Native functionality in triple catalytic cross-coupling: sp³ C-H bonds as latent nucleophiles

The use of sp³ C-H bonds - which are ubiquitous in organic molecules - as latent nucleophile equivalents for transition metal - catalyzed cross-coupling reactions has the potential to substantially streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C-H arylation protocol that activates a wide array of C-H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and α-oxy sp³ C-H bonds in both cyclic and acyclic systems.