Unraveling the mechanism and probing the origins of stereocontrol in cobalt-catalyzed carboamination reaction

Abstract

In the present study, the potential reaction mechanism for the cobalt-catalyzed carboamination of phenoxyacetamide with butyl acrylate was investigated using density functional theory (DFT) calculations. The computed energy profile indicates that the thermodynamically preferred pathway proceeds via sequential N-H deprotonation, C-H activation, [2,1]-alkene insertion, oxidative addition, reductive elimination, and final protonation of the oxygen and nitrogen atoms. By contrast, the alternative route involving [1,2]-alkene insertion is significantly higher in energy and thus less favorable. Stereochemical analysis confirms that the [2,1]-insertion mode governs the observed selectivity, leading predominantly to the S-configured isomer as the major product. Further insight from the activation strain model (ASM) and noncovalent interaction (NCI) analyses reveals that stabilizing noncovalent contacts dictate the stereoselectivity outcome.