Oxygen-enabled Fe-catalyzed heteroatom α-C(sp3)-H functionalization with nucleophiles.

Here, we report an iron-catalyzed aerobic transformation that activates N/O/S-α-C(sp3)-H bonds under blue light irradiation, forming hemiacetal-type analogues, amenable for trapping with diverse commercially available N-, O-, S-, and C-nucleophiles. The method achieves azolation, amination, acetalization, hydroxylation, thiolation, alkylation, and arylations across ethers, thioethers and pyrrolidines with high chemoselectivity and regioselectivity. Mechanistic studies indicate that this system synergizes iron-catalyzed photoinduced LMCT, followed by chlorine radical-initiated HAT and subsequent O2 trapping of the resulting alkyl radicals to afford key hemiacetal-type intermediates. Significantly, FeCl3 serves a triple catalytic role by generating chlorine radicals, functioning as a redox shuttle and acting as a Lewis acid activator.