Where Enantioselection is Set: A Mechanistic Framework for Asymmetric Hydrogen-Atom Transfer.

Hydrogen-atom transfer (HAT) lies at the heart of radical chemistry, yet asymmetric HAT has been difficult because the high reactivity of radicals often forces H-transfer to proceed through early, weakly organized transition states, yielding small ΔΔG‡ and allowing rapid racemic background pathways to compete. Recent advances across small-molecule, metalloradical, cooperative, peptide, and enzymatic catalysis show that high enantioselectivity is attainable when the catalyst is engineered to exert stereocontrol precisely at the H-transfer step that sets configuration. In this minireview, we organize asymmetric HAT into five regimes-donation-controlled termination, radical-centered control, abstraction-controlled HAT, cooperative bimetallic catalysis, and enzyme-mediated HAT-each specified by where chiral information is introduced during H-transfer. Through representative cases, we illustrate how catalysts achieve enantioselection by defining radical geometry, guiding H-delivery, enforcing selective hydrogen abstraction, or confining donor-acceptor pairs within organized chiral environments. This mechanistic framework provides a unified lens spanning synthetic and biocatalytic systems, clarifies the distinct stereochemical logics in each regime, and highlights emerging opportunities for expanding asymmetric radical chemistry through precisely orchestrated H-atom transfer.