Theoretical Study on the Mechanism and Diastereoselectivity of NaBH4 Reduction

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 113; no. 11; pp. 2578 - 2583
• Main Authors: Suzuki, Yasumitsu, Kaneno, Daisuke, Tomoda, Shuji
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19-03-2009
• Subjects: A: Molecular Structure, Quantum Chemistry, General Theory; Borohydrides - chemistry; Computer Simulation; Ketones - chemistry; Models, Chemical; Reducing Agents; Thermodynamics
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp809966u

As the first step to understand the reaction mechanism and diastereoselectivity of sodium borohydride reduction of ketones, ab initio Car−Parrinello molecular dynamics simulation has been performed on a solution of NaBH4 in liquid methanol. According to pointwise thermodynamic integration involving constrained molecular dynamics simulations, it was strongly suggested that Na+ and BH4 − are associated in the solvent forming contact ion pairs. Thus we propose a new transition state structure model that contains complexation of the carbonyl oxygen with sodium cation. Predicted diastereoselectivity of the reduction of some substituted cyclohexanones applying this novel transition state model is in good agreement with experimental data, showing its validity and effectiveness to investigate the diastereoselectivity of NaBH4 reduction of other ketones.