The synthesis of tetracyclic coumarins via decarboxylative asymmetric [4+2] cycloadditions enabled by Pd(0)/Cu(I) synergistic catalysis

Tetracyclic coumarins are a class of important compounds with diverse and superior pharmacological activities. However, a direct stereoselective method from simple and readily-made coumarins derivatives remains challenging due to the inertness of coumarins as dienophiles. Herein, we develop a decarboxylative asymmetric [4+2] cycloaddition of 3-cyanocoumarins with vinyl benzoxazinones, affording the coumarin-derived condensed rings bearing three continuous stereocenters in high yields with excellent diastereoselectivities (>20/1 d.r.) and enantioselectivities (up to 99% ee). This direct enantioselective reaction was achieved by a Pd(0)/Cu(I) bimetallic catalytic system. The mechanism studies indicated that the synergistic activation effect, in which chiral Cu(I) as an available Lewis acid catalyst activates 3-cyanocoumarin and chiral Pd(0) complex activates benzoxazinone by the formation of π-allyl-palladium intermediate, plays an important role on the stereoselective control. The current work provides a new activation modes of Cu catalyst in the Pd/Cu bimetallic catalytic system.