Chiral oxazaborolidines, known as CBS catalysts after the work of Corey, Bakshi and Shibata, are used for the stereoselective reduction of prochiral ketones to secondary chiral alcohols. Due to their relative low cost, ease of use and high selectivity, their popularity has remarkably grown in the last 15 years. Oxazaborolidine-catalysed reductions have been much studied, both experimentally and computationally by means of semiempirical methods. Though, a more accurate high level quantum mechanical study on the complete system, capable of elucidating reliably the origins of stereoselectivity, is still lacking. Therefore, the acetophenone (PhMK) reduction with Coreys oxazaborolidine has been modelled for the first time with ab-initio and DFT-B3LYP calculations on the complete system as well as with AM1. Calculations on the complexation of BH3 to CBS, that can occur only in a cis fashion with respect to the hydrogen on the stereogenic C-4 carbon atom, have allowed to confirm the great rigidity of Coreys catalyst, possibly determining its excellent enantioselectivity. Acetophenone-CBS-BH3 complexes were characterized at various levels of theory, and it was found that the picture obtained depends heavily on the method adopted. A computational strategy for identifying the hydride transfer transition states of the competing pathways was developed and tested, using a model system for which the transition state geometry was already known. The application of the TS search method to the reduction of acetophenone allowed the characterisation of the TSs for the competing pathways in this reaction, making it possible to predict with good quantitative accuracy the stereochemical outcome of the reaction at all the levels of theory adopted. The characterization of the intermediate oxazadiboretane products confirmed that the highly exothermic hydride transfer provides the thermodynamical drive for the reaction.
Quantum Mechanical Study of Stereoselectivity in the Oxazaborolidine-Catalysed Reduction of Acetophenone
Alagona G;
2003
Abstract
Chiral oxazaborolidines, known as CBS catalysts after the work of Corey, Bakshi and Shibata, are used for the stereoselective reduction of prochiral ketones to secondary chiral alcohols. Due to their relative low cost, ease of use and high selectivity, their popularity has remarkably grown in the last 15 years. Oxazaborolidine-catalysed reductions have been much studied, both experimentally and computationally by means of semiempirical methods. Though, a more accurate high level quantum mechanical study on the complete system, capable of elucidating reliably the origins of stereoselectivity, is still lacking. Therefore, the acetophenone (PhMK) reduction with Coreys oxazaborolidine has been modelled for the first time with ab-initio and DFT-B3LYP calculations on the complete system as well as with AM1. Calculations on the complexation of BH3 to CBS, that can occur only in a cis fashion with respect to the hydrogen on the stereogenic C-4 carbon atom, have allowed to confirm the great rigidity of Coreys catalyst, possibly determining its excellent enantioselectivity. Acetophenone-CBS-BH3 complexes were characterized at various levels of theory, and it was found that the picture obtained depends heavily on the method adopted. A computational strategy for identifying the hydride transfer transition states of the competing pathways was developed and tested, using a model system for which the transition state geometry was already known. The application of the TS search method to the reduction of acetophenone allowed the characterisation of the TSs for the competing pathways in this reaction, making it possible to predict with good quantitative accuracy the stereochemical outcome of the reaction at all the levels of theory adopted. The characterization of the intermediate oxazadiboretane products confirmed that the highly exothermic hydride transfer provides the thermodynamical drive for the reaction.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
