Can the Radical Channel Contribute to the Catalytic Cycle of N-Heterocyclic Carbene in Benzoin Condensation?

Abstract

NHC can catalyze benzoin condensation via the key Breslow intermediate. EPR spectroscopy recently confirmed the existence of the radical species, but its catalytic role is still unclear. Herein, we use density functional approaches to study the radical-associated pathway in comparison with the nonradical mechanism reported previously. Theoretical investigations show that the nonradical path (ΔG ⧧ = 18.7 kcal/mol) is more kinetically favorable than the radical route (ΔG ⧧ = 27.6 kcal/mol), which is initialized by the hydrogen abstraction from the Breslow intermediate by benzaldehyde, leading to a radical pair. The product formation is thus dominated by the nonradical pathway. In addition, the Breslow intermediate is less stable than its keto form, which blocks the benzoin condensation, and the radical species could play an important role in assisting the tautomerization and promoting the catalytic reaction.

Enols, Diamino Enols, and Breslow Intermediates: A Comparative Quantum Chemical Analysis

“…Several studies were carried out to explain mechanism of formation of BIs and their catalytic activity . In addition to these, there is a need to consider the properties of the BIs as independent species.…”

“…He and Xue performed quantum chemical study on the formation of BI from pyrido‐[1,2‐ a ]‐2‐ethy[1,2,4]triazole‐3‐ylidene and benzaldehyde. [15e] However, the electronic structure analysis to distinguish the characteristics of enols, diamino enols and BIs was not reported. In this article, a systematic electronic structure analysis has been taken up to explore this perspective.…”

Dipole‐bound states and substituent effects of Breslow intermediates in the enolate form

“…[13] We have demonstrated in our previous work that the radicals in benzoin condensation are actually the enolate radical. [14] The mechanism to form enolate radical via a hydrogen-atom transfer from Breslow intermediate to benzaldehyde (1 ! 2 in Scheme 2) is kinetically unfavored compared to the conventional umpolung pathway.…”

Mechanistic Investigations Towards a Successful PET with Breslow-Intermediates

“…2 Rather late in regard to the methodological development and mechanistic postulates and associated studies 3,4 the idea evolved that single electron transfer (SET) or proton-coupled electron transfer (PCET) may play a role in the pathways involving the key enaminol structure EA (Scheme 1). 5,6,7 Detailed studies regarding the origin of EPRobservable open-shell structures (R) and their potential role within the NHC-catalytic cycle let to the conclusion that most likely the Breslow intermediate is the direct precursor of such NHC-stabilized ketyl type radicals (OH-EA-R, EA-dep-R).…”