Stereoselective reactions. Part 23. Asymmetric Michael reaction of α-alkyl β-keto esters via chiral enamines. Dependence of the diastereofacial selection on the combination of solvents and additives

Abstract

Asymmetric Michael reaction of the chiral enamines prepared from α-alkyl β-keto esters and (S)valine tert-butyl ester is described. The diastereoselectivity of this reaction is highly sensitive to the solvent system. The lithiated chiral enamines react with di-tert-butyl methylenemalonate in toluene–HMPA to give α,α-dialkylated β-keto esters in 87–92% ee after hydrolysis. On the other hand, the reactions in THF give the corresponding antipodes in 84–95% ee.