Substrate-Photocatalyst Reactivity Matching Enables Broad Aryl Halide Scope in Light-Driven, Reductive Cross-Electrophile Coupling Using 13C NMR as a Predictor

The cross-electrophile coupling between aryl and alkyl halides is an important synthetic tool in the creation of Csp2–Csp3 bonds from abundant building blocks. These couplings have traditionally relied on thermally driven, reductive couplings using metallic Zn/Mn to generate reactive low-valent nickel species. Recent work has expanded this reactivity to visible light-driven methodologies utilizing a range of photocatalysts and terminal reductants. However, early photocatalyzed approaches required the use of precious metal photocatalysts and stoichiometric amounts of a costly silane. The work described herein expands photoredox catalyzed cross-electrophile coupling with a focus on the use of organic photocatalysts and an inexpensive, readily available sacrificial electron source (triethanolamine). To overcome limitations in substrate scope arising from redox incompatibilities between photocatalyst and substrate, we introduce two sets of conditions that minimize unwanted substrate-specific side reactivity. These synthetic protocols enable cross-electrophile couplings of challenging aryl bromide substrates, such as unprotected bromoindoles and 2-bromopyrimidines. We found that the propensity of aryl halide reagents to undergo side reactions is correlated with electronic parameters: the C–Br 13C chemical shift of aryl bromides is a robust predictor for this reactivity and enables facile reaction condition selection.