A new Brønsted acid derived from squaric acid and its application to Mukaiyama aldol and Michael reactions

Abstract

Bis- N-trifluoromethanesulfonyl squaramide was prepared as a new bench-stable strong Brønsted acid and applied to the Brønsted acid-catalyzed Mukaiyama aldol and Michael reactions with silyl enol ethers. The resulting Mukaiyama aldol products of aldehydes were obtained in quantitative yields, whereas expansion of the utility of this Brønsted acid to ketones was limited to electron-deficient ketones presumably due to lower reactivity of ketones as well as competing protodesilylation of silyl enol ether. The Brønsted acid was further applied to Mukaiyama Michael reaction of α,β-unsaturated ketones. It is noted that catalyst loading of all Mukaiyama reactions was only 1 mol % or less, which demonstrated the high reactivity of this acid. Mechanistic studies implied that the Mukaiyama aldol reaction might proceed through Brønsted acid catalysis, rather than through Lewis acid catalysis with silylated Brønsted acid.