Enantioselective silyl protection of alcohols promoted by a combination of chiral and achiral Lewis basic catalysts

Abstract

Catalytic enantioselective mono-silylations of diols and polyols furnish valuable alcohol-containing molecules in high enantiomeric purity. These transformations, however, require high catalyst loadings (20-30 mol%) and long reaction times (2-5 days). Here, we report that a counterintuitive strategy – involving the use of an achiral co-catalyst that is structurally similar to the chiral catalyst – provides an effective solution to this problem. A combination of seemingly competitive Lewis-basic molecules can function in concert such that one serves as an achiral nucleophilic promoter while the other performs as a chiral Brønsted base. Upon addition of 7.5-20 mol % of commercially available N-heterocycle (5-ethylthiotetrazole), reactions typically proceed within one hour, delivering the desired products in high yields and enantiomeric ratios. In some instances, there is no reaction in the absence of the achiral base, yet presence of the achiral co-catalyst results in facile formation of products in high enantiomeric purity.