To gain greater insight into catalyst SAR and rationalize the superior selectivity observed using TCYP (11) vs. TRIP (3), we undertook an in-depth computational evaluation of the system using the ONIOM method with B3LYP/6-31G** 22 for the QM region and UFF for the MM region. 24 Calculations were performed using Gaussian09 (see SI). A reaction profile for TRIP catalyst ( ) is shown in Figure (for full analysis, see SI). Benchmark substrate 1 preferentially adopts the lower energy s-trans conformation (2.2 kcal/mol preferred vs. s-cis; Figure ). Consistent with our previous model, the reaction proceeds through (1) complexation of 1 with 3 via a hydrogen bond to give 61, (2) nucleophilic addition of aniline, via 62, to the catalyst-substrate complex and proton transfer back to the catalyst to yield 63 (3) protonation of this prochiral enamine by the catalyst via 64, and (4) product dissociation. From a free energy perspective, the aniline addition and proton transfer to the catalyst form a concerted process leading to 63. For the TRIP-catalyzed process, the pathway to the experimentally obtained (R)-enantiomer is favored by ca. 4 kcal/mol in agreement with the experimentally observed enantiomer.