Asymmetric synthesis of cycloalkenyl and alkenyloxiranes from allylic sulfoximines and aldehydes and application to solid-phase synthesis

Article abstract of DOI:10.1002/ejoc.200300726

An asymmetric synthesis of cycloalkenyl and alkenyloxiranes from allylic sulfoximines and aldehydes is described. Lithiation and titanation of cyclic and acyclic allylic sulfoximines with chlorotris(diethylamino)titanium and subsequent treatment with aldehydes gave, as described previously, enantio-and diastereomerically pure, syn-configured, sulfoximine-substituted homoallylic alcohols. Treatment of the sulfoximine-substituted homoallylic alcohols with chloroethyl chloroformate resulted in a facile substitution of the sulfoximine group by a Cl atom, with formation of the corresponding alkenyl chlorohydrins. In the case of the cycloalkenyl derivatives the substitution proceeded with high diastereoselectivities with retention of configuration, while in the case of the alkenyl derivatives, medium diastereoselectivities with inversion of configuration were observed. While elimination reactions of the cycloalkenyl chlorohydrins gave the corresponding enantio- and diastereomerically pure cis-configured cycloalkenyloxiranes in good overall yields, the alkenyl chlorohydrins afforded mixtures of enantiomerically pure trans and cis isomers in which the trans isomers dominated. The solution-phase synthesis was extended to the solid phase by the synthesis of an enantiomerically pure, polymer-bound allylic sulfoximine and its conversion into an alkenyloxirane. The initial results proved that the concept of the utilization of the sulfoximine group as a traceless chiral linker is feasible and suggest that the solid-phase asymmetric synthesis of cycloalkenyloxiranes by this route should be possible. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300726

FULL PAPER
Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes From Allylic
Sulfoximines and Aldehydes and Application to Solid-Phase Synthesis
Hans-Joachim Gais,*[a] Gadamsetti S. Babu,[a] Markus Günter,[a] and Parthasarathi Das[a]
Keywords: Asymmetric synthesis / Chirality / Solid-phase synthesis / Substitution / Sulfoximine
An asymmetric synthesis of cycloalkenyl and alkenyloxir- reactions of the cycloalkenyl chlorohydrins gave the corres-
anes from allylic sulfoximines and aldehydes is described.
Lithiation and titanation of cyclic and acyclic allylic sulfoxim-
ines with chlorotris(diethylamino)titanium and subsequent
treatment with aldehydes gave, as described previously, en-
antio- and diastereomerically pure, syn-configured, sulfoxi-
mine-substituted homoallylic alcohols. Treatment of the sul-
ponding enantio- and diastereomerically pure cis-configured
cycloalkenyloxiranes in good overall yields, the alkenyl chlo-
rohydrins afforded mixtures of enantiomerically pure trans
and cis isomers in which the trans isomers dominated. The
solution-phase synthesis was extended to the solid phase by
the synthesis of an enantiomerically pure, polymer-bound al-
foximine-substituted homoallylic alcohols with chloroethyl lylic sulfoximine and its conversion into an alkenyloxirane.
chloroformate resulted in a facile substitution of the sulfoxim-
ine group by a Cl atom, with formation of the corresponding
The initial results proved that the concept of the utilization
of the sulfoximine group as a traceless chiral linker is feasible
alkenyl chlorohydrins. In the case of the cycloalkenyl deriv- and suggest that the solid-phase asymmetric synthesis of
atives the substitution proceeded with high diastereoselec-
tivities with retention of configuration, while in the case of
the alkenyl derivatives, medium diastereoselectivities with
inversion of configuration were observed. While elimination
cycloalkenyloxiranes by this route should be possible.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Chiral vinylic oxiranes are valuable intermediates in or-
ganic synthesis.[1,2] Their asymmetric synthesis has been ac-
complished by several methods, including the epoxidation
of allylic alcohols in combination with an oxidation and
olefination,[3] the epoxidation of dienes,[4] the chloroallyl-
ation of aldehydes in combination with an 1,2-elimin-
ation,[5,6] and reactions between S-ylides and aldehydes.[7]
Although some of these methods are very efficient for the
synthesis of alkenyloxiranes, they are all only poorly suited
for the attainment of cycloalkenyloxiranes of type I
(Scheme 1).[7c] We therefore developed an interest in the
asymmetric synthesis of both cycloalkenyl and alkenyloxir-
anes from aldehydes and allylic sulfoximines. We had pre-
viously shown that treatment of derivatives of the cyclic and
acyclic allylic sulfoximines IV, bearing a tris(diethylamino)-
titanium group at the α-position,[8Ϫ10] with aldehydes gives
the sulfoximine-substituted homoallylic alcohols III with
high regio- and diastereoselectivities.[9Ϫ11] It was speculated
that the sulfoximine group of the homoallylic alcohols III
might perhaps be stereoselectively replaceable by a Cl atom
with formation of the corresponding chlorohydrins II,
which upon base treatment should give the alkenyloxiranes
[a]
Institut für Organische Chemie der Rheinisch-Westfälischen
Technischen Hochschule (RWTH) Aachen,
Prof.-Pirlet-Str. 1, 52056 Aachen, Germany
gais@rwth-aachen.de
Scheme 1
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DOI: 10.1002/ejoc.200300726
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Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes
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I.[5,6] The feasibility of a Cl substitution of the sulfoximine seven-membered homoallylic alcohol 2c was obtained in
group had previously been shown in the case of S-alkylsul- good yield from the allylic sulfoximine 1b[15] and benzal-
foximines.[10b,12] A further stimulus for perusal of this route dehyde. NMR spectroscopic analysis of the crude reaction
was its potential for application to solid-phase synthesis. We product showed the hydroxyalkylation to be, as in all pre-
had previously described the synthesis of enantiomerically viously described cases, highly diastereoselective (Ն 95% de)
pure, N-polymer-bound S-methyl-S-phenylsulfoximine,[13]
a
and regioselective (Ն 98:2). To our delight, treatment of the
potential starting material for the synthesis of the polymer- sulfoximines 2aϪc with 1.2 to 1.3 equiv. of ClCO2CH-
bound allylic sulfoximines VI from aldehydes and ketones (Cl)Me at room temperature in CH2Cl2 for 1.5 h readily
by the additionϪeliminationϪisomerization route.[9] afforded the chlorohydrins 3aϪc, respectively, each in Ն
Hydroxyalkylation of the polymer-bound allylic sulfoxim- 98% de and in high yield. Substitution of the allylic sulfoxi-
ines VI followed by a Cl substitution of the polymer-bound mine group of 2aϪc occurred much more rapidly than in
homoallylic alcohols V might deliver the corresponding S-alkyl sulfoximines.[10,12] In addition to 3aϪc the sulfinam-
chlorohydrins II. If successful, the sulfoximine group would ide 4a was obtained in 92Ϫ94% yield (vide infra). The
function in this scheme as a chiral traceless linker, a concept chlorohydrins and the sulfinamide were separated by flash
of considerable interest.[14]
chromatography. Cyclization of the chlorohydrins 3aϪc
Here we describe a new method for the asymmetric syn- with DBU gave the enantio- and diastereomerically pure
thesis of cycloalkenyl and alkenyloxiranes from aldehydes cycloalkenyloxiranes 5aϪc, respectively, in high yields. The
and allylic sulfoximines and its extension to solid-phase oxiranes 5aϪc had cis configurations, as shown by the mag-
synthesis, a key step of which is facile Cl substitution of the nitudes of the vicinal coupling constants (3J ϭ 4.2Ϫ4.4 Hz)
allylic sulfoximine group.
in their 1H NMR spectra. Oxirane formation is expected to
occur with inversion of configuration.[5,6] The chlorohydrins
3aϪc thus had syn configurations and, remarkably, the sub-
stitution of the sulfoximine groups of 2aϪc by Cl atoms
had occurred with retention of configuration (vide infra).
Attempts to convert the homoallylic alcohols 2aϪc into the
oxiranes by methylation of the sulfoximine group with
Me3OBF4 followed by cyclization with DBU failed.[16,17]
Having recorded high selectivities in the synthesis of the
cycloalkenyloxiranes 5aϪc, we next investigated the pos-
sibility of an analogous synthesis of alkenyloxiranes from
acyclic allylic sulfoximines. Successive treatment of the E-
configured allylic sulfoximines 6a and 6b[18] with nBuLi and
ClTi(NEt2)3 gave the corresponding allylic titanium
complexes,[8Ϫ10] which upon treatment with benzaldehyde
afforded, as described previously, the enantio- and dia-
stereomerically pure syn-configured sulfoximine-substituted
homoallylic alcohols 7a and 7b, respectively, in good yields
(Scheme 3).[9] Substitution of the sulfoximine groups of 7a
and 7b upon treatment with ClCO2CH(Cl)Me proceeded
readily and gave, beside 4a, the chlorohydrins 8a and 8b,
respectively, as mixtures of anti and syn diastereomers in
ratios of 78:22 and 74:26, respectively, in high yields. Treat-
ment of the mixtures of chlorohydrins with DBU furnished
the oxiranes 9a and 9b, each as a mixture of trans and cis
isomers in ratios of 78:22 and 74:26, respectively, and in
high yields. The structures of the trans- and cis-configured
oxiranes 9a and 9b were assigned on the basis of the magni-
Results and Discussion
Solution-phase Synthesis
Successive lithiation and titanation of the six-membered
cyclic allylic sulfoximine 1a[15] with 1.1 equiv. of nBuLi and
1.2 equiv. of ClTi(NEt2)3 at Ϫ78 °C in diethyl ether af-
forded the corresponding allylic titanium complex, which
upon treatment with benzaldehyde and isobutyraldehyde at
Ϫ78 °C gave, as described previously, the diastereomerically
pure syn-configured sulfoximine-substituted homoallylic al-
cohols 2a and 2b, respectively, in medium to good yields
(Scheme 2).[9,10] Similarly, the new diastereomerically pure
1
tudes of the vicinal coupling constants in their H NMR
3
spectra, which amounted to J ϭ 1.9 Hz for the trans and
3J ϭ 4.3 Hz for the cis isomers.
In conclusion of the synthesis of the alkenyloxiranes from
the acyclic allylic sulfoximines, the conversion of the syn-
configured sulfoximine-substituted homoallylic alcohols
11a and 11b, with (Z)-configured double bonds, into the
corresponding alkenyloxiranes was investigated (Scheme 4).
This study was intended to probe the configurational sta-
bility of the double bond in the substitution of the sulfoxi-
mine group. The enantio- and diastereomerically pure
Scheme 2
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FULL PAPER
bonds. The substitution of the sulfoximine groups of 11a
and 11b had thus to a large extent been accompanied by
isomerization of the double bonds.
Solid-Phase Synthesis
The synthesis of the polymer-bound allylic sulfoximine
16 was accomplished by the additionϪeliminationϪ
isomerization route starting from the enantiomerically pure
polymer-bound, (S)-configured S-methyl-S-phenyl sulfoxi-
mine 13,[13] prepared as described previously from Merri-
field resin and sulfoximine 12 with a loading of 84% accord-
ing to CHN analysis (Scheme 5). Successive treatment of
Scheme 3
Scheme 4
homoallylic alcohols 11a and 11b[9,10] were synthesized in
good yields, as described previously, from the (Z)-config-
ured allylic sulfoximines 10a and 10b,[18] respectively, as
outlined in Scheme 4. Successive treatment of sulfoximines
11a and 11b with ClCO2CH(Cl)Me and DBU afforded the
alkenyloxiranes 9a (89%) and 9b (88%), but with (E)-config-
ured double bonds, each as a mixture of trans and cis iso-
1
mers in ratios of 75:25 and 80:20, respectively. H NMR
spectroscopy of the mixtures of trans-9a/cis-9a and trans-
9b/cis-9b showed the presence of an additional 11% and 7%
of the corresponding isomers with (Z)-configured double Scheme 5
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Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes
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resin 13 with nBuLi in THF and isovaleraldehyde furnished acyclic allylic sulfoximines 7a and 7b and the chloroformate
the polymer-bound alkoxide 14, which upon treatment with afforded the corresponding chlorohydrins predominantly
ClCO2Me and DBU afforded the polymer-bound vinylic with inversion of configuration. We had previously ob-
sulfoximine 15. The isomerization of 15 to the allylic sulfox- served that S-alkyl-N-methyl sulfoximines are also amen-
imine 16 was carried out with DBU in MeCN at reflux.
able to this type of Cl substitution, the mechanism of which
The loading of the resin 16 and the success of each step is not yet known. This substitution bears some resemblance
of the synthesis was determined by an off-bead analysis in- to the dealkylation of tertiary amines upon treatment with
volving the removal of the reaction products from the resin chloroformates, which gives the corresponding alkyl chlo-
through an oxidative hydrolysis of the sulfoximine group at rides and urethanes.[19] The first step seems to be acylation
the S-N bond by a method we have described recently.[13] of the sulfoximine groups of 2aϪc, 7a, and 7b at the N
Treatment of the resin Ϫ potentially containing 13, 14, and atom[10b,12,20] with formation of the aminosulfoxonium salts
15 as well as 16 Ϫ with m-chloroperbenzoic acid (MCPA) 24aϪc, 26a, and 26b, respectively (Scheme 6). The allylic
and 0.1 m aqueous HCl in THF at 40 °C afforded a mixture aminosulfoxonium groups of 24aϪc, 26a, and 26b would
of the sulfones 22ϩ23, 21, 20, and 19 in a ratio of 21:1.5:1:2 be expected to be excellent leaving groups.[21] Substitution
(1H NMR). The γ-hydroxy sulfone 23 was presumably of the allylic aminosulfoxonium salts by an SN1 mechanism
formed through epoxidation of the allylic sulfones 21 and with formation of the allylic carbenium ions 25aϪc, 27a,
22, followed by elimination of the corresponding epoxides. and 27b, respectively and the sulfinamide 4a thus seems to
In summary, the off-bead analysis showed the successful
anchoring of the allylic sulfoximine at the polymer in
good yield.
The lithiation, titanation, and hydroxyalkalytion of the
polymer-bound allylic sulfoximine 16 were carried out as
follows. Resin 16 was treated with nBuLi in THF at Ϫ78
°C and, after the mixture had warmed to room temperature,
the obtained resin Li-16 was titanated by addition of ClTi-
(NEt2)3 at Ϫ78 °C. The titanated resin Ti-16 was sub-
sequently treated with benzaldehyde to afford the polymer-
bound homoallylic alcohol 17 after workup. The cleavage
of the linker group of 17 was achieved through treatment
with ClCO2CH(Cl)Me in CH2Cl2 at room temperature, a
mixture of the chlorohydrins syn-8a and anti-8a being ob-
tained in a ratio of 2:1. HPLC analysis of the mixture of
the anti and syn chlorohydrins, with the aid of a mixture of
the enantiomerically pure compounds (HPLC) obtained by
solution-phase synthesis as references, showed the syn-con-
figured chlorohydrin syn-8a to be of 70% ee and the anti-
configured chlorohydrin anti-8a to be of Ն 53% ee (see Exp.
Sect.). Treatment of 16 with benzaldehyde after lithiation
and titanation had therefore given 17 with only 70% de at
the C atom bearing the hydroxy group. We had previously
observed that lithiated allylic sulfoximines react with alde-
hydes only with low diastereoselectivity at the α-position.
We therefore assume that the lower diastereoselectivity of
the formation of 17 is due to incomplete titanation of Li-
16 rather than to a lower diastereoselectivity of the
hydroxyalkylation of the polymer-bound, titanated allylic
sulfoximine. The chlorohydrins anti-8a and syn-8a were not
purified, but were treated with DBU, which gave a mixture
of the oxiranes trans-9a and cis-9a in a ratio of 2:1 in an
overall yield of 34% based on sulfoximine 12. Interestingly,
the Cl substitution of 17 had occurred with a different selec-
tivity than that of 7a.
Mechanistic Consideration of the Cl substitution of
Sulfoximines
The reactions between the cyclic allylic sulfoximines
2aϪc and ClCO2CH(Cl)Me proceeded with almost com-
plete retention of configuration, while those between the Scheme 6
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H.-J. Gais, G. S. Babu, M. Günter, P. Das
FULL PAPER
be very likely. Such a mechanism could explain the (Z)/(E) sulting chlorohydrin. The synthesis of the cyclic allylic sul-
isomerization that occurred in the case of the reactions of foximines is accomplished from commercially available en-
the (Z)-configured sulfoximine-substituted homoallylic al- antiomerically pure S-methyl-S-phenyl sulfoximine and the
cohols. To explain the stereochemistry of the substitution it cycloalkanone by a six-step sequence of transformations re-
is postulated: (1) that the cyclic allylic carbenium ions quiring the isolation and purification of only one intermedi-
25aϪc preferentially adopt the C(OH)ϪC(sp2)-confor- ate, N,S-dimethyl-S-phenyl sulfoximine.
A solid-phase
mation A, in which the hydroxy group is gauche to the H- asymmetric synthesis of cycloalkenyloxiranes by this route
atom at the C(sp2)-atom, and (2) the chloride ion attacks through the use of the sulfoximine group as a traceless chi-
with high selectivity from the Re face for steric reasons. The ral linker seems feasible. The asymmetric synthesis of alken-
conformation B of 25aϪc should be less preferred because yloxiranes by this route is also possible, but yields mixtures
of a destabilizing interaction between the hydroxy group of cis and trans isomers, in which the latter dominate. The
and the ring containing the double bond. In the case of the facile Cl substitution of the sulfoximine group with reten-
acyclic allylic cations 27a and 27b, an interpretation is more tion of configuration at the S atom and the recycling of the
difficult. One would have to propose that the chloride at- sulfinamide provide the basis for a full utilization of the
tacks 27a and 27b in the conformation depicted preferen- sulfoximine group as a chiral auxiliary.
tially from the Si face.
Recycling of the Chiral Auxiliary
Experimental Section
We had previously shown that treatment of (S)-config-
General Comments and Materials: All reactions were carried out
ured S-alkyl-N-methyl sulfoximines with ClCO2Me resulted
in the formation of the sulfinamide 4b with Ն 98% ee
(Scheme 7).[10b,12] Sulfinamide 4b was converted on treat-
ment with MeMgCl into the sulfoxide 28 of Ն 98% ee, the
conversion of which into the (S)-configured sulfoximine 12
of Ն 98% ee had already been described in the literature.[22]
Sulfoximine 12 is in turn the starting material for the syn-
thesis of allylic sulfoximines 1a, 1b, 6a, 6b, 10a, and 10b. In
order to examine whether 4a could also be used as starting
material for the synthesis of 12, the sulfinamide was treated
with MeMgCl, which gave sulfoxide 28 with 96% ee and in
85% yield. A similar experiment with the polymer-bound
sulfinamide 18 has not yet been carried out. However, re-
cycling of the chiral auxiliary from 18 by the route depicted
in Scheme 7 should be possible.
under argon in oven-dried glassware by use of Schlenk and syringe
[23]
techniques. ClTi(NEt2)3
of Ն 96% purity (1H NMR) was pre-
pared according to the literature. The allylic sulfoximine 1b[15] of
Ն 98% ee was synthesized from (S)-S-methyl-S-phenyl sulfoximine
and cycloheptanone according to the literature. Sulfoximine 12[24]
of Ն 99% ee was prepared as described previously. The sulfoximine-
substituted homoallylic alcohols 2a, 2b, 7a, and 7b were synthe-
sized according to the literature.[9] The polymer-bound sulfoximine
13[13] was prepared from sulfoximine 12 of Ն 98% ee and Merrifield
resin (PL-CMS resin, 1% cross-linked, 1.02 mmol/g, 35Ϫ75 µ m,
200Ϫ400 mesh) as described previously. Et2O and THF were dis-
tilled from sodium-lead/benzophenone. CH2Cl2 was distilled from
CaH2. Reagents were obtained from commercial sources and used
without further purification unless otherwise stated. nBuLi was
standardized by titration with diphenylacetic acid. Analytical thin-
layer chromatography (TLC) was performed with Merck pre-co-
ated TLC plates (silica gel 60 F254, layer thickness 0.2 mm). Gravity
column chromatography (denoted as chromatography) was per-
formed with E. Merck silica gel 60 (0.063Ϫ0.200 mm). Melting
points were determined with a Büchi 535 apparatus and are uncor-
rected. 1H and 13C NMR spectra were recorded with a Varian VXR
300, an Inova 400, or a Varian Unity 500 instrument. Chemical
shifts are reported relative to TMS (δ ϭ 0.00 ppm) as internal
standard. Splitting patterns in the 1H NMR spectra are designated
as s, singlet; d, doublet; dd, double doublet; t, triplet; q, quadruplet;
sept, septet; m, multiplet. Peaks in the 13C NMR spectra are de-
noted as "u" for carbon atoms with zero or two attached protons
or as "d" for carbon atoms with one or three attached protons,
as determined from the APT pulse sequence. Low-resolution mass
spectra were recorded with a Varian MAT 212 mass spectrometer
and secondary ion mass spectra were recorded with a Finnigan
MAT mass spectrometer. Optical rotations were measured with a
PerkinϪElmer Model 241 polarimeter at approximately 25 °C. El-
emental analyses were performed by the microanalytical laboratory
of the Institut für Organische Chemie.
Scheme 7
Conclusion
A highly selective asymmetric synthesis of cis-configured
cycloalkenyloxiranes, not hitherto efficiently accessible by
existing methods, has been developed. The three-step se-
quence consists of an allylation of an aldehyde with a cyclic
allylic sulfoximine bearing a tris(diethylamino)titanium
group, a Cl substitution of the sulfoximine group of the
(1R,2R)-2-(Cyclohept-1-enyl)-2-[(S)-N-methyl-S-phenylsulfon-
imidoyl]-1-phenylethanol (2c): nBuLi (3.12 mL, 5.0 mmol, 1.6 m
solution in hexane) was added at Ϫ78 °C to a solution of the cyclic
allylic sulfoximine 1b (1.20 g, 4.56 mmol) in Et2O (50 mL). After
the mixture had been stirred for 10 min at Ϫ78 °C, neat ClTi-
resulting homoallylic alcohol, and a cyclization of the re- (NEt2)3 (1.76 mL, 5.7 mmol) was added. The resulting mixture was
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Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes
FULL PAPER
stirred for 10 min at Ϫ78 °C, warmed to room temperature, and
stirred for 2 h. After the mixture had again been cooled to Ϫ78 °C,
benzaldehyde (869 mg, 8.2 mmol) was added dropwise. After the
3b (294 mg, 85%, Ն 98% de) and sulfinamide 4a (393 mg, 93%). [α ]D
ϭ Ϫ14.2 (c ϭ 0.30, CH2Cl2). 1H NMR (CDCl3, 400 MHz): δ ϭ
0.85 (d, J ϭ 6.8 Hz, 3 H), 0.95 (d, J ϭ 6.8 Hz, 3 H), 1.40Ϫ1.70 (m,
mixture had been stirred for 2 h at Ϫ78 °C, it was poured into 4 H), 1.75Ϫ1.90 (m, 4 H), 1.95Ϫ2.05 (m, 1 H), 2.10Ϫ2.20 (br. s, 1
aqueous (NH4)2CO3 solution and extracted with EtOAc. The com-
bined organic phases were dried (MgSO4) and concentrated in va-
cuo. Recrystallization from diethyl ether afforded 2c (1.17 g, 70%,
H), 3.55 (dd, J ϭ 8.2, J ϭ 3.3 Hz, 1 H), 4.35 (d, J ϭ 8.2 Hz, 1 H),
5.75 (m, 1 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 15.2 (d),
20.9 (d), 24.4 (u), 22.7 (u), 24.1 (u) 25.5 (u) 30.3 (d),74.3 (d), 76.9
Ն 98% de) as colorless crystals. M.p. 115Ϫ116 °C. [α ]D ϭ Ϫ21.4 (d), 128.5 (d), 135.3 (u) ppm. MS (CI, isobutane): m/z (%) ϭ 201
1
(c ϭ 1.00, CH2Cl2). H NMR (CDCl3,400 MHz): δ ϭ 0.90Ϫ1.06
(m, 4 H), 1.30Ϫ1.74 (m, 6 H), 2.70 (s, 3 H), 3.75 (m, 1 H), 5.46
[Mϩ Ϫ1] (2), 180 (4), 185 (9), 167 (35), 150 (33), 149 (100), 135
(14), 123 (22), 107 (14), 95 (19), 79 (11), 69 (19). IR (capillary): ν˜ ϭ
(br. d, J ϭ 9.7 Hz, 1 H), 7.48Ϫ7.72 (m, 5 H), 7.78Ϫ7.84 (m, 3 H) 3470 (m, br), 3043 (m), 2660 (s), 1730 (s), 1659 (s), 1465 (m), 1368
ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 21.1 (u), 24.3 (u), 28.2
(m), 1302 (s), 1270 (s), 1235 (m), 1173 (m), 1138 (m), 1061 (m), 971
(u), 28.5 (u), 28.6 (d), 28.7 (u), 71.9 (d), 72.4 (d), 125.9 (d), 126.0 (s), 920 (m), 891 (s), 848 (s), 817 (s), 778 (s), 715 (w) cmϪ1. HRMS
(d), 126.4 (d), 126.6 (d), 126.7 (d), 127.5 (d), 127.8 (d), 131.9 (d),
135.3 (u), 139.2 (u) ppm. MS (CI, isobutane): m/z (%) ϭ 370 (10)
[Mϩ ϩ1], 264 (44), 231 (10), 215 (43), 156 (100), 140 (13), 107 (19).
IR (capillary): ν˜ ϭ 3631 (s), 3460 (s, br), 3183 (w), 3056 (m), 3025
(s), 2962 (m), 2802 (w), 2802 (w), 2696 (S), 2475 (s), 2373 (s), 2344
(s), 2282 (s), 2160 (s), 2064 (s), 1985 (s), 1964 (s), 1918 (s), 1890 (s),
1809 (s), 1737 (s), 1702 (s), 1687 (s), 1605 (s), 1582 (s), 1545 (s),
1496 (s), 1170 (m), 896 (s), 856 (w), 822 (s) cmϪ1. C22H27NO2S
(369.52): calcd. C 71.51, H 7.36, N 3.79; found C 71.64, H 7.77,
N 3.65.
(EI, 70 eV) calcd. for C11H19ClO 202.112505; found 202.112443.
(1R,2R)-2-Chloro-2-(cyclohept-1-enyl)-1-phenylethanol (3c): Treat-
ment of 2c (525 mg, 1.42 mmol) with ClCO2CH(Cl)Me (0.18 mL,
1.70 mmol) as described in GP3 afforded the chlorohydrin 3c
(306 mg, 86%, Ն 98% de) and the sulfinamide 4a (341 mg, 92%).
[α]D ϭ Ϫ18.8 (c ϭ 1.00, CH2Cl2). 1H NMR (CDCl3, 400 MHz):
δ ϭ 1.30Ϫ1.45 (m, 3 H), 1.50Ϫ1.60 (m, 2 H), 1.8Ϫ2.0 (m, 3 H),
2.1Ϫ2.2 (m, 1 H), 2.30 (m, 1 H), 2.81 (br. s, 1 H), 4.58 (d, J ϭ
8.9 Hz, 1 H), 4.79 (d, J ϭ 8.9 Hz, 1 H), 5.65 (m, 1 H), 7.22Ϫ7.40
(m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 26.2 (u), 26.8
(u), 28.2 (u), 29.1 (u), 32.2 (u), 76.4 (d), 77.2 (d), 127.0 (d), 128.30
(d), 128.4 (d), 134.4 (d), 139.5 (u), 139.26 (u) ppm. MS (CI,
isobutane): m/z (%) ϭ 250 (1.5) [Mϩ], 232 (11), 155 (8), 144 (9),
141 (30), 129 (11), 108 (33), 107 (100), 105 (29), 91 (17), 79 (33),
77 (22). IR (capillary): ν˜ ϭ 3444 (s, br), 3020 (m), 2927 (w), 2853
(m), 1954 (s), 1882 (s),1703 (w), 1601 (s), 1493 (s), 1383 (s), 1318
General Procedure for the Substitution of Sulfoximine-Substituted
Homoallylic Alcohols (GP1): ClCO2CH(Cl)Me (1.3 mmol) was ad-
ded at room temperature to a solution of the sulfoximine-substi-
tuted homoallylic alcohol (1 mmol) in CH2Cl2 (10 mL). The pro-
gress of the reaction was monitored by TLC (EtOAc/n-hexane, 1:9).
After the mixture had been stirred at room temperature for 1.5 h,
it was concentrated in vacuo. Purification by flash chromatography
(EtOAc/n-hexane, 1:9) gave the alkenyl/cycloalkenyl chlorohydrin
and sulfinamide 4 as colorless oils.
(s), 1275 (s), 1147 (s), 1053 (m), 965 (s), 915 (s), 852 (s) cmϪ1
HRMS (EI, 70 eV) calcd. for C15H19ClO: 250.112421; found
250.112443.
.
General Procedure for the Elimination of Alkenyl/Cycloalkenyl
Chlorohydrins (GP2): DBU (1 mmol) was added at room tempera-
ture to a solution of chlorohydrin (1 mmol) in CH2Cl2 (10 mL).
The progress of the reaction was monitored by TLC (EtOAc/n-
hexane, 1:9). After the mixture had been stirred at room tempera-
ture for 1.5 h, CH2Cl2 was carefully evaporated under reduced
pressure (highly volatile compound!). Conventional workup fol-
lowed by purification by flash chromatography (EtOAc/n-hexane,
1:9) gave the alkenyloxirane as a colorless oil.
(2S,3R)-2-(Cyclohex-1-enyl)-3-phenyloxirane (5a): Treatment of 3a
(430 mg, 1.82 mmol) with DBU (0.29 mL, 2.00 mmol) as described
in GP2 afforded the oxirane 5a (342 mg, 94%, Ն 98% de). [α]D
ϭ
Ϫ14.0 (c ϭ 0.30, CH2Cl2). 1H NMR (CDCl3, 400 MHz): δ ϭ
1.20Ϫ1.34 (m, 4 H), 1.40Ϫ1.50 (m, 2 H), 1.65Ϫ2.00 (m, 2 H), 3.62
(m, 1 H), 4.12 (d, J ϭ 4.4 Hz, 1 H), 5.71 (m, 1 H), 7.20Ϫ7.25 (m,
5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 22.1 (u), 22.3 (u),
22.5 (u), 25.4 (u), 58.3 (d), 61.1 (d), 126.7 (d), 127.3(d), 127.5(d),
125.4 (d), 130.2 (u), 135.4 (u) ppm. MS (CI, isobutane): m/z (%) ϭ
201 (9) [Mϩ ϩ1], 200 (63) [Mϩ], 199 (100), 171 (72), 157(36), 143
(19), 129 (91), 105 (78), 91 (71). IR (capillary): ν˜ ϭ 3087 (m), 3061
(m), 3031 (m), 2859 (w), 2835 (w), 2673 (s), 1951 (s), 1885 (s), 1723
(m), 1671 (m), 1605 (m), 1585 (s), 1451 (w), 1410 (m), 1337 (m),
1315 (m), 1270 (m), 1251 (m), 1195 (m), 1137 (m), 1001 (m), 967
(m), 921 (w), 830 (m), 801 (m) cmϪ1. HRMS (EI, 70 eV) calcd. for
C14H16O 200.120047; found 200.120115.
(1R,2R)-2-Chloro-2-(cyclohex-1-enyl)-1-phenylethanol (3a): Treat-
ment of 2a (550 mg, 1.55 mmol) with ClCO2CH(Cl)Me (0.2 mL,
1.86 mmol) as described in GP2 afforded chlorohydrin 3a (322 mg,
88%, Ն 98% de) and sulfinamide 4 (380 mg, 94%). [α]D ϭ Ϫ10.8
1
(c ϭ 0.45, CH2Cl2). H NMR (CDCl3, 400 MHz): δ ϭ 1.34Ϫ1.54
(m, 4 H), 1.75Ϫ2.00 (m, 2 H), 2.05Ϫ2.15 (m, 2 H), 2.66 (br. s, 1
H), 4.51 (d, J ϭ 8.5 Hz, 1 H), 4.79 (d, J ϭ 8.5 Hz, 1 H), 5.52 (m,
1 H), 7.27Ϫ7.35 (m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ
21.8 (u), 22.2 (u), 24.5 (u), 25.0 (u), 75.3 (d), 76.2 (d), 126.6 (d),
128.0 (d), 128.1 (d), 129.0 (d), 133.7 (u), 139.3 (u) ppm. MS (CI,
isobutane): m/z (%) ϭ 236 [Mϩ] (11), 218 (66), 201(9), 183 (43),
159 (17), 141(100), 128(18), 115(31), 91 (35). IR (capillary): ν˜ ϭ
3450 (m, br), 3062 (m), 3031 (m), 2709 (s), 2667 (s), 1951 (s), 1884
(s),1767 (s), 1632 (s), 1600 (s), 1496 (m), 1372 (s), 1349 (m), 1324
(m), 1249 (m), 1190 (m), 1142 (m), 1085 (m), 1028 (m), 969 (w),
912 (s), 891 (s), 845 (s) cmϪ1. C14H17ClO (236.74): calcd. C 71.03,
H 7.24; found C 71.16, H 6.86.
(2S,3R)-2-(Cyclohex-1-enyl)-3-isopropyloxirane (5b): Treatment of
3b (420 mg, 2.08 mmol) with DBU (0.34 mL, 2.29 mmol) as de-
scribed in GP2 afforded the oxirane 5b (318 mg, 92%, Ն 98% de).
[α]D ϭ Ϫ43.4 (c ϭ 0.35, CH2Cl2). 1H NMR (CDCl3, 400 MHz):
δ ϭ 0.85 (d, J ϭ 6.6 Hz, 3 H), 1.05 (d, J ϭ 6.6 Hz, 3 H), 1.38Ϫ1.47
(m, 1 H), 1.50Ϫ1.70 (m, 4 H), 1.90Ϫ2.08 (m, 4 H), 2.68 (dd, J ϭ
4.1, J ϭ 9.0 Hz, 1 H), 3.29 (m, 1 H), 5.61 (m, 1 H) ppm. 13C NMR
(CDCl3, 100 MHz): δ ϭ 18.8 (d), 20.1 (d) 22.5 (u), 22.6 (u), 24.5
(u), 25.7 (d), 26.4 (u), 58.8 (d), 64.6 (d), 122.7 (d), 131.0 (u) ppm.
MS (CI, isobutane): m/z (%) ϭ 166 (45) [Mϩ], 150 (11), 149 (100),
113 (11), 71 (18), 70 (14), 57 (26), 55 (11). IR (capillary): ν˜ ؍ 2932
(1R,2R)-1-Chloro-1-(cyclohex-1-enyl)-3-methylbutan-2-ol
(3b):
Treatment of 2b (520 mg, 1.62 mmol) with ClCO2CH(Cl)Me (w), 2669 (s), 1729 (s), 1673 (s), 1462 (m), 1387 (s), 1364 (s), 1340
(0.21 mL, 1.94 mmol) as described in GP3 afforded chlorohydrin (s), 1252 (s), 1162 (s), 1136 (s), 1075 (s), 958 (m), 922 (m), 828 (s),
Eur. J. Org. Chem. 2004, 1464Ϫ1473
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1469

H.-J. Gais, G. S. Babu, M. Günter, P. Das
801 (s) cmϪ1. HRMS (EI, 70 eV) calcd. for C11H18O 166.135698; Compound anti-8b: 1H NMR (CDCl3, 400 MHz): δ ϭ 0.85Ϫ1.35
FULL PAPER
found 166.135765.
(m, 5 H), 1.48Ϫ1.72 (m, 5 H), 1.90Ϫ1.98 (m, 1 H), 2.84 (br. s, 1
H), 4.50Ϫ4.55 (m, 1 H), 4.90 (d, J ϭ 4.6 Hz, 1 H), 5.38Ϫ5.54 (m,
2 H), 7.28Ϫ7.36 (m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ
25.7 (u), 25.7 (u), 25.9 (u), 32.1 (u), 32.2 (u), 39.9 (d), 68.1 (d), 70.3
(d), 122.7 (d), 139.1 (u), 142.6 (d) ppm.
(2S,3R)-2-(Cyclohept-1-enyl)-3-phenyloxirane (5c): Treatment of 3c
(450 mg, 1.80 mmol) with DBU (0.29 mL, 1.98 mmol) as described
in GP2 afforded the oxirane 5c (347 mg, 90%, Ն 98% de). [α]D
Ϫ7.1 (c ϭ 1.80, CH2Cl2). 1H NMR (CDCl3, 400 MHz): δ ϭ
1.20Ϫ1.34 (m, 4 H), 1.40Ϫ1.55 (m, 4 H), 1.60Ϫ2.00 (m, 2 H), 3.67 (3R,2R)-
ϭ
and
(3R,2S)-2-(3-Methylbut-1-enyl)-3-phenyloxirane
(m, 1 H), 4.13 (d, J ϭ 4.2 Hz, 1 H), 5.88Ϫ5.93 (m, 1 H), 7.22Ϫ7.28
(trans-9a and cis-9a): Treatment of a mixture of anti-8a and syn-8a
(m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 25.7 (u), 26.7 (640 mg, 2.85 mmol) with DBU (0.43 mL, 2.85 mmol) as described
(u), 28.0 (u), 29.7 (u), 32.1 (u), 58.6 (d), 62.2 (d), 126.9 (d), 127.4 in GP2 afforded a mixture of the oxiranes trans-9a and cis-9a
(d), 127.5 (d), 129.8 (d), 135.2 (u), 135.6 (u) ppm. MS (CI,
isobutane): m/z (%) ϭ 215 (100) [Mϩ ϩ1], 214 [Mϩ] (27) 197 (34),
105 (27). IR (capillary): ν˜ ϭ 3030 (m), 2696 (s), 1946 (s), 1880 (m),
1730 (s), 1671 (s), 1605 (s), 1540 (s), 1495 (s), 1450 (w), 1407 (s),
1377 (s), 1274 (s), 1221 (s), 1193 (s), 1075 (s), 1027 (s), 966 (s), 899
(m), 860 (m) cmϪ1. C15H18O (214.30): calcd. C 84.07, H 8.47; found
C 84.28, H 8.27.
(504 mg, 94%) in a ratio of 78:22.
1
Compound cis-9a: H NMR (CDCl3,400 MHz): δ ϭ 0.88 (d, J ϭ
7.4 Hz, 3 H), 0.91 (d, J ϭ 6.9 Hz, 3 H), 2.21 (octd, J ϭ 6.6, J ϭ
1.1 Hz, 1 H), 3.64 (dd, J ϭ 4.1, J ϭ 8.5 Hz, 1 H), 4.20 (d, J ϭ
4.4 Hz, 1 H), 4.97 (ddd, J ϭ 8.5, J ϭ 15.4, J ϭ 1.1 Hz, 1 H), 5.94
(dd, J ϭ 6.9, J ϭ 15.4 Hz, 1 H), 7.25Ϫ7.37 (m, 5 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ ϭ 21.9 (d), 30.9 (d), 58.9 (d), 59.8 (d),
(1R,2S)- and (1R,2R)-2-Chloro-5-methyl-1-phenylhex-3-en-1-ol 120.2 (d), 126.3 (d), 127.1 (d), 127.9 (d), 135.29 (u), 146.5 (d) ppm.
(anti-8a and syn-8a): Treatment of 7a (650 mg, 1.89 mmol) with
Compounds cis-9a ؉ trans-9a: MS (CI, isobutane): m/z (%) ϭ 188
ClCO2CH(Cl)Me (0.26 mL, 2.46 mmol) as described in GP1 af-
forded a mixture of chlorohydrins anti-8a and syn-8a (377 mg, 89%)
(6) [Mϩ], 171 (16), 106 (10), 105 (100), 77 (34), 51 (12). IR (capil-
lary): ν˜ ϭ 3063 (s), 3031 (m), 2963 (w), 2872 (m), 1963 (s), 1884
in a ratio of 78:22 together with sulfinamide 4a (465 mg, 94%).
(s), 1692 (m), 1623 (s), 1598 (s), 1580 (s), 1495 (m), 1465 (m), 1386
1
Compound syn-8a: H NMR (CDCl3, 400 MHz): δ ϭ 0.80 (d, J ϭ (m), 1315 (s), 1179 (s), 1136 (s), 1106 (w), 1068 (w), 1009 (m), 969
6.7 Hz, 3 H), 0.86 (d, J ϭ 6.7 Hz, 3 H), 2.22Ϫ2.30 (m, 1 H),
2.32Ϫ2.40 (br. s, 1 H), 4.52 (dd, J ϭ 7.3, J ϭ 8.2 Hz, 1 H), 4.69
(d, J ϭ 7.3 Hz, 1 H), 5.36Ϫ5.46 (m, 2 H), 7.28Ϫ7.36 (m, 5 H) ppm.
13C NMR (CDCl3, 100 MHz): δ ϭ 21.6 (d), 21.7 (d), 30.6 (d), 70.0
(d), 77.6 (d), 123.6 (d), 139.2 (u), 142.9 (d) ppm.
(m), 894 (m), 842 (s), 760 (w) cmϪ1. C13H16O (188.27): calcd. C
82.93, H 8.57; found C 82.94, H 8.69.
Compound trans-9a: 1H NMR (CDCl3, 400 MHz): δ ϭ 1.01 (d, J ϭ
6.6 Hz, 3 H), 1.03 (d, J ϭ 6.6 Hz, 3 H), 2.32Ϫ2.41 (octd, J ϭ 6.9,
J ϭ 1.4 Hz, 1 H), 3.33 (dd, J ϭ 1.9, J ϭ 8.0 Hz, 1 H), 3.76 (d, J ϭ
2.2 Hz, 1 H), 5.26Ϫ5.30 (ddd, J ϭ 8.0, J ϭ 15.7, J ϭ 1.4 Hz, 1 H),
5.94Ϫ5.98 (dd, J ϭ 6.6, J ϭ 15.4 Hz, 1 H), 7.25Ϫ7.37 (m, 5 H)
Compounds syn-8a ؉ anti-8a: MS (CI, isobutene): m/z (%) ؍ 207
(23), 190 (14), 189 (100), 173 (10), 107 (13). IR (capillary): ν˜ ϭ
3425 (m, br), 3085 (s), 3062 (m), 3031 (m), 2929 (w), 2870 (w), 2386 ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 22.1 (d), 30.9 (d), 60.2
(s), 2286 (s), 1951 (s), 1882 (s), 1807 (s), 1663 (m), 1601 (s), 1546 (d), 63.3 (d), 124.0 (d), 125.5 (d), 127.1 (d), 127.9 (d), 137.40 (u),
(s), 1494 (m), 1454 (w), 1385 (m), 1366 (m), 1328 (m), 1232 (s), 144.2 (d) ppm.
1189 (m), 1054 (w), 1028 (w), 917 (s), 854 (m) cmϪ1
.
(3R,2R)- and (3R,2S)-2-(2-Cyclohexylvinyl)-3-phenyloxirane (trans-
9b and cis-9b): Treatment of a mixture of anti-8b and syn-8b
(450 mg, 1.7 mmol) with DBU (0.28 mL, 1.87 mmol) as described
Compound anti-8a: 1H NMR (CDCl3, 400 MHz): δ ϭ 0.90 (d, J ϭ
6.7 Hz, 3 H), 0.93 (d, J ϭ 6.7 Hz, 3 H), 2.22Ϫ2.30 (m, 1 H),
2.32Ϫ2.40 (br. s, 1 H), 4.50 (m, 1 H), 4.90 (d, J ϭ 4.7 Hz, 1 H), in GP2 afforded a mixture of oxiranes trans-9b and cis-8b (361 mg,
5.46Ϫ5.54 (m, 2 H), 7.25Ϫ7.35 (m, 5 H) ppm. 13C NMR (CDCl3, 93%) in a ratio of 74:26.
100 MHz): δ ϭ 21.8 (d), 31.1 (d), 68.1 (d), 77.1 (d), 122.4 (d), 139.3
Compound cis-9b: 1H NMR (CDCl3, 400 MHz): δ ϭ 0.90Ϫ1.30 (m,
5 H), 1.60Ϫ1.80 (m, 5 H), 3.64 (dd, J ϭ 4.4, J ϭ 8.8 Hz, 1 H), 4.20
(u), 143.6 (d) ppm.
(1R,2S)- and (1R,2R)-2-Chloro-4-cyclohexyl-1-phenylbut-3-en-1-ol (d, J ϭ 4.4 Hz, 1 H), 1.95Ϫ2.05 (m, 1 H), 4.97 (ddd, J ϭ 8.5, J ϭ
(anti-8b and syn-8b): Treatment of 7b (400 mg, 1.04 mmol) with
ClCO2CH(Cl)Me (0.26 mL, 2.46 mmol) as described in GP1 af-
forded a mixture of chlorohydrins anti-8b and syn-8b (249 mg, 90%)
in a ratio of 74:26 together with sulfinamide 4a (255 mg, 93%).
15.4, J ϭ 1.1 Hz, 1 H), 5.89 (dd, J ϭ 6.6, J ϭ 15.3 Hz, 1 H),
7.25Ϫ7.37 (m, 5 H,) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 26.2
(u), 26.5 (u), 29.7 (u), 32.7 (u), 32.8 (u), 41.1 (d), 60.6 (d), 63.7 (d),
120.9 (d), 145.5 (d), 125.8 (d), 128.7 (d), 128.3 (d), 135.7 (u) ppm.
Compound syn-8b: 1H NMR (CDCl3, 400 MHz): δ ϭ 0.85Ϫ1.35
Compounds cis-9b ؉ trans-9b: MS (CI, isobutane): m/z (%) ϭ 228
(m, 5 H), 1.48Ϫ1.72 (m, 5 H), 1.80Ϫ1.86 (m, 1 H), 2.55Ϫ2.59 (br. (5) [Mϩ], 145 (100), 144 (12), 146 (26), 127 (8), 117 (36), 105 (10),
s, 1 H), 4.50Ϫ4.55 (m, 1 H), 4.68 (d, J ϭ 7.6 Hz, 1 H), 5.38Ϫ5.54
91 (29), 77 (13), 55 (18). IR (capillary): ν˜ ؍ 3087 (s), 3063 (s), 2666
(s), 1948 (s), 1881 (s), 1807 (s), 1762 (s), 1691 (s), 1663 (s), 1604
(m, 2 H), 7.28Ϫ7.36 (m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz):
δ ϭ 25.6 (u), 25.7 (u), 25.9 (u), 32.1 (u), 32.2 (u), 40.1 (d), 68.1 (d), (m), 1542 (s), 1497 (m), 1449 (w), 1421 (s), 1374 (m), 1349 (s), 1255
70.3 (d), 123.9 (d), 139.1 (u), 141.9 (d) ppm.
(s), 1197 (s), 1152 (s), 1072 (s), 1027 (s), 966 (w), 916 (s), 878 (w),
849 (m) cmϪ1. HRMS (EI, 70 eV) calcd. for C16H20O 228.151504;
found 228.151415.
Compounds syn-8b ؉ anti-8b: MS (CI, isobutane): m/z (%) ϭ 264
(38) [Mϩ], 263 (14), 262 (100), 183 (8), 126 (14). IR (capillary): ν˜ ؍
3188 (m, br), 3028 (m), 2924 (w), 2853 (w), 2800 (m), 1656 (m),
1
Compound trans-9b: H NMR (CDCl3, 400 MHz): δ ϭ 0.90Ϫ1.30
1448 (w), 1384 (m), 1330 (m), 1235 (w), 1203 (m), 1177 (m), 1146 (m, 5 H), 1.55Ϫ1.80 (m, 5 H), 3.32 (dd, J ϭ 1.9, J ϭ 8.0 Hz, 1 H),
(w), 1107 (m), 1081 (w), 1049 (w), 997 (m), 913 (m), 865 (w), 851 3.76 (d, J ϭ 1.9 Hz, 1 H), 1.95Ϫ2.05 (m, 1 H), 5.28 (ddd, J ϭ 8.0,
(w) cmϪ1. C16H21ClO (264.79): calcd. C 72.58, H 7.99; found C
72.59, H 8.20.
J ϭ 15.6, J ϭ 1.4 Hz, 1 H), 5.90 (dd, J ϭ 6.6, J ϭ 15.3 Hz, 1 H),
7.25Ϫ7.37 (m, 5 H) ppm. 13C NMR (CDCl3, 100 MHz): δ ϭ 26.3
1470
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 1464Ϫ1473

Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes
FULL PAPER
(u), 26.4 (u), 30.1 (u), 32.8 (u), 32.9 (u), 40.8 (d), 59.4 (d), 60.3 (d),
120.9 (d), 143.3 (d), 126.7 (d), 127.8 (d), 127.7 (d), 137.6 (u) ppm.
(m), 1131 (m), 1068 (m), 1026 (m), 969 (m), 904 (m), 842 (m), 757
(s), 696 (s) cmϪ1
.
Synthesis of the Alkenyloxiranes trans-9a and cis-9a from 11a: Treat-
ment of 11a (400 mg, 1.04 mmol) with ClCO2CH(Cl)Me (1.32 mL,
1.25 mL) as described in GP1 afforded a mixture of chlorohydrins
anti-8a and syn-8a together with sulfinamide 4a (253 mg, 93%).
Treatment of the mixture of chlorohydrins with DBU (0.15 mL,
1 mmol) as described in GP2 afforded a mixture of trans-9a and
cis-9a (203 mg, 89%) in a ratio of 75:25, also containing 11% of
the corresponding Z isomers.
Off-Bead Analysis of Polymer-Bound Allylic Sulfoximine 16: m-
ClC6H4CO3H (1 g, 30% water, 4 mmol) and aqueous HCl (0.3 mL
of 0.1 m, 0.03 mmol) were added to a suspension of resin 16 (1 g)
in THF (15 mL). The mixture was then heated at 40 °C for 15 h
and then cooled to room temperature. After addition of aqueous
NaOH (50 mL of 1 m) to the mixture, the resin was filtered and
washed successively with water (5 ϫ 20 mL) and Et2O (5 ϫ 20 mL).
The aqueous layer was extracted with Et2O (3 ϫ 20 mL), and the
combined organic phases were dried (MgSO4). Concentration in
vacuo gave a mixture of sulfones 22ϩ23, 21, 20, and 19 (165 mg)
in a ratio of 21:1.5:1:2 (1H NMR). Chromatography of the mixture
(EtOAc/n-hexane, 4:1) afforded the pure sulfones.
Synthesis of the Alkenyloxiranes trans-9b and cis-9b from 11b: Treat-
ment of 11b (344 mg, 1.00 mmol) with ClCO2CH(Cl)Me (0.13 mL,
1.2 mmol) as described in GP1 afforded a mixture of chlorohydrins
syn-8b and anti-8b together with sulfinamide 4a (243 mg, 93%).
Treatment of the mixture of chlorohydrins with DBU (0.15 mL,
1 mmol) as described in GP2 afforded a mixture of the oxiranes
trans-9b and cis-9b (166 mg, 88%) in a ratio of 80:20, also contain-
ing 7% of the corresponding (Z) isomers.
4-Methyl-1-(phenylsulfonyl)pent-1-en-3-ol
(23):
1H
NMR
(400 MHz, CDCl3): δ ϭ 0.91 (d, J ϭ 6.9 Hz, 3 H), 0.95 (d, J ϭ
6.9 Hz, 3 H), 1.82 (br. S, 1 H), 1.87 (dsept, J ϭ 6.9, J ϭ 4.9 Hz, 1
H), 4.21 (m, 1 H), 6.62 (dd, J ϭ 14.8, J ϭ 1.9 Hz, 1 H), 7.01 (dd,
J ϭ 14.8, J ϭ 3.9 Hz, 1 H), 7.52Ϫ7.67 (m, 3 H), 7.87Ϫ7.97 (m, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 17.1 (d) 18.2 (d), 33.6
(d), 74.8 (d), 127.4 (d) 129.1 (d), 130.40 (d) 133.2 (d), 140.19 (u),
146.7 (d) ppm.
Sulfinamide (4a): [α]20 ϭ Ϫ69.4 (c ϭ 1.00, CH2Cl2). 1H NMR
D
(CDCl3, 400 MHz): δ ϭ 1.90 (d, J ϭ 6.0 Hz, 3 H), 2.70 (d, J ϭ
5.5 Hz, 3 H), 6.55Ϫ6.60 (m, 1 H), 7.25Ϫ7.37 (m, 5 H) ppm. 13C
NMR (CDCl3, 100 MHz): δ ϭ 25.2 (d), 25.3 (d), 83.5 (d) 124.9 (d),
129.2 (d), 131.95 (d), 141.71 (u) ppm. MS (CI, isobutane): m/z
(%) ϭ 261 [Mϩ] (2), 201 (3), 199 (40), 142 (22), 126 (10), 125 (100),
105 (12), 97 (21), 94 (25), 78 (12), 74 (10), 59 (11), 51 (16), 45 (18).
IR (capillary): ν˜ ؍ 3063 (m), 2940 (m), 1906 (w), 1949 (s), 1728 (s),
1726 (s), 1663 (s), 1495 (m), 1449 (m), 1371 (s), 1348 (s), 1260 (s),
(E)-(4-Methylpent-2-enylsulfonyl)benzene
(22):
1H
NMR
(400 MHz, CDCl3): δ ϭ 0.87 (d, J ϭ 6.6 Hz, 6 H), 2.23 (d, J ϭ
6.6 Hz, 1 H), 3.74 (d, J ϭ 6.3 Hz, 2 H), 5.32Ϫ5.45 (m, 2 H),
7.50Ϫ7.67 (m, 3 H), 7.83Ϫ7.94 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ ϭ 22.1 (d), 31.4 (d), 60.3 (u), 113.5 (d), 128.7
(d) 129.1 (d), 133.9 (d), 138.2 (u), 148.5 (d) ppm.
1196 (s), 1071 (s), 1027 (s), 967 (w), 916 (s), 879 (m), 843 (s) cmϪ1
.
HRMS (EI, 70 eV) calcd. for C10H12SClNO3 261.022674; found
261.022644.
(Z)-(4-Methylpent-2-enylsulfonyl)benzene
(21):
1H
NMR
(400 MHz, CDCl3): δ ϭ 0.71 (d, J ϭ 6.6 Hz, 6 H), 2.19Ϫ2.29 (m,
1 H), 3.87 (d, J ϭ 8.0 Hz, 2 H), 5.25Ϫ5.35 (m, 1 H), 5.52 (tt, J ϭ
10.7, J ϭ 1.1 Hz, 1 H), 7.50Ϫ7.59 (m, 2 H), 7.61Ϫ7.67 (m, 1 H),
7.87Ϫ7.92 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 22.2
(d), 26.8 (d), 55.2 (u), 112.5 (d), 128.3 (d) 128.8 (d), 133.4 (d), 138.3
(u) 146.1 (d) ppm.
Synthesis of Polymer-Bound Vinylic Sulfoximine 15: A suspension
of resin 13 (10.94 g of 0.78 mmol/g, 8.57 mmol) in dry THF
(140 mL) was stirred at room temperature for 30 min and then co-
oled to Ϫ78 °C. nBuLi (7.0 mL of 1.6 m in hexane, 11.2 mmol) was
added. After the mixture had been stirred at Ϫ78 °C for 30 min,
the cooling bath was removed for 15 min, the mixture was then
again cooled to Ϫ78 °C, and isovaleraldehyde (1.2 mL, 11.1 mmol)
was added dropwise. The mixture was stirred for 30 min at Ϫ78 °C
and then for 1.5 h at room temperature, and ClCO2Me (0.87 mL,
11.2 mmol) was subsequently added at Ϫ78 °C. After the mixture
had been stirred for 15 min at Ϫ78 °C, it was warmed to room
temperature and stirring at this temperature was continued for 1 h.
The mixture was then once more cooled to Ϫ78 °C, and DBU
(1.70 mL, 11.3 mmol) was added. The mixture was warmed to
room temperature over 15 h, and aqueous NH4Cl (30 mL) was ad-
ded. The resin was filtered and washed successively with water (3
ϫ 30 mL), EtOH (3 ϫ 30 mL), and CH2Cl2 (3 ϫ 30 mL). Drying
in vacuo gave resin 15 (11.10 g). IR (KBr): ν˜ ϭ 3081 (s), 3057 (s),
3024 (s), 2960 (s), 1944 (m), 1872 (m), 1804 (m), 1745 (s), 1678 (m),
1628 (m), 1601 (s), 1583 (m), 1510 (m), 1493 (s), 1442 (s), 1420 (s),
1368 (s), 1251 (s), 1126 (s), 1080 (s), 1021 (s), 972 (s), 937 (s), 906
(E)-(4-Methylpent-1-enylsulfonyl)benzene
(20):
1H
NMR
(400 MHz, CDCl3): δ ϭ 0.91 (d, J ϭ 6.9 Hz, 6 H), 1.72Ϫ1.84 (m,
1 H), 2.11 (m, 2 H), 6.32 (dm, J ϭ 15.1 Hz, 1 H), 6.98 (dt, J ϭ
15.1, J ϭ 7.4 Hz, 1 H), 7.50Ϫ7.62 (m, 3 H), 7.86Ϫ7.90 (m, 2 H)
ppm. 13C NMR (100 MHz, CDCl3): δ ϭ 22.2 (d), 27.6 (d), 40.47
(u), 127.3 (d) 129.0 (d), 131.0 (d) 133.2 (d), 140.5 (u), 145.9 (d)
ppm.
(Methylsulfonyl)benzene (19): 1H NMR (400 MHz, CDCl3): δ ϭ
3.06 (s, 3 H), 7.54Ϫ7.71 (m, 3 H), 7.90Ϫ7.98 (m, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ ϭ 44.6 (d), 127.4 (d) 129.5 (d), 133.8
(d), 140.6 (u) ppm.
Synthesis of Polymer-Bound Sulfoximine-Substituted Homoallylic
Alcohol 17: A suspension of resin 16 (6 g) in dry THF (80 mL) was
stirred for 30 min at room temperature and then cooled to Ϫ78 °C.
nBuLi (4.1 mL of 1.6 m in hexane, 6.6 mmol) was added dropwise.
The mixture was warmed to room temperature, then cooled to Ϫ78
°C, and ClTi(NEt2)3 (2.1 mL, 6.6 mmol) was added dropwise. The
(s), 840 (m), 815 (m) cmϪ1
.
Synthesis of Polymer-Bound Allylic Sulfoximine 16: Resin 15
(11.1 g) was suspended in dry CH3CN (70 mL), and DBU (2.5 mL,
16.7 mmol) was added. After the mixture had been stirred at 60 °C mixture was stirred for 15 min at Ϫ78 °C and then warmed to room
for 7 days, aqueous NH4Cl (30 mL) was added and the resin was
filtered and washed successively with water (3 ϫ 30 mL), EtOH (3
temperature. After the mixture had been stirred for 2 h at this tem-
perature, benzaldehyde (1.2 mL, 12.0 mmol) was added dropwise
ϫ 30 mL), and CH2Cl2 (3 ϫ 30 mL). Drying in vacuo afforded and stirring was continued for 3 h. Aqueous (NH4)2CO3 (100 mL)
resin 16 (10.2 g). IR (KBr): ν˜ ϭ 3081 (s), 3058 (m), 3024 (m), 2919 was then added and the mixture was stirred for 30 min. The resin
(s), 2848 (m), 1943 (m), 1870 (w), 1803 (w), 1748 (w), 1709 (w), was filtered and washed successively with aqueous (NH4)2CO3 (3
1662 (w), 1600 (m), 1492 (s), 1448 (s), 1364 (m), 1261 (m), 1217 ϫ 20 mL), water (3 ϫ 20 mL), EtOH (3 ϫ 20 mL), and CH2Cl2 (3
Eur. J. Org. Chem. 2004, 1464Ϫ1473
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1471

H.-J. Gais, G. S. Babu, M. Günter, P. Das
FULL PAPER
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ϫ 20 mL). Drying in vacuo gave resin 17 (6.79 g). IR (KBr): ν˜ ϭ
3651 (w), 3424 (m), 3081 (w), 3058 (w), 3023 (m), 2917 (s), 2848
(m), 1942 (w), 1870 (w), 1802 (w), 1655 (w), 1600 (s), 1543 (w),
1491 (s), 1448 (s), 1382 (w), 1364 (w), 1253 (w), 1202 (m), 1124
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K. G. Rasmussen, D. S.
(m), 1078 (m), 1025 (m), 967 (w), 906 (m) cmϪ1
.
[4d]
1995, 2009.
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Substitution of the Polymer-Bound Sulfoximine-Substituted Homoal-
lylic Alcohol 17: Resin 17 (5 g) was suspended in dry CH2Cl2
(50 mL), and ClCO2CH(Cl)Me (0.53 mL, 4.85 mmol) was added
dropwise. After the mixture had been stirred for 2.5 h at room tem-
perature, the resin was filtered and washed with CH2Cl2 (5 ϫ
20 mL). Concentration of the combined organic phases in vacuo
gave a crude mixture of syn-8a with 70% ee and anti-8a of Ն 53%
ee in a ratio of 2:1 (1H NMR). Chiracel-OD-H; n-hexane/iPrOH,
99:1 isocratic, flow 0.7 mL/min, 20 °C, tR [(1S,2S)-8a] ϭ 25.37 min,
tR [(1S,2R)-8a] ϭ 28.79 min, tR [(1R,2R)-8a] ϭ 32.79 min, tR
[(1R,2S)-8a] ϭ 49.41 min. Because of an overlap of the peaks of
(1S,2R)-8a and that of an impurity, no more accurate determi-
nation of the ee-value of anti-8a was possible.
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65, 2458.
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´
´
A. Solladie-Cavallo, L. Bouerat, M. Roje, Tetrahedron Lett.
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2.3:1 mixture of trans and cis isomers, the trans isomer having
an ee value of 90%, has been described.[7b]
`
The mixture of the crude chlorohydrins syn-8a and anti-8a was dis-
solved in dry CH2Cl2 (10 mL) and then treated with DBU (0.6 mL,
4.0 mmol), and the mixture was stirred for 2 h at room temperature.
Concentration in vacuo and purification by column chromatogra-
phy (silica gel, EtOAc/n-hexane, 1:9) gave a mixture of the oxiranes
cis-9a and trans-9a (232 mg, 34% overall yield based on 12) in a
ratio of 2:1.
[8]
[9]
P. Bruns, Ph.D. Thesis, RWTH Aachen 2003.
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[10b]
(S)-Methyl Phenyl Sulfoxide (28): MeMgCl (1.76 mL, 22wt% in
THF, 5.22 mmol) was added at Ϫ78 °C to a solution of 4a (681 mg
2.61 mmol) in THF (15 mL). After the mixture had been stirred
for 1 h, saturated aqueous NH4Cl was added and the aqueous
phase was extracted with EtOAc. The combined organic phases
were dried (MgSO4) and concentrated in vacuo. Purification by
chromatography (EtOAc/n-hexane, 4:1) afforded the sulfoxide 28
(310 mg, 85%) of 96% ee [GC, octakis(2,3-O-dipentyl-O-methyl)-
1996, 7, 2505.
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Support of this work by the Deutsche Forschungsgemeinschaft
(SFB, 380 "Asymmetric Synthesis With Chemical and Biological
Methods" and GK 440 "Methods in Asymmetric Synthesis") is
gratefully acknowledged. We thank Cornelia Vermeeren for the GC
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1472
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 1464Ϫ1473

Asymmetric Synthesis of Cycloalkenyl and Alkenyloxiranes
FULL PAPER
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Eur. J. Org. Chem. 2004, 1464Ϫ1473
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1473