Cobalt-Catalyzed Asymmetric Hydrogenation of Enamides: Insights into Mechanisms and Solvent Effects

The mechanistic details of the (PhBPE)­Co-catalyzed
asymmetric
hydrogenation of enamides are investigated using computational and
experimental approaches. Four mechanistic possibilities are compared:
a direct Co(0)/Co­(II) redox path, a metathesis pathway, a nonredox
Co­(II) mechanism featuring an aza-metallacycle, and a possible enamide–imine
tautomerization pathway. The results indicate that the operative mechanism
may depend on the type of enamide. Explicit solvent is found to be
crucial for the stabilization of transition states and for a proper
estimation of the enantiomeric excess. The combined results highlight
the complexity of base-metal-catalyzed hydrogenations but do also
provide guiding principles for a mechanistic understanding of these
systems, where protic substrates can be expected to open up nonredox
hydrogenation pathways.