PIDA/I₂-Mediated α- and β-C(sp³)-H Bond Dual Functionalization of Tertiary Amines

The α,β-C(sp³)-H bond dual functionalization of tertiary amines is still a challenging task for both organic and medicinal chemists. Herein a direct, mild, metal-free, and site-specific method mediated by PIDA/I₂ was developed for α,β-C(sp³)-H bond dual functionalization of tertiary amines, and this method can provide facile access to α-keto lactams or rarely studied α,α-diiodo lactams. Moreover, this method was used for the effective syntheses of three natural products [obscurumine C (13), obscurumine O (17), and strychnocarpine (18)] and direct preparation of mimics of the in vivo metabolites of two FDA-approved drugs (imatinib and donepezil) in 36-60% overall yield. The method represents a promising protocol for the late-stage α,β-C(sp³)-H bond oxidative dual functionalization of tertiary amine-containing drugs and complex natural products.