The H‐Bond activation mechanism and enantioselectivity in stepwise conjugate amine addition promoted by hydroxyl‐thiourea catalyst

The H‐bond activation mechanism and enantioselectivity of hydroxyl‐thiourea catalyst in conjugate amine addition of O‐benzyl hydroxylamine to pyrazole crotonate is investigated using density functional theory (DFT) calculations. Two competing activation models are explored in detail. C? N bond formation is stepwise in both of the two models. The enantioselective (S)‐channel is more favorable than (R)‐channel via the calculated barriers. The enantioselectivity originated from si face preferable than re face can be attributed to the H‐bonded network provided by thiourea and hydroxyl groups in rate‐determining step. The enantiomeric excess (ee) values predicted through ONIOM calculations are in line with the experiment. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011