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

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.

Key words

catalysis - enones - synthetic methods - C–C coupling - basicity

• 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
• 1b Armstrong RW. Combs AP. Tempest PA. Brown SD. Keating TA. Acc. Chem. Res. 1996; 29: 123
• 1c Dömling A. Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
• 1d Zhu J. Bienaymé H. Multicomponent Reactions . Wiley-VCH; New York: 2005
• 1e Ramón DJ. Yus M. Angew. Chem. Int. Ed. 2005; 44: 1602
• 2a Hegedus LS. Transition Metals in the Synthesis of Complex Organic Molecules . University Science Books; Sausalito: 1999
• 2b Tsuji J. Transition Metal Reagents and Catalysts . John Wiley and Sons; Sussex: 2000
• 2c Tietze LF. Brasche G. Gericke K. Domino Reactions in Organic Synthesis . Wiley-VCH; Weinheim: 2006
• 3a Molander GA. Harris CR. J. Am. Chem. Soc. 1996; 118: 4059
• 3b Tietze LF. Chem. Rev. 1996; 96: 115
• 3c Denmark SE. Thorarensen A. Chem. Rev. 1996; 96: 137
• 3d Grigg R. Sridharan V. J. Organomet. Chem. 1999; 576: 65
• 3e Montgomery J. Angew. Chem. Int. Ed. 2004; 43: 3890
• 3f Agapiou K. Cauble DF. Krische MJ. J. Am. Chem. Soc. 2004; 126: 4528
• 3g Miura T. Murakami M. Chem. Commun. 2007; 217
• 3h Youn SW. Song J.-Y. Jung DI. J. Org. Chem. 2008; 73: 5658
• 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
• 3j Ciofi L. Morvillo M. Sladojevich F. Guarna A. Trabocchi A. Tetrahedron Lett. 2010; 51: 6282
• 3k Ciofi L. Trabocchi A. Lalli C. Menchi G. Guarna A. Org. Biomol. Chem. 2012; 10: 2780
• 4a Basavaiah D. Rao AJ. Satyanarayana T. Chem. Rev. 2003; 103: 811
• 4b Basavaiah D. Reddy BS. Badsara SS. Chem. Rev. 2010; 110: 5447
• 5 Morita K. Suzuki Z. Hirose H. Bull. Chem. Soc. Jpn. 1968; 41: 2815
• 6 Baylis AB. Hillman ME. D. DE 2155113, 1972
• 7 Declerck V. Martinez J. Lamaty F. Chem. Rev. 2009; 109: 1
• 8 Basavaiah D. Rao PD. Hyma RS. Tetrahedron 1996; 52: 8001
• 9a Burke MD. Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
• 9b Galloway WR. J. D. Isidro-Llobet A. Spring DR. Nat. Commun. 2010; 1: 80
• 9c Trabocchi A. Drug Discovery and Chemical Biology. Diversity-Oriented Synthesis: Basics and Applications in Organic Synthesis. John Wiley and Sons; Hoboken, NJ: 2013
• 9d Lenci E. Guarna A. Trabocchi A. Molecules 2014; 19: 16506
• 9e Lenci E. Menchi G. Trabocchi A. Org. Biomol. Chem. 2016; 14: 808
• 9f Lenci E. Menchi G. Guarna A. Trabocchi A. J. Org. Chem. 2015; 80: 2182
• 10 Plata ER. Singleton DA. J. Am. Chem. Soc. 2015; 137: 3811
• 11a Simeonov SP. Nunes JP. M. Guerra K. Kurteva VB. Afonso CA. M. Chem. Rev. 2016; 116: 5744
• 11b Piancatelli G. Dauria M. Donofrio F. Synthesis 1994; 867
• 11c Gibson SE. Lewis SE. Mainolfi N. J. Organomet. Chem. 2004; 689: 3873
• 12a Gatri R. El Gaïed MM. Tetrahedron Lett. 2002; 43: 7835
• 12b Luo S. Mi X. Xu H. Wang PG. Cheng J.-P. J. Org. Chem. 2004; 69: 8413
• 12c Ito H. Takenaka Y. Fukunishi S. Iguchi K. Synthesis 2005; 3035
• 12d Bugarin A. Connell BT. J. Org. Chem. 2009; 74: 4638
• 12e Bugarin A. Connell BT. Chem. Commun. 2010; 46: 2644
• 12f Guerra KP. Afonso CA. M. Tetrahedron 2011; 67: 2562
• 12g Gomes JC. Rodrigues MT Jr. Moyano A. Coelho F. Eur. J. Org. Chem. 2012; 6861
• 13 Shi M. Jiang JK. Li CQ. Tetrahedron Lett. 2002; 43: 127
• 14 Davies HJ. Ruda AM. Tomkinson NC. O. Tetrahedron Lett. 2007; 48: 1461
• 15 Luo S. Wang PG. Cheng JP. J. Org. Chem. 2004; 69: 555
• 16 Gruttadauria M. Giacalone F. Lo Meo P. Marculescu AM. Riela S. Noto R. Eur. J. Org. Chem. 2008; 1589
• 17 Aroyan CE. Vasbinder MM. Miller SJ. Org. Lett. 2005; 7: 3849
• 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).
• 19a Rezgui F. El Gaied MM. Tetrahedron Lett. 1998; 39: 5965
• 19b Lee KY. Gong JH. Kim JN. Bull. Korean Chem. Soc. 2002; 23: 659
• 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.
• 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.
• 22 Ahrendt KA. Borths CJ. MacMillan DW. C. J. Am. Chem. Soc. 2000; 122: 4243
• 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.
• 24 Liao C. Nicklaus MC. J. Chem. Inf. Model. 2009; 49: 2801