Intramolecular Benzimidazole Hydroamination Enabled by Proton-Coupled Electron Transfer

Abstract

We present a catalytic anti-Markovnikov intramolecular hydroamination of unactivated alkenes with benzimidazoles enabled by a PCET activation of the benzimidazole N-H bond, inspired by previous hydroaminations and hydroamidations by the Knowles group. This work further demonstrates the potential of PCET for the direct homolytic activation of heteroatom-hydrogen bonds found in many common organic functional groups for useful synthetic transformations. This method works with complete conversion of starting material and high yield of product, and further optimization efforts will be pursued to improve yield. We also report mechanistic studies supporting a concerted PCET mechanism and computational studies of the thermodynamics and kinetics of the system. Future synthetic directions include evaluation of the substrate scope for different alkene substitution patterns, substituted and functionalized benzimidazoles, other nitrogen-containing heterocycles, and intermolecular variants of the reaction. Quantitative mechanistic analysis and extended computational modeling of additional substrates can also be performed to better understand the operative PCET mechanism and physical organic parameters for future reaction design.