Highly Regioselective Phosphine-Promoted [2+2+2] Annulations of Cyanoacetylenes and N-Tosylimines to 1,2-Dihydropyridine-3,5-dicarbonitrile Derivatives

Abstract

A series of fully functionalized dihydropyridine-3,5-dicarbonitrile derivatives were easily prepared through [2+2+2] annulations of cyanoacetylenes and N-tosylimines in the presence of tertiary phosphine. The scope of the cyclization reaction was investigated, and the high regioselectivity was explained by a rational reaction mechanism.

Key words

phosphine - annulations - cyanoacetylenes - N-tosylimines - regioselectivity

• References and Notes

• 1a Michael JP. Nat. Prod. Rep. 2005; 22: 627
• 1b Stout DM, Meyers AI. Chem. Rev. 1982; 82: 223
• 2a Abd El-MaksoudS. A, Fouda AS. Mater. Chem. Phys. 2005; 93: 84
• 2b Eissa AA. M, Farag NA. H, Soliman GA. H. Bioorg. Med. Chem. 2009; 17: 5059
• 2c Shinde SS, Jachak MN. Res. J. Recent. Sci. 2012; 1: 67
• 2d Baumane L, Krauze A, Krasnova L, Belyakov S, Duburs G, Stradiņš J. Chem. Heterocycl. Compd. 2014; 49: 1623
• 2e Lovesey AC. J. Med. Chem. 1970; 13: 693
• 3 Rangnekar D, Kanetkar V. Indian J. Fibre Text. Res. 1990; 15: 132
• 4 Basta A, Girgis A, El-Saied H. Dyes Pigments 2002; 54: 1
• 5 Bull JA, Mousseau JJ, Pelletier G, Charette AB. Chem. Rev. 2012; 112: 2642
• 6a Patil NT, Yamamoto Y. Chem. Rev. 2008; 108: 3395
• 6b Lewis JC, Bergman RG, Ellman JA. Acc. Chem. Res. 2008; 41: 1013
• 6c Chemler SR, Fuller PH. Chem. Soc. Rev. 2007; 36: 1153

For reviews, see:
• 7a Wang Z, Xu X, Kwon O. Chem. Soc. Rev. 2014; 43: 2927
• 7b Fan Y, Kwon O. Chem. Commun. 2013; 49: 11588
• 7c Zhao Q.-Y, Lian Z, Wei Y, Shi M. Chem. Commun. 2012; 48: 1724
• 7d Ye L.-W, Zhou J, Tang Y. Chem. Soc. Rev. 2008; 37: 1140
• 7e Denmark SE, Beutner GL. Angew. Chem. Int. Ed. 2008; 47: 1560
• 7f Nair V, Menon RS, Sreekanth AR, Abhilash N, Biji AT. Acc. Chem. Res. 2006; 39: 520
• 7g Methot JL, Roush WR. Adv. Synth. Catal. 2004; 346: 1035
• 7h Lu X, Zhang C, Xu Z. Acc. Chem. Res. 2001; 34: 535
• 8a Zhao G.-L, Huang J.-W, Shi M. Org. Lett. 2003; 5: 4737
• 8b Zhao G.-L, Shi M. J. Org. Chem. 2005; 70: 9975
• 8c Meng L.-G, Cai P, Guo Q, Xue S. J. Org. Chem. 2008; 73: 8491

For selected examples about [2+3] cycloadditions, see:
• 9a Xu Z, Lu X. J. Org. Chem. 1998; 63: 5031
• 9b Zhu X.-F, Henry CE, Kwon O. Tetrahedron Lett. 2005; 61: 6276
• 9c Fang Y.-Q, Jacobsen EN. J. Am. Chem. Soc. 2008; 130: 5660
• 9d Zhang B, He Z, Xu S, Wu G, He Z. Tetrahedron 2008; 64: 9471
• 9e Zheng S, Lu X. Org. Lett. 2008; 10: 4481
• 9f Wang Y.-Q, Zhang Y, Dong H, Zhang J, Zhao J. Eur. J. Org. Chem. 2013; 3764
• 9g Xu Z, Lu X. J. Org. Chem. 1998; 63: 5031

For selected examples about [2+4] cycloadditions, see:
• 10a Zhu X.-F, Lan J, Kwon O. J. Am. Chem. Soc. 2003; 125: 4716
• 10b Wurz RP, Fu GC. J. Am. Chem. Soc. 2005; 127: 12234
• 11 Tian J, Zhou R, Sun H, Song H, He Z. J. Org. Chem. 2011; 76: 2374
• 12 Shi Z, Loh T.-P. Angew. Chem. Int. Ed. 2013; 52: 8584
• 13 Li E, Jia P, Liang L, Huang Y. ACS Catal. 2014; 4: 600
• 14 Yang L.-J, Wang S, Nie J, Li S, Ma J.-A. Org. Lett. 2013; 15: 5214
• 15 Zhao H, Meng X, Huang Y. Chem. Commun. 2013; 49: 10513
• 16 Liu H, Zhang Q, Wang L, Tong X. Chem. Commun. 2010; 46: 312
• 17 Only one example about cyanoacetylene participated in cycloaddition under phosphine-catalyzed conditions, see: Heiko Dückert D.-C, Khedkar V, Waldmann H, Kumar K. Chem. Eur. J. 2011; 17: 5130
• 18 The X-ray crystal structure of 3q data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures (CCDC 1025786).
• 19 Typical Procedure for the Highly Regioselective Annulations of Cyanoacetylenes and N-TosyliminesTo a solution of cyanoacetylenes (0.4 mmol) with N-tosylimines (0.2 mmol) in toluene (2 mL) was added Ph₃P (0.2 mmol). The mixture was then stirred at 110 °C for 36 h in a reaction flask. Then the solvent was removed in vacuo, and residue was purified by column chromatography on silica gel to give the desired product 3a. Yield 82%; yellow solid; mp 230–231 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.63 (d, J = 8.0 Hz, 2 H), 7.54–7.38 (m, 13 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.24–7.19 (m, 2 H), 6.46 (s, 1 H), 2.39 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 153.5, 148.0, 145.8, 135.3, 134.1, 132.9, 132.4, 132.3, 130.8, 130.1, 130.0, 129.6, 129.3, 128.7, 128.5, 128.3, 127.1, 127.0, 116.0, 115.5, 102.1, 100.4, 58.7, 21.4. HRMS (ESI): m/z calcd for C₃₂H₂₄N₃O₂S [M + H]⁺: 514.1584; found: 514.1584.