Mechanistic investigations of alcohol silylation with isothiourea catalysts

Abstract

The mechanism of the asymmetric silylation of alcohols with isothiourea catalysts was studied by employing reaction progress kinetic analysis. These reactions were developed by the Wiskur group, and use triphenyl silyl chloride and chiral isothiourea catalysts to silylate the alcohols. While the order of most reaction components was as expected (catalyst, amine base, alcohol), the silyl chloride was determined to be a higher order. This suggested a multistep mechanism between the catalyst and silyl chloride, with the second equivalent of silyl chloride assisting in the formation of the reactive intermediate leading to the rate-determining step. Through the addition of additives and investigating changes in the silyl chloride, an understanding of the catalyst equilibrium emerged for this reaction and provided pathways for further reaction development.