Download PDF
Synlett 2006(7): 1071-1074  
DOI: 10.1055/s-2006-939706
LETTER
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Brønsted Acid Catalyzed Transfer Hydrogenation - New Organocatalytic Reduction of Quinolines

Magnus Rueping*, Thomas Theissmann, Andrey P. Antonchick
Degussa Endowed Professorship, Institute of Organic Chemistry and Chemical Biology, Johann-Wolfgang Goethe University Frankfurt am Main, Marie-Curie-Str. 11, 60439 Frankfurt, Germany
Fax: +49(69)79829248; e-Mail: M.Rueping@chemie.uni-frankfurt.de;
Further Information

Publication History

Received 1 February 2006
Publication Date:
24 April 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

The first metal-free Brønsted acid catalyzed hydrogenation of quinolines using Hantzsch dihydropyridine as the hydrogen source has been developed. This, so far unprecedented organocatalytic reduction of heteroaromatic compounds provides a variety of differently substituted 1,2,3,4-tetrahydroquinolines in excellent yields under mild reaction conditions using a remarkably low amount of Brønsted acid catalyst.

Key words

Brønsted acid - Hantzsch dihydropyridine - transfer ­hydrogenation - organocatalysis - reduction - 1,2,3,4-tetrahydro­quinoline

    References and Notes

  • 1 For review, see: Katritzky AR. Rachwal S. Rachwal B. Tetrahedron  1996,  52:  15031 
    CrossrefGoogle Scholar
  • For examples, see:
  • 2a Jacquemond-Collet I. Benoit-Vical F. . Valentin A. Stanislas E. Mallié M. Fourasté I. Planta Med.  2002,  68:  68 
    CrossrefGoogle Scholar
  • 2b Wallace OB. Lauwers KS. Jones SA. Dodge JA. Bioorg. Med. Chem. Lett.  2003,  13:  1907 
    CrossrefGoogle Scholar
  • 2c Di Fabio R. Tranquillini E. Bertani B. Alvaro G. Micheli F. Sabbatini F. Pizzi MD. Pentassuglia G. Pasquarello A. Messeri T. Donati D. Ratti E. Arban R. Dal Forno G. Reggiani A. Barnaby RJ. Bioorg. Med. Chem. Lett.  2003,  13:  3863 
    CrossrefGoogle Scholar
  • 2d Asolkar RN. Schröder D. Heckmann R. Lang S. Wagner-Döbler I. Laatsch H. J. Antibiot.  2004,  57:  17 
    CrossrefGoogle Scholar
  • 2e Lombardo LJ. Camuso A. Clark J. Fager K. Gullo-Brown J. Hunt JT. Inigo I. Kan D. Koplowitz B. Lee F. McGlinchey K. Qian LG. Ricca C. Rovnyak G. Traeger S. Tokarski J. Williams DK. Wu LI. Zhao YF. Manne V. Bhide RS. Bioorg. Med. Chem. Lett.  2005,  15:  1895 
    CrossrefGoogle Scholar
  • 2f Nallan L. Bauer KD. Bendale P. Rivas K. Yokoyama K. Horney CP. Pendyala PR. Floyd D. Lombardo LJ. Williams DK. Hamilton A. Sebti S. Windsor WT. Weber PC. Buckner FS. Chakrabarti D. Gelb MH. Van Voorhis WC. J. Med. Chem.  2005,  48:  3704 
    CrossrefGoogle Scholar
  • For some recent publications, see:
  • 3a Fujita K. Yamaguchi R. Synlett  2005,  560 
    CrossrefPubMedGoogle Scholar
  • 3b Lam KH. Xu LJ. Feng LC. Fan QH. Lam FL. Lo WH. Chan ASC. Adv. Synth. Catal.  2005,  347:  1755 
    CrossrefPubMedGoogle Scholar
  • 3c Xu LK. Lam KH. Ji JX. Wu J. Fan QH. Lo WH. Chan ASC. Chem. Commun.  2005,  1390 
    CrossrefPubMedGoogle Scholar
  • 3d Lu SM. Han XW. Zhou YG. Adv. Synth. Catal.  2004,  346:  909 
    CrossrefPubMedGoogle Scholar
  • 3e Yang PY. Zhou YG. Tetrahedron: Asymmetry  2004,  15:  1145 
    CrossrefPubMedGoogle Scholar
  • 3f Wang WB. Lu SM. Yang PY. Han XW. Zhou YG. J. Am. Chem. Soc.  2003,  125:  10536 
    CrossrefPubMedGoogle Scholar
  • 3g Michael JP. Nat. Prod. Rep.  2005,  22:  627 
    CrossrefPubMedGoogle Scholar
  • 4a Ranu BC. Jana U. Sarkar A. Synth. Commun.  1998,  28:  485 
    Google Scholar
  • 4b Srikrishna A. Reddy TJ. Viswajanani R. Tetrahedron  1996,  52:  1631 
    Google Scholar
  • 4c Nose A. Kudo T. Chem. Pharm. Bull.  1984,  32:  2421 
    Google Scholar
  • 5 Rueping M. Azap C. Sugiono E. Theissmann T. Synlett  2005,  2367 
    Article in Thieme ConnectGoogle Scholar
  • 6a Rueping M. Sugiono E. Azap C. Theissmann T. Bolte M. Org. Lett.  2005,  7:  3781 
    CrossrefPubMedGoogle Scholar
  • 6b For a subsequent optimization of this procedure, see: Hoffmann S. Seayad A. List B. Angew. Chem. Int. Ed.  2005,  44:  7424 ; Angew. Chem. 2005, 117, 7590
    CrossrefPubMedGoogle Scholar
  • 6c Storer RI. Carrera DE. Ni Y. MacMillan DWC. J. Am. Chem. Soc.  2006,  128:  84 
    CrossrefPubMedGoogle Scholar
  • For recent conjugate reductions of α,β-unsaturated aldehydes, see:
  • 7a Yang JW. Hechavarria Fonseca MT. List B. Angew. Chem. Int. Ed.  2004,  43:  6660 ; Angew. Chem. 2004, 116, 6829
    CrossrefGoogle Scholar
  • 7b Yang JW. Hechavarria Fonseca MT. Vignola N. List B. Angew. Chem. Int. Ed.  2005,  44:  108 ; Angew. Chem. 2005, 117, 110
    CrossrefGoogle Scholar
  • 7c Ouellet SG. Tuttle JB. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  32 
    CrossrefGoogle Scholar
  • 7d Adolfsson H. Angew. Chem. Int. Ed.  2005,  44:  3340 ; Angew. Chem. 2005, 117, 3404
    CrossrefGoogle Scholar
  • 7e Lui Z. Han B. Lui Q. Zhang W. Yang L. Lui ZL. Yu W. Synlett  2005,  1579 
    CrossrefGoogle Scholar
  • 7f Garden SJ. Guimarães CRW. Corréa B. Oliveira CAF. Pinto AC. Alencastro RB. J. Org. Chem.  2003,  68:  8815 
    CrossrefGoogle Scholar
  • For reviews on chiral Brønsted acid catalysis, see:
  • 9a Schreiner PR. Chem. Soc. Rev.  2003,  32:  289 
    CrossrefGoogle Scholar
  • 9b Pihko PM. Angew. Chem. Int. Ed.  2004,  43:  2062 ; Angew. Chem. 2004, 116, 2110
    CrossrefGoogle Scholar
  • 9c Bolm C. Rantanen T. Schiffers I. Zani L. Angew. Chem. Int. Ed.  2005,  44:  1758 ; Angew. Chem. 2005, 117, 1788
    CrossrefGoogle Scholar
  • For the use of chiral phosphoric acid catalysts, see:
  • 9d Akiyama T. Itoh J. Yokota K. Fuchibe K. Angew. Chem. Int. Ed.  2004,  43:  1566 ; Angew. Chem. 2004, 116, 1592
    CrossrefGoogle Scholar
  • 9e Uraguchi D. Terada M. J. Am. Chem. Soc.  2004,  126:  5356 
    CrossrefGoogle Scholar
  • 9f Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc.  2004,  126:  11804 
    CrossrefGoogle Scholar
  • 9g Akiyama T. Morita H. Itoh J. Fuchibe K. Org. Lett.  2005,  7:  2583 
    CrossrefGoogle Scholar
  • 9h Akiyama T. Saitoh Y. Morita H. Fuchibe K. Adv. Synth. Catal.  2005,  347:  1523 
    CrossrefGoogle Scholar
  • 9i Uraguchi D. Terada M. J. Am. Chem. Soc.  2004,  126:  5356 
    CrossrefGoogle Scholar
  • 9j Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc.  2004,  126:  11804 
    CrossrefGoogle Scholar
  • 9k Uraguchi D. Sorimachi K. Terada M. J. Am. Chem. Soc.  2005,  127:  9360 
    CrossrefGoogle Scholar
  • 9l Rowland GB. Zhang H. Rowland EB. Chennamadhavuni S. Wang Y. Antilla JC. J. Am. Chem. Soc.  2005,  127:  15696 
    CrossrefGoogle Scholar
  • 9m Terada M. Sorimachi K. Uraguchi D. Synlett  2006,  133 
    CrossrefGoogle Scholar
  • 9n Akiyama T. Tamura Y. Itoh J. Morita H. Fuchibe K. Synlett  2006,  141 
    CrossrefGoogle Scholar
  • 9o Rueping M. Sugiono E. Azap C. Angew. Chem. Int. Ed.  2006,  45:  2617 ; Angew. Chem.  2006,  118:  2679 
    CrossrefGoogle Scholar
  • 10 An extension of this procedure to an asymmetric variant by employing a chiral phosphate catalyst has been achieved: Rueping M. Antonchick AP. Theissmann T. Angew. Chem. Int. Ed.  2006,  45:  in press 
    Google Scholar
8

General Procedure for the Brønsted Acid Catalyzed Transfer Hydrogenation of Quinolines.
In a typical experiment quinoline (20 mg), diphenyl phosphate (1 mol%) and Hantzsch dihydropyridine 2 (2.4 equiv) were suspended in benzene (2 mL) in a screw-capped vial and flushed with argon. The resulting mixture was allowed to stir at 60 °C for 12 h. The solvent was removed under reduced pressure and purification of the crude product by column chromatography on silica gel afforded the pure 1,2,3,4-tetrahydroquinoline. For representative examples, see:
7-Chloro-1,2,3,4-tetrahydro-4-phenylquinoline (6o): yield 19.3 mg, 94%. IR (KBr): 3412, 3396, 2919, 1604, 1492, 1089, 700 cm-1. 1H NMR (250 MHz, CDCl3): δ = 1.88-2.18 (m, 2 H, C-3H), 3.08-3.28 (m, 2 H, C-2H), 3.94 (br s, 1 H, NH), 4.01 (t, J = 6.1 Hz, 1 H, C-4H), 6.39-6.48 (m, 2 H, Ar), 6.56-6.59 (m, 1 H, Ar), 6.99-7.07 (m, 2 H, Ar), 7.09-7.27 (m, 3 H, Ar). 13C NMR (250 MHz, CDCl3): δ = 30.7, 38.9, 42.4, 113.4, 116.8, 121.7, 126.3, 128.4, 128.6, 131.5, 132.6, 145.9, 146.0. MS-ESI: m/z = 243.8 [M+], 245.8 [M+]. Anal. Calcd for C15H14ClN (243.73): C, 73.92; H, 5.79; N, 5.75. Found: C, 73.69; H, 5.54; N, 5.74.
1,2,3,4-Tetrahydro-4,7-diphenylquinoline (6p): yield 18.6 mg, 91%. IR (KBr): 3356, 3292, 3024, 2945, 2924, 1562, 1485, 1468, 1319, 758, 698 cm-1. 1H NMR (250 MHz, CDCl3): δ = 1.93-2.27 (m, 2 H, C-3H), 3.13-3.34 (m, 2 H, C-2H), 3.96 (br s, 1 H, NH), 4.10 (t, J = 6.1 Hz, 1 H, C-4H), 6.69-6.73 (m, 3 H, Ar), 7.10-7.38 (m, 8 H, Ar), 7.45-7.50 (m, 2 H, Ar). 13C NMR (250 MHz, CDCl3): δ = 31.2, 39.4, 42.7, 112.7, 116.2, 122.7, 126.2, 127.0, 128.4, 128.6, 128.7, 130.8, 140.4, 141.5, 145.2, 146.5. MS-ESI: m/z = 285.8 [M+]. Anal. Calcd for C21H19N (285.38): C, 88.38; H, 6.71; N, 4.91. Found: C, 88.11; H, 6.80; N, 4.79.