Chromium-Catalyzed Stereodivergent Carbonyl Addition Dictated by Non-Covalent Interactions.

Catalytic stereodivergent synthesis, which accesses the full complement of stereoisomers from a common precursor set, is a paramount objective in drug discovery. However, achieving this control via radical-involved pathways remains a formidable frontier due to the transient nature of open-shell intermediates. Here, we report a unified chromium-catalyzed platform that harnesses a radical-polar crossover mechanism to achieve the fully ligand-controlled stereodivergent synthesis of chiral β-fluoro alcohols. We demonstrate that the stereochemical outcome is not inherent to the substrate but is dictated by the ancillary ligand through distinct non-covalent interactions: a chiral bisoxazoline ligand enforces a rigid transition state via fluorine-mediated hydrogen bonding to selectively deliver syn-diastereomers, whereas a chemically distinct pyridine-imidazoline ligand exploits electronic desymmetrization via π-π stacking to invert selectivity toward anti-isomers. Notably, this protocol enables the programmable assembly of all four stereoisomers of fluorosugar derivatives.