Reaction engineering enables selective chemoenzymatic transformation of alkynes into α-bromoketones and 1,2-dibromostyrenes

Catalytic synthesis of α-haloketones from alkenes and alkynes represents a step- and atom-economic pathway. However, traditional methods are challenged by poor chemoselectivity in the halogenation process. Herein, the vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) is used to generate reactive hypohalite in situ for the electrophilic halogenation of activated alkynes, directly yielding α-bromoketones and 1,2-dibromostyrenes. The distribution of the two products is highly influenced by the concentration of the halide source in the reaction medium, i.e., low KBr concentration resulted in α-bromoketones, while high KBr concentration resulted in 1,2-dibromostyrenes. This “KBr-switch” process enables the synthesis of a variety of functional products with an enzyme turnover number of up to 232 000. This study not only offers a facile and controllable route by combining chemoenzymatic catalysis with reaction engineering for potentially bioactive oxyhalogenated compounds, but also expands the oxidation chemistry of CiVCPO.