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

Jinhong Chen; Tan Kang Clarence; Jesus Rodrigalvarez; Shuai Zhang; Ruben Martin

doi:10.1002/anie.202406485

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

Angew Chem Int Ed Engl. 2024 May 21:e202406485. doi: 10.1002/anie.202406485. Online ahead of print.

Authors

Jinhong Chen¹, Tan Kang Clarence², Jesus Rodrigalvarez¹, Shuai Zhang¹, Ruben Martin³

Affiliations

¹ Institute of Chemical Research of Catalonia, ICIQ, SPAIN.
² Institute of Chemical Research of Catalonia, iciq, SPAIN.
³ Institute of Chemical Research of Catalonia, Institute of Chemical Research of Catalonia, Av. Paisos Catalans, 16, 43007, Tarragona, SPAIN.

PMID: 38770612
DOI: 10.1002/anie.202406485

Abstract

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp3)-H sites in aliphatic amines with 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 expedites the access to advanced sp3 architectures possessing valuable nitrogen-containing saturated heterocycles of interest in medicinal chemistry settings.

Keywords: C(sp3)-H functionalization; Hydrogen-atom transfer; amine; coupling; halogenation.