Convergent and Divergent Synthesis of Dihydroisoquinoline-1,4-diones Enabled by a Photocatalytic Skeleton-Editing [4+2] Strategy

Abstract

Dihydroisoquinolinediones, which 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 NHPI as bifunctional reagents as well as 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.