biostudies-literatureUnknown16(1)Sun ZChiral spirocyclic scaffolds have garnered significant attention in drug discovery and chiral ligand development due to their rigid structures and potential bioactive properties, yet stereodivergent synthesis of such systems, particularly those bearing non-adjacent stereocenters, remains a formidable challenge. Herein, we report a dynamic radical recombination (DRR) strategy that enables cobalt-hydride-catalyzed ligand-controlled stereodivergent olefin hydroalkylation, delivering a series of spirocyclic compounds bearing 1,3-non-adjacent stereocenters with up to >99:1 er and >20:1 dr. Density functional theory (DFT) calculations reveal that different ligands induce distinct reaction mechanism, resulting in diastereoselectivity reversal through dynamic radical recombination pathway. BiologiNature communications9449https://www.ebi.ac.uk/biostudies/studies/S-EPMC12559201biostudies-literatureDynamic radical recombination enabling stereodivergent construction of spirocycles with nonadjacent stereocenters.PMC12559201Huang JJin YSun ZXu JLi YPeng FShao ZZhang ZRen JLiang JOu YChen XZhao KfalseDynamic radical recombination enabling stereodivergent construction of spirocycles with nonadjacent stereocenters.Chiral spirocyclic scaffolds have garnered significant attention in drug discovery and chiral ligand development due to their rigid structures and potential bioactive properties, yet stereodivergent synthesis of such systems, particularly those bearing non-adjacent stereocenters, remains a formidable challenge. Herein, we report a dynamic radical recombination (DRR) strategy that enables cobalt-hydride-catalyzed ligand-controlled stereodivergent olefin hydroalkylation, delivering a series of spirocyclic compounds bearing 1,3-non-adjacent stereocenters with up to >99:1 er and >20:1 dr. Density functional theory (DFT) calculations reveal that different ligands induce distinct reaction mechanism, resulting in diastereoselectivity reversal through dynamic radical recombination pathway. Biologi2025-01-01T00:00:00Z2025 Oct2026-06-05T08:59:14.456Z2026-05-15T03:07:52.019ZS-EPMC125592014114547810.1038/s41467-025-64491-y