Electrochemically Cooperative Halogen Cation Delivery Enables Modular Electrophilic Haloesterification of Both Activated and Unactivated Alkenes

Abstract

Intermolecular haloesterification of alkenes is a practical platform for modular ester synthesis. However, current methods are restricted to aryl activated and directing-group contained alkenes, leaving low-reactivity, electron-deficient alkenes with alkyl substituents largely underexplored. Notably, electrophilic reaction involving chloroesterification of electron-deficient alkenes is also challenging duo to the difficulty of controlling selectivity. In this work, we present an electrochemically cooperative halogen cation delivery strategy that achieves modular electrophilic haloesterification of both activated and unactivated alkenes with good chemo-, regio-, and diastereoselectivity. It exhibits enhanced reactivity (with yields up to 90%) and selectivity (regioselectivities and diastereoselectivities exceeding 20:1), facilitated by the amide-mediated transfer of halogen cations to activate Cl⁺ donor and promote the generation of stable halogen-contained cation intermediates (β-halo carbocation or halonium), for the electrochemically oxidative ‘electrophile–nucleophile’ (‘E–Nu’) approach. Di-, tri-, and tetrasubstituted alkenes with various electronic properties, as well as terminal alkenes, have been successfully haloesterified, showcasing good tolerance to functional groups. Moreover, the strategy is applicable to gram-scale synthesis, and late-stage elaboration of bioactive compounds. It also enables the construction of quaternary carbons, even multiple contiguous ones in reactions.