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

摘要

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.