Ir-Catalyzed Cascade C–H Fusion of Aldoxime Ethers and Heteroarenes: Scope and Mechanisms

Abstract

A concise synthesis of phenanthridine derivatives is achieved by an iridium-catalyzed direct fusion of oxime ethers and heteroarenes, which is a successful example of a cascade C–H/C–H cross-coupling/cyclization strategy for polycyclic heteroaromatic synthesis. By subtle tuning of the reaction conditions, both benzo- and simple five-membered heteroarenes are suitable substrates under similar but different conditions. The key is the right choice of a silver salt. The detailed mechanistic study discloses that the first C–H/C–H cross-coupling step involves an [IrII]–[IrIV] catalytic cycle, which needs Ag2O as the oxidant. For the second cyclization step, a radical process takes control in the reactions of benzoheteroarenes and Ag2O is required; however, a C–H cyclization functions in the reactions of simple five-membered heteroarenes involving an [IrI]–[IrIII] catalytic cycle, and AgTFA is necessary.