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

Bis-N-trifluoromethanesulfonly squaramide was prepared as a new bench-stable strong Bronsted acid and applied to the Bronsted 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 Bronsted 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 Bronsted acid was further applied to Mukaiyama Michael reaction of alpha,beta-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 Bronsted acid catalysis, rather than through Lewis acid catalysis with silylated Bronsted acid. (C) 2009 Elsevier Ltd. All rights reserved.