Site‐Selective Distal C(sp3)−H Bromination of Aliphatic Amines as a Gateway for Forging Nitrogen‐Containing sp3 Architectures

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp3)−H sites in aliphatic amines with an excellent and predictable site‐selectivity pattern. The resulting halogenated building blocks serve as versatile linchpins to enable a series of carbon‐carbon and carbon‐heteroatom bond‐formations at remote C(sp3) sites, thus offering a new modular and unified platform that expediates the access to advanced sp3 architectures possessing valuable nitrogen‐containing saturated heterocycles of interest in medicinal chemistry settings. A site‐selective bromination of C(sp3)−H bonds in unprotected aliphatic amines has been developed, achieved by tuning of the electronics properties of the proximal C−H bonds via substrate protonation. Consecutive intramolecular cyclization of alkyl bromide offered a series of N‐containing heterocycles characterized by high ring strains. Moreover, the resulting C(sp3)−Br serves as a synthetic linchpin can be readily transferred to C(sp3)−C, N, O bonds, enabling diverse functionalization at previously untouched C(sp3)−H sites.