Cyclopropanation reactions of enones with lithiated sulfoximines: Application to the asymmetric synthesis of chiral cyclopropanes

Article abstract of DOI:10.1021/jo962216i

Stabilized lithiated sulfoximines 2 and 9 undergo highly diastereoselective Michael reactions with acyclic enones under kinetically controlled conditions. At rt the initially formed anionic Michael adducts undergo intramolecular displacement of the sulfonimidoyl group, with inversion of stereochemistry at the carbon bearing the nucleofuge, to give cyclopropanes. Lithiated sulfoximines derived from S-alkyl sulfoximines give mixtures of 1,2- and 1,4-adducts with enones mider kinetically controlled conditions. However, at rt the 1,2-adducts are in equilibrium with their corresponding 1,4-adducts. The 1,4-adducts are formed in a highly diastereoselective manner and are rapidly converted to diastereomerically pure cyclopropanes in good to excellent yields. Optically active versions of these sulfoximines give cyclopropanes in high enantiomeric purities.

Full text of DOI:10.1021/jo962216i

J . Org. Chem. 1997, 62, 2337-2343
2337
Cyclop r op a n a tion Rea ction s of En on es w ith Lith ia ted
Su lfoxim in es: Ap p lica tion to th e Asym m etr ic Syn th esis of Ch ir a l
Cyclop r op a n es
Stephen G. Pyne,*,† Zemin Dong,† Brian W. Skelton,‡ and Allan H. White‡
Department of Chemistry, University of Wollongong, Wollongong, New South Wales, 2522, Australia and
Department of Chemistry, University of Western Australia, Nedlands, Western Australia, 6009 Australia
Received November 26, 1996X
Stabilized lithiated sulfoximines 2 and 9 undergo highly diastereoselective Michael reactions with
acyclic enones under kinetically controlled conditions. At rt the initially formed anionic Michael
adducts undergo intramolecular displacement of the sulfonimidoyl group, with inversion of
stereochemistry at the carbon bearing the nucleofuge, to give cyclopropanes. Lithiated sulfoximines
derived from S-alkyl sulfoximines give mixtures of 1,2- and 1,4-adducts with enones under kinetically
controlled conditions. However, at rt the 1,2-adducts are in equilibrium with their corresponding
1,4-adducts. The 1,4-adducts are formed in a highly diastereoselective manner and are rapidly
converted to diastereomerically pure cyclopropanes in good to excellent yields. Optically active
versions of these sulfoximines give cyclopropanes in high enantiomeric purities.
Sch em e 1
In tr od u ction
We recently reported that enones undergo regio-
selective conjugate addition reactions with lithiated
N-tosyl-S-allyl-S-phenylsulfoximine at -78 °C to give
exclusively 1,4-R adducts.1 Cyclic enones gave mixtures
of diastereomeric 1,4-R adducts while the reactions that
involved acyclic enones were highly diastereoselective.2
Furthermore, we have demonstrated that the products
from the latter reactions can be converted, by further
highly diastereoselective reactions, to acyclic molecules
having three, well-defined stereogenic centers.3 With the
current interest in the asymmetric synthesis of cyclo-
propanes4 we became interested in developing the method
of J ohnson who first described the cyclopropanation of
chalcone using lithiated N-tosyl-S-alkyl-S-phenyl sulfox-
imines in 1973.5 In one example, an optically active (ee
49%) cyclopropane ((1S,2S) 2-phenylcyclopropyl phenyl
ketone) was prepared from the reaction of chalcone and
lithiated (R)-N-tosyl-S-methyl-S-phenylsulfoximine (ee
84%) at rt for 12 h. We report here a study of the
reactions of enones with lithiated S-allyl-, S-benzyl-, and
S-alkyl-N-tosylsulfoximines under kinetically controlled
conditions at -78 °C and under reversible conditions at
rt that give rise to cyclopropanes. Furthermore, the
stereochemistry and mechanism of these reactions is
described, and the application of this methodology to give
cyclopropanes in high enantiomeric purities is reported.
† University of Wollongong.
‡ University of Western Australia.
X Abstract published in Advance ACS Abstracts, April 1, 1997.
(1) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J . Chem. Soc.,
Chem. Commun. 1994, 751.
Resu lts a n d Discu ssion
S-Allyl- a n d S-Ben zyl-N-tosylsu lfoxim in es. Treat-
ment of a solution of racemic lithiated N-tosyl-S-allyl-S-
phenylsulfoximine (rac-2)1 at -78 °C with the acyclic
enones 1a -c (1.2 equiv) for 3 min gave, after quenching
at -78 °C with acetic acid, the racemic 1,4-R adducts
4a -c in modest to excellent yields (Scheme 1). The
product diastereoselection ranged from 90:10 to 94:6 as
(2) For previous studies on metalated allylic sulfoximines see: (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.; Gerlach, M.; Welcker, R. J . Am. Chem. Soc. 1996, 118,
4765 and references cited therein. (d) Hainz, R.; Gais, H. J .; Raabe, G.
Tetrahedron: Asymmetry 1996, 7, 2505 and references cited therein.
(3) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J . Chem. Soc.,
Chem. Commun. 1995, 445.
(4) For some recent examples see: Yeh, S.-M.; Huang, L. H.; Luh,
T.-Y. J . Org. Chem. 1996, 61, 3906. Doyle, M. P.; Peterson, C. S.;
Parker, D. L. Angew. Chem., Int. Ed. Engl. 1996, 35, 13349. Mash, E.
A.; Gregg, T. M.; Stahl, M. T. Walters, W. P. J . Org. Chem. 1996, 61,
2738 and references cited therein. Hanessian, S.; Andreotti, D.;
Gomtsyan, A. J . Am. Chem. Soc. 1995, 117, 10393. Pique, C.;
Fahndrich, B.; Pfaltz, A. Synlett 1995, 491. Charette, A. B.; Prescott,
S.; Brochu, C. J . Org. Chem. 1995, 60, 1081 and references cited
therein.
1
determined by H NMR analysis of the crude reaction
mixtures.6 The relative (3R*,4R*,SS*) stereochemistry
of 4a has been determined by X-ray structural analysis
and has been rationalized as occurring via the transition
(5) J ohnson, C. R.; Kirchhoff, R. A.; Reischer, R. J .; Katekar, G. F.
J . Am. Chem. Soc. 1973, 95, 4287.
(6) The stereochemistry of the minor diastereoisomers in Schemes
1, 5-7, and 10 and eq 1 have not been determined.
S0022-3263(96)02216-5 CCC: $14.00 © 1997 American Chemical Society

2338 J . Org. Chem., Vol. 62, No. 8, 1997
Pyne et al.
Sch em e 2
Sch em e 4
Sch em e 3
constants between H1, H2, and H3 in the 1H NMR
spectrum of 5b showed two trans couplings (J 1,2 ) J 2,3
)
6 Hz) and one cis coupling (J 1,3 ) 9.2 Hz).8 On the basis
of this information, and knowing the relative stereo-
chemistry of 4b, we assigned the absolute stereochemisty
of 5b as (1S,2R,3S). This stereochemisty is expected for
an intramolecular nucleophilic displacement reaction of
the sulfoximidoyl group from the intermediate 3b, with
inversion of stereochemistry at the carbon bearing the
sulfonimidoyl group (Scheme 4).
In contrast, the reactions of rac-2 with the cyclic enones
1d and 1e at -78 °C were poorly diastereoselective and
gave mixtures of the four possible diastereoisomers (eq
1). The major diastereoisomer 4d from these reaction of
rac-2 with 2-cyclopentenone had the relative
(3S*,1′R*,SS*) stereochemistry from a single crystal
state structure A in which the largest groups on the two
reacting partners (R2 and the sulfonimidoyl group) are
anti in order to minimize steric interactions (Scheme 2).1
Warming a solution of the anionic adducts 3a -c to rt
for 1 h gave the racemic vinylcyclopropanes 5a -c in good
yields (83-91% after column chromatography) and, in
the case of the cyclopropyl phenyl ketones 5a and 5c, in
lower diastereoselectivity than their respective Michael
adducts 4a and 4c (Scheme 1). In contrast, the diastereo-
selctivity observed for the cyclopropyl methyl ketone 5b
was essentially identical to that found in its related
Michael product 4b. Cyclopropane 5b was easily ob-
tained diastereomerically pure by column chromatogra-
phy. Enantiomerically enriched (1S,2R,3S)-5b was pre-
pared from the reaction of enantiomerically enriched (R)-
27 (prepared according to Scheme 3 from (S)-65 (ee 94%))
and 1b under identical reaction conditions and proce-
dures as described above. 1H NMR studies using the
chiral shift agent europium tris[3-[(heptafluoropropyl)-
hydroxymethylene]-(+)-camphorate] indicated that the
enantiomeric purity of 5b was 95% after correction for
the enantiomeric purity of (S)-2 (ee 94%). These studies
resulted in well-resolved separate signals for the methyl
ketone group of 5b for the two enantiomers of these
compounds in both racemic and optically active samples.
The stereochemistry of 5b was established by NMR
studies. NOE difference experiments on 5b showed a
1.2% enhancement of the signal due to H2 upon selective
irradiation of the alkene methine proton that established
their syn stereochemical relationship (Scheme 4). Fur-
thermore, an analysis of the proton vicinal coupling
X-ray analysis.1 The assignment of the same relative
stereochemistry to the major diastereoisomer of 4e,
however, is tenuous as this could not be unequivocally
determined. The reaction of rac-2 with (R)-carvone 1f,
intially at -78 °C followed by warming to rt for 1 h, gave
the vinylcyclopropane 5f in 72% yield and moderate
diastereoselectivity (dr ) 75:25).6 The stereochemistry
of the major diastereoisomer is that shown in structure
5f from 1H NMR studies. NOESY experiments on 5f
showed cross peaks between the allylic cyclopropyl proton
and the angular methyl group and the other cyclopropane
methine. The stereochemistry at C6 is that expected
from the known stereochemical outcome of nucleophilic
(8) J ackman, L. M.; Sternhell, S. In Applications of Nuclear Magnetic
Resonance Spectroscopy in Organic Chemistry, 2nd ed.; Pergamon:
Sydney, 1969; p 286.
(7) Upon deprotonation with BuLi, (S)-sulfoximines become (R)-
lithiated sulfoximines.

Cyclopropanation of Enones with Lithiated Sulfoximines
J . Org. Chem., Vol. 62, No. 8, 1997 2339
Sch em e 5
Sch em e 6
Sch em e 7
conjugate addition to 1f, that usually arises from addition
anti to the â′-2-propenyl group.9 The relative stereo-
chemistry at C1, C6, and C7 in 5f was that expected
based upon the stereochemical outcome of the reaction
of rac-2 with the achiral cyclic enone 1d and consistent
with our previously proposed chelated transition state1
for cyclic enones (compare with the transition state B (eq
2)).
(eq 2)
S-Alk yl-S-p h en yl-N-tosylsu lfoxim in es. The reac-
tion of optically active lithiated (S)-N-tosyl-S-methyl-S-
phenylsulfoximine ((R)-14 (ee 99%)5,7 with enone 1a at
-78 °C gave exclusively the 1,2-adduct 15 as a 58:42
diastereomeric mixture in quantitative yield (Scheme 7).
When this reaction was performed at rt the optically
active and diastereomerically pure cyclopropane 16a was
isolated in 88% yield (Scheme 7). The enantiomeric
Under conditions similar to those described above, the
reactions of lithiated racemic N-tosyl-S-benzyl-S-meth-
ylsulfoximine rac-9 and chalcone 1a gave the diastereo-
merically pure and racemic Michael adduct 10 at -78
°C and the diastereomerically pure cyclopropane 11 at
rt (Scheme 5). The relative (3R*,4R*,SS*) stereochem-
istry of 10 was established by X-ray diffraction (see
Supporting Information) and was identical to that ob-
tained from the reaction of 1a and rac-2, and consistent
with the transition state structure A (Scheme 2). The
purity of 16a ([R]27 -388° (c 0.05, acetone) was judged
D
to be 99% based on the reported specific rotation of
enantiomerically pure 16a (lit.5 [R]25 +390.5° (c 1.0,
D
acetone)). Treatment of 15 with LDA at -78 °C followed
by warming the reaction mixture to rt for 1 h gave the
diastereomerically pure cyclopropane 16a in 60% yield
(Scheme 8). Surprisingly, oxirane products, that could
potentially arise from nucleophilic displacement of the
sulfonimidoyl group by the alkoxide in 17,5 could not be
detected in the crude reaction mixture. This experiment
indicated that at rt the kinetically favored anionic 1,2-
adduct 15 is in equilibrium with the anionic 1,4-adduct
18 and that the latter undergoes intramolecular displace-
ment of the sulfonimidoyl group at a much faster rate
than the former anion that could give rise to an oxirane.
The reaction of rac-14 with enone 1c gave the cyclopro-
pane 16b in high diastereomeric purity (dr ) 98:2 from
GC analysis) in 95% yield. Treatment of (R)-carvone 1f
with rac-14 gave a mixture of the diastereomeric 1,2-
adducts 19 at -78 °C, the diastereomeric cyclopropanes
1
relative stereochemistry of 11 was evident from H NMR
spectroscopy and was that expected from an intramo-
lecular SN2 displacement reaction via the enolate anion
derived from 10. Not unexpectedly, the reaction of rac-9
and cyclohexenone gave a mixture of racemic and dia-
stereomeric Michael adducts 12 at -78 °C and a mixture
of racemic diastereomeric cyclopropanes 13 at rt. The
stereochemistry of the major diastereoisomer of 13 is that
shown in Scheme 6 from NOESY experiments that
showed cross peaks between the ortho aromatic protons
of the phenyl group and the three cyclopropane methines.
(9) Srikrishna, A.; J agadeeswar Reddy, T. J . Org. Chem. 1996, 61,
6422.

2340 J . Org. Chem., Vol. 62, No. 8, 1997
Pyne et al.
Sch em e 8
Sch em e 10
Sch em e 9
In conclusion, we have shown that stabilized lithiated
sulfoximines (2 and 9) undergo highly diastereoselective
Michael reactions with acyclic enones under kinetically
controlled conditions. At rt the initially formed anionic
Michael adducts undergo intramolecular displacement of
the sulfonimidoyl group, with inversion of stereochem-
istry at the carbon bearing the nucleofuge, to give
cyclopropanes. Lithiated sulfoximines derived from S-
alkyl sulfoximines give mixtures of 1,2- and 1,4-adducts
with enones under kinetically controlled conditions.
However, at rt the 1,2-adducts are in equilibrium with
their corresponding 1,4-adducts. The 1,4-adducts are
formed in a highly diastereoselective manner and are
rapidly converted to diastereomerically pure cyclopro-
panes in good to excellent yields. The absolute stereo-
chemistry of the Michael adducts has been unequivocally
determined from single crystal X-ray analysis and the
stereochemical outcomes of all these reactions is consist-
ent with the general transition state A (Scheme 2).
Optically active versions of these sulfoximines give
cyclopropanes in high enantiomeric purities.
20a ,b, and the double addition product 21 as a single
diastereoisomer at rt (Scheme 9). The diastereoselectiv-
ity in the case of 20 was similar to that obtained when
(R)-14 was employed. Compound 20 has been prepared
as a single diastereoisomer by Corey and Chaykovsky.10
Racemic and optically active (S)-N-tosyl-S-butyl-S-
phenylsulfoximine were prepared by alkylation of lithi-
ated rac-14 or (R)-145,7 (ee 97%) with bromopropane,
respectively. Treatment of lithiated racemic N-tosyl-S-
butyl-S-phenylsulfoximine (rac-22) with the acyclic enones
1a -c at -78 °C gave mixtures of 1,2 and 1,4-adducts
(Scheme 10). The latter were formed in high diastereo-
meric purities (dr ) 98-96:2-4) while the former were
formed as diastereoisomeric mixtures. The relative ster-
eochemistry of 23a was the same as that of 4a and 10 as
determined by X-ray diffraction.15 When these reactions
were performed at rt, the cyclopropanes 24a -c could be
isolated in high diastereomeric purities. Optically active
24a and 24c were obtained from the reaction of (R)-21
with 1a and 1c, respectively. The enantiomeric purity
Exp er im en ta l Section
General procedures were as described previously.11 All
NMR spectra were recorded in CDCl3 solution at 400 MHz (1H
NMR) or 100 MHz (13C NMR) unless otherwise noted. Pre-
parative HPLC was carried out using a Waters pump Model
510 and a Waters µ Porasil column (particle size 10 µm, pore
size 125, dimensions 25 mm × 100 mm). The UV detector was
a Waters Series 450 variable wavelength detector operating
at 254 nm. Full lists of spectral and characterization data are
included in the Supporting Information.
(S)-(+)-N-Tosyl-S-bu tyl-S-p h en ylsu lfoxim in e. To a so-
lution of (S)-(+)-N-tosyl-S-methyl-S-phenylsulfoximine5 (464
mg, 1.5 mmol, [R]23 +35, c 1.06, in acetone, 97% ee) in dry
1
of 24c was determined to be 98% from H NMR studies
D
THF (6 mL) at -78 °C was added n-BuLi (1.1 equiv, 1.4 mL,
1.2 M in hexane). The reaction mixture was stirred for 40 min
and was treated with bromopropane (0.3 mL, 2.2 mmol) at -78
°C. The solution was then warmed to rt and stirred overnight.
A saturated solution of aqueous NH4Cl (0.2 mL) was added
followed by water (15 mL), and the mixture was extracted with
CH2Cl2 (2 × 30 mL). The combined extracts were dried
(MgSO4) and evaporated, and the crude product was purified
using chiral shift reagents, while that of 24a could not
be determined in this manner. However the ee of 24a
was expected to be high based upon its diastereomeric
purity and the magnitude of its specific rotation when
compared to that of 24c.
(10) Corey, E. J .; Chaykovsky, M. J . Am. Chem. Soc. 1965, 87, 1353.

Cyclopropanation of Enones with Lithiated Sulfoximines
by column chromatography on silica gel. Elution with 25%
J . Org. Chem., Vol. 62, No. 8, 1997 2341
diastereoisomers. The yields given in the Experimental Sec-
tion refer to the diastereoisomeric mixture, unless otherwise
noted. The ratio of these diastereoisomers are given in the
schemes of Results and Discussion. In many cases the major
product was obtained diastereoisomerically pure by semi-
preparative HPLC using 0.2-0.5% ethyl acetate/hexane as
eluent.
(1S*,2R*,3S*)-(3-Eth en yl-2-p h en yl)cyclop r op yl p h en yl
k eton e (5a ): oil (206 mg, 83%); 1H NMR δ (major) 8.02-7.99
(2H, m), 7.58-7.55 (1H, m), 7.49-7.45 (2H, m), 7.32-7.30 (2H,
m), 7.24-7.20 (3H, m), 5.90 (1H, ddd, J ) 17.2, 10.4, 9.2 Hz),
5.28 (1H, ddd, J ) 17.2, 1.6, 0.8 Hz), 5.07 (1H, dd, J ) 10.0,
1.6 Hz), 3.26 (1H, dd, J ) 9.2, 5.6 Hz), 3.15 (1H, br t, J ) 6.0
Hz), 2.60 (1H, ddd, J ) 9.2, 9.2, 6.4 Hz); (minor) 8.07-8.05
(2H, m), 7.63-7.59 (1H, m), 7.54-7.50 (2H, m), 7.34-7.24 (5H,
m), 5.32 (1H, m), 5.31 (1H, dd, J ) 8.0, 0.8 Hz), 5.05 (1H, dd,
J ) 8.8, 3.6 Hz), 3.24 (1H, dd, J ) 9.2, 5.2 Hz), 3.22 (1H, s),
2.70-2.65 (1H, m); 13C NMR (75 MHz) δ (major) 196.3, 139.7,
138.3, 133.8, 132.9, 128.6, 128.1, 126.6, 126.4, 116.7, 37.4, 35.5,
32.4; (minor) 198.1, 137.7, 136.4, 134.6, 133.0, 129.1, 128.7,
128.4, 128.1, 126.8, 117.1, 35.8, 34.7, 31.8; MS (EI + ve): m/ z
248 (M+, 7%), 221 (10), 105 (100), 77 (50); HRMS: calcd for
C18H16O ) 248.120115; found 248.120846.
EtOAc/hexane gave the title compound (335 mg, 67%): [R]23
D
+95.5 (c 1.7, acetone); mp 96-97 °C; 1H NMR δ 7.98-7.96 (2H,
m), 7.85-7.83 (2H, m), 7.72-7.68 (1H, m), 7.62-7.58 (2H, m),
7.24 (2H, d, J ) 8.0 Hz), 3.55-3.38 (2H, m), 2.38 (3H, s), 1.68-
1.56 (2H, m), 1.34 (2H, dq, J ) 7.6, 7.2 Hz), 0.85 (3H, t, J )
7.2 Hz); MS (ES + ve): m/ z 352 (M + H+, 100%), 288 (10).
Anal. Calcd for C17H21NO3S2: C, 58.09; H, 6.02; N, 3.98.
Found: C, 57.89; H, 6.15; N, 3.84.
(S)-(+)-N-Tosyl-S-a llyl-S-p h en ylsu lfoxim in e [(S)-7] a n d
(S)-(+)-N-tosyl-S-(1-p r op en yl)-S-p h en ylsu lfoxim in e [(S)-
8]. To a solution of (S)-(+)-N-tosyl-S-methyl-S-phenylsulfox-
imine (0.72 g, 2.33 mmol) in anhydrous THF (11 mL) was
added n-BuLi (2.6 mL, 2.6 mmol, 1M in hexane) at -78 °C,
and the reaction was stirred for 40 min. Acetaldehyde (0.17
mL, 3.03 mmol) was added at -78 °C, and stirring was
continued for a further 30 min. A saturated solution of
aqueous NH4Cl (0.5 mL) was added at -78 °C and then water
(20 mL), and the mixture was extracted with CH2Cl2 (2 × 30
mL). The combined extracts were dried (MgSO4) and evapo-
rated, and the crude product was purified by column chroma-
tography on silica gel. Elution with 25% of EtOAc/hexane gave
the desired â-hydroxyl sulfoximine (556 mg, 68%). A solution
of this product (556 mg, 1.57 mmol) in CH2Cl2 (10 mL) was
cooled to 0 °C and treated with triethylamine (1.09 mL, 5
equiv) and then methanesulfonyl chloride (0.36 mL, 3 equiv).
The reaction was stirred for 3 h at 0 °C and was then treated
with DBU (1.4 mL, 6 equiv) at the same temperature. After
5 min, the reaction was warmed to rt and stirred overnight.
Ether (100 mL) was added, and the solution was washed with
water (30 mL), a saturated solution of aqueous NH4Cl (30 mL),
and a solution of 10% Na2CO3 (30 mL). The ether layer was
dried (MgSO4) and evaporated, and the crude product was
purified by column chromatography on silica gel. Elution with
25% EtOAc/hexane gave (S)-7 (130 mg) and (S)-8 (260 mg) in
a total yield of 74%. Spectral data of 7 and 8 were identical
to that of their respective racemic compounds.2b
(1S,4R,6S,7R)-1-Meth yl-4-(2-pr open yl)-7-eth en ylbicyclo-
[4.1.0]h ep ta n -2-on e (5f): oil (137 mg, 72%); 1H NMR (300
MHz) δ (major) 5.73 (1H, ddd, J ) 16.8, 10.2, 7.5 Hz), 5.26
(1H, br, dt, J ) 16.8, 1.5 Hz), 5.20 (1H, br. dt, J ) 10.2, 1.5
Hz), 4.84 (1H, q, J ) 1.2 Hz), 4.69 (1H, s), 2.62-2.54 (1H, m),
2.40 (1H, ddd, J ) 16.8, 6.3, 1.8 Hz), 2.22 (1H, dd, J ) 16.8,
4.8 Hz), 2.22-2.14 (1H, m), 1.96 (1H, ddd, J ) 14.7, 5.1, 3.6
Hz), 1.86 (1H, dt, J ) 7.8, 0.9 Hz), 1.75 (3H, t, J ) 0.9 Hz),
1.58 (1H, ddd, J ) 11.0, 9.0, 3.6 Hz), 1.26 (3H, s); (minor) 5.53
(1H, ddd, J ) 17.1, 10.2, 8.1 Hz), 5.21 (1H, ddd, J ) 17.1, 0.9
0.6 Hz), 5.13 (1H, ddd, J ) 10.2, 0.9, 0.6 Hz), 4.78 (1H, dt, J
) 0.9, 0.6 Hz), 4.73 (1H, s), 1.71 (3H, t, J ) 0.9 Hz), 1.21 (3H,
s); 13C NMR δ 210.4, 147.1, 132.3, 119.4, 110.9, 43.8, 40.8, 36.5,
32.4, 29.3, 23.7, 21.8, 21.5; MS (ES + ve): m/ z 191 (M + H+,
100%), 149 (80), 125 (40), 83 (50); HRMS: calcd for C13H18
O
N-Tosyl-S-ben zyl-S-m eth ylsu lfoxim in e. To a solution of
S-benzyl-S-methylsulfoximine12 (200 mg, 1.2 mmol) in pyridine
(3 mL) was added p-toluenesulfonyl chloride (228 mg, 1.2
mmol) in portion at 0 °C. The reaction mixture was then
warmed to rt and was stirred overnight. The mixture was
treated with water (20 mL) and extracted with dichloro-
methane (2 × 15 mL). The combined extracts were washed
with a solution of 10% HCl (2 × 10 mL) and water (2 × 10
mL), dried (MgSO4), and evaporated to give the title compound
) 190.13575; found 190.133841; [R]25 -229 (c 1.10, acetone).
D
2,3-Dip h en ylcyclop r op yl p h en yl k eton e (11): yield 143
mg (96%) of single diastereoisomer, reaction performed on 0.5
mmol scale; mp 142-144 °C (lit.11 148-149 °C); 1H NMR δ
7.97-7.94 (2H, m), 7.55-7.50 (1H, m), 7.46-7.41 (2H, m),
7.35-7.29 (4H, m), 7.28-7.16 (6H, m), 3.62 (1H, dd, J ) 6.8,
5.6 Hz), 3.38 (1H, dd, J ) 9.6, 5.6 Hz), 3.28 (1H, dd, J ) 9.6,
7.2 Hz); 13C NMR (75 MHz) δ 195.0, 140.0, 138.4, 135.5, 132.7,
129.1, 128.6, 128.5, 128.2, 128.1, 126.9, 126.7, 37.9, 36.5, 29.9;
MS (EI + ve): m/ z 298 (M+, 10%), 193 (65), 115 (45), 105 (100),
77 (40); HRMS: calcd for C14H18O ) 298.13575; found
298.135605. Anal. Calcd for C14H18O: C, 88.55; H, 6.08.
Found: C, 88.46; H, 6.04.
1
(370 mg, 97%): mp 109-110 °C (lit.14 128-129 °C); H NMR
(300 MHz) δ 7.86-7.83 (2H, m), 7.49-7.46 (2H, m), 7.44-7.40
(3H, m), 7.27-7.24 (2H, d, J ) 7.5 Hz), 4.78 (1H, d, J ) 14.1
Hz), 4.71 (1H, d, J ) 14.1 Hz), 3.04 (3H, s), 2.39 (3H, s).
P r ep a r a tion of Cyclop r op a n es: A Gen er a l Meth od . To
a solution of the sulfoximine (1 mmol) in dry THF (3 mL) was
added n-BuLi (1.2 equiv) at -78 °C, and the solution was
stirred at -78 °C under N2 for 40 min. The enone compound
(1.3 equiv) was added, and the solution was stirred for 10 min
at -78 °C. The reaction mixture was then warmed to rt,
stirred for a further 1 h, and then quenched by the addition
of a saturated solution of aqueous NH4Cl (0.2 mL). Water (15
mL) was added, and the mixture was extracted with CH2Cl2
(2 × 20 mL). The combined extracts were dried (MgSO4) and
evaporated, and the crude products were purified by column
chromatography on silica gel. Elution with EtOAc/hexane
(1R,6S,7R)-7-P h en ylbicyclo[4.1.0]h ep ta n -2-on e (13): oil
(67 mg (71%), reaction performed on 0.5 mmol scale); 1H NMR
(300 MHz) δ 7.30-7.25 (2H, m), 7.22-7.16 (1H, m, 7.09-7.06
(2H, m), 2.66 (1H, br t, J ) 4.5 Hz, 2.39 (1H, ddt, J ) 9.9, 5.1,
4.8 Hz), 2.19 (1H, dd, J ) 9.6, 3.5 Hz), 2.16-1.96 (4H, m),
1.84-1.77 (2H, m); 13C NMR (100 MHz) δ 206.6, 139.6, 128.5,
126.5, 126.0, 37.1, 36.9, 27.9, 26.8, 21.3, 18.7; MS (EI + ve):
m/ z 186 (M+, 45%), 130 (100), 115 (50), 77 (25); HRMS: calcd
for C13H14O ) 186.10445; found 186.104922.
(1S,2S)-2-P h en ylcyclopr opyl ph en yl keton e (16a): yield
143 mg (92%) of single diastereoisomer; mp 60-62 °C (lit.11
66-70 °C); 1H NMR δ 8.01-7.99 (2H, m), 7.56-7.54 (1H, m),
7.48-7.44 (2H, m), 7.34-731 (2H, m), 7.25-7.23 (1H, m),
7.20-7.18 (2H, m), 2.91 (1H, ddd, J ) 8.0, 5.2, 4.1 Hz), 2.71
(1H, ddd, J ) 9.2, 6.8, 4.0 Hz), 1.94 (1H, ddd, J ) 9.2, 5.2, 4.0
Hz), 1.57 (1H, ddd, J ) 8.0, 6.8, 4.0 Hz); 13C NMR (75 MHz) δ
198.5, 140.5, 137.7, 132.8, 128.6, 128.1, 126.6, 126.2, 29.9, 29.2,
19.1; MS (EI + ve): m/ z 222 (M+, 35%), 115 (25), 105 (100);
HRMS: calcd for C16H14O ) 222.10445; found 222.103776.
gave the desired cyclopropane, usually as
a mixture of
(11) Pyne, S. G.; Dong, Z.; Skelton, B. W.; White, A. H. J . Chem.
Soc., Perkin Trans. 1 1994, 2607.
(12) J ohnson, C. R.; Schroeck, C. W.; Shanklin, J . R. J . Am. Chem.
Soc. 1973, 95, 7424.
(13) J ohnson, C. R.; Kirchhoff, R. A.; Corkins, H. G. J . Org. Chem.
1974, 39, 2548.
(14) J ohnson, C. R.; Corkins, H. G. J . Org. Chem. 1978, 43, 4140.
(15) The author has deposited the atomic coordinates for the
structures 10 and 23a with the Cambridge Crystallography Data
Centre. These coordinates can be obtained, on request, from the
Director, Cambridge Crystallography Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, U.K.
[R]27 +388 (c 0.55, acetone).
D
(1S,4R,6S)-1-Meth yl-4-(2-pr open yl)bicyclo[4.1.0]h eptan -
2-on e (20): oil (69 mg (42%) of 20a and 20b); 1H NMR δ
(major (20a )) 4.76 (1H, t, J ) 1.2 Hz), 4.72 (1H, s), 2.48-2.25
(1H, m), 2.42 (1H, ddd, J ) 18.0, 5.2, 0.8 Hz), 2.17-1.96 (1H,

2342 J . Org. Chem., Vol. 62, No. 8, 1997
Pyne et al.
m), 2.02 (1H, dd, J ) 17.2, 6.0 Hz), 1.91-1.79 (1H, m), 1.70
(3H, s, 1.57 (1H, ddd, J ) 8.0, 5.6, 2.8 Hz), 1.37 (1H, dd, J )
5.6, 5.2 Hz), 1.23 (3H, s), 0.86 (1H, dd, J ) 8.0, 5.6 Hz); (minor)
4.88 (1H, s), 4.74 (1H, t, J ) 1.6 Hz), 1.72 (3H, s), 1.25 (3H, s),
0.99 (1H, d, J ) 6.8 Hz); 13C NMR (75 MHz) δ 210.1, 147.1,
110.1, 41.8, 36.7, 29.2, 27.0, 25.2, 20.5, 19.7, 17.6; MS (EI +
ve): m/ z 164 (M+, 95%), 149 (40), 96 (60), 68 (100), 41 (50);
HRMS: calcd for C11H16O ) 164.12010; found 164.120371.
7.41-7.31 (8H, m), 7.20-7.15 (4H, m), 7.13 (2H, d, J ) 8.0
Hz), 4.70-4.65 (2H, m), 3.38 (1H, dd, J ) 17.2, 9.6 Hz), 3.26
(1H, dd, J ) 17.2, 2.4 Hz), 2.81 (3H, s), 2.29 (3H, s); 13C NMR
(75 MHz) δ 196.6, 142.5, 140.8, 139.3, 136.7, 133.0, 130.7,
130.1, 129.5, 129.2, 129.1, 128.9, 128.7, 128.5, 127.8, 127.7,
126.5, 76.1, 43.1, 41.39, 41.35, 21.4; MS (ES + ve) m/ z 570
(M + K+, 30%), 554 (M + Na+, 50), 530 (M + H+, 30), 393
(20), 230 (100), 105 (70). Anal. Calcd for C30H29NO4S2: C,
67.72; H, 5.50; N, 2.64. Found: C, 67.18; H, 5.67; N, 2.31.
(1S,3S,4R,6S,1′R,2′S,5′R)-1-Meth yl-3-[2′-m eth yl-3′-oxo-
5′-(2-p r op en yl)cycloh exyl]-4-(2-p r op en yl)b icyclo[4.1.0]-
h ep ta n -2-on e (21): oil (78 mg (25%) of single diastereoisomer);
1H NMR δ 4.83-4.82 (2H, m), 4.77 (1H, t, J ) 1.2 Hz), 4.69
(1H, s), 2.52-2.35 (4H, m), 2.30-2.15 (3H, m), 1.99-1.95 (3H,
m), 1.71 (3H, s), 1.62-1.55 (1H, m), 1.50 (1H, dd, J ) 6.4, 6.4
Hz), 1.19 (3H, s), 1.18 (3H, d, J ) 9.2 Hz), 0.85 (1H, dd, J )
10.4, 6.4 Hz); 13C NMR (75 MHz) δ 212.4, 209.7, 147.7, 145.8,
113.2, 110.3, 47.0, 44.0, 42.0, 40.7, 39.8, 30.8, 30.2, 27.3, 25.6,
20.5, 20.1, 18.5, 16.7, 12.5; MS (EI + ve) m/z 314 (M+, 35%)
164 (75), 150 (100), 135 (80), 122 (100), 109 (70), 55 (80);
HRMS: calcd for C21H30O2 ) 314.22455; found 314.224875;
3-[S-P h en yl-(N-tosyl-S-m eth ylsu lfoxim id oyl)-1-cyclo-
1
h exa n on e (12): oil (171 mg, 82%); H NMR δ (major) 7.85
(2H, d, J ) 8.4 Hz), 7.46-7.41 (4H, m), 7.37-7.34 (1H, m),
7.31-7.29 (2H, m), 4.29 (1H, d, J ) 5.6 Hz), 3.06-2.84 (1H,
br), 2.99 (3H, s), 2.53-2.46 (1H, m), 2.44 (3H, s), 2.36-2.25
(1H, m), 2.18-2.03 (1H, m), 2.08 (1H, d, J ) 13.2 Hz), 2.00-
1.92 (2H, m), 1.64-1.44 (1H, m), 1.40-1.30 (1H, m); (minor)
4.40 (1H, d, J ) 7.2 Hz), 2.96 (3H, s); 13C NMR (75 MHz) δ
(major) 208.2, 143.0, 140.7, 130.42, 130.35, 129.8, 129.6, 129.4,
126.5, 74.8, 46.1, 42.2, 40.81, 38.1, 27.8, 24.3, 21.5; (minor)
208.6, 130.4, 130.2, 129.9, 75.1, 44.5, 42.3, 40.77, 38.4, 29.8,
29.7, 24.2; MS (ES + ve): m/ z 458 (M + K+, 20%), 442 (M +
Na+, 30), 437 (M + NH4+, 25), 420 (M + H+, 20), 234 (100),
187 (35).
[R]26 -46 (c 0.48, acetone).
D
(1S*,2R*,3S*)-2-P h en yl-3-pr opylcyclopr opyl ph en yl ke-
ton e (24a ): oil (236 mg, 90%); 1H NMR δ 8.03-8.00 (2H, m),
7.57-7.53 (1H, m), 7.48-7.45 (2H, m), 7.31-7.27 (2H, m), 7.21-
7.17 (3H, m), 3.00 (1H, dd, J ) 9.6, 5.2 Hz), 2.88 (1H, dd, J )
6.8, 5.2 Hz), 2.04-1.96 (1H, ddt, J ) 9.2, 7.2, 6.8 Hz), 1.71-
1.54 (2H, m), 1.43-1.26 (2H, m), 0.88 (3H, t, J ) 7.2 Hz);
(minor) 0.94 (3H, t, J ) 7.2 Hz); 13C NMR (75 MHz) δ 197.4,
141.0, 138.7, 132.6, 128.49, 128.46, 128.0, 126.4, 126.3, 34.9,
34.1, 32.3, 28.4, 22.7, 13.8; MS (EI + ve): m/ z 264 (M+, 15%),
221 (100), 115 (30), 105 (100), 77 (60); HRMS: calcd for
C19H20O ) 264.151415; found 264.151655; [R]23D +111.3 (c 1.01,
acetone).
P r ep a r a tion of 1,2-Ad d u cts a n d Mich a el Ad d u cts: A
Gen er a l Meth od . Lithiated sulfoximines 2, 9, 14, or 22 (0.5
mmol) were prepared by the general method described above.
The enone compound (0.65 mmol) was then added, and the
reaction mixture was stirred for 3 min (for 4a -c, 10, and 12)
or 30 min (for 15) or 1 h (for 23a -c) and then quenched by
the addition of a saturated solution of aqueous NH4Cl (0.2 mL)
at -78 °C. Water (15 mL) was added, and the mixture was
extracted with CH2Cl2 (2 × 20 mL). The combined extracts
were dried (MgSO4) and evaporated, and the crude products
were purified by column chromatography on silica gel using
EtOAc/hexane as eluent. The yields given in the Experimental
Section refer to the diastereoisomeric mixture, unless other-
wise noted.
2,4-Diph en yl-1-(N-tosyl-S-ph en ylsu lfoxim idoyl)-3-bu ten -
2-ol (15): oil (259 mg, 100%); 1H NMR δ (major) 7.95 (2H, d,
J ) 8.4 Hz), 7.72 (2H, d, J ) 8.4 Hz), 7.62 (1H, t, J ) 7.2 Hz),
7.50 (2H, t, J ) 8.0 Hz), 7.44-7.41 (2H, m,), 7.30-7.22 (6H,
m), 7.16-7.14 (2H, m), 6.97 (2H, d, J ) 8.0 Hz), 6.63 (1H, d,
J ) 16.0 Hz), 6.46 (1H, d, J ) 16 Hz), 5.25 (1H, s), 4.07 (1H,
d, J ) 14.8 Hz), 3.75 (1H, d, J ) 14.0 Hz), 2.22 (3H, s); (minor)
6.68 (1H, d, J ) 16.0 Hz), 6.38 (1H, d, J ) 16.0 Hz), 4.84 (1H,
s), 4.33 (1H, d, J ) 14.8 Hz), 3.96 (1H, dd, J ) 14.8, 2.0 Hz),
2.32 (3H, s); 13C NMR (75 MHz) δ (major) 143.2, 142.9, 140.2,
138.9, 136.2, 134.3, 130.9, 130.1, 129.7, 129.2, 128.7, 128.4,
128.2, 127.9, 127.8, 126.8, 126.5, 125.0, 75.4, 67.6, 21.4; (minor)
142.8, 141.9, 140.4, 138.5, 135.9, 133.9, 131.7, 129.8, 129.3,
129.1, 128.4, 128.3, 127.9, 127.5, 126.7, 126.5, 125.1, 75.5, 66.7,
21.4; MS (ES + ve) m/ z 540 (M + Na+, 15%), 518 (M + H+,
10), 500 (30), 296 (30), 262 (25), 142 (25), 90 (40), 74 (100).
(5R )-5-(2-P r op e n yl)-2-m e t h yl-1-[(N -t osyl-S -p h e n yl-
su lfoxim id oyl)m eth yl]-2-cycloh exen -1-ol (19): oil (193 mg,
1
84%); H NMR (300 MHz) δ (major) 8.03-8.00 (2H, m), 7.81
(2H, d, J ) 8.1 Hz), 7.71-7.66 (1H, m), 7.62-7.57 (2H, m),
7.23 (2H, dd, J ) 8.1, 0.6 Hz), 5.48 (1H, br), 4.71-4.69 (2H,
m), 4.03 (1H, d, J ) 14.4 Hz), 3.52 (1H, dd, J ) 14.4, 1.5 Hz),
3.15 (1H, s), 2.59 (1H, ddd, J ) 12.9, 1.2, 0.9 Hz), 2.45-2.35
(1H, m), 2.40 (3H, s), 2.17-2.06 (1H, m), 1.96-1.84 (1H, m),
1.67 (3H, s), 1.63 (1H, dd, J ) 12.9, 1.5 Hz), 1.59 (3H, dt, J )
1.5, 1.2 Hz); (minor) 8.02-8.00 (2H, m), 7.81 (2H, dt, J ) 8.4,
1.8 Hz), 7.72-7.67 (1H, m), 7.63-7.57 (2H, m), 7.25 (2H, dd,
J ) 7.8, 0.9 Hz), 5.45 (1H, br), 4.60 (1H, t, J ) 1.2 Hz), 4.51
(1H, s), 4.44 (1H, m), 3.88 (1H, dd, J ) 14.4, 1.5 Hz), 3.44 (1H,
d, J ) 14.4 Hz), 2.40 (3H, s), 2.36 (1H, ddd, J ) 12.9, 1.8, 1.8
Hz), 2.10-1.98 (2H, m), 1.92-1.80 (1H, m), 1.67 (3H, s), 1.58
(1H, dd, J ) 12.9, 1.5 Hz), 1.53 (3H, s); 13C NMR (75 MHz) δ
(major) 147.6, 142.8, 140.7, 140.0, 135.4, 134.1, 129.6, 129.5,
129.2, 127.9, 126.8, 126.5, 109.8, 74.4, 63.6, 39.4, 38.7, 30.8,
21.5, 20.3, 16.4; (minor) 147.4, 143.0, 140.5, 139.4, 136.1, 134.4,
129.8, 129.3, 127.9, 126.7, 125.9, 109.2, 74.1, 62.7, 39.1, 38.6,
30.6, 21.4, 20.2, 16.6; MS (EI + ve): m/ z 459 (M+, 10%), 316
(3R*,4R*,SS*)-1,3-Dip h en yl-4-(N-tosyl-S-p h en ylsu lfon -
im id oyl)-5-h exen -1-on e (4a ): yield 243 mg (90%); mp 131-
1
132 °C; H NMR δ (major) 7.92-7.04 (19H, m,), 5.89 (1H, dt,
J ) 17.2, 10.4 Hz), 5.34 (1H, dd, J ) 10.0, 0.8 Hz), 4.70 (1H,
d, J ) 16.8 Hz), 4.69 (1H, dt, J ) 11.6, 3.2 Hz), 3.92 (1H, dd,
J ) 10.8, 3.2 Hz), 3.62 (1H, dd, J ) 9.2, 3.2 Hz), 3.48 (1H, dd,
J ) 17.2, 11.2 Hz), 2.16 (1H, s); (minor) 5.37 (1H, dd, J ) 10,
0.8 Hz); 13C NMR δ (major) 196.4, 142.5, 141.0, 139.8, 136.63,
136.57, 134.2, 133.0, 129.3, 129.2, 129.1, 128.53, 128.49, 128.4,
128.3, 127.9, 127.3, 126.5,124.3,75.8, 39.3, 38.4, 21.3. MS (CI
+ ve) m/ z 544.2 (M + H+, 5%), 314 (15), 314 (15), 270 (50),
226 (50), 195 (65), 142 (40), 114 (85), 101 (100). Anal. Calcd
for C31H29NO4S2 C, 68.48; H, 5.38; N, 2.58. Found: C, 68.09;
H, 5.37; N, 2.46.
(20), 296 (90), 278 (100); HRMS: calcd for C24H29NO4S2
459.15376; found 459.152339.
)
3-[1′-(N-Tosyl-S-p h en ylsu lfon im id oyl)-2′-p r op en yl]-
cyclop en ta n on e (4d ): yield 181 mg (87%); mp 124-126 °C;
1H NMR δ (major) 7.98-7.23 (9H, m), 5.56 (1H, dt, J ) 16.4,
10.4 Hz), 5.41 (1H, dd, J ) 10.4, 1.0 Hz), 5.16 (1H, d, J ) 16.8
Hz), 4.08 (1H, dd, J ) 7.2, 7.2 Hz), 2.93, (1H, m), 2.56-1.55
(6H, m), 2.39 (3H, s); 13C NMR δ (major) 216, 142.8, 140.8,
135.5, 134.4, 129.24, 129.22, 127.7, 126.6, 125.6, 74.99, 43.3,
37.7, 35.3, 26.4, 21.5; MS (CI + ve) m/ z 418.2 (M + H+, 10%),
296 (100), 246 (15), 132.8 (50), 124.2 (100), 60.2 (40). Anal.
Calcd for C21H23NO4S2: C, 60.43; H, 5.52; N, 3.36. Found: C,
60.81; H, 5.68; N, 3.27.
1,3-Diph en yl-4-(N-tosyl-S-ph en ylsu lfoxim idoyl)h eptan -
1-on e (23a ): mp 178-180 °C; 1H NMR δ 7.96-7.94 (2H, m),
7.90-7.88 (2H, m), 7.79-7.77 (2H, m), 7.70-7.66 (1H, m), 7.60-
7.56 (3H, m), 7.46 (2H, t, J ) 7.6 Hz), 7.21-7.16 (3H, m), 7.13-
7.10 (2H, m), 7.07 (2H, d, J ) 7.6 Hz), 4.51 (1H, ddd, J ) 10.0,
3.2, 2.8 Hz), 3.79 (1H, dd, J ) 18.0, 4.0 Hz), 3.56 (1H, dd, J )
18.0, 6.4 Hz), 3.44 (1H, ddd, J ) 8.0, 5.2, 2.4 Hz), 2.21 (3H, s),
1.85-1.76 (1H, m), 1.72-1.64 (1H), 0.83-0.73 (2H, m), 0.64
(3H, t, J ) 7.2 Hz); (minor) 0.51 (3H, t, J ) 7.2 Hz); 13C NMR
(75 MHz) δ 197.2, 142.5, 141.1, 139.3, 137.6, 136.9, 134.2,
133.1, 129.6, 129.1, 128.9, 128.68, 128.61, 128.03, 128.01,
127.3, 126.6, 70.6, 38.8, 37.1, 25.8, 21.34, 21.30, 13.2; MS (ES
1,3,4-Tr ip h en yl-4-(N-t osyl-S-m et h ylsu lfoxim id oyl)-1-
bu ta n on e (10): yield 191 mg (72%); mp 130-132 °C; 1H NMR
δ 7.73-7.71 (2H, m), 7.66-7.64 (2H, m), 7.49-7.45 (1H, m),

Cyclopropanation of Enones with Lithiated Sulfoximines
J . Org. Chem., Vol. 62, No. 8, 1997 2343
+ ve): m/ z 598 (M + K+, 20%), 582 (M + Na+, 60), 560 (M +
H+, 20), 265 (100). Anal. Calcd for C32H33NO4S2: C, 68.67;
H, 5.95; N, 2.50. Found: C, 68.72; H, 5.86; N, 2.41.
19-21, 22a -c, and 23a -c plus the minor diastereomeric
products of 5a ,c, 15, and 19, and full lists of spectral and
characterization data (37 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of this journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
Ack n ow led gm en t. We thank the Australian Re-
search Council for financial support.
Su p p or tin g In for m a tion Ava ila ble: Copies of the 1H
NMR spectra for compounds 5a -c,f, 10, 11-13, 15, 16a ,b,
J O962216I