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.