Dual Iminium- and Lewis Base Catalyzed Morita–Baylis–Hillman Reaction on Cyclopent-2-enone

 

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Abstract

The application of iminium catalysis to the challenging Morita–Baylis–Hillman reaction on cyclopenten-2-one leads to the corresponding allylic alcohols in excellent yields. Experimental evidence shows that secondary amines act as co-catalysts activating the enone moiety towards the nucleophilic attack at the β-position by DABCO as the Lewis base catalyst, resulting in an augmented nucleophilic character towards the reaction with aldehydes.

• References and Notes

• 1a Ugi I. Lohberger S. Karl R. In Comprehensive Organic Synthesis . Vol. 2. Trost BM. Fleming I. Pergamon Press; Oxford: 1991: 1083
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 1b Armstrong RW. Combs AP. Tempest PA. Brown SD. Keating TA. Acc. Chem. Res. 1996; 29: 123
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 1c Dömling A. Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 1d Zhu J. Bienaymé H. Multicomponent Reactions . Wiley-VCH; New York: 2005
  MissingFormLabel

  Search in Google Scholar
• 1e Ramón DJ. Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 2a Hegedus LS. Transition Metals in the Synthesis of Complex Organic Molecules . University Science Books; Sausalito: 1999
  MissingFormLabel

  Search in Google Scholar
• 2b Tsuji J. Transition Metal Reagents and Catalysts . John Wiley and Sons; Sussex: 2000
  MissingFormLabel

  Search in Google Scholar
• 2c Tietze LF. Brasche G. Gericke K. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
  MissingFormLabel

  Search in Google Scholar
• 3a Molander GA. Harris CR. J. Am. Chem. Soc. 1996; 118: 4059
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 3b Tietze LF. Chem. Rev. 1996; 96: 115
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3c Denmark SE. Thorarensen A. Chem. Rev. 1996; 96: 137
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3d Grigg R. Sridharan V. J. Organomet. Chem. 1999; 576: 65
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 3e Montgomery J. Angew. Chem. Int. Ed. 2004; 43: 3890
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3f Agapiou K. Cauble DF. Krische MJ. J. Am. Chem. Soc. 2004; 126: 4528
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3g Miura T. Murakami M. Chem. Commun. 2007; 217
  MissingFormLabel

  PubMed
• 3h Youn SW. Song J.-Y. Jung DI. J. Org. Chem. 2008; 73: 5658
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3i Ji K.-G. Shu X.-Z. Chen J. Zhao S.-C. Zheng Z.-J. Lu L. Liu X.-Y. Liang Y.-M. Org. Lett. 2008; 10: 3919
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 3j Ciofi L. Morvillo M. Sladojevich F. Guarna A. Trabocchi A. Tetrahedron Lett. 2010; 51: 6282
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 3k Ciofi L. Trabocchi A. Lalli C. Menchi G. Guarna A. Org. Biomol. Chem. 2012; 10: 2780
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 4a Basavaiah D. Rao AJ. Satyanarayana T. Chem. Rev. 2003; 103: 811
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 4b Basavaiah D. Reddy BS. Badsara SS. Chem. Rev. 2010; 110: 5447
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 5 Morita K. Suzuki Z. Hirose H. Bull. Chem. Soc. Jpn. 1968; 41: 2815
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 6 Baylis AB. Hillman ME. D. DE 2155113, 1972
  MissingFormLabel

  PubMed
• 7 Declerck V. Martinez J. Lamaty F. Chem. Rev. 2009; 109: 1
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 8 Basavaiah D. Rao PD. Hyma RS. Tetrahedron 1996; 52: 8001
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 9a Burke MD. Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 9b Galloway WR. J. D. Isidro-Llobet A. Spring DR. Nat. Commun. 2010; 1: 80
  MissingFormLabel

  PubMedSearch in Google Scholar
• 9c Trabocchi A. Drug Discovery and Chemical Biology. Diversity-Oriented Synthesis: Basics and Applications in Organic Synthesis. John Wiley and Sons; Hoboken, NJ: 2013
  MissingFormLabel

  Search in Google Scholar
• 9d Lenci E. Guarna A. Trabocchi A. Molecules 2014; 19: 16506
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 9e Lenci E. Menchi G. Trabocchi A. Org. Biomol. Chem. 2016; 14: 808
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 9f Lenci E. Menchi G. Guarna A. Trabocchi A. J. Org. Chem. 2015; 80: 2182
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 10 Plata ER. Singleton DA. J. Am. Chem. Soc. 2015; 137: 3811
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 11a Simeonov SP. Nunes JP. M. Guerra K. Kurteva VB. Afonso CA. M. Chem. Rev. 2016; 116: 5744
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 11b Piancatelli G. Dauria M. Donofrio F. Synthesis 1994; 867
  MissingFormLabel

  Thieme Connect
• 11c Gibson SE. Lewis SE. Mainolfi N. J. Organomet. Chem. 2004; 689: 3873
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 12a Gatri R. El Gaïed MM. Tetrahedron Lett. 2002; 43: 7835
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 12b Luo S. Mi X. Xu H. Wang PG. Cheng J.-P. J. Org. Chem. 2004; 69: 8413
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 12c Ito H. Takenaka Y. Fukunishi S. Iguchi K. Synthesis 2005; 3035
  MissingFormLabel

  Thieme Connect
• 12d Bugarin A. Connell BT. J. Org. Chem. 2009; 74: 4638
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 12e Bugarin A. Connell BT. Chem. Commun. 2010; 46: 2644
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 12f Guerra KP. Afonso CA. M. Tetrahedron 2011; 67: 2562
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 12g Gomes JC. Rodrigues MT Jr. Moyano A. Coelho F. Eur. J. Org. Chem. 2012; 6861
  MissingFormLabel
• 13 Shi M. Jiang JK. Li CQ. Tetrahedron Lett. 2002; 43: 127
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 14 Davies HJ. Ruda AM. Tomkinson NC. O. Tetrahedron Lett. 2007; 48: 1461
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 15 Luo S. Wang PG. Cheng JP. J. Org. Chem. 2004; 69: 555
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 16 Gruttadauria M. Giacalone F. Lo Meo P. Marculescu AM. Riela S. Noto R. Eur. J. Org. Chem. 2008; 1589
  MissingFormLabel
• 17 Aroyan CE. Vasbinder MM. Miller SJ. Org. Lett. 2005; 7: 3849
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar
• 18 This base catalyst did not work using other solvents such as acetonitrile, dichloromethane, methanol, and toluene, as well as aqueous mixtures like DMF–water (9:1) and MeOH–water (1:1).
  MissingFormLabel
• 19a Rezgui F. El Gaied MM. Tetrahedron Lett. 1998; 39: 5965
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 19b Lee KY. Gong JH. Kim JN. Bull. Korean Chem. Soc. 2002; 23: 659
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 20 The concomitant iminium activation of the aldehyde was excluded in our MBH reaction conditions as a consequence of model experiments with ESI-MS (see Supporting Information) and of the fact that no Mannich-type reaction was observed.
  MissingFormLabel
• 21 A standard approach in this way was not found in the literature: Cheng reported the use of an excess of aldehyde;¹⁴ whereas in the paper by Gruttadauria¹⁵ an excess of cyclopent-2-enone was used.
  MissingFormLabel
• 22 Ahrendt KA. Borths CJ. MacMillan DW. C. J. Am. Chem. Soc. 2000; 122: 4243
  MissingFormLabel

  CrossrefSearch in Google Scholar
• 23 General Procedure for the Morita–Baylis–Hillman Reaction In a flask containing a solution of DABCO (0.12 mmol, 14 mg) in THF (0.5 mL) and 1 M aqueous solution of NaHCO₃ (2 mL), pyrrolidine (0.12 mmol, 10 μL), cyclopent-2-enone (0.6 mmol), and the aldehyde (1.8 mmol) were successively added. The reaction was stirred at room temperature for 40 h. Then, ethyl acetate (20 mL) was added, and the organic phase was washed with 1 M HCl, sat. aqueous NaHCO₃, and brine. The organic phase was dried over Na₂SO₄, filtered, concentrated under reduced pressure, and the crude product was purified by flash chromatography column (FCC). 2-[Hydroxy(3,4-dimethoxyphenyl)methyl]cyclopent-2-enone (13) Obtained in 37% yield. ¹H NMR (400 MHz, CDCl₃): δ = 6.95–6.81 (m, 4 H), 5.50 (s, 1 H), 3.87 (s, 3 H), 3.86 (s, 3 H) 2.58 (m, 2 H), 2.45 (m, 2 H). ¹³C NMR (50 MHz, CDCl₃): δ = 209.7, 159.3, 149.1, 148.6, 147.8, 133.9, 118.6, 110.9, 109.5, 69.7, 55.9 (2 C), 35.3, 26.6. ESI-MS: m/z (%) = 271.17 (100) [M + Na]⁺. Anal. Calcd for C₁₄H₁₆O₄ (248.27): C, 67.73; H, 6.50. Found: C, 67.80; H, 6.58. 2-[Hydroxy(2-thienyl)methyl]cyclopent-2-enone (15) Obtained in 69% yield. ¹H NMR (400 MHz, CDCl₃): δ = 7.45 (m, 1 H), 7.27–7.23 (m, 1 H), 7.00–6.95 (m, 2 H), 5.81 (s, 1 H), 3.68 (br, 1 H), 2.65–2.62 (m, 2 H), 2.49–2.47 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 209.3, 159.6, 146.9, 145.1, 126.7, 125.2 124.7, 66.2, 35.3, 26.7. ESI-MS: m/z (%) = 217.08 (100) [M + Na]⁺. Anal. Calcd for C₁₀H₁₀O₂S (442.52): C, 61.83; H, 5.19. Found: C, 62.00; H, 5.28.
  MissingFormLabel
• 24 Liao C. Nicklaus MC. J. Chem. Inf. Model. 2009; 49: 2801
  MissingFormLabel

  CrossrefPubMedSearch in Google Scholar

• Supplementary Material