Organocatalytic Enahtioselective Dipolar [3 + 2] Cycloadditions of Acetylenic Aldehydes with Nitrones for the Formation of Chiral 4-Isoxazolines

摘要

The first organocatalytic enantioselective protocol has been developed for the dipolar [3 + 2] cycloaddition between acetylenic aldehydes and nitrones through an iminium activation pathway. This protocol uses L-α,α-bis(3,5-ditrifluoromethyl-phenyl)prolinol as catalyst and 3,5-dinitrobenzoic acid as additive and is friendly for one-pat operation for the nitrone formation and the subsequent cycloaddition. It also exhibits a broad substrate scope and allows for the highly efficient production of chiral 4-isoxazolines with various substituents under mild conditions in high ylelds (68-92%) with high enantioselectivities (up to 96% ee).