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

Wei Jun Tang, Jing Tan, Li Jin Xu, Kim Hung Lam, Qing Hua Fan, Albert S.C. Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

80 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1055-1062
Number of pages8
JournalAdvanced Synthesis and Catalysis
Volume352
Issue number6
DOIs
Publication statusPublished - 19 Apr 2010

Keywords

  • Asymmetric hydrogenation
  • Iridium catal-ysis
  • P-Phos
  • Pyridines
  • Quinolines

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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