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 transfornations. An extensive network of C−H … H−C interactions provided by the heavily substituted phenyl rings of (R)-DTBM-SegPHOS results in increased stability of all intermediates and transition states in the corresponding catalytic cycles comkpared to the unsubstituted analogue. 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 ability 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. Catalysis, Enzymatic catalysis, asymmetric hydrogenation, enantioselectivity, catalytic activity, mechanism of stereoselection