Enantioselective Desymmetrization of Biaryls via Cooperative Photoredox/Brønsted Acid Catalysis and Its Application to the Total Synthesis of Ancistrobrevolines
Junsoo Moon, Eun Joo Shin, Yongseok Kwon
Abstract
Photoredox catalysis has emerged as a powerful tool for forming and breaking chemical bonds, further taking hold with its integration with asymmetric catalysis. While the dual-catalytic approach has led to successful examples of the control of stereogenic centers, the control of stereogenic axes has remained underexplored. In this study, an acylimine intermediate was generated through photoredox catalysis, and a symmetric substrate, 2-arylresorcinol, was desymmetrized with the aid of chiral phosphoric acid catalysis. Using this approach, a stereogenic center and stereogenic axis were successfully controlled to provide a natural-product-driven compound. The origins of enantioselectivity and diastereoselectivity were investigated through a density functional theory study of four possible enantiodetermining transition states. Consequently, the first total syntheses of the ring-contracted naphthylisoquinoline alkaloid ancistrobrevolines A and B were accomplished concisely. This approach provides not only a novel methodology and strategy to synthesize naphthylisoquinoline alkaloids but also a direction to advance catalytic research and total synthesis studies.