Optical resolution and absolute stereochemistry of trans-2,5-dimethyl-1-phenyl-1-silacyclopentane

Abstract

2,5-Dimethyl-1-phenyl-1-silacyclopentane (DMPSC) has been prepared in good yield, as a mixture of stereoisomers, by the reaction of 2,5-dibromohexane and dichlorophenylsilane with magnesium in tetrahydrofuran. The silane so prepared consists of a ca. 1:1:3 mixture of the cis-isomers 2, 3 and the racemic trans-isomer 4+5, respectively. Treatment of this product with copper(II) chloride in acetonitrile gives 1-chloro-DMPSC as a mixture of the cis-isomers 6, 7 and the racemic trans-isomer 8+9 in the approximate ratio 1:6:12. Mono-O-silylation of dimethyl L-tartrate with this mixture of chlorosilanes gave the silyl ether 11 and the diastereoisomeric pair of trans-compounds 12 and 13 as crystalline solids. The molecular structure of the cis-silyl ether 11 has been determined by X-ray diffraction. Corresponding monosilylation of (2S)-1,1,2-triphenylethane-1,2-diol [(S)-TPED] occurs selectively at the less hindered secondary OH group; the stereoisomeric products were separated by a combination of recrystallisation and column chromatography and the molecular structure of the (2S,5S)-silyl ether was determined by single-crystal X-ray diffraction. Reduction of this diastereoisomer with LiAlH₄ afforded (2S,5S)-(+)-DMPSC, [α]_D²²+27.8 (c 2.16, cyclohexane), with an estimated enantiomeric excess of >98%. The (2R,5R)-(–)-enantiomer was prepared in a similar manner using (R)-TPED as the resolving agent, which was readily recovered in an optically-pure state and could be recycled.