Copper‐Catalyzed Chemoselective Asymmetric Hydrogenation of C=O Bonds of Exocyclic α,β‐Unsaturated Pentanones

Abstract A highly chemoselective earth‐abundant transition metal copper catalyzed asymmetric hydrogenation of C=O bonds of exocyclic α,β‐unsaturated pentanones was realized using H 2 . The desired products were obtained with up to 99 % yield and 96 % ee (enantiomeric excess) (99 % ee, after recrystallization). The corresponding chiral exocyclic allylic pentanol products can be converted into several bioactive molecules. The hydrogenation mechanism was investigated via deuterium‐labelling experiments and control experiments, which indicate that the keto‐enol isomerization rate of the substrate is faster than that of the hydrogenation and also show that the Cu−H complex can only catalyze chemoselectively the asymmetric reduction of the carbonyl group. Computational results indicate that the multiple attractive dispersion interactions (MADI effect) between the catalyst with bulky substituents and substrate play important roles which stabilize the transition states and reduce the generation of by‐products.