Theoretical prediction on the synthesis of 2,3‐dihydropyridines through Co(III)‐catalysed reaction of unsaturated oximes with alkenes

Abstract

Cobalt‐based catalysts can replace the homologous group‐9 rhodium‐based ones. Herein, we used density functional theory (DFT) calculations to predict the synthesis of 2,3‐dihydropyridines using α,β‐unsaturated oxime pivalates and alkenes catalysed by [Cp*CoOAc]+ instead of [Cp*RhOAc]+. The catalytic cycle involves reversible acetate‐assisted metalation‐deprotonation, migratory insertion of alkenes, and reductive elimination/N‐O cleavage. The migratory insertion of alkenes was determined to be the rate‐determining step, and the reaction is irreversible due to the strongly exergonic reductive elimination/NO cleavage. When using the CF3‐substituted Cp*Co(III) catalyst, the apparent activation energy indicates that the title reaction can proceed at higher temperatures. Electron‐withdrawing substituent groups on Cp* facilitate the reaction. In contrast, substituting phenyl with the electron‐deficient p‐CF3‐phenyl at the 2‐position of α,β‐unsaturated oxime pivalate hinders the reaction, and so does the use of polarized alkenes with electron‐withdrawing substituent groups

Making Base-Assisted C–H Bond Activation by Cp*Co(III) Effective: A Noncovalent Interaction-Inclusive Theoretical Insight and Experimental Validation

“…It is worthy to note that most theoretical studies on the Cp*Co­(III)-catalyzed C–H activation did not investigate thoroughly the mechanism of cyclometalation, and focused on the influence of different substitutions on the reactive species. ,− ,, Most of them simplified the cyclometalation step. To the best of our knowledge no other DFT study followed a thorough NCI-inclusive approach of the cyclometalation part of the mechanism.…”

“…49 We now decided to test experimentally the conclusions drawn from the theoretical study of the Ni(II)/Pd(II) model dyad to the CMD mechanism-promoted cyclometallation reaction by focussing our interest on the Cp*Co(III) system, having in scope that a good part of the recent applications of Cp*Co(III) catalysts 17,55,56 to C-H bond functionalization apparently proceed by a different mechanism, i.e via the electrophilic activation 57 of the C-H bond. Recent reports tend indeed to priviledge the electrophilic pathway 58,59 even though in some cases the formal formulation of the mechanism makes the distinction with the CMD 16,60,61 one rather difficult. It is important to mention that known syntheses (scheme 1) of Cp*Co(III)-metallacycles are based on the use of sensitive Cp*Co(I)L2 (L=CO; Me3SiCH=CH2) complexes and rely on an oxidative addition step requiring expensive iodo-arene substrates such as 2-(2-iodophenyl)pyridine (oxidative addition).…”

“…via the electrophilic activation of the C–H bond. Recent reports tend indeed to privilege the electrophilic pathway , even though in some cases the formal formulation of the mechanism makes the distinction from the CMD ,, one rather difficult. It is important to mention that known syntheses (Scheme ) of Cp*Co­(III)-metallacycles are based on the use of sensitive Cp*Co­(I)­L 2 (L = CO; Me 3 SiCHCH 2 ) complexes and rely on an oxidative addition step requiring expensive iodo-arene substrates such as 2-(2-iodophenyl)­pyridine (oxidative addition) .…”