Chirality transfer from silicon to carbon via diastereoselective Simmons-Smith cyclopropanation of chiral alkenylsilanols

Article abstract of DOI:10.1016/S0957-4166(02)00056-3

Simmons-Smith cyclopropanation of a chiral alkenylsilanol with CH₂I₂-Et₂Zn proceeds diastereoselectively to give the corresponding cyclopropylsilanol product. Chirality transfer from silicon to the alkenyl carbons of the silicon substituent is observed. The stereochemistry of the obtained cyclopropylsilanol is confirmed by converting to cyclopropanol via Tamao oxidation.

Full text of DOI:10.1016/S0957-4166(02)00056-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 13–15
Chirality transfer from silicon to carbon via diastereoselective
Simmons–Smith cyclopropanation of chiral alkenylsilanols
Yuichi Yamamura, Fumihiko Toriyama, Tatsuhiro Kondo and Atsunori Mori*
Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama 226-8503, Japan
Received 18 January 2002; accepted 6 February 2002
Abstract—Simmons–Smith cyclopropanation of a chiral alkenylsilanol with CH2I2–Et2Zn proceeds diastereoselectively to give the
corresponding cyclopropylsilanol product. Chirality transfer from silicon to the alkenyl carbons of the silicon substituent is
observed. The stereochemistry of the obtained cyclopropylsilanol is confirmed by converting to cyclopropanol via Tamao
oxidation. © 2002 Elsevier Science Ltd. All rights reserved.
Silicon-centered stereogenicity attracts much attention
but has been less well studied compared with the exten-
sive works on the analogous carbon centres.1 Accord-
ingly, chirality transfer from silicon to neighboring
carbon atoms has seldom been investigated to date.2
However, the development of such highly efficient
transfer reactions involving stereogenic silicon atoms
could possibly open up a new area of stereochemical
studies in organic synthesis.
by the following methods, as shown in Scheme 1. (a)
The cleavage of cyclic siloxane with alkenyllithium
followed by hydrolysis of the formed lithium silanolate
to give 1 in 70% yield, and (b) alkenylation of a
dichlorosilane with the corresponding organolithium
reagent followed by careful hydrolysis of the obtained
chlorosilane (55–58% yield).
Cyclopropanation of the obtained alkenylsilanols was
carried out using diethylzinc and diiodomethane (1:2), a
system that is considered to generate (ICH2)2Zn.7 When
We recently reported the synthesis of silanols with a
stereogenic silicon center and their resolution via HPLC
with a chiral column.3 Hence, our continuing interest in
the chemistry of silanols4 has turned to chirality trans-
fer of these chiral silanols by diastereoselective reaction
to a functional group on one of the silicon substituents.
On the other hand, Simmons–Smith cyclopropanation
with CH2I2–Et2Zn to non-chiral alkenylsilanols was
shown to be accelerated by the hydroxy group to afford
cyclopropylsilanols.5 In such a reaction, the chirality of
silicon might be efficiently transferred to carbons when
the reaction proceeds in a highly diastereoselective
manner, as observed in that of allylic alcohols.6 Herein,
we report such a diastereoselective Simmons–Smith
cyclopropanation of chiral non-racemic alkenylsilanols.
The diastereoselective reaction was first examined with
several racemic silanols 1a–c under the standard condi-
tions for the Simmons–Smith cyclopropanation
reported previously.5 The synthesis of 1 was carried out
* Corresponding author. Tel.: +81-45-924-5231; fax: +81-45-924-5224;
e-mail: amori@res.titech.ac.jp
Scheme 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00056-3

14
Y. Yamamura et al. / Tetrahedron: Asymmetry 13 (2002) 13–15
the reaction of 1a was performed with 3 mol equiv. of
diethylzinc and 6 mol equiv. of diiodomethane in
diethyl ether at room temperature for 3 h, most of 1a
1
was consumed (as confirmed by H NMR analysis) and
the corresponding cyclopropylsilanol 2a was isolated in
80% yield after purification by column chromatography
on silica gel (Eq. (1)). The diastereoselectivity was
tentatively estimated by 1H NMR analysis via the
relative integration of the isomeric methylsilane signals,
which appeared at l=0.162 (minor) and 0.166 (major)
ppm, respectively. As summarized in Table 1, the
diastereoselectivity was consistently in the range 78–
84% when 1a was employed irrespective of the reaction
temperature. In addition, the combined use of
(ICH2)2Zn and a Lewis acid (Et2AlCl or TiCl4) at lower
temperature, previously shown to be an efficient system
to enhance the reaction rate in the Simmons–Smith
reaction of allylic alcohols,8 had little effect upon the
diastereoselectivity. Although the diastereoselectivity of
the Simmons–Smith reaction for (Z)-allylic alcohols is
known to be higher relative to the (E)-isomer,7 in this
case the reaction with the (Z)-isomer 3a (Chart 1)
occurred with lower diastereoselectivity (entry 7, 68:32).
Chart 1.
The stereochemistry of cyclopropylsilanol 2 was deter-
mined by conversion into cyclopropanol 4 via Tamao
oxidation.9 The cyclopropanation of (−)-1a (the latter
enantiomerically enriched; 92% e.e.), which was
obtained by separation with HPLC using chiral station-
ary phase column as reported previously,3 was carried
out to afford cyclopropylsilanol 2a, whose diastereose-
1
lectivity was confirmed to be 84:16 (68% d.e.) by H
NMR analysis. Tamao oxidation with 3-chloroperben-
zoic acid (m-CPBA) in DMF at room temperature over
3 h furnished the cyclopropanol (+)-4 in 31% yield. The
absolute configuration of 4 was confirmed to be
(1S,2R) by comparison with the literature.10 HPLC
analysis of the cyclopropanol after transformation to its
benzoate revealed it to have e.e. of 58%, suggesting that
the stereochemistry was retained through the oxidation.
Alkenylsilanol (+)-1a (80% e.e.), the antipode of (−)-1a,
was also subjected to a similar protocol (66% d.e. in the
Simmons–Smith reaction) to give (1R,2S)-2-phenyl-1-
cyclopropanol of 55% e.e.11
(1)
We next examined the effect of a silanol substituent on
the stereochemical course of the reaction. When a
phenyl group was employed instead of a 3,3,3-trifluoro-
propyl group, the selectivity for the reaction of silanol
1b was found to be much lower although the reaction
proceeded smoothly. In contrast, higher selectivity was
achieved in the reaction of 1c, bearing a cyclohexyl
substituent and a single diastereomer was observed by
Separation of ( )-1c was also successful by HPLC with
a chiral column (Daicel AD) to afford (+)-1c and
(−)-1c, each with e.e. of 98% and the cyclopropanation
of each enantiomer was conducted in a similar manner
to afford the corresponding cyclopropylsilanol as a
single diastereomer. The Tamao oxidation of 2c with
m-CPBA in the presence of KHF2 at room temperature
in DMF gave (−)-4 and (+)-4, each with 97% e.e., which
was also confirmed by HPLC analyses of the benzoate
derivatives. (Eq. (2))
1
measurement of the H NMR, l=0.04 ppm (CDCl3).
The results suggest that introduction of a sterically
encumbered substituent on the silicon atom is necessary
to improve the diastereoselectivity (chart 1).
Table 1. Diastereoselective Simmons–Smith cyclopropanation of alkenylsilanols 1a–c and 3aa
Entry
Substrate
Additive
Temp (°C)
Time (h)
Yield (%)
Selectivityb
1
2
3
4
5
6
7
8
9
1a
None
None
TiCl4
Rt
3
3
3
25
3
9
3
3
3
80
32
7
55
58
49
92
88
84
84:16
83:17
–
81:19
78:22
81:19
68:32c
55:45
\99:1
−20
−20
−20
−20
−40
Rt
TiCl4
Et2AlCl
Et2AlCl
None
None
None
3a
1b
1c
Rt
Rt
a The reaction was carried out in diethyl ether (entries 1, 2, and 7–9) or dichloromethane (entries 3–6) using 3 mol amounts of Et2Zn and 6 mol
amounts of CH2I2.
b The selectivity was estimated by a 1H NMR spectrum of the methyl signal on the silanol.
c Deduced from the results on the reaction of 1a.

Y. Yamamura et al. / Tetrahedron: Asymmetry 13 (2002) 13–15
15
port. Organosilicon reagents were kindly donated by
Shin-Etsu Chemicals Co. Ltd.
References
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In conclusion, the absolute configurations of cyclo-
propylsilanols 2 were confirmed to be (1R,2S) when
(+)-1 was employed, whilst (1S,2R)-isomers were fur-
nished from (−)-1, although the absolute configuration
of the silicon atom is not yet known. The stereogenicity
of the silicon center was successfully transferred to
carbon via Simmons–Smith cyclopropanation. When a
practical and preparative method to give chiral non-
racemic 1 is in hand, the present chirality transfer
would be a powerful tool for the synthesis of a variety
of chiral organic molecules.
Typical experimental procedure: To a solution of (+)-1c
(170 mg, 0.69 mmol) in diethyl ether (2.1 mL) were
added diethylzinc (1 M hexane solution, 2.07 mL, 2.07
mmol) and diiodomethane (0.34 mL, 4.14 mmol) at
0°C. The mixture was stirred at room temperature for 3
h and poured into sat. NH4Cl (20 mL) and diethyl
ether (10 mL). The aqueous phase was extracted with
diethyl ether (2×20 mL) and the combined organic layer
was dried over anhydrous sodium sulfate. Removal of
the solvent under reduced pressure left a crude oil,
which was separated by column chromatography on
silica gel (hexane–ethyl acetate=85:15) to yield 2c (152
5. (a) Hirabayashi, K.; Mori, A.; Hiyama, T. Tetrahedron
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Nishihara, Y.; Mori, A.; Hiyama, T. Bull. Chem. Soc.
Jpn. 1998, 71, 2409.
6. Charette, A. B.; Lebel, H. J. Org. Chem. 1995, 60, 2966
and references cited therein.
1
mg, 84%). [h]2D3=−58.4 (c 1.11, EtOH); H NMR (300
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MHz, CDCl3) l 0.05 (s, 3H), 0.09 (m, 1H), 0.78 (brs
1H), 0.98–1.06 (m, 2H), 1.12–1.33 (m, 5H), 1.61–1.56
(m, 5H), 1.86 (m, 1H), 7.07–7.16 (m, 3H), 7.23–7.28 (m,
2H); 13C NMR (75.5 MHz, CDCl3) l −3.73, 26.62,
26.65, 26.75, 26.78, 27.72, 125.5, 126.5, 128.2, 128.5,
137.9, 145.6; IR (neat) 3300 br, 2921, 2847, 1605, 1499,
1447, 1252, 1102, 911, 849 cm−1; HRMS: found
260.1594, calcd for C16H24OSi: 260.1595.
9. Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M.
Organometallics 1983, 2, 1694.
10. [h]2D6=−27.2 (c 1.5, EtOH) for 4 from (+)-1a; [h]2D6=+48.4
(c 1.5, EtOH) for 4 from (−)-1a. Lit. [h]2D4=−62.2 (c
0.629, EtOH) for (1R,2S)-isomer of 73% e.e.; Imai, T.;
Mineta, H.; Nishida, S. J. Org. Chem. 1990, 55, 4986.
11. The e.e. values of 2 can be estimated to be 63% (92%
e.e.×68% d.e.) from (−)-1 and 55% (80% e.e.×66% d.e.).
Acknowledgements
We thank Asahi Glass Foundation for financial sup-