Mechanisms of cobalt-catalyzed asymmetric hydrogenation of multi-substituted α,β-unsaturated carboxylic acids

Herein the reaction mechanisms and the origin of enantioselectivity of the Co-catalyzed asymmetric hydrogenation (AH) of multi-substituted α,β-unsaturated carboxylic acids involving Co(0)/Co(II) catalytic redox cycle and Co(II)/Co(II) non-redox one were investigated using density functional theory (DFT) method. For the AH reaction adopting Co(0)/Co(II) redox cycle by (R,R)-(^PhBPE)Co(0)(COD) system, it is revealed that the oxidative hydride transfer step is more favorable than the step-wise process including the oxidative addition step and the migratory insertion step in the hydrogenation process. The isomerization between Λ- and Δ-conformers along reaction pathway was proposed, interestingly, the AH pathway by Λ catalytic conformer is dominant to achieve R-product while that by Δ catalytic conformer is dominant to achieve S-product for tetra-substituted substrate. Unlike conventional models in which stereoselectivity is determined by a single step, the calculated results indicate that both the oxidative hydride transfer step and reductive elimination one cooperatively control the enantioselectivity of this reaction. Similarly, for that adopting Co(II)/Co(II) non-redox cycle by (R,R)-(^PhBPE)Co(II)-stearate system, the enantioselectivity is found to be cooperatively determined by the migratory insertion step and the σ‑bond metathesis one. In addition, the reversed enantioselectivity between tetra‑ and di-substituted substrates originates from steric bulk. Importantly, the Co(II)-monohydride species got involved instead of the Co(II)-dihydride species in either the Co(0)/Co(II) redox cycle or the Co(II)/Co(II) non‑redox cycle. This work not only agrees well with experimental observation, but also provides theoretical insights into the Co-catalyzed AH and establishes a valuable foundation for the development of efficient earth‑abundant metal catalysts