Diastereo- and enantiomerically pure allylboronates: Their synthesis and scope

DOI: 10.1002/chem.200800034

Diastereo- and Enantiomerically Pure Allylboronates:

Their Synthesis and Scope

Jçrg Pietruszka,*^[a]Niklas Schçne,^[a]Wolfgang Frey,^[b]and Li Grundl^[b]

Abstract: Allylboronates are highly at-

tractive reagents for allyl additions.

Enantiomerically pure, stable reagents

with a stereogenic centre in a-position

to boron are especially versatile, albeit

often difficult to synthesize. Starting

from boron-containing allyl alcohols 6

and 7, which are discussed in detail

herein, a set of reagents were obtained

via [3,3]-sigmatropic rearrangements

and consecutive transformations in the

side chain. The configurations could be

established first by chemical correla-

tion, but also by X-ray crystallography

(16, 18, 34, and 39). Allyl additions

were performed resulting in the forma-

tion of predominantly (Z)-configured

homoallylic alcohols (31, 43–45) with

high enantiomeric excess. Detailed in-

vestigations on the matched–mis-

matched interaction between the re-

agents 15/16 (and ent-15/ent-16, respec-

tively) and isopropylidene glyceralde-

hyde 42d are presented.

Keywords: allylation · asymmetric

synthesis · boron · rearrangement ·

sigmatropic reactions

Introduction

be needed. Exemplary systematic work on the issue has

been published by Hoffmann et al. who proved that by in-

creasing the steric bulk of the boronic ester protecting

group (“R¹”, Scheme 1) the (Z)-olefinic product would be

favored.^[4]Furthermore, an electron-withdrawing group “R³”

will also enhance the (Z)-selectivity. The relative “R²”/“R⁴”-

configuration is still determined by the configuration of the

double bond in the reagent and the favored equatorial posi-

tioning of the bulky substituent of the aldehyde.

Reagents for allyl additions are a key for the success of

many syntheses. From the range of possible allyl–metal com-

pounds, the boron derivatives are special: It can be assumed

that the reliability in terms of yield, selectivity and especial-

ly predictability is one reason. The reagents are also non-

toxic and usually not very costly. The transformations can

be performed using rather mild reaction conditions, thus

various functional groups are also tolerated.^[1]The enantio-

and diastereomerically pure allyl- and crotylboronic esters

introduced by Roush et al. in 1985,^[2]proved to be especially

versatile and many applications have been reported. Related

allylboranes were reported by Brown et al.^[3]A common fea-

ture of these reagents is that the stereochemical information

is in all cases in the periphery of the transition state for the

addition. A stereogenic centre in the core of the transition

state should be advantageous in terms of selectivity for the

formation of the homoallylic alcohol. To achieve the goal, a

substituent in position a to boron in the allyl moiety would

Scheme 1. Stereochemical reasoning of allyl additions.

Hoffmann et al. synthesized their reagents either by Mat-

teson homologation using a diastereo- and enantiomerically

pure dichloromethylboronic ester or by diastereoselective

crotylation of a pure boric ester. Alternatively, appropriate

enantiomerically pure alkenylboron derivatives could be re-

arranged using thionylchloride or sodium hydroxide. Purifi-

cation proved to be difficult in all cases, the separation of

diastereomers was not possible due to the lack of stability of

[a] Prof. Dr. J. Pietruszka, Dr. N. Schçne

Institut für Bioorganische Chemie der Heinrich-Heine-Universität

Düsseldorf im Forschungszentrum Jülich

Stetternicher Forst, Geb. 15.8, 52426 Jülich (Germany)

Fax : (+49)2461-616196

E-mail: j.pietruszka@fz-juelich.de

[b] Dr. W. Frey, Dr. L. Grundl

Institut für Organische Chemie der Universität Stuttgart

Pfaffenwaldring 55, 70569 Stuttgart (Germany)

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FULL PAPER

the intermediates. Nevertheless, the reagents have been suc-

cessfully applied in several natural product syntheses.^[5]Fang

and Aggarwal used enantiomerically pure sulphur ylides to

perform the stereoselective rearrangement: Alkenylboron

compounds were thus converted to a-substituted allylbor-

anes.^[6]Another elegant approach was recently published by

Roush et al. who used the (ꢀ)-diisopinocampheylborane for

the hydroboration of an allenylboronic ester thus generating

an allylboronic ester. After the first addition to an aldehyde,

a second allylboronic ester with a stereogenic centre a to

boron is generated that adds to a second aldehyde in a

highly diastereoselective manner. The configuration (also of

the double bond) is determined by the steric bulk of the

boronic ester. Allenes were also used as substrates for selec-

tive hydroborations or diborations including some kinetic

resolutions to furnish the corresponding reagents in high op-

tical purity.^[7]The Diels–Alder reaction could also be ap-

plied to yield allylboronic esters in a highly diastereo- and

enantioselective manner.^[5h,8]More recently Ito et al. report-

ed a successful allylic substitution utilizing bis(pinacolato)di-

borane to furnish the desired products.^[9]Hoppe et al.

proved that allyltitanium species—derived by enantioselec-

tive deprotonation of allylcarbonates—could not only be di-

rectly used for allyl additions, but were also transformed to

enantiomerically enriched allylboronic esters or allylstan-

nanes.^[10,11]It should be noted that among other methods, al-

lylstannanes could also be generated via Ireland and Es-

chenmoser rearrangement of tin-substituted allyl alcohols.

More broadly applicable are the corresponding allylsilanes

that are also accessible via the corresponding sigmatropic

reactions.^[12]Allyl additions with these reagents generally

lead to (E)-configured homoallylic alcohols. The (Z)-deriva-

tives are generally more difficult to access, an obvious ad-

vantage of bulky boron reagents.

Figure 1. Abbreviations and general synthetic scheme.

(Scheme 2);^[14e,16]subsequent deprotection under acidic con-

ditions furnished the desired product 6 in 66% yield. Direct

hydroboration of the TMS-ether 8a (TMS=Me₃Si) could

not be achieved. While the TMS-protecting group is cheap-

er, the TBS route (TBS=tBuMe₂Si) is favored by a higher

overall yield (up to 89%). The regioisomer

9 (see

In order to enhance the stability of boron derivatives, we

introduced diol 1—readily available in both enantiomeric

forms from tartrate^[13]—as a convenient protecting group

for boronic acids.^[13b,14]We demonstrated that a wide variety

of transformations in the side-chain “R” of esters 2 and 3,

Scheme 5) was only isolated after the deprotection step in

up to 5% yield.

ꢀ

respectively, are possible, without cleaving the carbon

boron bond. We speculated that the sometimes harsh reac-

tion conditions of [3,3]-sigmatropic rearrangements (general

scheme: see Figure 1) would not be a problem for this type

of compounds. Hence, the g,d-unsaturated esters 4 and 5

should be available from allyl alcohols 6 or 7. Indeed, we re-

cently demonstrated that the approach is feasible;^[15]herein

we describe the full details of our findings.

Scheme 2. a) i) Cyclohexene, H₃B·Me₂S, 1 h, DME, 08C!RT; ii) 8a, 1 h;

iii) Me₃NO; iv) 1; b) HCl, H₂O/EtOH, 66% over 2 steps; c) diol 1,

H₃B·Me₂S, 3 h, CH₂Cl₂, 508C, then 8b, 1208C; d) HF, MeCN, 08C, 89%

over 2 steps.

The synthesis of (Z)-alcohol 7 proved to be more difficult.

As an alternative to the previously reported route via the

corresponding vinyl iodide,^[14f]we pursued a sequence in-

volving the syn reduction of alkynylboronates^[17]which in

turn needed to be synthesized from alkyne 8 (8!10!11!

12). Despite some optimization with the pentyl-derivative

8c, we were unable to improve the yield beyond 49% (over

three steps). The limiting step was the formation of ester 11

that was achieved by treatment of the ate-complex 10 with

BF₃·Et₂O.^[18]However, omitting the step and directly per-

forming the transesterification only led to cleavage of the

Results and Discussion

Synthesis of allyl alcohols: The (E)-allyl alcohol 6 is readily

available from silyl-protected propargylic alcohols 8a or 8b,

either via direct hydroboration of 8b^[13b]and consecutive de-

protection or by using a conventional one-pot hydoboration

(with dicyclohexylborane), oxidation (with Me₃NO), transes-

terification (with diol 1) sequence with ether 8a as substrate

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5179

J. Pietruszka et al.

ꢀ

Table 1. Johnson rearrangement with allyl alcohol 6.

C B bond. With protected propargylic alcohols 8b and 8d

the yield further decreased and only 37 and 30% of alkynes

12b and 12d were obtained, respectively (Scheme 3). De-

Entry equiv

Catalyst

T

t

Yield [%]

MeC

A

[8C]

[h] 15+16

1

2

3

8.6

7.0

0.21equiv EtCO₂H 135

12

5

9

0

57

65

Amberlyst

Montmorillonite

KSF/O

135

4

7.0

0.06 equiv

EtCO₂H

135

3.5 78(+19 6)

G

Scheme 3. a) i) nBuLi, Et₂O, ꢀ788C; ii)

B(OiPr)₃; b) i) 1.33 equiv

BF₃·Et₂O, THF, ꢀ788C; ii) diol 1, THF, ꢀ788C!RT.

G

ic esters 15 or 16, the best results were obtained when using

standard conditions (entry 4: 0.06 equiv propionic acid,

3.5 h, 1358C) preventing prolonged heating and ensuring

continuous removal of ethanol. Along with the 1:1 diaste-

reomeric mixture of products (78%), 19% of the starting

material 6 could be recovered. It should be noted that the

highly stable and conveniently storable reagents are readily

separated into the diastereo- and enantiomerically pure al-

lylboronic esters 15 and 16 by means of MPLC. Under iden-

tical reaction conditions (Scheme 5) similar yields were ob-

tained when utilizing allyl alcohols ent-6 (yield: 71% of a

50:50 mixture of ent-15/ent-16 + 19% starting material re-

covered), 7 (yield: 59% of a 30:70 mixture of 15/16) or 9

(64% of 17).

spite the fact that the reduction of alkynylboronic ester 12b

with hydrogen in the presence of Lindlarꢁs catalyst was ach-

ieved to furnish (Z)-olefin 13 in high yield (95%,

Scheme 4), we looked for an alternative since its deprotec-

tion yielded alcohol 7 in only 62%. On the other hand, desi-

lylation of ether 12b was readily achieved and product 14

was isolated in 96% yield as a crystalline solid; its structure

was confirmed by X-ray crystallography. Unfortunately we

were unable to successfully perform a (Z)-selective reduc-

tion of the triple bond of 14; no alkenylboronic ester 7

could be isolated. In our hands, a one-pot sequence includ-

ing a Rh^I-catalyzed hydroboration with catecholborane was

most practical:^[19]After transesterification with diol 1 the

common intermediate 13 was directly obtained in moderate

yield (63%; Scheme 4).^[15c]

Scheme 4. a) Catecholborane, cat. [Rh(cod)Cl]₂, iPr₃P, Et₃N, cyclohexane,

U

RT; ii) diol 1, RT, 63%; b) HCl, H₂O/EtOH, 62%; c) see Scheme 3; d)

H₂, Lindlar catalyst, cyclohexane, toluene, 95%; e) HCl, H₂O/MeOH,

96%.

Scheme 5. a) 7.00 equiv MeC(OEt)₃, 0.06 equiv EtCO₂H, 1358C.

A

The Eschenmoser rearrangement proved to be more chal-

lenging with alcohols 6, 7 and 9.^[21]The temperature was cru-

cial for the success of the transformation to allylboronic

esters 18/19 (Table 2): At 608C no product could be detect-

ed (entry 1); however, when increasing the temperature,

ꢁ808C seem (entry 2) to be the optimum, since high degree

of decomposition was observed at elevated temperature

(use of xylene, entry 5, but at higher temperature). While ef-

fective removal of methanol is essential in all cases, the con-

centration of the substrate in toluene also has a marked in-

fluence on the yield (entries 2–4). Under these reaction con-

ditions a 50:50 separable, stable mixture of diastereomers

18/19 was isolated in 73% yield. While the same rearrange-

ment led to vinylboronic ester 20 in an unoptimized 44%

yield when starting from alcohol 9, none of the expected re-

A

possibility of [3,3]-sigmatropic rearrangements starting from

alkenylboronic esters 6, 7 and 9.^[15]The initial studies were

performed utilizing alcohol 6 in a modified Johnson reac-

tion.^[20]It was immediately obvious that prolonged reaction

times under the harsh reaction conditions (Table 1, entry 1)

used will always lead to decomposition of boronic esters; no

product 15 or 16 was obtained. While keeping the tempera-

ture high (1358C; lower temperatures dramatically de-

creased the rate and ultimately the yield), different acidic

catalysts or catalyst loadings were tested (e.g. entries 2–4).

Although both, amberlyst- and montmorillonite-catalyzed

transformations provided reasonable amounts of allylboron-

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Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

arrangement products were observed when using the (Z)-

olefin 7 (Scheme 6). Instead, the only product we found was

the highly interesting homoenolate equivalent 21. We previ-

nately, when treating either of the three esters 22–24 with

base (e.g. with LDA), only decomposition of the boronic

esters were observed. We then focused our efforts on the

imidates 25/26.

First, we tested thermal conditions to encourage the rear-

rangement of the chloro derivative 25 (Table 3). In refluxing

toluene no conversion was observed (entry 1), only at higher

temperature product formation was detected (entries 2–3).

Prolonged heating led to higher conversion of 25, but also

to partial decomposition of the product. While microwave

heating had no pronounced effect (entry 4), reducing the

substrate concentration resulted in highest isolated yield

(entry 5: 67% yield of 27 along with 10% starting material

25). The diastereomeric ratio of crude product was deter-

Scheme 6. Rearrangements using Eschenmoser conditions.^[24]

ously accounted an intramolecular complexation of the in-

termediate and a consecutive S_N2’-like substitution for its

formation. However, a clear explanation for the high diaste-

reoselectivity (only the shown diastereomer is formed!) is

still elusive.

Table 3. Overman rearrangement with trichloroacetimidate 25.

Entry

Solvent

T [8C]

(t [h])

Yield [%]

dr 27^[a]

(c=mmol 25 per mL)

1

toluene

110

(11)

155

(56)

170

no conversion

43 (27), 7 (25)

52 (27), 22 (25)

44% 27, 21% 25

67 (27), 10 (25)

57 (28)

–

Table 2. Eschenmoser rearrangement with allyl alcohol 6.

A

2

56:44

59:41

57:43

59:41

–

U

3

U

(10)

Entry

Solvent

T [8C]

t [h]

Yield [%]

18+19

4

170^[b]

E

(4.4)

170^[b]

(16)

80

1

2

3

4

5

toluene (2 mLmmol^ꢀ16)

toluene (4 mLmmol^ꢀ16)

toluene (1 mLmmol^ꢀ16)

xylene (1 mLmmol^ꢀ16)

60

80

78

80

18

36

20

25

24

0

5

AHCTREUNG

73

45

64

65

6^[c]

7^[d]

C

(23)

80

25, decomposition

–

A

(5)

[a] Determined by ¹H NMR spectroscopy of the crude reaction mixture;

[b] heated by microwave; [c] +5 mol% [PdCl₂(MeCN)₂]; [d] +5 mol%

[Pd(PPh₃)₄], K₂CO₃.

AHCTREUNG

Next, we looked for further alternatives to the above

shown reactions including Claisen–Ireland-,^[22]Carroll-,^[23]

and Overman-type^[24]rearrangements. The syntheses of the

precursors were straightforward: Direct acylation of alcohol

6 gave the desired products (yield 22: 98%; yield 23: 76%;

Scheme 7), the b-ketoester 24 was obtained utilizing dike-

tene (83%),^[25]and the trichloro- as well as the trifluoroace-

timidates 25 (98%) and 26 (77%), respectively, were syn-

thesized according to literature procedures.^[26,27]Unfortu-

mined to be ꢁ60:40 in all cases. Pd-catalyzed variants (e. g.

ref. [28]) that enabled lower reaction temperatures, either

led to partial decomposition of the starting material or alter-

natively to considerable amounts of the undesired chloride

28 in 57% yield (entry 6+7). At this stage we did not fur-

ther pursue the approach, since all attempts to separate the

diastereomers 27 failed. We envisaged that we might over-

come the problem with the related fluoro derivatives 29

(from 26; Table 4). Again, only the thermal rearrangement

was successful to a minor extent (entry 1: 20% product 29

and 14% starting material 26) while the Pd-catalyzed reac-

tions led to decomposition, only (entry 2+3). Separation of

diastereomers was unsuccessful and consequently no further

optimization was attempted.

In summary, while the boronic esters investigated proved

to be more robust then previously anticipated, at this stage

only few rearrangements could be successfully performed

and led to separable mixtures of diastereomers. Best results

were obtained utilizing standard Johnson conditions furnish-

ing the corresponding carboxylic esters. While—not surpris-

Scheme 7. a) Et₃N, cat. DMAP, CH₂Cl₂, Ac₂O for 22 or (EtCO)₂O for 23;

b) THF, DMAP, diketene, RT, 23 h; c) 0.20 equiv NaH, Et₂O, 0 8C,

1.20 equiv Cl₃CCN; d) 6.60 equiv F₃CCONH₂, 19.2 equiv DMSO, CH₂Cl₂,

ꢀ788C, 6.00 equiv (COCl)₂, 18.0 equiv Et₃N, 2.00 equiv DBU, then

1.00 equiv 6.

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J. Pietruszka et al.

Ozonolysis and reduction led to the known diol 33^[30]whose

configuration confirmed the structure of homoallylic alcohol

31a and—assuming a favored transition state as depicted in

Scheme 1—thus the configuration of allylboronic ester 15.

The same sequence allowed the assignment of the (R)-ester

21. Later, X-ray crystallography confirmed not only the con-

figuration of compound 16,^[15c]but also of amide 18.^[31]

Table 4. Overman rearrangement with trifluoroacetimidate 26.

Entry

Solvent

(c=mmol 26 per mL)

T [8C]

(t [h])

Yield [%]

dr 29^[a]

1

1,2-dichlorobenzene

176

(11)

80

(5)

80

20 (29), 14 (26)

decomposition

55:45

ACHTREUNG

2^[b]

3^[c]

–

Modification of side chain: Based on the knowledge that

our type of boronic ester is relatively stable, we envisaged

to broaden the scope of the new reagents, for example, in

view of various orthogonal protecting group strategies, by

simple functional group interconversions.^[15a]The carboxylic

ester moiety in 15 and 16 was the obvious choice for further

transformations (Scheme 9). Reduction of ester 15 to the

corresponding alcohol 34 was conveniently achieved by uti-

lizing DiBAlH (92%); the introduction of a silyl-protecting

group gave ether 35 in 98% yield. It should be noted that

X-ray crystallography confirmed the previously assigned

configuration of ester 15 by the solved structure of alcohol

34.^[31]By the same sequence as described above, ester 16

could be converted first to alcohol 36 and in a consecutive

step to the new reagent 37 in 94% overall yield. Further-

more, alcohol 34 could be completely reduced by superhy-

dride reduction of the corresponding mesylate 38 (95%)

giving the ethyl derivative 39 in 68% yield; its configuration

was secured by X-ray crystallography. Analogously, the dia-

stereomeric reagent 41 was obtained from alcohol 36 via

mesylate 40.

A

(2)

[a] Determined by ¹H NMR spectroscopy of the crude reaction mixture;

[b] +5 mol% [PdCl₂(MeCN)₂]; [c] +5 mol% [Pd(PPh₃)₄], K₂CO₃.

A

ACHTREUNG

ingly—low auxiliary induced diastereoselectivity was ob-

served throughout, substrate controlled rearrangements

were previously shown to be highly selective furnishing one

diastereomer only.^[15b]

Determination of configuration: Until now all configura-

tions presented were only assumed. In order to unequivocal-

ly assign them, we first turned to chemical correlations. Ini-

tially, compound 15 was directly converted to the known

diol 30 by means of reduction with LiAlH₄and oxidative

work-up (Scheme 8). The small-scale transformation fur-

nished the desired diol 30, but unfortunately as an impure

sample only. Nevertheless, the negative sign of the optical

rotation^[29]already hinted to the (S)-configuration in the al-

lylboronic ester 15, but it was obviously not the ultimate

proof. Next, we turned to the allyl addition with reagent 15

and found the exclusive formation of the (Z)-olefin 31a.

Scheme 8. Assignment of absolute configuration. a) LiAlH₄, THF,

ꢀ788C!RT, 2 h, then H₂O₂, 2 h; b) PhCHO, CH₂Cl₂, 08C!RT; c) i) O₃,

CH₂Cl₂, ꢀ788C, then Me₂S; ii) LiAlH₄, THF 08C, 1 h.

Scheme 9. a) DiBAlH, THF, ꢀ788C; b) TBSCl, imidazole, CH₂Cl₂, 12 h;

c) MeSO₂Cl, Et₃N, CH₂Cl₂; d) LiEt₃BH, THF.

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Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

Allyl additions: With a plethora of reagents in our hands

and the configurations completely assigned, we turned our

attention to allyl additions utilizing all allylboronic esters

synthesized (Scheme 10).

low (84% ee). Within the (R)-series no such problems oc-

curred and the homoallylic alcohols ent-31b and ent-43–45b

were formed exclusively as the (Z)-diastereomers (yield:

77–97%; ee > 94%). The general trend also remained

when using aldehyde 42c albeit to a lesser extent: Whereas

in the (S)-series regularly marginal amounts of the (E)-side-

product could be detected [yields of 31c and 43–45c:

86–92%; ee > 94%], the (R)-series furnished the pure

(Z)-products ent-31c and ent-43–45c (yield: 89–92%; ee

> 87%). In a preliminary experiment it was also found that

triethylsilyl-protected glycolic aldehyde was not a suitable

substrate for allyl additions; the yields were low.

The reason for the relatively high (E)-selectivity—espe-

cially when using aldehyde 42b and reagent 18—is not com-

pletely understood (Scheme 11). The favored transition

states A and B en route to homoallylic alcohols 43b and 46

(the configuration was confirmed by transformation to the

known diol 47 and comparison of the optical rotation) are

obvious; however, why these substituents support the

pseudo-equatorial positioning of all substituents (in B) re-

mains unclear. Nevertheless, when comparing transition

state B with the related transition state C for the (R)-series,

a notable difference became obvious: One bulky group of

the remote auxiliary [C; (R)-series only] is situated in the vi-

cinity of the residue in equatorial position thus rendering

this route irrelevant.

Scheme 10. Yields of allyl additions and ee values of their products.

In general, allyl additions of reagents 15, 18, 35 and 39

[abbreviated as the (S)-series] to benzaldehyde 42a were un-

problematic, the products were formed exclusively (as de-

tected by NMR of the crude products) as the (Z)-configured

olefins 31a, 43–45a (yield: 79–91%; ee > 94%). Similarly,

the enantiomers ent-31a and ent-43–45a were obtained

(yield: 67–89%; ee > 95%) from the diastereomeric boron-

ic esters 16, 19, 37 and 41 [the (R)-series]. The most unrelia-

ble substrate proved to be aldehyde 42b: Especially with

the (S)-series of reagents major amounts of the (E)-olefin

were detected in the crude product [crude 31b: 93%, Z/E

86:14; crude 43b: 98%, Z/E 70:30; crude 44b: 89%, Z/E

87:13]; yields given in Scheme 10 refer to isolated (Z)-prod-

ucts. It should be noted that (E)-43b was the only (E)-iso-

meric compound that could be obtained in pure form. When

isolating product 45b (91%) no second diastereomer was

detected. However, the enantiomeric ratio was surprisingly

Scheme 11. a) O₃, CH₂Cl₂, ꢀ788C; Me₂S. b) LiAlH₄, THF, 56% over 2

steps.

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5183

J. Pietruszka et al.

Allyl additions using isopropylidene glyceraldehyde: Finally,

we investigated matched/mismatched interactions between

diastereomeric reagents and an aldehyde bearing a stereo-

genic centre. Since the substrate selectivity is usually rela-

tively difficult to overcome when using isopropylidene glyc-

eraldehyde (42d),^[32]we took this aldehyde for our studies.

First, we looked at the ester reagents 15 and 16 (Table 5).

The (E)-product was not observed in any case; the yields

were generally high (86–92%). Substrate-controlled addi-

tion leads to the anti-product 31d, while reagent control will

either favor 31d (entry 1: reagent 15; dr 97:3) or epi-31d

(entry 2: reagent 16; dr 30:70). Obviously, the directing

effect of the substrate cannot be overruled completely in

any case; however, with reagent 16 favoring the (R)-product

epi-31d a distinct preference for its formation was found.

Beside the influence of the stereogenic centre in a-position

to the boron moiety, the configuration of the auxiliary could

also have a directing effect. Hence we turned our attention

to the enantiomeric reagents ent-15 and ent-16 (entry 3+4),

respectively. The effect of the auxiliary is small, but distinct:

Within the limits of NMR spectroscopy only one diastereo-

mer 31 could be detected when utilizing allylboronic ester

ent-16, while the syn-product epi-31d was formed with lower

selectivity (as compared to entry 2) with reagent ent-15

(entry 3: dr 35:65). In summary, substrate control was best

matched with the (3S,4’S,5’S)-reagent ent-16.

obtain a complete set of analytical data for the diastereoiso-

mers: An 80:20 diastereomeric mixture of homoallyl alco-

hols epi-43d and 43d were benzoylated furnishing esters

epi-48 and 48 in 90% yield; the products are readily separa-

ble by means of MPLC.

Table 6. Allyl additions of reagents 15, 16, ent-15 and ent-16 to aldehyde

42d.

Entry

Reagent

R²

Yield [%]

Product

dr^[a]

1

2

3

4

5

6

18

19

35

37

39

41

CONMe₂

CH₂OTBS

CH₃

63

75

69

90

81

91

43d/epi-43d

44d/epi-44d

45d/epi-45d

>99:1

27:73

89:11

29:71

95:5

CH₃

30:70

[a] Determined by ¹H NMR spectroscopy of the crude reaction mixture.

Table 5. Allyl additions of reagents 15, 16 ent-15 and ent-16 to aldehyde

42d.

Conclusion

We have reported the synthesis of a set of new enantio- and

diastereomerically pure boron reagents for allyl additions as

well as their configurational assignment. Key reactions were

[3,3]-sigmatropic rearrangements followed by standard

transformations, albeit in the presence of the boronic ester

moiety. The scope of the consecutive allylation was shown

in detail proving that the additions were dominated by the

stereogenic centre in a-position to boron thus furnishing

predominantly (Z)-homoallylic alcohols. In some cases the

products were obtained in up to quantitative yield and/or as

a single enantiomer. With a dominant chiral substrate 42d a

conclusive investigation of matched/mismatched interaction

was performed leading either exclusively to the anti-prod-

ucts or—overcoming to some extent the substrate-selectivi-

ty—with low selectivity for the syn-products.

Entry

Reagent

Yield [%]

dr 31d/epi-31d^[a]

1

2

3

4

15

16

ent-15

ent-16

86

89

92

91

97:3

30:70

35:65

>99:1

[a] Determined by ¹H NMR spectroscopy of the crude reaction mixture.

The same trend was observed when aldehyde 42d was

treated with the remaining sets of reagents (Table 6): Again,

only (Z)-products were observed in moderate to high yield

(63–91%). In all cases the anti-products 43d–45d were pre-

dominantly formed with good to excellent selectivity when

utilizing allylboronic esters of the (S)-series (entries 1,3,5),

while the (R)-series led to the syn-products epi-43d–epi-45d,

albeit with low diastereoselectivity (entries 2,4,6). Although

diastereomerically pure products were obtained in some

cases, it should be noted that the diastereomers are not

always easily separated by column chromatography. In one

case a further derivatization was performed in order to

Experimental Section

Unless specified the reactions were carried out by using standard Schlenk

techniques under dry N₂with magnetic stirring. Glassware was oven-

dried at 1208C over night. Solvents were dried and purified by conven-

tional methods prior to use; tetrahydrofuran (THF) was freshly distilled

from sodium/benzophenone. Common solvents for chromatography (pe-

troleum ether 40–608C, EtOAc) were distilled prior to use. Column chro-

5184

www.chemeurj.org

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

matography and flash column chromatography were performed on silica

gel 60, 0.040–0.063 mm (230–400 mesh). TLC (monitoring the course of

the reactions) was performed on pre-coated plastic sheets (Polygram SIL

G/UV254, Macherey-Nagel) with detection by UV (254 nm) or by colo-

ration with cerium molybdenum solution [phosphomolybdic acid (25 g),

S=0.942,

< 0.001, residual 1_max=0.241

H

atoms were treated as riding atoms, max. shift/error

ꢀ3

.

Synthesis of allyl alcohols

(4’R,5’R,2E)-3-[4’,5’-Bis(methoxydiphenylmethyl)-1’,3’,2’-dioxaborolan-2’-

yl]prop-2-en-1-ol (6) and (4’R,5’R)-2-[4’,5’-bis(methoxydiphenylmethyl)-

1’,3’,2’-dioxaborolan-2’-yl]prop-2-en-1-ol (9) and their enantiomers (ent-6

and ent-9): Hydroboration:^[14e,16a]A solution of cyclohexene (8.92 mL,

7.23 mg, 88.0 mmol, 2.00 equiv) and 1,2-dimethoxyethane (88.0 mL) was

cooled to 08C and stirred vigorously. H₃B·Me₂S (4.40 mL of a 10m solu-

tion in Me₂S, 44.0 mmol, 1.00 equiv) was added via syringe; dicyclohexyl-

borane was formed as a colorless precipitate. After 15 min the reaction

mixture was warmed to RT and stirring was continued for 1 h. Alkyne

8a^[16a,36](5.64 g, 44.0 mmol, 1.00 equiv) was added and stirring continued

for 1 h while the colorless solid disappeared. Anhydrous Me₃NO^[37]

(6.28 g, 83.6 mmol, 1.90 equiv) was added slowly (exothermic reaction!)

to the stirred mixture, followed by (after 1 h) diol 1 (20.0 g, 44.0 mmol,

1.00 equiv). After 12 h the mixture was concentrated under reduced pres-

sure. Flash column chromatography (520 g silica gel, petroleum ether/

EtOAc 90:10) gave a mixture of compounds (24.9 g) that was directly

used for the next step.

Ce(SO₄)₂·H₂O (10 g), concd. H₂SO₄(60 mL), H₂O (940 mL)]. Preparative

A

medium pressure liquid chromatography (MPLC) was performed with a

Labomatic pump (MD-50/80/100), a packed column (25300 mm or 40

475 mm), LiChroprep, Si 60 (15–25 mm) and UV detector (254 nm).

HPLC was performed on a Pharmacia device equipped with a Chiralcel

OD or a Dionex/Gynkotek device with a Chiralcel OD-H column. ¹H

and ¹³C NMR spectra were recorded at RT in CDCl₃with a Bruker ARX

300/500 or a Varian Inova 400. Chemical shifts are given in ppm relative

to TMS as internal standard [¹H: Si

(CH₃)₄=0.00 ppm] or relative to the

G

resonance of the solvent (¹³C: CDCl₃=77.0 ppm); coupling constants J

are given in Hz. Higher order d and J values are not corrected. ¹³C sig-

nals were assigned by means of H,H COSY and HSQC or HMBC spec-

troscopy. Microanalyses and gas chromatographic determinations were

performed at the Institut für Organische Chemie, Stuttgart. Melting

points or softening ranges (Büchi 510 and B-540) are not corrected re-

spectively. Specific rotations were measured at 208C. IR spectra were ob-

tained on a Perkin–Elmer 283, Bruker IFS 28 or a Perkin–Elmer Spec-

trum One. MS were recorded on a Finnigan MAT 95 [FAB (NBA: 3-ni-

trobenzyl alcohol), EI, CI], a Varian MAT 711 (EI), a Finnigan MAT

LC-Q (ESI-1, LC-MS-MS) or a Applied Biosystems/MDS SCIEX 4000

Q TRAP (ESI-2, LC-MS-MS); for HRMS perfluorokerosene was the ref-

erence; directly injected solution for LC-MS-MS: one part of a 0.5 mm

solution of the substance in CH₃CN, three parts CH₃CN, one part 0.1%

aqueous NH₄HCO₂solution. For convenience and data comparison the

boronate moieties B* and B^ent* are set to the last priority of substituents

contradicting the IUPAC nomenclature. Diol 1 and diol ent-1 were syn-

thesized according to literature procedures.^[13]1-Heptyne (8c) is commer-

cially available. Benzyl propargyl ether (8d) was prepared according to a

literature procedure, but with THF as the only solvent.^[33]The analytical

data are in full agreement to those previously reported.^[34](R)-Isopropyli-

dene glycerine aldehyde (42d) was prepared according to literature pro-

cedures.^[35]Triethylorthoacetate was distilled prior to use, whereas N,N-

dimethylacetamiddimethylacetal was used as purchased (90% purity).

O₃/O₂-mixtures were prepared with the Ozon generator 500 (Fischer

technology) with an O₂stream of 150 Lh^ꢀ1(the device was adjusted to

full power) or with the Sander Labor-Ozonisator 300.5 with an O₂stream

of 100 Lh^ꢀ1and adjusted to 0.33 A.

Deprotection: The mixture was dissolved in a minimum amount of

CH₂Cl₂and ethanol (240 mL) and a solution of concentrated HCl (7 mL)

in ethanol (22 mL) was added. After 45 min saturated aqueous NaHCO₃

solution (22 mL) was added and the organic solvent almost completely

removed under reduced pressure. After dilution with H₂O, the aqueous

phase was extracted three times with Et₂O. The combined organic layer

was washed with brine, dried over MgSO₄and concentrated under re-

duced pressure. Chromatography (900 g silica gel, petroleum ether/

EtOAc 85:15 ! 80:20) led to a spectroscopically pure colorless solid

foam (15.0 g, 28.9 mmol, 66% 6 over two steps). R_f=0.28 (petroleum

ether/EtOAc 85:15); spectroscopic data is in agreement with literature

data.^[13b]The regioisomer 9 was also isolated as a spectroscopically pure

colorless solid foam (7% 9, 1.53 g, 2.94 mmol) MPLC (petroleum ether/

EtOAc 85:15) afforded an analytically pure colorless solid foam. R_f=

0.36 (petroleum ether/EtOAc 85:15); all spectroscopic data are in full

agreement with those previously published {[a] (6)=ꢀ84 (c=0.50 in

CHCl₃); [a]²_D⁰(9)=ꢀ144 (c=1.0 in CHCl₃); [a]²_D⁰(ent-6)=+84 (c=1.12

in CHCl₃) (obtained when starting from ent-1)}.^[14g]

Synthesis of lithium alkynylboronates 10 (General procedure A):^[38]

Alkyne 8 (1.00 equiv) was dissolved in Et₂O (1.40 mL per mmol 8) and

cooled to ꢀ788C. nBuLi (1.00 equiv, 1.6m in hexane) was added and the

reaction mixture was stirred for 30 min. In a second flask B(OiPr)₃

A

X-ray crystallographic analysis:^[31]The crystal data for compounds 14, 18

and 34 were determined with a Siemens P4 diffractometer with graphite

monochromator in the w-scan mode with Cu_Ka(l=1.54178 ) radiation.

Alkynylboronate 14:^[31]C₃₃H₃₁BO₅, M_r=518.41, colorless, T=293 K, crys-

tal size 0.500.100.10 mm, orthorhombic, P2₁2₁2₁, a=10.1832(6), b=

(1.00 equiv) was dissolved in Et₂O and the solution was also cooled to

ꢀ788C. The alkynyllithium solution was added via insulated transfer can-

nula to the B(OiPr)₃solution whereupon lithium alkynylboronate 10 pre-

G

cipitated. The suspension was first stirred at ꢀ788C for 1 h, followed by

4 h at RT. After concentration under reduced pressure the remaining

solid was dried for 3 h under high vacuum, stored under N₂at ꢀ208C

and used without further purification and characterization.

15.8268(7), c=17.6158(15) , V=2839.1(3) ³, Z=4, 1_calcd=1.212 gcm^ꢀ3

m=0.641 mm^ꢀ1, F

(000)=1096, q range=3.75 to 59.958, 2270 measured/in-

,

ACHTREUNG

Synthesis of alkynylboronate 12 (General procedure B):^[39]Lithium alky-

nylboronate 10 (1.00 equiv) was suspended in THF (1.65 mL per mmol

10) and cooled to ꢀ788C. BF₃·Et₂O (1.33 equiv) was added dropwise; the

flask was briefly taken out of the cooling bath to dissolve the solid and

was then recooled to ꢀ788C. In a second flask was placed diol 1

(1.66 equiv) in THF (6.25 mL per mmol 1) at ꢀ788C. The solution was

added via insulated transfer cannula dropwise to the boronate solution.

Stirring was continued for 1 h and at RT for 30 min followed by concen-

tration of the mixture under reduced pressure and drying under high

vacuum.

dependent reflections, 1477 reflections with [I > 2s(I)]; the structure

was solved by direct methods and refined by full-matrix least-squares on

F²for all data weights to R=0.0952, wR=0.2081, S=1.045, H atoms

were treated as riding atoms, max. shift/error < 0.001, residual 1_max

=

0.197 ^ꢀ3. Alkynylboronate 18:^[31]C₃₇H₄₀BNO₅, M_r=589.53, colorless,

T=293 K, crystal size 0.200.150.05 mm, orthorhombic, P2₁2₁2₁, a=

10.7765(5), b=14.7879(9), c=20.8366(10) , V=3320.6(3) ³, Z=4,

1_calcd=1.179 gcm^ꢀ3

,

m=0.613 mm^ꢀ1

,

F(000)=1256, q range=3.67 to

A

59.998, 3200 measured/independent reflections, 1318 reflections with [I >

2s(I)]; the structure was solved by direct methods and refined by full-

matrix least-squares on F²for all data weights to R=0.1887, wR=0.2528,

(4’R,5’R)-(tert-Butyldimethylsilyl)-3-[4’,5’-bis(methoxydiphenylmethyl)-

S=1.068, H atoms were treated as riding atoms, max. shift/error

<

1’,3’,2’-dioxaborolan-2’-yl]propargyl ether (12b): According to GPA,

alkyne 8b^[40](2.03 mL, 1.70 g, 10.0 mmol) in Et₂O (14 mL) and nBuLi

(6.7 mL of a 1.6m solution in hexane, 10 mmol) were used in the first

0.001, residual 1_max=0.308 ^ꢀ3. Allylboronate 34:^[31]C₃₅H₃₇BO₅, M_r=

548.48, colorless, T=293 K, crystal size 0.550.100.07 mm, monoclinic,

P2₁, a=18.556(2), b=9.2194(18), c=19.929(3) , V=3038.9(8) ³, Z=4,

flask. In a second flask B(OiPr)₃(2.30 mL, 1.88 g, 10.0 mmol) was dis-

A

1_calcd=1.199 gcm^ꢀ3

,

m=0.623 mm^ꢀ1

,

F(000)=1168, q range=2.49 to

A

solved in Et₂O (33 mL). Lithium alkynylboronate 10b (ꢁ10 mmol) pre-

cipitated. According to GP B, lithium alkynylboronate 10b (346 mg,

0.95 mmol) in THF (1.57 mL) was used. The suspension was treated with

BF₃·Et₂O (156 mL, 180 mg, 1.27 mmol) and diol 1 (682 mg, 1.50 mmol) in

57.508, 4994 measured/independent reflections, 2513 reflections with [I >

2s(I)]; the structure was solved by direct methods and refined by full-

matrix least-squares on F²for all data weights to R=0.1255, wR=0.1666,

Chem. Eur. J. 2008, 14, 5178 – 5197

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

5185

J. Pietruszka et al.

THF (10 mL). Chromatography (57 g silica gel, petroleum ether/EtOAc

97:3, 85:15, 70:30) and MPLC furnished an analytically pure colorless

solid foam (220 mg, 0.29 mmol, 37%). R_f=0.55 (petroleum ether/EtOAc

90:10); softening range 72–808C; [a]²_D⁰=ꢀ17 (c=1.00 in CHCl₃);

167 (13) [Ph₂CH⁺], 105 (21) [PhCO⁺]; elemental analysis calcd (%) for

C₄₀H₃₇BO₅(608.5): C 78.95, H 6.13, found: C 78.89, H 6.18.

(4’R,5’R,2Z)-tert-Butyldimethylsilyl-3-[4’,5’-bis(methoxydiphenylmethyl)-

1’,3’,2’-dioxaborolan-2’-yl] prop-2-en-1-yl ether (13): Procedure 1:^[19]To a

¹H NMR (500 MHz, CDCl₃): d=0.04 [s, 6H, Si

(CH₃)₂], 0.85 (s, 9H, C-

G

solution of [Rh(cod)Cl]₂(7 mg, 14 mmol) in cyclohexane (3.00 mL) was

G

ACHTREUNG

added successively (iPr)₃P (13 mL, 11 mg, 60 mmol, purity: 90%), Et₃N

(139 mL, 101 mg, 1.00 mmol) and catecholborane (120 mg, 1.00 mmol).

After 30 min alkyne 8b (243 mL, 204 mg, 1.20 mmol) was added in one

batch. Diol 1 (681 mg, 1.50 mmol) was added after 5 h. After 12 h the

mixture was concentrated under reduced pressure. Purification by flash

column chromatography (30 g silica gel, petroleum ether/EtOAc 95:5)

A

G

ACHTREUNG

(C-4’,C-5’), 83.2 (CPh₂OCH₃), 100.8 (C-2), 127.5, 127.5, 127.5, 127.8,

128.4, 129.6 (arom. CH), 140.8, 141.0 ppm (arom. C_ipso); C-3 was not de-

tected; IR (KBr): n˜ =3420 (br); 3065, 3040, 3000 (arom. C-H-n); 2940,

2910, 2875, 2835 (aliph. C-H-n); 2805 (OCH₃, C-H-n); 2180 (C=C-n);

1590, 1575, 1480 (arom. C=C-n); 1440; 1380; 1360; 1325; 1215; 1060 (C-

O-C); 820, 795, 760 (TBS); 740 (Ph, C-H-d_{out of plane}); 680 (Ph, ring-d);

615 cm^ꢀ1; MS (FAB, matrix: NBA+NaI): m/z (%): 788 (2), 661 (2), 655

(7) [M+Na⁺], 638 (9), 197 (100) [Ph₂COMe⁺], 167 (11) [Ph₂CH⁺], 105

(11) [PhCO⁺], 77 (5) [Ph⁺]; elemental analysis calcd (%) for

C₃₉H₄₅BO₅Si (632.7): C 74.04, H 7.17, found: C 73.86, H 7.23.

gave

0.63 mmol). When increasing the amount of catalyst {0.03 equiv [Rh-

(cod)Cl]₂, 0.12 equiv (iPr)₃P and 2.00 equiv Et₃N} an improved yield

a slightly impure yellowish solid foam (63% 13, 398 mg,

AHCTREUNG

(81%) was observed in one case. Procedure 2: Lindlar catalyst (5 mg)

and alkyne 12b (32 mg, 0.05 mmol) were suspended/dissolved in toluene

(2 mL). The flask was briefly evacuated and flooded with H₂for several

times. The reaction mixture was stirred for 1 h while the flask was con-

nected to a ballon containing H₂. The mixture was directly loaded on a

column conditioned with petroleum ether (10 g silica gel); elution with

petroleum ether/EtOAc 97:3 furnished a slightly impure (the consecutive

(4’R,5’R)-1-[4’,5’-Bis(methoxydiphenylmethyl)-1’,3’,2’-dioxaborolan-2’-

yl]hept-1-yne (12c): According to GPA, 1-heptyne (8b) (1.31 mL,

963 mg, 10.0 mmol) in Et₂O (14 mL) and nBuLi (6.7 mL of a 1.6m solu-

tion in hexane, 10 mmol) were used in the first flask. In a second flask B-

MPLC

50 mmol). R_f=0.78 (petroleum ether/EtOAc 85:15); ¹H NMR (500 MHz

(CH₃)₂], 0.82 [s, 9H, C(CH₃)₃],

a spectroscopically pure) colorless solid foam (95%, 30 mg,

(OiPr)₃(2.30 mL, 1.88 g, 10.0 mmol) was dissolved in Et₂O (33 mL). Lith-

in CDCl₃): d=ꢀ0.12, ꢀ0.10 [2s, 6H, Si

U

ACHTREUNG

ium 1-heptyn-1-ylboronate (10c) (ꢁ10 mmol) precipitated. According to

(GP B), 10c (279 mg, 0.96 mmol) in THF (1.58 mL) was used. The sus-

pension was treated with BF₃·Et₂O (157 mL, 182 mg, 1.28 mmol) and diol

1 (727 mg, 1.60 mmol) in THF (10 mL). Chromatography (50 g silica gel,

petroleum ether/EtOAc 95:5) yielded an analytically pure colorless solid

foam (262 mg, 0.47 mmol, 49%). R_f=0.69 (petroleum ether/EtOAc

85:15); softening range 84–888C; [a]²_D⁰=ꢀ21 (c=0.26 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=0.04 (t, ³J=7.0 Hz, 3H, 7-H), 1.26 (m,

4H, 5-H, 6-H), 1.39–1.43 (m, 2H, 4-H), 2.08 (t, ³J=7.2 Hz, 2H, 3-H),

2.99 (s, 6H, OCH₃), 5.33 (s, 2H, 4’-H, 5’-H), 7.24–7.37 ppm (m, 20H,

arom. CH); ¹³C NMR (126 MHz in CDCl₃): d=13.9 (C-7), 19.4 (C-3),

22.1 (C-6), 27.6 (C-4), 30.8 (C-5), 51.8 (OCH₃), 77.8 (C-4’, C-5’), 83.1

(CPh₂OCH₃), 104.4 (C-2), 127.5, 127.5, 127.8, 128.4, 129.7 (arom. CH),

140.8, 141.0 ppm (arom. C_ipso), C-1 was not detected; IR (KBr): n˜ =3410

(br), 3065, 3035, 3000 (arom. C-H-n), 2935, 2910, 2835 (aliph. C-H-n),

2805 (OCH₃, C-H-n), 2175 (C=C-n), 1590, 1575, 1485 (arom. C=C-n),

1435, 1330, 1210, 1060 (C-O-C); 1020, 950, 740 (Ph, C-H-d_{out of plane}), 680

(Ph, ring-d), 615 cm^ꢀ1; MS (EI, 70 eV): m/z (%): 558 (0.2) [M⁺], 526 (2)

[MꢀMeOH⁺], 197 (100) [Ph₂COMe⁺], 167 (1) [Ph₂CH⁺], 105 (4)

[PhCO⁺], 77 (1) [Ph⁺]; elemental analysis calcd (%) for C₃₇H₃₉BO₄

(558.5): C 79.57, H 7.04, found: C 79.46, H 7.06.

¹³C NMR (126 MHz in CDCl₃): d=ꢀ5.3, ꢀ5.2 [Si

E

G

25.9 [C(CH₃)₃], 51.7 (OCH₃), 63.0 (C-1), 77.4 (C-4’, C-5’), 83.3

G

(CPh₂OCH₃), 115.7 (C-3), 127.3, 127.3, 127.5, 127.8, 128.3, 129.6 (arom.

CH), 141.1, 141.3 (arom. C_ipso), 154.7 ppm (C-2); IR (KBr): n˜ =3420 (br),

3070, 3040, 3000 (arom. C-H-n), 2940, 2910, 2875 (aliph. C-H-n), 2810

(OCH₃, C-H-n), 1620 (olef. C=C-n), 1590, 1570, 1485 (arom. C=C-n),

1435, 1410, 1245, 1170, 1070, 1060, 820, 795, 755 (TBS), 740 (Ph, C-H-

d_{out of plane}), 680 cm^ꢀ1(Ph, ring-d).

A

prop-2-yn-1-ol (14): TBS-protected propargyl alcohol 12b (260 mg,

0.41 mmol) was dissolved in MeOH (3 mL, 7.32 mL per mmol 12b) and a

solution of concentrated HCl (51 mL) in MeOH (0.45 mL) was added.

After 5 min the reaction mixture was diluted with CH₂Cl₂and 5% aque-

ous NaHCO₃solution (1.4 mL) was added. The aqueous layer was ex-

tracted twice with CH₂Cl₂(5 mL). The combined organic layer was

washed with brine, dried over Na₂SO₄and concentrated under reduced

pressure. Chromatography (20 g silica gel, petroleum ether/EtOAc 85:15)

gave an analytically pure colorless solid foam (205 mg, 0.40 mmol, 96%).

R_f=0.07 (petroleum ether/EtOAc 90:10); m.p. 196–1988C; [a]²_D⁰=ꢀ36

(c=0.50 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.39 (t, ³J=6.3 Hz,

(4’’R,5’’R)-Benzyl-3-[4’’,5’’-bis(methoxydiphenylmethyl)-1’’,3’’,2’’-dioxa-

borolan-2’’-yl] propargyl ether (12d): According to GPA, benzyl protect-

ed propargylic alcohol 8d (1.46 g, 10.0 mmol, 1.00 equiv) in Et₂O (14 mL,

1.40 mL per mmol 8d) and nBuLi (6.7 mL of a 1.6m solution in hexane,

3

1H, OH), 3.00 (s, 6H, OCH₃), 4.14 (d, J=6.3 Hz, 2H, 1-H), 5.36 (s, 2H,

10 mmol) were used in the first flask. In

a

second flask

B(OiPr)₃

A

4’-H, 5’-H), 7.23–7.34 ppm (m, 20H, arom. CH); ¹³C NMR (126 MHz,

CDCl₃): d=51.3 (C-1), 51.8 (OCH₃), 78.1 (C-4’,C-5’), 83.1 (CPh₂OCH₃),

127.5, 127.6, 127.6, 127.9, 128.4, 129.6 (arom. CH), 140.7, 140.8 ppm

(arom. C_ipso), C-2 and C-3 were not detected; IR (KBr): n˜ =3550 (br, O-

H-n); 3500 (br); 3070, 3040, 3015, 3005 (arom. C-H-n); 2955, 2950, 2915,

2880, 2840, 2830 (aliph. C-H-n); 2805 (OCH₃, C-H-n); 2180 (C=C-n);

1590, 1570, 1485 (arom. C=C-n); 1450; 1390; 1365; 1330; 1220; 1065 (C-

O-C); 1015; 1000; 950; 740 (Ph, C-H-d_{out of plane}); 690 (Ph, ring-d);

(2.30 mL, 1.88 g, 10.0 mmol) was dissolved in Et₂O (33 mL). Lithiumal-

kynyl boronate 10d (ꢁ10 mmol) precipitated. According to GP B, 10d

(323 mg, 0.95 mmol) in THF (1.58 mL) was used. The suspension was

treated with BF₃·Et₂O (156 mL, 180 mg, 1.27 mmol) and diol 1 (682 mg,

1.50 mmol, 1.58 equiv) in THF (10 mL). Chromatography (60 g silica gel,

petroleum ether/EtOAc 97:3) and MPLC yielded an analytically pure

colorless solid foam (175 mg, 0.29 mmol, 30%). R_f=0.42 (petroleum

ether/EtOAc 90:10); softening range 67–808C; [a]²_D⁰=ꢀ3 (c=0.80 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=3.00 (s, 6H, OCH₃), 4.04 (s,

2H, 1-H), 4.48 (s, 2H, 1’-H), 5.38 (s, 2H, 4’’-H, 5’’-H), 7.23–7.39 ppm (m,

25H, arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=51.8 (OCH₃), 57.3 (C-

1), 71.3 (C-1’), 78.1 (C-4’’, C-5’’), 83.1 (CPh₂OCH₃), 97.9 (C-2), 127.5,

127.5, 127.6, 127.9, 127.9, 128.1, 128.4, 128.4, 129.6 (arom. CH), 137.2,

140.7, 140.8 ppm (arom. C_ipso); C-3 was not detected; IR (KBr): n˜ =3435

(br); 3065, 3040, 3010 (arom. C-H-n); 2950, 2920, 2880 (aliph. C-H-n);

2815 (OCH₃, C-H-n); 2180 (C=C-n); 1590, 1575, 1480 (arom. C=C-n);

1435; 1380; 1360; 1325; 1215; 1060 (C-O-C); 740 (Ph, C-H-d_{out of plane}); 680

(Ph, ring-d); 610; 555; 465 cm^ꢀ1; MS (FAB, matrix: NBA+NaI): m/z

(%): 788 (2), 661 (1), 638 (11), 631 (4) [M+Na⁺], 197 (100) [Ph₂COMe⁺],

615 cm^ꢀ1

;

MS (EI, 70 eV): m/z (%): 518 (0.03) [M⁺], 486 (2)

[MꢀMeOH⁺], 197 (100) [Ph₂COMe⁺], 167 (3) [Ph₂CH⁺], 105 (12)

[PhCO⁺], 77 (5) [Ph⁺]; elemental analysis calcd (%) for C₃₃H₃₁BO₅

(518.4): C 76.46, H 6.03, found: C 76.38, H 6.12.

(4’R,5’R,2Z)-3-[4’,5’-Bis(methoxydiphenylmethyl)-1’,3’,2’-dioxaborolan-2’-

yl]prop-2-en-1-ol (7): Silylether 13 (561 mg, 0.88 mmol, 1.00 equiv) was

dissolved in the minimal amount of CH₂Cl₂and EtOH (6.70 mL). A solu-

tion of concentrated HCl (140 mL) in EtOH (1.30 mL) was added. After

1 h the mixture was neutralized with saturated aqueous NaHCO₃solution

(1 mL); the solvents were removed under reduced pressure. After addi-

tion of H₂O the aqueous layer was extracted three times with Et₂O. The

5186

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ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

combined organic layer was washed with brine, dried over MgSO₄and

concentrated under reduced pressure. Chromatography (17 g silica gel,

petroleum ether/EtOAc 87:13) gave a spectroscopically pure colorless

solid foam (340 mg, 0.65 mmol, 74%). R_f=0.22 (petroleum ether/EtOAc

85:15); softening range 60–788C, [a]²_D⁰=ꢀ148 (c=0.36 in CHCl₃), spec-

troscopic data are in full agreement to those previously reported.^[14f]

(1 mL, 1 mg, 0.01 mmol). The reaction mixture was heated for 3 h; dr

30:70 (determined by proton NMR of the crude mixture). Chromatogra-

phy (4 g silica gel, petroleum ether/EtOAc 93:7) yielded the mixture of

diastereomers 15/16 (68 mg, 0.12 mmol, 59%) as a slightly impure color-

less solid foam. Analytical data: see above.

(4’R,5’R)-Ethyl 4-[4’,5’-bis(methoxydiphenylmethyl)-1’,3’,2’-dioxaborolan-

ACHTREUNG

2’-yl]pent-4-enoate (17): According to GP C, allyl alcohol 9 (239 mg,

0.46 mmol) was treated with triethylorthoacetate (587 mL, 522 mg,

3.21 mmol) under catalysis of propionic acid (2 mL, 2 mg, 0.03 mmol.).

The reaction mixture was heated for 1 h. Chromatography (25 g silica

gel, petroleum ether/EtOAc 95:5) gave a slightly impure colorless solid

foam of 17 (184 mg, 0.31 mmol, 68%), MPLC (petroleum ether/EtOAc

98:2) furnished an analytically pure sample. R_f=0.61 (petroleum ether/

EtOAc 85:15); softening range: 37–438C; [a]²_D⁰=ꢀ122 (c=0.94 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=1.20 (t, ³J=7.1 Hz, 3H, 2’’-H),

a

(1.00 equiv) was dissolved in freshly distilled triethylorthoacetate

(7.00 equiv); propionic acid (0.06 equiv) was added. The reaction mixture

was heated to 1358C for the time indicated and the generated EtOH was

removed. The reaction mixture was cooled, concentrated under reduced

pressure and subjected to chromatographic purification.

(3S,4’R,5’R)- and (3R,4’R,5’R)-Ethyl 3-[4’,5’-bis(methoxydiphenylmeth-

yl)-1’,3’,2’-dioxaborolan-2’-yl]pent-4-enoate (15 and 16) and their enantio-

mers (ent-15 and ent-16): According to GP C allyl alcohol 6 (26.0 g,

50.0 mmol) was treated with triethylorthoacetate (63.9 mL, 65.5 g,

40.4 mmol,) under catalysis of propionic acid (225 mL, 222 mg,

3.00 mmol). The reaction mixture was heated for 3.5 h; the dr (as deter-

mined by proton NMR of the crude mixture) was 50:50. Chromatography

(700 g silica gel, petroleum ether/EtOAc 98:2 ! 85:15) gave the mixture

of diastereomers 15/16 (23.1 g, 39.1 mmol, 78%) and starting material 6

(5.05 g, 9.70 mmol, 19%). MPLC (petroleum ether/EtOAc 98:2) gave

two analytically pure solid foams (15 and 16). Allylboronate 15: R_f=0.68

(petroleum ether/EtOAc 85:15); softening range: 49–628C; [a]²_D⁰(15)=

ꢀ108 (c=0.67 in CHCl₃); [a]_D²⁰(ent-15)=+110 (c=1.19 in CHCl₃) (ob-

tained when starting from ent-6); ¹H NMR (500 MHz, CDCl₃): d=1.13

(t, ³J=7.1 Hz, 3H, 2’’-H), 1.90–1.94 (m, 1H, 3-H), 1.98–2.10 (m, 2H, 2-

H), 3.00 (s, 6H, OCH₃), 3.93 (q, ³J=7.1 Hz, 2H, 1’’-H), 4.70 (ddd, ³J=

17.2, ²J=1.5, ⁴J=1.5 Hz, 1H, 5-H_Z), 4.77 (ddd, ³J=10.5, ²J=1.5, ⁴J=

1.5 Hz, 1H, 5-H_E), 5.30 (s, 2H, 4’-H, 5’-H), 5.56 (ddd, ³J=17.2, ³J=10.5,

³J=6.9 Hz, 1H, 4-H); 7.24–7.35 ppm (m, 20H, arom. CH); ¹³C NMR

(126 MHz, CDCl₃): d=14.1 (C-2’’), 25.0 (C-3), 33.0 (C-2), 51.7 (OCH₃),

60.0 (C-1’’), 77.9 (C-4’, C-5’), 83.2 (CPh₂OCH₃), 112.7 (C-5), 127.3, 127.4,

127.5, 127.8, 128.4, 129.7 (arom. CH), 137.3 (C-4), 141.1, 141.1 (arom.

C_ipso), 173.1 ppm (C-1); IR (KBr): n˜ =3430 (br); 3060, 3040, 3000 (arom.

C-H-n); 2960, 2920, 2880 (aliph. C-H-n); 2805 (OCH₃, C-H-n); 1730 (C=

O-n); 1625 (olef. C=C-n); 1590, 1570, 1480 (arom. C=C-n); 1440; 1360;

1060 (C-O-C); 1020; 985, 950 (CH=CH₂, C-H-d_{out of plane}); 740 (Ph, C-H-

d_{out of plane}); 690 cm^ꢀ1(Ph, ring-d); MS (FAB, matrix: NBA+NaI): m/z

(%): 613 (14) [M+Na⁺], 333 (10), 197 (100) [CPh₂OMe⁺], 167 (5)

[Ph₂CH⁺], 105 (11) [PhCO⁺], 77 (5) [Ph⁺]; elemental analysis calcd (%)

for C₃₇H₃₉BO₆(590.5): C 75.26, H 6.66, found: C 75.25, H 6.67. Allylboro-

nate 16: R_f=0.68 (petroleum ether/EtOAc 85:15); softening range: 41–

608C; [a]²_D⁰(16)=ꢀ98 (c=0.32 in CHCl₃), [a]²_D⁰(ent-16)=+102 (c=1.19

in CHCl₃) (obtained when starting from ent-6); ¹H NMR (500 MHz,

CDCl₃): d=1.13 (t, ³J=7.1 Hz, 3H, 2’’-H), 1.90–1.94 (m, 1H, 3-H), 2.05–

2.14 (m, 2H, 2-H), 2.99 (s, 6H, OCH₃), 3.99 (q, ³J=7.1 Hz, 2H, 1’’-H),

4.70 (ddd, ³J=17.2, ²J=1.4, ⁴J=1.4 Hz, 1H, 5-H_Z), 4.75 (ddd, ³J=10.3,

²J=1.4, ⁴J=1.4 Hz, 1H, 5-H_E), 5.32 (s, 2H, 4’-H, 5’-H), 5.41 (ddd, ³J=

3

2.00–2.15 (m, 4H, 2-H, 3-H), 2.99 (s, 6H, OCH₃), 4.05 (q, J=7.1 Hz, 2H,

1’’-H), 5.35 (s, 2H, 4’-H, 5’-H), 5.40 (s, 2H, 5-H), 7.23–7.36 ppm (m, 20H,

arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=14.2 (C-2’’), 29.8 (C-3), 33.4

(C-2), 51.8 (OCH₃), 60.0 (C-1’’), 77.8 (C-4’, C-5’), 83.3 (CPh₂OCH₃),

127.2, 127.3, 127.5, 127.8, 128.4, 129.6 (arom. CH), 130.0 (C-5), 141.2,

141.4 (arom. C_ipso), 173.4 ppm (C-1), C-4 was not detected; IR (KBr): n˜ =

3440 (br); 3070, 3045, 3010 (arom. C-H-n); 2960, 2920, 2890 (aliph. C-H-

n); 2815 (OCH₃, C-H-n); 1730 (C=O-n); 1610 (olef. C=C-n); 1590, 1570,

1480 (arom. C=C-n); 1435; 1410; 1370; 1210; 1160; 1060 (C-O-C); 1015;

1000; 950; 740 (Ph, C-H-d_{out of plane}); 685 cm^ꢀ1(Ph, ring-d); MS (FAB,

matrix: NBA+NaI): m/z (%): 613 (54) [M+Na⁺], 333 (6), 197 (100)

[CPh₂OMe⁺], 167 (7) [Ph₂CH⁺], 105 (15) [PhCO⁺], 77 (6) [Ph⁺]; ele-

mental analysis calcd (%) for C₃₇H₃₉BO₆(590.5): C 75.26, H 6.66, found:

C 75.29, H 6.65.

(3S,4’R,5’R)- and (3R,4’R,5’R)-3-[4’,5’-Bis(methoxydiphenylmethyl)-

1’,3’,2’-dioxaborolan-2’-yl]-N,N-dimethylpent-4-enamide (18 and 19): A

flask containing allyl alcohol 6 (500 mg 0.96 mmol) dissolved in toluene

(2 mL) and N,N-dimethylacetamide dimethylacetal (281 mL, 255 mg,

1.92 mmol) was fitted to a Claisen condenser and a drying tube. The reac-

tion mixture was heated for 36 h at precisely 808C and the evolving

MeOH was removed. The mixture was concentrated under reduced pres-

sure; the dr (as determined by proton NMR of the crude mixture) was

50:50. Chromatography (25 g silica gel, petroleum ether/EtOAc 70:30)

yielded the slightly impure mixture of diastereomers 18/19, (415 mg,

0.71 mmol, 73%) and 2 (R=OH: 175 mg, 0.16 mmol, 16%). MPLC (pe-

troleum ether/EtOAc 70:30) furnished two analytically pure solid foams

(18 and 19). Allylboronate 18: R_f=0.11 (petroleum ether/EtOAc 85:15);

softening range: 51–728C; [a]²_D⁰=ꢀ124 (c=0.25 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=1.98 (d, ³J=7.5 Hz, 2H, 2-H), 2.10 (td, ³J=7.2,

³J=6.7 Hz, 1H, 3-H), 2.67, 2.74 [2s, 6H, N

(CH₃)₂)], 3.00 (s, 6H, OCH₃),

R

4.66 (ddd, ³J=17.2, ²J=1.6, ⁴J=1.6 Hz, 1H, 5-H_Z), 4.76 (ddd, ³J=10.5,

²J=1.6, ⁴J=1.6 Hz, 1H, 5-H_E), 5.30 (s, 2H, 4’-H, 5’-H), 5.62 (ddd, ³J=

3

17.2, J=10.5, J=6.7 Hz, 1H, 4-H), 7.24–7.33 ppm (m, 20H, arom. CH);

¹³C NMR (126 MHz, CDCl₃): d=24.9 (C-3), 30.8 (C-2), 35.4, 37.3 [N-

(CH₃)₂], 51.7, 51.7 (OCH₃), 77.8 (C-4’, C-5’), 83.2 (CPh₂OCH₃), 112.0 (C-

5), 127.2, 127.3, 127.5, 127.8, 128.5, 129.7 (arom. CH), 138.3 (C-4), 141.0,

141.1 (arom. C_ipso), 172.3 ppm (C-1); IR (KBr): n˜ =3420 (br); 3070, 3040,

3005 (arom. C-H-n); 2960, 2920, 2890 (aliph. C-H-n); 2810 (OCH₃, C-H-

n); 1640 (C=O-n); 1590, 1570, 1480 (arom. C=C-n); 1450, 1435; 1380;

1360; 1340; 1220; 1185; 1060 (C-O-C); 1015; 985, 950 (CH=CH₂, C-H-

3

17.2, J=10.3, J=7.8 Hz, 1H, 4-H), 7.25–7.32 ppm (m, 20H, arom. CH);

¹³C NMR (126 MHz, CDCl₃): d=14.2 (C-2’’), 25.4 (C-3), 33.8 (C-2), 51.8

(OCH₃), 60.0 (C-1’’), 77.9 (C-4’, C-5’), 83.3 (CPh₂OCH₃), 113.6 (C-5),

127.4, 127.4, 127.6, 127.8, 128.4, 129.7 (arom. CH), 136.8 (C-4), 141.2,

141.2 (arom. C_ipso), 172. 9 ppm (C-1); IR (KBr): n˜ =3420 (br); 3065, 3040,

3005 (arom. C-H-n); 2960, 2915, 2880 (aliph. C-H-n); 2805 (OCH₃, C-H-

n); 1730 (C=O-n); 1625 (olef. C=C-n); 1590, 1575, 1482 (arom. C=C-n);

1450; 1437; 1360; 1060 (C-O-C); 1020; 985, 950 (CH=CH₂, C-H-

d_{out of plane}); 740 (Ph, C-H-d_{out of plane}); 690 cm^ꢀ1(Ph, ring-d); MS (FAB,

matrix: NBA+NaI): m/z (%): 613 (12) [M+Na⁺], 333 (6), 197 (100)

[CPh₂OMe⁺], 167 (6) [Ph₂CH⁺], 105 (11) [PhCO⁺], 77 (4) [Ph⁺]; ele-

mental analysis calcd (%) for C₃₇H₃₉BO₆(590.5): C 75.26, H 6.66, found:

C 75.32, H 6.68.

d_{out of plane}); 740 (Ph, C-H-d_{out of plane}); 690 (Ph, ring-d); 680; 615; 590 cm^ꢀ1

;

MS (FAB, matrix: NBA+NaI): m/z (%): 612 (100) [M+Na⁺], 332 (17),

197 (24) [CPh₂OMe⁺], 168 (6) [Ph₂CH₂⁺], 105 (5) [PhCO⁺], 77 (3) [Ph⁺];

elemental analysis calcd (%) for C₃₇H₄₀BNO₅(589.5): C 75.38, H 6.84, N

2.38, found: C 75.10, H 6.96, N 2.38.

Allylboronate 19: R_f=0.08 (petroleum ether/EtOAc 85:15); softening

range: 52–718C; [a]²_D⁰=ꢀ108 (c=0.16 in CHCl₃); ¹H NMR (500 MHz,

CDCl₃): d=2.03 (ddd, ³J=11.4,³J=7.7, ³J=3.2 Hz, 1H, 3-H), 2.04 (dd,

²J=15.8, ³J=3.2 Hz, 1H, 2-H_a), 2.15 (dd, ²J=15.8, ³J=11.4 Hz, 1H, 2-

(3S,4’R,5’R)- and (3R,4’R,5’R)-Ethyl 3-[4’,5’-bis(methoxydiphenylmeth-

yl)-1’,3’,2’-dioxaborolan-2’-yl]pent-4-enoate (15 and 16): According to

GP C, allyl alcohol 7 (101 mg, 0.19 mmol) was treated with triethylor-

thoacetate (248 mL, 220 mg, 1.36 mmol,) under catalysis of propionic acid

H_b), 2.84, 2.84 [2s, 6H, N

(CH₃)₂], 2.99 (s, 6H, OCH₃), 4.68 (ddd, ³J=

G

17.1, ²J=1.5, ⁴J=1.5 Hz, 1H, 5-H_Z), 4.74 (ddd, ³J=10.2, ²J=1.5, ⁴J=

1.5 Hz, 1H, 5-H_E), 5.32 (s, 2H, 4’-H, 5’-H), 5.44 (ddd, ³J=17.1, ³J=10.2,

³J=7.7 Hz, 1H, 4-H), 7.24–7.34 ppm (m, 20H, arom. CH); ¹³C NMR

Chem. Eur. J. 2008, 14, 5178 – 5197

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

5187

J. Pietruszka et al.

(126 MHz, CDCl₃): d=25.3 (C-3), 32.3 (C-2), 35.4, 37.2 [N

(OCH₃), 77.9 (C-4’, C-5’), 83.4 (CPh₂OCH₃), 113.6 (C-5), 127.3, 127.4,

127.5, 127.8, 128.4, 129.7 (arom. CH), 137.5 (C-4), 141.1, 141.2 (arom.

A

NH₄Cl solution and H₂O, dried over MgSO₄and concentrated under re-

duced pressure. Chromatography (10 g silica gel, petroleum ether/EtOAc

93:7) yielded an analytically pure colorless solid foam of acetate 22

(554 mg, 0.70 mmol, 98%). R_f=0.58 (petroleum ether/EtOAc 85:15);

softening range: 61–678C; [a]²_D⁰=ꢀ68 (c=1.0 in CHCl₃); ¹H NMR

(300 MHz, CDCl₃): d=2.02 (s, 3H, 2-H), 3.00 (s, 6H, OCH₃), 4.47 (m,

2H, 1’-H), 5.28 (dt, J=18.1, J=1.8 Hz, 1H, 3’-H), 5.35 (s, 2H, 4’’-H, 5’’-

H), 6.17 (dt, ³J=18.1, ³J=4.6 Hz, 1H, 2’-H), 7.23–7.35 ppm (m, 20H,

arom CH); ¹³C NMR (126 MHz, CDCl₃): d=20.8 (C-2), 51.8 (OCH₃),

65.2 (C-1’), 77.7 (C-4’’, C-5’’), 83.3 (CPh₂OCH₃), 119.1 (C-3’), 127.3,

127.3, 127.5, 127.8, 128.4, 129.6 (arom. CH), 141.0, 141.2 (arom. C_ipso),

145.4 (C-2’), 170.4 ppm (C-1); IR (KBr): n˜ =3320 (br); 3070, 3040, 3000

(arom. C-H-n); 2940, 2910, 2880 (aliph. C-H-n); 2810 (OCH₃, C-H-n);

1740 (C=O-n); 1640 (olef. C=C-n); 1590, 1575, 1485 (arom. C=C-n);

1440; 1395; 1360; 1335; 1220; 1175; 1060 (C-O-C); 1020; 1000; 985; 950;

740 (Ph, C-H-d_{out of plane}); 690 (Ph, ring-d); 680; 615; 590 cm^ꢀ1; MS (FAB,

matrix: NBA+NaI): m/z (%): 585 (32) [M+Na⁺], 197 (100) [CPh₂OMe⁺],

167 (9) [Ph₂CH⁺], 105 (12) [PhCO⁺], 77 (5) [Ph⁺]; elemental analysis

calcd (%) for C₃₅H₃₅BO₆(562.5): C 74.74, H 6.27, found: C 74.82, H 6.49.

C

_ipso), 172.1 ppm (C-1); IR (KBr): n˜ =3430 (br); 3070, 3040, 3010 (arom.

C-H-n); 2920, 2890 (aliph. C-H-n); 2810 (OCH₃, C-H-n); 1640 (C=O-n);

1590, 1575, 1480 (arom. C=C-n); 1450, 1435; 1380; 1360; 1340; 1220;

1185; 1060 (C-O-C); 1020; 1000; 985, 950 (CH=CH₂, C-H-d_{out of plane}); 740

(Ph, C-H-d_{out of plane}); 690 (Ph, ring-d); 680; 610; 585 cm^ꢀ1; MS (FAB,

matrix: NBA+NaI): 612 (100) [M+Na⁺], 332 (46), 197 (49) [CPh₂OMe⁺

], 168 (13) [Ph₂CH₂⁺], 105 (6) [PhCO⁺], 77 (3) [Ph⁺]; elemental analysis

calcd (%) for C₃₇H₄₀BNO₅(589.5): C 75.38, H 6.84, N 2.38, found: C

75.15, H 6.94, N 2.19.

3

4

ACHTREUNG

0.57 mmol) was dissolved in toluene (570 mL) and N,N-dimethylforma-

mide dimethylacetal (167 mL, 152 mg, 1.14 mmol) was added. The reac-

tion mixture was heated for 16 h to 708C and was concentrated under re-

duced pressure. Chromatography (19 g silica gel, petroleum ether/EtOAc

70:30 ! 60:40) gave an analytically pure colorless solid foam of amide

20 (147 mg, 0.25 mmol, 44%). R_f=0.09 (petroleum ether/EtOAc 70:30);

softening range: 49–658C; [a]²_D⁰=ꢀ128 (c=0.54 in CHCl₃); ¹H NMR

(500 MHz, CDCl₃): d=1.90–2.13 (m, 4H, 2-H, 3-H), 2.71, 2.85 [2s, 6H,

(4’’R,5’’R,2’E)-3’-[4’’,5’’-Bis(methoxydiphenylmethyl)-1’’,3’’,2’’-dioxaboro-

lan-2’’-yl]prop-2’-en-1’-yl propionate (23): Allyl alcohol

6 (500 mg,

0.96 mmol) was dissolved in CH₂Cl₂(2 mL) and Et₃N (250 mL, 183 mg,

1.80 mmol), DMAP (12 mg, 0.10 mmol) and propionic anhydride

(230 mL, 232 mg, 1.78 mmol) were added. After 15 min saturated aqueous

NaHCO₃solution (5 mL) was added. The aqueous phase was extracted

thrice with CH₂Cl₂. The combined organic phase was washed with satu-

rated aqueous NH₄Cl solution and H₂O, dried over MgSO₄and concen-

trated under reduced pressure. Chromatography (15 g silica gel, petrole-

um ether/EtOAc 93:7) yielded an analytically pure colorless solid foam

of propionate 23 (420 mg, 0.73 mmol, 76%). R_f=0.65 (petroleum ether/

EtOAc 85:15); softening range: 50–638C; [a]²_D⁰=ꢀ65 (c=1.13 in CHCl₃);

¹H NMR (500 MHz, CDCl₃): d=1.11 (t, ³J=7.6 Hz, 3H, 3-H), 2.31 (q,

³J=7.6 Hz, 2H, 2-H), 3.00 (s, 6H, OCH₃), 4.48 (m, 2H, 1’-H), 5.28 (dt,

³J=18.1, ³J=1.9 Hz, 1H, 3’-H), 5.35 (s, 2H, 4’’-H, 5’’-H), 6.17 (dt, ³J=

18.1, ³J=4.6 Hz, 1H, 2’-H), 7.24–7.36 ppm (m, 20H, arom. CH);

¹³C NMR (126 MHz, CDCl₃): d=9.0 (C-3), 27.4 (C-2), 51.8 (OCH₃), 65.1

(C-1’), 77.7 (C-4’’, C-5’’), 83.3 (CPh₂OCH₃), 119.0 (C-3’), 127.3, 127.3,

127.5, 127.8, 128.4, 129.7 (arom. CH), 141.0, 141.2 (arom. C_ipso), 145.6 (C-

2’), 173.8 ppm (C-1); IR (KBr): n˜ =3450 (br); 3070, 3040, 3010 (arom. C-

H-n); 2960, 2920, 2890 (aliph. C-H-n); 2810 (OCH₃, C-H-n); 1740 (C=O-

n); 1640 (olef. C=C-n); 1590, 1573, 1483 (arom. C=C-n); 1440; 1395;

1375; 1360; 1230; 1170; 1065 (C-O-C); 1020; 1000; 985; 950; 740 (Ph, C-

H-d_{out of plane}); 690 (Ph-ring-d); 680; 615; 590 cm^ꢀ1; MS (FAB, matrix:

NBA+NaI): m/z (%): 599 (9) [M+Na⁺], 197 (100) [CPh₂OMe⁺], 167

(9) [Ph₂CH⁺], 105 (13) [PhCO⁺], 77 (4) [Ph⁺]; elemental analysis calcd

(%) for C₃₆H₃₇BO₆(576.5): C 75.00, H 6.47, found: C 74.76, H 6.47.

N

(CH₃)₂], 3.01 (s, 6H, OCH₃), 5.37 (s, 2H, 4’-H, 5’-H), 5.40 (d, ²J=

T

3.4 Hz, 1H, 5-H_a), 5.45 (d, ²J=3.4 Hz), 7.24–7.35 ppm (m, 20H, arom.

CH); ¹³C NMR (126 MHz, CDCl₃): d=31.3 (C-3), 33.5 (C-2), 35.2, 37.1

[N(CH₃)₂], 51.8 (OCH₃), 77.8 (C-4’, C-5’), 83.4 (CPh₂OCH₃), 127.2, 127.3,

T

127.5, 127.8, 128.5, 129.7 (arom. CH), 130.7 (C-5), 141.1, 141.3 (arom.

C_ipso), 173.0 ppm (C-1), C-4 was not detected; IR (KBr): n˜ =3420 (br);

3070, 3040, 3010 (arom. C-H-n); 2920 (br, aliph. C-H-n); 2810 (OCH₃, C-

H-n); 1650 (amide I, C=O-n); 1640 (amide II, N-H-bending); 1590, 1570,

1480 (arom. C=C-n); 1435; 1210; 1185; 1060 (C-O-C); 1020; 1000; 950;

740 (Ph, C-H-d_{out of plane}); 680 cm^ꢀ1(Ph, ring-d); MS (FAB, matrix: NBA+

NaI): m/z (%): 612 (89) [M+Na⁺], 332 (96), 197 (100) [CPh₂OMe⁺], 168

(18) [Ph₂CH₂⁺], 105 (10) [PhCO⁺], 77 (7) [Ph⁺]; elemental analysis

calcd (%) for C₃₇H₄₀BNO₅(589.5): C 75.38, H 6.84, N 2.38, found: C

75.25, H 6.94, N 2.22.

(1R,4’R,5’R)-1-(4’,5’-Bis(methoxydiphenylmethyl)-1’,3’,2’-dioxaborolan-

2’-yl)-1-methoxy-2-propene (21): Allyl alcohol 7 (160 mg, 0.31 mmol) was

dissolved in toluene (300 mL) and N,N-dimethylformamide dimethylace-

tal (90 mL, 82 mg, 0.62 mmol) was added. The reaction mixture was

heated to 708C for 4 h, concentrated under reduced pressure. Chroma-

tography (12 g silica gel, petroleum ether/EtOAc 95:5) gave a slightly

impure, MPLC (petroleum ether/EtOAc 95:5) an analytically pure color-

less solid foam of ether 21 (92 mg, 0.17 mmol, 56%). R_f=0.38 (petroleum

ether/EtOAc 90:10); softening range: 50–678C; [a]²_D⁰=ꢀ124 (c=0.54 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=3.00 (s, 6H, OCH₃), 3.09 (ddd,

³J=6.8, ⁴J=1.6, ⁴J=1.6 Hz, 1H, 1-H), 3.12 (s, 3H, 1-OCH₃), 4.97 (ddd,

³J=10.5, ²J=1.7, ⁴J=1.6 Hz, 1H, 3-H_E), 4.98 (ddd, ³J=17.2, ²J=1.7, ⁴J=

1.6 Hz, 1H, 3-H_Z), 5.36 (s, 2H, 4’-H, 5’-H), 5.48 (ddd, ³J=17.2, ³J=10.5,

³J=6.8 Hz, 1H, 2-H), 7.23–7.36 ppm (m, 20H, arom. CH); ¹³C NMR

(126 MHz, CDCl₃): d=51.7 (OCH₃), 58.0 (1-OCH₃), 72.4 (C-1), 78.0 (C-

4’, C-5’), 83.2 (CPh₂OCH₃), 114.3 (C-3), 127.4, 127.4, 127.5, 127.8, 128.4,

129.7 (arom. CH), 135.5 (C-2), 141.0, 141.1 ppm (arom. C_ipso); IR (KBr):

n˜ =3420 (br); 3070, 3040, 3010 (arom. C-H-n); 2960, 2920 (aliph. C-H-n);

2810 (OCH₃, C-H-n); 1630 (olef. C=C-n); 1590, 1570, 1480 (arom. C=C-

n); 1435; 1370; 1225; 1285; 1260; 1060 (C-O-C); 1020; 1000; 985, 950

(CH=CH₂, C-H-d_{out of plane}); 900; 740 (Ph, C-H-d_{out of plane}); 680 (Ph, ring-

d); 615; 590 cm^ꢀ1; MS (FAB, matrix: NBA+NaI): m/z (%): 557 (26)

[M+Na⁺], 197 (100) [CPh₂OMe⁺], 167 (9) [Ph₂CH⁺], 105 (9) [PhCO⁺],

77 (3) [Ph⁺]; elemental analysis calcd (%) for C₃₄H₃₅BO₅(534.5): C

76.41, H 6.60, found: C 76.22, H 6.82.

(4’’R,5’’R)-3’-[4’’,5’’-Bis(methoxydiphenylmethyl)-1’’,3’’,2’’-dioxaborolan-

2’’-yl] allyl 3-oxobutyrate (24): Allyl alcohol 6 (500 mg, 0.96 mmol) was

dissolved in THF (5 mL) and DMAP (11 mg, 0.09 mmol) and diketene

(83.5 mL, 91.6 mg, 1.09 mmol) were added, whereupon the reaction mix-

ture got warm. After 23 h to the mixture was added 0.1% aqueous

NaOH solution and Et₂O. The organic phase was washed with 0.1%

aqueous NaOH solution and saturated aqueous NaCl solution, dried over

MgSO₄and concentrated under reduced pressure. Chromatography (40 g

silica gel, petroleum ether/EtOAc 83:17) gave a slightly impure colorless

solid foam (83% 24, 485 mg, 0.80 mmol), MPLC (petroleum ether/

EtOAc 85:15) furnished an analytically pure sample. The ratio of keto to

enol form is 9:1 in favor of keto form (¹H NMR). R_f=0.36 (petroleum

ether/EtOAc 85:15); softening range: 52–678C; [a]²_D⁰=ꢀ62 (c=1.0 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃) keto form: d=2.23 (s, 3H, 4-H),

2.99 (s, 6H, OCH₃), 3.42 (s, 2H, 2-H), 4.53 (dd, ³J=4.8, ⁴J=1.7 Hz, 2H,

1’-H), 5.29 (dt, ³J=18.1, ⁴J=1.7 Hz, 3’-H), 5.35 (s, 2H, 4’’-H, 5’’-H), 6.15

(dt, ³J=18.1, ³J=4.8 Hz, 1H, 2’-H), 7.24–7.35 ppm (m, 20H, arom. CH);

different signals in enol form: d=1.94 (s, 3H, 4-H); 4.96 (s, 1H, 2-H);

6.15 ppm (dt, ³J=18.1, ³J=4.6 Hz, 1H, 2’-H); ¹³C NMR (126 MHz,

CDCl₃): d=30.1 (C-4), 49.8 (C-2), 51.8 (OCH₃), 66.1 (C-1’), 77.8 (C-4’’,

C-5’’), 83.3 (CPh₂OCH₃), 120.0 (C-3’), 127.3, 127.3, 127.5, 127.8, 128.4,

129.7 (arom. CH), 141.0, 141.2 (arom. C_ipso), 144.5 (C-2’), 166.5 (C-1),

200.2 ppm (C-3); IR (KBr): n˜ =3420 (br); 3070, 3040, 3010 (arom. C-H-

(4’’R,5’’R,2’E)-3’-[4’’,5’’-Bis(methoxydiphenylmethyl)-1’’,3’’,2’’-dioxaboro-

lan-2’’-yl]prop-2’-en-1’-yl acetate (22): Allyl alcohol 6 (520 mg 1.00 mmol)

was dissolved in CH₂Cl₂(2 mL) and Et₃N (277 mL, 202 mg, 2.00 mmol),

DMAP (12 mg, 0.10 mmol) and acetic anhydride (189 mL, 204 mg,

2.00 mmol) were added. After 15 min saturated aqueous NaHCO₃solu-

tion (5 mL) was added. The aqueous phase was extracted thrice with

CH₂Cl₂. The combined organic phase was washed with saturated aqueous

5188

www.chemeurj.org

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

n); 2940, 2920, 2890 (aliph. C-H-n); 2810 (OCH₃, C-H-n); 1740 (ester, C=

O-n); 1715 (keton, C=O-n); 1635 (olef. C=C-n); 1590, 1570, 1480 (arom.

C=C-n); 1435; 1370; 1335; 1230; 1170; 1060 (C-O-C); 1020; 1000; 950;

740 (Ph, C-H-d_{out of plane}); 690 (Ph, Ring-d); 680; 615; 590 cm^ꢀ1; MS (FAB,

matrix: NBA+NaI): m/z (%): 627 (71) [M+Na⁺], 401 (5), 197 (100)

[CPh₂OMe⁺], 167 (8) [Ph₂CH⁺], 105 (12) [PhCO⁺], 77 (6) [Ph⁺]; ele-

mental analysis calcd (%) for C₃₇H₃₇BO₇(604.5): C 73.52, H 6.17, found:

C 73.55, H 6.19.

[Ph⁺]; elemental analysis calcd (%) for C₃₅H₃₃BF₃NO₅(615.5): C 68.30,

H 5.40, N 2.28, found: C 68.21, H 5.43, N 2.18.

(1’R,4’’R,5’’R)- and (1’S,4’’R,5’’R)-N-{1’-[4’’,5’’-Bis(methoxydiphenylmeth-

yl)-1’’,3’’,2’’-dioxaborolan-2’’-yl]prop-2’-en-1’-yl}-2,2,2-trichloroacetamide

(27): Trichloroacetimidate 25 (50 mg, 0.08 mmol) was dissolved in 1,2-di-

chlorobenzene (15 mL). The solution was heated to 1718C for 10 h and

cooled to RT. The reaction mixture was loaded directly on a column

(10 g silica gel) which was conditioned with petroleum ether. Chromatog-

raphy (petroleum ether to petroleum ether/EtOAc 90:10) gave a mixture

of starting material 25 and product 27 (16:84), whereas the product 27

was a 59:41 diastereomeric mixture. The diastereomers could not be sep-

arated by MPLC, but the product 27 was furnished as an analytically

pure colorless solid foam with dr 59:41 (34 mg, 0.05 mmol, 67%); starting

material 25 was recovered (5 mg, 8 mmol, 10%). R_f=0.48 (petroleum

ether/EtOAc 90:10); melting range: 120–1268C; diastereomer A:

¹H NMR (500 MHz, CDCl₃): d=3.00 (s, 6H, OCH₃), 3.81 (m, 1H, 1’-H),

4.85 (ddd, ³J=17.1, ²J=2.3, ⁴J=0.8 Hz, 1H, 3’-H_Z), 4.90 (ddd, ³J=10.5,

²J=2.3, ⁴J=0.8 Hz, 1H, 3’-H_E), 5.35 (ddd, ³J=17.1, ³J=10.5, ³J=4.8 Hz,

1H, 2’-H), 5.43 (s, 2H, 4’’-H, 5’’-H), 6.49 (d, ³J=7.2 Hz, 1H, NH), 7.24–

7.42 ppm (m, 20H, arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=40.2 (C-

1’), 51.9 (OCH₃), 78.7 (C-4’, C-5’), 83.2 (CPh₂OCH₃), 92.7 (C-2), 113.1

(C-3’), 127.7, 127.7, 127.8, 127.9, 128.3, 129.6 (arom. CH), 132.9 (C-2’),

140.4, 140.6 (arom. C_ipso), 161.2 ppm (C-1); diastereomer B: ¹H NMR

(500 MHz, CDCl₃): d=3.02 (s, 6H, OCH₃), 3.75 (m, 1H, 1’-H), 4.90

(ddd, ³J=17.1, ²J=2.4, ⁴J=0.9 Hz, 1H, 3’-H_Z), 4.94 (ddd, ³J=10.5, ²J=

2.4, ⁴J=0.9 Hz, 1H, 3’-H_E), 5.40 (s, 2H, 4’’-H, 5’’-H), 5.54 (ddd, ³J=17.1,

³J=10.5, ⁴J=4.6 Hz, 1H, 2’-H), 6.38 (d, ³J=7.8 Hz, 1H, NH), 7.24–

7.42 ppm (m, 20H, arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=40.2 (C-

1), 51.8 (OCH₃), 78.7 (C-4’’, C-5’’), 83.3 (CPh₂OCH₃), 92.7 (C-2), 112.4

(C-3’), 127.6, 127.7, 127.8, 127.9, 128.2, 129.6 (arom. CH), 132.3 (C-2’),

140.5, 140.7 (arom. C_ipso), 161.5 ppm (C-1); IR (film, ATR): n˜ =3430 (N-

H-n); 3085, 3060, 3030 (arom. C-H-n); 2985, 2960, 2940, 2910 (aliph. C-

H-n); 2835 (OCH₃, C-H-n); 1720 (CONH, amide I); 1655 (olef. C=C-n);

1600, 1585, 1495 (arom. C=C-n); 1510 (CONH, amide II); 1445; 1390;

1350; 1240; 1200; 1075 (C-O-C); 1030; 1010; 820; 760 (Ph, C-H-

d_{out of plane}); 700 (Ph, ring-d); 635 cm^ꢀ1; MS (FAB, matrix: NBA+NaI): m/z

(%): 688 (25) [M+Na⁺], 197 (100) [CPh₂OMe⁺], 167 (8) [Ph₂CH⁺], 105

(22) [PhCO⁺], 77 (10) [Ph⁺]; elemental analysis calcd (%) for

C₃₅H₃₃BCl₃NO₅(664.8): C 63.23, H 5.00, N 2.11, found: C 63.45, H 5.10,

N 1.97.

(4’’R,5’’R,2’E)-3’-[4’’,5’’-Bis(methoxydiphenylmethyl)-1’’,3’’,2’’-dioxaboro-

lan-2’’-yl]-2’-propen-1’-yl 2,2,2-trichloroacetimidate (25): NaH (10 mg,

0.40 mmol) was suspended in Et₂O (2 mL) and a solution of allyl alcohol

6 (1.04 g, 2.00 mmol) in Et₂O (3 mL) was slowly dropwise. After 30 min

the reaction mixture was cooled to 08C and Cl₃CCN (241 mL, 347 mg,

2.40 mmol) was added dropwise. After 1 h at 08C and 2 h at RT the reac-

tion mixture was concentrated under reduced pressure. Chromatography

(70 g silica gel, petroleum ether/EtOAc 85:15) furnished an analytically

pure colorless solid foam of trichloroacetimidate 25 (1.30 g, 1.96 mmol,

98%). R_f=0.40 (petroleum ether/EtOAc 90:10); softening range: 80–

908C; [a]²_D⁰=ꢀ54 (c=1.00 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=

3.00 (s, 6H, OCH₃), 4.68 (dd, ³J=4.6, ⁴J=1.8 Hz, 2H, 1’-H), 5.34 (s, 2H,

4’’-H, 5’’-H), 5.42 (dt, ³J=18.1, ⁴J=1.8 Hz, 1H, 3’-H), 6.24 (dt, ³J=18.1,

³J=4.6 Hz, 1H, 2’-H), 7.24–7.35 (m, 20H, arom. CH), 8.26 ppm (s, 1H,

NH); ¹³C NMR (126 MHz, CDCl₃): d=51.8 (OCH₃), 69.9 (C-1’), 77.8 (C-

4’’, C-5’’), 83.3 (CPh₂OCH₃), 91.3 (C-2), 119.9 (C-3’), 127.3, 127.3, 127.5,

127.8, 128.4, 129.7 (arom. CH), 141.0, 141.2 (arom. C_ipso), 144.3 (C-2’),

162.3 ppm (C-1); IR (KBr): n˜ =3420 (br); 3325 (N-H-n); 3065, 3040, 3010

(arom. C-H-n); 2935, 2915, 2880 (aliph. C-H-n); 2810 (OCH₃, C-H-n);

1660 (C=N-n); 1635 (olef. C=C-n); 1590, 1575, 1480 (arom. C=C-n);

1435; 1370; 1360; 1340; 1295; 1230; 1175; 1060 (C-O-C); 1020; 1000; 975;

950; 810; 780; 740 (Ph, C-H-d_{out of plane}); 680 (Ph, ring-d); 630 (C-Cl);

615 cm^ꢀ1; MS (FAB, matrix: NBA+NaI): m/z (%): 688 (84) [M+Na⁺],

471 (2), 197 (100) [CPh₂OMe⁺], 167 (7) [Ph₂CH⁺], 105 (11) [PhCO⁺],

77 (6) [Ph⁺]; elemental analysis calcd (%) for C₃₅H₃₃BCl₃NO₅(664.8): C

63.23, H 5.00, N 2.11, found: C 63.28, H 5.14, N 2.10.

(4’’R,5’’R,2’E)-3’-[4’’,5’’-Bis(methoxydiphenylmethyl)-1’’,3’’,2’’-dioxaboro-

lan-2’’-yl]-2’-propen-1’-yl 2,2,2-trifluoroacetimidate (26): In

a 50 mL

three-necked round-bottom flask equipped with a stirring bar, a ther-

mometer, a septum and a nitrogen inlet were introduced trifluoroaceta-

mide (746 mg, 6.60 mmol), DMSO (1.36 mL, 1.50 g, 19.2 mmol,

19.2 equiv) and CH₂Cl₂(25 mL). The solution was cooled down to

ꢀ758C (internal) and a solution of (COCl)₂(516 mL, 762 mg, 6.00 mmol)

in CH₂Cl₂(2 mL) and a solution of Et₃N (2.51 mL, 1.82 g, 18.0 mmol) in

CH₂Cl₂(1 mL) were added slowly; no rise in temperature was observed

during this process. Stirring was continued at ꢀ788C for 30 min, DBU

(4’R,5’R,1E)-1-[4’,5’-Bis(methoxydiphenylmethyl)-1’,3’,2’-dioxaborolan-2’-

yl]-3-chloro-2-propene (28): Trichloroacetimidate 25 (100 mg, 0.15 mmol)

was dissolved in THF (2.5 mL) and cooled to 08C. A suspension of

[PdCl₂(CH₃CN)₂] (2 mg, 8 mmol) in THF (2 mL) was added and as no re-

R

(298 mL, 304 mg, 2.00 mmol) and

a solution of alcohol 6 (520 mg,

action occured, the reaction mixture was heated to 808C for 23 h, cooled

to RT and concentrated under reduced pressure. Chromatography (41 g

silica gel, petroleum ether/EtOAc 95:5) gave a spectroscopically pure col-

orless solid foam (57%, 46 mg, 0.09 mmol), MPLC yielded an analytically

pure sample. R_f=0.60 (petroleum ether/EtOAc 90:10); softening range:

80–908C; [a]²_D⁰=ꢀ65 (c=0.90 in CHCl₃); ¹H NMR (500 MHz, CDCl₃):

d=3.00 (s, 6H, OCH₃), 3.91 (dd, ³J=6.1, ⁴J=1.2 Hz, 2H, 3-H), 5.32 (dt,

1.00 mmol) in CH₂Cl₂(4 mL) were added slowly via syringe. The reaction

mixture was stirred at ꢀ788C and was then allowed to reach room tem-

perature over 10 h. Water was added and the aqueous layer was extracted

twice with CH₂Cl₂(15 mL). The combined organic phase was washed

with brine (30 mL), dried over Na₂SO₄and concentrated under reduced

pressure. Chromatography (108 g silica gel, petroleum ether/EtOAc

90:10) yielded a spectroscopically pure colorless solid foam of trifluoroa-

cetimidate 26 (471 mg, 0.77 mmol, 77%), MPLC (petroleum ether/

EtOAc 95:5) furnished an analytically pure sample. R_f=0.38 (petroleum

ether/EtOAc 90:10); softening range: 60–648C; [a]²_D⁰=ꢀ61 (c=0.50 in

CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=3.00 (s, 6H, OCH₃), 4.65 (dd,

4

3

³J=17.6, J=1.2 Hz, 1H, 1-H), 5.36 (s, 2H, 4’-H, 5’-H), 6.18 (dt, J=17.6,

³J=6.1 Hz, 1H, 2-H), 7.26–7.41 ppm (m, 20H, arom. CH); ¹³C NMR

(126 MHz, CDCl₃): d=45.9 (C-3), 51.8 (OCH₃), 77.7 (C-4’, C-5’), 83.3

(CPh₂OCH₃), 121.3 (C-1), 127.3, 127.3, 127.5, 127.8, 128.4, 129.6 (arom.

CH), 140.9, 141.2 (arom. C_ipso), 146.2 ppm (C-2); IR (film, ATR): n˜ =

3390 (br); 3090, 3055, 3025 (arom. C-H-n); 2955, 2940, 2905 (aliph. C-H-

n); 2830 (OCH₃, C-H-n); 1645 (olef. C=C-n); 1600, 1580, 1495 (arom. C=

C-n); 1445; 1400; 1375; 1355; 1240; 1200; 1075 (C-O-C); 1030; 1015; 760

(Ph, C-H-d_{out of plane}); 700 cm^ꢀ1(Ph, ring-d); MS (FAB, matrix: NBA+

NaI): m/z (%): 561 (8) [M+Na⁺], 197 (100) [CPh₂OMe⁺], 167 (10)

[Ph₂CH⁺], 105 (16) [PhCO⁺], 77 (7) [Ph⁺]; elemental analysis calcd (%)

for C₃₃H₃₂BClO₄(538.9): C 73.55, H 5.99, found: C 73.52, H 6.04.

4

3

³J=4.8, J=1.8 Hz, 2H, 1’-H), 5.36 (s, 2H, 4’’-H, 5’’-H), 5.36 (dt, J=18.1,

⁴J=1.8 Hz, 1H, 3’-H), 6.21 (dt, ³J=18.1, ³J=4.8 Hz, 1H, 2’-H), 7.24–7.35

(m, 20H, arom. CH), 8.14 ppm (s, 1H, NH); ¹³C NMR (126 MHz,

CDCl₃): d=51.8 (OCH₃), 68.3 (C-1’), 77.8 (C-4’’, C-5’’), 83.3

(CPh₂OCH₃), 115.5 (q, ¹J_C,F=280 Hz, C-2), 120.3 (C-3’), 127.3, 127.3,

127.5, 127.8, 128.4, 129.7 (arom. CH), 141.0, 141.2 (arom. C_ipso), 143.8 (C-

2

2’), 157.5 ppm (q, J_C,F=38 Hz, C-1); IR (KBr): n˜ =3410 (br); 3330 (N-H-

n); 3070, 3040, 3015, 3000 (arom. C-H-n); 2940, 2915, 2880 (aliph. C-H-

n); 2810 (OCH₃, C-H-n); 1680 (C=N-n); 1640 (olef. C=C-n); 1590, 1570,

1480 (arom. C=C-n); 1435; 1365; 1330; 1230, 1190, 1155 (br, C-F); 1060

(C-O-C); 1020; 1000; 950; 830; 740 (Ph, C-H-d_{out of plane}); 680 (Ph, ring-d);

615 cm^ꢀ1; MS (FAB, matrix: NBA+NaI): m/z (%): 638 (7) [M+Na⁺],

197 (100) [CPh₂OMe⁺], 167 (8) [Ph₂CH⁺], 105 (15) [PhCO⁺], 77 (6)

(1’R,4’’R,5’’R)- and (1’S,4’’R,5’’R)-N-{1’-[4’’,5’’-Bis(methoxydiphenylmeth-

yl)-1’’,3’’,2’’-dioxaborolan-2’’-yl]prop-2’-en-1’-yl}–2,2,2-trifluoroacetamide

(29): Trifluoroacetimidate 26 (50 mg, 0.08 mmol) was dissolved in 1,2-di-

chlorobenzene (5 mL). The solution was heated to 1768C for 29 h and

cooled to RT. The reaction mixture was loaded directly on a column

Chem. Eur. J. 2008, 14, 5178 – 5197

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

5189

J. Pietruszka et al.

(20 g silica gel) which was conditioned with petroleum ether. Chromatog-

raphy (petroleum ether to petroleum ether/EtOAc 95:5) gave a mixture

of starting material 26 and product 29 (41:59), whereas the product 29

was a 55:45-diastereomeric mixture. The diastereomers could not be sep-

arated by MPLC, but the product 29 was furnished as an analytically

pure colorless solid foam with dr 55:45 (10 mg, 0.016 mmol, 20%); start-

ing material 26 was recovered (7 mg, 11 mmol, 14%). R_f=0.45 (petro-

leum ether/EtOAc 90:10); diastereomer A: ¹H NMR (500 MHz, CDCl₃):

(1S)-1-Phenylpropane-1,3-diol (33): Allylboronate 21 (78 mg, 0.15 mmol)

was dissolved in CH₂Cl₂(73 mL) and PhCHO (21 mL, 22 mg, 0.20 mmol)

was added. After 16 h the reaction mixture was concentrated under re-

duced pressure and dried under high vacuum. According to GP F, the

residue was used for ozonolysis and reduction. Chromatography (5.8 g

silica gel, petroleum ether/EtOAc 50:50) gave a colorless slightly impure

oil (49% 33, 11 mg, 0.07 mmol). The analytical data are in full agreement

to those previously reported.^[30][a]_D²⁰=ꢀ64 (c=0.22 in CHCl₃); for fur-

ther characterisation see above.

3

2

d=3.00 (s, 6H, OCH₃), 3.78 (m, 1H, 1’-H), 4.81 (dd, J=17.1, J=2.0 Hz,

1H, 3’-H_Z), 4.90 (dd, ³J=10.6, ²J=2.0 Hz, 1H, 3’-H_E), 5.30 (ddd, ³J=

17.1, ³J=10.6, ³J=5.0 Hz, 1H, 2’-H), 5.44 (s, 2H, 4’’-H, 5’’-H), 5.89 (d,

³J=7.4 Hz, 1H, NH), 7.26–7.35 ppm (m, 20H, arom CH); ¹³C NMR

(126 MHz, CDCl₃): d=51.8 (OCH₃), 78.7 (C-4’’, C-5’’), 83.3 (CPh₂OCH₃),

113.3 (C-3’), 127.7, 127.7, 127.9, 128.0, 128.3, 129.6 (arom. CH), 132.2 (C-

2’), 140.3, 140.6 (arom. C_ipso), 156.8 ppm (q, ³J_C,F=38 Hz, C-1), C-1’ and

Modification of side chain

(3S,4’R,5’R)-tert-Butyldimethylsilyl-3-[4’,5’-bis(methoxydiphenylmethyl)-

1’,3’,2’-dioxaborolan-2’-yl]-4-penten-1-yl ether (35): Alcohol 34^[15a]

(768 mg, 1.40 mmol) and imidazole (105 mg, 1.54 mmol) were dissolved

in CH₂Cl₂(1.40 mL) and TBSCl (222 mg) was added wereupon a color-

less solid precipitated. The reaction mixture was stirred over night, dilut-

ed with Et₂O, and H₂O was added until the solid was dissolved complete-

ly. The aqueous phase was extracted thrice with Et₂O. The combined or-

ganic phase was washed with brine, dried over MgSO₄and concentrated

under reduced pressure. Chromatography (65 g silica gel, petroleum

ether/EtOAc 98:2) gave a spectroscopically pure colorless solid foam of

ether 35 (911 mg, 1.38 mmol, 98%), MPLC (petroleum ether/EtOAc

99:1) furnished an analytically pure sample. R_f=0.08 (petroleum ether/

EtOAc 98:2), 0.44 (petroleum ether/EtOAc 95:5); softening range: 46–

528C; [a]²_D⁰=ꢀ96 (c=1.12 in CHCl₃); ¹H NMR (500 MHz, CDCl₃): d=

1

C-2 were not detected; diastereomer B: H NMR (500 MHz, CDCl₃): d=

3.02 (s, 6H, OCH₃), 3.78 (m, 1H, 1’-H), 4.78 (dd, ³J=17.1, ²J=2.0 Hz,

1H, 3’-H_Z), 4.93 (dd, ³J=10.6, ²J=2.0 Hz, 1H, 3’-H_E,), 5.42 (s, 2H, 4’’-H,

5’’-H), 5.49 (ddd, ³J=17.1, ³J=10.6, ³J=4.8 Hz, 1H, 2’-H), 5.85 (d, ³J=

7.9 Hz, 1H, NH), 7.26–7.35 ppm (m, 20H, arom. CH); ¹³C NMR

(126 MHz, CDCl₃): d=51.8 (OCH₃), 78.7 (C-4’’, C-5’’), 83.2 (CPh₂OCH₃),

112.6 (C-3’), 127.5, 127.6, 127.9, 128.0, 128.4, 129.5 (arom. CH), 132.7 (C-

2’), 140.3, 140.4 (arom. C_ipso), 156.7 ppm (q, ³J_C,F=38 Hz, C-1), C-1’ and

C-2 were not detected; IR (film, ATR): n˜ =3440 (N-H-n); 3090, 3060,

3025 (arom. C-H-n); 2970, 2940, 2910 (aliph. C-H-n); 2835 (OCH₃, C-H-

n); 1730 (CONH, amide I); 1640 (olef. C=C-n); 1600, 1580, 1495 (arom.

C=C-n); 1535 (CONH, amide II); 1450; 1380; 1335; 1240, 1210, 1175 (C-

F); 1070 (C-O-C); 1035; 760 (Ph, C-H-d_{out of plane}); 700 cm^ꢀ1(Ph, Ring-d);

MS (FAB, matrix: NBA+NaI): m/z (%): 638 (25) [M+Na⁺], 358 (14),

197 (100) [CPh₂OMe⁺], 167 (6) [Ph₂CH⁺], 105 (12) [PhCO⁺], 77 (5)

[Ph⁺]; HRMS (FAB, matrix: NBA+NaI): m/z: calcd for

C₃₅H₃₃BF₃NNaO₅: 638.2302, found: 638.2308.

ꢀ0.07, ꢀ0.05 [2s, 6H, Si

C

G

3

2

3

2

3

7.5, J=7.0 Hz, 1H, 1-H_a), 3.34 (ddd, J=10.0, J=7.8, J=5.5 Hz, 1H, 1-

H_b), 4.69 (ddd, ³J=17.1, ²J=2.0, ⁴J=1.3 Hz, 1H, 5-H_Z), 4.75 (ddd, ³J=

10.3, ²J=2.0, ⁴J=1.1 Hz, 1H, 5-H_E), 5.29 (s, 2H, 4’-H, 5’-H), 5.44 (ddd,

³J=17.1, ³J=10.3, ³J=8.2 Hz, 1H, 4-H), 7.23–7.34 ppm (m, 20H, arom.

CH); ¹³C NMR (126 MHz, CDCl₃): d=ꢀ5.3, ꢀ5.3 [Si

(CH₃)₂], 18.3 [C-

Determination of configuration

N

Ozonolysis and reduction with LiAlH₄(General procedure F): Into a

flask equipped with Teflon stop cock and gas inlet frit (quickfit with

Teflon gasket), the homoallyl alcohol (about 0.1 mmol) was dissolved in

CH₂Cl₂(10 mL) and cooled to ꢀ788C: A O₃/O₂mixture was bubbled

through the solution until it shows a persisting blue color. Excess O₃was

expelled by a stream of O₂. To the reaction mixture was added Me₂S

(1 mL), it was allowed to warm to room temperature, concentrated under

reduced pressure and dried under high vacuum. The residue was dis-

solved in THF (10 mL) and cooled to ꢀ788C. LiAlH₄(100 mg,

2.64 mmol) was added and the reaction mixture was allowed to warm to

RT. After 1 h Et₂O (10 mL) was added and cooled to 08C. Successively

H₂O (121 mL), 15% aqueous NaOH solution (121 mL) and H₂O (358 mL)

1), 77.7 (C-4’, C-5’), 83.4 (CPh₂OCH₃), 113.1 (C-5), 127.2, 127.3, 127.5,

127.8, 128.5, 129.7 (arom. CH), 138.6 (C-4), 141.3, 141.4 ppm (arom.

C_ipso); IR (KBr): n˜ =3420 (br); 3070, 3040, 3005 (arom. C-H-n); 2930,

2910, 2830 (aliph. C-H-n); 2810 (OCH₃, C-H-n); 1620 (olef. C=C-n);

1590, 1570, 1480 (arom. C=C-n); 1460; 1450; 1435; 1370; 1340; 1240;

1185; 1075; 1060 (C-O-C); 1020; 1000; 950; 885; 815, 795, 755 (TBS); 740

(Ph, C-H-d_{out of plane}); 680 (Ph, ring-d); 615; 590 cm^ꢀ1; MS (FAB, matrix:

NBA+NaI): m/z (%): 685 (5) [M+Na⁺], 197 (100) [CPh₂OMe⁺], 167

(12) [Ph₂CH⁺], 105 (9) [PhCO⁺], 73 (11) [MeSi(O)CH₂⁺]; elemental

analysis calcd (%) for C₄₁H₅₁BO₅Si (662.7): C 74.30, H 7.76, found: C

74.25, H 7.75.

(3R,4’R,5’R)-tert-Butyldimethylsilyl-3-[4’,5’-bis(methoxydiphenylmethyl)-

1’,3’,2’-dioxaborolan-2’-yl]-4-penten-1-yl ether (37): The reaction was ac-

complished according to the synthesis of ether 35: Alcohol 36 (1.12 g,

2.05 mmol), CH₂Cl₂(2.05 mL), imidazole (153 mg, 2.25 mmol) and

TBSCl (324 mg, 2.15 mmol) were used. Chromatography (85 g silica gel,

petroleum ether/EtOAc 98:2) furnished an analytically pure colorless

solid foam of ether 37 (1.38 g, 2.08 mmol, quantitative). R_f=0.11 (petro-

leum ether/EtOAc 98:2), 0.48 (petroleum ether/EtOAc 95:5); softening

range: 42–538C; [a]²⁰=ꢀ103 (c=0.88 in CHCl₃); ¹H NMR (500 MHz,

were carefully added and stirred (about 30 min) until

a precipitate

formed that can be readily filtered through a pad of Celite; the filter

cake was washed thoroughly with Et₂O. The filtrate was concentrated

under reduced pressure and dried in high vacuum.

(1S)-1-Phenylpropane-1,3-diol (33): According to GP F, homoallyl alco-

hol 31a (25 mg, 0.11 mmol; synthesis: see below) was used. Chromatog-

raphy (0.7 g silica gel, petroleum ether/EtOAc 50:50) gave a colorless

spectroscopically pure oil of diol 33 (6.0 mg, 0.04 mmol, 37%). The ana-

lytical data were in full agreement to those previously reported.^[30]R_f=

0.13 (petroleum ether/EtOAc 50:50), 0.27 (petroleum ether/EtOAc

25:75); [a]²_D⁰=ꢀ70 (c=0.12 in CHCl₃), ref.: [30] [a]²_D²(33)=ꢀ71 (c=1.02

CDCl₃): d=ꢀ0.05, ꢀ^D0.04 [2s, 6H, Si

A

G

2

3

1.30 (m, 1H, 2-H_a), 1.40–1.44 (m, 1H, 3-H), 1.47 (dddd, J=12.6, J=8.5,

³J=7.4, ³J=5.2 Hz, 1H, 2-H_b), 3.00 (s, 6H, OCH₃), 3.25 (ddd, ²J=10.0,

³J=7.7, ³J=7.4 Hz, 1H, 1-H_a), 3.32 (ddd, ²J=10.0, ³J=8.5, ³J=4.7 Hz,

1H, 1-H_b), 4.69 (ddd, ³J=17.1, ²J=2.0, ⁴J=1.1 Hz, 1H, 5-H_Z), 4.73 (ddd,

³J=10.3, ²J=2.0, ⁴J=0.7 Hz, 1H, 5-H_E), 5.29 (s, 2H, 4’-H, 5’-H), 5.33

(ddd, ³J=17.1, ³J=10.3, ³J=8.5 Hz, 1H, 4-H); 7.24–7.34 ppm (m, 20H,

1

2

3

in CHCl₃); H NMR (300 MHz, CDCl₃): d=1.93 (dddd, J=14.6, J=5.5,

³J=4.7, ³J=4.0 Hz, 1H, 2-H_a), 2.03 (dddd, ²J=14.6, ³J=8.5, ³J=6.5, ³J=

5.4 Hz, 1H, 2-H_b), 2.44 (brs, 1H, 3-OH), 2.86 (brs, 1H, 1-OH), 3.82–3.89

(m, 2H, 3-H), 4.96 (dd, ³J=8.5, ³J=4.0 Hz, 1H, 1-H), 7.25–7.38 ppm (m,

5H, arom. CH); ¹³C NMR (75 MHz, CDCl₃): d=40.5 (C-2), 61.5 (C-3),

74.4 (C-1), 125.6, 127.6, 128.5 (arom. CH), 144.3 ppm (arom. C_ipso); IR

(solution in CDCl₃): n˜ =3600 (O-H-n); 3500 (br, O-H-n); 3065, 3045,

3010 (arom. C-H-n); 2920, 2860 (aliph. C-H-n); 1480 (arom. C=C-n);

1440 (aliph. C-H-d); 1410 (O-H-d); 1035 cm^ꢀ1(C-OH); MS (EI, 70 eV):

m/z (%): 152 (33) [M⁺], 107 (100) [PhCHOH⁺], 77 (24) [Ph⁺]; HRMS

(EI, 70 eV): m/z: calcd for C₉H₁₂O₂: 152.0837, found: 152.0837.

arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=ꢀ5.3 [Si

A

G

N

1), 77.7 (C-4’, C-5’), 83.4 (CPh₂OCH₃), 113.4 (C-5), 127.2, 127.3, 127.5,

127.8, 128.5, 129.7 (arom. CH), 138.4 (C-4), 141.3, 141.4 ppm (arom.

C_ipso); IR (KBr): n˜ =3420 (br); 3070, 3040, 3010 (arom. C-H-n); 2935,

2910, 2880, 2835 (aliph. C-H-n); 2810 (OCH₃, C-H-n); 1620 (olef. C=C-

n); 1590, 1570, 1480 (arom. C=C-n); 1460; 1450; 1435; 1365; 1340; 1240;

5190

www.chemeurj.org

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

1185; 1070; 1060 (C-O-C); 1020; 1000; 950; 885; 815, 795, 755 (TBS); 740

(Ph, C-H-d_{out of plane}); 680 (Ph, ring-d); 615; 590 cm^ꢀ1; MS (FAB, matrix:

NBA+NaI): m/z (%): 685 (7) [M+Na⁺], 197 (100) [CPh₂OMe⁺], 167

(12) [Ph₂CH⁺], 105 (10) [PhCO⁺], 73 (12) [MeSi(O)CH₂⁺]; elemental

analysis calcd (%) for C₄₁H₅₁BO₅Si (662.7): C 74.30, H 7.76, found: C

74.33, H 7.77.

action mixtures were stirred at 08C for 24 h and at RT for 48 h. Chroma-

tography (petroleum ether/EtOAc 90:10 ! 85:15) furnished a spectro-

scopically pure colorless oils (ent-31b: 86 mg, 0.33 mmol, 97%; HPLC: ee

92%), MPLC (petroleum ether/EtOAc 85:15) furnished an analytically

pure sample (31b: 60 mg, 0.23 mmol, 67%; HPLC: ee 98%). R_f=0.09

(petroleum ether/EtOAc 85:15), 0.28 (petroleum ether/EtOAc 75:25);

[a]²_D⁰(31b)=ꢀ7 (c=1.14 in CHCl₃, ee 98%), [a]²_D⁰(ent-31b)=+7 (c=

1.18 in CHCl₃, ee 92%); HPLC (Chiralcel OD, hexane/iPrOH 96:4): t_R

(31b)=9.2 min, t_R(ent-31b)=6.5 min; ¹H NMR (500 MHz, CDCl₃): d=

Allyl additions

Allyl addition (General procedure D): The allylboronate (1.00 equiv)

was dissolved in CH₂Cl₂(0.5 mL per mmol of the allylboronate) and

cooled to 08C. The aldehyde (1.20–1.50 equiv) was added and the reac-

tion mixture was allowed to warm slowly (ice/water mixture in a Dewar

pot) to RT over night. Stirring was continued at RT until complete trans-

formation was detected by TLC. The reaction mixture was concentrated

under reduced pressure, dried under high vacuum, and finally analysed

by NMR spectroscopy. After concentration under reduced pressure, it

was loaded on a conditioned chromatography column as a solution in the

solvent for the chromatography with some silica gel; no pressure was ap-

plied during separation.

3

1.25 (t, J=7.1 Hz, 3H, 2’-H), 1.79 (m, 2H, 7H), 2.17 (d, J=3.4 Hz, 1H,

OH), 2.26 (m, 2H, 5-H), 2.69 (ddd, ²J=13.7, ³J=8.9, ³J=7.5 Hz, 1H, 8-

H_a), 2.82 (ddd, ²J=13.7, ³J=8.8, ³J=6.5 Hz, 1H, 8-H_b), 3.08 (ddd, ²J=

16.5, ³J=7.0, ⁴J=1.4 Hz, 1H, 2-H_a), 3.15 (ddd, ²J=16.5, ³J=7.4, ⁴J=

3

1.4 Hz, 1H, 2-H_b), 3.67 (m, 1H, 6-H), 4.13 (q, J=7.1 Hz, 2H, 1’-H), 5.65

3

4

3

(dtt, ³J=10.8, J=7.7, J=1.4 Hz, 1H, 4-H), 5.72 (dddt, J=10.8, J=7.4,

³J=7.0, ⁴J=1.3 Hz, 1H, 3-H), 7.16–7.21, 7.25–7.29 ppm (m, 5H, arom.

CH); ¹³C NMR (126 MHz, CDCl₃): d=14.1 (C-2’), 32.1 (C-8), 33.0 (C-2),

35.6 (C-5), 38.6 (C-7), 60.9 (C-1’), 70.1 (C-6), 124.1 (C-3), 125.7, 128.3,

128.4 (arom. CH); 129.3 (C-4), 142.0 (arom. C_ipso), 172.0 ppm (C-1); IR

(solution in CDCl₃): n˜ =3430 (O-H-n); 3065, 3040, 3005 (arom. C-H-n);

2960, 2910, 2840 (aliph. C-H-n); 1730 (C=O-n); 1650 (olef. C=C-n); 1595,

1575, 1485 (arom. C=C-n); 1440 (aliph. C-H-d); 1390; 1360; 1310; 1240;

1160; 1080; 1015; 915; 840; 730 (Ph, C-H-d_{out of plane}); 680 cm^ꢀ1(Ph, ring-

d); MS (EI, 70 eV): m/z (%): 262 (3) [M⁺], 244 (7) [MꢀH₂O⁺], 216 (2)

Allyl addition followed by direct LiAlH₄reduction (General procedure

E): The allylboronate (1.00 equiv) was dissolved in CH₂Cl₂(0.5 mL per

mmol of the allylboronate) and cooled to 08C. The aldehyde (1.20–

1.50 equiv) was added and the reaction mixture was allowed to warm

slowly (ice/water mixture in a Dewar pot) to RT over night. Stirring was

continued at RT until complete transformation was detected by TLC.

The reaction mixture was concentrated under reduced pressure and dried

under high vacuum, and finally analysed by NMR spectroscopy. After

concentration under reduced, the residue was dissolved in THF (10 mL

per mmol of the allylboronate) and LiAlH₄(4.00 equiv) were added.

After 1 h the reaction mixture was diluted with 20 mL Et₂O and with vig-

orous stirring successivly H₂O (46 mL per mmol LiAlH₄), 15% aqueous

NaOH solution (46 mL per mmol LiAlH₄) and H₂O (136 mL per mmol

LiAlH₄) were added carefully. After 30 min a precipitate was formed

that was filtered through a pad of Celite and washed thoroughly with

Et₂O. The filtrate was concentrated under reduced pressure and subject-

ed to flash column chromatography.

[MꢀH₂OꢀC₂H₄⁺],

198

(4)

[Mꢀ2H₂OꢀC₂H₄⁺],

128

(100)

[MꢀPhCH₂CH₂CHO⁺], 117 (32) [C₉H₉⁺], 91 (58) [PhCH₂⁺]; elemental

analysis calcd (%) for C₁₆H₂₂O₃(262.3): C 73.25, H 8.48, found: C 73.06,

H 8.59.

A

and (6R,3Z)-ethyl 6-hydroxy-7-(5’-methoxybenzyloxy)hept-3-enoate (ent-

31c) According to GP D allylboronate 15 (6.51 g, 11.1 mmol) in CH₂Cl₂

(5.50 mL) with 4’’-methoxybenzyloxyacetaldehyde (42c; 2.38 g,

13.2 mmol) was used. The reaction mixture was stirred at 08C for 24 h

and at RT for 3 d. Chromatography (450 g silica gel, petroleum ether/

EtOAc 85:15 ! 75:25) furnished a spectroscopically pure colorless oil

(31c: 3.43 g, 11.1 mmol, quant.; HPLC: ee 99%), MPLC (petroleum

ether/EtOAc 70:30) afforded an analytically pure sample. According to

GP D allylboronate 16 (3.0 g, 5.1 mmol) in CH₂Cl₂(2.5 mL) with 42c

(1.1 g, 6.1 mmol) was used. The reaction mixture was stirred at 08C for

24 h and at RT for 3 d. Chromatography (220 g silica gel, petroleum

ether/EtOAc 85:15 ! 75:25) furnished a spectroscopically pure colorless

oil (ent-31c: 1.6 g, 5.1 mmol, quant. HPLC: ee 87%); R_f=0.05 (petro-

leum ether/EtOAc 85:15), 0.16 (petroleum ether/EtOAc 70:30); [a]_D²⁰

(31c)=ꢀ6 (c=1.92 in CHCl₃, ee 99%), [a]²_D⁰(ent-31c)=+6 (c=1.94 in

CHCl₃, ee 87%); HPLC (Chiralcel OD-H, hexane/iPrOH 90:10): t_R

(31c)=26.8 min, t_R(ent-31c)=32.1 min; ¹H NMR (400 MHz, CDCl₃):

A

6-hydroxy-6-phenylhex-3-enoate (ent-31a): According to GP D allylboro-

nates 15 or 16 (240 mg, 0.41 mmol, 1.00 equiv), respectively, in CH₂Cl₂

(200 mL) with benzaldehyde (62 mL, 65 mg, 0.61 mmol, 1.50 equiv) were

used. The reaction mixtures were stirred at 08C over night and at RT for

10 h. Chromatographic purification (petroleum ether to petroleum ether/

EtOAc 90:10) gave a spectroscopically pure colorless oil (31a: 87 mg,

0.37 mmol, 91%; Mosher ester:^[41,15c]ee 89%; ent-31a: 85 mg, 0.36 mmol,

89%; Mosher ester: ee > 99%), repeated chromatography furnished an

analytically pure sample. R_f(31a)=0.25 (petroleum ether/EtOAc 85:15);

[a]²_D⁰(31a)=ꢀ82 (c=0.84 in CHCl₃), [a]²_D⁰(ent-31a)=+85 (c=1.22 in

CHCl₃). ¹H NMR (500 MHz, CDCl₃): d=1.25 (t, ³J=7.1 Hz, 3H, 2’-H),

2.45–2.57 (m, 2H, 5-H), 2.61 (d, ³J=3.7 Hz, 1H, OH), 3.01 (ddd, ²J=

16.6, ³J=7.1, ⁴J=1.5 Hz, 1H, 2-H_a), 3.08 (ddd, ²J=16.6, ³J=7.4, ⁴J=

1.5 Hz, 1H, 2-H_b), 4.13 (q, ³J=7.1 Hz, 2H, 1’-H), 4.73 (ddd, ³J=7.7, ³J=

5.2, ³J=3.7 Hz, 1H, 6-H), 5.63 (m, 1H, 4-H), 5.71 (dddt, ³J=10.8, ³J=

7.4, ³J=7.1, ⁴J=1.4 Hz, 1H, 3-H), 7.25–7.37 ppm (m, 5H, arom. CH);

¹³C NMR (126 MHz, CDCl₃): d=14.1 (C-2’), 33.0 (C-2), 37.5 (C-5), 60.8

(C-1’), 73.3 (C-6), 124.3 (C-3), 125.7, 127.5, 128.4 (arom. CH), 128.9 (C-

4), 144.0 (arom. C_ipso), 171.9 ppm (C-1); IR (solution in CDCl₃): n˜ =3590

(O-H-n); 3450 (br); 3065, 3045, 3010 (arom. C-H-n); 2960, 2920, 2880

(aliph. C-H-n); 2810; 1720 (C=O-n); 1650 (olef. C=C-n); 1595, 1575, 1485

(arom. C=C-n); 1440 (aliph. C-H-d); 1390 (O-H-d); 1360; 1315; 1175

(ester, C-O); 1060; 1015 cm^ꢀ1; MS (EI, 70 eV): m/z (%): 234 (2) [M⁺],

216 (0.08) [MꢀH₂O⁺], 189 (0.6) [MꢀOEt⁺], 171 (6) [MꢀH₂OꢀEtO⁺],

128 (100) [MꢀPhCHO⁺], 107 (66) [PhCHOH⁺], 77 (49) [Ph⁺]; HRMS

(EI, 70 eV): m/z: calcd for C₁₄H₁₈O₃: 234.1256, found: 234.1257; elemen-

tal analysis calcd (%) for C₁₄H₁₈O₃(234.3): C 71.77, H 7.74, found: C

71.48, H 7.88.

3

d=1.25 (t, J=7.1 Hz, 3H, 2’’’-H), 2.27 (ddd, J=7.3, J=6.4, J=1.3 Hz,

2H, 5-H), 2.49 (brs, 1H, OH), 3.09 (ddd, ²J=16.0, ³J=7.0, ⁴J=1.4 Hz,

1H, 2-H_a), 3.10 (ddd, ²J=16.0, ³J=7.0, ⁴J=1.4 Hz, 1H, 2-H_b), 3.36 (dd,

²J=9.5, ³J=7.0 Hz, 1H, 7-H_a), 3.47 (dd, ²J=9.5, ³J=3.7 Hz, 1H, 7-H_b),

3

3.80 (s, 3H, OCH₃), 3.84 (dtd, J=7.0, J=6.4, J=3.7 Hz, 1H, 6-H), 4.13

(q, ³J=7.1 Hz, 2H, 1’’’-H), 4.48 (s, 2H, 1’-H), 5.63 (dtt, ³J=10.8, ³J=7.3,

⁴J=1.4 Hz, 1H, 4-H), 5.70 (dtt, ³J=10.8, ³J=7.0, ⁴J=1.3 Hz, 1H, 3-H),

6.88 (m, 2H, 3’’-H), 7.25 ppm (m, 2H, 2’’-H); ¹³C NMR (101 MHz,

CDCl₃): d=14.1 (C-2’’’), 31.5 (C-5), 33.0 (C-2), 55.2 (OCH₃), 60.7 (C-1’’’),

69.8 (C-6), 73.0 (C-1’), 73.4 (C-7), 113.8 (C-3’’), 123.7 (C-3), 128.5 (C-4),

129.3 (C-2’’), 130.0 (C-1’’), 159.2 (C-4’’), 171.8 ppm (C-1); IR (film,

ATR): n˜ =3450 (O-H-n); 3030 (arom. C-H-n); 2980, 2935, 2905, 2860

(aliph. C-H-n); 2835 (OCH₃, C-H-n); 1730 (C=O-n); 1660 (olef. C=C-n);

1610, 1585, 1510 (arom. C=C-n); 1465, 1365; 1325; 1300; 1245, 1030;

1175; 1095; 945; 930; 845; 820 (1,4-disubstituted benzene ring); 755;

705 cm^ꢀ1; MS (ESI-1): m/z (%): 326 (100) [M+NH₄⁺]; MS2 (326@16): m/z

(%): 309 (100) [M+H⁺]; elemental analysis calcd (%) for C₁₇H₂₄O₅

(308.4): C 66.21, H 7.84, found: C 66.16, H 7.93.

A

(6R,3Z)-6-hydroxy-6-phenylhex-3-enoic acid dimethylamide (ent-43a):

According to GP D allylboronate 18 (284 mg, 0.48 mmol) in CH₂Cl₂

(240 mL) and benzaldehyde (69 mL, 72 mg, 0.67 mmol) was used. The re-

action mixture was stirred at RT for 20 h. Chromatography (22 g silica

hydroxy-8-phenyloct-3-enoate (ent-31b): According to GP D allylboro-

nates 15 or 16 (200 mg, 0.34 mmol), respectively, in CH₂Cl₂(170 mL) with

3-phenyl propionaldehyde (54 mL, 55 mg, 0.41 mmol) were used. The re-

Chem. Eur. J. 2008, 14, 5178 – 5197

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

5191

J. Pietruszka et al.

gel, EtOAc) gave a spectroscopically pure colorless oil (43a: 89 mg,

0.38 mmol, 79%; Mosher ester:^[41]ee 94%). Following GP D, allylboro-

nate 19 (100 mg, 0.17 mmol) in toluene (1 mL) with benzaldehyde

(17 mL, 18 mg, 0.17 mmol) was used. The reaction mixture was set up at

ꢀ1008C and was allowed to reach room temperature slowly. It was

stirred at RT for 6 d. Chromatography (7 g silica gel, EtOAc) furnished a

spectroscopically colorless oil (ent-43a: 35 mg, 0.15 mmol, 88%; Mosher

ester: ee > 99%). To avoid long reaction times, the originally GP D

should preferentially be used. R_f=0.28 (EtOAc), 0.05 (petroleum ether/

EtOAc 50:50); [a]²_D⁰(43a)=ꢀ128 (c=0.20 in CHCl₃, ee 94%), [a]²_D⁰(ent-

(aliph. C-H-n); 1625 (C=O-n); 1495 (arom. C=C-n); 1455; 1400; 1260;

1140; 1055; 970; 750 (Ph, C-H-d_{out of plane}); 700 cm^ꢀ1; MS (ESI-2): m/z

(%): 300 (7) [M+K⁺], 284 (85) [M+Na⁺], 262 (7) [M+H⁺];

(3R)-5-Phenylpentan-1,3-diol (47): According to GP F homoallyl alcohol

46 (18 mg, ꢁ0.07 mmol) was used. Chromatography (2 g silica gel, petro-

leum ether/EtOAc 40:60) gave cololurless spectroscopically pure oil of

diol 47 (7.0 mg, 0.04 mmol, ꢁ56%). The analytical data are in full agree-

ment to those previously reported:^[42]R_f(47)=0.14 (petroleum ether/

EtOAc 40:60); [a]²_D⁰=ꢀ18 (c=0.35 in CHCl₃), [a]²_D⁴=ꢀ13 (c=0.35 in

EtOH), ref.:^[42][a]²_D⁴=ꢀ10.2 (c=1.32 in EtOH); ¹H NMR (300 MHz,

CDCl₃): d=1.70–1.87 (m, 4H, 2-H, 4-H), 2.37, 2.54 (2brs, 2H, OH), 2.69

(ddd, ²J=13.7, ³J=8.8, ³J=6.9 Hz, 1H, 5-H_a), 2.79 (ddd, ²J=13.7, ³J=

9.2, ³J=6.5 Hz, 1H, 5-H_b), 3.79–3.94 (m, 3H, 1-H, 3-H), 7.16–7.32 ppm

(m, 5H, arom. CH); ¹³C NMR (151 MHz, CDCl₃): d=29.7 (C-5), 38.4,

39.4 (C-2, C-4), 61.8 (C-1), 71.6 (C-3), 125.9, 128.4, 128.4 (arom. CH),

141.9 ppm (arom. C_ipso); IR (film, ATR): n˜ =3340 (br, O-H-n); 3085,

3060, 3025 (arom. C-H-n); 2935, 2860 (aliph. C-H-n); 1605, 1585, 1495

(arom. C=C-n); 1455; 1055 (C-O-n); 745 (C-H-d_{out of plane}); 700 cm^ꢀ1(Ph,

ring-d).

43a)=+132 (c=0.64 in CHCl₃, ee

>

99%); ¹H NMR (500 MHz,

(CH₃)₂], 3.00–

CDCl₃): d=2.46–2.58 (m, 2H, 5-H), 2.92, 2.97 [2s, 6H, N

ACHTREUNG

3.11 (m, 2H, 2-H), 3.77 (d, ³J=4.2 Hz, 1H, OH), 4.75 (ddd, ³J=7.6, ³J=

4.5, ³J=4.2 Hz, 1H, 6-H), 5.62 ꢀ5.70 (m, 2H, 3-H, 4-H), 7.22–7.39 ppm

(m, 5H, arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=31.8 (C-2), 35.6,

37.3 [N(CH₃)₂], 37.7 (C-5), 72.9 (C-6), 124.9 (C-3), 125.6, 127.0, 128.1

E

(arom. CH), 128.9 (C-4), 144.5 (arom. C_ipso), 171.5 ppm (C-1); IR (solu-

tion in CDCl₃): n˜ =3600 (O-H-n); 3360 (br); 3070, 3045, 3010 (arom. C-

H-n); 2920, 2870 (aliph. C-H-n); 1625 (C=O-n); 1480 (arom. C=C-n);

1440 (aliph. C-H-d); 1390; 1250; 1130; 1040 cm^ꢀ1; MS (EI, 70 eV): m/z

(%): 233 (2) [M⁺], 215 (1) [MꢀH₂O⁺], 127 (87) [MꢀPhCHO⁺], 107 (12)

[PhCHOH⁺], 105 (19) [PhCO⁺], 77 (18) [Ph⁺], 72 (100) [Me₂NCO⁺];

HRMS (AUTO-CI): m/z: calcd for C₁₄H₂₀NO₂: 234.1494, found:

234.1486; elemental analysis calcd (%) for C₁₄H₁₉NO₂(233.3): C 72.07, H

8.21, N 6.00, found: C 71.41, H 8.42, N 5.78.

A

amide (43c) and (6R,3Z)-6-hydroxy-7-(4’’-methoxybenzyloxy)hept-3-

enoic acid dimethylamide (ent-43c): According to GP D allylboronates

18 or 19 (200 mg, 0.34 mmol), respectively, in CH₂Cl₂(170 mL) with 42c

(73 mg, 0.41 mmol) were used. The reaction mixtures were stirred at 08C

for 24 h and at RT for 24 h. Chromatography (16 g silica gel, petroleum

ether/EtOAc 60:40 ! EtOAc) furnished analytically pure colorless oils

A

(6S,3E)-6-Hydroxy-8-phenyloct-3-enoic acid dimethylamide (46) and

(6S,3Z)-6-hydroxy-8-phenyloct-3-enoic acid dimethylamide (ent-43b):

According to GP D allylboronates 18 or 19 (200 mg, 0.34 mmol), respec-

tively, in CH₂Cl₂(170 mL) with 3-phenylpropionaldehyde (54 mL, 55 mg,

0.41 mmol) were used. The reaction mixtures were stirred at 08C for 24 h

and at RT for 4 d. Chromatography (14 g silica gel, petroleum ether/

EtOAc 70:30 ! EtOAc) yielded spectroscopically pure colorless oils

[from 18 (43b: 58 mg, 0.22 mmol, 65%; HPLC: ee > 99%; 46: 26 mg,

0.10 mmol, 29%) and 19 (ent-43b: 83 mg, 0.32 mmol, 94%; HPLC: ee

94%)]. R_f(43b)=0.19 (EtOAc), R_f(46)=0.15 (EtOAc); [a]²_D⁰(43b)=

ꢀ16 (c=0.90 in CHCl₃, ee > 99%), [a]²_D⁰(46)=ꢀ14 (c=1.25 in CHCl₃),

[a]²_D⁰(ent-43b)=+14 (c=1.20 in CHCl₃, ee 94%); HPLC (Chiralcel OD-

H, hexane/iPrOH 80:20): t_R(43b)=22.4 min, t_R(ent-43b)=19.6 min; ho-

moallyl alcohol 43b: ¹H NMR (300 MHz, CDCl₃): d=1.70–1.89 (m, 2H,

(43c: 90 mg, 0.29 mmol, 86%; HPLC: ee

> 99%; ent-43c: 94 mg,

0.31 mmol, 90%; HPLC: ee 96%); R_f=0.15 (EtOAc); [a]²_D⁰(43c)=ꢀ25

(c=1.80 in CHCl₃, ee > 99%), [a]²_D⁰(ent-43c)=+24 (c=1.86 in CHCl₃,

ee 96%); HPLC (Chiralcel OD-H, hexane/iPrOH 80:20): t_R(43c)=

27.0 min, t_R(ent-43c)=31.9 min; ¹H NMR (400 MHz, CDCl₃): d=2.29

3

(ddd, J=7.4, J=6.3, J=1.3 Hz, 2H, 5-H), 2.93, 3.00 [2s, 6H, N(CH₃)₂],

A

3.11 (ddd, ²J=9.3, ³J=6.9, ⁴J=1.4 Hz, 1H, 2-H_a), 3.12 (ddd, ²J=9.3, ³J=

6.9, ⁴J=1.4 Hz, 1H, 2-H_b), 3.19 (brs, 1H, OH), 3.40 (dd, ²J=9.5, ³J=

6.4 Hz, 1H, 7-H_a), 3.46 (dd, ²J=9.5, ³J=4.5 Hz, 1H, 7-H_b), 3.80 (s, 3H,

OCH₃), 3.84 (dtd, ³J=6.4, ³J=6.3, ³J=4.5 Hz, 1H, 6-H), 4.48 (s, 2H, 1’-

H), 5.64 (dtt, ³J=10.9, ³J=7.4, ⁴J=1.4 Hz, 1H, 4-H), 5.70 (dtt, ³J=10.9,

³J=6.9, ⁴J=1.3 Hz, 1H, 3-H), 6.87 (m, 2H, 3’’-H), 7.25 ppm (m, 2H, 2’’-

H); ¹³C NMR (101 MHz, CDCl₃): d=31.8 (C-2), 32.0 (C-5), 35.5, 37.2 [N-

A

2

3

7H), 2.20–2.34 (m, 2H, 5-H), 2.70 (ddd, J=13.7, J=9.3, J=7.2 Hz, 1H,

124.7 (C-3), 128.3 (C-4), 129.2 (C-2’’), 130.0 (C-1’’), 159.1 (C-4’’),

171.3 ppm (C-1); IR (film, ATR): n˜ =3410 (O-H-n); 3025 (arom. C-H-n);

2930, 2910, 2860 (aliph. C-H-n); 2840 (OCH₃, C-H-n); 1625 (C=O-n);

1615, 1585, 1510 (arom. C=C-n); 1465, 1395; 1300; 1245; 1030; 1175;

1085; 820 (1,4-disubstituted benzene ring); 710 cm^ꢀ1; MS (ESI-2): m/z

(%): 346 (76) [M+K⁺], 330 (100) [M+Na⁺], 308 (59) [M+H⁺]; elemen-

tal analysis calcd (%) for C₁₇H₂₅NO₄(307.4): C 66.43, H 8.20, N 4.56,

found: C 66.32, H 8.22, N 4.55.

8-H_a), 2.84 (ddd, ²J=13.7, ³J=9.5, ³J=5.8 Hz, 1H, 8-H_b), 2.95, 3.04 [2s,

6H, N(CH₃)₂], 3.08–3.21 (m, 3H, 2-H, OH), 3.66 (m, 1H, 6-H), 5.64–5.75

N

(m, 2H, 3-H, 4-H), 7.14–7.31 ppm (m, 5H, arom. CH); ¹³C NMR

(101 MHz, CDCl₃): d=31.9 (C-2), 32.2 (C-8), 35.7 (C-5, NC_aH₃), 37.4

(NC_bH₃), 38.9 (C-7), 69.9 (C-6), 124.9 (C-3), 125.7, 128.3, 128.5 (arom.

CH), 129.4 (C-4), 142.3 (arom. C_ipso), 171.6 ppm (C-1); IR (film, ATR):

n˜ =3400 (O-H-n); 3085, 3060, 3025 (arom. C-H-n); 2930, 2860 (aliph. C-

H-n); 1625 (C=O-n); 1495 (arom. C=C-n); 1455; 1395 (O-H-d); 1260;

1140; 1050; 750 (Ph, C-H-d_{out of plane}); 700 cm^ꢀ1; MS (EI, 70 eV): m/z (%):

261 (10) [M⁺], 243 (10) [MꢀH₂O⁺], 156 (21) [MꢀPhCH₂CH₂⁺], 134 (2)

[PhCH₂CH₂CHO⁺], 127 (84) [MꢀPhCH₂CH₂CHO⁺], 126 (8)

[MꢀPhCH₂CH₂CHOH⁺], 91 (31) [PhCH₂⁺], 87 (16) [MeCONMe₂⁺], 72

(100) [OCNMe₂⁺]; MS (ESI-1): m/z (%): 262 (100) [M+H⁺]; HRMS

(EI, 70 eV): m/z: calcd for C₁₆H₂₃NO₂: 261.1729, found: 261.1729; ele-

mental analysis calcd (%) for C₁₆H₂₃NO₂(261.4): C 73.53, H 8.87, N 5.36,

A

(1R,3Z)-6-(tert-butyldimethylsilyloxy)-1-phenylhex-3-en-1-ol (ent-44a):

According to GP E allylboronates 35 or 37 (200 mg, 0.30 mmol), respec-

tively, in CH₂Cl₂(150 mL) with benzaldehyde (42 mg, 0.39 mmol) were

used. The reaction mixtures were stirred at 08C for 24 h and at RT for

48 h. For the reduction THF (10 mL) and LiAlH₄(60 mg, 1.58 mmol)

were utilized, for the work up H₂O (69 mL), 15% aqueous NaOH solu-

tion (69 mL) and H₂O (205 mL) were added. Chromatography (15 g silica

gel, petroleum ether/EtOAc 96:4) furnished analytically pure colorless

oils (44a: 74 mg, 0.24 mmol, 80%; HPLC: ee 87%; ent-44a: 71 mg,

0.23 mmol, 77%; HPLC: ee 96%); R_f=0.11 (petroleum ether/EtOAc

95:5), 0.43 (petroleum ether/EtOAc 85:15); [a]²_D⁰(44a)=ꢀ55 (c=1.36 in

CHCl₃, ee 87%), [a]²_D⁰(ent-44a)=+58 (c=1.36 in CHCl₃, ee 96%),

HPLC (Chiralcel OD, hexane/iPrOH 99.4:0.6): t_R(44a)=9.4 min, t_R(ent-

found:

C 72.94, H 9.01, N

5.11; homoallyl alcohol 46: ¹H NMR

2 3

(300 MHz, CDCl₃): d=1.71–1.83 (m, 2H, 7H); 2.17 (ddddt, J=13.9, J=

7.9, ³J=7.7, ⁴J=0.9, ⁵J=0.9 Hz, 1H, 5-H_a), 2.30 (brs, 1H, OH), 2.31

(ddddt, ²J=13.9, ³J=6.4, ³J=4.2, ⁴J=1.1, ⁵J=1.0 Hz, 1H, 5-H_b), 2.68

(ddd, ²J=13.8, ³J=8.3, ³J=7.9 Hz, 1H, 8-H_a), 2.82 (ddd, ²J=13.8, ³J=

8.0, ³J=7.5 Hz, 1H, 8-H_b), 2.94, 3.00 [2s, 6H, N

(CH₃)₂], 3.10 (m, 2H, 2-

A

3

H), 3.64 (dddd, J=7.9, J=6.8, J=5.8, J=4.2 Hz, 1H, 6-H), 5.53 (dddt,

³J=15.4, ³J=7.7, ³J=6.4, ⁴J=1.4 Hz, 1H, 4-H), 5.67 (dtdd, ³J=15.4, ³J=

6.5, ⁴J=1.1, ⁴J=0.9 Hz, 1H, 3-H), 7.15–7.31 ppm (m, 5H, arom. CH);

44a)=7.4 min; ¹H NMR (500 MHz, CDCl₃): d=0.06 [s, 6H, Si

(CH₃)₂],

N

2

3

4

0.90 [s, 9H, C(CH₃)₃], 2.24 (ddddd, J=14.1, J=7.2, J=6.7, J=6.5, J=

A

1.5 Hz, 1H, 5-H_a), 2.33 (ddddd, ²J=14.1, ³J=7.2, ³J=6.7, ³J=6.4, ⁴J=

1.5 Hz, 1H, 5-H_b), 2.45 (d, ³J=3.4 Hz, 1H, OH), 2.47 (dddd, ²J=14.2,

³J=6.8, ³J=5.0, ⁴J=1.4 Hz, 1H, 2-H_a), 2.56 (dddd, ²J=14.2, ³J=7.9, ³J=

6.8, ⁴J=1.4 Hz, 1H, 2-H_b), 3.59 (dt, ²J=9.9, ³J=6.7, ³J=6.7 Hz, 1H, 6-

¹³C NMR (75 MHz, CDCl₃): d=32.0 (C-8), 35.5, 37.3 [br, N

(CH₃)₂], 37.4

A

(C-2), 38.5 (C-7), 40.7 (C-5), 69.9 (C-6), 125.7, 128.3, 128.4 (arom. CH),

126.7 (C-3), 129.8 (C-4), 142.2 (arom. C_ipso), 171.3 ppm (C-1); IR (film,

ATR): n˜ =3395 (O-H-n); 3085, 3060, 3025 (arom. C-H-n); 2930, 2860

5192

www.chemeurj.org

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

3

H_a), 3.61 (ddd, ²J=9.9, J=6.5, J=6.4 Hz, 1H, 6-H_b), 4.69 (ddd, J=7.9,

7.25 ppm (m, 2H, 2’’-H); ¹³C NMR (101 MHz, CDCl₃): d=ꢀ5.3, ꢀ5.3 [Si-

³J=5.0, J=3.4 Hz, 1H, 1-H), 5.50 (dtt, J=10.9, J=6.8, J=1.5 Hz, 1H,

3-H), 5.57 (dtt, ³J=10.9, ³J=7.2, ⁴J=1.4 Hz, 1H, 4-H), 7.24–7.27, 7.31–

7.37 ppm (m, 5H, arom. CH); ¹³C NMR (126 MHz, CDCl₃): d=ꢀ5.3 [Si-

(CH₃)₂], 18.4 [C

U

G

3

4

(OCH₃), 62.7 (C-7), 70.1 (C-2), 73.0 (C-1’), 73.6 (C-1), 113.8 (C-3’’), 126.5

(C-5), 128.9 (C-4), 129.3 (C-2’’), 130.0 (C-1’’), 159.2 ppm (C-4’’); IR (film,

ATR): n˜ =3450 (O-H-n); 3010 (arom. C-H-n); 2955, 2930, 2900, 2855

(aliph. C-H-n); 2840 (OCH₃, C-H-n); 1655 (olef. C=C-n); 1615, 1585,

1515 (arom. C=C-n); 1470; 1465; 1360; 1300; 1250 (TBS); 1175; 1090

(TBS); 1035; 1005; 935; 830, 815, 755 cm^ꢀ1(TBS); MS (ESI-2): m/z (%):

419 (58) [M+K⁺], 403 (100) [M+Na⁺], 398 (42) [M+NH₄⁺]; 381 (47)

[M+H⁺]; elemental analysis calcd (%) for C₂₁H₃₆O₄Si (380.6): C 66.27, H

9.53, found: C 66.22, H 9.49.

A

G

N

6), 73.6 (C-1), 125.8, 127.3, 128.3 (arom. CH), 126.7 (C-3), 129.9 (C-4),

144.2 ppm (arom. C_ipso); IR (film, ATR): n˜ =3380 (O-H-n); 3070, 3040,

3005 (arom. C-H-n), 2935, 2905, 2865, 2835 (aliph. C-H-n); 1645 (olef. C=

C-n); 1595, 1575, 1480 (arom. C=C-n); 1460, 1450, 1440 (aliph. C-H-d);

1390; 1375; 1350; 1240; 1080; 1035; 910; 820, 790, 755 (TBS); 755 (Ph, C-

H-d_{out of plane}); 680 cm^ꢀ1(Ph, ring-d); MS (EI, 70 eV): m/z (%): 306 (0.06)

[M⁺], 288 (0.4) [MꢀH₂O⁺], 157 (61) [PhC₆H₈⁺], 143 (22) [C₁₁H₁₁⁺], 107

(30) [PhCHOH⁺], 105 (37) [PhCO⁺], 75 (100) [Me₂SiOH⁺], 73 (42)

[MeSi(O)CH₂⁺]; elemental analysis calcd (%) for C₁₈H₃₀O₂Si (306.5): C

70.53, H 9.87, found: C 70.30, H 9.83.

A

(ent-45a): According to GP D allylboronate 39 (196 mg, 0.37 mmol,

1.00 equiv) in CH₂Cl₂(184 mL) with benzaldehyde (45 mL, 47 mg,

0.44 mmol, 1.20 equiv) was used. Analogously, allylboronate 41 (193 mg,

0.36 mmol, 1.00 equiv) in CH₂Cl₂(181 mL) with benzaldehyde (44 mL,

46 mg, 0.44 mmol, 1.20 equiv) was subjected to the reaction conditions.

The reaction mixtures were stirred at 08C for 24 h and at RT for 24 h.

Chromatography (16 g silica gel, petroleum ether/EtOAc 95:5 ! 85:15)

furnished spectroscopically pure colorless oils (45a: 54 mg, 0.31 mmol,

ACHTREUNG

According to GP E allylboronates 35 or 37 (200 mg, 0.30 mmol), respec-

tively, in CH₂Cl₂(150 mL) with 3-phenylpropionaldehyde (48 mL, 49 mg,

0.36 mmol) were used. The reaction mixtures were stirred at 08C for 24 h

and at RT for 24 h. For the reduction THF (5 mL) and LiAlH₄(69 mg,

1.81 mmol), for the work up H₂O (83 mL), 15% aqueous NaOH solution

(83 mL) and H₂O (246 mL) was used. Chromatography (16 g silica gel, pe-

troleum ether/EtOAc 95:5) furnished spectroscopically pure colorless oils

(ent-44b: 93 mg, 0.28 mmol, 92%; HPLC: ee 92%), MPLC (petroleum

ether/EtOAc 95:5) yielded an analytically pure sample (44b: 53 mg,

0.16 mmol, 52%; HPLC: ee 99%). R_f=0.08 (petroleum ether/EtOAc

95:5), 0.39 (petroleum ether/EtOAc 85:15); [a]²_D⁰(44b)=+3 (c=1.06 in

CHCl₃, ee 99%), [a]²_D⁰(ent-44b)=ꢀ3 (c=1.30 in CHCl₃, ee 92%); HPLC

(Chiralcel OD, hexane/iPrOH 98:2): t_R(44b)=8.0 min, t_R(ent-44b)=

83%; HPLC: 99%, GC:

> 99%; ent-45a: 44 mg, 0.25 mmol, 69%;

HPLC: >99%). Analytical data are in agreement with those reported in

the literature.^[32]R_f=0.10 (petroleum ether/EtOAc 95:5); [a]²_D⁰(45a)=

ꢀ58 (c=1.80 in CHCl₃, ee > 99%), [a]²_D⁰(ent-45a)=+65 (c=0.76 in

CHCl₃, ee > 99%), ref.:^[32][a]_D²⁵(ent-45a)=+63 (c=0.82 in CHCl₃, ee

>

99%); HPLC (Chiralcel OD, hexane/iPrOH 99.4:0.6): t_R(45a)=

12.5 min, t_R(ent-45a)=9.4 min; ¹H NMR (500 MHz, CDCl₃): d=0.91 (t,

³J=7.5 Hz, 3H, 6-H), 2.01 (dqdd, ²J=14.6, ³J=7.5, ³J=7.3, ⁴J=1.6 Hz,

1H, 5-H_a), 2.03 (dqdd, ²J=14.6, ³J=7.5, ³J=7.3, ⁴J=1.6 Hz, 1H, 5-H_b),

2.12 (d, ³J=2.6 Hz, 1H, OH), 2.45 (dddd, ²J=14.3, ³J=6.9, ³J=5.4, ⁴J=

1.6 Hz, 1H, 2-H_a), 2.55 (dddd, ²J=14.3, ³J=6.9, ³J=7.8, ⁴J=1.6, 1H, 2-

H_b), 4.67 (ddd, ³J=7.8, ³J=5.4, ³J=2.6 Hz, 1H, 1-H), 5.34 (dtt, ³J=10.8,

4.7 min; ¹H NMR (500 MHz, CDCl₃): d=0.06 [s, 6H, Si

(CH₃)₂], 0.90 [s,

3

9H, C

(CH₃)₃], 1.27–1.38 (m, 2H, 7H), 2.15 (d, J=4.4 Hz, 1H, OH), 2.25

(m, 2H, 5-H), 2.28 (m, 1H, 2-H_a), 2.36 (m, 1H, 2-H_b), 2.68 (ddd, ²J=

13.7, ³J=9.2, ³J=7.3 Hz, 1H, 8-H_a), 2.81 (ddd, ²J=13.7, ³J=9.0, ³J=

6.4 Hz, 1H, 8-H_b), 3.59–3.69 (m, 3H, 1-H, 6-H), 5.46 (dtt, ³J=10.9, ³J=

6.8, ⁴J=1.4 Hz, 1H, 4-H), 5.51 (dtt, ³J=10.9, ³J=6.8, ⁴J=1.3 Hz, 1H, 3-

H), 7.16–7.21, 7.25–7.29 ppm (m, 5H, arom. CH); ¹³C NMR (126 MHz,

³J=6.9, J=1.6 Hz, 1H, 3-H), 5.54 (dtt, J=10.8, J=7.3, J=1.6 Hz, 1H,

4-H), 7.23–7.27, 7.31–7.36 ppm (m, 5H, arom. CH); ¹³C NMR (126 MHz,

CDCl₃): d=14.1 (C-6), 20.6 (C-5), 37.1 (C-2), 73.9 (C-1), 124.0 (C-3),

125.8, 127.4, 128.3 (arom. CH), 135.2 (C-4), 144.1 ppm (arom. C_ipso); IR

(film): n˜ =3530 (O-H-n); 3360 (br); 3070, 3040, 3010 (arom. C-H-n);

2990, 2940, 2910, 2850 (aliph. C-H-n); 1645 (olef. C=C-n); 1590, 1480

(arom. C=C-n); 1440; 1030; 735 (Ph, C-H-d_{out of plane}); 680 cm^ꢀ1(Ph, ring-

d); MS (CI, NH₃): m/z (%): 194 (26) [M+NH₄⁺], 176 (100) [M⁺];

HRMS (EI, 70 eV): m/z: calcd for C₁₂H₁₆O: 176.1201, found: 176.1202;

elemental analysis calcd (%) for C₁₂H₁₆O (176.3): C 81.77, H 9.15, found:

C 81.05, H 9.10.

4

3

4

CDCl₃): d=ꢀ5.4, ꢀ5.3 [Si

(CH₃)₂], 18.4 [C

G

A

(C-2), 32.1 (C-8), 35.5 (C-5), 38.6 (C-7), 62.7 (C-1), 70.4 (C-6), 127.0 (C-

3), 125.7, 128.3, 128.4 (arom. CH), 129.9 (C-4); 142.2 ppm (arom. C_ipso);

IR (film): n˜ =3570 (O-H-n); 3370 (br, O-H-n); 3070, 3040, 3005 (arom.

C-H-n), 2930, 2905, 2880, 2835 (aliph. C-H-n); 1640 (olef. C=C-n); 1595,

1575, 1485 (arom. C=C-n); 1460, 1450, 1440; 1375; 1350; 1240, 1080

(TBS); 910; 815, 790, 755 (TBS); 755 (Ph, C-H-d_{out of plane}); 675 cm^ꢀ1(Ph,

ring-d); MS (EI, 70 eV): m/z (%): 334 (0.8) [M⁺], 185 (90)

[MꢀC₁₀H₁₃O⁺], 143 (62) [C₁₁H₁₁⁺], 117 (60) [C₉H₉⁺], 105 (93) [PhCO⁺],

91 (100) [C₇H₇⁺], 75 (93) [HOSiMe₂⁺], 73 (40) [MeSi(O)CH₂⁺]; elemen-

tal analysis calcd (%) for C₂₀H₃₄O₂Si (334.6): C 71.80, H 10.24, found: C

71.60, H 10.28.

(3R,5Z)-1-Phenyloct-5-en-3-ol (45b) and (3S,5Z)-1-phenyloct-5-en-3-ol

(ent-45b): According to GP D allylboronates 39 or 41 (200 mg,

0.38 mmol), respectively, in CH₂Cl₂(189 mL) with 3-Phenylpropionalde-

hyde (60 mL, 61 mg, 0.45 mmol) were used. The reaction mixtures were

stirred at 08C for 24 h and at RT for 4 d. Chromatography (14 g silica

gel, petroleum ether/EtOAc 95:5 ! 90:10) and MPLC (petroleum ether/

EtOAc 95:5) furnished spectroscopically pure colorless oils (45b: 70 mg,

0.34 mmol, 91%; HPLC: ee 84%; ent-45b: 70 mg, 0.34 mmol, 91%;

HPLC: ee 95%); the analytical data are in agreement with those previ-

ously reported.^[43]R_f=0.08 (petroleum ether/EtOAc 95:5), 0.30 (petro-

leum ether/EtOAc 85:15); [a]²_D⁰(45b)=+9 (c=0.88 in CHCl₃, ee 84%),

[a]²_D⁰(ent-45b)=ꢀ12 (c=0.96 in CHCl₃, ee 95%), ref.:^[43][a]²_D⁰(ent-

(2S,4Z)-7-(tert-Butyldimethylsilyloxy)-1-(4’’-methoxybenzyloxy)hept-4-

en-2-ol (44c) and (2R,4Z)-7-(tert-butyldimethylsilyloxy)-1-(4’’-methoxy-

benzyloxy)hept-4-en-2-ol (ent-44c): According to GP E allylboronates 35

or 37 (200 mg, 0.30 mmol), respectively, in CH₂Cl₂(151 mL) with 42c

(65 mg, 0.36 mmol) were used. The reaction mixtures were stirred at 08C

for 24 h and at RT for 5 d. For the reduction THF (3 mL) and LiAlH₄

(46 mg, 1.21 mmol), for the work up H₂O (55 mL), 15% aqueous NaOH

solution (55 mL) and H₂O (164 mL) was used respectively. Chromatogra-

phy (16 g silica gel, petroleum ether/EtOAc 90:10) furnished spectroscop-

45b)=ꢀ27 (c=1.00 in CHCl₃, ee

> 99%); HPLC (Chiralcel OD,

hexane/iPrOH 95:5): t_R(45b)=16.0 min, t_R(ent-45b)=24.7 min;

¹H NMR (300 MHz, CDCl₃): d=0.96 (t, ³J=7.5 Hz, 3H, 8-H), 1.70 (brs,

1H, OH), 1.79 (m, 2H, 2-H), 2.07 (qddt, ³J=7.5, ³J=7.2, ⁴J=1.6, ⁵J=

0.7 Hz, 2H, 7-H), 2.24 (m, 2H, 4-H), 2.68 (ddd, ²J=13.8, ³J=9.2, ³J=

7.3 Hz, 1H, 1-H_a), 2.81 (ddd, ²J=13.8, ³J=8.8, ³J=6.9 Hz, 1H, 1-H_b),

3.64 (dddd, ³J=7.6, ³J=6.8, ³J=5.6, ³J=4.8 Hz, 1H, 3-H), 5.36 (dtt, ³J=

10.9, ³J=7.3, ⁴J=1.6 Hz, 1H, 5-H), 5.57 (dtt, ³J=10.9, ³J=7.2, ⁴J=

1.4 Hz, 1H, 6-H), 7.15–7.31 ppm (m, 5H, arom. CH); ¹³C NMR

(101 MHz, CDCl₃): d=14.2 (C-8), 20.7 (C-7), 32.1 (C-1), 35.3 (C-4), 38.4

(C-2), 70.6 (C-3), 124.2 (C-5), 125.7, 128.3, 128.4 (arom. CH), 135.3 (C-6),

142.1 ppm (arom. C_ipso); IR (film): n˜ =3565 (O-H-n); 3350 (br, O-H-n);

3085, 3065, 3025, 3010 (arom. C-H-n), 2960, 2930, 2875 (aliph. C-H-n);

1655 (olef. C=C-n); 1605, 1585, 1495 (arom. C=C-n); 1455; 1070; 1050;

ically pure colorless oils (44c: 105 mg, 0.28 mmol, 91%; H NMR:^[15a]ee

1

> 95%; ent-44c: 106 mg, 0.28 mmol, 92%; ¹H NMR:^[15a]ee > 95%),

MPLC (petroleum ether/EtOAc 82:18) yielded an analytically pure

sample. R_f=0.16 (petroleum ether/EtOAc 85:15), 0.42 (petroleum ether/

EtOAc 75:25); [a]²_D⁰(44c)=ꢀ4 (c=2.08 in CHCl₃, ee > 95%), [a]²_D⁰(ent-

44c)=+5 (c=2.12 in CHCl₃, ee > 95%); ¹H NMR (400 MHz, CDCl₃):

d=0.05 [s, 6H, Si

N

6-H), 2.56 (brs, 1H, OH), 3.35 (dd, ²J=9.5, ³J=7.2 Hz, 1H, 1-H_a), 3.47

(dd, ²J=9.5, ³J=3.7 Hz, 1H, 1-H_b), 3.62 (t, ³J=6.7 Hz, 2H, 7-H), 3.80 (s,

3H, OCH₃), 3.82 (dddd, ³J=9.9, ³J=7.2, ³J=6.2, ³J=3.7 Hz, 1H, 2-H),

4.48 (s, 2H, 1’-H), 5.46–5.56 (m, 2H, 4-H, 5-H), 6.88 (m, 2H, 3’’-H),

Chem. Eur. J. 2008, 14, 5178 – 5197

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

5193

J. Pietruszka et al.

1030; 745 (Ph, C-H-d_{out of plane}); 720; 695 cm^ꢀ1(Ph, ring-d); MS (CI, CH₄):

m/z (%): 205 (6) [M+H⁺], 187 (100) [MꢀOH⁺].

2H, 1’’-H), 5.71 ppm (m, 2H, 3-H, 4-H); ¹³C NMR (126 MHz, CDCl₃):

d=14.1 (C-2’’), 25.2, 26.6 (2’-CH₃), 31.5 (C-5), 33.0 (C-2), 61.0 (C-1’’),

65.9 (C-5’), 71.1 (C-6), 78.1 (C-4’), 109.1 (C-2’), 124.3 (C-3), 128.9 (C-4),

172.1 ppm (C-1); IR (solution in CDCl₃): n˜ =3565 (O-H-n); 3450 (br);

3010 (olef. C-H-n); 2970, 2920, 2870 (aliph. C-H-n); 1720 (C=O-n); 1650

(olef. C=C-n); 1440; 1370, 1360 (CH₃, C-H-d_s); 1315; 1240; 1200; 1165;

1145; 1050; 1015; 830 cm^ꢀ1; MS (AUTO-CI): m/z (%): 259 (100) [M+H⁺],

243 (54) [MꢀCH₃⁺]; HRMS (AUTO-CI): m/z: calcd for C₁₃H₂₃O₅:

259.1545, found: 259.1547; elemental analysis calcd (%) for C₁₃H₂₂O₅

(258.3): C 60.45, H 8.58, found: C 60.33, H 8.64; epi-31d: ¹H NMR

(500 MHz, CDCl₃): d=1.26 (t, ³J=7.1 Hz, 3H, 2’-H), 1.36, 1.44 (2s, 6H,

2’-CH₃), 2.24–2.32 (m, 2H, 5-H), 2.54 (d, ³J=4.9 Hz, 1H, OH), 3.06–3.17

(m, 2H, 2-H), 3.59 (m, 1H, 6-H), 3.78 (dd, ³J=7.9, ³J=6.5 Hz, 1H, 5’-

H_a), 4.00–4.07 (m, 2H, 4’-H, 5’-H_b), 4.14 (q, ³J=7.1 Hz, 2H, 1’’-H), 5.65–

5.76 ppm (m, 2H, 3-H, 4-H); ¹³C NMR (75 MHz, CDCl₃): d=14.1 (C-2’’),

25.1, 26.4 (2’-CH₃), 31.8 (C-5), 32.9 (C-2), 60.7 (C-1’’), 65.8 (C-5’), 71.2

(C-6), 78.1 (C-4’), 109.3 (C-2’), 123.9 (C-3), 128.4 (C-4), 171.8 ppm (C-1);

IR (solution in CDCl₃): n˜ =3565 (O-H-n); 3450 (br); 3010 (olef. C-H-n);

2970, 2920, 2890, 2870 (aliph. C-H-n); 1720 (C=O-n); 1650 (olef. C=C-n);

1590; 1440; 1370, 1360 (CH₃, C-H-d_s); 1315; 1240; 1200; 1170; 1140;

1050; 1015; 835 cm^ꢀ1; MS (CI, CH₄): m/z (%): 259 (100) [M+H⁺], 243

(65) [MꢀCH₃⁺]; HRMS (AUTO-CI): m/z: calcd for C₁₃H₂₃O₅: 259.1545,

found: 259.1545; elemental analysis calcd (%) for C₁₃H₂₂O₅(258.3): C

60.45, H 8.58, found: C 60.10, H 8.59.

(2S,4Z)-1-(4’-Methoxybenzyloxy)hept-4-en-2-ol (45c) and (2R,4Z)-1-(4’-

methoxybenzyloxy)hept-4-en-2-ol (ent-45c) According to GP D allylbor-

onates 39 or 41 (200 mg, 0.38 mmol), respectively, in CH₂Cl₂(188 mL)

with 42c (135 mg, 0.75 mmol) were used. The reaction mixtures were

stirred at 08C for 24 h and at RT for 24 h. Chromatography (16 g silica

gel, petroleum ether/EtOAc 90:10) furnished spectroscopically pure col-

orless oils (ent-45c: 84 mg, 0.34 mmol, 89%; HPLC: ee 89%), MPLC

(petroleum ether/EtOAc 85:15) yielded the corresponding analytically

pure samples (45c: 83 mg, 0.33 mmol, 88%; HPLC: ee 94%). R_f=0.27

(petroleum ether/EtOAc 80:20), 0.45 (petroleum ether/EtOAc 70:30;

[a]²_D⁰(45c)=+2 (c=1.66 in CHCl₃, ee 94%), [a]²_D⁰(ent-45c)=ꢀ3 (c=

1.64 in CHCl₃, ee 89%); HPLC (Chiralcel OD-H, hexane/iPrOH

99.6:0.4): t_R(45c)=112.6 min, t_R(ent-45c)=100.8 min; ¹H NMR

(400 MHz, CDCl₃): d=0.96 (t, ³J=7.5 Hz, 3H, 7-H), 2.05 (qddt, ³J=7.5,

³J=7.2, ³J=1.5, ⁴J=0.7 Hz, 2H, 6-H), 2.23 (ddddt, ²J=14.4, ³J=7.4, ³J=

3

2

3

6.5, J=1.5, J=0.7 Hz, 1H, 3-H_a), 2.26 (ddddt, J=14.4, J=7.4, J=6.5,

3

2

3

³J=1.5, J=0.7 Hz, 1H, 3-H_b), 2.41 (brs, 1H, OH), 3.34 (dd, J=9.5, J=

7.4 Hz, 1H, 1-H_a), 3.49 (dd, ²J=9.5, ³J=3.3 Hz, 1H, 1-H_b), 3.80 (s, 3H,

OCH₃), 3.81 (dtd, ³J=7.4, ³J=6.5, ³J=3.3 Hz, 1H, 2-H), 4.48 (s, 2H, 1’-

H), 5.49 (dtt, ³J=10.8, ³J=7.4, ⁴J=1.5 Hz, 1H, 4-H), 5.53 (dtt, ³J=10.8,

³J=7.2, ⁴J=1.5 Hz, 1H, 5-H), 6.88 (m, 2H, 3’’-H), 7.26 ppm (m, 2H, 2’’-

H); ¹³C NMR (101 MHz, CDCl₃): d=14.1 (C-7), 20.6 (C-6), 31.1 (C-3),

55.2 (OCH₃), 70.2 (C-2), 73.0 (C-1’), 73.6 (C-1), 113.8 (C-3’’), 123.9 (C-4),

129.3 (C-2’’), 130.0 (C-1’’), 134.4 (C-5), 159.2 ppm (C-4’’); IR (film,

ATR): n˜ =3440 (O-H-n); 3005 (arom. C-H-n); 2960, 2935, 2905, 2870

(aliph. C-H-n); 2835 (OCH₃, C-H-n); 1655 (olef. C=C-n); 1610, 1585,

1515 (arom. C=C-n); 1465; 1300; 1245; 1175; 1100; 1035; 820 (1,4-disub-

stituted benzene ring); 720 cm^ꢀ1; MS (EI, 70 eV): m/z (%): 250 (6) [M⁺],

121 (100) [C₈H₉O⁺]; HRMS (EI, 70 eV): m/z: calcd for C₁₅H₂₂O₃:

250.1569, found: 250.1569; elemental analysis calcd (%) for C₁₅H₂₂O₃

(250.3): C 71.97, H 8.86, found: C 71.63, H 8.85.

(6S,4’R,3Z)-6-(2’,2’-Dimethyl-1’,3’-dioxolan-4’-yl)-6-hydroxyhex-3-enoic

acid dimethylamide (43d): According to GP D allylboronate 18 (152 mg,

0.26 mmol) was treated with (R)-aldehyde 42d (47 mg, 0.36 mmol) in

CH₂Cl₂(ꢁ150 mL). The reaction mixture was stirred at RT for 43 h.

Chromatography (EtOAc) gave a spectroscopically pure colorless oil

[42 mg, 0.16 mmol, 63%; ¹H NMR: dr (43d/epi-43d) > 99:1]; R_f=0.19

(EtOAc); [a]²_D⁰=ꢀ24 [c=0.32, CHCl₃, dr (43d/epi-43d)

> 99:1],

¹H NMR (500 MHz, CDCl₃): d=1.36, 1.42 (2s, 6H, 2’-CH₃), 2.31 (dddd,

3

2

3

²J=14.0, J=8.9, J=8.5, J=1.3 Hz, 1H, 5-H_a), 2.45 (dddd, J=14.0, J=

3

6.8, J=3.2, J=1.3 Hz, 1H, 5-H_b), 2.95, 3.07 [2s, 6H, N(CH₃)₂], 3.15 (dd,

A

Allyl additions to 2,3-O-isopropylidene-d-glyceraldehyde (42d)

³J=7.5, ⁴J=1.3 Hz, 2H, 2-H), 3.60 (dddd, ³J=8.5, ³J=7.2, ³J=4.2, ³J=

3.2 Hz, 1H, 6-H), 3.87 (d, ³J=4.2 Hz, 1H, OH), 3.93–3.99, 4.1 (2m, 3H,

4’-H, 5’-H), 5.68 (dtt, ³J=10.8, ³J=7.6, ³J=1.3 Hz, 1H, 3-H), 5.76 ppm

(dddt, ³J=10.8, ³J=8.9, ³J=6.8, ³J=1.3 Hz, 1H, 4-H); ¹³C NMR

(126 MHz, CDCl₃): d=25.3, 26.7 (2’-CH₃), 31.6 (C-2), 31.9 (C-5), 35.8,

(6S,4’R,3Z)- and (6R,4’R,3Z)-ethyl 6-(2’,2’-dimethyl-1’,3’-dioxolan-4’-yl)-

6-hydroxyhex-3-enoate (31d and epi-31d): According to GP D allylboro-

nate 15 (232 mg, 0.39 mmol) was treated with a solution of (R)-aldehyde

42d (72 mg, 0.55 mmol) in CH₂Cl₂(ꢁ200 mL). The reaction mixture was

stirred at RT for 30 h. Chromatography (petroleum ether/EtOAc 85:15

! 80:20) gave a spectroscopically pure colorless oil [88 mg, 0.34 mmol,

86%; ¹H NMR: dr (31d/epi-31d) 97:3], one additional chromatography

(10 g silica gel, petroleum ether/EtOAc 85:15) furnished an analytically

pure sample. According to GP D allylboronate 16 (233 mg, 0.40 mmol)

was treated with a solution of (R)-aldehyde 42d (72 mg, 0.55 mmol) in

CH₂Cl₂(ꢁ200 mL). The reaction mixture was stirred at RT for 22 h.

Chromatography (petroleum ether/EtOAc 85:15) gave a spectroscopical-

ly pure colorless oil [91 mg, 0.35 mmol, 89%; ¹H NMR: dr (31d/epi-31d)

30:70], further chromatography furnished an analytically pure sample.

According to GP D allylboronate ent-15 (300 mg, 0.51 mmol) was treated

with a solution of (R)-aldehyde 42d (187 mg, 1.44 mmol) in CH₂Cl₂

(ꢁ450 mL). The reaction mixture was stirred at 08C for 24 h and at RT

37.5 [N(CH₃)₂], 67.0 (C-5’), 71.7 (C-6), 78.4 (C-4’), 109.1 (C-2’), 124.9 (C-

U

3), 129.5 (C-4), 171.7 ppm (C-1); IR (solution in CDCl₃): n˜ =3580 (O-H-

n); 3340 (br); 3005 (olef. C-H-n); 2970, 2920, 2870 (aliph. C-H-n); 1625

(C=O-n, olef. C=C-n); 1485; 1475; 1440; 1430; 1390; 1370, 1360 (CH₃, C-

H-d_s); 1245; 1200; 1140; 1050; 830 cm^ꢀ1; MS (CI, CH₄): m/z (%): 258

(100) [M+H⁺], 242 (19) [MꢀCH₃⁺]; HRMS (AUTO-CI): m/z: calcd for

C₁₃H₂₄NO₄: 258.1705, found: 258.1708.

(6R,4’R,3Z)-6-(2’,2’-Dimethyl-1’,3’-dioxolan-4’-yl)-6-hydroxyhex-3-enoic

acid dimethylamide (epi-43d): According to GP D allylboronate 19

(142 mg, 0.24 mmol) was treated with (R)-aldehyde 42d (44 mg,

0.34 mmol) in CH₂Cl₂(ꢁ150 mL). The reaction mixture was stirred at RT

for 18 h. Chromatography (EtOAc) yielded a spectroscopically pure col-

orless oil [47 mg, 0.18 mmol, 75%; ¹H NMR: dr (43d/epi-43d) 27:73];

R_f=0.15 (EtOAc); [a]²_D⁰=+28 [c=0.18, CHCl₃, dr (43d/epi-43d) 13:87

(enriched fraction)]; ¹H NMR (500 MHz, CDCl₃), d=1.37, 1.45 (2s, 6H,

2’-CH₃), 2.22–2.27 (m, 1H, 5-H_a), 2.30–2.36 (m, 1H, 5-H_b), 2.95, 3.04 [2s,

for 3 d and 19 h. Chromatography (petroleum ether/EtOAc 85:15

!

75:25) gave a spectroscopically pure colorless oil [121 mg, 0.47 mmol,

92%; ¹H NMR: dr (31d/epi-31d) 35:65]. According to GP D allylboro-

nate ent-16 (300 mg, 0.51 mmol) was treated with a solution of (R)-alde-

hyde 42d (187 mg, 1.44 mmol) in CH₂Cl₂(ꢁ450 mL). The reaction mix-

ture was stirred at 08C for 24 h and at RT for 3 d and 19 h. Chromatogra-

phy (petroleum ether/EtOAc 85:15 ! 75:25) furnished a spectroscopical-

ly pure colorless oil [120 mg, 0.47 mmol, 91%; ¹H NMR: dr (31d/epi-

6H, N

(CH₃)₂], 3.02 (d, ³J=5.5 Hz, 1H, OH), 3.14–3.16 (m, 2H, 2-H),

G

3.60 ꢀ3.64 (m, 1H, 6-H), 3.82 (dd, ²J=8.1, ³J=6.7 Hz, 1H, 5’-H_a), 4.02

(dd, ²J=8.1, ³J=6.7 Hz, 1H, 5’-H_b), 4.10 (ddd, ³J=6.7, ³J=6.7, ³J=

5.0 Hz, 1H, 4’-H), 5.66–5.77 ppm (m, 2H, 3-H, 4-H); ¹³C NMR

(126 MHz, CDCl₃), d=25.2, 26.5 (2’-CH₃), 31.8 (C-5), 32.1 (C-2), 35.6,

31d)

> 99:1]. R_f(31d)=R_f(epi-31d)=0.07 (petroleum ether/EtOAc

80:20); [a]²_D⁰=ꢀ5 [c=0.96 in CHCl₃, dr (31d/epi-31d) 97:3], [a]²_D⁰=ꢀ5

37.4 [N(CH₃)₂], 65.9 (C-5’), 71.1 (C-6), 78.2 (C-4’), 109.3 (C-2’), 125.0 (C-

A

>

99:1], [a]²_D⁰=+14 [c=1.22 in

3), 128.5 (C-4), 171.3 ppm (C-1); IR (solution in CDCl₃): n˜ =3570 (O-H-

n); 3340 (br); 3010 (olef. C-H-n); 2970, 2920, 2870 (aliph. C-H-n); 1625

(C=O-n, olef. C=C-n); 1480; 1440; 1390; 1370, 1360 (CH₃, C-H-d_s); 1245;

1200; 1140; 1050; 835 cm^ꢀ1; MS (EI, 70 eV): m/z (%): 242 (8) [MꢀCH₃⁺],

199 (12) [MꢀC₃H₆O⁺], 156 (59) [MꢀC₅H₉O₂⁺], 127 (37) [C₇H₁₅NO⁺],

101 (10) [C₅H₉O₂⁺], 72 (100) [Me₂NCO⁺]; HRMS (AUTO-CI): m/z:

calcd for C₁₃H₂₄NO₄: 258.1705, found: 258.1707.

[c=1.44 in CHCl₃, dr (31d/epi-31d)

CHCl₃, dr (31d/epi-31d) 35:65]; epi-31d: ¹H NMR (500 MHz, CDCl₃):

d=1.26 (t, ³J=7.1 Hz, 3H, 2’’-H), 1.36, 1.42 (2s, 6H, 2’-CH₃), 2.22–2.29

(m, 1H, 5-H_a), 2.34–2.40 (m, 1H, 5-H_b), 2.75 (brs, 1H, OH), 3.05–3.17

(m, 2H, 2-H), 3.70 (ddd, ³J=8.2, ³J=5.8, ³J=4.1 Hz, 1H, 6-H), 3.95 (dd,

²J=7.5, ³J=5.9 Hz, 1H, 5’-H_a), 3.99 (ddd, ³J=6.0, ³J=5.9, ³J=5.8 Hz,

1H, 4’-H), 4.05 (dd, ²J=7.5, ³J=6.0 Hz, 1H, 5’-H_b), 4.15 (q, ³J=7.1 Hz,

5194

www.chemeurj.org

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2008, 14, 5178 – 5197

Diastereo- and Enantiomerically Pure Allylboronates

FULL PAPER

3

(1S,4’R,3Z)-6-(tert-Butyldimethylsilyloxy)-1-(2’,2’-dimethyl-1’,3’-dioxolan-

4’-yl)-3-hexen-1-ol (44d): According to GP E allylboronate 35 (200 mg,

0.30 mmol) in CH₂Cl₂(ꢁ200 mL) was treated with (R)-aldehyde 42d

(59 mg, 0.45 mmol) in CH₂Cl₂(ꢁ50 mL). The reaction mixture was

stirred at 08C for 24 h and at RT for 48 h. For the reduction THF

(10 mL) and LiAlH₄(106 mg, 2.79 mmol), for the workup H₂O (128 mL),

15% aqueous NaOH solution (128 mL) and H₂O (380 mL) were used.

Chromatography (petroleum ether/EtOAc 90:10) furnished a spectro-

scopically pure colorless oil [81 mg, 0.25 mmol, 81%; ¹³C NMR: dr (44d/

epi-44d) 89:11]. R_f(44d)=0.15 (petroleum ether/EtOAc 85:15), 0.44 (pe-

0.8 Hz, 1H, 2-H_b), 3.75 (dddd, J=7.6, J=5.5, J=4.9, J=3.2 Hz, 1H, 1-

2

3

2

3

H), 3.94 (dd, J=7.4, J=6.2 Hz, 1H, 5’-H_a), 4.00 (dd, J=7.4, J=6.2 Hz,

1H, 5’-H_b), 4.03 (ddd, ³J=6.2, ³J=6.2, ³J=4.9 Hz, 1H, 4’-H), 5.38 (dtt,

³J=10.8, ³J=7.5, ⁴J=1.6 Hz, 1H, 3-H), 5.58 ppm (dtt, ³J=10.8, ³J=7.3,

⁴J_4,2=1.5 Hz, 1H, 4-H); ¹³C NMR (101 MHz, CDCl₃): d=14.2 (C-6), 20.6

(C-5), 25.2 (2’-C_aH₃), 26.5 (2’-C_bH₃), 30.9 (C-2), 65.1 (C-5’), 71.0 (C-1),

78.1 (C-4’), 109.0 (C-2’), 123.5 (C-3), 135.4 ppm (C-4); IR (film): n˜ =3465

(O-H-n); 3000 (olef. C-H-n); 2985, 2965, 2935, 2875 (aliph. C-H-n); 1655

(olef. C=C-n); 1455; 1380, 1370 (CH₃, C-H-d_s); 1250; 1210; 1155; 1060;

850 cm^ꢀ1; MS (EI, 70 eV): m/z (%): 200 (5) [M⁺], 185 (29) [MꢀCH₃⁺],

182 (4) [MꢀH₂O⁺], 142 (8) [MꢀC₃H₆O⁺], 131 (23) [C₆H₁₁O₃⁺], 101

(100) [C₅H₉O₂⁺], 59 (73) [C₃H₇O⁺], 43 (90) [C₂H₃O⁺]; HRMS (EI,

70 eV): m/z: calcd for C₁₁H₂₀O₃: 200.1413, found: 200.1413.

troleum ether/EtOAc 70:30); [a]²_D⁰=+3 [c=1.26, CHCl₃, dr (44d/epi-

1

44d) 89:11]; H NMR (400 MHz, CDCl₃): d=0.06 [s, 6H, Si

ACHTREUNG

[s, 9 H, C

A

ACHTREUNG

3

H), 2.56 (d, J=3.7 Hz, 1H, OH), 3.61–3.69 (m, 3H, 1-H, 6-H), 3.94 (dd,

²J=6.6, ³J=5.4 Hz, 1H, 5’-H_a), 3.98 (ddd, ³J=5.8, ³J=5.6, ³J=5.4 Hz,

1H, 4’-H), 4.03 (dd, ²J=6.6, ³J=5.6 Hz, 1H, 5’-H_b), 5.51–5.62 ppm (m,

(1R,4’R,3Z)-1-(2’,2’-Dimethyl-1’,3’-dioxolan-4’-yl)-3-hexen-1-ol (epi-45d):

According to GP E allylboronate 41 (200 mg, 0.38 mmol) in CH₂Cl₂

(ꢁ200 mL) was treated with a solution of (R)-aldehyde 42d (73 mg,

0.56 mmol) in CH₂Cl₂(ꢁ50 mL). The reaction mixture was stirred at 08C

for 24 h and at RT for 48 h. For the reduction THF (4 mL) and LiAlH₄

(57 mg, 1.50 mmol), for the workup H₂O (69 mL), 15% aqueous NaOH

solution (69 mL) and H₂O (205 mL) were used. Chromatography (petro-

leum ether/EtOAc 90:10) furnished a slightly impure colorless oil [54 mg,

0.27 mmol, 72%; ¹H NMR: dr (45d/epi-45d) 30:70]; R_f(epi-45d)=0.17

(petroleum ether/EtOAc 85:15), 0.59 (petroleum ether/EtOAc 70:30);

[a]²_D⁰=+9 [c=1.04, CHCl₃, dr (45d/epi-45d) 30:70]; ¹H NMR (400 MHz,

CDCl₃): d=0.97 (t, ³J=7.5 Hz, 3H, 6-H), 1.37 (s, 3H, 2’-CH_a3), 1.44 (s,

2H, 3-H, 4-H); ¹³C NMR (101 MHz, CDCl₃): d=ꢀ5.4, ꢀ5.4 [Si

A

18.4 [C

(CH₃)₃], 25.3, 26.6 [C

G

N

5), 62.7 (C-6), 65.9 (C-5’), 71.3 (C-1), 78.1 (C-4’), 109.0 (C-2’), 126.4 (C-

4), 130.1 ppm (C-3); IR (film, ATR): n˜ =3470 (br, O-H-n); 3010 (olef. C-

H-n); 2985, 2955, 2930, 2885, 2860 (aliph. C-H-n); 1655 (olef. C=C-n);

1470; 1465; 1380, 1370 (CH₃, C-H-d_s); 1255 (TBS); 1215; 1155; 1095

(TBS); 1065; 930; 830, 805, 775 cm^ꢀ1(TBS); MS (EI, 70 eV): m/z (%):

330 (0.01) [M⁺], 315 (7) [MꢀCH₃⁺], 273 (1) [MꢀCMe₃⁺], 215 (22)

[MꢀTBS⁺]; HRMS (CI, CH₄): m/z: calcd for C₁₇H₃₅O₄Si: 331.2299,

found: 331.2305.

3

3H, 2’-CH_b3), 2.06 (m, 2H, 5-H), 2.27 (d, J=5.4 Hz, 1H, OH), 2.16–2.31

(1R,4’R,3Z)-6-(tert-Butyldimethylsilyloxy)-1-(2’,2’-dimethyl-1’,3’-dioxo-

lan-4’-yl)hex-3-en-1-ol (epi-44d): According to GP E allylboronate 37

(200 mg, 0.30 mmol) in CH₂Cl₂(ꢁ200 mL) was treated with (R)-aldehyde

42d (59 mg, 0.45 mmol) in CH₂Cl₂(ꢁ50 mL). The reaction mixture was

stirred at 08C for 24 h and at RT for 48 h. For the reduction THF

(10 mL) and LiAlH₄(46 mg, 1.21 mmol), for the workup H₂O (56 mL),

15% aqueous NaOH solution (56 mL) and H₂O (164 mL) were used.

Chromatography (18 g silica gel, petroleum ether/EtOAc 90:10) gave a

spectroscopically pure colorless oil [90 mg, 0.27 mmol, 90%; ¹³C NMR:

dr (44d/epi-44d) 29:71]. R_f(epi-44d)=0.15 (petroleum ether/EtOAc

85:15), 0.44 (petroleum ether/EtOAc 70:30); [a]²_D⁰=+9 (c=1.80, CHCl₃,

dr (44d/epi-44d) 29:71]; ¹H NMR (400 MHz, CDCl₃): d=0.06 [s, 6H, Si-

(m, 2H, 2-H), 3.55 (dddd, ³J=7.1, ³J=5.6, ³J=5.5, ³J=5.4 Hz, 1H, 1-H),

3.76 (dd, ²J=7.4, ³J=6.2 Hz, 1H, 5’-H_a), 3.97–4.07 (m, 2H, 5’-H_b, 4’-H),

5.40 (dtt, ³J=10.8, ³J=7.3, ⁴J=1.5 Hz, 1H, 3-H), 5.54 ppm (dtt, ³J=10.8,

³J=7.2, ⁴J=1.5 Hz, 1H, 4-H); ¹³C NMR (101 MHz, CDCl₃): d=14.1 (C-

6), 20.6 (C-5), 25.3 (2’-C_aH₃), 26.6 (2’-C_bH₃), 31.6 (C-2), 66.1 (C-5’), 71.8

(C-1), 78.3 (C-4’), 109.3 (C-2’), 123.6 (C-3), 134.7 ppm (C-4); IR (film):

n˜ =3465 (O-H-n); 3000 (olef. C-H-n); 2985, 2965, 2935, 2875 (aliph. C-H-

n); 1655 (olef. C=C-n); 1455; 1380, 1370 (CH₃, C-H-d_s); 1250; 1210; 1155;

1060; 855; 700 cm^ꢀ1; MS (EI, 70 eV): m/z (%): 200 (5) [M⁺], 185 (29)

[MꢀCH₃⁺], 182 (3) [MꢀH₂O⁺], 142 (8) [MꢀC₃H₆O⁺], 131 (61)

[C₆H₁₁O₃⁺], 101 (93) [C₅H₉O₂⁺], 59 (100) [C₃H₇O⁺], 43 (93) [C₂H₃O⁺];

HRMS (EI, 70 eV): m/z: calcd for C₁₁H₂₀O₃: 200.1413, found: 200.1413.

A

N

G

(6R,4’R,3Z)-6-Benzoyloxy-6-(2’,2’-dimethyl-1’,3’-dioxolan-4’-yl)-hex-3-

enoic acid dimethylamide (48) and (6S,4’R,3Z)-6-benzoyloxy-6-(2’,2’-di-

methyl-1’,3’-dioxolan-4’-yl)hex-3-enoic acid dimethylamide (epi-48): The

mixture of diastereomers 43d/epi-43d ꢁ24:76 (50 mg, 0.19 mmol) was

dissolved in CH₂Cl₂(583 mL) and pyridine (583 mL) was added. Benzoyl

chloride (25 mL, 0.214 mmol) was added three times for completion of

the reaction, whereas a colorless solid precipitated. Chromatography (6 g

(m, 4H, 2-H, 5-H), 2.38 (d, ³J=5.3 Hz, 1H, OH), 3.56 (dddd, ³J=7.4,

³J=5.3, ³J=5.3, ³J=5.3 Hz, 1H, 1-H), 3.63 (m, 2H, 6-H), 3.76 (dd, ²J=

7.7, ³J=6.4 Hz, 1H, 5’-H_a), 4.00 (dd, ²J=7.7, ³J=6.5 Hz, 1H, 5’-H_b), 4.05

(ddd, ³J=6.5, ³J=6.4, J=5.3 Hz, 1H, 4’-H), 5.50–5.62 ppm (m, 2H, 3-H,

4-H); ¹³C NMR (101 MHz, CDCl₃): d=ꢀ5.3, ꢀ5.3 [Si

U

A

N

(C-6), 66.6 (C-5’), 71.7 (C-1), 78.3 (C-4’), 109.3 (C-2’), 126.3 (C-4),

129.2 ppm (C-3); IR (film, ATR): n˜ =3475 (O-H-n); 3000 (C-H-n); 2985,

2955, 2930, 2885, 2860 (aliph. C-H-n); 1655 (olef. C=C-n); 1470, 1465;

1380, 1370 (CH₃, C-H-d_s); 1255 (TBS); 1215; 1155; 1095 (TBS); 1065;

930; 830, 805, 775 cm^ꢀ1(TBS); MS (EI, 70 eV): m/z (%): 330 (0.07) [M⁺],

315 (3) [MꢀMe⁺], 273 (11) [MꢀCMe₃⁺], 215 (42) [MꢀTBS⁺]; MS (CI,

CH₄): m/z (%): 331 (90) [M+H⁺], 315 (49) [MꢀMe⁺], 273 (100)

[MꢀCMe₃⁺], 215 (78) [MꢀTBS⁺]; HRMS (CI, CH₄): m/z: calcd for

C₁₇H₃₅O₄Si: 331.2299, found: 331.2303.

silica gel, EtOAc) yielded

a spectroscopically pure colorless oil

1

(0.17 mmol, 63 mg, 90%; H NMR: dr (48/epi-48) 28:72). The two diaste-

reomers were almost completely separated by means of MPLC: Analyti-

cal data for 48 [25 mg, 0.07 mmol, 36%; ¹H NMR: dr (48/epi-48) 6:94];

R_f=0.27 (EtOAc); [a]²_D⁰=+11 [c=1.15, CHCl₃, dr (48/epi-48) 6:94];

¹H NMR (500 MHz, CDCl₃): d=1.36, 1.48 (2s, 6H, 2’-CH₃), 2.58 (m, 2H,

5-H), 2.92, 2.98 [2s, 6H, N

(CH₃)₂], 3.13 (ddd, ²J=16.6, ³J=6.7, ³J=

A

1.9 Hz, 1H, 2-H_a), 3.20 (ddd, ²J=16.6, ³J=7.1, ³J=1.9 Hz, 1H, 2-H_b),

3.81 (dd, ²J=8.5, ³J=6.3 Hz, 1H, 5’-H_a), 4.05 (dd, ²J=8.5, ³J=6.8 Hz,

1H, 5’-H_b), 4.34 (ddd, ³J=6.8, ³J=6.3, ³J=3.9 Hz, 1H, 4’-H), 5.17 (td,

³J=6.8, ³J=3.9, 1H, 6-H), 5.63 (dtt, ³J=10.8, ³J=7.5, ³J=1.9 Hz, 1H, 4-

(1S,4’R,3Z)-1-(2’,2’-Dimethyl-1’,3’-dioxolan-4’-yl)hex-3-en-1-ol (45d): Ac-

cording to GP E allylboronate 39 (200 mg, 0.38 mmol) in CH₂Cl₂

(ꢁ200 mL) was treated with (R)-aldehyde 42d (73 mg, 0.56 mmol)in

CH₂Cl₂(ꢁ50 mL). The reaction mixture was stirred at 08C for 24 h and

at RT for 48 h. For the reduction THF (4 mL) and LiAlH₄(57 mg,

1.50 mmol), for the work up H₂O (69 mL), 15% aqueous NaOH solution

(69 mL) und H₂O (205 mL) were used. Chromatography (petroleum ether/

EtOAc 90:10) furnisged a slightly impure colorless oil [52 mg, 0.26 mmol,

69%; ¹H NMR: dr (45d/epi-45d) 96:4]. R_f=0.12 (petroleum ether/

EtOAc 85:15), 0.54 (petroleum ether/EtOAc 70:30); [a]²_D⁰=+14 [c=1.65,

CHCl₃, dr (45d/epi-45d 96:4]; ¹H NMR (400 MHz, CDCl₃): d=0.97 (t,

³J=7.5 Hz, 3H, 6-H), 1.37 (s, 3H, 2’-CH_a3), 1.43 (s, 3H, 2’-CH_b3), 2.01 (d,

3

4

H), 5.77 (dddt, J=10.8, J=7.1, J=6.7, J=1.5 Hz, 1H, 3-H), 7.43–7.46,

7.55–7.59, 8.05–8.07 ppm (3 m, 5H, arom CH), ¹³C NMR (126 MHz,

CDCl₃): d=25.3, 26.4 (2’-CH₃), 29.2 (C-5), 32.4 (C-2), 35.5, 37.2 [N-

A

126.2 (C-3), 128.4, 129.7, 133.1 (arom. CH), 130.1 (arom. C_ipso), 166.1

(PhCO), 170.9 ppm (C-1); IR (film, ATR): n˜ =3030 (arom. C-H-n); 2985,

2935, 2885 (aliph. C-H-n); 1715 (C=O-n, ester); 1645 (C=O-n, amide);

1490; 1450; 1395; 1380, 1370 (CH₃, C-H-d_s); 1270; 1215; 1110; 1065 cm^ꢀ1

;

MS (EI, 70 eV): m/z (%): 361 (2) [M⁺], 346 (10) [MꢀCH₃⁺], 303 (6)

[MꢀC₃H₆O⁺], 240 (52) [MꢀPhCO₂⁺], 239 (14) [MꢀPhCO₂H⁺], 105

(100) [PhCO⁺]; elemental analysis calcd (%) for C₂₀H₂₇NO₅(361.4): C

66.46, H 7.53, N 3.88, found: C 66.26, H 7.61, N 3.76. Analytical data for

3

4

5

³J=3.2 Hz, 1H, OH), 2.07 (qddddd, J=7.5, J=7.3, J=1.6, J=0.8, J=

0.7 Hz, 2H, 5-H), 2.23 (ddddt, ³J=14.5, ³J=7.6, ³J=7.5, ⁴J=1.5, ⁵J=

0.7 Hz, 1H, 2-H_a), 2.27 (ddddt, ³J=14.5, ³J=5.5, ³J=7.5, ⁴J=1.5, ³J=

1

epi-48 [7 mg, 0.02 mmol, 10%; H NMR: dr (48/epi-48) > 99:1]; R_f=0.27

Chem. Eur. J. 2008, 14, 5178 – 5197

ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

5195

J. Pietruszka et al.

(EtOAc); [a]²_D⁰=+35 [c=0.10, CHCl₃, dr (48/epi-48) > 99:1]; ¹H NMR

(500 MHz, CDCl₃): d=1.36, 1.39 (2s, 6H, 2’-CH₃), 2.58 (m, 2H, 5-H),

122 , 90 3 –9 09; for an alternative, see: g) M. M. Midland, S. B. Pres-

ton, J. Am. Chem. Soc. 1982 , 104 , 233 0 –2 331; by synthesis via

Diels–Alder reactions: h) M. Vaultier, F. Truchet, B. Carboni, R. W.

Hoffmann, I. Denne, Tetrahedron Lett. 1987 , 28 , 416 9 –4 172; appli-

cation in natural product synthesis, e.g.: i) A. Schlapbach, R. W.

Hoffmann, Eur. J. Org. Chem. 2001 , 32 3 –3 28; j) R. Stürmer, R. W.

Hoffmann, Chem. Ber. 1994 , 127 , 251 9 –2 526; k) M. W. Andersen, B.

Hildebrand, G. Dahmann, R. W. Hoffmann, Chem. Ber. 1991 , 124 ,

212 7 –2 139.

2.90, 2.94 [2s, 6H, N

(CH₃)₂], 3.12 (m, 2H, 2-H), 3.93 (dd, ²J=8.5, ³J=

A

5.9 Hz, 1H, 5’-H_a), 4.09 (dd, ²J=8.5, ³J=6.5 Hz, 1H, 5’-H_b), 4.30 (ddd,

³J=6.5, ³J=6.2, ³J=5.9 Hz, 1H, 4’-H), 5.23 (m, 1H, 6-H), 5.65 (dtt, ³J=

10.9, ³J=7.4, ⁴J=1.8 Hz, 1H, 4-H), 5.77 (dtt, ³J=10.9, ³J=6.9, ⁴J=

1.5 Hz, 1H, 3-H), 7.43–7.46, 7.55–7.59, 8.01–8.03 ppm (3 m, 5H, arom

CH); ¹³C NMR (126 MHz, CDCl₃): d=25.3, 26.6 (2’-CH₃), 29.1 (C-5),

32.5 (C-2), 35.5, 37.2 [N(CH₃)₂], 66.4 (C-5’), 73.9 (C-6), 75.9 (C-4’), 109.7

G

(C-2’), 125.9 (C-4), 126.1 (C-3), 128.4, 129.7, 133.2 (arom. CH), 130.0

(arom. C_ipso), 165.8 (PhCO), 170.9 ppm (C-1); IR (solution in CDCl₃): n˜ =

3050, 3010 (arom. C-H-n); 2970, 2920, 2870 (aliph. C-H-n); 1710 (C=O-n,

ester); 1630 (C=O-n); 1590; 1575; 1480; 1440; 1390; 1370, 1360 (CH₃, C-

H-d_s); 1300; 1260; 1200; 1165; 1100; 1055 cm^ꢀ1; MS (CI, CH₄): m/z (%):

362 (33) [M+H⁺], 346 (16) [MꢀCH₃⁺], 240 (100) [MꢀPhCO₂⁺], 105

(50) [PhCO⁺]; HRMS (AUTO-CI, 70 eV): m/z: calcd for C₂₀H₂₈NO₅:

362.1967, found: 362.1951; elemental analysis calcd (%) for C₂₀H₂₇NO₅

(361.4): C 66.46, H 7.53, N 3.88, found: C 67.08, H 7.79, N 3.70.

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Acknowledgements

We gratefully acknowledge the Deutsche Forschungsgemeinschaft, the

Otto-Rçhm-Gedächtnisstiftung and the Landesgraduiertenfçrderung

Baden Württemberg (Graduiertenstipendium for N.S.) for the generous

support of our projects. Donations from the Boehringer Ingelheim KG,

the Degussa AG, the Bayer AG, the BASF AG, the Wacker AG, and the

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Published online: April 30, 2008

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Diastereo- and enantiomerically pure allylboronates: Their synthesis and scope

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