A desilylative approach to alkyl substituted C(1)-ammonium enolates : application in enantioselective [2+2] cycloadditions

Abstract

The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96% yield and >99:1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75% yield and >99:1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.