Controlled generation of ortho-quinone methides and (4+3) cyclization with 2-indolylalcohols by dual photoredox/Brønsted acid relay catalysis

Abstract

Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely construct and manipulate such ring systems in chemical research. In this area, the intermolecular, multicomponent cyclization for the synthesis of diversely substituted seven-membered ring oxacycles under simple conditions is still a challenge. Here, we report a dual photoredox/Brønsted acid relay catalytic strategy for in situ generation of ortho-quinone methides and subsequent (4 ​+ ​3) cyclization with 2-indolylalcohols. In this one-pot multicomponent reaction, two C–C and one C–O bonds are formed, providing de novo access to various biologically important indole-fused, oxygen-containing seven-membered heterocycles. By virtue of a chiral phosphoric acid, an asymmetric version can also be achieved with good to excellent levels of enantioselectivity (up to 96:4 er).