Highly enantioselective hydrogenation of quinoline and pyridine derivatives with iridium-(P-Phos) catalyst

The use of a chiral iridium catalyst gener-ated in situ from the (cyclooctadiene)iridium chlo-ride dimer, [Ir(COD)Cl]₂, the P-Phos ligand [4, 4'-bis(diphenylphosphino)-2, 2', 6, 6'-tetramethoxy-3, 3'-bi-pyridine] and iodine (I₂) for the asymmetric hydroge-nation of 2, 6-substituted quinolines and trisubstituted pyridines [2-substituted 7, 8-dihydroquinolin-5(6H)-one derivatives] is reported. The catalyst worked ef-ficiently to hydrogenate a series of quinoline deriva-tives to provide chiral 1, 2, 3, 4-tetrahydroquinolines in high yields and up to 96% ee. The hydrogenation was carried out at high S/C (substrate to catalyst) ratios of 2000-50000, reaching up to 4000 h^-1 TOF (turnover frequency) and up to 43000 TON (turn-over number). The catalytic activity is found to be additive-controlled. At low catalyst loadings, de-creasing the amount of additive I₂ was necessary to maintain the good conversion. The same catalyst system could also enantioselectively hydrogenate tri-substituted pyridines, affording the chiral hexahydro-quinolinone derivatives in nearly quantitative yields and up to 99% ee. Interestingly, increasing the amount of I₂ favored high reactivity and enantiose-lectivity in this case. The high efficacy and enantiose-lectivity enable the present catalyst system of high practical potential.