Highly Enantiopure (tert-Butyldiphenylsilyloxymethyl)Oxiranes from Barium Carbonate

Abstract

The synthesis of (2R)-(tert-butyldiphenylsilyloxymethyl)oxirane and the (2S)-enantiomer from barium carbonate was developed. Methyl glycolate or the hydroxamate analog was prepared and in turn reacted with (S)-(-)-methyl p-tolylsulfoxide or the (R)-enantiomer to make β-keto sulfoxides. From the sulfoxides, we made the diastereoisomeric alcohols in a highly selective sulfoxide group directed hydride reduction, and a Pummerer rearrangement reaction followed by deprotection yielded the enantiomeric diols. (2R)-(tert-Butyldiphenylsilyloxymethyl)oxirane and its (2S)-enantiomer were derived from these diols in an overall yield of 56% from barium carbonate. This method was developed to provide a convenient access to isotope-labeled analogs of these compounds.