Challenging the major/minor concept in Rh-catalyzed asymmetric hydrogenation

Herein, we provide evidence showing that the long-held major-minor concept for catalytic asymmetric reactions needs to be readdressed. The asymmetric hydrogenation of enamide 1 catalyzed by the chiral Rh(I) complex of (R,R)-BenzP∗ quantitatively yields the corresponding hydrogenated R-product 2 with 89.6% ee. The most abundant catalyst-substrate species in the reaction pool was found to be [Rh((R,R)-BenzP)(Ph(MeCONH)C=CH₂)]⁺SbF₆^- (5). This species is also the most reactive to hydrogen among the various Rh complexes. Low-temperature hydrogenation experiments showed direct transformation of 5 to 2 with over 98% ee (R). However, the oxidative addition of H₂ to 5 would yield the S-product. Computation has now revealed a low-energy R-enantioselective route, whereby H₂ addition to 5 is followed by π-bond dissociation, isomerization of nonchelating Rh species, and recoordination of the double bond before C-H bond formation occurs.