Relay Catalysis-Enabled Enantioselective Annulations of β,γ-Alkynyl-α-imino Esters with 1,3-Diones for the Divergent Synthesis of Chiral Oxacycles.

Abstract

A novel protocol for the chemically divergent synthesis of chiral oxacycles has been developed using organo/metal relay catalysis. The methodology integrates a stereospecific Mannich reaction between β,γ-alkynyl-α-imino esters and 1,3-diones catalyzed by a chiral bifunctional squaramide, followed by Lewis acid-catalyzed regioselective annulation reactions. By switching the Lewis acid employed, we achieved a divergent pathway to construct structurally related pyran and furan derivatives from a common intermediate. The (3+3) and (3+2) annulation products were obtained in high yields and excellent stereoselectivities. Comprehensive mechanistic studies were conducted to establish the reaction mechanism.