Unlocking the Alkynyl Bromide Radical Anion With Alternating Current for Inverse Sonogashira C─H Coupling

Abstract

Carbon–bromine bond cleavage is a fundamental step in many chemical transformations. Over the past two decades, the reductive cleavage of C(Ar)─Br bonds (via a stepwise pathway) and C(alkyl)─Br bonds (via a concerted pathway) has been extensively studied. In contrast, the cleavage of the C(alkynyl)─Br bond remains unreported. We hypothesized that this bond may follow a distinct dissociation pathway, diverging from the established mechanisms. Indeed, the possible generation of reactive alkynyl bromide radical anion intermediates could significantly enrich the synthetic toolbox. However, chemical additives are less attractive than an electrochemical approach. Herein, we report an alternating current (AC)‐promoted, Pd‐catalyzed ortho‐aryl C─H alkynylation employing unprecedented alkynyl bromide radical anion species. This “inverse” Sonogashira synthetic scheme accommodates a broad substrate scope, delivering alkynylated stilbene derivatives with excellent arene site selectivity. Mechanistic investigations, EPR spectroscopy, and DFT calculations suggest the involvement of a Pd(II)/Pd(III) pathway assisted by transient alkynyl bromide radical anion intermediates. This work opens a new method for bromoalkyne activation, demonstrates the capability of electrochemistry to enable efficient electrophilic alkynylation, and expands the synthetic toolkit for constructing complex stilbene‐based frameworks.