Oxazaborolidine catalytic asymmetric reduction of prochiral ketones Stereoselectivity theory
|Course||Physical and chemical|
|Keywords||AM1 B3LYP/6-36G ~ * Asymmetric reduction 1,3,2 - mouth oxazole borane Optically active|
In this paper, semi-empirical molecular orbital AM1 and DFT B3LYP/6-31G * sup> Method of five 1,3,2 - Oxazaborolidines catalytic four kinds of aromatic ketones (a total of six systems) asymmetric reduction reaction. Electronic micro level reveals the asymmetric reduction of such micro-process analysis of the catalyst and the substrate ketone structure and reactivity stereoselective intrinsic association. Control step generates using stereo R and S enantiomers of the activation energy required for the difference, and R and S-type transition state entropy, enthalpy and the quantitative calculation of the parameters of the asymmetric reduction reaction of the optically active final product, the result experimental basic agreement, which the catalyst molecule design work of great significance. Firstly, using the AM1 method were studied two (R) -1,3,2 - Oxazaborolidines catalytic phenylethanone and two types of (S) -1,3,2 - Oxazaborolidines chlorobenzene catalyzed group B asymmetric reduction of ketones (a total of four systems), focusing on structure and reactivity of catalyst stereoselective association. Calculated for each step of the reaction the heat of reaction and three-dimensional control step of the activation energy. The results show that the first three-step process was exothermic, and the second and fourth step is the endothermic process, and heat up to the fourth step. According dimensional control step generates the R and S enantiomer of the difference between the predicted activation stereoselective asymmetric reduction reaction, the theoretical analysis of the optically active product is consistent with the experimental results. (R) -1,3,2 - oxazaborolidine molecule substituent at position 4 is (CH 3 ) 3 C (CH 2 ) 5 stereoselectivity significantly better than four substituents (CH 3 ) 3 C (CH 2 < / sub>) 2 ; (S) -1,3,2 - oxazaborolidine PhO group into the molecule, the catalyst significantly improved stereoselectivity. Secondly DFT (B3LYP/6-31G * sup>) to study the (S) -4 - benzyl-5 ,5 - diphenyl-1 ,3,2 - Oxazaborolidines catalysis (3-N-morpholino) -1 - phenyl-1 - acetone asymmetric reduction reaction to obtain a reaction system reactants, intermediates and the resultant optimized geometry and electronic structure parameters, effects of reaction microscopic processes. Borane and ketones on reaction coordinate calculations show that one can borane spontaneous reaction, thereby theoretically explained in such asymmetric reduction required 2mol of BH 3 experimental facts, also found that the evil yl borane - alkoxy borane adduct BOBN a stable four-membered ring structure. Finally AM1 studied (S) -4 - benzyl -5,5 - diphenyl-1 ,3,2 - Oxazaborolidines catalytic reduction of α-and β-amino ketones, mainly inspected two substrate ketone structural differences associated with the reaction stereoselectivity. Through three-dimensional control of the reaction coordinate calculation step response obtained R and S-type transition states optimized geometries of entropy and enthalpy winded wow turn borane catalyzed asymmetric reduction of prochiral ketones Stereoselectivity theoretical study Chinese Summary and other thermodynamic parameters, which quantitatively calculate the theoretical final product. . Values ??coincide with the experimental values. Calculations show that p-amino ketones stereoselectively significantly better than a root cause of an amino ketone is three-dimensional control step in which R and S-type transition state entropy difference is large, ie, the transition state entropy factor is asymmetric reduction of such three-dimensional Selective determinants.