The asymmetric hydrogenation of 2-phenethylacrylic acid as the key step for the enantioselective synthesis of Citralis Nitrile®

A catalytic approach to the enantioselective synthesis of Citralis Nitrile (3-methyl-5-phenyl-pentanenitrile, a citrus-type odorant) is described. The key step is the transition-metal catalyzed asymmetric hydrogenation of 2-phenethylacrylic acid. Among the different catalysts tested, the most efficient appears to be the one formed by combining in situ [Ru(benzene)Cl2]2 with the atropisomeric diphosphine MeOBIPHEP and triethylamine, which allows us to obtain enantiomeric excesses up to 98% under mild conditions. Very good results (ees >80%) have also been obtained using iridium cationic complexes in combination with a phosphinooxazoline ligand.