Asymmetric Reduction of Unactivated Alkenes

The asymmetric reduction of unactivated alkenes remains a key challenge in synthesis due to their inherent lack of polarity and steric bias. Advances range from hydrogenation with molecular hydrogen and precious transition-metal catalysts, such as Crabtree's Ir and Noyori's Ru systems, to modern approaches employing abundant metals or radical-mediated hydrogen atom transfer (HAT) under mild conditions. Over the past decades, chemists have assembled a diverse mechanistic toolbox, with each strategy achieving excellent results under specific substrate, selectivity, and operating conditions. Clear trends have emerged toward greater sustainability, lower costs, and operational simplicity. Biocatalysis, previously limited to activated alkenes such as enones, has advanced via engineered promiscuous reductases, photobiocatalysis, and multifunctional enzymes, offering complementary and highly selective transformations. Enzymatic strategies for the reduction of unactivated alkenes, however, are still rare and highly substrate-specific. Recent innovations, such as BioHAT integrate radical-based mechanisms into engineered proteins and represent a potential first step toward general and practical biocatalytic solutions. The development of asymmetric reduction of unactivated alkene and synergistic integration of chemical and enzymatic strategies are summarized.