Direct alkylation of heteroarenes with unactivated bromoalkanes using photoredox gold catalysis

Abstract

Although visible light photoredox catalysis has emerged as a powerful tool for the construction of C-C bonds, common catalysts and/or their photoexcited states suffer from low redox potentials, limiting their applicability to alkyl radical generation from substrates with activated carbon-halogen bonds. Radicals derived from these activated compounds, being highly electrophilic or stabilized, do not undergo efficient addition to heteroarenes. Herein we describe the photocatalytic generation of nucleophilic alkyl radicals from unactivated bromoalkanes as part of a universal and efficient cross-coupling strategy for the direct alkylation of heteroarenes using a dimeric gold(i) photoredox catalyst, [Au₂(bis(diphenylphosphino)methane)₂]Cl₂. The method proves to be efficient for alkylation of arenes under mild conditions in the absence of directing groups.

Fig. 1. Previous and present work in direct C–H alkylations.

Fig. 2. Proposed mechanism of the direct C–H alkylation of heteroarenes.

Fig. 3. Kinetic study of the absolute rate of alkyl radical addition to lepidine, ratio of unopened to opened methylcyclobutane addition vs. [lepidine] (M).