Aza-[4+2]-cycloaddition of benzocyclobutenones into isoquinolinone derivatives enabled by photoinduced regio-specific C–C bond cleavage

Abstract

The activation of C−C bond of benzocyclobutenones under mild reaction conditions remains a challenge. We herein report a photoinduced catalyst-free regio-specific C1−C8 bond cleavage of benzocyclobutenones, enabling the generation of versatile ortho-quinoid ketene methides for aza-[4 + 2]-cycloaddition with imines, which offers a facile route to isoquinolinone derivatives, including seven family members of protoberberine alkaloids, gusanlung A, B, D, 8-oxotetrahydroplamatine, tetrahydrothalifendine, tetrahydropalmatine, and xylopinine. Furthermore, the catalytic enantioselective version of this strategy was realized by merging synergistic photocatalysis and chiral Lewis acid catalysis. Mechanistic studies provided compelling evidence to rationalize the photoisomerization/cycloaddition cascade process.