Direct Organocatalysed Double Michael Addition of α-Angelica Lactone to Enones

The direct vinylogous Michael addition of unactivated α-Angelica lactone to enones under iminium activation using 9-amino-9-deoxy-epi-quinine as catalyst along with 2-hydroxy-1-naphthoic acid as co-catalyst has led to the formation of γ,γ-disubstituted butenolides in high yields, moderate-to-good diastereoselectivities and excellent enantioselectivities. The readily available catalytic system over-rides the steric hindrance, which would otherwise lead to the preferential formation of the syn isomer, to afford the anti isomer instead. Under enamine activation, the anti isomer selectively undergoes cyclisation to the hexahydrobenzofuran-2(3H)-one, which is readily separated from the left-over syn isomer. Mechanistic details, including the fate of the pro-nucleophile and the origin of the diastereoselectivity, are also discussed