Atroposelective synthesis of eight-membered lactam-bridged N-arylindoles via stepwise cut-and-sew strategy

Abstract

The development of efficient processes for the preparation of structurally diverse axially chiral biaryls has been an important goal in synthetic organic chemistry and asymmetric catalysis. However, in sharp contrast to the well-established open-chain biaryls, the catalytic enantioselective construction of medium-sized bridged biaryls remains underdeveloped. In particular, no enantioselective synthesis of such frameworks possessing a configurationally stable stereogenic C-N axis with step- or pot-economy has been disclosed. Herein, we report a practical synthesis of atropisomeric eight-membered lactam-bridged N-arylindoles through a conceptually intriguing stepwise cut-and-sew strategy. The key to success lies in the development of a silver-catalyzed atroposelective ring-opening/cyclization cascade reaction of N-arylindole lactams with isocyanoacetates to establish C-N axial chirality. This method features operational simplicity, good functional group tolerance, high efficiency, as well as good to high enantiocontrol. It is also noteworthy that these scaffolds exhibit large Stokes shifts, demonstrating their potential applications as fluorescent dyes.