Asymmetric Mannich-type reactions with a chiral acetate: effect of Lewis acid on activation of aldimine

We introduce here a strategy that enables effective addition of lithium eno lates of acetates to aldimines. The new method depends strongly on the use of ortho-alkoxy (or ortho-fluoro) aniline-derived aldimines which found to have a potential effect on the enolate addition. This scope was expanded to the asymmetric process using the chiral acetate, which has optically pure 2,6-bis(2-isopropylphenyl)-3,5-dimethylphenol as a chiral auxiliary with ax ial chirality. A Lewis acid additive is likely to have a complementary role in the pronounced activation of imine functionalities in the Mannich-type addition of the bulky chiral acetate. (C) 2001 Elsevier Science Ltd. All ri ghts reserved.