Regiodivergent and stereoselective hydroxyazidation of alkenes by biocatalytic cascades

Asymmetric functionalization of alkenes allows the direct synthesis of a wide range of chiral compounds. Vicinal hydroxyazidation of alkenes provides a desirable path to 1,2-azidoalcohols; however, existing methods are limited by the control of stereoselectivity and regioselectivity. Herein, we describe a dual-enzyme cascade strategy for regiodivergent and stereoselective hydroxyazidation of alkenes, affording various enantiomerically pure 1,2-azidoalcohols. The biocatalytic cascade process is designed by combining styrene monooxygenase-catalyzed asymmetric epoxidation of alkenes and halohydrin dehalogenase-catalyzed regio-selective ring opening of epoxides with azide. Additionally, a one-pot chemo-enzymatic route to chiral beta-hydroxytriazoles from alkenes is developed via combining the biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.

Automated summary

A dual-enzyme cascade strategy was developed for regiodivergent and stereoselective hydroxyazidation of alkenes, leading to the synthesis of various enantiomerically pure 1,2-azidoalcohols. This approach combines the asymmetric epoxidation of alkenes and regio-selective ring opening of epoxides with azide catalyzed by styrene monooxygenase and halohydrin dehalogenase. Additionally, a one-pot chemo-enzymatic route to chiral beta-hydroxytriazoles from alkenes was achieved by combining biocatalytic cascades and Cu-catalyzed azide-alkyne cycloaddition.