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

Ljiljana Pavlovic; Lauren N Mendelsohn; Hongyu Zhong; Paul J Chirik; Kathrin H Hopmann

doi:10.1021/acs.organomet.2c00180

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

Organometallics. 2022 Jul 25;41(14):1872-1882. doi: 10.1021/acs.organomet.2c00180.

Authors

Ljiljana Pavlovic¹, Lauren N Mendelsohn², Hongyu Zhong², Paul J Chirik², Kathrin H Hopmann¹

Affiliations

¹ Department of Chemistry, UiT - The Arctic University of Norway, N-9037 Tromsø, Norway.
² Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States.

Abstract

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.