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

• Published in: Journal of organic chemistry Vol. 83; no. 24; pp. 15202 - 15209
• Main Authors: Hsieh, Ming-Hsiu, Huang, Gou-Tao, Yu, Jen-Shiang K
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.12.2018
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.8b02483

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.