Combining photocatalysis with imine reductases to access stereodefined pyrrolidines from oxime benzoates

Abstract

In this paper, we present the first combination of commercially available imine reductases (IREDs) with the photocatalytic hydroimination of alkene-tethered iminyl radicals. Notably, the photochemical step was achieved from simple oxime benzoates lacking additional electron-withdrawing activation. This hybrid cascade enabled the synthesis of diverse 2,5-disubstituted pyrrolidines with good functional group compatibility and tolerance to sterically demanding substrates. Additionally, our methodology was extended to the preparation of a novel all cis analogue of (−)-codonopsinine. Mechanistic studies suggested the generation of the key iminyl radical from the benzoate by triplet–triplet energy transfer (TTE_nT).