Photoinduced Asymmetric [4 + 2] Cycloaddition of Benzocyclobutenones with Ketones into 3,4-Dihydroisocoumarins.

A photoinduced asymmetric catalytic [4 + 2] cycloaddition of benzocyclobutenones with aryl alkyl ketones was realized via C-C single-bond activation, delivering a series of enantioenriched 3,4-dihydroisocoumarins featuring a sterically hindered quaternary stereocenter. This transformation exhibited good functional group tolerance and offered a convenient route for the late-stage modification of several drug molecules. Mechanistic studies revealed that the reaction involved regiospecific C1-C8 bond cleavage of benzocyclobutenones via a chiral Lewis acid-assisted radical addition of triplet state ketones to benzocyclobutenones, followed by intramolecular radical-radical coupling.