CC BY-ND-NC 4.0 · Synlett 2019; 30(04): 483-487
DOI: 10.1055/s-0037-1610384
letter
Copyright with the author

Catalytic Enantioselective Synthesis of 4-Amino-1,2,3,4-tetrahydropyridine Derivatives from Intramolecular Nucleophilic Addition Reaction of Tertiary Enamides

Shuo Tong*
,
Mei-Xiang Wang  *
MOE Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China   Email: tongshuo@mail.tsinghua.edu.cn   Email: wangmx@mail.tsinghua.edu.cn
› Author AffiliationsWe thank the National Natural Science Foundation of China (No. 21320102002, 91427301) for financial support.
Further Information

Publication History

Received: 30 September 2018

Accepted after revision: 22 October 2018

Publication Date:
15 November 2018 (online)

   Permissions and Reprints All articles of this category


Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

A general and efficient method for the synthesis of highly enantiopure 4-amino-1,2,3,4-tetradydropyridine derivatives based on chiral phosphoric acid catalyzed intramolecular nucleophilic addition of tertiary enamides to imines has been developed. We have also demonstrated a substrate engineering strategy to significantly improve the enantioselectivity of asymmetric catalysis

Key words

tertiary enamides - 1,2,3,4-tetrahydropyridines - asymmetric catalysis - chiral phosphoric acid - substrate engineering

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610384.
  • Supporting Information
 

  • References and Notes

  • 1 Watson PS, Jiang B, Scott B. Org. Lett. 2000; 2: 3679
    CrossrefPubMed
    • 2a Ofner S, Hauser K, Schilling W, Vassout A, Veenstra SJ. Bioorg. Med. Chem. Lett. 1996; 6: 1623
      Crossref
    • 2b Veenstra SJ, Hauser K, Schilling W, Betschart C, Ofner S. Bioorg. Med. Chem. Lett. 1996; 6: 3029
      Crossref
  • 3 Patrizio M, Markus B, Patrick DG, Holger F, Michael H, Joerg H, Buelent K, Bernd K, Bernd ML, Alexander M, Robert N, Etienne R, Elena S, Urs S. Bio. Med. Chem. Lett. 2010; 20: 11009
    • 4a Van Niel MB, Collins I, Beer MS, Broughton HB, Cheng SK. F, Goodacre SC, Heald A, Locker KL, MacLeod AM, Morrison D, Moyes CR, O’Connor D, Pike A, Rowley M, Russell MG. N, Sohal B, Stanton JA, Thomas S, Verrier H, Watt AP, Castro JL. J. Med. Chem. 1999; 42: 2087
      CrossrefPubMed
    • 4b Lübbers T, Böhringer M, Gobbi L, Hennig M, Hunziker D, Kuhn B, Löffler B, Mattei P, Narquizian R, Peters J.-U, Ruff Y, Wessel HP, Wyss P. Bioorg. Med. Chem. Lett. 2007; 17: 2966
      CrossrefPubMed
    • 4c Benmehdi H, Lamouri A, Serradji N, Pallois F, Heymans F. Eur. J. Org. Chem. 2008; 299
    • 4d Barluenga J, Mateos C, Aznar F, Valdés C. Org. Lett. 2002; 4: 3667
      CrossrefPubMed
    • 4e Badorrey R, Portaña E, Díaz-de-Villegas MD, Gálvez JA. Org. Biomol. Chem. 2009; 7: 2912
      CrossrefPubMed
    • 5a Sun H, Scott DO. ACS Med. Chem. Lett. 2011; 2: 638 ; and references cited therein
      CrossrefPubMed
    • 5b Manetti D, Martini E, Ghelardini C, Dei S, Galeotti N, Guandalini L, Romanelli MN, Scapecchi S, Teodori E, Bartolini A, Gualtieri F. Bioorg. Med. Chem. Lett. 2003; 13: 2303
      CrossrefPubMed

      For reviews of enamide syntheses, see:
    • 6a Dehli JR, Legros J, Bolm C. Chem. Commun. 2005; 973
      PubMed
    • 6b Tracey MR, Hsung RP, Antoline J, Kurtz KC, Shen L, Slafer BW, Zhang Y. Category 3, Compounds with Four and Three Carbon Heteroatom Bonds . In Science of Synthesis . Vol. 21. Weinreb SM. Thieme; Stuttgart: 2005: 387
      Google Scholar
  • 7 For an overview, see: Wang M.-X. Chem Commun. 2015; 51: 6039
    CrossrefPubMed
  • 8 Carbery DR. Org. Biomol. Chem. 2008; 6: 3455
    CrossrefPubMed
  • 9 Gopalaiah K, Kagan HB. Chem. Rev. 2011; 111: 4599
    CrossrefPubMed

      • Secondary enamides are active aza-ene components to undergo aza-ene addition reactions with highly electron-deficient unsaturated compounds. For reviews, see:
    • 10a Matsubara R, Kobayashi S. Acc. Chem. Res. 2008; 41: 292
      CrossrefPubMed
    • 10b Bernadat G, Masson G. Synlett 2014; 25: 2842
      Article in Thieme Connect
    • 11a Yang L, Deng G, Wang D.-X, Huang Z.-T, Zhu J, Wang M.-X. Org. Lett. 2007; 9: 1387
      CrossrefPubMed
    • 11b Yang L, Zheng Q.-Y, Wang D.-X, Huang Z.-T, Wang M.-X. Org. Lett. 2008; 10: 2461
      CrossrefPubMed
    • 11c Yang L, Lei C.-H, Wang D.-X, Huang Z.-T, Wang M.-X. Org. Lett. 2010; 12: 3918
      CrossrefPubMed
    • 12a Yang L, Wang D.-X, Huang Z.-T, Wang M.-X. J. Am. Chem. Soc. 2009; 131: 10390
      CrossrefPubMed
    • 12b Tong S, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Angew. Chem. Int. Ed. 2012; 51: 4417
      CrossrefPubMed
    • 12c He L, Zhao L, Wang D.-X, Wang M.-X. Org. Lett. 2014; 16: 5972
      CrossrefPubMed
    • 12d Zhu W, Zhao L, Wang M-X. J. Org. Chem. 2015; 80: 12047
      CrossrefPubMed
    • 12e Xu X.-M, Zhao L, Zhu J, Wang M.-X. Angew. Chem. Int. Ed. 2016; 55: 3799
      CrossrefPubMed
    • 12f Xu X.-M, Lei C.-H, Tong S, Zhu J, Wang M.-X. Org. Chem. Front. 2018; 5: 3138
      Crossref
    • 13a Shono T, Matsumura Y, Tsubata K, Sugihara Y, Yamane S, Kanazawa T, Aoki T. J. Am. Chem. Soc. 1982; 104: 6697
      Crossref
    • 13b Andan L, Miesch L. Org. Lett. 2018; 20: 3430
      CrossrefPubMed
    • 14a Lei C.-H, Wang D.-X, Zhao L, Zhu J, Wang M.-X. J. Am. Chem. Soc. 2013; 135: 4708
      CrossrefPubMed
    • 14b Lei C.-H, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Chem. Eur. J. 2013; 19: 16981
      CrossrefPubMed
  • 15 Zhang X.-Y, Xu X.-M, Zhao L, You J, Zhu J, Wang M.-X. Tetrahedron Lett. 2015; 56: 3898
    Crossref
  • 16 Tong S, Yang X, Wang D.-X, Zhao L, Zhu J, Wang M.-X. Tetrahedron 2012; 68: 6492
    Crossref
  • 17 Zhou Q.-L. Privileged Chiral Ligands and Catalysts . Wiley-VCH; Weinheim: 2011
    Google Scholar
    • 18a Akiyama T, Itoh J, Fuchibe K. Angew. Chem. Int. Ed. 2004; 43: 1566
      CrossrefPubMed
    • 18b Yamanaka M, Itoch J, Fuchibe K, Akiyama T. J. Am. Chem. Soc. 2007; 129: 6756
      CrossrefPubMed
  • 19 Uraguchi D, Terada M. J. Am. Chem. Soc. 2004; 126: 5356
    CrossrefPubMed

      • For recent reviews on chiral phosphoric acids, see:
    • 20a Parmar D, Sugiono E, Raja S, Rueping M. Chem. Rev. 2014; 114: 9047
      CrossrefPubMed
    • 20b Lv J, Luo S. Chem. Commun. 2013; 49: 847
      CrossrefPubMed
    • 20c Li P, Yamamoto H. Top. Curr. Chem. 2011; 37: 161
    • 20d Yu J, Shi F, Gong LZ. Acc. Chem. Res. 2011; 44: 1156
      CrossrefPubMed
    • 20e Kampen D, Reisinger CM, List B. Top. Curr. Chem. 2010; 291: 395
      PubMed
    • 20f Mahlan M, List B. Angew. Chem. Int. Ed. 2013; 52: 518
      CrossrefPubMed
    • 20g Terada M. Synthesis 2010; 1929
      Article in Thieme Connect
    • 20h Hatano M, Ishihara K. Synthesis 2010; 3785
      Article in Thieme Connect
    • 20i Zamfir A, Schenker S, Freund M, Tsogoeva SB. Org. Biomol. Chem. 2010; 8: 5262
      PubMed
    • 20j Yu X, Wang W. Chem. Asian J. 2008; 3: 516
      CrossrefPubMed
    • 20k Akiyama T. Chem. Rev. 2007; 107: 5744
      CrossrefPubMed
    • 21a Nelson DL, Cox MM. Lehninger Principles of Biochemistry . W. H. Freeman and Company; New York: 2005. 4th ed., Chap. 6
      Google Scholar
    • 21b Faber K. Biotransformations in Organic Chemistry . Springer; Berlin: 1997. 3rd ed. Chap. 1
      CrossrefGoogle Scholar

      For select examples about substrate engineering in biocatalytic transformations, see:
    • 22a Braunegg G, De Raadt A, Feichtenhofer S, Griengl H, Kopper I, Lehmann A, Weber H.-J. Angew. Chem. Int. Ed. 1999; 38: 2763
      CrossrefPubMed
    • 22b De Raadt A, Griengl H, Weber H. Chem. Eur. J. 2001; 7: 27
      CrossrefPubMed
    • 22c Ma D.-Y, Zheng Q.-Y, Wang D.-X, Wang M.-X. Org. Lett. 2006; 8: 3231
      CrossrefPubMed
    • 22d Ma D.-Y, Wang D.-X, Pan J, Huang Z.-T, Wang M.-X. J. Org. Chem. 2008; 73: 4087
      CrossrefPubMed
  • 23 General Reaction Procedure A mixture of enamides 1a (0.5 mmol) and amines 2b (0.5 mmol) in dry CCl4 (25 mL) was stirred at ambient temperature for 5 min. Chiral phosphoric acid catalyst CC8 (75 mg, 0.1 mmol, 0.2 equiv) was added to the reaction system. Upon completion of the reaction, which was monitored by TLC, the reaction mixture was quenched with 10 mL sat. NaHCO3 solution, then extracted with 3 × 10 mL CH2Cl2. The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. After removal of the solvent, the residue was purified by column chromatography on silica gel to yield pure product 4ab. Oil (98% yield); ee 88.8% (chiral HPLC analysis). IR (KBr): 3422, 1723, 1656, 1601 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.21–7.44 (m, 17 H), 6.99 (br s, 2 H), 5.50 (br s, 1 H), 5.08 (s, 1 H), 4.05 (br s, 1 H), 3.74 (br s, 1 H), 3.41 (br s, 1 H), 2.00 (br s, 2 H), 1.62 (br s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 170.9, 144.0, 143.8, 140.6, 137.8, 136.2, 131.2, 130.7, 128.7, 128.6, 128.3, 128.1, 127.5, 127.34, 127.27, 127.2, 121.3, 118.6, 64.4, 48.8, 44.1, 31.2. HRMS (ESI): m/z calcd for C31H27BrN2O [M + Na]+, [M + 2 + Na]+: 521.1229, 523.1213; found: 521.1226, 523.1216.