Affiliation:
1. Department of Chemical Science and Engineering Tokyo Institute of Technology O-okayama, Meguro-ku Tokyo 152-8550 Japan
2. Graduate School of Pharmaceutical Sciences The University of Tokyo 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033 Japan
Abstract
AbstractDearomative construction of multiply‐fused 2D/3D frameworks, composed of aromatic two‐dimensional (2D) rings and saturated three‐dimensional (3D) rings, from readily available quinolines has greatly contributed to drug discovery. However, dearomative cycloadditions of quinolines in the presence of photocatalysts usually afford 5,6,7,8‐tetrahydroquinoline (THQ)‐based polycycles, and dearomative access to 1,2,3,4‐THQ‐based structures remains limited. Herein, we present a chemo‐, regio‐, diastereo‐, and enantioselective dearomative transformation of quinolines into 1,2,3,4‐THQ‐based 6–6–4‐membered rings without any catalyst, through a combination of nucleophilic addition and borate‐mediated [2+2] photocycloaddition. Detailed mechanistic studies revealed that the photoexcited borate complex, generated from quinoline, organolithium, and HB(pin), accelerates the cycloaddition and suppresses the rearomatization that usually occurs in conventional photocycloaddition. Based on our mechanistic analysis, we also developed further photoinduced cycloadditions affording other types of 2D/3D frameworks from isoquinoline and phenanthrene.
Funder
Japan Society for the Promotion of Science
Fusion Oriented REsearch for disruptive Science and Technology
Core Research for Evolutional Science and Technology
Asahi Glass Foundation