Regio- and enantioselective substitution of acyclic allylic sulfoximines with butylcopper in the presence of lithium iodide and boron trifluoride

Article abstract of DOI:10.1021/jo960027u

Enantiomerically pure N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(phenyl)cinnamylsulfoximmes as well as the corresponding crotylsulfoximines have been prepared from N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(lithiomethyl)sulfoximines and carbonyl com

Full text of DOI:10.1021/jo960027u

J . Org. Chem. 1996, 61, 4379-4390
4379
Regio- a n d En a n tioselective Su bstitu tion of Acyclic Allylic
Su lfoxim in es w ith Bu tylcop p er in th e P r esen ce of Lith iu m Iod id e
a n d Bor on Tr iflu or id e
Matthias Scommoda, Hans-J oachim Gais,* Stephan Bosshammer, and Gerhard Raabe
Institut fu¨r Organische Chemie der Rheinisch-Westfa¨lischen Technischen Hochschule Aachen,
Prof.-Pirlet Strasse 1, 52062 Aachen, Germany
Received J anuary 2, 1996X
Enantiomerically pure N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(phenyl)cinnamylsulfoximines
as well as the corresponding crotylsulfoximines have been prepared from N-methyl-, N-benzyl-,
and N-(methoxyethyl)-S-(lithiomethyl)sulfoximines and carbonyl compounds by an addition-
elimination-isomerization reaction sequence. Under basic conditions, complete isomerization of
the vinylic sulfoximines, obtained as intermediates, to the corresponding allylic sulfoximines takes
place. Chromatographically separable mixtures of (E) and (Z) allylic sulfoximines were isolated in
the case of â,γ-disubstituted allylic sulfoximines. The (E/ Z) ratio depends on the nature of the
substituents in the â- and γ-positions, and the equilibrium amount of the (Z) isomer varies from
68% to nil. The allylic N-methylsulfoximines do not racemize thermally, and their rearrangement
to the corresponding allylic sulfinamides is negligible. Upon prolonged treatment with boron
trifluoride at low temperatures allylic N-methylsulfoximines are recovered unchanged. The crystal
structure of S-(3,4-dihydronaphthalen-2-ylmethyl)-N-methyl-S-phenylsulfoximine was determined.
Reaction of the allylic sulfoximines with butylcopper in the presence of lithium iodide and boron
trifluoride leads with very high γ-selectivities and moderate to high enantioselectivities to the
corresponding chiral alkenes. Their configuration was determined by chemical correlation through
ozonolysis to the corresponding carbonyl compounds. The asymmetric induction exerted by the
chiral N-methyl-S-phenylsulfoximine group strongly depends on the double bond configuration and
the substituents in the â- and γ-positions. The (E) allylic sulfoximines are substituted with low to
moderate enantioselectivities (2-66%), whereas the (Z) allylic sulfoximines react with much higher
enantioselectivities (69-92%). Interestingly, substitution of the â-methyl-γ-phenyl-substituted (Z)
allylic sulfoximine and its â-phenyl-γ-methyl isomer proceeded with almost the same degree of
asymmetric induction but with the opposite sense. Replacement of the N-methyl group by a benzyl
or a methoxyethyl group has no significant influence on the regio- and enantioselectivity of the
substitution.
In tr od u ction
with organocuprates with high selectivity in the R-posi-
tion and with the corresponding organocopper reagents
in the presence of boron trifluoride and lithium iodide
with equal high selectivity in the γ-position. Asymmetric
induction by the N-methyl-S-phenylsulfoximine group,
which serves as an excellent nucleofuge (in the presence
of boron trifluoride), was moderate to high. These
investigations were restricted, however, to cyclic allylic
sulfoximines where the double bond was contained in a
five- or six-membered ring and thus constrained to the
(E) configuration.7 It was therefore of interest to study
the regio- and enantioselectivity of the substitution of
acyclic allylic sulfoximines. In particular, answers were
sought as to what extent the asymmetric induction
depends on the geometry of the double bond and its
substitution pattern as well as on the nature of its
substituents. Here we report on the synthesis and
reaction of (Z) and (E) acyclic allylic sulfoximines bearing
alkyl and phenyl groups with organocopper reagents.
Asymmetric induction exerted by a chiral leaving group
in the substitution of an allylic substrate has received
much attention in recent years.1-4 High enantioselec-
tivities have been reported for the reaction of chiral allylic
acetals,1 carbamates,2 pyrrolidines,3 and sulfides4 with
organocopper reagents. We have recently found that the
chiral N-methyl-S-phenylsulfoximine group not only
exerts asymmetric induction in the reaction of metallated
allylic sulfoximines with electrophiles5 but also in the
substitution of allylic sulfoximines with copperorganyls.6,7
Primary allylic N-methyl-S-phenylsulfoximines react
X Abstract published in Advance ACS Abstracts, May 15, 1996.
(1) (a) Alexakis, A.; Mangeney, P.; Ghribi, A.; Marek, I.; Sedranu,
R.; Guir, C.; Normant, J . Pure Appl. Chem. 1988, 60, 1. (b) Alexakis,
A.; Mangeney, P. Tetrahedron: Asymmetry 1990, 1, 477.
(2) Denmark, S. E.; Marble, L. K. J . Org. Chem. 1990, 55, 1984.
(3) Tamura, R.; Watabe, K. I.; Ono, N.; Yamamoto, Y. J . Org. Chem.
1992, 57, 4895.
(4) Calo´, V.; Fiandanese, V.; Nacci, A.; Scilimati, A. Tetrahedron
1994, 50, 7283.
(5) (a) Harmata, M.; Claassen, R. J ., II. Tetrahedron Lett. 1991, 32,
6497. (b) Pyne, S. G.; Boche, G. Tetrahedron 1993, 49, 8449. (c)
Reggelin, M.; Weinberger, H. Tetrahedron Lett. 1992, 33, 6959. (d)
Reggelin, M.; Weinberger, H. Angew. Chem. 1994, 106, 489; Angew.
Chem., Int. Ed. Engl. 1994, 33, 444. (e) Gais, H.-J .; Mu¨ller, H.; Decker,
J .; Hainz, R. Tetrahedron Lett. 1995, 36, 7437. (f) Pyne, S. G.; Dong,
Z.; Skelton, B. W.; White, A. H. J . Chem. Soc., Chem. Commun. 1994,
751.
(6) Bund, J .; Gais, H.-J .; Erdelmeier, I. J . Am. Chem. Soc. 1991,
113, 1442.
(7) Gais, H.-J .; Mu¨ller, H.; Bund, J .; Scommoda, M.; Brandt, J .;
Raabe, G. J . Am. Chem. Soc. 1995, 117, 2453.
Resu lts a n d Discu ssion
Syn th esis a n d P r op er ties of Acyclic Allylic Su l-
foxim in es. (i) Syn th esis. For the synthesis of the
enantiomerically pure acyclic allylic sulfoximines 9-13,
15-18, and 27-31 (Schemes 3-5) as well as the cyclic
allylic sulfoximine 14 (Scheme 3) on a preparative scale,
the same route used previously for the synthesis of cyclic
allylic sulfoximines6,7 was followed. Educts are an enan-
S0022-3263(96)00027-8 CCC: $12.00 © 1996 American Chemical Society

4380 J . Org. Chem., Vol. 61, No. 13, 1996
Scommoda et al.
Ta ble 1. Syn th esis of â-Hyd r oxysu lfoxim in es 3-8 a n d 24-26 a n d Allylic Su lfoxim in es 9-18 a n d 27-31
hydroxysulfoximine
R2 a yieldb (%)
allylic sulfoximine
yieldb (%)
compd
R1 a
elimin
isomerizn time
compd
E/Zc
e
e
3
4
5
6
7
8
Ph
Ph
Me
Me
Ph
H
Me
Ph
Et
67
80
71
Id
9
57
83
80
84
83
49h
100:0
61:39
36:64
32:68
63:37
100:0
Id
10/11
17/18
12/13
15/16
14
IIf
Id
5 d
6 d
79
CH2Ph
68g
44g
IIf
Id
39 h
e
24
25
26
Ph
Ph
Ph
H
Me
Me
69
70
48
Id
Id
Id
12 h
12 h
18 h
27
28/29
30/31
72
72
61
100:0
84:16
54:46
a
b
R1 and R2 originate from R1CH2COR2. Of isolated compounds. c The E/Z ratio may not in all cases represent the equilibrium
composition. I: (1) MsCl, NEt3; (2) DBU. e In the elimination step the allylic sulfoximine was obtained directly. f II: (1) n-BuLi; (2)
ClCOOMe; (3) KOtBu. CeCl3 was added prior to the addition of the carbonyl compound. After a 2-fold recrystallization from 15% ethyl
acetate-n-hexane, yield of the crude product was 78%.
d
g
h
Sch em e 1
Sch em e 2
Sch em e 3
tiomerically pure (lithiomethyl)sulfoximine and an alde-
hyde or a ketone, which are converted via the steps of
addition,8 elimination,9-11 and isomerization6 to the allylic
sulfoximines (Schemes 1-5). The ready availability of
aldehydes and ketones as well as of both enantiomers of
N,S-dimethyl-S-phenylsulfoximine, 1 and ent-1,12,13 in
enantiomerically pure form conveys high synthetic utility
to this route, except that the allylic sulfoximines bearing
two substituents at the double bond are generally ob-
tained as (E/ Z) mixtures (Table 1). This necessitates
separation and lowers the yield. On the other hand, the
attainment of separable (E/Z) mixtures was highly
welcome for the present reactivity study since it provides
access to (Z) allylic sulfoximines not easily obtainable
otherwise.5,14 Thus, reaction of the S-(lithiomethyl)-
sulfoximine 215 with phenylacetaldehyde, phenylacetone,
ethyl phenyl ketone, and diethyl ketone led to the
isolation of the hydroxysulfoximines 3-6, respectively,
in yields of 67-80% (Scheme 1, Table 1).
Addition of 2 to dibenzyl ketone and â-tetralone gave,
however, the hydroxysulfoximines 7 and 8, respectively,
in only 33% yield (Scheme 2).16,17 Treatment of 2 with
cerium trichloride18 prior to the addition of the carbonyl
compound raised the yield of the â-hydroxysulfoximines
7 and 8 to 68% and 44%, respectively. The hydroxysul-
foximines from phenylacetaldehyde, phenylacetone, and
ethyl phenyl ketone were obtained as diastereomeric
mixtures, which was, however, of no importance for the
synthesis of the corresponding allylic sulfoximines.
For the elimination of the â-hydroxysulfoximines to the
vinylic sulfoximines there are several methods avail-
able.9-11 In the case of the hydroxysulfoximines 3 and
4, sequential treatment with mesyl chloride, triethyl-
amine, and diazabicyclo[5.4.0]undec-7-ene (DBU) gave,
with the corresponding mesylates and vinylic sulfox-
imines as intermediates, the (E) allylic sulfoximine 919
in 57% yield and a mixture of the (E) and (Z) allylic
sulfoximines 1019 and 1119 in a ratio of 61:39 in 83% yield,
respectively (Scheme 3). Sulfoximines 10 and 11 were
readily separated by chromatography. The hydroxysul-
foximine 6 gave, after treatment with mesyl chloride,
triethylamine, and DBU, a mixture of the allylic sulfox-
(8) J ohnson, C. R.; Zeller, J . R. Tetrahedron 1984, 40, 1225.
(9) Erdelmeier, I; Gais, H.-J .; Lindner, H. J . Angew. Chem. 1986,
98, 912; Angew. Chem., Int. Ed. Engl. 1986, 25, 935.
(10) Pyne, S. G. J . Org. Chem. 1986, 51, 81.
(11) Craig, D.; Geach, N. J . Synlett 1993, 481.
(12) (a) J ohnson, C. R.; Schroeck, C. W.; Shanklin, J . R. J . Am.
Chem. Soc. 1973, 95, 7424. (b) J ohnson, C. R.; J onsson, E. U.;
Wambsgans, A. J . Org. Chem. 1979, 44, 2061.
(13) Shiner, C. S.; Berks, A. H. J . Org. Chem. 1988, 53, 5542.
(14) Reaction of sulfonimidates with (E/Z)-crotylmagnesium bromide
gave nearly exclusively the corresponding (E) allylic sulfoximine; see
ref 5c.
(15) Gais, H. J .; Erdelmeier, I.; Lindner, H. J . Angew. Chem. 1986,
98, 914; Angew. Chem., Int. Ed. Engl. 1986, 25, 938.
(16) For similar observations, see ref 8.
(17) Scommoda, M. Ph.D. Thesis, RWTH Aachen, 1995.
(18) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.;
Kamiya, Y. J . Am. Chem. Soc. 1989, 111, 4392.
(19) Gais, H.-J .; Scommoda. M.; Lenz. D. Tetrahedron Lett. 1994,
35, 7361.

Substitution of Acyclic Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 13, 1996 4381
Sch em e 4
Sch em e 5
imines 12 and 13 and the corresponding vinylic sulfox-
imine. Complete isomerization of the latter to a mixture
of the (E) and (Z) allylic sulfoximines 12 and 13 in a ratio
of 32:68 in 50% yield was achieved upon further treat-
ment with an excess of DBU in acetonitrile at room
temperature. The pure isomers 12 and 13 were readily
obtained by chromatographic separation.
at the stage of the starting N-(H)sulfoximine 21. The
latter route has two steps less, but it lacks synthetic
flexibility if different N-substituted allylic sulfoximines
with the same allylic moiety are to be prepared. We have
chosen the second route because of its shortness (Scheme
5).
Elimination of the hydroxysulfoximines 5 and 7 and
isomerization of the corresponding vinylic sulfoximines
were accomplished best by the sequential treatment with
n-butyllithium, methyl chloroformate, potassium tert-
butoxide,11 and finally DBU in acetonitrile at room
temperature. A mixture of the (E) and (Z) allylic sul-
foximines 15 and 16 in a ratio of 63:37 in 83% yield and
a mixture of the (E) and (Z) allylic sulfoximines 17 and
18 in a ratio of 36:64 in 56% yield were obtained (Scheme
4). Chromatography of the corresponding (E/ Z) mixtures
gave the pure allylic sulfoximines 15-18. For the NMR
spectroscopic differentiation between allylic and vinylic
sulfoximines (vide infra), the pure vinylic sulfoximines
19 and 20 (Scheme 4) were prepared as reference
compounds from alcohol 5 by the above sequence, but
omitting the isomerization step with DBU. The hydroxy-
sulfoximine 8 gave, upon sequential treatment with
mesyl chloride, triethylamine and DBU, a 93:7 mixture
of the allylic sulfoximine 14 and its allylic isomer in 78%
yield. After recrystallization, the pure allylic sulfoximine
14 was obtained in 49% yield (Scheme 3).
Allylic sulfoximines with alkyl groups other than a
methyl group at the N atom were prepared in order to
study the influence of the N-substituent upon the sub-
stitution reaction. The various substituents at the sul-
foximine N atom can be introduced in two different ways.
In the first route, followed previously in the synthesis of
cyclic allylic sulfoximines,7 the allylic sulfoximine bearing
a trimethylsilyl protecting group at the N atom20 is
synthesized by the sequence described. After removal
of the silyl group, different groups can be attached to the
N atom of the allylic N-(H)sulfoximine.11,21 In the second
route, the appropriate substituent is introduced already
Two different alkyl groups were introduced starting
from the parent N-(H)sulfoximine 21 by using the
procedure described recently by J ohnson et al.22 The
N-benzylsulfoximine 22 was prepared from 21 and benzyl
bromide in 78% yield, and the sulfoximine 23 carrying
the potentially chelating methoxyethyl group at the N
atom was synthesized from 21 and methoxyethyl bromide
in 78% yield. Lithiation of the sulfoximines 22 and 23
followed by the addition of phenylacetaldehyde and
benzyl methyl ketone, respectively, led to the isolation
of the hydroxysulfoximines 24-26 as mixtures of dia-
stereomers in 48-69% yield (Scheme 5). By the elimina-
tion-isomerization route (vide supra) the (E) allylic
sulfoximines 27, 28, and 30 were prepared in 72%, 61%,
and 33% yield, respectively, and the (Z) allylic sulfox-
imines 29 and 31 in 11% and 28% yield, respectively. As
before, (E/Z) mixtures of 28/29 and 30/31 were obtained
which could be separated by chromatography. In the
case of sulfoximine 31, however, a contamination by one
of the diastereomeric hydroxysulfoximines 26 could not
be removed.
The structure of the allylic sulfoximines 9-13, 15-
18, and 27-31 was assigned by NMR spectroscopy. The
coupling patterns, the chemical shifts, and, in the case
of the allylic sulfoximines 11, 15, 16, 29, and 31, the
1J (C,H) value for the proton at the double bond (which
is ∼20 Hz smaller for an allylic sulfoximine, 17 and 18,
than for a vinylic sulfoximine, 19 and 20) were instru-
mental for the differentiation between vinylic and the
corresponding allylic sulfoximines. Assignment of the
double bond configuration of the allylic sulfoximines
(20) (a) Hwang, K.-J .; Logusch, E. W.; Brannigan, L. H.; Thompson,
M. R. J . Org. Chem. 1987, 52, 3435. (b) Pyne, S. G.; Dikic, B.
Tetrahedron Lett. 1990, 31, 5231.
(21) (a) J ohnson, C. R. In Comprehensive Organic Chemistry; Barton,
D., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 1, p 223.
(b) J ohnson, C. R. Aldrichim. Acta 1985, 18, 3.
3
9-13 and 15-18 was done based on the J (H,H) values
(22) J ohnson, C. R.; Lavergne, O. M. J . Org. Chem. 1993, 58, 1922.

4382 J . Org. Chem., Vol. 61, No. 13, 1996
Scommoda et al.
or on 1H{1H} NOE experiments (cf. Experimental Sec-
tion). Assignment of the configuration of 27-31 was
done in analogy to that of 9-11.
(ii) (E/Z) Isom er iza tion of Allylic Su lfoxim in es.
Under basic conditions, (E) and (Z) allylic sulfoximines
are in equilibrium. Upon treatment of the pure (Z) allylic
sulfoximine 11 for 12 days with DBU in methylene
chloride, a 79:21 mixture of 10 and 11 was formed. In a
similar experiment, but this time starting from the pure
(E) allylic sulfoximine 10, the equilibrium was ap-
proached from the opposite side. After 6 days at room
temperature, an 83:17 mixture of 10 and 11 was ob-
tained. This proves that sulfoximines 10 and 11 are
interconvertible under basic conditions and that the
equilibrium lies on the side of the (E) isomer. A quite
similar observation was made in the case of the â-benzyl-
substituted sulfoximines 15 and 16. Here, the isomer-
ization was carried out under anhydrous conditions with
fluoride (Bu4NF‚3H2O) as base in tetrahydrofuran at
room temperature. The equilibrium mixture consists of
36% of the (Z) allylic sulfoximine 16 and 64% of the (E)
allylic sulfoximine 15. A similar situation is encountered
with the γ-phenyl-substituted sulfoximines 27, 28/29, and
30/31 carrying a N-benzyl and a N-methoxyethyl group.
In the case of the γ-methyl-substituted sulfoximines 12/
13 and 17/18 the (Z) isomer is favored (Table 1). The
equilibrium between the vinylic sulfoximine and the
allylic sulfoximine was in all cases completely on the side
of the latter.23 This shows that the allylic sulfoximines
are the thermodynamically more stable compounds in the
cases studied.
F igu r e 1. View of the structure of sulfoximine 14 in the
crystal.
previous studies.7,25,26a,b Knowledge of the structure of
allylic sulfoximines is desirable for an understanding of
the stereochemistry of the substitution (vide infra). We
have therefore determined the crystal structure of the
bicyclic allylic sulfoximine 14 by X-ray analysis.26c The
bonding situation around the S atom in 14 is typical for
N-methylsulfoximines7,9,25-27 (Figure 1).
The S atom is coordinated in a distorted tetrahedral
fashion. The O-S-N bond angle is 122.9°, and the C1-
S-N angle is, at 102.1°, the smallest tetrahedral angle
at the S atom. The N-methyl group is gauche to the O
atom and to the phenyl group. The S-phenyl group is
rotated by 37.6° out of the N-S-C13 plane, as it is in
the crystal structures of N-tosyl-S-phenyl-S-methylcy-
clopentenylsulfoximine7 and S-(3,3-dimethylbutenyl)-N-
methylsulfoximine.28 The N-S-C1-C2 dihedral angle
is 172.2°, which indicates an almost antiperiplanar
arrangement of the allylic moiety and the N-methyl
fragment. This means that the large dihydronaphtha-
lene group and the phenyl group are arranged in a
synclinal fashion. This seems to be a preferred confor-
mation of allylic N-methylsulfoximines in the crystal and
perhaps also in solution.26
Su bstitu tion of Allylic Su lfoxim in es. The major
intention of this study was the determination of the
influence of (a) the substituent in the â-position, (b) the
substituent in the γ-position, (c) the substituent at the
N atom, and (d) the configuration of the double bond on
the regio- and enantioselectivity of the substitution of
acyclic allylic sulfoximines. Butylcopper (32) was chosen
as the organocopper compound for the substitution reac-
tions because of its high reactivity toward allylic sulfox-
imines.7 All reactions were performed with 3-4 equiv
of 32‚LiI at -78 °C. Purified copper(I) iodide29 served
as source of copper(I), and it was solubilized with a small
amount of dimethyl sulfide as cosolvent. On the basis
of 32, lithium iodide was always present in equimolar
amounts in the substitution reactions described due to
the mode of the preparation of the former. Boron
trifluoride was used in all substitution reactions as an
additive.
(iii) Ch em ica l a n d Op t ica l St a b ilit y of Allylic
Su lfoxim in es. At high temperatures the γ-phenyl-
substituted allylic sulfoximines 9 and 10 undergo a slow
and rather incomplete thermal rearrangement to the
corresponding isomeric allylic sulfinamides.19,24 This
rearrangement is characterized by a complete retention
of the configuration at the S atom. Most important,
however, is the observation that during this process no
racemization of the allylic sulfoximines 9 and 10 occurs.
They are recovered enantiomerically pure. A similar
thermal rearrangement of the other allylic sulfoximines
described herein was not observed. Because of the
slowness of this rearrangement at room temperature,
application of allylic sulfoximines in asymmetric synthe-
sis is not hampered.
Since a γ-substitution of allylic N-methylsulfoximines
with organocopper reagents occurs only in the presence
of boron trifluoride, determination of the chemical and
optical stability of allylic sulfoximines in the presence of
this Lewis acid under the reaction conditions employed
was deemed necessary. Treatment of enantiomerically
pure (E) sulfoximine 17 with 3 equiv of boron trifluoride
in THF at -60 °C for 20 h and subsequent workup with
pyridine-hydrogen fluoride led to a 94% recovery of the
optically pure compound. Thus, allylic N-methylsulfox-
imines seem to be chemically and optically stable in
tetrahydrofuran solution in the presence of boron tri-
fluoride under such conditions.
(25) Gais, H.-J .; Lenz, D.; Raabe, G. Tetrahedron Lett. 1995, 36,
7437.
(26) (a) Gais, H.-J .; Schmitz, E.; Raabe, G. Unpublished results. (b)
Gais, H.-J .; Pommerenke, A.; Raabe, G. Unpublished results. (c) The
authors have deposited atomic coordinates for 14 with the Cambridge
Crystallographic Data Centre. The coordinates can be obtained, on
request, from the Director, Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge, CB2 1EZ, UK.
(27) (a) Dong, Z.; Pyne, S. G.; Skelton, B. W.; White, A. H. Aust. J .
Chem. 1993, 46, 143.
(28) Gais, H.-J .; Giesen, A.; Raabe, G. Unpublished results.
(29) Kauffman, G. B.; Teter, L. A. Inorg. Synth. 1963, 7, 10.
(iv) Str u ctu r e of Allylic Su lfoxim in es. Only a few
crystal structures of allylic sulfoximines are known from
(23) The four-membered cyclic allylic N-methyl-S-phenylsulfoximine
is an exception of this rule; see ref 7.
(24) For a quantitative palladium-catalyzed rearrangement of allylic
N-tosylsulfoximines to the corresponding allylic sulfinamides, see:
Pyne, S. G.; Dong, Z. Tetrahedron Lett. 1995, 36, 3029.

Substitution of Acyclic Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 13, 1996 4383
Ta ble 2. Su bstitu tion of (E) Allylic Su lfoxim in es w ith n -Bu Cu ‚LiI + BF 3
entry
sulfoximine
R1
R2
solvent
t (h)
γ-product
yielda (%)
γ/Rb
ee (%)
confign
1
2
3
4
5
6
7
8
9
9
9
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
H
H
THFc
Et2Oc
THFc
Et2Oc
THFc
THF
Et2O
THF
Et2O
6
5.5
7
16
39
16
16
16
16
33
33
34
34
35
39
39
40
40
86
76
78
75
33g
89
97
90
86
98:2
93:7
>99:1
96:4
33d
33d
47f
60f
22h
2f
Re
Re
R
R
S
R
R
R
R
10
10
15
17
17
12
12
Me
Me
PhCH2
Ph
Ph
Et
99:1
>99:1
>99:1
>99:1
>99:1
4f
71f
72f
Et
a
b
After chromatography. γ/R-ratios were determined by capillary GC analysis or by integration of the olefinic signals in the 1H NMR
spectra. c Three equiv of copperorganyl was used. Determined by 1H NMR spectroscopy in the presence of Ag(fod) (1 equiv) and Pr(tfc)3
d
(1 equiv). e Tentative assignment. f Determined by capillary GC analysis on
a
2,3-di-O-pentyl-6-O-methyl-γ-cyclodextrin column.
Sulfoximine 15 was recovered in 57% yield. Determined by 1H NMR spectroscopy in the presence of Ag(fod) (0.8 equiv) and Pr(tfc)3
g
h
(0.8 equiv).
(i) (E) Allylic Su lfoxim in es. Reaction of the allylic
sulfoximine 9, which bears as substituent only a phenyl
group in the γ-position, gave with 32‚LiI the alkene 33
with high γ-regioselectivity but low enantioselectivity
(Table 2, entries 1 and 2). An additional methyl group
in the â-position of the allylic sulfoximine, as in 10, raised
the enantioselectivity of the γ-substitution in addition to
a high γ-selectivity (Table 2, entry 3). Substitution of
allylic sulfoximine 10 in ether instead of tetrahydrofuran
gave alkene 34 with a slightly lower regioselectivity
(96:4) but with a significantly higher enantioselectivity
of 60% ee (Table 2, entry 4).
Sch em e 6
The higher enantioselectivity in the reaction of the
â-methyl-substituted allylic sulfoximine 10 led to the
notion that a larger group in the â-position might perhaps
be necessary for a highly enantioselective substitution.
Thus, substitution of the allylic sulfoximine 15, which
bears a sterically more demanding benzyl group in the
â-position, was studied. Reaction of the sulfoximine 15
with 32‚LiI gave the alkene 35 with high γ-regioselec-
tivity (99:1) but with an enantioselectivity of only 22%
ee (Table 2, entry 5). The reaction of 15 with 32‚LiI in
tetrahydrofuran was much slower as compared to 10,
however, and in ether practically no substitution oc-
curred.17
In the sulfoximines 10 and 15 the γ-phenyl ring is most
likely not coplanar with the double bond because of steric
reasons. It was therefore of interest to study the
substitution of the bicyclic sulfoximine 1443 where copla-
narity of these structural elements is enforced (Scheme
6). Furthermore, comparison of the substitution of 14
with that of the monocyclic cyclohexenyl analog 367 was
deemed interesting.
Reaction of 14 with 32‚LiI gave with high γ-regio-
selectivity the exocyclic alkene 38 in high yield with ee-
values of 52% and 66%, respectively. Here, too, a solvent
effect on the enantioselectivity was observed. The sub-
stitution of 36 with 32‚LiI gave the (S) alkene 37 with
an ee-value of 60%.7 Thus, the substitution of the
S-cyclohexenylsulfoximine 36, the S-dihydronaphtha-
lenylsulfoximine 14, and the methyl-substituted cin-
namylsulfoximine 10 proceed with a similar degree of
asymmetric induction and, presumably, with the same
sense.
and of the dialkyl-substituted sulfoximine 12 were stud-
ied. The reaction of the sulfoximine 17 with 32‚LiI gave
exclusively the γ-substitution product 39 in high yield.
However, the reaction had occurred with almost no
asymmetric induction (Table 2, entries 6 and 7). Sub-
stitution of the sulfoximine 12, which bears an ethyl
group in the â-position and a methyl group in the
γ-position, with 32‚LiI gave, with very high γ-regio-
selectivity and with the highest enantioselectivity in the
series of the (E)-sulfoximines, the alkene 40 in 86-90%
yield. Here, the ee-value of 40 was almost independent
of the solvent used (Table 2, entries 8 and 9). In all
substitution reactions N-methyl-S-phenylsulfinamide12b
in the (S) configuration was isolated in yields g80% with
ee-values g95%.
(ii) (Z) Allylic Su lfoxim in es. The substitution of the
(Z)-sulfoximines 11, 13, 16, and 18 was studied because
of their availability. The â-methyl-substituted sulfox-
imine 11 showed a reactivity similar to that of its (E)
isomer 10 and gave the alkene ent-34 of opposite config-
uration in 79-80% yield with very high regioselectivity.
The enantioselectivity of the substitution of 11, however,
was much higher than that of 10. Substitution in
tetrahydrofuran gave ent-34 with an ee-value of 78%, and
in ether ent-34 was obtained with an ee-value of 87%
(Table 3, entries 1 and 2).
Reaction of the â-benzyl substituted (Z)-sulfoximine 16
with 32‚LiI in tetrahydrofuran proceeded much faster
than with its (E) isomer 15. Even in ether, substitution
Finally the substitutions of the sulfoximine 17, where
the substitution pattern is reversed as compared to 10,

4384 J . Org. Chem., Vol. 61, No. 13, 1996
Ta ble 3. Su bstitu tion of (Z) Allylic Su lfoxim in es w ith n -Bu Cu ‚LiI + BF 3
Scommoda et al.
entry
sulfoximine
R1
R2
Me
solvent
t (h)
γ-product
yielda (%)
γ/Rb
ee (%)
confign
1
2
3
4
5
6
7
8
11
11
16
16
18
18
13
13
Ph
Ph
Ph
Ph
Me
Me
Me
Me
THFc
Et2Oc
THFc
Et2Of
THF
Et2O
THF
Et2O
21
16
25
63
16
16
16
16
ent-34
ent-34
35
35
39
39
40
40
80
79
80
87
85
93
75
87
>99:1
>99:1
>99:1
99:1
>99:1
95:5
78d
87d
87e
92e
82d
69d
30d
12d
S
S
S
S
R
R
R
R
Me
PhCH2
PhCH2
Ph
Ph
Et
95:5
>99:1
Et
a
b
d
After chromatography. γ/R-ratios were determined by capillary GC analysis. c Three equiv of copperorganyl was used. Determined
by capillary GC analysis on a 2,3-di-O-pentyl-6-O-methyl-γ-cyclodextrin column. e Determined by 1H NMR spectroscopy in the presence
of Ag(fod) (0.8 equiv) and Pr(tfc)3 (0.8 equiv). f Four equiv of copperorganyl was used.
Ta ble 4. Su bstitu tion of a llylic N-Ben zyl- a n d N-(Meth oxyeth yl)su lfoxim in es w ith n -Bu Cu ‚LiI + BF 3
entry
sulfoximine
R2
R3
solvent
t (h)
γ-product
yielda (%)
γ/Rb
ee (%)
confign
1
2
3
4
5
6
27
27
28
28
30
30
H
H
Me
Me
Me
Me
PhCH2
PhCH2
PhCH2
PhCH2
MeO(CH2)2
MeO(CH2)2
THFc
6
6
17
7
6
9
33
33
34
34
34
34
83
82
70
58
82
85
92:8
97:3
>99:1
96:4
>99:1
91:9
23d
33d
40f
52f
40f
64f
Re
Re
R
R
R
THF/Et2Oc
THFc
Et2Oc
THFc
Et2Oc
R
a
b
After chromatography. γ/R-ratios were determined by capillary GC analysis or by integration of the olefinic signals in the 1H NMR
spectra. c Three equiv of copperorganyl was used. Determined by 1H NMR spectroscopy in the presence of Ag(fod) (1 equiv) and Pr(tfc)3
d
(1 equiv). e Tentative assignment. f Determined by capillary GC analysis on a 2,3-di-O-pentyl-6-O-methyl-γ-cyclodextrin column.
of 16 went to completion, although the reaction time was
much longer. In tetrahydrofuran, alkene 35 was ob-
tained in 80% yield and with 87% ee and, if ether was
used as solvent, both the yield and the ee-value went up
to 87% and 92%, respectively (Table 3, entries 3 and 4).
Most surprising, however, was the observation that the
alkene isolated from the reaction of 16 had the same
configuration as the one obtained from the (E) isomer 15.
While the substitution of the (E)-sulfoximine 17 gave
practically the racemic alkene rac-39, the substitution
of its (Z) isomer 18 proceeded with high enantioselectivity
and gave alkene 39 with 82% and 69% ee, respectively
(Table 3, entries 5 and 6). Here, too, substitution of the
isomeric sulfoximines 17 and 18 gave, in both cases,
preferentially the alkene 39. Substitution of the sulfox-
imine 13, which bears an ethyl group in the â-position,
occurred with high regioselectivity but low enantioselec-
tivity (Table 3, entries 7 and 8). This was the only case
where the substitution of a (Z)-sulfoximine proceeded
with a lower enantioselectivity than that of its (E) isomer.
In all the above substitution reactions N-methyl-S-
phenylsulfinamide12b of the (S) configuration was isolated
in yields g80% with ee-values g95%.
species 27 and 28 with 32‚LiI proceeded with similar
regioselectivities and slightly lower enantioselectivities
(Table 4, entries 1-4) as compared to their N-methyl-
substituted analogs (Table 2).
In the case of the sulfoximine 30 bearing an N-
methoxyethyl group, the substitution in tetrahydrofuran
gave the alkene 34 with an ee-value of 40% (Table 4,
entry 5), which is 7% lower than that of the sample of
34 obtained in the substitution of the corresponding
N-methylsulfoximine 10. Reaction of 30 in ether gave
the alkene 34 with an ee-value of 64% (Table 4, entry 7),
which is 4% higher. Thus, both N-alkyl substituents
have no significant influence on the asymmetric induction
imparted by the sulfoximine group. Together with our
previous investigations7 of N-substituted sulfoximines
other than the one described here, these results show that
the N-methylsulfoximines are not only the easiest to
synthesize but also those which show the highest reactiv-
ity (in the presence of boron trifluoride) and whose
substitution occurs with the highest asymmetric induc-
tion.
(iv) Con figu r a tion of Alk en es. The configuration
of the alkenes ent-34, 35, 39, and 40 was determined by
chemical correlation with the corresponding ketones
(Scheme 7).
Ozonolysis of the terminal alkene (-)-ent-34 gave the
ketone (-)-41 of known absolute configuration30 in 97%
yield. The sign of optical rotation indicated that the
sample of ketone (-)-41 obtained had the (R) configura-
tion, and thus, (-)-ent-34 has the (S) configuration.
Determination of the ee-value of ketone (-)-41 by capil-
(iii) N-Ben zyl- an d N-(Meth oxyeth yl)su lfoxim in es.
The influence of the substituent at the N atom of the
sulfoximine group on the regio- and enantioselectivity of
the substitution reaction was studied in the case of the
sulfoximines 27, 28, and 30 bearing a phenyl group in
the γ-position, a methyl group or a H atom in the
â-position, and a benzyl or a methoxyethyl group at the
N atom. The substitution reaction of the N-benzyl

Substitution of Acyclic Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 13, 1996 4385
Sch em e 7
has the (R) configuration. Since it seems highly unlikely
that the substitutions of the allylic sulfoximine 18 with
butylcopper and ethylcopper proceed with the same
degree of asymmetric induction but with the opposite
sense, the above assignment of the absolute configuration
of at least the alkene 39 ought to be correct.
(v) Mech a n istic Con sid er a tion s. The asymmetric
induction exerted by the (S)-configurated N-methylsul-
foximine group in the substitution of allylic sulfoximines
9-13, 15-18, 27, 28, and 30 depends strongly and
apparently irregularly on the configuration and the
substituents in the â- and γ-positions of the double bond.
In the series of the (E)-cinnamylsulfoximines 9, 10, and
15, which bear an H atom and a methyl and a benzyl
group in the â-position, and of the (E)-crotylsulfoximines
12 and 17, which carry an ethyl and a phenyl group in
the â-position, the asymmetric induction is, with the
exception of 17, where it is practically nil, low to
moderate (33-72% ee). On the basis of the reaction
depicted in Table 2, CC-bond formation occurs preferen-
tially from the rear of the double bond in all cases except
15. The benzyl group in the â-position of 15, however,
not only decreases the rate of the substitution consider-
ably but also leads to a preferential bond formation from
the front of the double bond (cf. reaction in Table 2).
Surprisingly, a phenyl group in the â-position leads to
an almost unselective substitution as exemplified by the
substitution of the sulfoximine 17 as compared to that
of the â-ethyl-substituted sulfoximine 12.
In the series of the (Z)-cinnamyl- and (Z)-crotylsulfox-
imines 11, 16, 13, and 18, respectively, asymmetric
induction is significantly higher (69-92% ee), except for
the substitution of the ethyl-substituted crotylsulfoximine
13. On going from the cinnamyl species 11 and 16 to
the crotyl species 13 and 18, however, the sense of
asymmetric induction is reversed. Whereas in 11 and
16, CC-bond formation occurs preferentially from the rear
of the double bond, in 13 and 18 CC-bond formation takes
place preferentially from the front of the double bond (cf.
reaction in Table 3). Thus, one is faced with the situation
that the substitution of isomeric cinnamylsulfoximines,
10 and 11, gives preferentially enantiomeric alkenes and
the substitution of isomeric crotylsulfoximines, 12 and
13 as well as 17 and 18, gives preferentially the same
alkene. â-Benzyl-substituted cinnamylsulfoximines, 15
and 16, are the exception in that they give the same
alkene.
lary GC analysis on a 2,3-di-O-pentyl-6-O-methyl-γ-
cyclodextrin column revealed that ozonolysis was not
accompanied by racemization.7 Ozonolysis of the alkene
(-)-35 gave the ketone (-)-42 in 90% yield. On the
reasonable assumption that ketone (-)-42 should have
the same sign of optical rotation as its R-methyl31 and
R-ethyl analogs32 (methyl or ethyl instead of n-butyl),
whose configuration is known, the (R) configuration was
assigned to ketone (-)-42 and thus the (S) configuration
to alkene (-)-35. Ozonolysis of the alkene (-)-39 afforded
the ketone (-)-43 in 85% yield. For the corresponding
ketone having an ethyl group instead of the n-butyl
group, a negative sign of optical rotation correlates with
the (R) configuration.33 We therefore also assigned to the
alkene (-)-39 the (R) configuration. Ozonolysis of the
alkene (-)-40 led to the ketone (-)-44 in 76% yield. Here,
the absolute configuration of the analogous ketones
bearing an ethyl34 or a n-propyl35 group instead of a
n-butyl group is known, and a negative sign of optical
rotation correlates with the (R) configuration. Therefore,
the ketone (-)-44 and the alkene (-)-40 were assigned
the (R) configuration.36 To further substantiate the
assignment of the absolute configuration of alkene 39,
the allylic sulfoximine 18 was converted with ethylcopper
in the presence of lithium iodide and boron trifluoride in
tetrahydrofuran into the alkene (-)-45 (92%; 85% ee)
(Scheme 7). Thus, the substitutions of 18 with butyl-
copper and ethylcopper occur with similar enantioselec-
tivities. Ozonolysis of the alkene (-)-45 gave the ketone
(-)-46 of known absolute configuration. The sign of
optical rotation indicated that the sample of ketone (-)-
46 obtained had the (R) configuration, and thus (-)-45
Replacement of the methyl group at the sulfoximine
N atom by a sterically more demanding or a potentially
complexing group has resulted so far in no significant
changes in the degree and the sense of the asymmetric
induction of the substitution. The N-methyl-S-phenyl-
sulfoximines, which are the easiest to synthesize, give
the best results thus far.
We assume that the substitution of allylic sulfoximines
by organocopper reagents proceeds by a mechanism
similar to the one proposed for the substitution of allylic
(30) (a) J acques, J .; Gros C.; Bourcier, S. In Stereochemistry,
Fundamentals and Methods, Absolute Configurations of 6000 Selected
Compounds with One Asymmetric Carbon Atom; Kagan, H. B., Ed.;
Georg Thieme Verlag: Stuttgart, 1977. (b) Mislow, K.; Hamermesh,
C. L. J . Am. Chem. Soc. 1955, 77, 1590.
acetates, carbonates, mesylates, etc.37
A characteristic
(31) (a) Meyers, A. I.; Williams, D. R. J . Org. Chem. 1978, 43, 3245.
(b) Meyers, A. I.; Williams, D. R.; White, S.; Erickson, G. W. J . Am.
Chem. Soc. 1981, 103, 3088.
(32) Takeuchi, S.; Miyoshi, N.; Ohgo, Y. Chem. Lett. 1992, 551.
(33) Smolinsky, G.; Feuer, B. I. J . Am. Chem. Soc. 1964, 86, 3085.
(34) (a) Bartlett, P. D.; Stauffer, C. H. J . Am. Chem. Soc. 1935, 57,
2580. (b) Lardicci, L. L.; Salvadori, P.; Botteghi, C.; Pino, P. J . Chem.
Soc., Chem. Commun. 1968, 381.
(35) Enders, D.; Eichenauer, H. Angew. Chem. 1979, 91, 425; Angew.
Chem., Int. Ed. Engl. 1979, 18, 397.
(36) Ozonolysis of alkene 33 under the conditions described gave
the corresponding dimethyl acetal instead of the aldehyde.
stereochemical feature of these substitutions is the anti-
orientation of the nucleophile and the nucleofuge with
respect to the allylic fragment. We have shown that in
the substitution of cyclic allylic sulfoximines lithium
iodide plays an essential role. It most likely converts the
organocopper compound to the corresponding hetero-
cuprate,38 which seems to be the reacting species.7
Furthermore, in these studies it was found that boron
trifluoride is another essential ingredient in the case of

4386 J . Org. Chem., Vol. 61, No. 13, 1996
Scommoda et al.
Sch em e 8a
D (ent-D) in turn undergoes a reductive elimination with
formation of the γ-substitution product E (ent-E). Ac-
cording to the current view, regioselectivity depends on
whether D (ent-D) is a di- or a triorganocoopper com-
pound. In the case of a diorganocopper species D,
reductive elimination is supposed to be fast, leading to
the selective formation of the γ-substitution product E.
If D is a triorganocopper species (R3 instead of I) then
reductive elimination is supposedly preceded by a fast
reversible rearrangement to the isomeric σ-allyl complex
followed by its preferential reductive elimination, because
of steric reasons, to the isomeric R-substitution product.
Formation of each enantiomer of the σ-allyl complex, D
and ent-D, can occur from the two diastereomeric π-alk-
ene complexes, anti-Si-C/syn-Si-C and anti-Re-C/syn-Re-
C, respectively. Thus, the ratio of the enantiomeric
alkenes, E/ent-E, is determined by the relative propor-
tions of the competing Re and Si as well as syn and anti
reaction paths followed in the substitution. Now the
question arises of which factors determine the relative
proportions of these pathways. We have observed that
the substitution of the endocyclic allylic sulfoximines
(S,1S)- and (S,1R)-S-(1-cyclopent-1-enylethyl)-S-phenyl-
N-methylsulfoximine with 32‚LiI in the presence of boron
trifluoride proceeds with high anti-selectivity.40 For the
substitution of acyclic allylic sulfoximines, the stereo-
chemical course in regard to syn or anti is not known.
From the results obtained, it seems as if both pathways
are followed, depending on the steric and electronic
nature of the substituents. In attempting to propose a
transition state model for the rationalization of the
experimental data, one has consider, however, that the
existence of diorganocopper(III) species of type D (ent-
D)41 and of π-alkene complexes of type C42 are speculative
and their structure is thus not known. Even the impor-
tant question whether the formation of D (ent-D) is
irreversible or not is controversial.37 Furthermore, the
nature of the reacting organocopper species is a matter
of debate.37i Thus, despite a considerable body of experi-
mental data the long-standing question of the mechanism
of the allylic substitution with homo- and heterocuprates
remains unsettled.37,41 This, taken together with our
rather limited knowledge of the mode of the coordination
of boron trifluoride to the sulfoximine group and the
preferred CR-S conformation in the diastereomeric π-
alkene complexes upon their conversion to the enantio-
meric σ-allyl complexes (cf. Scheme 8), makes the inter-
pretation of the sense of asymmetric induction difficult
at present even in seemingly clearcut cases (entries 1 and
5, Table 3). Clearly, further and more specific experi-
ments are needed.
The descriptors Re and Si refer to the γ-C-atom in cases R2
*
a
H.
the substitution of N-methylsulfoximines. Presumably,
it coordinates to the N or O atom of the sulfoximine
group39 and thereby activates the substrate or an inter-
mediate.
Thus, in analogy to the currently accepted substitution
mechanism of allylic substrates,37 the boron trifluoride-
complexed allylic sulfoximine A is expected to react in a
perhaps reversible manner with the heterocuprate B,
which is arbitrarily depicted as a monomer, with forma-
tion of the π-alkene complex C (Scheme 8). This complex
is converted irreversibly through an oxidative addition-
substitution to the σ-allyl complex D (ent-D). Complex
Con clu sion
(37) (a) Goering, H. L.; Kantner, S. S. J . Org. Chem. 1981, 46, 2144.
(b) Goering, H. L.; Kantner, S. S. J . Org. Chem. 1983, 48, 721. (c) Tseng,
C. C. T.; Paisley, S. D.; Goering, H. L. J . Org. Chem. 1986, 51, 2884.
(d) Underiner, T. L.; Paisley, S. D.; Schmitter, J .; Lesheski, L.; Goering,
H. L. J . Org. Chem. 1989, 54, 2369. (e) Underiner, T. L.; Goering, H.
L. J . Org. Chem. 1990, 55, 2757. (f) Ba¨ckvall, J .-E.; Selle´n, M.; Grant,
B. J . Am. Chem. Soc. 1990, 112, 6615. (g) Nakanishi, N.; Matsubara,
S.; Utimoto, K.; Kozima, S.; Yamaguchi, R. J . Org. Chem. 1991, 56,
3278. (h) Ba¨ckvall, J .-E.; Persson, E. S. M.; Bombrun, A. J . Org. Chem.
1994, 59, 4126. (i) Lipshutz, B. H.; Sengupta, S. Org. React. 1992, 41,
135. (j) Lipshutz, B. H. In Organometallics in Synthesis; Schlosser,
M., Ed.; Wiley: New York, 1994; p 283.
(38) NMR spectroscopic studies of [(trimethylsilyl)methyl]copper in
the presence of lithium iodide gave evidence for the formation of a
heterocuprate: Gais, H.-J .; Brandt, J . Unpublished results.
(39) NMR spectroscopic studies of N-methylsulfoximines in the
presence of boron trifluoride gave evidence for the formation of a
complex: Gais, H.-J .; Pommerenke, A.; Bund, J ; Mu¨ller, H. Unpub-
lished results.
Enantiomerically pure acyclic (Z) and (E) allylic sul-
foximines bearing different substituents at the allylic
(40) Pommerenke, A. Diploma Thesis, RWTH Aachen, 1994.
(41) (a) Willert-Porada, M. A.; Burton, D. J .; Baenzinger, N. C. J .
Chem. Soc., Chem. Commun. 1989, 1633. (b) Power, P. P. Prog. Inorg.
Chem. 1991, 39, 75. (c) de la Pradilla, R. F.; Rubio, N. B.; Marino, J .
P.; Viso, A. Tetrahedron Lett. 1992, 33, 4985. (d) Naumann, D.; Roy,
T.; Tebbe, K.-F.; Crump, W. Angew. Chem. 1993, 105, 1555; Angew.
Chem., Int. Ed. Engl. 1993, 32, 1482. (e) Snyder, J . P. Angew. Chem.
1995, 107, 112; Angew. Chem., Int. Ed. Engl. 1995, 34, 80. (f) Dorigo,
A. E.; Wanner, J .; Schleyer, P. v. R. Angew. Chem. 1995, 107, 492;
Angew. Chem., Int. Ed. Engl. 1995, 34, 476.
(42) For a proposal regarding the structure of π-alkene complexes
of type C, see: Corey, E. J .; Boaz, N. W. Tetrahedron Lett. 1984, 29,
3063.

Substitution of Acyclic Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 13, 1996 4387
yellow suspension had been stirred for 2 h at -78 °C, dibenzyl
ketone (3.15 g, 15.0 mmol) in THF (20 mL) was added. The
heterogeneous reaction mixture was stirred for 17 h at -78
°C, and saturated aqueous NH4Cl was added. The pH was
adjusted to 5-6 by dropwise addition of 10 M HCl, and the
resulting homogeneous solution was extracted with EtOAc.
The combined organic extracts were dried (MgSO4) and
concentrated in vacuum. The residue was dissolved in EtOAc
(10 mL), and n-hexane (40 mL) was added. The solution was
cooled to -24 °C to give hydroxysulfoximine 7 (3.09 g, 54%)
as colorless crystals. The mother liquor was concentrated in
vacuum and the residue purified by chromatography (50%
n-hexane-EtOAc) to give a further crop of hydroxysulfoximine
7 (0.78 g, 14%): mp 134 °C; [R]D +94.1 (c 2.98, THF); 1H NMR
(300 MHz, CDCl3) δ 7.78-7.74 (m, 2 H), 7.60-7.45 (m, 3 H),
7.35-7.08 (m, 10 H), 6.97 (s, 1 H), 3.55 (d, J AB ) 13.84 Hz, 1
H), 3.33 (d, J AB ) 13.84 Hz, 1 H), 3.14 (d, J AB ) 13.83 Hz, 1
moiety and at the N atom can be readily prepared from
carbonyl compounds and S-methyl-S-phenylsulfoximines.
In the case of â,γ-disubstituted compounds, (E/ Z) mix-
tures are obtained, which necessitates chromatographic
separation but makes, at the same time, both isomers
available. Unlike acyclic allylic sulfoxides, acyclic allylic
sulfoximines do not racemize thermally and the rear-
rangement to the corresponding allylic sulfinamides is
negligible. Substitution of acyclic allylic sulfoximines
with butylcopper in the presence of lithium iodide and
boron trifluoride proceeds, like that of cyclic allylic
sulfoximines, with very high γ-selectivity. Asymmetric
induction in the substitution of the (E) allylic sulfox-
imines investigated is low to moderate (2-66% ee) but,
with one exception, is high in the substitution of the
corresponding (Z) isomers (62-92% ee). Rationalization
of the sense of asymmetric induction in dependence of
the substituents, the double bond configuration, and the
configuration at the S atom, is difficult at the present
time because of the limited knowledge of the mechanism
of the substitution and its stereochemical course in
regard to syn and anti.
H), 3.02 (d, J AB ) 13.83 Hz, 1 H), 2.60 (s, 3 H), 2.80 (d, J AB
)
14.18 Hz, 1 H), 2.53 (d, J AB ) 14.18 Hz, 1 H); 13C NMR (75
MHz, CDCl3) δ 139.08 (u), 137.42 (u), 136.57 (u), 133.19 (d),
131.11 (d), 130.85 (d), 129.64 (d), 128.90 (d), 128.17 (d), 128.04
(d), 126.53 (d), 126.50 (d), 75.03 (u), 61.45 (u), 46.60 (u), 46.36
(u), 28.99 (d); MS (EI) m/ z (relative intensity) 379 (M+, 0.3),
288 (49), 156 (40), 140 (13), 133 (21), 125 (36), 106 (19), 105
(18), 91 (100), 77 (18), 65 (18). Anal. Calcd for C23H25NO2S:
C, 72.79; H, 6.64; N, 3.69. Found: C, 72.48; H, 6.58; N, 3.76.
(+)-(S,E)-N-Meth yl-S-(2-m eth yl-3-p h en yl-2-p r op en yl)-
S-p h en ylsu lfoxim in e (10) a n d (-)-(S,Z)-N-Meth yl-S-(2-
m eth yl-3-p h en yl-2-p r op en yl)-S-p h en ylsu lfoxim in e (11).
To a solution of hydroxysulfoximine 4 (5.92 g, 19.5 mmol)
(diastereomeric mixture) in CH2Cl2 (100 mL) and NEt3 (13.6
mL, 98 mmol) was added MeSO2Cl (4.6 mL, 59.4 mmol) at 0
°C. The solution was stirred for 30 min, and DBU (17.7 mL,
117 mmol) was added. After the reaction mixture had been
stirred for 16 h at room temperature, it was diluted with ether.
The solution was washed with water, saturated aqueous NH4-
Cl, and 10% aqueous Na2CO3 (in this order), dried (MgSO4),
and concentrated in vacuum. Purification of the oily residue
by chromatography (33% n-hexane-EtOAc) gave allylic sul-
foximine 11 (1.78 g, 32%) as a waxy, colorless solid and allylic
sulfoximine 10 (2.97 g, 51%) as a colorless oil. Analytical data
Exp er im en ta l Section
Instruments, general experimental techniques, solvent and
reagent purification, analytical measurements, and notations
for the listing of spectral data were applied as previously
described.7
(S,2R)- an d (S,2S)-1-(N-Meth yl-S-ph en ylsu lfon im idoyl)-
2-m eth yl-3-p h en yl-2-p r op a n ol (4). To a solution of sulfox-
imine 1 (4.23 g, 25 mmol) in THF (60 mL) was added n-BuLi
(25 mmol, 16.7 mL of 1.50 M in n-hexane) at -5 °C. The
resulting orange solution was cooled to ∼-78 °C, and phenyl-
acetone (3.35 g, 25 mmol) in THF (20 mL) was added. The
reaction mixture was slowly warmed to 0 °C (4.5 h) and then
diluted with saturated aqueous NH4Cl. The organic phase was
separated, and the aqueous phase was extracted with EtOAc.
The combined organic phases were dried (MgSO4) and con-
centrated in vacuum. Purification of the oily residue by
chromatography (33% n-hexane-EtOAc) gave a mixture of
hydroxysulfoximine (S,2R)-4 and hydroxysulfoximine (S,2S)-4
(6.07 g, 80%) as a colorless solid. Analytical data are given
for the mixture of diastereomers (I, major diastereomer; II,
minor diastereomer): mp 126-127 °C; 1H NMR (300 MHz,
CDCl3) δ 7.93-7.88 (m, 2 H, II), 7.84-7.79 (m, 2 H, I), 7.66-
7.51 (m, 3 H, I), 7.32-7.14 (m, 5 H), 6.86 (s, 1 H), 3.34-3.21
1
for 10: [R]D +48.1 (c 2.44, THF); H NMR (300 MHz, CDCl3)
δ 7.87-7.83 (m, 2 H, o-PhS), 7.62-7.49 (m, 3 H, m,p-PhS),
7.31-7.16 (m, 3 H, m,p-PhC), 7.04-7.01 (m, 2 H, o-PhC), 5.97
(m, 1 H, PhCH), 3.97 (s, 2 H,CH2S), 2.77 (s, 3 H, NCH3), 1.94
(s, 3 H, CCH3); 1H{1H} NOE CCH3 f NCH3 (m), CCH3 f CH2S
(s), CCH3 f o-PhC (s), CCH3 f o-PhS (m), NCH3 f o-PhS (s),
CH2S f CCH3 (s), CH2S f NCH3 (m), CH2S f PhCH (s), CH2S
f o-PhS (m), PhCH f CH2S (s), PhCH f o-PhC (m); 13C NMR
(75 MHz, CDCl3) δ 136.88 (u), 136.74 (u), 134.83 (d), 132.90
(d), 129.90 (d), 129.16 (d), 128.71 (d), 128.14 (d), 127.04 (d),
126.76 (u), 67.10 (u), 29.92 (d), 18.79 (d); MS (EI) m/ z (relative
intensity) 285 (M+, 0.58), 167 (17), 160 (16), 132 (11), 131 (100),
(m, 3 H, II), 3.15 (d, J AB ) 13.84 Hz, 1 H, II), 2.97 (d, J AB
)
13.84 Hz, 1 H, I), 2.69 (s, 3 H, II), 2.59 (s, 3 H, I), 1.67 (s, 3 H,
I), 1.09 (s, 3 H, II); 13C NMR (75 MHz, CDCl3) δ 139.25 (u),
138.95 (u), 137.48 (u), 136.26 (u), 133.26 (d), 133.23 (d), 130.85
(d), 129.68 (d), 129.02 (d), 128.18 (d), 128.08 (d), 126.74 (d),
126.43 (d), 72.85 (u), 72.59 (u), 64.05 (u), 64.01 (u), 50.26 (u),
47.25 (u), 29.07 (d), 28.93 (d), 28.00 (d), 26.80 (d); MS (EI) m/ z
(relative intensity) 303 (M+, 1.43), 212 (68), 170 (12), 156 (82),
154 (65), 140 (36), 125 (99), 107 (13), 106 (39), 104 (30), 97
(11), 94 (12), 92 (14), 91 (100), 78 (21), 77 (36), 65 (25), 51 (17),
43 (48). Anal. Calcd for C17H21NO2S: C, 67.30; H, 6.98; N,
4.62. Found: C, 67.08; H 7.12; N 4.80.
129 (13), 116 (13), 115 (15), 91 (36). Anal. Calcd for C17H19
-
NOS: C, 71.54; H, 6.71; N, 4.91. Found: C, 71.61; H, 6.88;
N, 4.92. Analytical data for 11: [R]D -0.79 (c 1.76, THF); 1H
NMR (300 MHz, CDCl3) δ 7.72-7.69 (m, 2 H, o-PhS), 7.57-
7.40 (m, 3 H, m,p-PhS), 7.20-7.15 (m, 3 H, m,p-PhC), 7.00-
6.95 (m, 2 H, o-PhC), 6.59 (m, J C,H ) 154 Hz, 1 H, Ph-CHdC),
4.13 (d, J AB ) 13.84 Hz, 1 H, CH2S), 4.08 (d, J AB ) 13.84 Hz,
4
1 H, CH′2S), 2.68 (s, 3 H, NCH3), 2.09 (d, J ) 1.35 Hz, 3 H,
1
CCH3); H{1H} NOE CCH3 f CH2S (s), NCH3 f o-PhS (m),
PhCHdC f CCH3 (m), PhCHdC f o-PhC (m), o-PhC f Ph-
CHdC (m), o-PhC f m,p-PhC (s), o-PhS f m,p-PhS (m); 13C
NMR (75 MHz, CDCl3) δ 137.92 (u), 136.40 (u), 134.27 (d),
132.71 (d), 129.30 (d), 129.20 (d), 128.26 (d), 128.24 (d), 126.94
(u), 126.90 (d), 59.69 (u), 29.79 (d), 24.32 (d); MS (EI) m/ z
(relative intensity) 285 (M+, 0.65), 167 (16), 160 (14), 132 (12),
131 (100), 115 (14), 114 (15), 91 (47), 77 (10). Anal. Calcd for
C17H19NOS: C, 71.54; H, 6.71; N, 4.91. Found: C, 71.70; H,
6.65; N, 4.89.
(+)-(S,E)-S-(2-Ben zyl-3-p h en yl-2-p r op en yl)-N-m eth yl-
S-p h en ylsu lfoxim in e (15) a n d (+)-(S,Z)-S-(2-Ben zyl-3-
p h en yl-2-p r op en yl)-N-m eth yl-S-p h en ylsu lfoxim in e (16).
To a solution of hydroxysulfoximine 7 (3.89 g, 10.3 mmol) in
THF (50 mL) was added n-BuLi (10.3 mmol, 6.3 mL of 1.64 M
(+)-(S)-2-Ben zyl-1-(N-m eth yl-S-p h en ylsu lfon im id oyl)-
3-p h en yl-2-p r op a n ol (7). CeCl3‚H2O (8.31 g, 22.2 mmol) was
heated to 135-140 °C under vacuum (0.2 Torr). Heating was
continued for 2 h at this temperature in vacuum while the
solid was slowly stirred. After being cooled to room temper-
ature in vacuum, the flask was flushed with argon. Freshly
distilled THF (66 mL) was added, and the resulting white
suspension was kept for 2 h in a ultrasonic bath at room
temperature. Meanwhile, sulfoximine 1 (3.15 g, 18.6 mmol)
in THF (60 mL) was deprotonated with n-BuLi (18.6 mmol,
12.5 mL of 1.49 M in n-hexane) at -10 °C. After the contents
of both flasks were cooled to -78 °C, the solution of the
lithiosulfoximine 2 was added to the CeCl3-THF suspension
with the aid of a double-ended needle. After the resulting

4388 J . Org. Chem., Vol. 61, No. 13, 1996
Scommoda et al.
in n-hexane) at -78 °C. The reaction mixture was stirred for
15 min at -78 °C, and ClCOOMe (0.80 mL, 10.3 mmol) was
added dropwise. After 5 min the cooling bath was removed,
and the reaction mixture was stirred for 1 h at room temper-
ature. After the mixture was cooled to -78 °C, KOt-Bu (1.16
g, 10.3 mmol) in THF (10 mL) was added. The reaction
mixture was warmed to room temperature overnight, and
saturated aqueous NH4Cl was added. The mixture was
extracted with EtOAc, and the combined organic extracts were
dried (MgSO4) and concentrated in vacuum. The residue was
dissolved in CH3CN (40 mL), and DBU (3.0 mL, 20.0 mmol)
was added at room temperature. After the dark red reaction
mixture had been stirred for 39 h at room temperature under
an atmosphere of dry argon, saturated aqueous NH4Cl was
added. The mixture was extracted with EtOAc, dried (MgSO4),
and concentrated in vacuum. Purification of the residue by
chromatography (50% n-hexane-EtOAc) gave the allylic sul-
foximine 16 (1.14 g, 31%) as a light yellow oil and the allylic
sulfoximine 15 (1.94 g, 52%) as a colorless, waxy solid.
Analytical data for 15: mp 71 °C; [R]D +68.8 (c 1.47, THF);
1H NMR (500 MHz, CDCl3) δ 7.89-7.86 (m, 2 H, o-PhS), 7.64-
7.54 (m, 3 H, m,p-PhS), 7.29-7.16 (m, 6 H), 7.11-7.04 (m, 4
H, o-PhCH2, o-PhCHdC), 6.21 (sbr, J C,H ) 154.3 Hz, 1 H,
CdCH f o-PhS (s), CdCH f p-PhS (s), CH2CH3 f CdCH
(s), CH2CH3 f CH2CH3 (s), CH2CH3 f m-PhS (s); 13C NMR
(75 MHz, CDCl3) δ 158.58 (u), 139.44 (u), 136.78 (u), 131.76
(d), 129.18 (d), 128.79 (d), 128.53 (d), 127.77 (d), 127.77 (d),
127.64 (d), 34.13 (u), 29.18 (d), 11.79 (d); MS (EI) m/ z (relative
intensity) 286 (M+ + H, 12), 285 (M+, 50), 284 (16), 237 (11),
231 (55), 206 (13), 191 (11), 179 (24), 178 (10), 165 (10), 160
(60), 145 (15), 144 (16), 132 (52), 131 (64), 130 (18), 129 (22),
128 (21), 117 (17), 116 (17), 115 (35), 107 (15), 106 (100), 91
(95), 79 (11), 78 (16), 77 (45), 65 (17), 53 (12), 51 (25), 42 (28),
41 (14), 39 (10); HRMS (EI) calcd for C17H19NOS 285.11874,
found 285.1188. Analytical data for 20: [R]D +99.5 (c 0.97,
MeOH); 1H NMR (500 MHz, CDCl3) δ 7.98-8.00 (m, 2 H,
m-PhS), 7.51-7.59 (m, 3 H, o/p-PhS), 7.32-7.38 (m, 5 H, PhC),
6.59 (s, J C,H ) 175 Hz, 1 H, CdCH), 2.98 (dq, J AB ) 13.6, J )
7.0 Hz, 1 H, CH2CH3), 2.93 (dq, J AB ) 13.7, J ) 7.0 Hz, 1 H,
CH2CH3), 2.73 (s, 3 H, NCH3), 0.74 (t, J ) 7.5 Hz, 3 H,
1
CH2CH3); H{1H} NOE CdCH f C-Ph (s), CdCH f m-PhS
(s), CH2CH3 f CH2CH3 (s), CH2CH3 f C-Ph (s), CH2CH3
f
m-PhS (s), CH2CH3 f NCH3 (m); 13C NMR (75 MHz, CDCl3)
δ 159.01 (u), 141.36 (u), 139.33 (u), 132.94 (d), 129.99 (d),
129.74 (d), 129.30 (d), 129.22 (d), 128.34 (d), 127.27 (d), 29.92
(d), 23.57 (u), 12.82 (d); MS (EI) m/ z (relative intensity) 285
(M+, 20), 238 (19), 237 (100), 222 (25), 207 (15), 206 (83), 205
(71), 204 (10), 191 (13), 132 (14), 131 (27), 130 (17), 129 (54),
128 (26), 125 (22), 117 (19), 116 (16), 115 (42), 107 (17), 106
(23), 105 (19), 103 (12), 91 (95), 78 (15), 77 (38), 65 (14), 51
(23), 42 (19); HRMS (EI) calcd for C17H19NOS 285.11874, found
285.11870
PhCHdC), 3.87 (d, J AB ) 13.47 Hz, 1 H, CH2S), 3.80 (d, J AB
)
13.73 Hz, 1 H, CH′2S), 3.78 (d, J AB ) 15.41 Hz, 1 H, PhCH2),
3.67 (d, J AB ) 15.41 Hz, 1 H, PhCH′2), 2.74 (s, 3 H, NCH3);
1H{1H} NOE NCH3 f o-PhS (m), CH2S f PhCHdC (s),
PhCHdC f CH2S (m), PhCHdC f CH′2S (m), PhCHdC f
o-PhCHdC (s); 13C NMR (75 MHz, CDCl3) δ 138.40 (u), 137.05
(u), 136.37 (u), 136.44 (d), 132.95 (d), 130.00 (d), 129.45 (u),
129.25 (d), 128.94 (d), 128.70 (d), 128.38 (d), 127.41 (d), 126.50
(d), 62.67 (u), 36.20 (u), 29.93 (d); MS (EI) m/ z (relative
(+)-(S)-N-Ben zyl-S-m eth yl-S-p h en ylsu lfoxim in e (22). A
solution of sulfoximine 21 (776 mg, 5.0 mmol) in DME (10 mL)
was added to a suspension of potassium hydride (629 mg, 5.5
mmol, 35% suspension in mineral oil) in DME (10 mL). The
resulting suspension was stirred for 30 min at room temper-
ature. Then solid n-Bu4NBr (80 mg, 0.25 mmol) and benzyl
bromide (1.28 g, 7.5 mmol) were added. The reaction mixture
was stirred for 2 h at room temperature, and ice cold 2 M
sulfuric acid was added slowly until a pH of 1.0 was reached.
Ether was added, and the organic phase was separated. The
aqueous phase was neutralized by careful addition of solid Na2-
CO3 and extracted with EtOAc. The combined organic extracts
were dried (MgSO4) and concentrated in vacuum. Purification
of the residue by chromatography (EtOAc) gave sulfoximine
22 (986 mg, 78%) as a light yellow oil: [R]D +68.4 (c 1.82,
MeOH); 1H NMR (300 MHz, CDCl3) δ 7.95-7.91 (m, 2 H),
7.64-7.50 (m, 3 H), 7.38-7.15 (m, 5 H), 4.17 (d, J AB ) 14.17
Hz, 1 H), 3.99 (J AB ) 14.17 Hz, 1 H), 3.10 (s, 3 H); 13C NMR
(75 MHz, CDCl3) δ 141.20 (u), 139.45 (u), 132.87 (d), 129.40
(d), 128.60 (d), 128.20 (d), 127.55 (d), 126.48 (d), 47.31 (u), 45.26
(u); MS (EI) m/ z (relative intensity) 245 (M+, 75), 244 (69),
168 (23), 141 (98), 140 (85), 126 (21), 125 (100), 124 (18), 105
(76), 97 (24), 91 (77), 77 (66), 65 (26), 51 (42). Anal. Calcd for
C14H15NOS: C, 68.54; H, 6.16; N, 5.71. Found: C, 68.35; H,
6.21; N, 5.88.
intensity) 361 (M+, 0.08), 91 (100). Anal. Calcd for C23H23
-
NOS: C, 76.42; H, 6.41; N, 3.87. Found: C, 76.26; H, 6.72;
1
N, 4.03. Analytical data for 16: [R]D +3.2 (c 1.18, THF); H
NMR (500 MHz, CDCl3) δ 7.71-7.67 (m, 2 H, o-PhS), 7.54-
7.50 (m, 1 H, p-PhS), 7.44-7.39 (m, 2 H, m-PhS), 7.31-7.27
(m, 2 H, m-PhCH2), 7.23-7.15 (m, 6 H, m,p-PhCHdC, m,p-
PhCH2), 7.01-6.98 (m, 2 H, o-PhCHdC), 6.65 (sbr, J C,H ) 155
Hz, 1 H, PhCHdC), 4.08 (d, J AB ) 14.04 Hz, 1 H, CH2S), 4.01
(d, J AB ) 14.04 Hz, 1 H, CH′2S), 3.84 (d, J AB ) 14.65 Hz, 1 H,
PhCH2), 3.69 (d, J AB ) 14.96 Hz, PhCH′2), 2.68 (s, 3 H, NCH3);
1H{1H} NOE NCH3 f o-PhS (m), PhCH2 f PhCHdC (m),
PhCH2 f o-PhCH2 (m), PhCHdC f o-PhCHdC (s), PhCHdC
f o-PhCH2 (m), o-PhCHdC f PhCHdC (s); 13C NMR (125
MHz, CDCl3) δ 138.69 (u), 137.85 (u), 136.11 (u), 135.36 (d),
132.72 (d), 130.53 (u), 129.39 (d), 129.22 (d), 128.57 (d), 128.32
(d), 128.29 (d), 127.07 (d), 126.55 (d), 56.56 (u), 43.11 (u), 29.74
(d); MS (EI) m/ z (relative intensity) 361 (M+, 0.17); 91 (100).
Anal. Calcd for C23H23NOS: C, 76.42; H, 6.41; N, 3.87.
Found: 76.24; H, 6.54; N, 3.87.
(+)-(S,Z)-N-Met h yl-S-p h en yl-S-(2-p h en yl-1-b u t en yl)-
su lfoxim in e (19) a n d (+)-(S,E)-N-Meth yl-S-p h en yl-S-(2-
p h en yl-1-bu ten yl)su lfoxim in e (20). To a solution of hy-
droxysulfoximine 5 (3.45 g, 11.4 mmol) (diastereomeric mixture)
in THF (40 mL) was added n-BuLi (11.4 mmol, 7.5 mL of 1.52
M in n-hexane) at -78 °C. The resulting yellow solution was
stirred at this temperature for 1 h and cooled to -85 °C, and
ClCOOMe (0.88 mL, 11.4 mmol) was added. The solution was
stirred at room temperature for 30 min and cooled to -78 °C,
and KOt-Bu (1.28 g, 11.4 mmol) in THF (10 mL) was added
dropwise. After the solution had been stirred for 45 min at
this temperature and 45 min at room temperature, saturated
aqueous NH4Cl was added. The mixture was extracted with
EtOAc. The combined organic extracts were dried (MgSO4)
and concentrated in vacuum. Purification of the residue by
chromatography (50% EtOAc-n-hexane) gave sulfoximine 20
(916 mg, 28%) and sulfoximine 19 (1.38 g, 42%) as colorless
oils. Analytical data for 19: [R]D +59.5 (c 1.53, MeOH); 1H
NMR (500 MHz, CDCl3) δ 7.35-7.39 (m, 3 H, o/ p-PhS), 7.22-
7.26 (m, 2 H, m-PhS), 7.17-7.20 (m, 1 H, p-PhC), 7.10-7.14
(S,2R)- an d (S,2S)-1-(N-Ben zyl-S-ph en ylsu lfon im idoyl)-
2-m eth yl-3-p h en ylp r op a n -2-ol (25). To a solution of sul-
foximine 22 (2.15 g, 8.7 mmol) in THF (40 mL) was added
n-BuLi (8.7 mmol, 5.84 mL of 1.5 M in n-hexane) at -10 °C.
The resulting orange solution was cooled to -78 °C, and
phenylacetone (1.18 g, 8.7 mmol) in THF (10 mL) was added.
The reaction mixture was slowly warmed to 0 °C (3 h) and
then diluted with saturated aqueous NH4Cl. The organic
phase was separated, and the aqueous phase was extracted
with EtOAc. The combined organic phases were dried (MgSO4)
and concentrated in vacuum. The residue was purified by
chromatography (EtOAc), and the excess of phenylacetone was
removed in vacuum at 50 °C (10-4 Torr). A mixture of
hydroxysulfoximine (S,2R)-25 and hydroxysulfoximine (S,2S)-
25 (2.32 g, 70%) was obtained as a viscous oil. Analytical data
are given for the mixture of diastereomers (I, major diastere-
omer; II, minor diastereomer): 1H NMR (300 MHz, CDCl3) δ
7.95-7.90 (m, 2 H, II), 7.88-7.82 (m, 2 H, I), 7.65-7.14 (m,
13 H), 6.84 (s, 1 H), 4.30 (d, J AB ) 14.51 Hz, 1 H, II), 4.19 (d,
J AB ) 14.51 Hz, 1 H, I), 4.01 (d, J AB ) 14.51 Hz, 1 H, II), 3.89
(m, 2 H, m-PhC), 6.85-6.88 (m, 2 H, m-PhS), 6.59 (m, J C,H
175 Hz, 1 H, CdCH), 2.57 (s, 3 H, NCH3), 2.38 (dqd, J AB
)
)
16.0, J ) 7.3, 1.5 Hz, 1 H, CH2CH3), 2.34 (dqd, J AB ) 16.2, J
) 7.3, 1.5 Hz, 1 H, CH2CH3), 1.02 (t, J ) 7.3 Hz, 3 H, CH2CH3);
1H{1H} NOE CdCH f CH2CH3 (s), CdCH f CH2CH3 (s),
(d, J AB ) 14.51 Hz, 1 H, I), 3.44-3.18 (m, 3 H), 3.03 (d, J AB
)
13.83 Hz, 1 H, II), 2.80 (m, 2 H, I), 1.71 (s, 3 H, I), 1.11 (s, 3

Substitution of Acyclic Allylic Sulfoximines
J . Org. Chem., Vol. 61, No. 13, 1996 4389
H, II); 13C NMR (75 MHz, CDCl3) δ 140.83 (u), 140.77 (u),
139.72 (u), 139.43 (u), 137.43 (u), 136.18 (u), 133.40 (d), 133.37
(d), 130.88 (d), 130.73 (d), 129.70 (d), 128.96 (d), 128.95 (d),
128.45 (d), 128.38 (d), 128.23 (d), 128.11 (d), 127.41 (d), 127.37
(d), 126.79 (d), 126.74 (d), 126.69 (d), 126.47 (d), 73.02 (u), 72.71
(u), 64.49 (u), 50.28 (u), 47.12 (u), 46.95 (u), 28.04 (d), 26.76
(d); MS (EI) m/ z (relative intensity) 379 (M+, 0.61), 288 (14),
232 (24), 125 (56), 106 (44), 91 (100), 77 (11), 43 (20). Anal.
Calcd for C23H25NO2S: C, 72.79; H, 6.64; N, 3.69. Found: C,
72.78; H, 6.71; N, 3.82.
(66). Anal. Calcd for C23H23NOS: C, 76.42; H, 6.41; N, 3.87.
Found: C, 76.22; H, 6.48; N, 4.00.
Isom er iza tion of (E)-Su lfoxim in e 15. To a solution of
sulfoximine 15 (0.70 g, 1.94 mmol) in THF (15 mL) was added
Bu4NF‚3H2O (0.63 g, 2.00 mmol) at room temperature under
an atmosphere of dry argon. The red brown solution was
stirred for 5 d at room temperature. Saturated aqueous NH4-
Cl was added, and the resulting mixture was extracted with
EtOAc. The combined organic phases were dried (MgSO4) and
concentrated in vacuum. Analysis of the oily residue by 1H
NMR spectroscopy showed the presence the allylic sulfox-
imines 15 and 16 in a ratio of 64:36.
Isom er iza tion of (Z)-Su lfoxim in e 16. To a solution of
sulfoximine 16 (1.10 g, 3.04 mmol) in THF (20 mL) was added
Bu4NF‚3H2O (1.120 g, 3.55 mmol) at room temperature under
an atmosphere of dry argon. The red brown solution was
stirred for 5 d at room temperature. Saturated aqueous NH4-
Cl was added, and the resulting mixture was extracted with
EtOAc. The combined organic phases were dried (MgSO4) and
concentrated in vacuum. Analysis of the oily residue by 1H
NMR spectroscopy showed the presence of the allylic sulfox-
imines 15 and 16 in a ratio of 64:36.
Sta bility of (E)-Su lfoxim in e 17 tow a r d Bor on Tr iflu o-
r id e. To a solution of sulfoximine 17 (50 mg, 0.18 mmol; [R]D
+5.3 (c 1.00, THF)) in THF (5 mL) was added at -78 °C BF3‚
OEt2 (86 µL, 0.70 mmol). After the mixture had been stirred
for 20 h, hydrogen fluoride-pyridine (0.1 mL) was added at
-60 °C. Then saturated aqueous NaHCO3 was added, and
the mixture was warmed to room temperature. The mixture
was extracted with EtOAc (3 × 30 mL), and the combined
organic extracts were dried (MgSO4) and concentrated in
vacuum. Purification of the residue by chromatography (50%
EtOAc-n-hexane) gave 17 (47 mg, 94%; [R]D +5.3 (c 1.00,
THF)).
(+)-(S,E)-N-Ben zyl-S-p h en yl-S-(3-p h en yl-2-p r op en yl)-
S-p h en ylsu lfoxim in e (27). To a solution of hydroxysulfox-
imine 24 (1.64 g, 4.5 mmol) in CH2Cl2 (80 mL) and NEt3 (3.13
mL, 22.5 mmol) was added MeSO2Cl (1.54 g, 13.5 mmol) at 0
°C. The solution was stirred for 30 min, and DBU (4.02 mL,
26.9 mmol) was added. After the reaction mixture had been
stirred for 12 h at room temperature, it was diluted with ether
(150 mL). The solution was washed with water, saturated
aqueous NH4Cl, and 10% aqueous Na2CO3 (in this order), dried
(MgSO4), and concentrated in vacuum. Crystallization of the
oily residue from EtOAc (10 mL) at -24 °C gave sulfoximine
27 (1.13 g, 72%) as colorless, needle-shaped crystals: mp 102-
1
103 °C; [R]D +13.7 (c 2.50, THF); H NMR (500 MHz, CDCl3)
δ 7.84 (m, 2 H), 7.56 (m, 1 H), 7.48 (m, 2 H), 7.42-7.18 (m, 10
H), 6.26 (d, J ) 15.87 Hz, 1 H), 6.11 (dt, J trans ) 15.87, J )
7.47 Hz, 1 H), 4.31 (d, J AB ) 14.65 Hz), 4.12 (d, J AB ) 14.65
3
4
Hz, 1 H), 4.06 (ddd, J AB ) 13.8, J ) 7.48, J ) 1.07 Hz, 1 H),
4.03 (ddd, J AB ) 13.8, J ) 7.48, J ) 1.07 Hz, 1 H); 13C NMR
(75 MHz, CDCl3) 141.58 (u), 138.64 (d), 137.55 (u), 136.09 (u),
133.02 (d), 129.73 (d), 129.20 (d), 128.68 (d), 128.33 (d), 127.59
(d), 126.66 (d), 128.38 (d), 126.60 (d), 116.34 (d), 60.93 (u), 47.43
(u); MS (EI) m/ z (relative intensity) 347 (M+, 347), 222 (23),
117 (100), 115(26), 91 (38). Anal. Calcd for C22H21NOS: C,
76.05; H, 6.09; N, 4.03. Found: C, 75.75; H, 6.32; N, 4.17.
3
4
Su bstitu tion of (E)-Su lfoxim in e 10: (+)-(R)-1-[1-(1-
Met h ylet h en yl)p en t yl]b en zen e (34). To a solution of
Cu(I)I (590 mg, 3.1 mmol) in ether (20 mL) and Me2S (2.0 mL)
was added n-BuLi (3.0 mmol, 2.0 mL of 1.50 M in n-hexane)
at -60 °C. The resulting black solution was stirred for 45 min
and subsequently warmed to -50 °C. After the solution was
cooled to -78 °C, BF3·OEt2 (0.37 mL, 3.0 mmol) was added.
After the mixture had been stirred for 10 min, it was cooled
to -100 °C, and sulfoximine 10 (285 mg, 1.0 mmol) in ether
(8 mL) was added. The solution was stirred for 16 h at -78
°C, and then a 10:1 mixture of saturated aqueous NH4Cl and
concentrated aqueous NH3 was added. The resulting mixture
was extracted with Et2O. The combined organic extracts were
dried (MgSO4) and concentrated in vacuum (20 Torr, 20 °C).
Purification of the residue by chromatography (n-hexane) gave
a 96:4 mixture of alkene 34 and the corresponding R-substitu-
tion product (141 mg, 75%) as a colorless liquid with an ee-
value of 60% for 34.
(-)-(S,E)-N-Ben zyl-S-(2-m eth yl-3-p h en yl-2-p r op en yl)-
S-p h en ylsu lfoxim in e (28) a n d (-)-(S,Z)-N-Ben zyl-S-(2-
m eth yl-3-p h en yl-2-p r op en yl)-S-p h en ylsu lfoxim in e (29).
To a solution of hydroxysulfoximine 25 (2.28 g, 6.00 mmol)
(diastereomeric mixture) in CH2Cl2 (35 mL) and NEt3 (4.2 mL,
30.0 mmol) was added MeSO2Cl (1.4 mL, 18.0 mmol) at 0 °C.
The solution was stirred for 45 min at 0 °C, and DBU (5.4
mL, 36.0 mmol) was added. After the orange red reaction
mixture was stirred for 4 d at room temperature, it was diluted
with ether (100 mL). The solution was washed once with
water, saturated aqueous NH4Cl, and 10% aqueous Na2CO3
(in this order), dried (MgSO4), and concentrated in vacuum.
The residue was separated in two fractions by chromatography
(33% n-hexane-EtOAc). The first contained mainly the
sulfoximine 28 and the second the sulfoximine 29. Both
fractions contained unreacted hydroxysulfoximine 25. There-
fore, the mesylation-elimination was repeated once more with
these fractions. Purification of the resulting two fractions by
MPLC (33% EtOAc-cyclohexane) gave sulfoximine 28 (1.331
g, 61%) and sulfoximine 29 (0.235 g, 11%) as colorless viscous
Su bstitu tion of (Z)-Su lfoxim in e 11: (-)-(S)-1-[1-(1-
Meth yleth en yl)p en tyl]ben zen e (en t-34). To a solution of
Cu(I)I (590 mg, 3.1 mmol) in ether (20 mL) and Me2S (2.0 mL)
was added n-BuLi (3.0 mmol, 2.0 mL of 1.50 M in n-hexane)
at -60 °C. The resulting black solution was stirred for 45 min
and subsequently warmed to -50 °C. After the solution was
cooled to -78 °C, BF3·OEt2 (0.37 mL, 3.0 mmol) was added.
After the mixture had been stirred for 10 min, it was cooled
to -100 °C, and sulfoximine 11 (285 mg, 1.0 mmol) in ether
(8 mL) was added. The solution was stirred for 16 h at -78
°C, and then a 10:1 mixture of saturated aqueous NH4Cl and
concentrated aqueous NH3 was added. The resulting mixture
was extracted with Et2O. The combined organic extracts were
dried (MgSO4) and concentrated in vacuum (20 Torr, 20 °C).
Purification of the residue by chromatography (n-hexane) gave
the alkene ent-34 (149 mg, 79%) as a colorless liquid with an
ee-value of 87% which contained only traces (≈0.4%) of the
corresponding R-substitution product. Analytical data for
1
oils. Analytical data for 28: [R] -8.46 (c 3.2, THF); H NMR
(300 MHz, CDCl3) δ 7.90-7.85 (m, 2 H), 7.62-7.16 (m, 11 H),
7.04-6.99 (m, 2 H), 5.99 (sbr, 1 H), 4.32 (d, J AB ) 14.84 Hz),
4
4.11 (d, J AB ) 14.84 Hz), 4.03 (s, 2 H), 1.96 (d, J ) 1.35 Hz,
3 H); 13C NMR (75 MHz, CDCl3) δ 141.65 (u), 137.46 (u), 136.80
(u), 134.97 (d), 132.98 (d), 129.91 (d), 129.17 (d), 128.75 (d),
128.31 (d), 128.19 (d), 127.57 (d), 126.82 (u), 127.08 (d), 126.54
(d), 67.52 (u), 47.55 (u), 18.93 (d); MS (EI) m/ z (relative
intensity) 361 (M+, 0.43), 243 (13), 236 (14), 132 (13), 131 (100),
129 (14), 125 (14), 115 (12), 91 (77). Anal. Calcd for C23H23
-
NOS: C, 76.42; H, 6.41; N, 3.87. Found: C, 76.04; H, 6.62;
N, 4.12. Analytical data for 29: [R]D -45.89 (c 1.41, THF);
1H NMR (300 MHz, CDCl3) δ 7.74-7.69 (m, 2 H), 7.52-7.12
(m, 11 H), 7.02-6.97 (m, 2 H), 6.58 (s, J C,H ) 154.3 Hz, 1 H),
4.24 (d, J AB ) 14.59 Hz, 1 H), 4.16 (s, 2 H), 4.00 (d, J AB
)
14.59 Hz, 1 H), 2.12 (d, J AB ) 1.36 Hz, 3 H); 13C NMR (75
MHz, CDCl3) δ 141.65 (u), 138.63 (u), 136.49 (u), 134.41 (d),
132.80 (d), 129.29 (d), 129.23 (d), 128.36 (d), 128.31 (d), 128.26
(d), 127.56 (d), 126.99 (u), 126.96 (d), 126.49 (d), 60.14 (u), 47.24
(u), 24.55 (d); MS (EI) m/ z (relative intensity) 361 (M+, 0.69),
243 (12), 236 (11), 132 (12), 131 (100), 129 (11), 125 (12), 91
1
ent-34: [R]D -41.9 (c 2.44, THF); H NMR (300 MHz, CDCl3)
δ 7.30-7.14 (m, 5 H), 4.91-4.89 (m, 1 H), 4.83-4.80 (m, 1 H),
3.18 (t, J ) 7.6 Hz, 1 H), 1.87-1.65 (m, 2 H), 1.56 (s, 3 H),
1.38-1.10 (m, 4 H), 0.87 (t, J ) 7.09 Hz, 3 H); 13C NMR (75
MHz, CDCl3) δ 148.35 (u), 144.06 (u), 128.24 (d), 127.91 (d),
126.13 (d), 110.23 (u), 52.92 (d), 32.78 (u), 30.16 (u), 22.88 (u),

4390 J . Org. Chem., Vol. 61, No. 13, 1996
Scommoda et al.
21.00 (d), 14.15 (d); MS (EI) m/ z (relative intensity) 188 (M+,
11), 132 (43), 131 (100), 117 (19), 116 (13), 115 (16), 91 (55),
51 (11), 41 (23); HRMS calcd for C14H20 188.15650, found
188.15654.
Su bstitu tion of Su lfoxim in e 28: (+)-(R)-1-[1-(1-Meth -
yleth en yl)p en tyl]ben zen e (34). Substitution of 28 (362 mg,
1.00 mmol) with 32‚LiI in the presence of BF3·OEt2 in Et2O
as described for the substitution of the N-methylsulfoximine
10 gave, after a reaction time of 7 h, a 96:4 mixture of the
alkene 34 with an ee-value of 52% and the corresponding
R-substitution product (109 mg, 58%).
Ozon olysis of Alk en e en t-34: (-)-(S)-3-P h en yl-2-h ep -
ta n on e (41). Ozone was passed into a solution of alkene ent-
34 (153 mg, 0.81 mmol) in CH2Cl2 (30 mL) and MeOH (15 mL)
at -60 °C until the blue color of ozone persisted. After the
solution had been purged with argon, Me2S (6 mL) was added
at -50 °C, and the mixture was subsequently warmed to room
temperature. After the solution had been stirred for 3 h at
room temperature, it was concentrated in vacuum (20 Torr).
Purification of the residue by chromatography (20% EtOAc-
n-hexane) gave ketone 41 (152 mg, 97%) as a colorless liquid,
which had a purity of 99% according to GC and an ee-value of
91%: [R]D -275.3 (c 1.19, toluene); 1H NMR (300 MHz, CDCl3)
δ 7.35-7.14 (m, 5 H), 3.59 (t, J ) 7.42 Hz, 1 H), 2.04 (s, 3 H),
2.09-1.96 (m, 1 H), 1.75-1.62 (m, 1 H), 1.35-1.05 (m, 4 H),
0.85 (t, J ) 7.09 Hz, 3 H); 13C NMR (75 MHz, CDCl3) δ 208.61
(u), 139.22 (u), 128.90 (d), 128.28 (d), 127.21 (d), 59.86 (d), 31.58
(u), 29.71 (u), 29.06 (d), 22.69 (u), 13.97 (d); MS (EI) m/ z
(relative intensity) 190 (M+, 1), 147 (15), 134 (18), 105 (15),
91 (100), 43 (20).
Ack n ow led gm en t. This work has been supported
by the Deutsche Forschungsgemeinschaft (SFB 380). We
thank Dr. J . Runsink for the NOE experiments, and
Professor Dr. R. Woody for reading parts of the manu-
script and correcting our English.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and characterization data for compounds 3, 5, 6, 8, 9,
12-14, 17, 18, 23, 24, 26, 30, 31, 33, 35, 38-40, and 42-46
1
and copies of H NMR spectra of compounds 19, 20, 24, 33-
35, 38-41, and 43-46 (35 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O960027U