Transient-Directing Group-Enabled Manganese-Catalyzed C–H Alkylation

Abstract

Abstract The construction of C–C bonds by manganese-catalyzed C–H activation thus far relies on permanent directing groups that need to be installed and removed, while the use of transient directing groups remains an elusive challenge. In sharp contrast, we herein describe a manganese-catalyzed intramolecular C–H alkylation of indole-3-carboxaldehydes enabled by the use of a transient directing group in catalytic quantities. Our strategy provided access to a wide range of N1/C2-fused polycyclic indoles, generating a tertiary C-center in excellent yields and concomitant good functional group tolerance. The desired polycyclic indole underwent late-stage diversification guided by the native formyl directing group through C4–H activation, as well as leading to the decoration with barbituric acid moiety. Additionally, computational mechanistic insight by DFT provided support for a rate-determining migratory insertion.