Solvent effects on the sodium borohydride reduction of 2-halocyclohexanones

Author(s)

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

• Document type: Journal article
• Source: JOURNAL OF PHYSICAL ORGANIC CHEMISTRY; v. 36, n. 10, p. 8-pg., 2023-07-04.

Abstract

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)

• FAPESP's process: 18/03910-1 - Physicochemical studies of fluorinated organic compounds: experimental and theoretical approaches
• Grantee: Rodrigo Antonio Cormanich
• Support Opportunities: Research Grants - Young Investigators Grants