Size is Important: Artificial Catalyst Mimics Behavior of Natural Enzymes

Heavily substituted (R)-DTBM-SegPHOS is active in the asymmetric Pd(II)-catalyzed hydrogenation or C-O bond cleavage of α-pivaloyloxy-1-(2-furyl)ethanone, whereas (R)-SegPHOS fails to catalyze either of these transformations. An extensive network of C-H ··· H-C interactions provided by the heavily substituted phenyl rings of (R)-DTBM-SegPHOS leads to increased stabilities of all intermediates and transition states in the corresponding catalytic cycles compared with the unsubstituted analogues. Moreover, formation of the encounter complex and its rearrangement into the reactive species proceeds in a fashion similar to that seen in natural enzymatic reactions. Computations demonstrate that this feature is the origin of enantioselection in asymmetric hydrogenation, since the stable precursor is formed only when the catalyst is approached by one prochiral plane of the substrate.