The azepino[1,2-a]indole scaffold is present in numerous indole alkaloids and pharmaceutically-relevant compounds. Current approaches to synthesizing this framework include olefin metatheses, hetero-[5+2] cycloadditions, or gold-catalyzed intramolecular cyclization cascades. Unfortunately, these approaches are hindered by several factors: high catalyst loadings, limited functional group tolerance, and the formation of reaction by-products. In response, a novel strategy for a catalytic, diastereoselective formal [5+2] cycloaddition of N-indolyl alkylidene �-amide esters and alkenes has been developed. This transformation proceeds via a Sc(OTf)3-catalyzed formal [2+2] cycloaddition of an alkene with and N-indolyl alkylidene �-amide ester to form a putative donor-acceptor cyclobutane intermediate which subsequently undergoes an intramolecular ring-opening cyclization. Azepino[1,2-a]indoles are formed in up to 92% yield with high degrees of diastereoselection (up to 34:1 dr). Various functionalized alkylidenes and alkenes are amenable to this method, thus demonstrating its versatility and scope.                                                       

Catalytic, diastereoselective synthesis of azepino[1,2-a]indoles via formal [5+2] cycloadditions of N-indolyl alkylidene �-amide esters and alkenes: Putative donor-acceptor cyclobutanes as reactive intermediates

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.