Convergent and divergent synthesis of dihydroisoquinoline-1,4-diones enabled by a photocatalytic skeleton-editing [4 + 2] strategy

Abstract

Dihydroisoquinolinediones are ubiquitous nitrogen-containing fused heterocyclic units in natural products, drug molecules, and functional materials. However, straightforward synthesis of dihydroisoquinolinediones from simple and readily available precursors remains challenging and underdeveloped. Herein, we developed an unprecedented photocatalytic [4 + 2] skeleton-editing strategy enabled direct synthesis of dihydroisoquinoline-1,4-diones from vinyl azides and carboxylic NHPI esters. The key to success is the use of NHPIs as bifunctional reagents and in the skeleton-edit enabled [4 + 2] cyclization cascade. Notably, vinyl azides serve as α-primary amino alkyl radicals followed by a radical initiated ring-enlargement event. Impressively, the reaction provides convergent access to identical dihydroisoquinolinedione from different NHPIs and divergent access to different dihydroisoquinolinediones from identical NHPI. The reaction cleaves two C–N bonds and forges one C–N bond, two C–C bonds and a ring.