Copper(I)‐Mediated Site‐Selective Tertiary <i>δ</i>–<i>κ</i>‐C(<i>sp</i>³)−H Bond Chlorination of Ketones and Carboxylic Esters and Amides by Dichloramine‐T

Abstract A synthetic method to prepare δ – κ ‐chloroketones, ‐esters and ‐amides that relies on the copper(I)‐mediated chlorination at the unactivated tertiary δ – κ ‐C( sp 3 )−H bond of ketones, carboxylic esters, and amides by dichloramine‐T is presented. By exploiting the ability of the N ‐chloramide to act as both the hydrogen atom transfer (HAT) and chlorination reagent, the reactions were shown to be site‐selective with halogenation only occurring at the unactivated tertiary carbon center situated four to ten C−C bond distances away from the carbonyl functional group in the substrate. The site‐selectivity of the chlorination protocol was further exemplified by the installing of the C−Cl bond at the distal position of one example containing two tertiary carbon centers and the late‐stage functionalization of two drug molecules.