Alkene hydrogenation is a cornerstone of chemical synthesis, yet enzymatic strategies remain limited to electron deficient substrates via hydride transfer. Using heme enzymes, we unlock a hydrogenation pathway for the asymmetric reduction of unactivated olefins. A silane promoted heme-cysteine redox cycle in the active site catalyzes sequential hydrogen atom transfer to challenging scaffolds including 1,1-disubstituted as well as tri- and tetrasubstituted alkenes. The evolved enzymes are promiscuous, oxygen-tolerant, utilize earth-abundant iron, and can operate on gram scale under ambient conditions. Orthogonal hydrogen atom sources enable site-divergent asymmetric isotope labeling. Mechanistic and computational studies support a stepwise radical process. Our work introduces a biochemical approach for stereoselective olefin reduction and provides a platform for next-generation biocatalytic hydrogenation.
Vallapurackal et al. (Thu,) studied this question.