Cobalt-Catalyzed Desymmetrizing Hydrogenation of Cyclic Anhydrides
Lei Yang1, Denghong Yan1, Yuanzheng Wang1
1Department of Chemistry and Shenzhen Grubbs Institute, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen, China.
Abstract:
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.
Related Concept Videos
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
02:13Reduction of Alkenes: Catalytic Hydrogenation
Metals like palladium, platinum, and nickel are commonly used in their solid forms — fine powder on an inert surface. As these catalysts remain insoluble in the reaction mixture, they are referred to as heterogeneous catalysts.
The hydrogenation process takes place on the surface of...
01:28Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation
02:44Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...