Biocatalytic asymmetric radical alkene hydration

Asymmetric alkene hydration provides direct access to enantiopure alcohols and has been extensively developed through ionic mechanisms. Radical pathways remain largely unexplored, despite their potential for late-stage functionalization and functional-group tolerance. In this context, the Drago-Mukaiyama hydration—which proceeds via a metal–hydride hydrogen atom transfer (MHAT) mechanism—has found numerous applications in total synthesis, yet achieving high stereocontrol remains challenging. Here we show that cytochrome P450BM3 can be repurposed as a radical hydratase that catalyzes the asymmetric radical hydration of both terminal and internal alkenes under aerobic conditions, affording a range of enantioenriched alcohols with up to 99% enantiomeric excess. Mechanistic investigations reveal a pathway initiated by metal–hydride hydrogen atom transfer (MHAT) and asymmetric intermolecular radical addition of dioxygen. A subsequent kinetic resolution of the hydroperoxide intermediate further upgrades the enantioselectivity of the alcohol product. This study highlights that radical alkene hydration can be catalyzed by haemoproteins, thus expanding the scope of challenging asymmetric reactions accessible to haemoproteins.