Asymmetric Reduction of Unactivated Alkenes.

Abstract

The asymmetric reduction of unactivated alkenes, which lack inherent polarity and steric differentiation, poses a persistent challenge in synthetic chemistry. This review covers a broad mechanistic landscape: classical hydrogenation using molecular hydrogen with precious-metal catalysts (Ir- and Ru-based systems), as well as newer methods employing earth-abundant metals or radical hydrogen atom transfer (HAT) under mild conditions. Trends toward sustainability, cost reduction, and operational simplicity are highlighted. In biocatalysis, engineered promiscuous reductases, photobiocatalytic systems, and multifunctional enzymes have expanded substrate scope beyond activated alkenes such as enones, yet enzymatic reduction of unactivated alkenes remains rare and substrate-specific. Emerging approaches such as BioHAT, which embed radical-based mechanisms within engineered proteins, are identified as early steps toward broadly applicable biocatalytic solutions. The review synthesizes progress in both chemical and enzymatic domains and discusses their potential synergistic integration.

Mechanism

Key mechanisms include hydrogenation via precious-metal catalysts (Ir, Ru) with molecular hydrogen, radical-mediated hydrogen atom transfer (HAT) using abundant metals, and BioHAT, which incorporates radical-based pathways into engineered proteins to enable biocatalytic reduction of unactivated alkenes.