Chemo- and Stereoselective Semireduction of Alkynes to E -Alkenes Catalyzed by Nonheme Iron Enzymes

The semireduction of alkynes represents a powerful yet challenging transformation that requires simultaneous control of stereoselectivity and chemoselectivity. Currently, synthetic methods for the trans-reduction of alkynes to E-alkenes remain limited, particularly in the realm of biocatalysis. Herein, we report the repurposing of a nonheme iron dioxygenase for the trans-reduction of alkynes. Through screening and directed evolution, we obtained variants of gentisate 1,2-dioxygenase that enable the preparation of structurally diverse E-alkenes in high yields (up to 99% yield) with excellent stereoselectivity (16 examples with E/Z ratios of 99/1) and chemoselectivity (21 cases with 0% alkane). Mechanistic studies suggest a pathway involving hydride attack to generate a trans anion intermediate, followed by protonation to directly furnish the E-alkene. This metalloenzymatic trans-reduction pathway is mechanistically distinct from the classical syn-addition/isomerization pathway typically observed in transition-metal catalysis.