Copper(I)-catalysed site-selective C(sp 3)–H bond chlorination of ketones, (E)-enones and alkylbenzenes by dichloramine-T

Jianwen Jin, Yichao Zhao, Sara Helen Kyne, Kaveh Farshadfar, Alireza Ariafard, Philip Wai Hong Chan

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4 Citations (Scopus)


Strategies 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.

Original languageEnglish
Article number4065
Number of pages12
JournalNature Communications
Issue number1
Publication statusPublished - Dec 2021

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