Stereoselective Reaction of α-Sulfinyl Carbanion Derived from Chiral 2-(Trialkylsilyl)ethyl Sulfoxides: Evidence for a Novel Silicon - Oxygen Interaction

Article abstract of DOI:10.1021/jo9913560

Reactions of α-sulfinyl carbanions, derived from p-tolyl sulfoxides bearing various alkyl groups, with various electrophiles were examined. The reaction of α-sulfinyl carbanions, derived from the β-silylethyl sulfoxides, with ketones or trimethyl phosphate, gave the syn products with high stereoselectivity. Interaction between the silicon in the trialkylsilyl group and the carbonyl oxygen in nucleophiles was postulated to stabilize the transition state, leading preferably to the syn diastereisomers. This novel silicon-oxygen interaction was supported by an MO calculation study using the MOPAC 93/PM3 and the Gaussian 94 Beche3LYP/3-21+G* methods.

Full text of DOI:10.1021/jo9913560

J . Org. Chem. 2000, 65, 469-474
469
Ster eoselective Rea ction of r-Su lfin yl Ca r ba n ion Der ived fr om
Ch ir a l 2-(Tr ia lk ylsilyl)eth yl Su lfoxid es: Evid en ce for a Novel
Silicon -Oxygen In ter a ction
Shuichi Nakamura,† Hirofumi Takemoto,† Yoshio Ueno,† Takeshi Toru,*,†
Terumitsu Kakumoto,‡ and Tsuneo Hagiwara§
Department of Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Nagoya 466-8555, J apan,
Osaka Gas Co., Ltd., 6-19-9 Torishima, Konohana-ku, Osaka 554-0051, J apan, and Teijinseiki Co., Ltd.,
3-2-1 Sakato, Takatsu-ku, Kawasaki 213-0012, J apan
Received August 25, 1999
Reactions of R-sulfinyl carbanions, derived from p-tolyl sulfoxides bearing various alkyl groups,
with various electrophiles were examined. The reaction of R-sulfinyl carbanions, derived from the
â-silylethyl sulfoxides, with ketones or trimethyl phosphate, gave the syn products with high
stereoselectivity. Interaction between the silicon in the trialkylsilyl group and the carbonyl oxygen
in nucleophiles was postulated to stabilize the transition state, leading preferably to the syn
diastereisomers. This novel silicon-oxygen interaction was supported by an MO calculation study
using the MOPAC 93/PM3 and the Gaussian 94 Beche3LYP/3-21+G* methods.
In tr od u ction
with aldehydes proceeded with extremely high stereose-
lectivity on the face of the carbanion R to the sulfinyl
Asymmetric carbon-carbon bond formation induced by
chiral R-sulfinyl groups has been extensively studied, and
it is the subject of several excellent reviews.1 However,
this type of reaction often proceeds with low stereoselec-
tivity;2 e.g., the reaction of R-sulfinyl carbanions derived
from alkyl p-tolyl sulfoxides3 with aldehydes results in
the formation of all four possible diastereomeric adducts
with poor stereoselectivity.2g There are several isolated
examples of improved stereoselectivity such as the reac-
tion via lithium metal exchange,2c,3a,f and reactions of
sulfoxides bearing a sterically bulky group such as the
tert-butyl2a,3a or 1-naphthyl groups.4 However, no highly
stereoselective reactions of R-sulfinyl carbanions, gener-
ated from the generally used phenyl or p-tolyl sulfoxides,
have been reported.
group (Scheme 1).5
Sch em e 1
Recently, we reported that the reaction of R-sulfinyl
carbanions derived from â-(trimethylsilyl)ethyl sulfoxides
This reaction provides a convenient method for the
preparation of optically pure allylic alcohols via subse-
quent thermal elimination of the sulfinyl group or
concurrent elimination of the sulfinyl and silyl groups.
More recently, we communicated highly stereoselective
â-addition of the â-silyl-R-sulfinyl carbanion to R,â-
unsaturated carbonyl compounds as well as stereoselec-
tive intramolecular cyclizations.5b We now report, in
detail, the reactions of the R-sulfinyl carbanion, derived
from p-tolyl sulfoxides bearing various alkyl groups such
as â-(trialkylsilyl)ethyl, γ-(trimethylsilyl)propyl, propyl,
and 3,3-dimethylbutyl groups, with various electrophiles,
and we propose a novel silicon-oxygen interaction in the
transition state.
† Nagoya Institute of Technology.
‡ Osaka Gas Co., Ltd.
§ Teijinseiki Co., Ltd.
(1) For recent reviews, see: (a) Carren˜o, M. C. Chem. Rev. 1995,
95, 1717. (b) Walker, A. J . Tetrahedron: Asymmetry 1992, 3, 961. (c)
Solladie, G. Pure Appl. Chem. 1988, 60, 1699. (d) Solladie, G. Synthesis
1981, 185.
(2) (a) Casey, M.; Mukherjee, I.; Trabsa, H. Tetrahedron Lett. 1992,
33, 127. (b) Bravo, P.; Frigerio, M.; Resnati, G. J . Org. Chem. 1990,
55, 4216. (c) Demailly, G.; Greck, C.; Solladie, G. Tetrahedron Lett.
1984, 25, 4113. (d) Colombo, L.; Gennari, C.; Scolastico, C. J . Chem.
Soc., Perkin Trans. 1 1981, 1278. (e) Colombo, L.; Gennari, C.;
Scolastico, C. J . Chem. Soc., Chem. Commun. 1979, 591. (f) Kunieda,
N.; Kinoshita, M.; Nokami, J . Chem. Lett. 1977, 289. (g) Kingsbury,
C. A. J . Org. Chem. 1972, 37, 102 (h) Tsuchihashi, G.; Iriuchijima, S.;
Ishibashi, M. Tetrahedron Lett. 1972, 4605.
(3) (a) Pyne, S. G.; Boche, G. J . Org. Chem. 1989, 54, 2663. (b) Sato,
T.; Itoh, T.; Fujisawa, T. Tetrahedron Lett. 1987, 28, 5677. (c) Tanikaga,
R.; Hosoya, K.; Hazumasa, K.; Kaji, A. Tetrahedron Lett. 1987, 28,
3705. (d) Williams, D. R.; Phillips, J . G.; White, F. H.; Huffman, J . C.
Tetrahedron 1986, 42, 3003. (e) Cinquini, M.; Manfredi, A.; Molinari,
H.; Restelli, A. Tetrahedron 1985, 41, 4929. (f) Braun, M.; Hild, W.
Chem. Ber. 1984, 117, 413. (g) Annunziata, R.; Cinquini, M.; Cozzi,
F.; Montanari, F.; Restelli, A. J . Chem. Soc., Chem. Commun. 1983,
1138. (h) Williams, D. R.; Phillips, J . G.; Huffman, J . C. J . Org. Chem.
1981, 46, 4101 (i) Mioskowski, C.; Solladie, G. Tetrahedron 1980, 36,
227. (j) Mioskowski, C.; Solladie, G. J . Chem. Soc., Chem. Commun.
1977, 162.
Resu lts a n d Discu ssion
P r ep a r a tion of Su lfoxid es 1. The starting sulfoxides
1a , 1b, and 1f were prepared by alkylation of the
R-sulfinyl carbanions derived from the corresponding
chiral methyl p-tolyl sulfoxides with (iodomethyl)trialkyl-
silane as previously reported.5a Chiral propyl p-tolyl
(5) (a) Kusuda, S.; Ueno, Y.; Toru, T. Tetrahedron 1994, 50, 1045.
(b) Toru, T.; Nakamura, S.; Takemoto, H.; Ueno, Y. Synlett 1997, 449.
(4) Sakuraba, H.; Ushiki, S. Tetrahedron Lett. 1990, 31, 5349.
10.1021/jo9913560 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/29/1999

470 J . Org. Chem., Vol. 65, No. 2, 2000
Nakamura et al.
Ta ble 2. Sign ifica n t 1H NMR Ch em ica l Sh ifts for th e
Con figu r a tion a l Assign m en t of th e â-Hyd r oxy Su lfoxid es
product
Me
syn-2
anti-2
HR HO OH
no.
R
R′
HS
HO OH
2a SiMe3
2.57 7.41 2.00 3.02 7.71 5.71
2.66 1.83
2.32 7.47 2.63 2.75 7.70 5.71
2b SiMePh2
2c CH3
Me
Me
F igu r e 1.
2d CH3
2e CH2SiMe3 Me
-(CH2)5- 2.30 7.45 2.69 2.71 7.69 5.27
2.32 7.45 2.80 2.82 7.69 5.55
2f CH2SiMe3 -(CH2)5- 2.34 7.44 2.87 2.70 7.67 5.21
2g tBu
Me 2.68 7.50 2.37 2.95 7.69 5.43
Ta ble 1. Rea ction of Cer ta in â-Su bstitu ted Eth yl p-Tolyl
Su lfoxid es 1a -e w ith Aceton e a n d Cycloh exa n on e
silylethyl (1b), propyl (1c), 3-(trimethylsilyl)propyl (1d ),
and 3,3-dimethylbutyl groups (1e) were treated with 1.2
equiv of LDA in THF at -78 °C for 5 min to generate
the lithium carbanion, which was then reacted with
acetone or cyclohexanone at the same temperature for 5
min, giving the products syn-2 and anti-2 in high yields.
The diastereoselectivity was determined by the 1H NMR
spectra of the crude mixture. The reaction of the R-sulfi-
nyl carbanions, derived from 2-(trimethylsilyl)- and
2-(methyldiphenylsilyl)ethyl sulfoxides 1a and 1b, with
acetone proceeded with high stereoselectivity to give
products 2a and 2b in syn/anti ratios of 94:6 (Table 1,
entry 1) and >98:2 (Table 1, entry 2). On the other hand,
the reaction of the propyl sulfoxide 1c proceeded with
lower stereoselectivity, giving the products 2c and 2d
with both in syn/anti ratios of 88:12 with acetone and
with cyclohexanone (Table 1, entries 3 and 4). The
remarkable role of the â-silyl group on the stereoselection
of the R-sulfinyl carbanion was further verified by the
reaction of the 3-(trimethylsilyl)propyl sulfoxide 1d with
acetone or cyclohexanone, in which the products 2e and
2f were formed with considerably low stereoselectivity
(Table 1, entries 5 and 6). Furthermore, the 3,3-dimeth-
ylbutyl sulfoxide 1e, in which the trimethylsilyl group
in 1a was replaced with a tert-butyl group, showed
reversed stereoselectivity, resulting in the predominant
formation of the 1,2-anti compound. This fact suggests
that the high stereoselectivity in the reaction of 1a would
not result from the steric demands of the â-trimethylsilyl
group, but possibly be due to some electronic reasons.
All these results show that the â-silyl group plays a
crucial role in inducing high stereoselectivity on the
carbanion face.
substrate
yield
entry no.
R
R′2CO
Me2CO
1b SiMePh2 Me2CO
product (%) syn/antia
1
2
3
4
5
6
7
1a SiMe3
2a
2b
2c
2d
2e
2f
88
73
89
80
93
88
98
96:4
>98:2
88:12
88:12
73:27
84:16
33:67
1c CH3
1c CH3
1d CH2SiMe3 Me2CO
Me2CO
cyclohexanone
1d CH2SiMe3 cyclohexanone
1e tBu
Me2CO
2g
Determined by 1H NMR.
a
sulfoxide (1c), p-tolyl 3-(trimethylsilyl)propyl sulfoxide
(1d ), and p-tolyl 3,3-dimethylbutyl sulfoxide (1e) were
prepared on treatment of (-)-menthyl (S)-p-toluenesulfi-
nate with propylmagnesium bromide, 3-(trimethylsilyl)-
propylmagnesium chloride, and 3,3-dimethylbutylmag-
nesium bromide, respectively. The sulfoxides 1f and 1g
were prepared by treatment of (R)-tert-butyl methyl
sulfoxide or (S)-methyl 2,4,6-triisopropylphenyl sulfoxide6
with 1.1 equiv of LDA at -78 °C and subsequently with
(iodomethyl)trimethylsilane (Figure 1).
Rea ction of Su lfoxid es 1 w ith Keton es. We have
already reported that the R-sulfinyl carbanion, having a
trialkylsilyl group at the â-position, reacts with an
electrophile with high stereoselectivity at the R-position.5
It is noteworthy that the R-sulfinyl carbanion derived
from â-trialkylsilylethyl sulfoxides shows extremely high
stereoselection on the carbanion face. To clarify the
mechanism leading to the exceptionally high stereose-
lective reaction, we first studied the stereoselectivity in
the reaction of the R-sulfinyl carbanions bearing various
alkyl groups. The results obtained in the reaction of the
R-sulfinyl carbanion generated from several chiral sul-
foxides with ketones are summarized in Table 1.
The configurations of the products 2a -g were deter-
mined as follows. The relative stereochemistry of the
major product 2d was assigned to be 1,2-syn (see the
tentative numbering in Table 1) by the X-ray crystal
structure analysis. The absolute configuration of the
sulfinyl-substituted carbon of syn-2d was determined to
be S. The stereochemistry of the adduct syn-2b was
deduced by the X-ray crystal structure analysis of the
absolute configuration of the sulfone, which was prepared
by the m-CPBA oxidation of 2b. The stereochemistry of
other products 2a -c,e-g was assigned to be the same
as that of syn-2d by comparison of the difference in the
chemical shifts between the major and minor products
in the NMR spectra (Table 2).
(R)-p-Tolyl sulfoxides carrying various alkyl groups
such as 2-(trimethylsilyl)ethyl (1a ), 2-(methyldiphenyl)-
(6) 1g was prepared from diacetone D-gulucosyl 2,4,6-triisopropyl-
benzenesulfinate: Mase, N.; Watanabe, Y.; Ueno, Y.; Toru, T. J . Org.
Chem. 1997, 62, 7794. More recently, we reported an efficient method
for the preparation of sulfinates: Watanebe, Y.; Mase, N.; Tateyame,
M.; Toru, T. Tetrahedron: Asymmetry 1999, 10, 737.
1
In the H NMR spectra, the major products showed an
upfield shift in comparison with the minor adducts in

Evidence for a Novel Silicon-Oxygen Interaction
J . Org. Chem., Vol. 65, No. 2, 2000 471
Ta ble 3. Meth yla tion Rea ction of p-Tolyl Su lfoxid es
1a -e
Sch em e 2
substrate
methylating
agent
yield syn-3/
(%) anti-3a
entry no.
R
product
1
2
3
4
5
6
7
8
9
1a SiMe3
1a SiMe3
1b SiMePh2
1b SiMePh2
1c CH3
MeI
(MeO)3PO
MeI
(MeO)3PO
MeI
(MeO)3PO
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
91
94
92
69
57
64
83
80
84
68
50:50
96:4
51:49
94:6
triisopropylphenyl sulfoxides bearing a â-silylethyl group
1f and 1g were examined as the reaction having a bulky
group (Scheme 2).
54:46b
88:12b
61:39
83:17
28:72
19:81
1c CH3
1d CH2SiMe3 MeI
The reaction of alkyl tert-butyl sulfoxides with carbonyl
compounds is known to lead to the exclusive formation
of the 1,2-anti diastereomers.3a The reaction of sulfoxides
having a bulky substituted such as the tert-butyl group
is supposed to proceed through a boatlike transition state.
The stereochemical outcome in the reaction of 1f and 1g
is partly similar to those previously reported; the reaction
proceeded with predominant formation of the 1,2-anti
diastereomers, but not with complete 1,2-anti selectivity,
showing that the â-silyl group has some role to divert
the stereoselection favorably into 1,2-syn stereoselectiv-
ity. The problem is what kind of effects would be expected
for the silyl group to induce the 1,2-syn stereoselection.
The steric demands of the silyl group would not be so
important since 3,3-dimethylbutyl sulfoxide 1e did not
give the product with high stereoselectivity. We have to
take into account the stereoelectronic effect of the silyl
group. The diastereoselective deprotonation is unlikely,
since the carbanion R to the sulfinyl group is reported to
be sp2 or configurationally labile.8 In fact, we found that
the carbanion, derived from 1a and LDA, gave a diaster-
eomeric mixture of deuterated sulfoxides in a ratio of ca.
7:3 upon treatment with D2O or MeOD. Provided that
deuteration of the R-sulfinyl carbanion proceeded with
retention of configuration,7a,9 deprotonation of 1a would
form a mixture of the two diastereomeric R-sulfinyl
carbanions a n ion s 1 and 2 (Figure 2), giving the corre-
sponding syn and anti diastereomers, respectively, when
reacted with electrophiles. Nonetheless, â-silylethyl sul-
foxides 1a and 1b show great preference for the formation
of the syn diastereomer. These facts are in good accord
with the assumption that the R-sulfinyl carbanion should
be configurationally labile. In addition, it was confirmed
that no retroaldol reaction occurred in the present system
as follows: The R-sulfinyl carbanion prepared from 1a
was treated with hexanal at -78 °C and subsequently
with benzaldehyde (Scheme 3).
1d CH2SiMe3 (MeO)3PO
1e tBu
1e tBu
MeI
(MeO)3PO
10
a
b
Determined by 1H NMR. Determined by HPLC.
signals due to the ortho protons of the aromatic ring, the
methine protons R to the sulfinyl, and the hydroxy
protons.
Meth yla tion of Su lfoxid es 1. We next studied the
methylation reaction of carbanions derived from sulfox-
ides 1. The methylation was carried out with methyl
iodide or trimethyl phosphate. The reactions with methyl
iodide were performed at -78 °C in a manner similar to
the reaction with ketones, whereas the R-sulfinyl car-
banion was treated with trimethyl phosphate at 0 °C. The
results are summarized in Table 3.
The methylation of 1a -e with methyl iodide gave
products syn-3 and anti-3 with low stereoselectivity
(Table 3, entries 1, 3, 5, and 7). On the other hand, the
methylation with trimethyl phosphate proceeded with
high stereoselectivity in the reaction of sulfoxides 1a and
1b bearing a trimethylsilyl or methyldiphenylsilyl group
at the position â to the sulfinyl group (Table 3, entries 2
and 4). The reactions starting with other sulfoxides 1c
and 1d lowered the stereoselectivity (Table 3, entries 6
and 8) as in the reactions with ketones. The selectivity
was again reversed in the reaction of 3,3-dimethylbutyl
sulfoxide 1e (Table 3, entries 9 and 10). The configuration
of the major methylated products formed in the reaction
with trimethyl phosphate was tentatively assigned as 1,2-
syn by analogy with the stereochemical outcome obtained
above in the reactions with carbonyl compounds, since
it is known that the methylation of lithium carbanions
with trimethyl phosphate proceeds with chelation to
phosphate oxygen.7
P r op osed Rea ction Mech a n ism th r ou gh a Novel
Si-O In ter a ction . The results show that the silyl group
in p-tolyl 2-(trimethylsilyl)ethyl sulfoxide 1a or p-tolyl
2-(methyldiphenylsilyl)ethyl sulfoxide 1b has a signifi-
cant effect on the stereoselection of the R-carbanion face,
and the silyl group should be placed at the position â to
the sulfinyl to induce the high stereoselectivity. The
reactions of the lithium carbanions of tert-butyl and
As a result, the hexanal-reacted aldol product was
exclusively formed, indicating that no retroaldol reaction
occurred through the course of the reaction. In addition,
(8) (a) Chassaing, G.; Marquet, A. Tetrahedron 1978, 34, 1399. (b)
Lett, R.; Chassaing, G. Tetrahedron 1978, 34, 2705. (c) Marsch, M.;
Massa, W.; Harms, K.; Baum, G.; Boche, G. Angew. Chem., Int. Ed.
Engl. 1986, 25, 1011. (d) Boche, G. Angew. Chem., Int. Ed. Engl. 1989,
28, 277.
(9) (a) Yamamoto, Y.; Maruyama, K. J . Chem. Soc., Chem. Commun.
1980, 239. (b) Hoppe, D.; Carstens, A.; Kra¨mer, T. Angew. Chem., Int.
Ed. Engl. 1990, 24, 1424.
(7) (a) Biellmann, J . F.; Vicens, J . J . Tetrahedron Lett. 1978, 467.
(b) Chassaing, G.; Lett, P.; Marquet, A. Tetrahedron Lett. 1978, 471.

472 J . Org. Chem., Vol. 65, No. 2, 2000
Nakamura et al.
F igu r e 3. Calculation for anions 1 and 2 by PM3 and
Beche3LYP/3-21+G*.
F igu r e 2. Proposed transition state for 1a with carbonyl
compound.
Sch em e 3
treatment of a THF solution of 2a (syn/anti ) 96:4) with
1.5 equiv of LDA at -78 °C resulted in complete recovery
of 2a . The above results suggest that the stereoselective
outcome in the reaction of 1a should be kinetically
controlled. Provided that the reaction proceeds via a
chairlike transition state that has been postulated in the
reaction of R-sulfinyl carbanions,2d,3a the syn diastereomer
is formed via TS-1 (Figure 2), where TS-1 is assumed to
be much more stable than TS-2. We should propose that
the silicon of the trialkylsilyl group interacts with the
carbonyl or the sulfinyl oxygen in the transition state,
stabilizing TS-1.
We examined the calculations of energies of the
intermediates as well as the transition states to prove
the stereochemical course of the reactions with ketones.
The R-sulfinyl carbanion, generated from â-silylethyl
sulfoxides with LDA, would exist as an equilibrating
mixture of a n ion 1 and a n ion 2 which have four-
centered chelating structures.8a,10 Indeed, calculations for
the carbanions of the simplified methyl â-silylethyl
sulfoxide by both the Gaussian 94 Beche3LYP/3-21+G*11
and MOPAC93/PM3 methods12 showed only small energy
differences between the anions corresponding to a n ion
a
F igu r e 4. Geometry optimization of the product. The struc-
tures syn-c and anti-c were less stable and moved to syn-b and
anti-b, respectively, on optimization.
1 and a n ion 2, 0.056 and 0.502 kcal/mol, respectively,
as shown in Figure 3.
To gain more quantitative insight, the stabilities of the
lithiated products were estimated by the MO calculation.
The calculation with PM3 was carried out using the
reaction product of the simplified â-silylethyl sulfoxide
such as CH3SOCH2CH2SiH3 and CH2O. Calculations
were performed starting from two sets of three gauche
conformers from the syn and anti cyclic structures in
which the silylethyl groups are placed at the axial and
equatorial positions. The relative energies of the opti-
(11) (a) Gaussian 94, Revision E.2: Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman,
J . R.; Keith, T.; Petersson, G. A.; Montgomery, J . A.; Raghavachari,
K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.;
Cioslowski, J .; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.;
Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.;
Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.;
Defrees, D. J .; Baker, J .; Stewart, J . P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J . A. Gaussian, Inc., Pittsburgh, PA, 1995. (b) For the
Becke3LYP hybrid method, see: P. J . Stephens, F. J . Devlin, C. F.
Chabalowski, M. J . Frisch, J . Phys. Chem. 1994, 98, 11623.
(12) (a) Stewart, J . J . P. J . Comput. Chem. 1989, 10, 209. (b) For
the lithium parameter for PM3, see: Anders, E.; Koch, R.; Freunscht,
P. J . Comput. Chem. 1993, 14, 1301.
(10) (a) Boche, G. Angew. Chem., Int. Ed. Engl. 1989, 28, 277. (b)
Nakamura, K.; Higaki, M.; Adachi, S.; Oka, S.; Ohno, A. J . Org. Chem.
1987, 52, 1414. (c) Marsch, M.; Massa, W.; Harms, K.; Baum, G.; Boche,
G. Angew. Chem., Int. Ed. Engl. 1986, 25, 1011. (d) Wolf, S.; Lajohn,
L. A.; Weaver, D. F. Tetrahedron Lett. 1984, 27, 2863. (e) Biellmann,
J . F.; Vicens, J . J . Tetrahedron Lett. 1978, 467. (f) Biellmann, J . F.;
Vicens, J . J . Tetrahedron Lett. 1974, 2915.

Evidence for a Novel Silicon-Oxygen Interaction
J . Org. Chem., Vol. 65, No. 2, 2000 473
typical hypercoordinated silicon compounds, it shows a
certain but weak attracting interaction between the
silicon and the carbonyl oxygen. This is the first example
of the interaction in the transition state verified by MO
calculations, although there are reports in which Si-O
and Si-N interactions have seen assumed in the transi-
tion state.16 In general, the pentacoordinated silicons
have at least an electron-withdrawing atom or group such
as F, Cl, Br, OR, SiR3, or CF3.13c,17 A similar bicyclic
transition state involving Si-O interaction would also
be the one for the methylation of â-silyl-R-sulfinyl car-
banion with trimethyl phosphate to give the 1,2-syn
products with high stereoselectivity (Table 3). The meth-
ylation with iodomethane, on the other hand, showed low
stereoselectivity, because it does not proceed through the
cyclic transition state involving a silicon interaction.
We showed that an extremely high stereoselectivity in
the reaction of R-carbanions, derived from â-silylethyl
p-tolyl sulfoxides, with electrophiles is due to a novel
silicon-carbonyl oxygen interaction in the transition
state on the basis of the stereochemical results from the
reactions of several sulfoxide derivatives as well as the
MO calculations. Furthermore, readily accessible â-si-
lylethyl p-tolyl sulfoxides are synthetically useful as a
chiral vinyl anion equivalent. Extending the methodology
to other substrates and understanding further the mech-
anism of the reaction will be the focus of future work.
F igu r e 5. Transition-state calculation for the reaction of
â-silylsulfoxide.
mized structure obtained by calculations are depicted in
Figure 4. The calculation starting from the gauche
conformer in which the SiH3 group is directed toward the
lithium resulted in the most stable conformer syn-a, in
which the silicon possesses a trigonal bipyramidal struc-
ture.13 Calculations with Beche3LYP/3-21+G* gave simi-
lar results.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of Su lfoxid e.
(R)-P r op yl p-Tolyl Su lfoxid e (1c). A solution of propylmag-
nesium bromide, prepared from propyl iodide (0.925 mL, 10.2
mmol), magnesium (210.5 mg, 8.66 mg atom), and ether (8.5
mL), was slowly added to a solution of (-)-menthyl (S)-p-
toluenesulfinate (1.00 g, 3.39 mmol) in a mixture of anhydrous
ether (15 mL) and THF (7 mL) at temperature ranging from
0 to 10 °C. The mixture was stirred at room temperature for
25 min and then hydrolyzed with saturated aqueous NH4Cl
solution. The aqueous solution was extracted with CH2Cl2. The
combined organic extracts were washed with brine and dried
over Na2SO4. The solvent was removed under reduced pressure
to leave a residue that was purified by column chromatography
(silica gel, hexane/ethyl acetate ) 70:30) to give 1c (592 mg,
A similar result was also obtained by further optimiza-
tion of syn-a performed by MP2/6-31+G*. In the opti-
mized structure, the distance of Si-OA is 2.04 Å, which
is shorter than the sum (3.62 Å) of the van der Waals
radii of silicon and oxygen.14 The bond angles shown at
the bottom in Figure 4 indicate that the silicon has a
trigonal bipyramidal structure. These results strongly
suggest that the reaction proceeds via the transition state
including a silicon-carbonyl oxygen interaction. To con-
firm the mechanistic hypothesis, the transition state
optimization was carried out by PM3 for the reaction of
â-silylethyl sulfoxide. The transition structure was fully
optimized without any constraint and was characterized
by vibrational frequency calculations, leading to a transi-
tion state with a negative frequency. The results of the
calculations are shown in Figure 5 as energy differences
relative to the most stable transition state TS-1a .
The calculations showed that the six-membered transi-
tion structures bearing the silylmethyl group at the axial
position were more stable than the equatorial transition
structures. In the most stable transition state TS-1a , the
silicon atom comes closer to the carbonyl oxygen and is
situated at a distance of 3.54 Å from the carbonyl oxygen
atom.15 Although this distance is longer than that of
96%) as a colorless solid: [R]20 +201.0° (c 0.90, EtOH) (lit.18
D
[R]21 +202.0° (c 0.90, EtOH)).
D
(R)-p-Tolyl 3-(Tr im eth ylsilyl)p r op yl Su lfoxid e (1d ).
The reaction was carried out as described above using (-)-
menthyl (S)-p-toluenesulfinate (1.00 g, 3.40 mmol) and 3-(tri-
methylsilyl)propylmagnesium chloride, prepared from 1-chloro-
3-(trimethylsilyl)propane (1.75 mL, 10.2 mmol) and magnesium
(228 mg, 9.38 mg atom). Purification by column chromatog-
raphy (silica gel, hexane/ethyl acetate ) 80/20) afforded 1d
(858 mg, 99%): [R]24D +174.8 (c 0.32, acetone); 1H NMR δ 0.01
(s, 9H), 0.45-0.76 (m, 2H), 1.51-1.90 (m, 2H), 2.42 (s, 3H),
2.50-2.95 (m, 2H), 7.33 (d, 1H, J ) 8.3 Hz), 7.51 (d, 2H, J )
8.3 Hz); IR (KBr) 3045, 1300, 1245, 1080 cm-1; SIMS m/z (rel
intensity) 254 (M+, 20), 91 (100). Anal. Calcd for C13H22OSSi:
C, 61.36; H, 8.71. Found: C,61.10; H, 8.97.
(R)-3,3-Dim eth ylbu tyl p-Tolyl Su lfoxid e (1e). The reac-
tion was carried out as described above except using (-)-
(13) Unfortunately, we failed to detect isolated signals due to 29Si
in the NMR spectra of the mixture (-78 °C) prepared from 2a and
LDA or n-BuLi, probably because of the rapid conformational change.
For hypervalent silicates, see: (a) Sheldrick, W. S. Structural chemistry
of organic silicon compounds. In The chemistry of organic silicon
compounds; Patai, S., Rappoport, Z., Eds.; J ohn Wiley and Sons: 1989;
p 227. (b) Williams, E. A. NMR spectroscopy of organosilicon com-
pounds in the chemistry of organic silicon compounds; Patai, S.,
Rappoport, Z., Eds.; J ohn Wiley and Sons: 1989; p 511. (c) Chuit, C.;
Corriu, R. J . P.; Reye, C.; Toung, J . C. Chem. Rev. 1993, 93, 1371.
(14) Bondi, A. J . Phys. Chem. 1964, 68, 441.
(16) (a) Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J . Am.
Chem. Soc. 1989, 111, 393. (b) Kolomeitsev, A.; Bissky, G.; Lork, E.;
Movchun, V.; Rusanov, E.; Kirsch, P.; Ro¨schenthaler, G. Chem.
Commun. 1999, 1107.
(17) (a) Iio, H.; Fujii, A.; Ishii, M.; Tokoroyama, T. J . Chem. Soc.,
Chem. Commun. 1991, 1390. (b) Ahmed, A.; Bragg, R. A.; Clayden, J .;
Lai, L. W.; McCarthy, C.; Pink, J . H.; Westlund, N.; Yasin, S. A.
Tetrahedron 1998, 54, 13277.
(15) The transition structure could not be fully optimized by ab initio
calculation (Becke3LYP/3-21+G*).
(18) Bickart, P.; Carson, F. W.; J acobus, J .; Miller, E. G.; Mislow,
K. J . Am. Chem. Soc. 1968, 90, 4868.

474 J . Org. Chem., Vol. 65, No. 2, 2000
Nakamura et al.
menthyl (S)-p-toluenesulfinate (1.00 g, 3.40 mmol) and 3,3-
dimethylbutylmagnesium bromide, prepared from 1-bromo-
3,3-dimethylbutane (1.68 g, 10.2 mmol) and magnesium (220.0
mg, 9.05 mg atom). Purification by column chromatography
(silica gel, hexane/ethyl acetate ) 80/20) afforded 1e (687 mg,
layer was extracted with CH2Cl2, and the combined organic
extracts were washed with brine, dried over Na2SO4, filtered,
and concentrated under reduced pressure to give the crude
product, which was purified by column chromatography (silica
gel, dichloromethane/diethyl ether ) 90:10) to give syn-2a (45.5
mg, 82%) and anti-2a (3.7 mg, 6%). The syn-2a /anti-2a ratio
was determined to be 96:4 by the 1H NMR analysis of the crude
product. syn-2a : 1H NMR δ -0.33 (s, 9H), 0.63 (dd, 1H, J )
7.2, 16.6 Hz), 1.14 (dd, 1H, J ) 3.4, 16.6 Hz), 1.44 (s, 3H),
1.51 (s, 3H), 1.8-2.2 (br, 1H), 2.41 (s, 3H), 2.57 (dd, 1H, J )
3.4, 7.2 Hz), 7.32 (d, 2H, J ) 8.5 Hz), 7.41 (d, 2H, J ) 8.5 Hz);
13C NMR δ -1.2, 5.4, 21.3, 28.1, 28.8, 73.0, 73.4, 124.3, 129.8,
137.8, 140.8; IR (KBr) 3375, 1295, 1040 cm-1; SIMS m/z (rel
intensity) 298 (M+, 12), 69 (100). Anal. Calcd for C15H26O2SSi:
C, 60.35; H, 8.78. Found: C, 60.18; H, 8.73. anti-2a : 1H NMR
δ -0.35 (s, 9H), 0.30 (dd, 1H, J ) 3.0, 16.3 Hz), 0.55 (dd, 1H,
J ) 7.6, 16.3 Hz), 1.22 (s, 3H), 1.60 (s, 3H), 2.44 (s, 3H), 3.02
(dd, 1H, J ) 3.0, 7.6 Hz), 5.71 (d, 1H, J ) 0.8 Hz), 7.34 (d, 2H,
J ) 8.1 Hz), 7.71 (d, 2H, J ) 8.1 Hz); IR (neat) 3380, 1250,
1010 cm-1; SIMS m/z (rel intensity) 298 (M+, 11), 69 (100).
Anal. Calcd for C15H26O2SSi: C, 60.35; H, 8.78. Found: C,
60.16; H, 8.97.
Rep r esen ta tive P r oced u r e for th e Rea ction of Su lfox-
id es w ith Meth yl Iod id e. (2R)- a n d (2S)-2-[(R)-p-Tolyl-
su lfin yl]-1-(tr im eth ylsilyl)p r op a n e (syn -3a a n d a n ti-3a ).
The R-sulfinyl carbanion was prepared as described above
using 1a (38.7 mg, 0.161 mmol), diisopropylamine (0.030 mL,
0.213 mmol), n-butyllithium (1.44 mol L-1 in hexane, 0.135
mL, 0.194 mmol). To the resulting solution was added methyl
iodide (0.015 mL, 0.241 mmol) at -78 °C, and the mixture was
stirred for 15 min. Usual workup gave the crude product,
which was purified by column chromatography (silica gel,
hexane/ethyl acetate ) 80:20) to afford a mixture of syn-3 and
anti-3 (37.1 mg, 91%). The syn-3a /anti-3a ratio was deter-
mined to be 50:50 by the 1H NMR analysis of the crude
product.
90%): [R]21 +181.8 (c 0.33, acetone); 1H NMR δ 0.88 (s, 9H),
D
1.45-1.60 (m, 2H), 2.43 (s, 3H), 2.65-2.85 (m, 2H), 7.94 (d,
1H, J ) 7.4 Hz), 8.24 (d, 2H, J ) 7.4 Hz); IR(KBr) 3040, 1040
cm-1; SIMS m/z (rel intensity) 224 (M+,35), 209 (50), 91 (100).
Anal. Calcd for C13H20OS: C, 69.53; H, 8.99. Found: C, 69.32;
H, 9.25.
(R)-ter t-Bu tyl 2-(Tr im eth ylsilyl) Su lfoxid e (1f). To a
solution of diisopropylamine (0.090 mmol, 0.640 mmol) in THF
(2.0 mL) was added n-butyllithium (1.53 mol L-1 in hexane,
0.39 mL, 0.598 mmol) at 0 °C, and the mixture was stirred for
30 min. The mixture was then cooled to -78 °C, and a solution
of (R)-tert-butyl methyl sulfoxide (800 mg, 10.1 mmol) in THF
(4.0 mL) was added. After the mixture was stirred for 1 h at
the same temperature, (iodemethyl)trimethylsilane (2.16 g,
10.1 mmol) was added, and the temperature was allowed to
rise to ambient temperature over a period of 2 h. Saturated
aqueous NH4Cl was added under vigorous stirring, and the
aqueous solution was extracted with CH2Cl2. The combined
organic extracts were washed with brine and dried over
Na2SO4. The solvent was removed under reduced pressure to
leave a residue that was purified by column chromatography
(silica gel, hexane/ethyl acetate ) 60:40) to give 1f (1.17 g,
85%): [R]19 -123.0 (c 0.66, acetone); 1H NMR δ 0.06 (s, 3H),
D
0.78 (ddd, 1H, J ) 6.0, 12.6, 14.2 Hz), 1.21 (ddd, 1H, J ) 5.6,
12.6, 14.2 Hz), 1.25 (s, 9H), 2.37 (ddd, 1H, J ) 5.6, 12.6, 12.6
Hz), 2.47 (ddd, 1H, J ) 6.0, 12.6, 12.6 Hz); IR (neat) 1030 cm-1
;
MS (EI) m/z (rel intensity) 206 (M+, 77), 101 (59). Anal. Calcd
for C9H22OSSi: C, 52.37; H, 10.74. Found: C, 52.39; H, 10.54.
(S)-2,4,6-Tr iisopr opylph en yl 2-(Tr im eth ylsilyl)eth yl Su l-
foxid e (1g). To a solution of diisopropylamine (0.090 mmol,
0.640 mmol) in THF (0.60 mL) was added n-butyllithium (1.53
mol L-1 in hexane, 0.39 mL, 0.598 mmol) at 0 °C, and the
mixture was stirred for 30 min. The mixture was then cooled
to -78 °C, and a solution of (S)-methyl 2,4,6-triisopropylphenyl
sulfoxide (106.5 mg, 0.400 mmol) in THF (0.40 mL) was added.
After the mixture was stirred for 1 h at the same temperature,
(iodemethyl)trimethylsilane (115 mg, 0.539 mmol) was added,
and the temperature was allowed to rise to ambient temper-
ature over a period of 2 h. Saturated aqueous NH4Cl was added
under vigorous stirring, and the aqueous solution was ex-
tracted with CH2Cl2. The combined organic extracts were
washed with brine and dried over Na2SO4. The solvent was
removed under reduced pressure to leave a residue that was
purified by column chromatography (silica gel, hexane/ethyl
Rep r esen ta tive P r oced u r e for th e Rea ction of Su lfox-
id es w ith Tr im eth yl P h osp h a te. The R-sulfinyl carbanion
was prepared as described above using 1a (38.7 mg, 0.161
mmol), diisopropylamine (0.035 mL, 0.249 mmol), n-butyl-
lithium (1.44 mol L-1 in hexane, 0.17 mL, 0.245 mmol). To
the resulting solution was added trimethyl phosphate (0.030
mL, 0.256 mmol). After 15 min, usual workup gave the crude
product, which was purified by column chromatography (hex-
ane/ethyl acetate ) 70/30) to afford a mixture of syn-3a and
anti-3a (48.5 mg, 94%). The diastereomeric ratio of the
1
products syn-3a and anti-3a was determined to be 96:4 by H
NMR of the crude product. syn-3a : 1H NMR δ 0.01 (s, 9H),
0.50 (dd, 1H, J ) 12.1, 13.6 Hz), 1.07 (dd, 1H, J ) 2.5, 12.1
Hz), 1.14 (d, 3H, J ) 6.8 Hz), 2.42 (s, 3H), 2.79 (ddq, 1H, J )
2.5, 6.8, 13.6 Hz), 7.30 (d, 2H, J ) 8.2 Hz), 7.48 (d, 2H, J )
8.2 Hz). anti-3a : 1H NMR δ 0.01 (s, 9H), 0.49 (dd, 1H, J )
11.9, 14.3 Hz), 1.08 (dd, 1H, J ) 2.6, 11.9 Hz), 1.11 (d, 3H, J
) 6.4 Hz), 2.42 (s, 3H), 2.70-2.90 (m, 1H), 7.31 (d, 2H, J )
8.2 Hz), 7.47 (d, 2H, J ) 8.2 Hz). Mixture of syn-3a and anti-
3a : IR (KBr) 3040, 1300, 1250, 1050 cm-1; SIMS m/z (rel
intensity) 254.1 (M+,100), 239.1 (30), 114.2 (100). Anal. Calcd
for C13H22OSSi: C, 61.36; H, 8.71. Found: C, 61.29; H, 8.83.
acetate ) 85:15) to give 1g (99 mg, 70%) as a colorless solid:
1
[R]21 -104.1 (c 0.36, acetone); H NMR δ 0.04 (s, 9H), 0.71
D
(ddd, 2H, J ) 4.5, 14.1, 14.1 Hz), 1.21 (ddd, 2H, J ) 3.9, 14.1,
14.5 Hz), 1.20-1.35 (m, 18H), 2.75-3.00 (m, 2H), 3.28 (ddd,
1H, J ) 3.9, 12.9, 14.1 Hz), 3.75-4.15 (m, 2H), 7.08 (s, 2H);
IR (neat) 2970, 1370, 1250, 1050 cm-1; SIMS m/z (rel intensity)
352.2 (M+,10), 102.1 (100). Anal. Calcd for C20H36OSSi: C,
68.12; H, 10.29. Found: C, 68.15; H, 10.30.
Rep r esen ta tive P r oced u r e for th e Rea ction of Su lfox-
id es w ith Ca r bon yl Com p ou n d s. (3R)- a n d (3S)-2-Meth yl-
3-[(R)-p -t olylsu lfin yl]-4-(t r im et h ylsilyl)-2-b u t a n ol (syn -
2a a n d a n ti-2a ). To a solution of diisopropylamine (0.035 mL,
0.249 mmol) in THF (0.23 mL) was added n-butyllithium (1.53
mol L-1 in hexane, 0.145 mL, 0.222 mmol) at 0 °C, and the
mixture was stirred for 10 min. The reaction mixture was
cooled to -78 °C, and then a solution of 1a (44.7 mg, 0.186
mmol) in THF (0.19 mL) was added dropwise over a period of
20 min. The mixture was stirred for an additional 20 min.
Acetone (0.020 mL, 0.272 mmol) was then added, and the
mixture was stirred for 5 min, the solution was quenched
rapidly with saturated aqueous NH4Cl (3 mL) under vigorous
stirring, and the organic layer was separated. The aqueous
Ack n ow led gm en t. We thank Dr. Shinya Kusuda,
Ono Pharmaceutical Co., Ltd., for X-ray crystallographic
analysis. This work was partly supported by a Grant-
in Aid for Scientific Research (no. 11650890) from the
Ministry of Education, Science and Culture of J apan.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic char-
acterization for the products 2 and 3. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O9913560