A General Photocatalytic Strategy for Nucleophilic Amination of Primary and Secondary Benzylic C–H Bonds

Abstract

We report a visible-light photoredox-catalyzed method that enables nucleophilic amination of primary and secondary benzylic C(sp 3 )−H bonds. A novel amidyl radical precursor and organic photocatalyst operate in tandem to transform primary and secondary benzylic C(sp 3 )−H bonds into carbocations via sequential hydrogen atom transfer (HAT) and oxidative radicalpolar crossover. The resulting carbocation can be intercepted by a variety of N-centered nucleophiles, including nitriles (Ritter reaction), amides, carbamates, sulfonamides, and azoles, for the construction of pharmaceutically relevant C(sp 3 )−N bonds under unified reaction conditions. Mechanistic studies indicate that HAT is amidyl radical-mediated and that the photocatalyst operates via a reductive quenching pathway. These findings establish a mild, metal-free, and modular protocol for the rapid diversification of C(sp 3 )−H bonds to a library of aminated products.

Dataset Design for Building Models of Chemical Reactivity

“…Isolated versus analytical yields for (A) literature-extracted Ni-catalyzed C–O couplings and (B) a reported photocatalytic C–H activation substrate scope . Common reasons for the discrepancies between the yields are given.…”

Visible‐Light‐Driven Four‐Component Radical Relay Aminocarbonylation of Unactivated Alkenes†

“…The results of luminescence quenching experiments showed that it should be the amine that initially quenches the photoexcited state 4CzIPN to form highly reducing photocatalyst, thus initiating the catalytic cycle. Moreover, recent research by the Doyle [ 18 ] group has also demonstrated that the organic photocatalyst CF 3 ‐4CzIPN also exhibited potent reducing properties when it interacted with reductive amines. Indeed, in the current four‐component radical aminocarbonylation of perfluoroalkyl iodides, the addition of N ‐cyclohexylmorpholine as additive produced superior results.…”

Photocatalytic Cyclization Cascades by Radical Relay toward Pyrrolo[1,2-a]indoles: Synthesis, Mechanism, and Application

“…Photocatalytic transformation has attracted the ever-growing attention of chemists. − Crucially, the transformations often needed the use of organic small molecules as photocatalysts (PC). While chemists have turned their attention to catalytic intermolecular additions by radical relay over several years, − it is still of great significance to realize cyclization cascades by radical addition-based photocatalytic radical relay. Enlightened by the versatility of hydrogen-atom-abstraction (HAA) in radical chemistry, − in this paper, we would like to develop a photocatalytic radical cyclization cascade that involved radical relay and the HAA process for preparing the privileged core pyrrolo­[1,2- a ]­indole from N -alkene-linked indoles. , Distinctively, the key intermediate A derived from the radical relay process would undergo a HAA process instead of an oxidative RPC pathway.…”