Chemoselectivity and enantioselectivity in the conjugate reduction of cinnamate esters and a tandem conjugate reduction-ester hydrogenation using manganese catalysts

An improved synthesis of manganese(I) tricarbonyl complexes of the Phosphino-Ferrocenyl-Amino-Methyl-Pyridine (PFAMPy) ligand family is reported. A comparison of both the neutral form [Mn(PFAMPy)(CO)₂Br] and the cationic form [Mn(PFAMPy)(CO)₃]Br was made for an enantioselective ketone hydrogenation, with both catalysts giving high yields and enantiomer ratios over 98:2. The [Mn(PFAMPy)(CO)₃]Br catalyst was then applied in tandem conjugate reduction-ester hydrogenation to convert cinnamate esters into aryl propanols. This could be achieved for disubstituted cinnamates with the problematic inseparable allyl alcohol side products almost eliminated below 0.5%. A strategy to prevent C═O bond reduction preceding C═C reduction, and hence allylic alcohol side products, is to use a tert-butyl ester and mild conditions for the first few hours of reaction, prior to increasing temperature to promote ester hydrogenation. This approach is needed for trisubstituted cinnamate esters, which otherwise give mixtures. It is possible to carry out just conjugate reductions to saturated esters at lower temperatures without significant ester hydrogenation. Examples of manganese-catalyzed asymmetric hydrogenation of alkenes are presented in the form of an enantioselective and chemoselective conjugate reduction of trisubstituted cinnamate esters.