Catalytic diastereoselective construction of multiple contiguous quaternary carbon stereocenters via [2 + 2] cycloaddition and mechanistic insight

Abstract

Multiple contiguous quaternary carbon stereocenters (CQS) are highly challenging, yet important structural motifs in organic synthesis. Here, we describe a visible light induced catalytic [2 + 2] cycloaddition approach that constructed up to four CQS in a pentacyclic fused ring system diastereoselectively, from the readily accessible dienamides with pendent heteroaryls. Variously substituted dienamides have been cyclized with heteroaryls to provide a range of novel CQS-containing scaffolds (26 examples, up to 96% yield and >20:1 dr ratio). Mechanistic studies revealed that it may proceed through an uncommon β-C radical initiated 7-endo cyclization from the biradical intermediate.