C O M M U N I C A T I O N S
Table 2. Diastereoselective Silacyclopropanation of
1,1-Disubstituted Alkenes (R ) CH2OEt) by Lithium Reduction of
t-Bu2SiCl2
Our results demonstrate that steric interactions, rather than oxygen-
directing effects, control the diastereoselectivity for silacyclopro-
panation, most likely because the sterically demanding nature of
the di-tert-butylsilylene species prevents coordination. Thermolysis
conditions exhibit broad functional group tolerance and increased
yields relative to lithium reduction conditions; the elevated tem-
peratures required for silylene transfer, however, cannot be
employed for silacyclopropanation of cyclohexenes and 1,1-
disubstituted alkenes. Ultimately, we envision employing a mild
one-step protocol with broad substrate generality for silacyclopro-
panation and ring-expansion to convert a chiral functionalized
alkene to a complex polyoxygenated product.
Acknowledgment. This research was supported by the National
Institutes of Health (General Medical Sciences, GM54909). K.A.W.
thanks the Camille and Henry Dreyfus Foundation, Merck Research
Laboratories, Johnson and Johnson, and the Sloan Foundation for
awards to support research. A.K.F. thanks Abbott Laboratories for
a graduate research fellowship. T.G.D. thanks Eli Lilly and
Company for a graduate research fellowship. We thank Dr. John
Greaves and Dr. John Mudd for mass spectrometric data and Dr.
Joseph Ziller for crystallographic analyses.
a Based on analysis of 1H and 29Si NMR spectra. b Based on analysis of
1H NMR spectra with 1,3,5-trimethoxybenzene as an internal standard.
c Thermal transfer afforded 22 with 70:30 diastereoselectivity. d Thermal
transfer led to decomposition of silacyclopropane 1.
Silacyclopropanation of a series of 1,1-disubstituted alkenes (19-
21) proceeded with excellent diastereoselectivity (g97:3) using the
lithium reduction conditions (Table 2). We believe that minimization
of 1,2-allylic strain accounts for the acyclic stereocontrol observed
for formation of silacyclopropanes 22-24.19,20 Silacyclopropanation
of 1,1-disubstituted alkenes with the thermolysis conditions led to
decomposition of silacycle 1 and reduced diastereoselectivities (70:
30) due to the elevated temperatures (125 °C) required for silylene
transfer.
The synthetic utility of diastereoselective silacyclopropanation
was demonstrated by elaboration of the strained silanes 8a and 23
to afford complex polyoxygenated structures. Metal-catalyzed
formamide insertion,21 followed by nucleophilic addition and
oxidation of the C-Si bond,22,23 afforded cyclopentane 26 in high
yield and with excellent regio- and stereoselectivity (eq 5).14 Stereo-
Supporting Information Available: Experimental procedures,
spectral data for all compounds, and crystallographic data (PDF). This
References
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(12) Yields are reported for isolated silacyclopropanes purified by using bulb-
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(13) Yields for lithium reduction conditions were determined by analysis of
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(14) Stereochemistry was proven by X-ray crystallographic analysis of the
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We have shown that thermal silylene transfer and lithium
reduction of t-Bu2SiCl2 are complementary methods for the
diastereoselective silacyclopropanations of functionalized alkenes.
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