Diphenylprolinol Silyl Ether Catalyzed Asymmetric Michael Reaction of Nitroalkanes and β, β-Disubstituted α, β-Unsaturated Aldehydes for the Construction of All-Carbon Quaternary Stereogenic Centers

The asymmetric Michael reaction of nitroalkanes and beta, beta-disubstituted alpha, beta-unsaturated aldehydes was catalyzed by diphenylprolinol silyl ether to afford 1,4-addition products with an all-carbon quaternary stereogenic center with excellent enantioselectivity. The reaction is general for beta-substituents such as beta-aryl and beta-alkyl groups, and both nitromethane and nitroethane can be employed. The addition of nitroethane is considered a synthetic equivalent of the asymmetric Michael reaction of ethyl and acetyl substituents by means of radical denitration and Nef reaction, respectively. The short asymmetric synthesis of (S)-ethosuximide with a quaternary carbon center was accomplished by using the present asymmetric Michael reaction as the key step. The reaction mechanism that involves the E/Z isomerization of alpha, beta-unsaturated aldehydes, the retro-Michael reaction, and the different reactivity between nitromethane and nitroethane is discussed.