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Synlett 2009(20): 3287-3290  
DOI: 10.1055/s-0029-1218354
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Organocatalytic Synthesis of Terminal Propargylamine Derivatives by Tandem Amination-Alkynylation

Yu Wang, Fangzhi Peng, Hongbin Zhang, Zhihui Shao*
Key Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University), Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, P. R. of China
e-Mail: +86(871)5035538; e-Mail: 20070114@ynu.edu.cn; e-Mail: zhihui_shao@hotmail.com;
Further Information

Publication History

Received 7 August 2009
Publication Date:
13 November 2009 (online)

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Abstract

The first organocatalytic synthesis of terminal propargylic amines from aldehydes via tandem amination/Seyferth-­Gilbert alkynylation has been developed. The described protocol provides the formal addition products of acetylene (HC≡CH) to ali­phatic imines, which are not easily obtained directly.

Key words

amination - organocatalysis - Seyferth-Gilbert alkynylation - tandem reactions - terminal propargylamines

    References and Notes

  • For reviews, see:
  • 1a Trost BM. Weiss AH. Adv. Synth. Catal.  2009,  351:  963 
    Google Scholar
  • 1b Zani L. Bolm C. Chem. Commun.  2006,  4263 
    Google Scholar
  • 2 Wright JL. Gregory TF. Kesten SP. Boxer PA. Serpa KA. Meltzer LT. Wise LD. Espitia SA. Konkoy CS. Whittemore ER. Woodward RM. J. Med. Chem.  2000,  43:  3408 
    CrossrefPubMedGoogle Scholar
  • For selected examples, see:
  • 3a Wei C.-M. Li C.-J. J. Am. Chem. Soc.  2002,  124:  5638 
    Google Scholar
  • 3b Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2002,  41:  2535 
    Google Scholar
  • 3c Gommermann N. Koradin C. Polborn K. Knochel P. Angew. Chem. Int. Ed.  2003,  42:  5763 
    Google Scholar
  • 3d Knopfel TF. Aschwanden P. Ichikawa T. Watanabe T. Carreira EM. Angew. Chem. Int. Ed.  2004,  42:  5971 
    Google Scholar
  • 3e Wei C.-M. Mague JT. Li C.-J. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5749 
    Google Scholar
  • 3f Colombo F. Benaglia M. Orlandi S. Usuelli F. J. Mol. Catal. A: Chem.  2006,  260:  128 
    Google Scholar
  • 3g Colombo F. Benaglia M. Orlandi S. Usuelli F. Celentano G. J. Org. Chem.  2006,  71:  2064 
    Google Scholar
  • 3h Dodda R. Zhao C.-G. Org. Lett.  2007,  9:  165 
    Google Scholar
  • 3i Dodda R. Zhao C.-G. Tetrahedron Lett.  2007,  48:  4339 
    Google Scholar
  • 3j Ji J.-X. Yeung TTLA. Wu J. Yip CW. Chan ASC. Adv. Synth. Catal.  2004,  346:  42 
    Google Scholar
  • 3k Ji J.-X. Wu J. Chan ASC. Proc. Natl. Acad. Sci. U.S.A.  2005,  102:  11196 
    Google Scholar
  • 3l Zhou L. Jiang H.-F. Li C.-J. Adv. Synth. Catal.  2008,  350:  2226 
    Google Scholar
  • 3m Bisai A. Singh VK. Org. Lett.  2006,  8:  2405 
    Google Scholar
  • 3n Rueping M. Antonchick AP. Brinkmann C. Angew. Chem. Int. Ed.  2007,  46:  6903 
    Google Scholar
  • 3o Blay G. Cardona L. Climent E. Pedro JR. Angew. Chem. Int. Ed.  2008,  47:  5593 
    Google Scholar
  • 3p Irmaka M. Boysena MMK. Adv. Synth. Catal.  2008,  350:  403 
    Google Scholar
  • 3q Hatano M. Asai T. Ishihara K. Tetrahedron Lett.  2008,  49:  379 
    Google Scholar
  • 3r Liu J. Liu B. Jia X. Li X. Chan ASC. Tetrahedron: Asymmetry  2007,  18:  396 
    Google Scholar
  • 3s Wang J. Shao Z.-H. Ding K. Yu WY. Chan ASC. Adv. Synth. Catal.  2009,  351:  1250 
    Google Scholar
  • 3t Lu Y.-D. Johnstone TC. Arndtsen BA. J. Am. Chem. Soc.  2009,  131:  11284 ; see also ref. 5
    Google Scholar
  • For general reviews, see:
  • 4a Bertelsen S. Jørgensen KA. Chem. Soc. Rev.  2009,  38:  2178 
    Google Scholar
  • 4b Dondoni A. Massi A. Angew. Chem. Int. Ed.  2008,  47:  4638 
    Google Scholar
  • 4c Dalko PI. Enantioselective Organocatalysis: Reactions and Experimental Procedures   Wiley-VCH; Weinheim: 2007. 
    Google Scholar
  • 4d Berkessel A. Groger H. Asymmetric Organocatalysis-From Biomimetic Concepts to Powerful Methods for Asymmetric Synthesis   Wiley-VCH; Weinheim: 2005. 
    Google Scholar
  • 4e Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 
    Google Scholar
  • For excellent examples of metal-catalyzed synthesis of propargylic amines using silylacetylene as pre-nucleophiles, see:
  • 5a Fischer C. Carreira EM. Org. Lett.  2001,  3:  4319 
    Google Scholar
  • 5b Gommermann N. Knochel P. Chem. Commun.  2004,  2324 
    Google Scholar
  • 5c Gommermann N. Knochel P. Tetrahedron  2005,  61:  11418 
    Google Scholar
  • 5d Traverse JF. Hoveyda AH. Snapper ML. Org. Lett.  2003,  5:  3273 
    Google Scholar
  • 6a Shao Z.-H. Pu X.-W. Li X.-J. Fan B.-M. Chan ASC. Tetrahedron: Asymmetry  2009,  20:  225 
    Google Scholar
  • 6b Shao Z.-H. Wang J. Ding K. Chan ASC. Adv. Synth. Catal.  2007,  349:  2375 
    Google Scholar
  • 6c Shao Z.-H. Chan ASC. Synthesis  2008,  2868 
    Google Scholar
  • For a general review on chiral primary amine-catalyzed reactions, see:
  • 7a For examples, see: Peng F.-Z. Shao Z.-H. J. Mol. Catal. A: Chem.  2008,  285:  1 
    Google Scholar
  • 7b Peng F.-Z. Shao Z.-H. Fan B.-M. Song H. Li G.-P. Zhang H.-B.
    J. Org. Chem.  2008,  73:  5202 
    Google Scholar
  • 7c Peng F.-Z. Shao Z.-H. Pu X.-W. Zhang H.-B. Adv. Synth. Catal.  2008,  350:  2199 
    Google Scholar
  • 7d Pu X.-W. Li P.-H. Peng F.-Z. Li X.-J. Zhang H.-B. Shao Z.-H. Eur. J. Org. Chem.  2009,  4622 
    Google Scholar
  • 8 For a review on the concept of catalysis through combining transition-metals and organocatalysis, see: Shao ZH. Zhang H.-B. Chem. Soc. Rev.  2009,  38:  2745 
    CrossrefPubMedGoogle Scholar
  • 9a Bogevig A. Juhl K. Kumaragurubaran N. Zhuang W. Jorgensen KA. Angew. Chem. Int. Ed.  2002,  41:  1790 
    Google Scholar
  • 9b List B. J. Am. Chem. Soc.  2002,  124:  5656 
    Google Scholar
  • 9c Chowdari NS. Barbas CF. Org. Lett.  2005,  7:  867 
    Google Scholar
  • 9d Suri JT. Steiner DD. Barbas CF. Org. Lett.  2005,  7:  3885 
    Google Scholar
  • 9e Franzen J. Marigo M. Fielenbach D. Wabnitz TC. Kjærsgaard A. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  18296 
    Google Scholar
  • 9f Marigo M. Schulte T. Franzen J. Jørgensen KA. J. Am. Chem. Soc.  2005,  127:  15710 
    Google Scholar
  • 10a Ohira S. Synth. Commun.  1989,  19:  561 
    Google Scholar
  • 10b Müller S. Liepold B. Roth GJ. Bestmann HJ. Synlett  1996,  521 
    Google Scholar
  • 11 Jiang H. Falcicchio A. Jensen KL. Paixao MW. Bertelsen S. Jørgensen KA. J. Am. Chem. Soc.  2009,  131:  7153 
    CrossrefGoogle Scholar
  • 12 Ding H. Friestad GK. Org. Lett.  2004,  6:  637 
    CrossrefGoogle Scholar
  • 13 Coutts R, Baker G, Sloley D, Shan J, and Pang PKT. inventors; US Patent  6060516. 
14

Typical procedure for one-pot, tandem α-amination-alkynylation of aldehydes: Proline (0.1 mmol, 10 mol%) was added to a stirring solution of aldehyde 1a (1 mmol) and DIAD (1 mmol) in CH2Cl2 (3 mL). After 2 h of vigorous stirring at r.t., MeOH (15 mL), Ohira-Bestmann reagent (1.2 mmol, 1.2 equiv) and K2CO3 (2 mmol, 2 equiv) were added. After stirring for 12 h at r.t., the reaction mixture was diluted with Et2O. The excess solvents were removed under reduced pressure and the residue was purified by flash silica gel chromatography to give the desired product 2a. IR (film): 3254, 2985, 1743, 1678, 1529, 1417, 1233, 1109 cm-¹; ¹H NMR (300 MHz, CDCl3): δ = 6.39 (br s, 1 H), 5.06 (br s, 1 H), 4.89 (sept, J = 6.2 Hz, 2 H), 2.23 (s, 1 H), 1.36 (d, J = 6.9 Hz, 3 H), 1.18 (d, J = 6.1 Hz, 12 H); ¹³C NMR (75 MHz, CDCl3): δ = 156.1, 154.7, 82.1, 71.5, 70.6, 69.8, 45.8, 22.0, 21.9, 19.2; HRMS (ESI): m/z [M + H]+ calcd for C12H20N2O4: 257.1496; found: 257.1490.