Solvent effects on the sodium borohydride reduction of 2-halocyclohexanones

Autor(es)

Silva, Daniela Rodrigues ; Zeoly, Lucas A. ; Vermeeren, Pascal ; Cormanich, Rodrigo A. ; Hamlin, Trevor A. ; Guerra, Celia Fonseca ; Freitas, Matheus P.

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PHYSICAL ORGANIC CHEMISTRY; v. 36, n. 10, p. 8-pg., 2023-07-04.

Resumo

We have investigated the stereoselectivity and reactivity of the sodium borohydride reduction of 2-X-cyclohexanones (X=H, Cl, Br) using a combined approach of competitive experiments and density functional theory calculations. Our results show that the hydride addition proceeds via a late transition state in which the C-H bond is nearly formed, consistent with the mild reducing power of NaBH4. The reaction barrier decreases from the 2-halocyclohexanones to the unsubstituted cyclohexanone, in line with relative reactivities observed in the competitive experiments. Furthermore, we provide a protocol to solve the longstanding issue of properly modelling the axial-equatorial facial selectivity of hydride addition to the carbonyl group substituted with a vicinal polar group. The inclusion of implicit solvation in combination with an explicit solvent molecule is crucial to reproduce the stereoselective formation of the cis product observed experimentally. (AU)

• Processo FAPESP: 18/03910-1 - Estudos físico-químicos de compostos orgânicos fluorados: abordagens experimental e teórica
• Beneficiário: Rodrigo Antonio Cormanich
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores