Reactivity of Cobalt(III) vs Rhodium(III): Role of Multispin Energy Surfaces in the Regio- and Enantioselective Intermolecular Carboamination

Abstract

Asymmetric nonannulative intermolecular carboamination via C–H activation represents a powerful strategy for converting inexpensive alkene feedstocks into value-added products. A comprehensive study was conducted on the reaction mechanism and origin of selectivity with acrylate and N-phenoxyacetamide as substrates, which affords valuable unnatural tyrosine analogues with high regio- and enantioselectivity. By integrating detailed computational studies with available experimental evidence, we demonstrate that the observed selectivity is governed by reduced activation strain energy in conjunction with extensive noncovalent interactions. In particular, favorable dispersion and electrostatic interactions selectively stabilize the transition state leading to the S-configured stereocenter. Notably, the key spin-crossover event within the cobalt catalytic manifold is crucial for rendering the reaction feasible. The origin of the underperformance of the analogous rhodium catalyst is also examined using various analysis techniques. Furthermore, computational predictions for new alkene partners, namely styrene and vinyltrimethylsilane, indicate excellent enantiomeric excess, highlighting the broader synthetic potential of this catalytic system.