Jin, JianwenZhao, YichaoKyne, Sara HelenFarshadfar, KavehAriafard, AlirezaChan, Philip Wai Hong2025-12-162025-12-162041-1723PubMed:34210971ORCID:/0000-0003-2383-6380/work/198195220https://hdl.handle.net/1885/733795534Strategies that enable intermolecular site-selective C–H bond functionalisation of organic molecules provide one of the cornerstones of modern chemical synthesis. In chloroalkane synthesis, such methods for intermolecular site-selective aliphatic C–H bond chlorination have, however, remained conspicuously rare. Here, we present a copper(I)-catalysed synthetic method for the efficient site-selective C(sp3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T at room temperature. A key feature of the broad substrate scope is tolerance to unsaturation, which would normally pose an immense challenge in chemoselective aliphatic C–H bond functionalisation. By unlocking dichloramine-T’s potential as a chlorine radical atom source, the product site-selectivities achieved are among the most selective in alkane functionalisation and should find widespread utility in chemical synthesis. This is exemplified by the late-stage site-selective modification of a number of natural products and bioactive compounds, and gram-scale preparation and formal synthesis of two drug molecules.This work was supported by a Discovery Project Grant (DP210103425) from the Australian Research Council.12en© 2021, The Author(s).2021-12-0110.1038/s41467-021-23988-y85109171415