Organocatalytic asymmetric electrochemical synthesis of epibromohydrins from allylic alcohols

Abstract

Optically active epibromohydrins represent a structurally privileged family of chiral building blocks, yet their asymmetric synthesis remains hampered by a reliance on stoichiometric chemical oxidants and multi-step protocols. Herein, we report an organocatalytic asymmetric electrochemical bromoetherification of allylic tertiary alcohols that constructs these densely functionalized scaffolds in a single operational step. By merging interfacial electrosynthesis with a synergistic chiral phase-transfer catalyst (PTC) and chiral phosphoric acid (CPA) counter anion framework, the high reactivity of electrogenerated Br2 species is tightly regulated, successfully suppressing unselective, racemic background pathways. Utilizing inexpensive NaBr as the bromine source in a DCM/H2O biphasic system, a range of allylic tertiary alcohols were smoothly converted into the corresponding bromoepoxides in high yields and with high enantioselectivities. Control experiments and cyclic voltammetry studies suggested that stereocontrol is sensitive to the balance between anodic bromide generation and phase-transfer-mediated trapping. This strategy is complementary to the conventional synthesis of epibromohydrins by chemical oxidation.