-coordinate trigonal prismatic

transition states TS1 and TS2 and the cis,trans,cis-config-

ured diastereomer (Figure 10). This twist mechanism does

not require the rupture of any of the TiϪO, TiϪC, or TiϪN

bonds.^[86]Such a mechanism is plausible considering the

exchange of unsymmetrical β-diketonate ligands in octa-

hedral bis(chelate) complexes of the type Ti(u-chel)₂X₂

(X ϭ Cl, Br, F, OR).^[85,87]However, because of the limited

data available at present, it cannot be ruled out that the

ligand exchange of rac-γ,γ-20a occurs through an alternat-

ive mechanism involving rupture of the TiϪN and/or TiϪC

bond(s) (vide infra) with generation of a five- or four-co-

ordinate intermediate. Indeed, the rather long TiϪC1(A)

bond in rac-γ,γ-20a could even be taken as an indication

that the cleavage of the TiϪC-α bond leading to formation

of a five-coordinate intermediate having an NϪTi-bonded

allylic aminosulfoxonium ylide as ligand (vide infra) may

be a facile process. The latter mechanistic scenario would

imply that the C-1 atoms of rac-γ,γ-20a are configura-

tionally labile, and that their configuration is determined by

that of the S atom. The observed relative configuration,

Figure 8. Crystal structure of the bis(alkenyl)diiso-

propyloxytitanium complex rac-γ,γ-20a·Et₂O (the ether molecule

and the H atoms have been omitted for the sake of clarity); selected

˚

bond lengths [A] and bond angles [°]: TiϪC1A 2.447(13), TiϪC1B

2.292(15), TiϪN1A 2.09(1), TiϪN1B 2.21(1), C1AϪC2A 1.47(2),

C1BϪC2B 1.46(2), C2AϪC3A 1.31(2), C2BϪC3B 1.35(2),

S1AϪC1A 1.71(1), S1BϪC1B 1.74(1); C1AϪTiϪN1A 64.9(4),

C1BϪTiϪN1B 65.9(5), N1AϪTiϪN1B 90.1(5), C1AϪTiϪC1B

101.0(5), S1AϪC1AϪC2A 115.0(9), TiϪC1AϪS1A 87.6(5),

TiϪC1AϪC2A 124.3(9), S1BϪC1BϪC2B 115(1), TiϪC1BϪS1B

119(1), TiϪC1BϪC2B 90.2(6)

˚

Table 6. Selected bond lengths [A] in rac-γ,γ-20a·Et₂O, rac-Li-6b,

and rac-6b

Bond

rac-γ,γ-20a·Et₂O

rac-Li-6b

rac-6b

C1ϪC2

C2ϪC3

SϪC1

SϪPh

SϪN

1.47(2)/1.46(2)

1.31(2)/1.35(2)

1.71(2)/1.74(1)

1.78(2)/1.80(2)

1.53(1)/1.54(1)

1.447(9)/1.438(9)

1.402(5)

1.375(4)

1.659(3)

1.798(3)

1.526(3)

1.456(2)

1.494(5)

1.336(4)

1.773(4)

1.792(4)

1.506(3)

1.451(3)

SϪO

signals of the two isopropyloxy groups and the two allylic

moieties of rac-γ,γ-20a proves unequivocally that the new

sets of signals observed at low temperatures belong to one

species and not to two equilibrating diastereomers. The fur-

ther ROESY data of rac-γ,γ-20a point to a close similarity

between its structure in solution and that in the crystal.

Based on the coalescence of the NMe signals in the ¹H

NMR spectrum (500 MHz), a ∆G^϶₂₃₃value of 47.3 Ϯ 1.3 kJ/

mol was estimated^[72]for the exchange of the allylic moieties

at the coalescence temperature. A similar barrier has been

determined for the exchange of symmetrical diketonate li-

gands in octahedral titanium(IV) complexes of the type

Ti(chel)₂(OR)₂.^[84,85]The NMR data of rac-γ,γ-20a show

unequivocally that the exchange of the allylic moieties pro-

Figure 9. ROESY spectrum of the bis(alkenyl)diiso-

propyloxytitanium complex rac-γ,γ-20a in [D₈]THF at Ϫ90 °C;

filled spots indicate positive and unfilled spots negative signals; sig-

ceeds under retention of the configuration at C-1. The ex- nals marked with * are due to diethyl ether and/or [D₈]THF

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3985

H.-J. Gais et al.

FULL PAPER

R_S,S_C, would be in accordance with this line of thought ured allylic sulfoximines rac-epi-17b and rac-17b in a ratio

since it has the vinylic group and the S-phenyl group in the of 68:32 in 67% chemical yield (Scheme 16). The allylic sul-

thermodynamically more stable trans position.

foximine rac-6a was recovered in 28% yield. An increase in

the chemical yield of rac-epi-17b and rac-17b (69:31) to 79%

was observed when, in the above experiment, the temper-

ature of the reaction mixture was gradually allowed to in-

crease from Ϫ78 °C to ambient. Likewise, the reaction of a

1:1 mixture of the complexes rac-γ,γ-20a and rac-γ,γ-20b,

admixed with Ti(OiPr)₄, with propanal at Ϫ78 °C in THF

reached 72% completion and afforded a mixture of rac-epi-

17b and rac-17b in a ratio of 69:31 in 51% chemical yield.

No difference in reactivity was seen between the racemic

and enantiopure complexes. This was demonstrated by the

fact that starting from 6b and rac-6b, the reactions fur-

nished a mixture of epi-17b and 17b in a ratio of 69:31 in

52% chemical yield, and a mixture of rac-epi-17b and rac-

17b in a ratio of 69:31 in 52% chemical yield, respectively.

Crystallization of the former mixture afforded diastereop-

ure epi-17b in 38% yield. These results show that the bis(al-

kenyl)diisopropyloxytitanium complexes derived from Li-

6b, γ,γ-20a, and γ,γ-20b, react with propanal in the same

way as the bis(alkenyl)diisopropyloxytitanium complex de-

rived from Z-Li-4c (cf. Scheme 5) and the mono(alkenyl)-

tris(diethylamino)titanium complex derived from Li-6b (cf.

Scheme 11), with high regioselectivity at the α-position.

However, the facial selectivity of the aldehyde towards the

aminotitanium complex is much higher than that towards

Figure 10. Putative twist mechanism of the ligand exchange of rac-

γ,γ-20a (transition states TS1 and TS2 are not shown); the diastere-

otopic bidentate ligands are symbolized with CʝN and C*ʝN*,

and the diastereotopic isopropyloxy groups with O and O*; the

complexes are viewed along the imaginary C₃axis about which the

twist is performed; the lower face of the octahedron (dotted bonds)

is twisted with respect to the upper face (bold bonds), which is

thought of as remaining constant

We have so far been unable to isolate the putative com- the isopropyloxytitanium complexes.

plex rac-γ,γ-20b. The incomplete NMR data set obtained

for rac-γ,γ-20b in the mixture with rac-γ,γ-20a and

Ti(OiPr)₄may also be compatible with a structure differing

from rac-γ,γ-20a in the configuration at the Ti atom or/and

1

at C-α. Although H NMR spectroscopy (500 MHz) of a

mixture of rac-γ,γ-20a and rac-γ,γ-20b [D₈]THF in the pres-

ence of Ti(OiPr)₄at 25 °C gave no indication (line

Scheme 16. Reaction of the bis(alkenyl)diisopropyloxytitanium

broadening) of an equilibrium between the two com-

plexes,^[77]a re-examination of a sample of pure rac-γ,γ-

20a·Et₂O in [D₈]THF, which had been kept at room temper-

ature in a sealed NMR tube for 12 d, revealed the formation

of up to 20% of rac-γ,γ-20b besides other unidentified prod-

ucts.^[77]NMR saturation-transfer experiments^[88]at 25 °C

showed a slow exchange between the isopropyloxy groups

of Ti(OiPr)₄and those of rac-γ,γ-20a and rac-γ,γ-20b,^[78]

which was, however, much faster in the case of rac-γ,γ-20b.

Unfortunately, similar saturation-transfer experiments with

the allylic moieties of the two complexes were unsuccessful

because of signal overlap.

The six-coordinate bis(alkenyl)complex rac-γ,γ-20a can

exist in eight diastereomeric forms, not counting those that

are possible by changing the configurations at C-α and the

S atom. However, within the limits of detection, the low-

temperature NMR spectra of the cic,cis,cis-complex rac-γ,γ-

20a gave no indication of an equilibrium with other diaster-

eomers.

complex rac-γ,γ-20a with propanal

The configuration of epi-17b was confirmed by X-ray

structure analysis (Figure 11).^[67]In the crystal, epi-17b ex-

hibits an intramolecular hydrogen bond between the hy-

droxy group and the N atom incorporated in a six-mem-

bered ring. The ethyl group is in a pseudoequatorial posi-

tion, while the vinylic and S-phenyl groups are in pseudoax-

ial positions. According to NOE experiments and in view

of the magnitude of the coupling constants ³J(α-H,β-H)

3

and J(β-H,γ-H), in solution epi-17b also preferentially ad-

opts such a hydrogen-bond stabilized conformation.

Attempted Rationalization of the Regio- and

Stereoselectivities of the Titanium Complexes

Mono(alkenyl)tris(diethylamino)titanium Complexes

Finally, it was of interest to determine the reactivity of

The selectivities of the reactions of the mono(alkenyl)tris-

rac-γ,γ-20a·Et₂O towards aldehydes. Treatment of a solu- (diethylamino)titanium complexes of acyclic and cyclic al-

tion of the pure complex rac-γ,γ-20a in THF at Ϫ78 °C lylic sulfoximines (cf. Schemes 13 and 15) with aldehydes

with propanal gave a mixture of the anti- and syn-config- can be summarized as follows:

3986

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

equilibria between the complexes is fast relative to the time

scale of their reactions with aldehydes. Thirdly, the reac-

tions of the titanium complexes with aldehydes proceed

through cyclic six-membered transition states. On the basis

of these assumptions, the following proposals are made:

Complex 19A reacts preferentially via the chair-like trans-

ition state TS19A, in which the sulfoximine N atom is co-

ordinated to the six-coordinate Ti atom, to give the anti-

configured γ-adduct Ti-7, while 19B reacts preferentially via

the chair-like transition state TS19B, having a five-coordin-

ate Ti atom, to furnish the syn-configured α-adduct Ti-10

(Scheme 18). Transition states TS19A and TS19B are of

similar energy in the case of small groups R¹and R³and

when the CC double bond has the (E) configuration. Hence,

Ti-7 and Ti-10 will be formed with low regio- but high dias-

tereoselectivities. In cases where the groups R¹and R³are

sterically more demanding, and the double bond has either

Figure 11. Crystal structure of sulfoximine epi-17b (some H atoms

have been omitted for the sake of clarity); selected bond lengths

˚

[A]: SϪN 1.537(6), SϪO 1.453(5), SϪC 1.812(7), SϪPh 1.780(6)

(a) The (E)-configured complexes E-19 react with high the (Z)-configuration or bears two substituents at the γ-

diastereoselectivities at both the α- and γ-positions to give position, transition state TS19A is less favorable as a result

the (E)-syn-configured α-adduct E-10 and the (Z)-anti-con- of destabilizing steric interactions and transition state

figured γ-adduct 7, respectively. The regioselectivity is TS19B is preferred. Consequently, Ti-10 and Ti-17 are

strongly dependent on the size of the aldehyde and of the formed with high regio- and diastereoselectivities. Complex

substituent at the CC double bond. Except in cases where epi-19A is less reactive than complex 19A because in the

both are small, the reaction occurs with high selectivity at transition state TSepi19A, in which the sulfoximine N atom

the α-position. The (S)-configuration of the sulfonimidoyl is also coordinated to the six-coordinate Ti atom, the

group in the starting allylic sulfoximine leads to a Si,Si pro- phenyl group is in the sterically hindering endo position,

cess in the α-hydroxyalkylation and a Re,Re process in the whereas in transition state TS19A it is in the sterically non-

γ-hydroxyalkylation.

hindering exo position. The fact that no Ti-21 was formed

(b) The (Z)-configured complexes Z-19 and the γ,γ-di- is in accordance with these assumptions and proposals. The

substituted complexes γ,γ-19 react with high regio- and dia- regio- and stereoselectivity of the reaction of the diethylam-

stereoselectivities at their α-positions, irrespective of the size inotitanium complex derived from the cyclic carbanion Li-

of the reactants, to give the corresponding (Z)-syn-config- 15 with aldehydes could also be rationalized as outlined in

ured α-adduct Z-10 and the syn-configured α-adduct 17, Scheme 17.

respectively. The (S)-configuration of the sulfonimidoyl

group in the starting allylic sulfoximine leads to a Si,Si pro-

cess, and the configuration at the double bond in the start-

ing material is retained.

(c) The reactions of complexes E-19, Z-19, and γ,γ-19 are

equally fast.

(d) The titanium complex derived from the cyclic allylic

sulfoximine 15 reacts with high diasteroselectivities at both

the α- and γ-positions to give the syn-configured α-adducts

18 and the (Z)-anti-configured γ-adducts 16. The regioselec-

tivity depends on the size of the aldehyde. Except with small

aldehydes, reaction occurs with high selectivity at the α-po-

Scheme 17. (L ϭ NEt₂) Alleged dynamic behavior of the mono(alk-

sition. The (S)-configuration of the sulfonimidoyl group in

enyl)tris(amino)titanium complexes 19

15 leads to a Si,Si process.

For the rationalization of the regio- and stereoselectivities

of the reactions of the mono(alkenyl)aminotitanium com-

The two key assumptions expressed in Schemes 17 and

plexes E-19, Z-19, and γ,γ-19 with aldehydes, we make the 18 are the existence of configurationally and constitution-

following assumptions, which are mainly based on the ally labile complexes 19A, epi-19A, and 19B, and the stereo-

results of a variable-temperature NMR study of E-19a selectivity of the hydroxyalkylation thus being dependent

and the crystal structure of rac-γ,γ-20a·Et₂O. Complex only on the configuration of the sulfonimidoyl group. The

19 is an equilibrium mixture of the Cα-titanium complexes key complex 19B may be regarded as an (N-titanyl-N-

19A and epi-19A and the N-titanium complex 19B methylamino)sulfoxonium ylide. (N,N-Dialkylamino)sul-

(Scheme 17). Secondly, the reactions of 19A, epi- foxonium ylides bearing alkyl groups at C-α are synthetic-

19A, and 19B with aldehydes are governed by the ally well-established stable S-ylides, which are endowed with

CurtinϪHammett principle,^[89]i.e. the establishment of the a high reactivity towards aldehydes.^[2,90]An efficient stabil-

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3987

H.-J. Gais et al.

FULL PAPER

lylic N-methyl-S-phenylsulfoximine in the crystal and for

the free counterion of an allylic N-methyl-S-phenylsulfoxi-

mine by ab initio calculations.^[18]According to the calcula-

tions, in this conformation the anion gains an additional

stabilization through an n_C-σ*_SPhinteraction. In addition,

experiment and calculation show that allylic sulfonimidoyl

carbanions have a low CαϪS rotational barrier and thus a

low configurational stability at C-α, even at low temper-

atures. Although, the CαϪS rotational barrier for 19B is

not known, it may well be that the allylic ylide also has a

low configurational stability at C-α. Further possible equi-

librium species of 19 not discussed thus far are the four-

coordinate Cγ-titanium complexes 19C and epi-19C (cf.

Scheme 17), derived from 19A and epi-19A by a [1,3-C/C]-

shift. These complexes could, in principle, also react with

aldehydes to give the α-adducts Ti-10 and Ti-17. Although

not observed by low-temperature NMR spectroscopic ana-

lysis of E-19a, the presence of 19C and epi-19C as minor

equilibrium components cannot be excluded. Such a fast

[1,3-C/C]-shift has been proposed for sulfenyl-substituted

(2-alkenyl)titanium complexes in order to rationalize the

observed dependence of the regioselectivity of hydroxyalk-

ylation on the structure of the allylic moiety.^[92]However, as

yet there is no direct experimental proof for such fluxional

behavior of these S-substituted titanium complexes.^[93]For

the reactions of 19C and epi-19C with aldehydes, a chair-

like transition state of type TS19C or the corresponding

boat-like transition state (not shown) would have to be con-

sidered (cf. Scheme 18). However, it is difficult to see why

in the case of sterically demanding groups R¹and R³, a

Scheme 18. (L ϭ NEt₂) Attempted rationalization of the selectivit-

ies of the reaction of mono(alkenyl)tris(amino)titanium complexes

19 with aldehydes

ization of the negative charge on 19B should not only be (Z)-configured double bond, and a γ,γ-disubstituted double

provided by the group [PhS(O)(N(Me)TiL₃)]^ϩ, but also by bond, where exclusive α-attack leading to highly selective

allylic delocalization. The efficiency with which the dialkyl- formation of the syn-adducts was observed, these transition

substituted group [PhS(O)(NR₂)]^ϩstabilizes a carbanion is states should be preferred to such an extent over TS19A.

illustrated by a pK_avalue of 14.4 for the (dimethylamino)- Similar arguments can be put forward in the case of the

methylphenylsulfoxonium cation, [PhS(O)(NMe₂)Me]^ϩ.^[90f]transition state TSepi19C. It seems interesting to note in

The isomeric ylides containing the group [Ph(SOR)(NR)]^ϩthis context that the α-attack of aldehydes on the above

are not known. Thus, we believe that the structure of 19B, discussed sulfenyl-substituted (2-alkenyl)titanium com-

in which the titanyl group is bonded to the N and not to plexes, where the existence of a γ-isomer of type 19C as an

the O atom, should be more stable. This would be consist- equilibrium component has been held responsible for the

ent with the bonding situation in the complex rac-γ,γ- formation of the corresponding α-hydroxyalkyl deriva-

20a·Et₂O. The [1,3-C/N]-shift of the titanyl group of 19A tive,^[10e]is highly anti- but not syn-selective as in the case

could occur via the four-membered transition state TS19, a of 19.

model for which may be seen in the complex rac-γ,γ-

20a·Et₂O, where the allylic moieties are coordinated to the

Ti atom through C-α and the N atom. A further key as- Bis(alkenyl)diisopropyloxytitanium Complexes

sumption inherent in Scheme 18 is the involvement of cyclic

six-membered transitions states of the type depicted. While

The selectivities of the reactions of the bis(alkenyl)diisop-

the evidence for the existence of such transition states is ropyloxytitanium complexes of acyclic and cyclic allylic sul-

only circumstantial^[2,10e]and cyclic four-membered trans- foximines (cf. Schemes 13 and 15) with aldehydes can be

ition states^[10c,64,91](S_Ereaction) must, in principle, also be summarized as follows:

considered, they have regularly been invoked with much

(a) The (E)-configured complexes E-20 react with high

success for the rationalization of the regio- and stereoselect- regio- and diastereoselectivities at the γ-position, irrespect-

ivities of reactions of allylic titanium reagents. Transition ive of the size of the aldehyde and the substituent at the CC

state TS19B features a CαϪS conformation of the ylide, in double bond, with formation of the γ-adducts 7. The (S)-

which the lone-pair orbital at C-α is periplanar to the SϪPh configuration of the sulfonimidoyl group in the starting al-

bond. Such a conformation has been found for the anion lylic sulfoximine leads to a Re,Re process. At low temper-

of the solvent-separated contact ion-pair of a lithiated al- atures, only one allylic moiety of E-20 is transferred with

3988

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

high γ- and (E)-anti-selectivities. The second allylic moiety is tural information gained in the case of rac-γ,γ-20a, know-

transferred at ambient temperatures with high α-selectivity. ledge of the structure and dynamics of the bis(alkenyl)titan-

However, the stereoselectivity is high only with regard to C- ium complexes 20 is meagre. Hence, it cannot be excluded

α, which bonds to the aldehyde in a Re process. In the pres- that, for example, complexes 20 are configurationally and

ence of one equivalent of ClTi(OiPr)₃, however, both allylic constitutionally more stable than 19, and that the selectivit-

moieties of E-20 are transferred at low to ambient temper- ies of their hydroxyalkylation are determined by the regio-

atures with high γ- and (E)-anti-selectivities to yield 7.

and diastereoselectivity of the titanation of the starting

(b) The (Z)-configured complexes Z-20 react with low lithiated allylic sulfoximine, both of which might be high.

diastereoselectivities at the α- and γ-positions to yield the Considering this scenario, the reactivity of the bis(alkenyl)-

corresponding (E)-anti- and (E)-syn-configured γ-adducts titanium complexes may be partly rationalized by making

and the (Z)-syn- and (Z)-anti-configured α-adducts, re- the following proposals: Complex E-20 (R¹ϭ alkyl, R²ϭ

spectively. The regioselectivity depends on the size of the H), having a similar structure as rac-γ,γ-20a (R¹ϭ R²ϭ

substituent at the CC double bond. In the case of large Ph), reacts with the aldehyde via transition state TS22 to

substituents, only α-hydroxyalkylation occurs. However, in yield the (2-alkenyl)titanium complex 24 incorporating 7 as

cases where the sulfonimidoyl group has the (S)-configura- a ligand. While intermediate 24 is attacked at C-γ by a se-

tion, the diastereoselectivity is high only with regard to C- cond molecule of the aldehyde in the presence of

α, which bonds to the aldehyde in a Re process. Complexes ClTi(OiPr)₃to yield two molecules of the γ-adduct 7, in

Z-20 react much more slowly than the isomeric complexes the absence of the titanium reagent attack occurs at the α-

E-20.

position to ultimately afford the α-adducts 10 and epi-10

(c) The γ,γ-disubstituted complexes γ,γ-20 react with besides the γ-adduct 7. Although the role of the chlorotitan-

high selectivities at the α-position. However, in cases where ium reagent has not yet been elucidated, one mode of ac-

the sulfonimidoyl group has the (S)-configuration, the dias- tion might involve its coordination to one of the sulfonimi-

tereoselectivity is high only with regard to C-α, which doyl groups of 24, thereby generating a free coordination

bonds to the aldehyde in a Re process.

side at the Ti atom. Complexes Z-20 (R¹ϭ H, R²ϭ Me,

(d) The titanium complex derived from the cyclic allylic Et) bearing one small group at the γ-position may react via

sulfoximine 15 reacts with high γ-selectivity and high dias- a transition state similar to TS22, but having the sulfonimi-

tereoselectivity to give the (Z)-anti-configured γ-adducts 16. doyl group in an equatorial position, the group R²in an

The (S)-configuration of the sulfonimidoyl group in 15 axial position, and the group R³in either an equatorial or

leads to a Re,Re process.

axial position, to finally afford a mixture of 8 and 9 (cf.

The reactions of the six-coordinate bis(alkenyl)isopropyl- Scheme 5). Secondly, because of steric hindrance, complexes

oxytitanium complexes E-, Z-, and γ,γ-20 and those derived Z-20 (R¹ϭ H, R²ϭ iPr) and γ,γ-20 (R¹ϭ R²ϭ alkyl,

from Li-15 with aldehydes are more complicated and thus aryl) bearing either one large group or two groups at the γ-

more difficult to rationalize than those of 19 because of the position would react with the aldehyde not at the γ-position

presence of two allylic moieties. These are expected to be but via transition state TSepi23 at the α-position to give the

transferred in a stepwise manner. Thus, six-coordinate (2-alkenyl)titanium complex epi-25 incorporating epi-10 or

mono(alkenyl)diisopropyloxytitanium complexes of types epi-17b as a ligand. Transition state TSepi23 would arise in

24, epi-25, and 25, where the Ti atom bears a vinylic or an S_Ereaction of Z-20 and γ,γ-20 involving a frontside at-

allylic hydroxy sulfoximine as a ligand, have to be consid- tack of the aldehyde at the TiϪCα bond, which would thus

ered as reactive intermediates (Scheme 19). An indication proceed under retention of configuration at C-α. In the fi-

of the formation of such intermediates may be seen in the nal step, intermediate epi-25 would combine with a second

noteworthy results obtained with E-20 in the presence and molecule of the aldehyde in a similar S_Ereaction to give

absence of ClTi(OiPr)₃at low and ambient temperatures two molecules of the α-adduct. Because of similar steric in-

(vide supra). It is remarkable that E-20 and the mono(alk- teractions between the group R³and the allylic moiety in

enyl)isopropyloxytitanium complexes 24 derived therefrom TSepi23 and between the group R³and the vinylic group

both react with aldehydes with similarly high γ- and anti- in TS23, the transition states are similar in energy and the

selectivities, at least in cases where only the γ-adduct is facial selectivity of the aldehyde is thus low, leading to mix-

formed. Moreover, it is striking that in all reactions of com- tures of epi-10 and 10 or epi-17b and 17b.

plexes 20 with aldehydes, the (S)-configuration of the sul-

It has already been stated in the introductory section that

fonimidoyl group in the starting allylic sulfoximine leads to the titanation of lithiated cyclic and acyclic allylic sulfoxim-

a Re process at C-α and to a Si process at C-γ. While some ines bearing a chiral (silyloxy)alkyl group at the N atom

aspects of the transfer of the first allylic moiety in the reac- (Scheme 20) with ClTi(OiPr)₃furnishes (2-alkenyl)titanium

tion of 20 with aldehydes may be rationalized by making complexes, which react with aldehydes with high anti-(Z)-

similar assumptions and proposals as in the case of 19 (cf. stereoselectivity exclusively at the γ-position.^[11,12,30]How-

Schemes 17 and 18), other aspects can not. For example, ever, besides Li-XIII, no further lithiated acyclic allylic sulf-

the invariance of the regioselectivity of the γ-hydroxyalkyl- oximines of this type have been investigated. Thus, little

ation of E-20 using a variety of groups R¹and R³and the can be said at present concerning the dependence of the

low facial selectivity of the aldehyde in the reactions of Z- regioselectivity of the hydroxyalkylation on the substituents

20 and γ,γ-20 fall into the latter category. Despite the struc- on the allylic moiety and the configuration at the double

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3989

H.-J. Gais et al.

FULL PAPER

saturation of the coordination sphere of the Ti atom by the

O atom of the substituent at the N atom. Although the

dynamic behavior of the titanium complexes derived from

Li-XIII is not known at present, it has been suggested that

it is the complex XIV having the S_Cα,R_Sconfiguration that

reacts with the aldehyde through a transition state of type

TS19A to give the γ-hydroxyalkylation product.^[2]

Conclusion

Cyclic and acyclic allylic N-methylsulfoximines are read-

ily accessible in good yields from aldehydes or ketones and

sulfoximines 1 or ent-1 by the AEI route. Whereas this route

is unproblematic in the case of symmetrical ketones, with

aldehydes and acyclic unsymmetrical ketones mixtures of

the (E)- and (Z)-configured allylic sulfoximines are ob-

tained, which necessitates a chromatographic separation. Of

synthetic advantage, however, is the fact that by judicious

choice of the reaction conditions, the (E)- and (Z)-config-

ured acyclic allylic sulfoximines can each be obtained as the

major isomer.

Titanation of lithiated allylic N-methylsulfoximines with

ClTi(OiPr)₃gives the corresponding bis(2-alkenyl)diisopro-

pyloxytitanium(IV) complexes, while that with ClTi(NEt₂)₃

yields the corresponding mono(2-alkenyl)tris(diethylamino)-

titanium(IV) complexes. Reaction of the bis(alkenyl)iso-

propyloxytitanium complexes of acyclic and cyclic allylic

N-methyl sulfonimidoyl carbanions with aldehydes in the

presence of one equivalent of ClTi(OiPr)₃furnishes δ-sul-

fonimidoyl-substituted anti-configured homoallylic alco-

hols in good yields with high selectivities, whereas the reac-

tion of the corresponding mono(alkenyl)diethylaminotitan-

ium complexes gives the isomeric β-sulfonimidoyl-substi-

tuted syn-configured homoallylic alcohols, also in good

yields and with high selectivities. The only exception to this

rule is the reaction of the mono(crotyl)aminotitanium com-

plex with ethanal, which proceeds with low regioselectivity.

It is noteworthy that the bis(alkenyl)isopropyloxytitanium

complexes and the corresponding mono(alkenyl)diethylami-

notitanium complexes give the same α- and γ-adducts and

show similarly high stereoselectivities.

Scheme 19. (L ϭ OiPr, R ϭ Me) Attempted rationalization of the

selectivities of the reaction of the bis(alkenyl)diisopropyloxytitan-

ium complexes 20 with aldehydes

The determination of the structure of rac-γ,γ-20a, the

first C-functionalized allylic titanium(IV) complex to be

structurally characterized, revealed a bis(2-alkenyl)diisopro-

Scheme 20. (R¹ϭ H, Me; R²ϭ SitBuMe₂) Lithiated and titanated

allylic sulfoximines having a (silyloxy)alkyl substituent at the N pyloxytitanium complex with a distorted octahedral coor-

atom

dination geometry, where the allylic moieties are bound via

their C and N atoms to the Ti atom and undergo rapid

bond. Recently, Reggelin et al. reported that the reaction of topomerization with retention of the configuration at C-α.

Li-XIII with ClTi(OiPr)₃furnishes the mono(2-alkenyl)tit-

Although a considerable body of indirect and direct in-

anium complexes XIV rather than the bis(2-alkenyl)titan- formation has been gathered on the structure of the tita-

ium complexes XV and provided selected room temperature nium complexes of allylic N-methylsulfonimidoyl car-

NMR spectroscopic data for XIV in the case of R¹

ϭ

banions, further structural studies are clearly required be-

H.^[2,94]The apparently different reactivity of the N-methyl fore a less speculative rationalization of the regio- and ste-

sulfoximines Li-4 and the N-(silyloxy)alkyl sulfoximines Li- reochemistry of their reactions with aldehydes can be

XIII towards ClTi(OiPr)₃was attributed to an inhibition of proposed. The origin and the mechanism of the dynamic

the formation of XV from XIV^[95]due to an intramolecular phenomena observed and, in particular, the question of a

3990

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

[1,3-C/N]- and/or a [1,3-C/C]-shift of the titanyl group in Table 7. Crystal data and parameters of data collection for sulfoxi-

mines 7g and 7j

these titanium complexes need further clarification.

As anticipated, the substituted homoallylic alcohols II

7g

7j

and III represent interesting starting materials for the syn-

thesis of enantio- and diastereopure building blocks of

types IV؊VII (cf. Scheme 20). We and others have already

succeeded in the realization of transformations II Ǟ

IV,^[15,96]II Ǟ V,^[30][97]III Ǟ VI,^[98]and III Ǟ VII.^[34]

Formula

M_r

C₁₅H₂₃NO₂S

281.42

C₂₀H₂₅NO₂S

343.49

Color and habit

colorless, irregular

0.3 ϫ 0.3 ϫ 0.4

orthorhombic

P 2₁2₁2₁(19)

8.951(1)

9.846(2)

21.544(2)

90.0

Crystal size, ca. mm 0.5 ϫ 0.5 ϫ 0.5

Crystal system

orthorhombic

P 2₁2₁2₁(19)

9.1474(5)

12.8943(8)

13.7833(8)

90.0

Space group (No.)

˚

a [A]

˚

b [A]

˚

c [A]

Experimental Section

α [°]

β [°]

γ [°]

90.0

3

˚

General: All reactions were carried out in absolute solvents under

an argon atmosphere in oven-dried glassware using syringe and

Schlenk techniques. Solutions of titanium complexes for NMR

spectroscopic investigations were placed in oven-dried, argon-filled

NMR tubes, which were then sealed. THF and diethyl ether were

distilled under argon from potassium/benzophenone and sodium/

benzophenone, respectively, or from sodium/lead alloy. CH₂Cl₂and

MeCN were distilled from calcium hydride; toluene was distilled

V [A ]

1625.73

4

1898.71

Z

4

D_calcd[g cm^Ϫ3

]

1.150

1.202

µ [cm^Ϫ1

]

17.12

15.54

Diffractometer

T [°C]

CDA4 EnrafϪNoniusCDA4 EnrafϪNonius

25

Radiation

Cu-K_α

1.54179

graphite

Ω/2θ

Cu-K_α

1.54179

graphite

Ω/2θ

˚

λ [A]

Monochromator

Scan method

Θ_max[°]

from sodium. The titanium reagents ClTi(OiPr)₃,^[64,99]

75.2

3995

75.2

Cl₂Ti(OiPr)₂,^[99,100]and ClTi(NEt₂)₃

were prepared with No. of data colld.

9319

[101,102]

purities Ն96% (¹H NMR) according to literature procedures. En-

antiopure (ϩ)- and (Ϫ)-N,S-dimethyl-S-phenylsulfoximines were

prepared according to the literature.^[9,32,33]Ϫ TLC: Merck silica

gel 60 F₂₅₄plates. Ϫ Column chromatography: Merck silica gel 60

(0.063Ϫ0.200 mm). Ϫ MPLC: Kronwald, Merck LiChroprep Si 60

(15Ϫ25 µm). Ϫ HPLC: Merck Nova Prep 5000, Merck Hibar

LiChrosorb Si 60 (7 µm). Ϫ Melting points: Büchi apparatus, un-

corrected values. Ϫ Optical rotations: PerkinϪElmer model 241;

measurements were made at ca. 22 °C, specific rotations are in

grad ϫ mL/dm ϫ g, c in g/100 mL. Ϫ ¹H and ¹³C NMR: Varian

VXR 300, Varian Gemini 300, Varian Inova 400, and Varian Unity

500; peaks in the ¹³C NMR spectra are denoted as ‘‘u’’ for carbons

with zero or two attached protons or ‘‘d’’ for carbons with one or

three attached protons, as determined using the APT pulse se-

quence. Ϫ GC analyses: Chrompack CP-9000 (DB-5: 30 m ϫ

0.32 mm; 50 kPa H₂). Ϫ IR spectra: PerkinϪElmer PE 1759 FT,

only peaks of ν˜ Ͼ 700 cm^Ϫ1are listed. Ϫ GC-MS: Magnum Finni-

gan (HT-5: 25 m, 0.25 mm; 50 kPa He, CI, 40 eV, MeOH). Ϫ MS:

Varian MAT 212S (EI, 70 eV); other than the parent peak, only

peaks of m/z Ͼ 70 and with an intensity Ͼ 10% are listed. Ϫ Ele-

mental analyses: Microanalytical laboratories of the Institut für Or-

ganische Chemie and of the Institut für Anorganische Chemie,

RWTH Aachen. Ϫ The term ‘‘diastereopure’’ is used for cases

where no other diastereomer could be detected in the ¹H NMR

spectrum (Ն98% ds); cy ϭ chemical yield.

No. of unique data 3310

3929

Obsn. criterion

I Ͼ 2σ(I)

218

No. of params. refd. 173

No. of data obsd.

2162

2893

[a]

R, R_w

0.062, 0.062

Ϫ0.8/ϩ0.4

2.168

0.071, 0.068

Ϫ0.4/ϩ0.5

3.213

Ϫ3

˚

∆(ρ) [e A

]

GoF

R ϭ Σ| |F_o| Ϫ |F_c| |/Σ|F_o|; R_wϭ [Σw(|F_o| Ϫ |F_c|)²/Σw |F_o|²]^1/2; w ϭ

1/σ²(F_o), where F_oand F_care observed and calculated structure fac-

tors.

[a]

with equal population distribution. Molecular structures were visu-

alized with the program SCHAKAL 92.^[105]

(؉)-(E,S)-N-Methyl-S-(1-butenyl)-S-phenylsulfoximine (3a): To a

solution of 1 (10.26 g, 60.6 mmol) in THF (150 mL) at Ϫ78 °C was

added nBuLi (41.2 mL, 1.60  solution in hexane, 66 mmol). After

stirring the mixture for 30 min, propanal (4.8 mL, 66 mmol) was

added. The mixture was stirred for 2 h and then ClCOOMe

(5.1 mL, 66 mmol) was added. After allowing the mixture to warm

to room temperature, it was stirred for 1 h. It was then cooled to

Ϫ78 °C once more, whereupon DBU (10 mL, 66 mmol) was added,

which led to the deposition of a colorless precipitate. After allowing

the mixture to warm to room temperature over a period of 12 h, it

was treated with saturated aqueous NH₄Cl solution and extracted

with EtOAc. The combined organic phases were dried (MgSO₄)

and the solvent was removed in vacuo. Purification of the residue

by chromatography (EtOAc/hexane, 4:1) gave 3a (9.75 g, 78%) as a

colorless oil; [α]_Dϭ ϩ25.8 (c ϭ 1.00, CHCl₃). Ϫ ¹H NMR

(300 MHz, CDCl₃): δ ϭ 1.06 (t, J ϭ 7.4 Hz, 3 H, CH₃), 2.26 (qdd,

J ϭ 7.4, J ϭ 6.0, J ϭ 1.7 Hz, 2 H, CH₂), 2.73 (s, 3 H, NϪCH₃),

6.33 (dt, J ϭ 15.1, J ϭ 1.7 Hz, 1 H, 1-H), 6.92 (dt, J ϭ 15.1, J ϭ

6.0 Hz, 1 H, 2-H) 7.48Ϫ7.62 (m, 3 H, Ph), 7.84Ϫ7.90 (m, 2 H, Ph).

X-ray Analyses: The crystal data and the most salient experimental

parameters relating to the X-ray measurements and the crystal

structure analyses are reported in Table 7, Table 8, and Table 9. The

crystal structures of 7g, 7j, E-10i, Z-10e, 16c, 16d, and epi-17b were

solved using direct methods as implemented in the XTAL3.2 pack-

age of crystallographic routines.^[103]The crystal structure of rac-

γ,γ-20a·Et₂O was solved by direct methods using SHELX-86^[104]

and refined using XTAL3.2. The high R value and the relatively

high residual electron density of rac-γ,γ-20a are due to the poor

quality of the crystal, which stems in part from the co-crystalliza-

Ϫ

¹³C NMR (75 MHz, CDCl₃): δ ϭ 11.8 (d), 24.7 (u), 29.4 (d),

128.7 (d), 129.2 (d), 129.3 (d), 132.5 (d), 136.8 (u), 148.3 (d). Ϫ IR

(CHCl₃): ν˜ ϭ 2968 (m), 2934 (m), 2913 (m), 1628 (m), 1445 (s),

1288 (m), 1246 (s), 1150 (s), 1109 (m), 1081 (m), 1069 (m), 868 (m),

tion of the complex with one molecule of diethyl ether in the asym- 835 (m). Ϫ MS: m/z (%) ϭ 210 [M^ϩϩ 1] (2), 209 [M^ϩ] (11), 181

metric unit. Furthermore, interpretation of the structural para-

meters is hampered by the disorder of the two isopropyloxy groups,

which has been resolved in two isotropically refined components

(6), 154 (7), 126 (14), 125 (19), 109 (12), 107 (17), 106 (25), 97 (14),

84 (100), 78 (46), 77 (50). Ϫ C₁₁H₁₅NOS (209.3): calcd. C 63.12,

H 7.22, N 6.69; found C 63.01, H 7.46, N 6.97.

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3991

H.-J. Gais et al.

FULL PAPER

Table 8. Crystal data and parameters of data collection for sulfoximines Z-10e, E-10i, and 16c

Z-10e

E-10i

16c

Formula

M_r

C₁₄H₂₁NO₂S

267.39

C₁₇H₂₇NO₂S

309.47

C₁₈H₂₇NO₂S

321.49

Color and habit

Crystal size, ca. mm

Crystal system

Space group (No.)

colorless, irregular

0.5 ϫ 0.5 ϫ 0.5

monoclinic

P2₁(4)

colorless, irregular

0.3 ϫ 0.3 ϫ 0.5

monoclinic

P2₁(4)

colorless, irregular

0.3 ϫ 0.3 ϫ 0.3

orthorhombic

P2₁2₁2₁(19)

9.2016(4)

9.912(4)

19.062(1)

90.0

˚

a [A]

9.2125(4)

8.0612(4)

9.876(2)

90.0

5.767(1)

16.577(2)

10.265(1)

90.0

˚

b [A]

˚

c [A]

α [°]

β [°]

γ [°]

90.83(1)

90.0

106.043(8)

90.0

3

˚

V [A ]

733.35

943.07

1738.56

4

Z

2

D_calcd[g cm^Ϫ3

]

1.211

1.090

1.228

µ [cm^Ϫ1

]

18.74

15.11

16.57

Diffractometer

T [°C]

CDA4 EnrafϪNonius

Ϫ123

CDA4 EnrafϪNonius

25

CAD4 EnrafϪNonius

Ϫ123

Radiation

Cu-K_α

˚

λ [A]

1.54179

graphite

ω/2θ

1.54179

graphite

Ω/2θ

1.54179

graphite

ω/2θ

monochromator

scan method

Θ_max[°]

75.2

74.8

75.5

No. of data colld.

No. of unique data

Obsn. criterion

No. of params. refd.

No. of data obsd.

4841

8230

7992

1621

3891

3605

I Ͼ 2σ(I)

162

I Ͼ 2σ(I)

189

I Ͼ 2σ(I)

199

1597

3568

3491

[a]

R, R_w

0.077, 0.069

Ϫ1.24/ϩ1.27

2.128

0.055, 0.057

Ϫ0.3/ϩ0.3

2.909

0.067, 0.063

Ϫ1.68/ϩ0.96

2.220

Ϫ3

˚

∆(ρ) [e A

]

GoF

^[a]R ϭ Σ| |F_o| Ϫ |F_c| |/Σ|F_o|; R_wϭ [Σw(|F_o| Ϫ |F_c|)²/Σw |F_o|²]^1/2; w ϭ 1/σ²(F_o), where F_oand F_care observed and calculated structure factors.

Table 9. Crystal data and parameters of data collection for sulfoximines 16d, epi-17b, and rac-γ,γ-20a·Et₂O

16d

epi-17b

rac-γ,γ-20a·Et₂O

Formula

C₂₁H₂₅NO₂S

355.55

C₂₅H₂₇NO₂S

405.56

C₅₄H₆₄N₂O₅S₂Ti

933.15 (incl. Et₂O)

orange-red, irregular

0.3 ϫ 0.3 ϫ 0.3

monoclinic

P2₁/c (19)

21.62(2)

11.003(7)

21.680(9)

90.0

M_r

Color and habit

Crystal size, ca. mm

Crystal system

Space group (No.)

colorless, irregular

0.6 ϫ 0.4 ϫ 0.4

orthorhombic

P2₁2₁2₁(19)

5.8355(4)

11.352(1)

28.217(6)

90.0

colorless, irregular

0.3 ϫ 0.3 ϫ 0.3

orthorhombic

P2₁2₁2₁(19)

8.872(1)

15.110(1)

16.264(5)

90.0

˚

a [A]

˚

b [A]

˚

c [A]

α [°]

β [°]

γ [°]

90.0

99.70(2)

90.0

3

˚

V [A ]

1869.23

4

2180.37

4

5083.61

Z

4

D_calcd[g cm^Ϫ3

]

1.263

1.236

1.219

µ [cm^Ϫ1

]

15.97

14.31

25.44

Diffractometer

T [°C]

CAD4 EnrafϪNonius

Ϫ123

CDA4 EnrafϪNonius

Ϫ123

CDA4 EnrafϪNonius

Ϫ20

radiation

Cu-K_α

˚

λ [A]

1.54179

graphite

Ω/2θ

1.54179

graphite

ω/2θ

1.54179

Monochromator

Scan method

graphite

Ω/2θ

Θ_max[°]

75.2

75.5

55.1

No. of data colld.

No. of unique data

Obsn. criterion

No. of params. refd.

No. of data obsd.

4683

5267

7113

3869

2574

6777

I Ͼ 2σ(I)

226

I Ͼ 2σ(I)

262

I Ͼ 2σ(I)

538

3485

1881

3148

[a]

R, R_w

0.056, 0.065

Ϫ0.5/ϩ1.0

2.294

0.104, 0.056

1.67

0.100, 0.098

Ϫ1.5/ϩ1.2

2.488

Ϫ3

˚

∆(ρ) [e A

]

GoF

1.372

^[a]R ϭ Σ| |F_o| Ϫ |F_c| |/Σ|F_o|; R_wϭ [Σw(|F_o| Ϫ |F_c|)²/Σw |F_o|²]^1/2; w ϭ 1/σ²(F_o), where F_oand F_care observed and calculated structure factors.

3992 Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

idue by chromatography (EtOAc/hexane, 4:1) afforded a mixture of

2b and epi-2b (12.30 g, 99%, 70:30) as a colorless oil; [α]_Dϭ ϩ71.1

(c ϭ 1.91, MeOH).

Following the same procedure, but starting from rac-1, sulfoximine

rac-3a was prepared.

General Procedure for the Rearrangement of Vinylic to Allylic Sul-

foximines (GP1): A solution of the vinylic sulfoximine 3 (50 mmol)

in MeCN (150 mL) was treated with DBU (9.7 mL, 65 mmol) at

room temperature.

2b: ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.92 (t, J ϭ 7.0 Hz, 3 H,

CH₃), 1.30Ϫ1.63 (m, 4 H, CH₂), 2.62 (s, 3 H, NϪCH₃), 2.95 (dd,

J ϭ 13.6, J ϭ 1.0 Hz, 1 H, 1-H), 3.23 (dd, J ϭ 10.1, J ϭ 13.6 Hz,

1 H, 1-H), 4.49 (m, 1 H, 2-H), 5.8 (br. s, OH), 7.57Ϫ7.72 (m, 3 H,

Ph), 7.86Ϫ7.94 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ

13.8 (d), 18.2 (u), 29.0 (d), 38.6 (u), 62.2 (u), 65.0 (d), 129.1 (d),

129.7 (d), 133.3 (d), 138.0 (u).

Synthesis of Z-4 (GP1.1): Stirring of the aforementioned reaction

mixture at room temperature was continued until TLC of GC in-

dicated complete consumption of the starting material (approxim-

ately 15 h). Work-up as described below gave a mixture of Z-4 and

E-4, with the former being predominant.

epi-2b: ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.84 (t, J ϭ 7.0 Hz, 3 H,

CH₃), 1.30Ϫ1.63 (m, 4 H, CH₂), 2.70 (s, 3 H, NϪCH₃), 3.03 (dd,

J ϭ 14.1, J ϭ 1.7 Hz, 1 H, 1-H), 3.18 (dd, J ϭ 14.4, J ϭ 9.7 Hz,

1 H, 1-H), 3.85 (m, 1 H, 2-H), 5.8 (br. s, 1 H, OH), 7.57Ϫ7.72 (m,

3 H, Ph), 7.86Ϫ7.94 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ 14.2 (d), 18.2 (u), 29.0 (d), 38.5 (u), 61.5 (u), 65.7 (d), 129.5

(d), 129.7 (d), 133.4 (d), 137.0 (u). Ϫ MS: m/z (%) ϭ 241 [M^ϩ] (1),

194 (35), 156 (37), 155 (21), 154 (41), 126 (28), 125 (100), 107 (76),

106 (55), 105 (24), 98 (63), 97 (22), 78 (59), 77 (52). Ϫ C₁₂H₁₉NO₂S

(241.3): calcd. C 59.72, H 7.93, N 5.80; found C 59.78, H 8.44,

N 5.77.

Synthesis of E-4 (GP1.2): The temperature of the mixture obtained

according to GP 1.1 was increased to 60 °C and stirring was con-

tinued until the ratio of the (E) and (Z) isomers remained constant

(approximately 48 h). Diethyl ether (750 mL) was then added and

the mixture was washed with water (2ϫ), saturated aqueous NH₄Cl

solution, and 10% aqueous Na₂CO₃. The organic phase was dried

(MgSO₄) and concentrated in vacuo to give a mixture of E-4 and

Z-4, with the former being predominant. The isomers were separ-

ated by MPLC or HPLC.

(؉)-(E,S)- and (؉)-(Z,S)-N-Methyl-S-(2-butenyl)-S-phenylsulfoxi-

mine (E-4a and Z-4a): Treatment of 3a (6.90 g, 33 mmol) with DBU

according to GP1.1 and GP1.2 gave mixtures of E-4a and Z-4a in

ratios of 30:70 and 76:24, respectively, as colorless oils (6.55 g,

95%). Sulfoximines E-4a and Z-4a were isolated as colorless oils

by HPLC (EtOAc/cyclohexane, 7:1) of the latter mixture. Their

analytical data were identical to those reported in the literature.^[7]

(؉)-(E,S)-N-Methyl-S-(1-pentenyl)-S-phenylsulfoximine

(3b): To a solution of a 7:3 mixture of 2b and epi-2b (12.30 g,

51 mmol) in CH₂Cl₂(100 mL) at 0 °C were added dropwise NEt₃

(14.2 mL, 102 mmol) and MeSO₂Cl (6.2 mL, 66 mmol). The mix-

ture was stirred for 3 h at 0 °C, filtered, and DBU (9.9 mL,

66 mmol) was added to the filtrate. After stirring the resulting mix-

ture for 15 h at room temperature, diethyl ether (1200 mL) was ad-

ded, and the solution was washed with water (200 mL), saturated

aqueous NH₄Cl solution (200 mL), and 10% aqueous Na₂CO₃

(200 mL). The organic phase was dried (MgSO₄) and concentrated

in vacuo. Purification of the residue by chromatography (EtOAc/

hexane, 4:1) gave 3b (11.15 g, 98%), R_fϭ 0.42 (EtOAc/hexane, 4:1);

Following the same procedure, but starting from rac-3a, sulfoxim-

ines rac-E-4a and rac-Z-4a were obtained.

Synthesis of E-4a and Z-4a by the Shortened Route: To a solution

of 1 (24.0 g, 0.14 mol) in THF (250 mL) at Ϫ78 °C was added

nBuLi (97 mL, 1.60  solution in hexane, 0.16 mol). After stirring

the mixture for 30 min, propanal (11.2 mL, 0.16 mol) was added.

The mixture was stirred for 2 h and then ClCOOMe (12 mL,

0.16 mmol) was added. After warming the resulting mixture to

room temperature, it was stirred for 1 h. It was then cooled to Ϫ78

°C once more, whereupon DBU (27 mL, 0.18 mol) was added,

which led to the deposition of a colorless precipitate. After allowing

the mixture to warm to room temperature over a period of 12 h, it

was treated with half-saturated aqueous NH₄Cl solution and ex-

tracted with EtOAc. The combined organic phases were dried

(MgSO₄) and the solvent was removed in vacuo. The residue was

redissolved in acetonitrile (300 mL) and DBU (27 mL, 0.18 mol)

was added. After heating the mixture to 50 °C for 4 d, it was al-

lowed to cool to room temperature, treated with half-saturated

aqueous NH₄Cl, and extracted with EtOAc. The combined organic

phases were dried (MgSO₄) and the solvent was removed in vacuo.

Purification of the residue by chromatography (EtOAc/hexane, 4:1)

gave a mixture of E-4a and Z-4a (22.5 g, 76%) in a ratio of 70:30

as a colorless oil.

1

[α]_Dϭ ϩ6.9 (c ϭ 1.08, MeOH). Ϫ H NMR (300 MHz, CDCl₃):

δ ϭ 0.90 (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.48 (sext, J ϭ 7.4 Hz, 2 H, 4-

H), 2.20 (td, J ϭ 7.4, J ϭ 1.3 Hz, 2 H, 3-H), 2.74 (s, 3 H, NϪCH₃),

6.31 (dt, J ϭ 15.1, J ϭ 1.3 Hz, 1 H, 1-H), 6.85 (dt, J ϭ 15.1, J ϭ

6.7 Hz, 1 H, 2-H), 7.49Ϫ7.61 (m, 3 H, Ph), 7.88 (m, 2 H, Ph). Ϫ

¹³C NMR (75 MHz, CDCl₃): δ ϭ 13.6 (d), 21.0 (u), 29.4 (d), 33.4

(u), 128.7 (d), 129.3 (d), 130.3 (d), 132.5 (d), 139.6 (u), 146.7 (d).

Ϫ IR (neat): ν˜ ϭ 3060 (w), 2958 (s), 2929 (m), 2871 (m), 2803 (w),

1630 (w), 1466 (m), 1446 (s), 1382 (w), 1338 (w), 1246 (s), 1150 (s),

1109 (m), 1082 (m), 1069 (m), 969 (m), 866 (m), 812 (w), 752 (m).

Ϫ MS: m/z (%) ϭ 223 [M^ϩ] (20), 195 (19), 194 (55), 156 (17), 155

(19), 154 (49), 126 (27), 125 (59), 117 (14), 109 (18), 107 (57), 106

(59), 105 (19), 98 (100), 97 (17), 78 (59), 77 (50). Ϫ C₁₂H₁₇NOS

(223.3): calcd. C 64.54, H 7.67, N 6.27; found C 64.57, H 7.87,

N 6.43.

(؉)-(E,S)- and (؊)-(Z,S)-N-Methyl-S-(2-pentenyl)-S-phenylsulfoxi-

mine (E-4b and Z-4b): Treatment of 3b (11.15 g, 49.9 mmol) with

DBU according to GP1.1 and GP1.2 gave mixtures of E-4b and Z-

4b in ratios of 25:75 and 75:25, respectively, as colorless oils

(10.14 g, 91%). Sulfoximines E-4b and Z-4b were isolated as color-

less oils by HPLC (EtOAc/cyclohexane, 4:1) of the latter mixture.

(2R)- and (2S)-1-[(S)-N-Methyl-S-phenylsulfonimidoyl]pentan-2-ol

(2b and epi-2b): To a solution of 1 (8.63 g, 51 mmol) in THF

(120 mL) at Ϫ35 °C was added nBuLi (35.4 mL, 1.60  solution

in hexane, 57 mmol). The mixture was allowed to warm to room

temperature, then cooled to Ϫ78 °C, whereupon n-butanal (5.2 mL,

59 mmol) was added dropwise. After stirring the mixture for 2 h at

Ϫ78 °C, it was allowed to warm to room temperature. Stirring was

continued for 13 h at room temperature, and then the mixture was

poured into saturated aqueous NH₄Cl solution. The aqueous phase

was extracted with EtOAc and the combined organic phases were

dried (MgSO₄) and concentrated in vacuo. Purification of the res-

E-4b: R_fϭ 0.39 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ59.7 (c ϭ 1.51,

1

MeOH). Ϫ H NMR (300 MHz, CDCl₃): δ ϭ 0.87 (t, J ϭ 7.4 Hz,

3 H, CH₃), 1.98 (m, 2 H, 4-H), 2.72 (s, 3 H, NϪCH₃), 3.79 (d, J ϭ

6.1 Hz, 2 H, 1-H), 5.38 (dm, J ϭ 15.4 Hz, 1 H, 3-H), 5.47 (dd, J ϭ

15.4, J ϭ 5.5 Hz, 1 H, 2-H), 7.63Ϫ7.50 (m, 3 H, Ph), 7.80 (dt, J ϭ

6.4, J ϭ 2.0 Hz, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ

13.0 (d), 26.0 (u), 29.7 (d), 60.2 (u), 115.8 (d), 129.1 (d), 129.8 (d),

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3993

H.-J. Gais et al.

FULL PAPER

132.8 (d), 136.9 (u), 142.6 (d). Ϫ IR (neat): ν˜ ϭ 3060 (w), 2959 (s), (19.40 g, 76.0 mmol) in CH₂Cl₂(300 mL) at 0 °C were added drop-

2929 (s), 2871 (s), 2803 (m), 1662 (w), 1582 (w), 1465 (m), 1446 (s), wise NEt₃(21 mL, 158 mmol) and MeSO₂Cl (7.7 mL, 103 mmol).

1403 (m), 1376 (w), 1340 (w), 1247 (s), 1147 (s), 1108 (m), 1082 The mixture was stirred at this temperature for 3 h, and then DBU

(m), 970 (m), 922 (w), 873 (m), 858 (m), 769 (m), 738 (s). Ϫ MS:

(28.4 mL, 130 mmol) was added. After stirring the resulting mix-

m/z (%) ϭ 223 [M^ϩ] (2), 194 (100), 155 (22), 154 (61), 125 (48), 107 ture for 15 h at room temperature, diethyl ether (600 mL) was ad-

(50), 106 (49), 105 (21), 98 (16), 78 (55), 77 (38). Ϫ C₁₂H₁₇NOS ded and the solution was washed with water, saturated aqueous

(223.3): calcd. C 64.54, H 7.67, N 6.27; found C 64.18, H 7.79,

N 6.65.

NH₄Cl solution, and 10% aqueous Na₂CO₃. The organic phase

was dried (MgSO₄) and concentrated in vacuo. Purification of the

residue by chromatography (EtOAc/hexane, 4:1) gave 3c (16.10 g,

89%) as a colorless oil, R_fϭ 0.41 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ5.2

Z-4b: R_fϭ 0.41 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ59.5 (c ϭ 2.38,

1

MeOH). Ϫ H NMR (300 MHz, CDCl₃): δ ϭ 0.70 (t, J ϭ 7.4 Hz,

1

(c ϭ 1.58, MeOH). Ϫ H NMR (300 MHz, CDCl₃): δ ϭ 0.88 (d,

3 H, CH₃), 1.70 (m, 2 H, 4-H), 2.73 (s, 3 H, NϪCH₃), 3.91 (m, 2

H, 1-H), 5.41 (m, 1 H, 2-H), 5.65 (m, 1 H, 3-H), 7.51Ϫ7.64 (m, 3

H, Ph), 7.84 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ

13.4 (d), 20.6 (u), 29.7 (d), 55.0 (u), 115.3 (d), 129.1 (d), 129.8 (d),

132.8 (d), 137.0 (u), 140.5 (d). Ϫ IR (neat): ν˜ ϭ 3062 (w), 3020 (w),

2961 (s), 2930 (m), 2870 (m), 2803 (m), 1655 (w), 1582 (w), 1466

(m), 1446 (s), 1411 (w), 1393 (w), 1305 (w), 1246 (s), 1145 (s), 1107

(s), 1082 (m), 1019 (w), 999 (w), 906 (m), 855 (m), 793 (w), 758

(m), 718 (s). Ϫ MS: m/z (%) ϭ 223 [M^ϩ] (2), 194 (89), 156 (42),

155 (28), 154 (100), 125 (58), 107 (59), 106 (70), 105 (32), 98 (21),

97 (14), 78 (61), 77 (52). Ϫ C₁₂H₁₇NOS (223.3): calcd. C 64.54, H

7.67, N 6.27; found C 64.19, H 7.89, N 6.56.

J ϭ 6.4 Hz, 3 H, CH₃), 0.90 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.76 [sept,

J ϭ 6.7 Hz, 1 H, CH(CH₃)₂], 2.10 (td, J ϭ 7.4, J ϭ 1.3 Hz, 2 H,

3-H), 2.74 (s, 3 H, NϪCH₃), 6.31 (dt, J ϭ 15.1, J ϭ 1.3 Hz, 1 H,

1-H), 6.83 (dt, J ϭ 15.1, J ϭ 7.4 Hz, 1 H, 2-H), 7.50Ϫ7.60 (m, 3 H,

Ph), 7.88 (dt, J ϭ 6.4, J ϭ 2.0 Hz, 2 H, Ph). Ϫ ¹³C NMR (75 MHz,

CDCl₃): δ ϭ 22.2 (d), 22.3 (d), 27.7 (d), 29.4 (d), 40.6 (u), 128.6

(d), 129.3 (d), 131.0 (d), 132.5 (d), 139.5 (u), 146.0 (d). Ϫ IR (neat):

ν˜ ϭ 3060 (w), 2958 (s), 2929 (m), 2871 (m), 2803 (w), 1630 (w),

1466 (m), 1446 (m), 1386 (w), 1368 (w), 1246 (s), 1150 (s), 1109

(m), 1082 (m), 1069 (m), 975 (m), 866 (m), 804 (w), 791 (w), 750

(m). Ϫ GC/MS: m/z (%) ϭ 239 (14), 238 [M^ϩϩ 1] (100), 236 (12),

209 (4), 192 (4), 149 (5), 126 (7), 125 (18), 117 (7), 115 (8), 112

(31), 109 (8), 107 (17), 106 (12), 97 (12), 81 (21), 79 (12), 78 (13),

77 (16). Ϫ C₁₃H₁₉NOS (237.3): calcd. C 65.76, H 8.07, N 5.92;

found C 65.50, H 8.28, N 6.07.

Synthesis of E-4b and Z-4b by the Shortened Route: Following the

procedure described for the synthesis of E-4a and Z-4a, a mixture

of E-4b, Z-4b, and E-3b in a ratio of 86:12:2 was obtained in 95%

overall yield starting from 1 and n-butanal.

(؉)-(E,S)- and (؉)-(Z,S)-N-Methyl-S-(4-methyl-2-pen-

tenyl)-S-phenylsulfoximine (E-4c and Z-4c): Treatment of 3c

(16.10 g, 67.8 mmol) with DBU according to GP1.1 and GP1.2

gave mixtures of E-4c and Z-4c in ratios of 17:83 and 83:17, re-

spectively, as colorless oils (14.5 g, 90%). Sulfoximines E-4c and Z-

4c were isolated as colorless oils by MPLC (EtOAc/cyclohexane,

6:1) of the latter mixture.

(2R)- and (2S)-1-[(S)-N-Methyl-S-phenylsulfonimidoyl]-4-methyl-

pentan-2-ol (2c and epi-2c): To a solution of 1 (13.60 g, 80.3 mmol)

in THF (100 mL) at Ϫ35 °C was added nBuLi (58.7 mL, 1.50 

solution in hexane, 88 mmol). The mixture was allowed to warm

to room temperature, then cooled to Ϫ78 °C, whereupon 3-methyl-

butanal (9.5 mL, 88 mmol) was added dropwise. After stirring the

resulting mixture for 2 h at Ϫ78 °C, it was allowed to warm to

room temperature and stirring was continued for a further 13 h. It

was then poured into saturated aqueous NH₄Cl solution and the

aqueous phase was extracted with EtOAc. The combined organic

phases were dried (MgSO₄) and concentrated in vacuo. Purification

of the residue by chromatography (EtOAc/hexane, 4:1) furnished a

mixture of 2c and epi-2c (19.40 g, 95%, 66:34) as a colorless oil.

E-4c: R_fϭ 0.37 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ62.2 (c ϭ 6.53,

MeOH). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.84 (d, J ϭ 6.6 Hz,

3 H, CH₃), 0.86 (d, J ϭ 6.0 Hz, 3 H, CH₃), 2.22 (oct, J ϭ 6.6 Hz,

1 H, 4-H), 2.73 (s, 3 H, NϪCH₃), 3.78 (d, J ϭ 6.3 Hz, 2 H, 1-H),

5.30 (dd, J ϭ 15.4, J ϭ 5.8 Hz, 1 H, 3-H), 5.37 (dt, J ϭ 15.4, J ϭ

6.9 Hz, 1 H, 2-H), 7.63Ϫ7.50 (m, 3 H, Ph), 7.80 (dt, J ϭ 6.6, J ϭ

1.9 Hz, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 21.8 (d),

29.8 (d), 31.2 (d), 60.1 (u), 129.0 (d), 129.9 (d), 132.8 (d), 134.0 (d),

136.6 (u), 147.9 (d). Ϫ IR (neat): ν˜ ϭ 3060 (w), 2959 (s), 2929 (s),

2871 (s), 2803 (m), 1662 (w), 1582 (w), 1465 (m), 1446 (s), 1403

(m), 1384 (w), 1364 (w), 1247 (s), 1147 (s), 1108 (m), 1082 (m), 973

(m), 955 (w), 893 (m), 858 (m), 769 (m), 738 (s). Ϫ GC/MS: m/z

(%) ϭ 238 [M^ϩϩ 1] (8), 194 (84), 125 (100), 107 (28), 106 (17), 97

(23), 78 (30), 77 (28). Ϫ C₁₃H₁₉NOS (237.3): calcd. C 65.76, H

8.07, N 5.92; found C 65.53, H 8.30, N 6.10.

2c: ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.90 (d, J ϭ 6.7 Hz, 3 H,

CH₃), 0.93 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.08 (m, 1 H, 3-H), 1.13 (m,

1 H, 3-H), 1.82 (sept, J ϭ 6.7 Hz, 1 H, 4-H), 2.62 (s, 3 H, NϪCH₃),

2.92 (dd, J ϭ 13.6, J ϭ 1.0 Hz, 1 H, 1-H), 3.24 (dd, J ϭ 13.6, J ϭ

10.1 Hz, 1 H, 1-H), 4.57 (tdd, J ϭ 9.6, J ϭ 4.7, J ϭ 1.0 Hz, 1 H,

2-H), 6.8 (br. s, OH), 7.56Ϫ7.70 (m, 3 H, Ph), 7.86Ϫ7.94 (m, 2 H,

Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 21.9 (d), 23.2 (d), 24.1

(d), 28.9 (d), 45.6 (u), 62.5 (u), 63.5 (d), 129.1 (d), 129.7 (d), 133.4

(d), 137.9 (u).

Z-4c: R_fϭ 0.39 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ63.0 (c ϭ 3.54,

MeOH). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.63 (d, J ϭ 6.4 Hz,

3 H, CH₃), 0.72 (d, J ϭ 6.7 Hz, 3 H, CH₃), 2.18 (dseptd, J ϭ 9.7,

J ϭ 6.7, J ϭ 0.7 Hz, 1 H, 4-H), 2.72 (s, 3 H, NϪCH₃), 3.88 (ddd,

J ϭ 14.1, J ϭ 7.7, J ϭ 1.3 Hz, 1 H, 1-H), 3.94 (ddd, J ϭ 14.1, J ϭ

8.0, J ϭ 1.3 Hz, 1 H, 1-H), 5.30 (dtd, J ϭ 10.7, J ϭ 7.7, J ϭ 0.7 Hz,

1 H, 2-H), 5.47 (ddt, J ϭ 11.1, J ϭ 9.7, J ϭ 1.0 Hz, 1 H, 3-H),

7.51Ϫ7.63 (m, 3 H, Ph), 7.84 (dt, J ϭ 1.7, J ϭ 6.4 Hz, 2 H, Ph).

epi-2c: ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.78 (d, J ϭ 6.7 Hz, 3

H, CH₃), 0.83 (d, J ϭ 6.4 Hz, 3 H, CH₃), 1.44Ϫ1.58 (m, 2 H, 3-

H), 1.72 (sept d, J ϭ 6.4, J ϭ 1.7 Hz, 1 H, 4-H), 2.70 (s, 3 H,

NϪCH₃), 3.02 (dd, J ϭ 14.1, J ϭ 1.7 Hz, 1 H, 1-H), 3.17 (dd, J ϭ

14.4, J ϭ 9.7, 1 H, 1-H), 3.90 (dtd, J ϭ 9.2, J ϭ 4.7, J ϭ 1.7 Hz,

1 H, 2-H), 6.8 (br. s, 1 H, OH), 7.56Ϫ7.70 (m, 3 H, Ph), 7.86Ϫ7.94

(m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 22.0 (d), 22.9

(d), 24.1 (d), 29.0 (d), 45.3 (d), 61.8 (d), 64.2 (u), 129.5 (d), 129.7

(d), 133.5 (d), 136.9 (u). Ϫ MS: m/z (%) ϭ 255 [M^ϩ] (2), 198 (20),

156 (100), 125 (67), 107 (32), 78 (21). Ϫ C₁₃H₂₁NO₂S (255.3): calcd.

C 61.14, H 8.29, N 5.48; found C 61.36, H 8.52, N 5.83.

Ϫ

¹³C NMR (75 MHz, CDCl₃): δ ϭ 22.4 (d), 22.4 (d), 26.9 (d),

29.7 (d), 55.1 (u), 113.5 (d), 129.1 (d), 129.9 (d), 132.8 (d), 137.0

(u), 145.8 (d). Ϫ IR (neat): ν˜ ϭ 3062 (w), 3020 (w), 2958 (s), 2924

(m), 2870 (m), 2803 (m), 1655 (w), 1582 (w), 1466 (m), 1446 (m),

1411 (w), 1379 (w), 1362 (w), 1305 (w), 1246 (s), 1149 (s), 1107 (s),

1082 (m), 1013 (w), 999 (w), 926 (w), 898 (w), 856 (w), 824 (w),

(؉)-(E,S)-N-Methyl-S-(4-methyl-1-pentenyl)-S-phenyl-

sulfoximine (3c): To a solution of a mixture of 2c and epi-2c (66:34)

3994

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

793 (w), 758 (m), 733 (s). Ϫ GC/MS: m/z (%) ϭ 238 [M^ϩϩ 1] (35),

FULL PAPER

Z-4d: R_fϭ 0.49 (EtOAc/hexane, 4:1); m.p. 62 °C; [α]_Dϭ ϩ84.0

194 (49), 156 (52), 154 (31), 125 (69), 112 (19), 107 (54), 106 (50), (c ϭ 2.42, acetone). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ

105 (24), 97 (22), 78 (44), 77 (43). Ϫ C₁₃H₁₉NOS (237.3): calcd. C 0.75Ϫ1.30 (m, 6 H, C₆H₁₁), 1.48Ϫ1.65 (m, 4 H, C₆H₁₁), 1.77 (dtt,

65.76, H 8.07, N 5.92; found C 65.90, H 8.25, N 6.25.

J ϭ 10.5, J ϭ 10.5, J ϭ 3.3 Hz, 1 H, 4-H), 2.73 (s, 3 H, NϪCH₃),

3.89 (dd, J ϭ 14.1, J ϭ 7.7 Hz, 1 H, 1-H), 3.97 (dd, J ϭ 14.1, J ϭ

8.1 Hz, 1 H, 1-H), 5.30 (ddd, J ϭ 10.5, J ϭ 8.1, J ϭ 7.7 Hz, 1 H,

2-H), 5.48 (dd, J ϭ 10.5, J ϭ 10.5 Hz, 1 H, 1-H), 7.51Ϫ7.63 (m, 3

H, Ph), 7.82Ϫ7.87 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ 25.5 (u), 25.7 (u), 29.7 (d), 32.4 (u), 36.7 (d), 55.1 (u), 113.7

(u), 129.1 (d), 129.9 (d), 132.8 (d), 136.8 (u), 144.4 (d). Ϫ IR (KBr):

ν˜ ϭ 2921 (s), 2850 (s), 2798 (m), 1699 (w), 1578 (w), 1445 (s), 1399

(m), 1247 (m), 1150 (s), 1106 (s), 1080 (s), 1004 (m), 908 (m), 882

(s), 850 (s), 800 (m), 759 (s), 729 (s). Ϫ GC/MS: m/z (%) ϭ 277

[M^ϩ] (1), 194 (58), 156 (54), 155 (18), 154 (27), 152 (11), 126 (15),

125 (90), 107 (62), 106 (31), 105 (13), 97 (22), 81 (100), 79 (32), 78

(48), 77 (52), 70 (11). Ϫ C₁₆H₂₃NOS (277.4): calcd. C 69.27, H

8.36, N 5.05; found C 68.99, H 8.30, N 4.98.

Synthesis of E-4c and Z-4c by the Shortened Route: Following the

procedure described for the synthesis of E-4a and Z-4a, a mixture

of E-4c, Z-4c, and E-3c in a ratio of 88:9:3 was obtained in 92%

overall yield starting from 1 and 3-methylbutanal.

(؉)-(E,S)-N-Methyl-S-(3-cyclohexyl-1-propenyl)-S-phenyl-

sulfoximine (3d): To a solution of 1 (8.46 g, 50.0 mmol) in THF

(100 mL) at Ϫ78 °C was added nBuLi (40.3 mL, 1.49  solution

in hexane, 60 mmol). The mixture was allowed to warm to room

temperature, then cooled to Ϫ78 °C, whereupon cyclohexylethanal

(9.11 mL, 65 mmol) was added dropwise. The resulting mixture was

allowed to warm to room temperature and stirred for 3 h, then

cooled to 0 °C, whereupon NEt₃(20.8 mL, 150 mmol) and Me-

SO₂Cl (5.0 mL, 65 mmol) were added dropwise. After stirring the

resulting mixture for 20 h at room temperature, it was poured into

saturated aqueous NH₄Cl solution (150 mL), and the aqueous

phase was extracted with EtOAc. The combined organic phases

were dried (MgSO₄) and concentrated in vacuo. Purification of the

residue by chromatography (EtOAc/hexane, 4:1) furnished 3d

(13.20 g, 95%) as a slowly crystallizing colorless oil; [α]_Dϭ ϩ26.9

(c ϭ 2.32, acetone). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ

0.81Ϫ0.97 (m, 2 H, C₆H₁₁), 1.01Ϫ1.30 (m, 3 H, C₆H₁₁), 1.35Ϫ1.50

(m, 1 H, 4-H), 1.55Ϫ1.70 (m, 5 H, C₆H₁₁), 2.10 (td, J ϭ 7.4, J ϭ

1.4 Hz, 2 H, 3-H), 2.74 (s, 3 H, NϪCH₃), 6.31 (dt, J ϭ 14.8, J ϭ

1.4 Hz, 1 H, 1-H), 6.84 (dt, J ϭ 14.8, J ϭ 7.4 Hz, 1 H, 2-H),

7.48Ϫ7.61 (m, 3 H, Ph), 7.86 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz,

CDCl₃): δ ϭ 26.1 (u), 26.2 (u), 29.5 (d), 33.0 (u), 33.0 (u), 37.1 (d),

39.3 (u), 128.6 (d), 129.3 (d), 130.8 (d), 132.5 (d), 139.6 (u), 145.9

(d). Ϫ IR (neat): ν˜ ϭ 3013 (m), 2918 (s), 2849 (s), 2799 (m), 1633

(m), 1580 (w), 1475 (w), 1447 (s), 1242 (s), 1151 (s), 1106 (s), 1080

(s), 977 (m), 871 (s), 856 (s), 805 (s), 755 (s). Ϫ MS: m/z (%) ϭ 277

[M^ϩ] (9), 249 (15), 195 (21), 156 (22), 155 (20), 152 (69), 126 (36),

125 (68), 121 (22), 117 (21), 116 (12), 115 (15), 109 (16), 108 (10),

107 (100), 106 (36), 97 (20), 95 (42), 93 (20), 83 (19), 81 (15), 79

(27), 78 (30), 77 (33), 70 (56). Ϫ C₁₆H₂₃NOS (277.4): calcd. C

69.27, H 8.36, N 5.05; found C 69.23, H 8.52, N 5.06.

Synthesis of E-4d and Z-4d by the Shortened Route: Following the

procedure described for the synthesis of E-4a and Z-4a, a mixture

of E-4d, Z-4d, and E-3d in a ratio of 88:9:3 was obtained in 90%

overall yield starting from 1 and cyclohexanecarbaldehyde.

(؊)-(E,S)-N-Methyl-S-(3-methyl-1-butenyl)-S-phenyl-

sulfoximine (5a): To a solution of 1 (8.04 g, 47.5 mmol) in THF

(100 mL) at Ϫ78 °C was added nBuLi (32.3 mL, 1.60  solution in

hexane, 51.7 mmol). The mixture was allowed to warm to room

temperature, then cooled to Ϫ78 °C, whereupon 2-methylpropanal

(3.2 mL, 56 mmol) was added dropwise. The mixture was allowed

to warm to room temperature and stirred for 3 h, and then cooled

to 0 °C, whereupon NEt₃(19.5 mL, 141 mmol) and MeSO₂Cl

(4.7 mL, 61 mmol) were added dropwise. After stirring for 20 h at

room temperature, the mixture was poured into saturated aqueous

NH₄Cl solution (150 mL) and the aqueous phase was extracted

with EtOAc. The combined organic phases were dried (MgSO₄)

and concentrated in vacuo. Chromatography of the residue

(EtOAc/hexane, 4:1) gave 5a (6.74 g, 64%) as a colorless oil; R_fϭ

0.42 (EtOAc/hexane, 4:1); [α]_Dϭ Ϫ9.7 (c ϭ 2.67, MeOH). Ϫ ¹H

NMR (300 MHz, CDCl₃): δ ϭ 1.04 (d, J ϭ 2.0 Hz, 3 H, CH₃),

1.07 (d, J ϭ 2.0 Hz, 3 H, CH₃), 2.49 (dt, J ϭ 6.4, J ϭ 1.7 Hz, 1 H,

3-H), 2.73 (s, 3 H, NϪCH₃), 6.27 (dd, J ϭ 15.1, J ϭ 1.3 Hz, 1 H,

1-H), 6.86 (dd, J ϭ 15.1, J ϭ 6.4 Hz, 1 H, 2-H), 7.50Ϫ7.62 (m,

3 H, Ph), 7.84Ϫ7.90 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ 20.9 (d), 21.0 (d), 29.5 (d), 30.6 (u), 128.0 (d), 128.7 (d), 129.3

(d), 132.5 (d), 139.5 (u), 152.7 (d). Ϫ IR (neat): ν˜ ϭ 3060 (w), 2964

(m), 2932 (m), 2827 (m), 2802 (m), 1670 (w), 1624 (m), 1582 (m),

1445 (s), 1304 (m), 1245 (s), 1149 (s), 1107 (m), 1082 (m), 1069 (m),

975 (m), 870 (m), 816 (m), 753 (m). Ϫ GC/MS: m/z (%) ϭ 224 [M^ϩ

ϩ 1] (100), 222 (7), 156 (1), 125 (3), 107 (7), 98 (9). Ϫ C₁₂H₁₇NOS

(223.3): calcd. C 64.53, H 7.67, N 6.27; found C 64.36, H 6.83,

N 6.27.

(؉)-(E,S)- and (؉)-(Z,S)-N-Methyl-S-(3-cyclohexyl-2-pro-

penyl)-S-phenylsulfoximine (E-4d and Z-4d): Treatment of 3d

(13.00 g, 46.8 mmol) with DBU according to GP1.1 and GP 1.2

gave mixtures of E-4d and Z-4d in ratios of 20:80 and 90:10, re-

spectively, as colorless oils (11.7 g, 90%). Sulfoximines E-4d and Z-

4d were isolated as a colorless oil and as colorless crystals, respect-

ively, by MPLC (EtOAc/hexane, 4:1) of the latter mixture.

E-4d: R_fϭ 0.48 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ71.7 (c ϭ 2.74, acet-

one). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.79Ϫ1.00 (m, 2 H),

1.00Ϫ1.15 (m, 4 H), 1.23Ϫ1.68 (m, 4 H), 1.82Ϫ1.97 (m, 1 H, 4-H),

2.73 (s, 3 H, NϪCH₃), 3.78 (d, J ϭ 6.4 Hz, 2 H, 1-H), 5.27 (dd,

J ϭ 15.4, J ϭ 6.1 Hz, 1 H, 2-H), 5.37 (dtd, J ϭ 15.4, J ϭ 7.1, J ϭ

0.6 Hz, 1 H, 3-H), 7.49Ϫ7.63 (m, 3 H, Ph), 7.79 (m, 2 H, Ph). Ϫ

¹³C NMR (75 MHz, CDCl₃): δ ϭ 25.7 (u), 26.0 (u), 29.8 (d), 32.3

(u), 32.3 (u), 40.7 (d), 60.3 (u), 114.4 (d), 129.0 (d), 129.9 (d), 132.7

(d), 136.6 (u), 146.7 (d). Ϫ IR (neat): ν˜ ϭ 3060 (w), 2924 (s), 2851

(s), 2802 (m), 1661 (w), 1582 (w), 1446 (s), 1403 (m), 1248 (s), 1147

(s), 1109 (s), 1082 (s), 970 (s), 896 (m), 856 (m), 766 (m), 736 (s).

Ϫ MS: m/z (%) ϭ 277 [M^ϩ] (1), 194 (51), 156 (40), 155 (33), 154

(17), 152 (14), 126 (13), 125 (50), 123 (3), 107 (100), 106 (21), 105

(11), 81 (90), 79 (26), 78 (67), 77 (25). Ϫ C₁₆H₂₃NOS (277.4): calcd.

C 69.27, H 8.36, N 5.05; found C 69.42, H 8.33, N 4.94.

(؉)-( S)-N-M et hy l- S-(3 -m ethy l-2-b u teny l)-S-phenyl-

sulfoximine (6a): Treatment of 5a (6.36 g, 28.5 mmol) with DBU

according to GP1.2 and subsequent chromatography (EtOAc/hex-

ane, 4:1) afforded 6a (4.79 g, 75%) as a colorless oil; R_fϭ 0.29

(EtOAc/hexane, 4:1); [α]_Dϭ ϩ37.7 (c ϭ 2.66, MeOH). Ϫ ¹H NMR

(300 MHz, CDCl₃): δ ϭ 1.23 (s, 3 H, CH₃), 1.68 (s, 3 H, CH₃),

2.73 (s, 3 H, NϪCH₃), 3.81 (dd, J ϭ 14.3, J ϭ 8.0 Hz, 1 H, 1-H),

3.87 (dd, J ϭ 14.3, J ϭ 8.0 Hz, 1 H, 1-H), 5.20 (m, 1 H, 2-H),

7.49Ϫ7.64 (m, 3 H, Ph), 7.79Ϫ7.84 (m, 2 H, Ph). Ϫ ¹³C NMR

(75 MHz, CDCl₃): δ ϭ 17.7 (d), 25.8 (d), 29.7 (d), 56.1 (u), 111.1

(d), 129.1 (d), 129.8 (d), 132.8 (d), 137.0 (u), 142.2 (u). Ϫ IR (neat):

ν˜ ϭ 3060 (m), 2971 (m), 2915 (m), 2876 (m), 2803 (m), 1668 (w),

1582 (w), 1445 (s), 1378 (m), 1304 (w), 1246 (s), 1153 (s), 1103 (s),

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3995

H.-J. Gais et al.

FULL PAPER

1083 (s), 1060 (m), 910 (m), 860 (m), 755 (m), 740 (m). Ϫ MS: m/z was stirred for 10 min at Ϫ78 °C, allowed to warm to 0 °C, and

(%) ϭ 223 [M^ϩ] (Ͻ1), 155 (73), 126 (11), 125 (39), 119 (12), 107

stirred for 45 min at this temperature. It was then cooled to Ϫ78

(100), 106 (26), 98 (27), 97 (20), 78 (81), 77 (40). Ϫ C₁₂H₁₇NOS °C once more, whereupon the aldehyde (2 mmol) was added. The

(223.3): calcd. C 64.53, H 7.67, N 6.27; found C 64.22, H 7.66,

N 6.27.

mixture thus obtained was stirred for 2 h at Ϫ78 °C and then slowly

allowed to warm to room temperature over a period of 3 h. It was

then poured into saturated aqueous (NH₄)₂CO₃solution and ex-

tracted with EtOAc. The combined organic phases were dried

(MgSO₄) and concentrated in vacuo. The vinylic sulfoximine was

isolated by chromatography, crystallization, or by chromatography

following silylation.

(؎)-(RS)- and (؉)-(S)-N-Methyl-S-(3,3-diphenyl-2-propenyl)-S-

phenylsulfoximine (6b and rac-6b): To a solution of rac-1 (11.79 g,

69.7 mmol) in THF (50 mL) at Ϫ60 °C was added nBuLi (47.8 mL,

1.60  solution in hexane, 76.5 mmol). The mixture was allowed to

warm to room temperature, then cooled to Ϫ40 °C, whereupon a

solution of diphenylethanal (13.84 g, 70.5 mmol) in THF (20 mL)

was added dropwise. The resulting mixture was allowed to warm

to room temperature, stirred for 1 h, then cooled to Ϫ78 °C and

treated with ClCOOEt (6.7 mL, 70.0 mmol). The mixture was then

allowed to warm to room temperature once more, cooled again to

Ϫ78 °C, and treated with KOtBu (7.82 g, 70.0 mmol). After stirring

the resulting mixture for 13 h at room temperature, it was poured

into saturated aqueous NH₄Cl solution and the aqueous phase was

extracted with diethyl ether. The combined organic phases were

dried (MgSO₄) and concentrated in vacuo. Chromatography

(EtOAc/hexane/NEt₃, 75:24:1) of the residue and subsequent crys-

tallization (diethyl ether) gave rac-6b (13.10 g, 54%) as a colorless

solid. Following the same procedure, but starting from 1 (5.42 g,

32.0 mmol), chromatography (EtOAc/hexane/NEt₃, 75:24:1) fur-

nished sulfoximine 6b (6.60 g, 59%) as a slightly yellow oil; R_fϭ

General Procedure for the Silylation of the Hydroxy Sulfoximine 7

(GP4): To a mixture of the hydroxy sulfoximine 7 (1 mmol), sulfoxi-

mine 4, and N-methyl-S-phenylsulfinamide in DMF (2 mL) was

added imidazole (273 mg, 4 mmol) and then ClSiEt₃(4.0 mmol)

was added dropwise. After stirring the mixture for 20 h at room

temperature, half-saturated aqueous NaHCO₃was added and the

resulting mixture was extracted with diethyl ether. The combined

organic phases were dried (MgSO₄) and concentrated in vacuo.

Chromatography gave the silyl ether 7-SiEt₃.

General Procedure for the Deprotection of the Silyl Ether 7-SiEt₃

(GP5): To a vigorously stirred solution of the silyl ether 7-SiEt₃

(1 mmol) in THF (5 mL) and acetic acid (1 mL) at room temper-

ature was added aqueous HCl (0.15 , 5 mL). Stirring was con-

tinued at the same temperature until TLC showed complete con-

sumption of the silyl ether. The mixture was then neutralized by

the addition of saturated aqueous NaHCO₃solution and extracted

with EtOAc. The combined organic phases were dried (MgSO₄)

and concentrated in vacuo. Sulfoximine 7 was purified by chroma-

tography.

1

0.54 (EtOAc/hexane, 4:1); [α]_Dϭ ϩ28.9 (c ϭ 2.32, acetone). Ϫ H

NMR (300 MHz, CDCl₃): δ ϭ 2.72 (s, 3 H, NϪCH₃), 3.93 (dd,

J ϭ 14.1, J ϭ 7.7 Hz, 1 H, 1-H), 3.99 (dd, J ϭ 14.1, J ϭ 8.1 Hz, 1

H, 1-H), 6.14 (t, J ϭ 7.7 Hz, 1 H, 2-H), 6.61 (m, 2 H, Ph),

7.28Ϫ7.10 (m, 8 H, Ph), 7.45Ϫ7.55 (m, 2 H, Ph), 7.55Ϫ7.62 (m, 1

H, Ph), 7.60Ϫ7.71 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ 29.7 (d), 57.1 (u), 115.1 (d), 127.6 (d), 128.1 (d), 128.2 (d),

127.4 (d), 128.3 (d), 129.2 (d), 129.3 (d), 129.8 (d), 132.8 (d), 137.0

(u) 138.0 (u), 141.0 (u), 149.0 (u). Ϫ IR (neat): ν˜ ϭ 3057 (s), 3027

(m), 2963 (m), 2913 (s), 2876 (s), 2804 (s), 2103 (w), 1964 (w), 1901

(w), 1816 (w), 1736 (m), 1664 (w), 1627 (w), 1599 (w), 1579 (w),

1494 (m), 1445 (s), 1399 (m), 1249 (s), 1143 (s), 1109 (s), 1082 (s),

914 (m), 861 (s), 765 (s), 743 (s), 702 (s). Ϫ MS: m/z (%) ϭ 347

[M^ϩ] (1), 222 (7), 194 (20), 193 (100), 191 (9), 178 (22), 165 (8),

115 (56), 91 (15), 77 (8). Ϫ C₂₂H₂₁NOS (347.4): calcd. C 76.05, H

6.09, N 4.03; found C 75.73, H 6.11, N 4.01.

(؊)-(Z)-(2S,3R)-1-[(S)-N-Methyl-S-phenylsulfonimidoyl]-

3-methylpent-4-en-2-ol (7a): Reaction of a mixture of E-4a and Z-

4a (3.60 g, 17.2 mmol, 3:1) with ethanal according to GP2 gave a

mixture of 7a (44% cy, Ն96% ds), an (E)-isomer and a (Z)-isomer

of 7a (7% cy) derived from Z-4a in a ratio of 3:2, recovered E-4a

(21%), recovered Z-4a (25%), and N-methyl-S-phenylsulfinamide

(2% cy). Crystallization (diethyl ether) afforded diastereopure 7a

(1.35 g, 31%) as colorless crystals, m.p. 74 °C; [α]_Dϭ Ϫ142.7 (c ϭ

1

0.92, MeOH). Ϫ H NMR (300 MHz, CDCl₃): δ ϭ 0.85 (d, J ϭ

6.6 Hz, 3 H, CH₃), 1.27 (d, J ϭ 6.0 Hz, 3 H, CH₃), 2.66 (s, 3 H,

NϪCH₃), 3.46 (m, 1 H) and 3.55 (m, 1 H) (2-H and 3-H), 3.80 (br.

s, 1 H, OH), 6.14 (t, J ϭ 10.7 Hz, 1 H, 4-H), 6.42 (d, J ϭ 10.7 Hz,

1 H, 5-H), 7.57 (m, 3 H, Ph), 7.89 (m, 2 H, Ph). Ϫ ¹³C NMR

(75 MHz): δ ϭ 17.0 (d), 22.7 (d), 29.7 (d), 40.8 (d), 71.8 (d), 129.4

(d), 129.9 (d), 133.4 (d), 132.4 (d), 140.3 (u), 148.8 (d). Ϫ IR (KBr):

ν˜ ϭ 3265 (s), 2968 (s), 1235 (s), 1196 (s), 1147 (s), 1101 (s), 866 (s),

748 (s). Ϫ MS: m/z (%) ϭ 253 [M^ϩ] (12), 238 (10), 208 (6), 163

(18), 156 (43), 149 (34), 131 (21), 125 (100), 109 (33), 97 (46), 83

(42), 73 (37). Ϫ C₁₃H₁₉NO₂S (253.4): calcd: C 61.63, H 7.56, N

5.53; found C 61.51, H 7.56, N 5.51.

General Procedure for the γ-Hydroxyalkylation of Allylic Sulfoxim-

ines Using 1.2 Equiv. of ClTi(OiPr)₃(GP2): To a solution of the

allylic sulfoximine 4 (1.0 mmol) in THF (10 mL) at Ϫ78 °C was

added nBuLi (0.68 mL, 1.60  solution in hexane, 1.1 mmol). After

stirring the mixture for 10 min at Ϫ78 °C, ClTi(OiPr)₃(1.2 mmol),

either neat or in THF (2 mL), was added. The resulting mixture

was stirred for a further 10 min at Ϫ78 °C, allowed to warm to 0

°C, and stirred for 45 min at this temperature. The mixture was

subsequently cooled to Ϫ78 °C once more, whereupon the aldehyde

(2 mmol) was added dropwise and stirring was continued for

80 min at Ϫ78 °C. The mixture was then poured into saturated

aqueous (NH₄)₂CO₃solution and extracted with EtOAc. The com-

bined organic phases were dried (MgSO₄) and concentrated in va-

cuo. The vinylic sulfoximine was isolated by chromatography, crys-

tallization, or by chromatography following silylation.

(؊)-(Z)-(3S,4R)-1-[(S)-N-Methyl-S-phenylsulfonimidoyl]-

4-methylhex-5-en-3-ol (7b): Reaction of a mixture of E-4a and Z-

4a (3.76 g, 18.0 mmol, 3:2) with propanal according to GP2 fur-

nished a mixture of 7b (37% cy, Ն96% ds), recovered E-4a (18%),

recovered Z-4a (37%), and two (E)-isomers of 7b (4% cy) derived

from Z-4a in a ratio of 6:1. Chromatography (EtOAc/hexane, 4:1)

afforded, besides a 1:2 mixture of E-4a and Z-4a (1.72 g, 46%), the

diastereopure sulfoximine 7b (1.56 g, 32%) as colorless crystals;

General Procedure for the γ-Hydroxyalkylation of Allylic Sulfoxim-

ines Using 2.1 Equiv. of ClTi(OiPr)₃(GP3): To a solution of the R_fϭ 0.17 (EtOAc/hexane, 4:1); m.p. 76 °C; [α]_Dϭ Ϫ100.0 (c ϭ

1

allylic sulfoximine 4 (1.0 mmol) in THF (10 mL) at Ϫ78 °C was 0.67, CH₂Cl₂). Ϫ H NMR (300 MHz, CDCl₃): δ ϭ 0.82 (d, J ϭ

added nBuLi (0.68 mL, 1.60  solution in hexane, 1.1 mmol). After

stirring the mixture for 10 min at Ϫ78 °C, ClTi(OiPr)₃(2.1 mmol),

either neat or in THF (2 mL), was added. The resulting mixture

6.7 Hz, 3 H, CH₃), 1.01 (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.43 (dquin,

J ϭ 14.1, J ϭ 7.2 Hz, 1 H, 2-H), 1.68 (dqd, J ϭ 14.1, J ϭ 7.4, J ϭ

3.7 Hz, 1 H, 2-H), 2.65 (s, 3 H, NϪCH₃), 3.34 (td, J ϭ 7.3, J ϭ

3996

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

3.7 Hz, 1 H, 3-H), 3.57 (dquin, J ϭ 11.0, J ϭ 6.8 Hz, 1 H, 4-H),

FULL PAPER

2-methylpropanal according to GP2 gave a mixture of 7c (44% cy,

3.57 (br. s, 1 H, OH), 6.17 (t, J ϭ 11.0 Hz, 1 H, 5-H), 6.42 (d, J ϭ Ն96% ds), recovered E-4a (32%), recovered Z-4a (22%), and N-

11.0 Hz, 1 H, 6-H), 7.52Ϫ7.64 (m, 3 H, Ph), 7.90 (m, 2 H, Ph). Ϫ

methyl-S-phenylsulfinamide (2% cy). Silylation of this mixture ac-

¹³C NMR (75 MHz, CDCl₃): δ ϭ 9.3 (d), 16.5 (d), 28.1 (u), 29.2 cording to GP4 afforded diastereopure 7c-SiEt₃(3.13 g, 38%);

(d), 37.8 (d), 76.0 (d), 128.9 (d), 129.4 (d), 131.6 (d), 132.9 (d),

[α]_Dϭ Ϫ103.7 (c ϭ 1.12, MeOH). Ϫ C₂₁H₃₇NO₂SSi (395.7): calcd.

139.9 (u), 148.4 (d). Ϫ IR (KBr): ν˜ ϭ 3678 (w), 3219 (vs), 3088

C 63.75, H 9.43, N 3.54; found C 63.35, H 9.60, N 3.37. The other

(m), 3052 (m), 2999 (m), 2974 (s), 2962 (vs), 2925 (vs), 2891 (s), analytical data were identical to those of rac-7c-SiEt₃.

2870 (s), 2799 (s), 2659 (m), 1624 (s), 1581 (w), 1475 (m), 1445 (vs),

1423 (s), 1412 (s), 1384 (m), 1376 (m), 1367 (s), 1353 (m), 1340 (w),

1315 (m), 1251 (vs), 1220 (vs), 1150 (vs), 1104 (vs), 1080 (vs), 1062

Deprotection of 7c-SiEt₃(304 mg, 0.77 mmol) according to GP6

furnished 7c (184 mg, 85%) as a colorless solid; m.p. 119 °C; [α]_Dϭ

Ϫ141.5 (c ϭ 1.03, MeOH). Ϫ C₁₅H₂₃NO₂S (281.4): calcd. C 64.02,

(s), 1039 (m), 1024 (m), 1000 (m), 983 (s), 965 (vs), 898 (m), 868

H 8.24, N 4.98; found C 63.80, H 8.32, N 4.90.

(vs), 835 (s), 744 (vs), 735 (vs). Ϫ MS: m/z (%) ϭ 268 (3), 267 [M^ϩ]

(؊)-(Z)-(3S,4R)-2,4-Dimethyl-6-[(S)-N-methyl-S-phenyl-

sulfonimidoyl]hex-5-en-3-ol (7c): Reaction of a mixture of E-4a and

Z-4a (9.88 g, 47.2 mmol, 3:1) with 2-methylpropanal according to

GP2 gave a mixture of 7c (46% cy, Ն96% ds), recovered E-4a (31%),

recovered Z-4a (21%), and N-methyl-S-phenylsulfinamide (2% cy).

Crystallization (cyclohexane) furnished diastereopure 7c (4.78 g,

36%) as colorless crystals; m.p. 119 °C; [α]_Dϭ Ϫ141.5 (c ϭ 1.03,

MeOH). Ϫ C₁₅H₂₃NO₂S (281.4): calcd. C 64.02, H 8.24, N 4.98;

found C 63.80, H 8.32, N 4.90. The other analytical data were

identical to those of rac-7c.

(2), 238 (27), 209 (5), 182 (5), 163 (9), 161 (8), 156 (53), 131 (16),

129 (11), 126 (12), 125 (100), 109 (17), 107 (17), 97 (12), 83 (17),

78 (15), 77 (18). Ϫ C₁₄H₂₁NO₂S (267.4): calcd. C 62.89, H 7.92, N

5.24; found C 62.85, H 8.05, N 5.23.

(؎)-Triethyl-{(Z)-(1RS,2SR)-1-isopropyl-4-[(RS)-N-

methyl-S-phenylsulfonimidoyl]-2-methylbut-3-enyloxy}silane

(rac-7c-SiEt₃): Reaction of a mixture of rac-E-4a and rac-Z-4a

(1.56 g, 7.46 mmol, 3:1) with 2-methylpropanal according to GP2

gave a mixture of rac-7c (52% cy, Ն96% ds), recovered rac-E-4a

(36%), recovered rac-Z-4a (23%), and N-methyl-S-phenylsulfinam-

ide (6% cy). Silylation of this mixture according to GP4 afforded,

besides a mixture of rac-E-4a, rac-Z-4a, and N-methyl-N-triethylsi-

Silylation of 7c (1.97 g, 7.0 mmol) according to GP5 gave 7c-SiEt₃

(2.57 g, 93%).

lyl-S-phenylsulfinamide, the diastereopure silyl ether rac-7c-SiEt₃(؎)-tert-Butyl-{(Z)-(1RS,2RS)-4-[(SR)-N-methyl-S-phenyl-

(835 mg, 38%) as colorless crystals; m.p. 38Ϫ40 °C. Ϫ ¹H NMR

(300 MHz, CDCl₃): δ ϭ 0.53Ϫ0.64 (m, 9 H), 0.90Ϫ1.01 (m, 15 H),

sulfonimidoyl]-2-methyl-1-phenylbut-3-enyloxy}dimethylsilane (rac-

7d-SitBuMe₂): Reaction of rac-E-4a (418 mg, 2.0 mmol) with

1.65 [oct, J ϭ 6.5 Hz, 1 H, CH(CH₃)₂], 2.66 (s, 3 H, NϪCH₃), 3.32 benzaldehyde according to GP2 and subsequent chromatography

(dd, J ϭ 6.4, J ϭ 2.0 Hz, 1 H, 1-H), 3.62 (m, 1 H, 2-H), 6.30 (d, (EtOAc/hexane, 1:1) gave a mixture of rac-7d (53% cy, 96% ds)

J ϭ 11.1 Hz, 1 H, 4-H), 6.46 (dd, J ϭ 11.1, J ϭ 10.7 Hz, 1 H, 3- and recovered rac-E-4a (22%). This mixture was dissolved in DMF

H), 7.50Ϫ7.61 (m, 3 H, Ph), 7.88Ϫ7.94 (m, 2 H, Ph). Ϫ ¹³C NMR (10 mL), treated with imidazole (170 mg, 2.5 mmol), and then

(75 MHz, CDCl₃): δ ϭ 5.4 (u), 7.1 (d), 17.8 (d), 18.5 (d), 19.1 (d), ClSitBuMe₂(300 mg, 2.0 mmol) was slowly added. After stirring

29.2 (d), 34.0 (d), 34.1 (d), 81.4 (d), 128.9 (u), 129.2 (u), 129.4 (d),

for 16 h at room temperature, the mixture was poured into ice/

132.4 (d), 140.8 (u), 148.9 (d). Ϫ IR (KBr): ν˜ ϭ 3039 (s), 2956, water and extracted with cyclohexane. The combined organic

2936, 2910, 2875 (vs), 2800 (s), 1623 (m), 1386 (s), 1249 (s), 1218

(s), 1146 (s), 1124 (s), 1083 (s), 1045 (s), 1020 (vs), 970 (s), 864 (s),

phases were dried (MgSO₄) and concentrated in vacuo. Chromato-

graphy (EtOAc/hexane, 1:4) afforded rac-7d-SitBuMe₂(387 mg,

832 (s), 810 (s), 765 (s), 737 (vs). Ϫ MS: m/z (%) ϭ 395 [M^ϩ] (6), 45%) containing 3% of a (Z)-diastereomer as a colorless oil.

366 (14), 354 (12), 353 (29), 352 (100), 209 (14), 159 (13), 116 (11),

1

rac-7d: H NMR (300 MHz, CDCl₃): δ ϭ 0.73 (d, J ϭ 6.7 Hz, 3

115 (89), 103 (18), 87 (70), 75 (20). Ϫ C₂₁H₃₇NO₂SSi (395.6): calcd.

H, CH₃), 2.68 (s, 3 H, NϪCH₃), 3.86Ϫ4.00 (m, 1 H, 2-H), 4.29 (d,

C 63.74, H 9.43, N 3.54; found C 63.88, H 9.55, N 3.67.

J ϭ 9.1 Hz, 1 H, 1-H), 6.20 (t, J ϭ 11.1 Hz, 1 H, 3-H), 6.42 (d,

J ϭ 11.1 Hz, 1 H, 4-H), 7.20Ϫ7.40 (m, 5 H, Ph), 7.45Ϫ7.62 (m, 3

H, Ph), 7.86Ϫ7.92 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ 16.7 (d), 29.3 (d), 40.7 (d), 78.2 (d), 126.8 (d), 127.5 (d), 128.3

(d), 128.8 (d), 129.4 (d), 132.0 (d), 132.9 (d), 139.3 (u), 143.5 (u),

148.0 (d).

(؎)-(Z)-(3RS,4SR)-2,4-Dimethyl-6-[(RS)-N-methyl-S-phenyl-

sulfonimidoyl]hex-5-en-3-ol (rac-7c): Deprotection of rac-7c-SiEt₃

(304 mg, 0.77 mmol) according to GP5 afforded diastereopure rac-

7c (184 mg, 85%) as a colorless solid; m.p. 119 °C. Ϫ ¹H NMR

(300 MHz, CDCl₃): δ ϭ 0.85 (d, J ϭ 6.4 Hz, 3 H, CH₃), 0.93 (d,

J ϭ 6.7 Hz, 3 H, CH₃), 1.05 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.80 (septd,

J ϭ 6.6, J ϭ 3.0 Hz, 1 H, 2-H), 2.64 (s, 3 H, NϪCH₃), 3.17 (dd,

J ϭ 8.7, J ϭ 3.0 Hz, 1 H, 3-H), 3.74 (m, 1 H, 4-H), 4.31 (br. s, 1

H, OH), 6.15 (dd, J ϭ 11.1, J ϭ 10.7 Hz, 1 H, 5-H), 6.38 (d, J ϭ

10.7 Hz, 1 H, 6-H), 7.52Ϫ7.64 (m, 3 H, Ph), 7.85Ϫ7.90 (m, 2 H,

Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 14.5 (d), 16.5 (d), 20.4

(d), 29.1 (d), 30.0 (d), 36.5 (d), 79.1 (d), 128.9 (d), 129.4 (d), 131.4

(d), 132.9 (d), 139.7 (u), 148.6 (d). Ϫ IR (KBr): ν˜ ϭ 3450 (m, br),

3230 (s), 2960 (m), 2925 (m), 2890 (m), 2850 (m), 1630 (m), 1480

(w), 1430 (m), 1240 (s), 1215 (vs), 1150 (s), 1110 (s), 1080 (s), 1000

(s), 860 (vs), 770 (s), 730 (s). Ϫ MS: m/z (%) ϭ 281 [M^ϩ] (7), 239

(10), 238 (74), 156 (65), 131 (14), 129 (11), 126 (12), 125 (100), 109

(11), 107 (18), 83 (18), 78 (17), 77 (17). Ϫ C₁₅H₂₃NO₂S (281.4):

calcd. C 64.02, H 8.24, N 4.98; found C 64.05, H 8.56, N 5.07.

1

rac-7d-SitBuMe₂: H NMR (300 MHz, CDCl₃): δ ϭ 0.19 (s, 3 H,

SiϪCH₃), 0.24 (s, 3 H, SiϪCH₃), 1.08 (s, 9 H, tBu), 0.95 (d, J ϭ

6.7 Hz, 3 H, CH₃), 2.69 (s, 3 H, NϪCH₃), 3.92Ϫ4.02 (m, 1 H, 2-

H), 4.83 (d, J ϭ 4.7 Hz, 1 H, 1-H), 6.27Ϫ6.36 (m, 2 H, 4-H, 3-H),

7.20Ϫ7.50 (m, 5 H, Ph), 7.61Ϫ7.75 (m, 3 H, Ph), 8.00Ϫ8.07 (m, 2

H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ Ϫ5.1 (d), Ϫ4.6 (d),

15.6 (d), 25.8 (d), 29.2 (d), 40.0 (d), 77.7 (d), 126.6 (d), 127.2 (d),

127.9 (d), 128.5 (d), 129.0 (d), 130.1 (d), 133.3 (d), 140.7 (u), 142.6

(u), 147.8 (d). Ϫ MS: m/z (%) ϭ 430 [M^ϩ] (6), 429 (17), 372 (50),

274 (34), 222 (18), 221 (100), 217 (34), 142 (20), 128 (15), 75 (45),

73 (93).

(؊)- (Z)- (2S, 3R)- 3 -E thy l -5 -[ (S)- N-methyl -S-phenyl-

sulfonimidoyl]pent-4-en-2-ol (7e): Compound E-4b (300 mg,

1.34 mmol) was treated with ethanal according to GP3, with the

modifications that the mixture was allowed to warm to room tem-

perature, stirred at this temperature for 1 h, and cooled to Ϫ78 °C

prior to addition of the aldehyde, and that the reaction mixture

(؊)-Triethyl-{(Z)-(1S,2R)-1-isopropyl-4-[(RS)-N-methyl-

S-phenylsulfonimidoyl]-2-methylbut-3-enyloxy}silane (7c-SiEt₃): Re-

action of a mixture of E-4a and Z-4a (5.88 g, 28.1 mmol, 3:1) with

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3997

H.-J. Gais et al.

FULL PAPER

was stirred for 10 h at room temperature. Work-up gave a mixture

of 7e (80% cy, 92% ds) and recovered E-4b (20%). Crystallization

(diethyl ether) afforded diastereopure 7e (156 mg, 44%) as colorless

CDCl₃): δ ϭ 0.62 (d, J ϭ 6.9 Hz, 3 H, CH₃), 0.79 (d, J ϭ 6.9 Hz,

3 H, CH₃), 0.94 (d, J ϭ 6.8 Hz, 3 H, CH₃), 1.07 (d, J ϭ 6.8 Hz, 3

H, CH₃), 1.81 (sept, J ϭ 6.9 Hz, 1 H, 7-H), 1.82 (oct, J ϭ 6.8 Hz,

crystals; m.p. 68 °C; [α]_Dϭ Ϫ132.1 (c ϭ 0.93, CH₂Cl₂). Ϫ ¹H 1 H, 2-H), 2.62 (s, 3 H, NϪCH₃), 3.38 (dd, J ϭ 9.5, J ϭ 2.7 Hz, 1

NMR (400 MHz, CDCl₃): δ ϭ 0.57 (t, J ϭ 7.7 Hz, 3 H, 7-H), 1.10 H, 3-H), 3.57 (ddd, J ϭ 11.9, J ϭ 9.5, J ϭ 4.0 Hz, 1 H, 4-H), 4.3

(dquad, J ϭ 7.4, J ϭ 13.2, J ϭ 2.2 Hz, 1 H, 6-H), 1.30 (d, J ϭ

(br. s, 1 H, OH), 6.31 (dd, J ϭ 11.8, J ϭ 11.0 Hz, 1 H, 5-H), 6.57

6.0 Hz, 3 H, 5-H), 1.50 (dquad, J ϭ 7.7, J ϭ 13.3, J ϭ 1.6 Hz, 1 (d, J ϭ 10.7 Hz, 1 H, 6-H), 7.51Ϫ7.63 (m, 3 H, Ph), 7.89 (dt, J ϭ

H, 6-H), 2.64 (s, 3 H, NϪCH₃), 3.21Ϫ3.32 (m, 1 H, 3-H), 3.61 (m, 7.0, J ϭ 1.5 Hz, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ

1 H, 4-H), 3.84 (br. s, 1 H, OH), 6.10 (t, J ϭ 11.0 Hz, 1 H, 2-H),

14.3 (d), 15.8 (d), 20.6 (d), 21.8 (d), 27.4 (d), 29.1 (d), 29.8 (d), 46.5

6.57 (d, J ϭ 10.8 Hz, 1 H, 1-H), 7.52Ϫ7.63 (m, 3 H, Ph), 7.89 (m, (d), 75.3 (d), 129.1 (d), 129.4 (d), 132.9 (d), 134.1 (d), 139.7 (u),

2 H, Ph). Ϫ ¹³C NMR (100 MHz, CDCl₃): δ ϭ 11.4 (d), 22.4 (d),

145.0 (d). Ϫ IR (KBr): ν˜ ϭ 3200 (s, br), 3067 (m), 3025 (m), 2960

24.4 (u), 29.1 (u), 47.3 (d), 69.4 (d), 128.8 (d), 129.1 (d), 132.6 (d),

(s), 2924 (m), 2898 (m), 2871 (m), 2802 (m), 1655 (w), 1618 (m),

133.5 (u), 139.6 (d), 147.8 (d). Ϫ IR (KBr): ν˜ ϭ 3245 (s, br), 3067 1468 (m), 1446 (m), 1385 (w), 1369 (w), 1297 (m), 1251 (s), 1209

(m), 3032 (m), 3009 (m), 2962 (s), 2920 (s), 2868 (s), 2798 (m), 2320 (s), 1157 (s), 1114 (s), 1067 (w), 1047 (m), 1026 (w), 862 (s), 836

(w), 1896 (w), 1624 (s), 1586 (m), 1479 (m), 1458 (s), 1447 (s), 1418

(m), 1375 (m), 1313 (m), 1287 (m), 1243 (s), 1209 (s), 1150 (s), 1111

(w), 782 (s), 760 (m), 735 (s). Ϫ MS: m/z (%) ϭ 309 [M^ϩ] (6), 266

(31), 236 (18), 156 (90), 125 (100), 111 (19), 107 (27), 81 (23), 78

(s), 1084 (s), 1065 (s), 1041 (s), 1020 (s), 1000 (m), 956 (m), 898 (28), 77 (18). Ϫ C₁₇H₂₇NO₂S (309.4): calcd. C 65.98, H 8.79, N

(m), 861 (s), 847 (s), 789 (s), 755 (s), 731 (s), 684 (s), 621 (s). Ϫ

MS: m/z (%) ϭ 269 (15), 268 [M^ϩϩ 1] (100), 266 (4), 239 (2), 224

(3), 155 (3). Ϫ C₁₄H₂₁NO₂S (267.4): calcd. C 62.88, H 7.91, N 5.24;

found C 62.85, H 8.34, N 5.25.

4.53; found C 66.02, H 8.95, N 4.70.

(؊)-(Z)-(1R,2R)-2-Isopropyl-4-[(S)-N-methyl-S-phenyl-

sulfonimidoyl]-1-phenylbut-3-en-1-ol (7j): Reaction of a mixture of

E-4c and Z-4c (4.13 g, 17.3 mmol, 9:1) with benzaldehyde accord-

(؊)-(Z)-(2S,3R)-3-Isopropyl-5-[(S)-N-methyl-S-phenyl- ing to GP2 afforded a mixture of 7j (48% cy, Ն96% ds), recovered

sulfonimidoyl]pent-4-en-2-ol (7g): Reaction of a mixture of E-4c and

Z-4c (3.10 g, 13.1 mmol, 15:1) with ethanal according to GP2 gave

a mixture of 7g (48% cy, Ն96% ds), recovered E-4c (42%), reco-

vered Z-4c (6%), and N-methyl-S-phenylsulfinamide (3% cy). Crys-

tallization (diethyl ether) afforded diastereopure 7g (1.18 g, 32%)

as colorless crystals. Chromatography (EtOAc/hexane, 4:1) of the

mother liquor furnished, besides a mixture of E-4c and Z-4c

(1.40 g, 45%, 7:1), an additional crop of 7g (520 mg, 14%); R_fϭ

0.12 (EtOAc/hexane, 4:1); m.p. 109 °C; [α]_Dϭ Ϫ218.0 (c ϭ 0.66,

E-4c (35%), and recovered Z-4c (15%). Crystallization (diethyl

ether) gave diastereopure 7j (2.56 g, 43%) as colorless crystals; m.p.

152 °C; [α]_Dϭ Ϫ147.4 (c ϭ 1.04, MeOH). Ϫ ¹H NMR (300 MHz):

δ ϭ 0.57 (d, J ϭ 6.7 Hz, 3 H, CH₃), 0.87 (d, J ϭ 6.3 Hz, 3 H,

CH₃), 1.40 [septd, J ϭ 7.0, J ϭ 3.3 Hz, 1 H, CH(CH₃)₂], 2.69 (s, 1

H, NϪCH₃), 3.88 (ddd, J ϭ 10.4, J ϭ 10.3, J ϭ 3.3 Hz, 1 H, 2-

H), 4.48 (d, J ϭ 9.7 Hz, 1 H, 1-H), 5.93 (br. s, 1 H, OH), 6.42 (t,

J ϭ 11.4 Hz, 1 H, 3-H), 6.68 (d, J ϭ 10.7 Hz, 1 H, 4-H), 7.26Ϫ7.45

(m, 5 H, Ph), 7.53Ϫ7.64 (m, 3 H, Ph), 7.91Ϫ7.96 (m, 2 H, Ph). Ϫ

MeOH). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.67 (d, J ϭ 6.9 Hz, ¹³C NMR (75 MHz): δ ϭ 15.7 (d), 21.8 (d), 27.7 (d), 29.3 (d), 51.5

3 H, CH₃), 0.70 (d, J ϭ 6.9 Hz, 3 H, CH₃), 1.32 (d, J ϭ 6.0 Hz, 3

H, CH₃), 1.80 (oct, J ϭ 6.9 Hz, 1 H, 6-H), 2.64 (s, 3 H, NϪCH₃),

(d), 75.2 (d), 126.7 (d), 127.6 (d), 128.5 (d), 129.1 (d), 129.5 (d),

133.1 (d), 135.5 (d), 139.2 (u), 144.2 (u), 143.8 (d). Ϫ IR (KBr):

3.25 (ddd, J ϭ 11.8, J ϭ 7.4, J ϭ 5.5 Hz, 1 H, 3-H), 3.80 (sext, J ϭ ν˜ ϭ 3087 (s, br), 3021 (s), 2984 (s), 2962 (s), 2893 (s), 2871 (s), 2729

6.4 Hz, 1 H, 2-H), 3.90 (br. s, 1 H, OH), 6.27 (dd, J ϭ 11.8, J ϭ (m), 1617 (m), 1445 (s), 1246 (vs), 1214 (s), 1189 (s), 1152 (vs), 1114

11.1 Hz, 1 H, 4-H), 6.61 (d, J ϭ 11.1 Hz, 1 H, 5-H), 7.52Ϫ7.64 (m,

3 H, Ph), 7.90 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ m/z (%) ϭ 343 [M^ϩ] (10), 237 (36), 236 (22), 222 (30), 194 (14), 170

16.9 (d), 21.3 (d), 22.9 (d), 28.3 (d), 29.2 (d), 50.9 (d), 67.8 (d), (25), 156 (69), 155 (21), 145 (59), 125 (100), 107 (47), 106 (46), 105

(vs), 1055 (s), 863 (vs), 786 (vs), 764 (vs), 755 (vs), 703 (vs). Ϫ MS:

129.1 (d), 129.3 (d), 132.8 (d), 134.3 (d), 139.8 (u), 145.2 (d). Ϫ IR (50), 77 (67). Ϫ C₂₀H₂₅NO₂S (343.5): calcd. C 69.94, H 7.34, N

(KBr): ν˜ ϭ 3281 (s, br), 3059 (w), 3028 (w), 2966 (s), 2930 (s), 2889 4.08; found C 69.57, H 7.32, N 4.00.

(s), 2871 (s), 2799 (m), 2101 (w), 1614 (m), 1470 (m), 1445 (s), 1386

(m), 1367 (m), 1310 (m), 1271 (m), 1243 (s), 1208 (vs), 1149 (vs),

1128 (s), 1105 (vs), 1078 (s), 1043 (s), 1026 (w), 999 (w), 982 (w),

(؊)-(Z)-(3S,4R)-4-Cyclohexyl-1-[(S)-N-methyl-S-phenyl-

sulfonimidoyl]hex-5-en-3-ol (7k): Reaction of E-4d (930 mg,

3.35 mmol) with propanal according to GP3 gave a mixture of 7k

952 (w), 916 (w), 865 (vs), 844 (m), 786 (s), 759 (s), 731 (s). Ϫ MS:

(77% cy, 96% ds), recovered E-4d (6%), E-10k (17% cy) as a mixture

m/z (%) ϭ 281 [M^ϩ] (5), 266 (2), 236 (5), 156 (28), 125 (57), 107

of diastereomers in a ratio of 19:37:22:11, and N-methyl-S-phenyl-

sulfinamide (2% cy). Chromatography (EtOAc/hexane, 4:1) af-

(20), 83 (18), 82 (10), 81 (23), 78 (39), 77 (29). Ϫ C₁₅H₂₃NO₂S

(281.4): calcd. C 64.02, H 8.24, N 4.98; found C 64.09, H 8.26,

N 5.10.

forded diastereopure 7k (710 mg, 69%) as a colorless solid, m.p. 86

°C; [α]_Dϭ Ϫ105.9 (c ϭ 1.06, acetone). Ϫ ¹H NMR (300 MHz,

(؊)-(Z)-(3S,4R)-4-Isopropyl-2-methyl-6-[(S)-N-methyl-S-phenyl-

sulfonimidoyl]hex-5-en-3-ol (7i): Reaction of a mixture of E-4c and

Z-4c (3.38 g, 14.2 mmol, 9:1) with 2-methylpropanal according to

CDCl₃): δ ϭ 0.65Ϫ0.87 (m, 2 H, C₆H₁₁), 0.90Ϫ1.22 (m, 3 H,

C₆H₁₁), 1.03 (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.33Ϫ1.51 (m, 3 H, C₆H₁₁),

1.52Ϫ1.66 (m, 3 H, C₆H₁₁), 1.74 (dqd, J ϭ 14.0, J ϭ 7.4, J ϭ

GP2, with the modification that the reaction mixture was allowed 3.3 Hz, 2 H, CH₂), 2.63 (s, 3 H, NϪCH₃), 3.34 (ddd, J ϭ 12.1, J ϭ

to warmed to room temperature after the addition of the aldehyde,

gave a mixture of 7i (48% cy, Ն96% ds), recovered E-4c (20%), Z-

6.9, J ϭ 5.2 Hz, 4-H), 3.63 (dt, J ϭ 7.4, J ϭ 3.3 Hz, 1 H, 3-H),

3.65 (br. s, 1 H, OH), 6.31 (dd, J ϭ 12.1, J ϭ 11.1 Hz, 1 H, 5-H),

4c recovered (4%), and 10i (26% cy) as a mixture of diastereomers 6.55 (d, J ϭ 11.0 Hz, 1 H, 6-H), 7.51 (m, 3 H, Ph), 7.86Ϫ7.92 (m,

in a ratio of 31:32:30:7. Crystallization (diethyl ether/pentane, 2:1)

furnished diastereopure 7i (1.91 g, 44%) as colorless crystals. Reac-

tion of E-4c (590 mg, 2.49 mmol) with 2-methylpropanal according

2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 9.4 (d), 26.4 (u),

26.4 (u), 26.6 (u), 27.8 (u), 28.5 (u), 29.2 (d), 31.7 (u), 38.4 (d), 48.0

(d), 71.8 (d), 129.2 (d), 129.3 (d), 132.8 (d), 133.5 (d), 139.9 (u),

˜ ϭ 3205 (s, br), 3063 (m), 3021 (m), 2928

to GP3 gave a mixture of 7i (82% cy, Ն96 ds), recovered E-4c (8%), 146.2 (d). Ϫ IR (KBr): ν

and 10i (9% cy) as a mixture of diastereomers. Crystallization (di-

(s), 2854 (s), 2801 (m), 1991 (w), 1963 (w), 1896 (w), 1805 (w), 1765

ethyl ether) afforded diastereopure 7i as colorless crystals; m.p. 141 (w), 1612 (m), 1586 (w), 1450 (s), 1385 (m), 1348 (m), 1317 (m),

°C; [α]_Dϭ Ϫ181.4 (c ϭ 1.36, MeOH). Ϫ ¹H NMR (300 MHz,

1250 (s), 1222 (s), 1200 (s), 1153 (s), 1113 (s), 1054 (m), 1026 (s),

3998

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

998 (m), 967 (m), 867 (s), 810 (s), 767 (s), 728 (s). Ϫ MS: m/z (%) ϭ concentrated in vacuo to give a mixture of 7l (45% cy, Ն96% ds),

336 [M^ϩ] (2), 335 (7), 277 (13), 194 (17), 157 (7), 156 (100), 154 recovered E-4d (54%), and N-methyl-S-phenylsulfinamide (1% cy).

(10), 151 (16), 126 (13), 125 (99), 109 (13), 107 (73), 105 (12), 97

(25), 93 (16), 91 (16), 86 (34), 84 (57), 81 (79), 79 (32), 78 (45), 77

(44). Ϫ C₁₉H₂₉NO₂S (336.5): calcd. C 67.81, H 8.99, N 4.17; found

C 67.71, H 8.74, N 4.14.

With 1.1 Equiv. of Cl₂Ti(OiPr)₂at ؊78 °C Ǟ 25 °C: To a solution

of E-4d (2.00 g, 7.22 mmol) in THF (120 mL) at Ϫ78 °C was added

nBuLi (4.73 mL, 1.6  solution in hexane, 7.57 mmol). After stir-

ring for 20Ϫ30 min at Ϫ78 °C, Cl₂Ti(OiPr)₂(1.79 g, 7.57 mmol)

was added, and the resulting mixture was stirred for 10 min at Ϫ78

(؊)-(Z)-(3S,4R)-4-Cyclohexyl-2-methyl-6-[(S)-N-methyl-

°C, warmed to 25 °C, and stirred for 45 min at this temperature. It

S-phenylsulfonimidoyl]hex-5-en-3-ol (7l):

was then cooled to Ϫ78 °C once more, whereupon 2-methylpro-

panal (1.31 mL, 14.42 mmol) was added dropwise, stirring was con-

tinued for 2 h at Ϫ78 °C, and then the mixture was allowed to

warm to room temperature over a period of 14 h. It was then

poured into saturated aqueous (NH₄)₂CO₃solution and extracted

with EtOAc. The combined organic phases were dried (MgSO₄)

and concentrated in vacuo to give a mixture of 7l (78% cy, Ն96%

ds), recovered E-4d (16%), and N-methyl-S-phenylsulfinamide (6%

cy). Crystallization (diethyl ether/hexane, 1:1) afforded diastereo-

pure 7l (1.74 g, 70%) as colorless crystals.

With 1.2 Equiv. of ClTi(OiPr)₃: Reaction of E-4d (2.03 g,

7.31 mmol) with 2-methylpropanal according to GP2 gave a mix-

ture of 7l (52% cy, Ն96% ds), recovered E-4d (47%), and N-methyl-

S-phenylsulfinamide (1% cy).

With 2.1 Equiv. of ClTi(OiPr)₃: Reaction of E-4d (2.03 g,

7.31 mmol) with 2-methylpropanal according to GP3 afforded a

mixture of 7l (82% cy, Ն96% ds), recovered E-4d (16%), and N-

methyl-S-phenylsulfinamide (2% cy). Crystallization (diethyl ether)

gave diastereopure 7l (1.84 g, 72%) as colorless crystals; m.p. 149

°C; [α]_Dϭ Ϫ77.3 (c ϭ 1.20, acetone). Ϫ ¹H NMR (300 MHz,

CDCl₃): δ ϭ 0.74Ϫ1.25 (m, 6 H, C₆H₁₁), 0.94 (d, J ϭ 6.7 Hz, 3 H,

CH₃), 1.06 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.35Ϫ1.90 (m, 6 H, 5-H,

C₆H₁₁), 2.62 (s, 3 H, NϪCH₃), 3.46 (dd, J ϭ 9.4, J ϭ 2.4 Hz, 1 H,

3-H), 3.58 (ddd, J ϭ 11.4, J ϭ 9.4, J ϭ 4.0 Hz, 1 H, 4-H), 4.29

(br. s, 1 H, OH), 6.35 (t, J ϭ 11.4 Hz, 1 H, 5-H), 6.52 (d, J ϭ

11.1 Hz, 1 H, 6-H), 7.52Ϫ7.62 (m, 3 H, Ph), 7.87Ϫ7.93 (m, 2 H,

Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 14.4 (d), 20.6 (d), 26.5

(u), 26.7 (u), 29.2 (d), 29.9 (d), 32.1 (u), 38.0 (d), 46.4 (d), 74.8 (d),

129.1 (d), 129.3 (d), 132.8 (d), 133.6 (d), 139.8 (u), 145.9 (d). Ϫ IR

(KBr): ν˜ ϭ 3216 (s, br), 3064 (m), 3021 (m), 2932 (s), 2905 (s), 2873

(s), 2852 (s), 2803 (m), 1804 (w), 1612 (m), 1448 (s), 1386 (m), 1366

(m), 1297 (m), 1249 (s), 1220 (s), 1199 (s), 1153 (s), 1112 (s), 1041

(s), 999 (w), 971 (w), 944 (w), 924 (w), 861 (s), 805 (s), 777 (s), 759

(m), 732 (s). Ϫ MS: m/z (%) ϭ 349 [M^ϩ] (4), 306 (22), 276 (12),

156 (100), 151 (27), 149 (13), 126 (11), 125 (96), 109 (13), 107 (29),

97 (14), 95 (11), 93 (14), 91 (14), 83 (15), 81 (24), 79 (22), 78 (18),

77 (21), 73 (11). Ϫ C₂₀H₃₁NO₂S (349.5): calcd. C 68.73, H 8.94, N

4.01; found C 68.64, H 8.75, N 3.93.

(؊)-Triethyl-{(Z)-(1S,2S)-1-isopropyl-4-[(R)-N-methyl-S-phenyl-

sulfonimidoyl]-2-phenylbut-3-enyloxy}silane (ent-7n-SiEt₃): Reac-

tion of ent-E-4e (3.00 g, 11.06 mmol) with 2-methylpropanal ac-

cording to GP2 gave a mixture of ent-7n (40% cy, Ն96% ds), reco-

vered ent-E-4e (34%), and N-methyl-S-phenylsulfinamide (24% cy).

Treatment of this mixture with ClSiEt₃according to GP4 and sub-

sequent chromatography (EtOAc/hexane, 2:1) furnished diastereo-

pure ent-7n-SiEt₃(1.75 g, 34%) as a colorless solid; m.p. 58Ϫ60 °C;

R_fϭ 0.65 (EtOAc/hexane, 2:1); [α]_Dϭ Ϫ9.4 (c ϭ 0.57, CHCl₃). Ϫ

¹H NMR (300 MHz, CDCl₃): δ ϭ 0.18Ϫ0.36 (m, 6 H), 0.77 (t, J ϭ

7.7 Hz, 9 H), 0.96 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.01 (d, J ϭ 7.0 Hz,

3 H, CH₃), 1.69 [d, J ϭ 6.7 Hz, 1 H, CH(CH₃)₂], 2.63 (s, 3 H,

NϪCH₃), 3.64 (dd, J ϭ 6.1, J ϭ 2.7 Hz, 1 H, 1-H), 4.83 (dd, J ϭ

10.7, J ϭ 2.7 Hz, 1 H, 2-H), 6.50 (dd, J ϭ 11.1, J ϭ 0.7 Hz, 1 H,

4-H), 6.80Ϫ6.86 (m, 2 H, Ph), 6.92 (dd, J ϭ 11.1, J ϭ 10.7 Hz, 1

H, 3-H), 7.00Ϫ7.07 (m, 3 H, Ph), 7.12Ϫ7.20 (m, 2 H, Ph),

7.25Ϫ7.32 (m, 1 H, Ph), 7.51Ϫ7.56 (m, 2 H, Ph). Ϫ ¹³C NMR

(75 MHz, CDCl₃): δ ϭ 5.1 (u), 7.0 (d), 18.7 (d), 19.0 (d), 29.1 (d),

33.8 (d), 44.2 (d), 82.6 (d), 126.2 (d), 128.00 (d), 128.1 (d), 128.6

(d), 128.7 (d), 131.1 (d), 132.0 (d), 139.3 (u), 141.4 (u), 145.8 (d).

Ϫ IR (KBr): ν˜ ϭ 3450 (m, br), 3060 (m), 3026 (m), 2957 (s), 2911

(s), 2875 (vs), 2802 (m), 1627 (m), 1600 (m), 1583 (m), 1493 (s),

1448 (s), 1415 (s), 1379 (s), 1254 (vs), 1206 (s), 1175 (s), 1145 (vs),

1081 (vs), 1016 (s), 975 (s), 941 (s), 863 (vs), 853 (vs), 832 (vs), 812

(s), 781 (s), 740 (vs). Ϫ MS: m/z (%) ϭ 458 [M^ϩϩ 1] (10), 457

[M^ϩ] (22), 428 (11), 416 (13), 415 (33), 414 (100), 271 (23), 187

(11), 159 (23), 125 (10), 117 (10), 116 (15), 115 (90), 103 (13), 87

(55). Ϫ C₂₆H₃₉NO₂SSi (457.7): calcd. C 68.22, H 8.59, N 3.06;

found C 67.94, H 8.65, N 3.23.

With 0.50 Equiv. of Cl₂Ti(OiPr)₂at ؊78 °C: To a solution of E-4d

(370 mg, 1.34 mmol) in THF (20 mL) at Ϫ78 °C was added nBuLi

(0.87 mL, 1.60  solution in hexane, 1.39 mmol). After stirring the

mixture for 20Ϫ30 min at Ϫ78 °C, Cl₂Ti(OiPr)₂(160 mg,

0.67 mmol) was added, and the resulting mixture was stirred for

10 min at Ϫ78 °C, warmed to 25 °C, and stirred for 45 min at this

temperature. It was subsequently cooled to Ϫ78 °C once more,

whereupon 2-methylpropanal (0.243 mL, 2.68 mmol) was added

dropwise. After stirring for 2 h at Ϫ78 °C, the mixture was poured

into saturated aqueous (NH₄)₂CO₃solution and extracted with

EtOAc. The combined organic phases were dried (MgSO₄) and

concentrated in vacuo to give a mixture of 7l (10% cy), recovered

E-4d (80%), and N-methyl-S-phenylsulfinamide (10% cy).

Reaction of rac-E-4e (1.00 g, 3.66 mmol) with 2-methylpropanal

according to GP2 gave a mixture of rac-7n (42% cy, Ն96% ds),

recovered rac-E-4e (30%), and N-methyl-S-phenylsulfinamide

(21% cy).

With 1.1 Equiv. of Cl₂Ti(OiPr)₂at ؊78 °C: To a solution of E-4d

(370 mg, 1.34 mmol) in THF (20 mL) at Ϫ78 °C was added nBuLi

(0.87 mL, 1.60  solution in hexane, 1.4 mmol). After stirring the

(؊)-(Z)-(3R,4S)-1-[(R)-N-Methyl-S-phenylsulfonimidoyl]-

2-methyl-4-phenylhex-5-en-3-ol (ent-7n): Deprotection of ent-7n-

SiEt₃(320 mg, 0.70 mmol) according to GP5 afforded diastereop-

mixture for 20Ϫ30 min at Ϫ78 °C, Cl₂Ti(OiPr)₂(348 mg, ure ent-7n (209 mg, 87%) as a colorless oil; [α]_Dϭ Ϫ105.1 (c ϭ

1.47 mmol) was added, and the resulting mixture was stirred for

10 min at Ϫ78 °C, warmed to 25 °C, and stirred for 45 min at

this temperature. It was subsequently cooled to Ϫ78 °C once more,

whereupon 2-methylpropanal (0.243 mL, 2.68 mmol) was added

dropwise. After stirring for 2 h at Ϫ78 °C, the mixture was poured

into saturated aqueous (NH₄)₂CO₃solution and extracted with

EtOAc. The combined organic phases were dried (MgSO₄) and

0.68, CHCl₃). Ϫ ¹H NMR (300 MHz, CDCl₃): δ ϭ 0.92 (d, J ϭ

6.7 Hz, 3 H, CH₃), 0.97 (d, J ϭ 7.0 Hz, 3 H, CH₃), 1.46 (septd,

J ϭ 6.8, J ϭ 2.4 Hz, 1 H, 2-H), 2.67 (s, 3 H, N-CH₃), 3.73 (dd, J ϭ

9.7, J ϭ 2.4 Hz, 1 H, 3-H), 4.50 (br. s, 1 H, OH), 4.84 (ddd, J ϭ

9.7, J ϭ 8.4, J ϭ 2.3 Hz, 1 H, 4-H), 6.47 (m, 2 H, 5-H, 6-H),

6.98Ϫ7.03 (m, 2 H, Ph), 7.15Ϫ7.28 (m, 3 H, Ph,), 7.49Ϫ7.63 (m, 3

H, Ph), 7.85Ϫ7.90 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

Eur. J. Org. Chem. 2000, 3973Ϫ4009

3999

H.-J. Gais et al.

FULL PAPER

δ ϭ 14.3 (d), 20.5 (d), 29.2 (d), 29.8 (d), 48.6 (d), 78.7 (d), 127.1

(d), 127.8 (d), 128.9 (d), 129.0 (d), 129.4 (d), 132.0 (d), 132.9 (d),

139.5 (u), 146.7 (d). Ϫ IR (CHCl₃): ν˜ ϭ 3480 (m), 3245 (m, br),

(؊)- (E)- (2S, 3R)- 3 -E thy l -5 - [ (S)-N-m e thyl -S-phenyl-

sulfonimidoyl]pent-4-en-2-ol (8b): Sulfoximine Z-4b (300 mg,

1.34 mmol) was treated with ethanal according to GP3, with the

3062 (m), 3026 (m), 2962 (s), 2931, 2910 (m), 2873 (s), 1619 (m), modifications that after the titanation the mixture was allowed to

1600 (m), 1493 (m), 1446 (s), 1239 (m), 1146 (vs), 1104 (s), 1080

warm to room temperature, stirred for 1 h, and then cooled to Ϫ78

(s), 860 (s), 756 (vs), 702 (vs). Ϫ MS: m/z (%) ϭ 343 [M^ϩ] (13), 300 °C, and that after the addition of the aldehyde the mixture was

(45), 271 (15), 170 (11), 156 (65), 146 (16), 145 (18), 125 (69), 117

stirred at Ϫ78 °C for 1.5 h and thereafter at room temperature for

(100), 116 (34), 115 (80), 109 (12), 91 (26), 78 (13), 77 (21), 72 (24). 10 h. Work-up afforded a mixture of 8b (32% cy), epi-8b (1%), reco-

Ϫ C₂₀H₂₅NO₂S (343.5): calcd. C 69.95, H 7.34, N 4.08; found C vered Z-4b (44%), and Z-10e (22% cy, Ն96% ds). Chromatography

69.90, H 7.42, N 4.34.

(EtOAc/cyclohexane, 4:1) followed by crystallization (diethyl ether)

furnished diastereopure 8b (105 mg, 26%) as colorless crystals; m.p.

75 °C; [α]_Dϭ Ϫ121.5 (c ϭ 1.29, CH₂Cl₂). Ϫ H NMR (400 MHz,

(؎)-tert-Butyl-{(E)-(1RS,2RS)-4-[(SR)-N-methyl-S-phenyl-

sulfonimidoyl]-2-methyl-1-phenylbut-3-enyloxy}dimethylsilane (rac-

1

CDCl₃): δ ϭ 0.85 (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.05 (d, J ϭ 6.3 Hz,

3 H, CH₃), 1.38 (dq, J ϭ 13.7, J ϭ 7.4 Hz, 1 H, CH₂), 1.70 (dquad,

J ϭ 7.7, J ϭ 13.7, J ϭ 4.1 Hz, 1 H, CH₂), 2.15 (m, 1 H, 3-H), 2.43

(br. s, 1 H, OH), 2.74 (s, 3 H, NϪCH₃), 3.75 (dqua, J ϭ 6.1, J ϭ

12.6 Hz, 1 H, 2-H), 6.35 (dd, J ϭ 15.1, J ϭ 0.8 Hz, 1 H, 5-H), 6.67

(dd, J ϭ 15.1, J ϭ 9.3 Hz, 1 H, 4-H), 7.50Ϫ7.60 (m, 3 H, Ph), 7.86

(m, 2 H, Ph). Ϫ ¹³C NMR (100 MHz, CDCl₃): δ ϭ 11.9 (d), 20.6

(d), 22.6 (u), 29.4 (u), 51.4 (d), 69.3 (d), 128.3 (d), 129.1 (d), 131.6

(d), 132.4 (d), 139.2 (u), 147.0 (d). Ϫ IR (KBr): ν˜ ϭ 3225 (s, br),

3051 (m), 2977 (s), 2951 (s), 2933 (s), 2893 (m), 2871 (s), 2798 (m),

2281 (w), 1627 (m), 1584 (w), 1448 (s), 1406 (w), 1383 (m), 1373

(m), 1338 (m), 1321 (m), 1308 (m), 1223 (s), 1149 (s), 1103 (s), 1082

(s), 1040 (m), 1020 (m), 994 (s), 943 (w), 898 (w), 872 (s), 859 (s),

797 (s), 750 (s), 701 (m), 689 (s), 607 (s), 541 (s). Ϫ MS: m/z (%) ϭ

269 (16), 268 [M^ϩϩ 1] (100), 266 (1), 239 (3), 224 (2), 192 (2), 155

(3). Ϫ C₁₄H₂₁NO₂S (267.4): calcd. C 62.88, H 7.91, N 5.24; found

C 63.07, H 7.77, N 5.21.

8a-SitBuMe₂)

and

(؎)-tert-Butyl-{(E)-(1RS,2SR)-4-[(RS)-N-

methyl-S-phenylsulfonimidoyl]-2-methyl-1-phenylbut-3-enyloxy}-

dimethylsilane (rac-9a-SitBuMe₂): Reaction of rac-Z-4a (418 mg,

1.99 mmol) with benzaldehyde according to GP2 and subsequent

chromatography (EtOAc/hexane, 2:1) gave a mixture of rac-8a and

rac-9a (27% cy) in a ratio of 66:34, along with recovered rac-Z-4a

(34%). The mixture was dissolved in DMF (5 mL), treated with

imidazole (170 mg, 2.5 mmol), and then ClSitBuMe₂(300 mg,

2.0 mmol) was slowly added. After stirring for 16 h at room tem-

perature, the mixture was poured into ice/water and extracted with

cyclohexane. The combined organic phases were dried (MgSO₄)

and concentrated in vacuo. Chromatography (EtOAc/hexane, 1:1)

afforded a mixture of rac-8a-SitBuMe₂and rac-9a-SitBuMe₂

(219 mg, 26%) in a ratio of 66:34.

1

rac-8a: H NMR (300 MHz, CDCl₃): δ ϭ 1.09 (d, J ϭ 6.7 Hz, 3

H, CH₃), 2.58Ϫ2.72 (m, 1 H, 2-H), 2.62 (s, 3 H, NϪCH₃), 4.57 (d,

J ϭ 6.4 Hz, 1 H, 1-H), 6.14 (dd, J ϭ 15.1, J ϭ 1.3 Hz, 1 H, 4-H),

6.77 (dd, J ϭ 15.1, J ϭ 7.7 Hz, 1 H, 3-H), 7.13Ϫ7.21 (m, 5 H, Ph),

7.43Ϫ7.62 (m, 3 H, Ph), 7.68Ϫ7.72 (m, 2 H, Ph). Ϫ ¹³C NMR

(75 MHz, CDCl₃): δ ϭ 14.6 (d), 29.3 (d), 43.7 (d), 76.4 (d), 126.4

(d), 127.6 (d), 128.2 (d), 128.6 (d), 129.2 (d), 130.4 (d), 132.4 (d),

139.4 (u), 142.7 (u), 148.8 (d).

(Z)-(3S,4R)-2,7-Dimethyl-4-[(S)-N-methyl-S-phenylsulfonimidoyl]-

oct-5-en-3-ol (epi-Z-10i): Sulfoximine Z-4c (136 mg, 0.57 mmol)

was treated with 2-methylpropanal according to GP2. Work-up af-

forded a mixture of epi-Z-10i and Z-10i (45% cy) in a ratio of 2:1,

recovered Z-4c (48%), and N-methyl-S-phenylsulfinamide (5% cy).

Chromatography (EtOAc/hexane, 4:1) gave a mixture of epi-Z-10i

and Z-10i (47.7 mg, 28%) in a ratio of 64:36.

1

rac-9a: H NMR (300 MHz, CDCl₃): δ ϭ 0.99 (d, J ϭ 6.7 Hz, 3

1

H, CH₃), 2.58Ϫ2.72 (m, 1 H, 2-H), 2.65 (s, 3 H, NϪCH₃), 4.52 (d,

J ϭ 6.4 Hz, 1 H, 1-H), 6.22 (dd, J ϭ 15.1, J ϭ 1.0 Hz, 1 H, 4-H),

6.99 (dd, J ϭ 15.2, J ϭ 7.9 Hz, 1 H, 3-H), 7.13Ϫ7.21 (m, 5 H, Ph),

7.43Ϫ7.62 (m, 3 H, Ph), 7.76Ϫ7.81 (m, 2 H, Ph). Ϫ ¹³C NMR

(75 MHz, CDCl₃): δ ϭ 16.0 (d), 29.3 (d), 43.8 (d), 77.2 (d), 126.4

(d), 127.5 (d), 128.1 (d), 128.5 (d), 129.2 (d), 130.4 (d), 132.4 (d),

139.2 (u), 142.4 (u), 148.6 (d).

epi-Z-10i: R_fϭ 0.63 (EtOAc/hexane, 4:1). Ϫ H NMR (300 MHz,

CDCl₃): δ ϭ 0.59 (d, J ϭ 6.7 Hz, 3 H, CH₃), 0.94 (d, J ϭ 6.7 Hz,

3 H, CH₃), 0.96 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.00 (d, J ϭ 6.7 Hz, 3

H, CH₃), 1.60 [dsept, J ϭ 9.1, J ϭ 6.7 Hz, 1 H, CH(CH₃)₂], 2.49

[dsept, J ϭ 10.4, J ϭ 6.7 Hz, 1 H, CH(CH₃)₂], 2.71 (s, 3 H,

NϪCH₃), 3.54 (dd, J ϭ 9.1, J ϭ 1.0 Hz, 1 H, 3-H), 3.85 (d, J ϭ

10.4 Hz, 1 H, 4-H), 5.63 (t, J ϭ 10.8 Hz, 1 H, 6-H), 5.82 (dd, J ϭ

10.8, J ϭ 10.4 Hz, 1 H, 5-H), 7.50Ϫ7.69 (m, 3 H, Ph), 7.80Ϫ7.89

(m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃): δ ϭ 18.1 (d), 19.3

(d), 22.5 (d), 22.8 (d), 28.3 (d), 29.2 (d), 31.4 (d), 65.3 (d), 73.9 (d),

111.8 (d), 129.5 (d), 129.9 (d), 133.2 (d), 136.9 (u), 148.2 (d).

rac-8a-SitBuMe₂: ¹H NMR (300 MHz, CDCl₃): δ ϭ Ϫ0.28 (s, 3 H,

CH₃), Ϫ0.04 (s, 3 H, CH₃), 0.82 (s, 9 H, tBu), 1.05 (d, J ϭ 6.7 Hz,

3 H, CH₃), 2.55Ϫ2.64 (m, 1 H, 2-H), 2.69 (s, 3 H, NϪCH₃),

4.44Ϫ4.49 (m, 1 H, 1-H), 6.13 (m, 1 H, 4-H), 6.66 (dd, J ϭ 15.1,

J ϭ 8.4 Hz, 1 H, 3-H), 7.02Ϫ7.19 (m, 5 H, Ph), 7.46Ϫ7.62 (m, 3

H, Ph), 7.74Ϫ7.85 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ Ϫ5.2 (d), Ϫ4.7 (d), 16.4 (d), 29.4 (d), 29.8 (d), 45.2 (d), 78.5

(d), 126.4 (d), 127.3 (d), 127.9 (d), 127.8 (d), 128.8 (d), 129.2 (d),

138.2 (u), 142.8 (u), 148.7 (d).

(؊)-(Z)-(3S,4R)-1-(tert-Butyldimethylsilanyloxy)-4-meth-

yl-6-[(S)-N-methyl-S-phenylsulfonimidoyl]hex-5-en-3-ol (12): Reac-

tion of a mixture of E-4a and Z-4a (4.10 g, 19.6 mmol, 7:3) with

aldehyde 11 according to GP2 and subsequent chromatography

(EtOAc/hexane, 4:1) gave, besides a mixture of recovered E-4a and

Z-4a (53%) in a 1:1 ratio and recovered 11 (56%), the diastereopure

sulfoximine 12 (2.50 g, 32%) as a colorless oil; R_fϭ 0.32 (EtOAc/

hexane, 4:1); [α]_Dϭ Ϫ134.9 (c ϭ 1.18, MeOH). Ϫ ¹H NMR

(300 MHz, CDCl₃): δ ϭ 0.07 (s, 3 H, CH₃), 0.08 (s, 3 H, CH₃),

0.76 (d, J ϭ 6.7 Hz, 3 H, CH₃), 0.90 (s, 9 H, tBu), 1.58Ϫ1.75 (m,

1 H, 2-H), 1.75 (dtd, J ϭ 14.4, J ϭ 4.3, J ϭ 2.3 Hz, 1 H, 2-H),

2.66 (s, 3 H, NϪCH₃), 3.46 (dqd, J ϭ 11.0, J ϭ 6.7, J ϭ 4.3 Hz,

1 H, 4-H), 3.72 (ddd, J ϭ 9.7, J ϭ 4.3, J ϭ 4.3 Hz, 1 H, 3-H),

3.77Ϫ3.94 (m, 2 H, 1-H), 4.04 (br. s, 1 H, OH), 6.31 (dd, J ϭ 11.0,

J ϭ 11.0 Hz, 1 H, 5-H), 6.45 (d, J ϭ 11.0, 1 H, 6-H), 7.50Ϫ7.62

rac-9a-SitBuMe₂: ¹H NMR (300 MHz, CDCl₃): δ ϭ Ϫ0.30 (s, 3 H,

CH₃), Ϫ0.06 (s, 3 H, CH₃), 0.78 (s, 9 H, tBu), 0.98 (d, J ϭ 6.7 Hz,

3 H, CH₃), 2.55Ϫ2.64 (m, 1 H, 2-H), 2.71 (s, 3 H, NϪCH₃),

4.44Ϫ4.49 (m, 1 H, 1-H), 6.13 (m, 1 H, 4-H), 6.89 (dd, J ϭ 15.1,

J ϭ 8.1 Hz, 1 H, 3-H), 7.02Ϫ7.19 (m, 5 H, Ph), 7.46Ϫ7.62 (m, 3

H, Ph), 7.74Ϫ7.85 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, CDCl₃):

δ ϭ Ϫ5.2 (d), Ϫ4.7 (d), 15.0 (d), 29.8 (d), 29.4 (d), 45.1 (d), 77.8

(d), 126.5 (d), 127.3 (d), 127.8 (d), 128.7 (d), 128.8 (d), 129.2 (d),

139.5 (u), 142.1 (u), 148.5 (d).

4000

Eur. J. Org. Chem. 2000, 3973Ϫ4009

N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes

FULL PAPER

(m, 3 H, Ph), 7.87Ϫ7.93 (m, 2 H, Ph). Ϫ ¹³C NMR (75 MHz, 3.66 (t, J ϭ 10.1 Hz, 1 H, CHOH), 3.78 (dd, J ϭ 11.1, J ϭ 4.4 Hz,

CDCl₃): δ ϭ Ϫ5.5 (d), 16.0 (d), 18.1 (u), 25.9 (d), 29.2 (d), 37.3 1 H, CH), 4.36 (d, J ϭ 9.4 Hz, 1 H, OH), 6.33 (br. s, 1 H, ϭCH),

(u), 37.8 (d), 62.5 (u), 74.6 (d), 128.8 (d), 129.2 (d), 131.4 (d), 132.5

(d), 140.4 (u), 148.0 (d). Ϫ IR (CHCl₃): ν˜ ϭ 3500 (m, br), 2955 (s), NMR (75 MHz, [D₈]THF): δ ϭ 15.2 (d), 22.0 (u), 22.4 (d), 29.3

7.56Ϫ7.61 (m, 3 H, m-, p-Ph), 7.81Ϫ7.88 (m, 2 H, o-Ph). Ϫ ¹³C

2929 (s), 2857 (s), 1622 (m), 1472 (m), 1463 (m), 1446 (s), 1250 (vs),

(u), 29.5 (u), 30.3 (d), 31.5 (d), 34.0 (d), 42.6 (d), 75.1 (d), 128.9

1148 (vs), 1099 (vs), 1082 (vs), 861 (m), 836 (s), 776 (s), 753 (s). Ϫ

(d), 130.7 (d), 131.0 (d), 134.2 (d), 142.6 (u), 162.2 (u). Ϫ MS (CI):

MS: m/z (%) ϭ 397 [M^ϩ] (21), 382 (5), 340 (66), 238 (31), 209 (20), m/z (%) ϭ 324 (7), 323 (20), 322 [M^ϩϩ 1] (100), 293 (5), 250 (18),

185 (32), 156 (55), 131 (92), 125 (81), 101 (91), 89 (20), 75 (100). Ϫ 167 (7), 156 (27), 75 (7). Ϫ C₁₈H₂₇NO₂S (321.49): calcd. C 67.25,

C₂₀H₃₅NO₃SSi (397.6): calcd. C 60.41, H 8.87, N 3.52; found C

60.22, H 8.67, N 3.90.

H 8.47, N 4.36; found C 67.10, H 8.42, N 4.24.

(؊)-(Z)-(R)-1-{(R)-2-[(S)-N-Methyl-S-phenylsulfonimidoyl]-

methylenecyclohexyl}-1-phenylmethanol (16d): Reaction of 15

(1.0 g, 4.01 mmol) with benzaldehyde according to GP6 furnished

a mixture of recovered 15 (38%) and 16d (62% cy, Ն96% ds). Crys-

tallization (diethyl ether) of the residue afforded diastereopure 16d

(Z)-(1R,2R)-3-Methyl-4-[(S)-N-methyl-S-phenylsulfon-

imidoyl]-1,2-diphenylbut-3-en-1-ol (14): Reaction of 13 (571 mg,

2.0 mmol) with benzaldehyde according to GP2 gave crude 14 (51%

cy, 97% ds). Subsequent chromatography (EtOAc/hexane, 2:1) af-

forded 14 (317 mg, 41%) containing 3% of a diastereomer. Ϫ ¹H

NMR (300 MHz, CDCl₃): δ ϭ 1.85 (d, J ϭ 1.3 Hz, 3 H, CH₃),

2.76 (s, 3 H, NϪCH₃), 5.20 (d, J ϭ 11.1 Hz, 1 H, 2-H), 5.70 (d,

J ϭ 11.1 Hz, 1 H, 1-H), 6.42 (br. s, 2 H, 4-H, OH), 7.04Ϫ7.18 (m,

6 H, Ph), 7.19Ϫ7.26 (m, 2 H, Ph), 7.41Ϫ7.46 (m, 2 H, Ph),

7.56Ϫ7.68 (m, 3 H, Ph), 7.89Ϫ8.02 (m, 2 H, Ph). Ϫ ¹³C NMR

(75 MHz, CDCl₃): δ ϭ 19.8 (d), 29.6 (d), 54.4 (d), 74.3 (d), 127.0

(d), 127.1 (d), 127.4 (d), 128.3 (d), 128.3 (d), 129.2 (d), 129.3 (d),

129.6 (d), 129.8 (d), 133.1 (d), 137.3 (u), 139.3 (u), 143.7 (u), 155.8

(u). Ϫ MS: m/z (%) ϭ 391 [M^ϩ] (1), 236 (15), 167 (15), 160 (16),

131 (100), 129 (27), 124 (20), 115 (20), 106 (67), 105 (63), 91 (39),

78 (15), 77 (66).

(667 mg, 47%, Ն98% ds) as colorless crystals; m.p. 149 °C; [α]_D

ϭ

Ϫ10.24 (c ϭ 1.25, CH₂Cl₂). Ϫ ¹H NMR (400 MHz, [D₈]THF): δ ϭ

1.12Ϫ1.23 (m, 1 H, CH₂), 1.26Ϫ1.47 (m, 3 H, CH₂), 1.73 (br. s, 1

H, CH₂), 1.92 (m, 1 H, CH₂), 2.18 (m, 1 H, CH₂), 2.50Ϫ2.60 (tdd,

J ϭ 13.8, J ϭ 4.8, J ϭ 1.9 Hz, 1 H, CH₂), 2.63 (s, 3 H, NϪCH₃),

4.00 (dd, J ϭ 10.7, J ϭ 4.4 Hz, 1 H, CH), 4.74 (t, J ϭ 10.4 Hz, 1

H, CHOH), 5.77 (d, J ϭ 9.1 Hz, 1 H, OH), 6.46 (d, J ϭ 1.9 Hz, 1

H, ϭCH), 7.19Ϫ7.25 (m, 1 H, p-Ph), 7.29Ϫ7.35 (m, 2 H, m-Ph),

7.40Ϫ7.44 (m, 2 H, o-Ph), 7.55Ϫ7.63 (m, 3 H, m-, p-Ph), 7.90Ϫ7.93

(m, 2 H, o-Ph). Ϫ ¹³C NMR (100 MHz, [D₈]THF): δ ϭ 21.5 (u),

28.7 (u), 28.9 (u), 29.7 (d), 33.4 (u), 46.8 (d), 74.8 (d), 127.8 (d),

128.0 (d), 128.7 (d), 129.0 (d), 129.9 (d), 130.2 (d), 133.4 (d), 141.6

(u), 146.8 (u), 160.6 (u). Ϫ MS (EI): m/z (%) ϭ 356 [M^ϩ] (4), 250

(15), 171 (6), 158 (5), 157 (9), 156 (100), 125 (38), 124 (5), 107 (5),

96 (5), 95 (58), 76 (11).

General Procedure for γ-Hydroxyalkylation of the Allylic Sulfoxim-

ine 15 Using 2.1 Equiv. of ClTi(OiPr)₃(GP6): To a solution of 15

(1.0 mmol) in Et₂O (10 mL) at Ϫ78 °C was added nBuLi (0.68 mL,

1.6  solution in hexane, 1.1 mmol). After stirring for 10 min at

Ϫ78 °C, ClTi(OiPr)₃(2.1 mmol), either neat or in Et₂O (2 mL), was

added. The resulting mixture was stirred for 10 min at Ϫ78 °C,

allowed to warm to room temperature, and stirred for 2 h. It was

then cooled to Ϫ78 °C once more, whereupon the aldehyde

(2 mmol) was added dropwise and stirring was continued for 2 h at

Ϫ78 °C. The mixture was then poured into aqueous NaHCO₃solu-

tion and extracted with EtOAc. The combined organic phases were

dried (MgSO₄) and concentrated in vacuo.

General Procedure for α-Hydroxyalkylation of Allylic Sulfoximines

(GP7): To a solution of the allylic sulfoximine 4 or 6 (1.0 mmol) in

THF (5 mL) at Ϫ78 °C was added nBuLi (0.68 mL, 1.60  solution

in hexane, 1.1 mmol). After stirring for 10 min at Ϫ78 °C, ClTi(-

NEt₂)₃(1.2 mmol), either neat of in THF (2 mL), was added drop-

wise and stirring was continued for a further 10 min at Ϫ78 °C.

The mixture was then allowed to warm to 0 °C, stirred for 30 min

at this temperature, and cooled to Ϫ78 °C once more, whereupon

the aldehyde (1.5Ϫ2 mmol) was added dropwise. After stirring for

2 h at Ϫ78 °C, the mixture was poured into saturated aqueous

(NH₄)₂CO₃solution and extracted with EtOAc. The combined or-

ganic phases were dried (MgSO₄) and concentrated in vacuo. The

allylic sulfoximine 10 was isolated by crystallization or chromato-

graphy.

(Z)-(S)-1-{(R)-2-[(S)-N-Methyl-S-phenysulfonimidoyl]l-

methylenecyclohexyl}propan-1-ol (16b): Reaction of 15 (501 mg,

2.00 mmol) with propanal according to GP6 furnished a mixture

of recovered 15 (23%) and 16b (77% cy, Ն96% ds). Ϫ ¹H NMR

(300 MHz, CDCl₃): δ ϭ 1.05 (t, J ϭ 7.4 Hz, 3 H, CH₃), 1.32Ϫ1.58

(m, 4 H, CH₂), 1.74Ϫ1.92 (m, 3 H, CH₂CH₃, CH₂), 2.15 (m, 2 H,

CH₂CH₃, CH₂), 2.45 (td, J ϭ 13.2, J ϭ 5.2 Hz, 1 H, CH₂), 2.59

(s, 3 H, NϪCH₃), 3.73 (br. dd, J ϭ 10.4, J ϭ 4.0 Hz, 1 H, CH),

3.79 (br. td, J ϭ 8.5, J ϭ 2.7 Hz, 1 H, CHOH), 6.30 (d, J ϭ 1.7 Hz,

1 H, ϭCH), 7.49Ϫ7.64 (m, 3 H, m-, p-Ph), 7.78Ϫ7.92 (m, 2 H, o-

Ph). Ϫ ¹³C NMR (100 MHz, CDCl₃): δ ϭ 8.6 (d), 20.1 (u), 22.4

(u), 25.4 (u), 29.6 (d), 32.7 (u), 42.4 (d), 71.0 (d), 126.3 (d), 128.6

(d), 129.6 (d), 132.5 (d), 139.6 (u), 160.8 (u).

(E)-(2R,3R)-3-[(S)-N-Methyl-S-phenylsulfonimidoyl]hex-4-

en-2-ol (E-10a): Reaction of E-4a (210 mg, 1.00 mmol) with ethanal

according to GP7 gave a mixture of recovered E-4a (23%), E-10a

(31% cy, Ն96% ds), and 7a (46% cy, 92% ds) besides a (Z)-diastere-

omer.

E-10a: ¹H NMR (400 MHz, C₆D₆): δ ϭ 1.14 (dd, J ϭ 6.3, J ϭ

1.6 Hz, 3 H, 6-H), 1.20 (d, J ϭ 6.3 Hz, 3 H, 1-H), 2.61 (s, 3 H,

NϪCH₃), 3.47 (dd, J ϭ 9.3, J ϭ 9.3 Hz, 1 H, 3-H), 4.58 (dq, J ϭ

15.1, J ϭ 6.6 Hz, 1 H, 2-H), 4.87 (dq, J ϭ 9.1, J ϭ 6.3 Hz, 1 H,

5-H), 5.15 (ddq, J ϭ 10.4, J ϭ 10.4, J ϭ 1.7 Hz, 1 H, 4-H), 7.2

(br. s, 1 H, OH), 6.92Ϫ6.96 (m, 3 H, m-Ph, p-Ph), 7.56Ϫ7.62 (m,

2 H, o-Ph).

(؊)-(Z)-(S)-1-{(R)-2-[(S)-N-Methyl-S-phenylsulfonimidoyl]-

methylenecyclohexyl}-2-methylpropan-1-ol (16c): Reaction of 15

(501 mg, 2.00 mmol) with 2-methylpropanal according to GP6 fur-

nished a mixture of recovered 15 (23%) and 16c (77% cy, 96% ds).

Crystallization of the residue (diethyl ether) gave the diastereopure

sulfoximine 16c (381 mg, 59%) as colorless crystals; m.p. 101 °C;

[α]_Dϭ Ϫ130.1 (c ϭ 0.99, diethyl ether). Ϫ ¹H NMR (300 MHz,

[D₈]THF): δ ϭ 0.87 (d, J ϭ 6.7 Hz, 3 H, CH₃), 1.08 (d, J ϭ 7.1 Hz,

3 H, CH₃), 1.15Ϫ1.55 (m, 4 H, CH₂), 1.69 (m, 1 H, CH₂),

(E)-(3R,4R)-4-[(S)-N-Methyl-S-phenylsulfonimidoyl]hept-

5-en-3-ol (E-10b): Reaction of E-4a (230 mg, 1.10 mmol) with pro-

panal according to GP7 gave a mixture of E-10b (50% cy, Ն96%

ds), recovered E-4a (38% cy), and 7b (12% cy, Ն96% ds).

1.76Ϫ1.88 (m, 2 H, 2-H, CH₂), 2.08 (br. d, J ϭ 14.1 Hz, 1 H, CH₂), E-10b: ¹H NMR (400 MHz, CDCl₃): δ ϭ 0.95 (t, J ϭ 7.3 Hz, 3 H,

2.44 (dd, J ϭ 4.9, J ϭ 1.3 Hz, 1 H, CH₂), 2.45 (s, 3 H, NϪCH₃),

Eur. J. Org. Chem. 2000, 3973Ϫ4009

1-H), 1.27Ϫ1.40 (m, 1 H, 2-H), 1.50 (dd, J ϭ 6.3, J ϭ 1.7 Hz, 3

4001

H.-J. Gais et al.

FULL PAPER

H, 7-H), 1.55Ϫ1.65 (m, 1 H, 2-H), 2.65 (s, 3 H, NϪCH₃), 3.53 (dd,

106 (20), 95 (24), 78 (48), 77 (19). Ϫ C₁₄H₂₁NO₂S (267.3): calcd. C

J ϭ 9.9, J ϭ 9.9 Hz, 1 H, 4-H), 4.38 (ddd, J ϭ 9.3, J ϭ 9.3, J ϭ 62.89, H 7.92, N 5.24; found C 63.13, H 7.62, N 5.26.

3.0 Hz, 1 H, 3-H), 4.97 (dq, J ϭ 15.4, J ϭ 6.3 Hz, 1 H, 6-H), 5.20

(؉)-(E)-(3R,4R)-4-[(S)-N-Methyl-S-phenylsulfonimidoyl]-2-

(ddq, J ϭ 10.4, J ϭ 10.4, J ϭ 1.7 Hz, 1 H, 5-H), 7.0 (br. s, 1 H,

methyloct-5-en-3-ol (E-10f): Reaction of E-4b (320 mg, 1.43 mmol)

OH), 7.50Ϫ7.56 (m, 2 H, m-Ph), 7.57Ϫ7.62 (m, 1 H, p-Ph),

with 2-methylpropanal according to GP7 gave a mixture of E-10f

7.72Ϫ7.76 (m, 2 H, o-Ph). Ϫ ¹³C NMR (100 MHz, CDCl₃): δ ϭ

(94% cy, Ն96 ds) and 7f (3% cy, Ն96 ds). Subsequent chromato-

graphy (EtOAc/hexane/NEt₃, 75:24:1) afforded diastereopure E-10f

8.6 (d), 18.0 (d), 27.6 (u), 29.7 (d), 69.1 (d), 73.4 (d), 119.7 (d),

128.8 (d), 130.0 (d), 132.8 (d), 135.6 (d).

(200 mg, 47%) as a colorless oil; [α]_Dϭ ϩ231.5 (c ϭ 1.22, CH₂Cl₂).

1

Ϫ H NMR (400 MHz, CDCl₃): δ ϭ 0.73 (t, J ϭ 7.5 Hz, 3 H, 8-

Reaction of E-4a (145 mg, 0.69 mmol) with propanal according to

H), 0.79 [d, J ϭ 6.6 Hz, 3 H, CH(CH₃)₂], 1.08 [d, J ϭ 6.8 Hz, 3 H,

GP7, with the modifications that the aldehyde was added at room

CH(CH₃)₂], 1.71 (dsept, J ϭ 6.8, J ϭ 2.0 Hz, 1 H, 7-H), 1.85 (m,

temperature and that the mixture was stirred for 2 h at room tem-

perature, gave a mixture of E-10b (79% cy, Ն96% ds), recovered E-

2 H, 7Ј-H, 2-H), 2.64 (s, 3 H, NϪCH₃), 3.59 (dd, J ϭ 9.9, J ϭ

10.2 Hz, 1 H, 4-H), 4.33 (dd, J ϭ 9.6, J ϭ 2.2 Hz, 1 H, 3-H), 5.02

4a (9%), and 7b (11% cy, Ն96% ds).

(dt, J ϭ 15.4, J ϭ 6.3 Hz, 1 H, 6-H), 5.18 (ddd, J ϭ 15.4, J ϭ 10.4,

J ϭ 1.4 Hz, 1 H, 5-H), 6.81 (br. s, 1 H, OH), 7.52Ϫ7.64 (m, 3 H,

(؉)-(E)-(3R,4R)-2-Methyl-4-[(S)-N-methyl-S-phenylsulfon-

Ph), 7.76 (m, 2 H, Ph). Ϫ ¹³C NMR (100 MHz, CDCl₃): δ ϭ 12.9

imidoyl]hept-5-en-3-ol (E-10c): Reaction of E-4a (247 mg,

(d), 13.0 (d), 20.0 (d), 25.5 (u), 29.7 (d), 30.6 (d), 71.6 (d), 72.6 (d),

1.18 mmol) with 2-methylpropanal according to GP7 gave a mix-

117.3 (d), 128.8 (d), 130.0 (d), 132.9 (d), 135.6 (u), 142.3 (d). Ϫ IR

ture of E-10c (93% cy, Ն96% ds), recovered E-4a (3%), and 7c (4%

(CHCl₃): ν˜ ϭ 3261 (s, br), 3064 (m), 3008 (m), 2964 (s), 2932 (s),

cy, Ն96% ds). Subsequent chromatography (EtOAc/hexane/NEt₃,

75:24:1) furnished diastereopure E-10c (252 mg, 76%) as a colorless

2874 (s), 2806 (m), 1969 (w), 1817 (w), 1663 (w), 1583 (m), 1446

(s), 1371 (m), 1383 (m), 1366 (m), 1355 (m), 1305 (w), 1282 (m),

1237 (s), 1202 (s), 1177 (s), 1150 (s), 1112 (s), 1082 (s), 1070 (s),

1025 (m), 1000 (s), 972 (m), 942 (m), 901 (w), 861 (s), 757 (s), 717

(m). Ϫ MS: m/z (%) ϭ 296 [M^ϩϩ 1] (1), 266 (6), 252 (10), 223

(15), 208 (5), 156 (61), 155 (20), 125 (52), 123 (14), 107 (100), 106

(13), 97 (13), 78 (41), 77 (14), 71 (34). Ϫ C₁₆H₂₅NO₂S (295.4):

calcd. C 64.99, H 8.53, N 4.74; found C 64.55, H 8.25, N 4.34.

oil; [α]_Dϭ ϩ170.9 (c ϭ 1.10, CH₂Cl₂). Ϫ ¹H NMR (400 MHz,

CDCl₃): δ ϭ 0.77 [d, J ϭ 6.4 Hz, 3 H, CH(CH₃)₂], 1.07 [d, J ϭ

6.9 Hz, 3 H, CH(CH₃)₂], 1.48 (dd, J ϭ 6.6, J ϭ 1.6 Hz, 3 H, 7-H),

1.71 (septd, J ϭ 6.9, J ϭ 2.2 Hz, 1 H, 2-H), 2.64 (s, 3 H, NϪCH₃),

3.55 (dd, J ϭ 9.9, J ϭ 9.8 Hz, 1 H, 4-H), 4.33 (dd, J ϭ 9.6, J ϭ

1.9 Hz, 1 H, 3-H), 4.97 (dq, J ϭ 15.4, J ϭ 6.7 Hz, 1 H, 6-H), 5.20

(ddq, J ϭ 10.4, J ϭ 10.4, J ϭ 1.7 Hz, 1 H, 5-H), 6.84 (br. s, 1 H,

OH), 7.50Ϫ7.56 (m, 2 H, m-Ph), 7.57Ϫ7.62 (m, 1 H, p-Ph),

7.72Ϫ7.76 (m, 2 H, o-Ph). Ϫ ¹³C NMR (100 MHz, CDCl₃): δ ϭ

13.5 (d), 18.4 (d), 20.4 (u), 29.9 (d), 31.0 (d), 72.0 (d), 73.0 (d),

119.7 (d), 129.1 (d), 130.4 (d), 133.2 (d), 135.9 (d), 136.1 (u). Ϫ IR

(CHCl₃): ν˜ ϭ 3259 (w, br), 3063 (w), 3010 (w), 2965 (s), 2934 (m),

2916 (m), 2874 (m), 2806 (w), 1472 (m), 1446 (s), 1366 (w), 1281

(w), 1237 (vs), 1177 (w), 1151 (vs), 1111 (m), 1082 (s), 1023 (w),

1005 (m), 970 (m), 861 (m), 758 (vs), 728 (m), 713 (m). Ϫ MS (EI):

m/z (%) ϭ 238 [M^ϩϪ CH(CH₃)₂] (16), 208 (22), 161 (14), 156 (73),

155 (24), 138 (27), 126 (13), 125 (62), 107 (100), 97 (11), 78 (55),

71 (28). Ϫ MS (CI): m/z (%) ϭ 282 [M^ϩϩ 1] (32), 156 (100), 127

(17).Ϫ C₁₅H₂₃NO₂S (281.4): calcd. C 64.02, H 8.24, N 4.98; found

C 63.93, H 8.39, N 5.02.

(؉)-(Z)-(2R,3R)-6-Methyl-3-[(S)-N-methyl-S-phenylsulfon-

imidoyl]hept-4-en-2-ol (E-10g): Reaction of E-4c (240 mg,

1.01 mmol) with ethanal according to GP7 gave a mixture of reco-

vered E-4c (46%), E-10g (27% cy, Ն96% ds), and 7g (27% cy, 85%

ds) besides a Z-diastereomer.

E-10g: ¹H NMR (400 MHz, CDCl₃): δ ϭ 0.71 [d, J ϭ 6.6 Hz, 3

H, CH(CH₃)₂], 0.76 [d, J ϭ 6.9 Hz, 3 H, CH(CH₃)₂], 1.15 (d, J ϭ

6.3 Hz, 3 H, 1-H), 2.10 (octd, J ϭ 6.8, J ϭ 1.2 Hz, 1 H, 6-H), 2.64

(s, 3 H, NϪCH₃), 3.49 (dd, J ϭ 9.9, J ϭ 9.3 Hz, 1 H, 3-H), 4.56

(dq, J ϭ 9.3, J ϭ 6.3 Hz, 1 H, 2-H), 4.98 (dd, J ϭ 15.4, J ϭ 6.9 Hz,

1 H, 5-H), 5.11 (ddd, J ϭ 15.4, J ϭ 10.2, J ϭ 1.2 Hz, 1 H, 4-H),

6.80 (br. s, 1 H, OH), 7.50Ϫ7.63 (m, 3 H, m-Ph, p-Ph), 7.74Ϫ7.82

(m, 2 H, o-Ph).

(؉)-(E)-(2R,3R)-3-[(S)-N-Methyl-S-phenylsulfonimidoyl]-

hept-4-en-2-ol (E-10e): Reaction of E-4b (610 mg, 2.73 mmol) with

ethanal according to GP7, with the modification that the aldehyde

was added at Ϫ30 °C, gave a mixture of E-10e (50% cy, Ն96 ds),

recovered E-4b (8%), and 7e (42% cy, Ն96% ds). Crystallization

(diethyl ether) gave diastereopure E-10e (352 mg, 48%) as colorless

crystals; m.p. 142 °C; [α]_Dϭ ϩ229.5 (c ϭ 1.31, MeOH). Ϫ ¹H

Reaction of E-4c (178 mg, 0.75 mmol) with ethanal according to

GP7, with the modifications that the aldehyde was added at room

temperature and that the mixture was stirred for 2 h at room tem-

perature, gave a mixture of recovered E-4c (72%), E-10g (18% cy,

Ն96% ds), and 7g (10% cy, 90% ds) besides a (Z)-diastereomer.

(؉)-(E)-(3R,4R)-7-Methyl-4-[(S)-N-methyl-S-phenylsulfonimidoyl]-

NMR (400 MHz, CDCl₃): δ ϭ 0.74 (t, J ϭ 7.4 Hz, 3 H, 7-H), 1.85 oct-5-en-3-ol (E-10h): Reaction of E-4c (240 mg, 1.01 mmol) with

(m, 2 H, 6-H), 1.28 (d, J ϭ 6.1 Hz, 3 H, 1-H), 2.65 (s, 3 H, propanal according to GP7, with the modifications that the alde-

NϪCH₃), 3.49 (t, J ϭ 9.6 Hz, 1 H, 3-H), 4.56 (dq, J ϭ 9.4, J ϭ hyde was added at room temperature and that the mixture was

6.2 Hz, 1 H, 2-H), 5.04 (dd, J ϭ 15.4, J ϭ 6.3 Hz, 1 H, 4-H), 5.16 stirred for 2 h at room temperature, furnished crude E-10h with

(dt, J ϭ 15.4, J ϭ 9.4 Hz, 1 H, 5-H), 6.89 (br. s, 1 H, OH), 7.53 Ն96% ds, containing less than 1% of 7h. Crystallization (diethyl

(m, 2 H, Ph), 7.59 (m, 1 H, Ph), 7.76 (m, 2 H, Ph). Ϫ ¹³C NMR

ether) afforded diastereopure E-10h (259 mg, 87%) as colorless

(100 MHz, CDCl₃): δ ϭ 11.4 (d), 21.4 (d), 24.3 (u), 29.7 (d), 65.3 crystals; m.p. 82 °C; [α]_Dϭ ϩ134.8 (c ϭ 0.95, CH₂Cl₂). Ϫ ¹H

(d), 69.2 (d), 118.0 (d), 129.0 (d), 130.1 (d), 133.1 (d), 135.8 (u), NMR (400 MHz, CDCl₃): δ ϭ 0.70 [d, J ϭ 6.6 Hz, 3 H,

148.0 (d). Ϫ IR (KBr): ν˜ ϭ 3240 (s, br), 3061 (m), 3028 (m), 2965 CH(CH₃)₂], 0.75 [d, J ϭ 6.9 Hz, 3 H, CH(CH₃)₂], 0.95 (t, J ϭ

(s), 2930 (s), 2870 (s), 2801 (m), 2002 (w), 1910 (w), 1818 (w), 1779 7.4 Hz, 3 H, 1-H), 1.34 (dquin, J ϭ 14.0, J ϭ 7.4 Hz, 1 H, 2-H),

(w), 1698 (w), 1656 (w), 1583 (m), 1467 (s), 1443 (s), 1371 (m), 1342 1.58 (dqd, J ϭ 14.0, J ϭ 7.4, J ϭ 3.3 Hz, 1 H, 2-H), 2.10 (octd,

(m), 1317 (m), 1235 (s), 1210 (s), 1148 (s), 1120 (s), 1082 (s), 1069

(s), 1027 (m), 999 (m), 936 (m), 856 (s), 812 (w), 798 (w), 760 (m), J ϭ 9.9, J ϭ 9.6 Hz, 1 H, 4-H), 4.39 (ddd, J ϭ 9.3, J ϭ 7.7, J ϭ

728 (s). Ϫ MS: m/z (%) ϭ 268 [M^ϩϩ 1] (1), 238 (21), 223 (43),

3.3 Hz, 1 H, 3-H), 4.94 (dd, J ϭ 15.4, J ϭ 6.9 Hz, 1 H, 6-H), 5.13

208 (17), 156 (38), 155 (29), 154 (21), 138 (13), 125 (60), 107 (100), (ddd, J ϭ 15.4, J ϭ 10.2, J ϭ 1.2 Hz, 1 H, 5-H), 6.90 (br. s, 1 H,

J ϭ 6.7, J ϭ 1.1 Hz, 1 H, 7-H), 2.64 (s, 3 H, NϪCH₃), 3.53 (dd,

4002

Eur. J. Org. Chem. 2000, 3973Ϫ4009

Article Doi

N-methylsulfonimidoyl-substituted (2-alkenyl)titanium complexes: Application to the synthesis of β- and δ-sulfonimidoyl-substituted chiral homoallylic alcohols, x-ray crystal structure analysis, and fluxional behavior

DOI: 10.1002/1099-0690(200012)2000:24<3973::AID-EJOC3973>3.0.CO;2-B

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Full text of DOI:10.1002/1099-0690(200012)2000:24<3973::AID-EJOC3973>3.0.CO;2-B

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