Expedient Cyano-hydroxylation of Alkenes Enabled by Halogen Atom Transfer Induced Radical Ring-Opening Elaboration of 3-Bromo-isoxazoline Cycloadducts

Herein, we present a highly efficient one-pot, two-step synthesis of β-hydroxy nitrile scaffolds, which possess both significant synthetic value and notable biological activity, starting from readily accessible alkenes. This methodology relies crucially on the seamless integration of a highly regioselective (3+2) cycloaddition reaction, employing the commercially available 1,1-dibromoformaldoxime as the 1,3-dipole precursor, with a subsequent halogen atom transfer-induced radical ring-opening elaboration of the resulting 3-bromo-2-isoxazoline cycloadducts. This protocol is featured by mild reaction conditions, broad alkene scope and various derivatizations of the obtained cyano-hydroxylation products, offering a versatile and practical pathway to accessing multi-functionalized molecules.