Copper(i)-catalyzed highly enantioselective [3 + 3]-cycloaddition of γ-alkyl enoldiazoacetates with nitrones

Abstract

Chiral copper(I) catalysts are preferred over chiral dirhodium(II) catalysts for [3 + 3]-cycloaddition reactions of γ-alkyl-substituted enoldiazoacetates compounds with nitrones. Using the In-SaBox ligand these reactions effectively produce cis-3,6-dihydro-1,2-oxazine derivatives under mild conditions in high yield and with exceptional stereocontrol, and enantioselectivity increases with the size of the γ-substituent. Mechanistic studies show that cycloaddition occurs solely through the formation of (Z)-γ-substituted metallo-enolcarbene intermediates that are catalytically gennerated from both (Z)- and (E)-γ-substituted enoldiazoactates via donor–acceptor cyclopropene intermediates.