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, (IrA2, 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.