Stereoselective ZrCl4-Catalyzed Mannich-type Reaction of beta-Keto Esters with Chiral Trifluoromethyl Aldimines

摘要

A method for the synthesis of fluorinated beta'-amino beta-dicarbonyl compounds using a Zr-catalyzed Mannich-type reaction has been developed, starting from N-protected trifluoromethyl aldimines and cyclic or acyclic beta-keto esters bearing different ester residues. The in situ generated metallic complex reacted with optically pure trifluoromethyl aldimine derived from (R)-alpha-methylbenzylamine, giving a highly diastereoselective asymmetric Mannich-type addition with formation of a chiral quaternary center. The absolute configuration at the new chiral centers was assigned through two-dimensional nuclear Overhauser effect spectroscopic analysis coupled with computational studies.