Cobalt-Catalyzed Desymmetrizing Hydrogenation of Cyclic Anhydrides.

Achieving general asymmetric catalytic manifolds that accommodate broad substrate diversity remains a long-standing and highly sought-after goal in synthetic chemistry. Herein, we report an efficient cobalt-catalyzed desymmetric hydrogenation of structurally diverse cyclic 1,2- and 1,3-diacid anhydrides, enabling access to pharmaceutically relevant chiral γ- and δ-lactones with broad substrate scope and excellent enantioselectivity (up to 99% ee). The reaction is readily scalable, as demonstrated by gram-scale synthesis of several representative products. Notably, this 3d-metal catalytic platform represents a rare example that outperforms platinum-group-metal-based counterparts in both generality and stereoselectivity. DFT studies identify a catalytically active d7 Co(II) dihydride complex with an outer-sphere hydride transfer mechanism, wherein a relatively flexible chiral pocket underlies the broad substrate compatibility of this catalytic system.