Hydrogen atom transfer (HAT)^[1] is a powerful technology in organic synthesis especially when coupled with photoredox catalysis. However, inducing enantioselectivity in these transformations proceeding through neutral radical intermediates is an outstanding challenge.^[2] The major impediments are represented by the scarce amenability of HAT catalysts for asymmetric design and by controlling the highly reactive and short-lived open-shell intermediates in a chiral microenvironment.^[3] While traditional approaches to chiral catalyst design rely on constructing a covalent chiral environment around the active site, we have disclosed a distinct approach. We have paired chiral phosphate ions, derived from privileged chiral phosphoric acids with commercial 2-mercaptopyridines.^[4] The chiral counterions render the achiral HAT catalysts (2-mercaptopyridines) effectively chiral.^[5] The two-component catalyst design is highly tunable and interchangeable, giving potentially access to numerous chital HAT catalysts while maintaining a low synthesis demand. We have applied our conceptual catalyst design to the photochemical deracemization of 2-aryl pyrrolidines, a prevalent subunit in active pharmaceutical ingredients. Mechanistic studies reveal that ion-pairing is the main non-covalent interaction shaping the assembly and that enantioenrichment occurs via enantioselective hydrogen atom relay in which the chiral HAT assembly induces enantioselectivity in hydrogen atom abstraction and delivery.

[1] L. Capaldo, D. Ravelli, M. Fagnoni Chem. Rev. 2022, 122, 1875.
[2] M. J. Genzink, J. B. Kidd, W. B. Swords, T. P. Yoon. Chem. Rev. 2022, 122, 1654.
[3] H. Subramanian, M. P. Sibi. Asian J. Org. Chem. 2023, 12, e202300175.
[4] Yalamanchili, N.; Alexandre, J. H.; Zuccarello, G. ChemRxiv. 2026; doi:10.26434/chemrxiv-2026- qwhqp.
[5] M. Mahlau, B. List, Angew. Chem. Int. Ed Engl. 2013, 52, 518–533.