Red-shifted photoredox generation and trapping of alkyl radicals towards bioorthogonality

Abstract

The photocatalytic generation and trapping of alkyl radicals is a powerful synthetic tool in organic chemistry, but it remains underexplored in biological settings. Here, we present two photoredox systems that leverage green- or red-light irradiation for the activation and subsequent Giese coupling of redox-active alkyl phthalimide esters. Besides utilizing mild low-energy light sources, these reactions operate with biocompatible BnNAH or NADH as electron donor. Notably, they display compatibility with air, water and biologically relevant conditions, including cell-culture media or even cell lysates. This work marks a significant step towards integrating synthetic alkyl-radical chemistry into biological settings.