Enantioselective decarboxylative Mannich reaction of β-keto acids with C-alkynyl N-Boc N,O-acetals: access to chiral β-keto propargylamines

Abstract

The chiral keto-substituted propargylamines are an essential class of multifunctional compounds in the field of organic and pharmaceutical synthesis and have attracted considerable attention, but the related synthetic approaches remain limited. Therefore, a concise and efficient method for the enantioselective synthesis of β-keto propargylamines via chiral phosphoric acid-catalyzed asymmetric Mannich reaction between β-keto acids and C-alkynyl N-Boc N,O-acetals as easily available C-alkynyl imine precursors has been demonstrated here, affording a broad scope of β-keto N-Boc-propargylamines in high yields (up to 97%) with generally high enantioselectivities (up to 97 : 3 er).