Anilines as Substrates in Consecutive Four-Component Synthesis of Novel 1-Aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones

Dedicated to Prof. Dr. Klaus Theodor Wanner on the occasion of his 60^th birthday

Abstract

The consecutive four-component synthesis of 5-acylpyridin-2(1H)-ones initiated by a copper-free alkynylation in a one-pot fashion has been expanded to include considerably less nucleophilic anilines as the amine component in the Michael addition step by altering the solvent system to 1,4-dioxane; 17 examples for the synthesis of 1-aryl-5-benzoyl-6-phenyl-3,4-dihydropyridin-2(1H)-ones were obtained in moderate to good yields.

Key words

multicomponent reactions - C–C coupling - alkynes - heterocycles - palladium

• References

• 1a Stille JR, Barta NS. Stud. Nat. Prod. Chem. 1996; 18: 315
• 1b Cook GR, Beholz LG, Stille JR. J. Org. Chem. 1994; 59: 3575
• 1c Paulvannan K, Stille JR. J. Org. Chem. 1994; 59: 1613
• 1d Shen W, Coburn CA, Bornmann WG, Danishefsky SJ. J. Org. Chem. 1993; 58: 611
• 1e Fang FG, Danishefsky SJ. Tetrahedron Lett. 1989; 30: 3621
• 2 For an example against pulmonary disease, see: Gielen-Haertwig H, Albrecht B, Bauser M, Keldenich J, Volkhart L, Pernerstorfer J, Schlemmer K.-H, Tellan L. US 2008,045,541, 2008

For examples of HIV-1 specific reverse transcriptase inhibitory activities, see:
• 3a Dolle V, Fan E, Nguyen CH, Aubertin AM, Kirn A, Andreola ML, Jamieson G, Tarragolitvak L, Bisagni E. J. Med. Chem. 1995; 38: 4679
• 3b Wai JS, Williams TM, Bamberger DL, Fisher TE, Hoffman JM, Hudcosky RJ, MacTough SC, Rooney CS, Saari WS, Thomas CM, Goldman ME, Obrien JA, Emini EA, Nunberg JH, Quintero JC, Schleif WA, Anderson PS. J. Med. Chem. 1993; 36: 249

For examples of 5α-reductase inhibitory activities, see:
• 4a McCarthy AR, Hartmann RW, Abell AD. Bioorg. Med. Chem. Lett. 2007; 17: 3603
• 4b Picard F, Schulz T, Hartmann RW. Bioorg. Med. Chem. 2002; 10: 437
• 4c Hartmann RW, Reichert M, Göhring S. Eur. J. Med. Chem. 1994; 29: 807
• 5a Hickmott PW, Sheppard G. J. Chem. Soc. C 1971; 65: 1358
• 5b Hickmott PW, Sheppard G. J. Chem. Soc. C 1971; 65: 2112
• 6 Barta NS, Brode A, Stille JR. J. Am. Chem. Soc. 1994; 116: 6201
• 7 Paulvannan K, Stille JR. J. Org. Chem. 1992; 57: 5319
• 8a Ulanovskaya OA, Cui J, Kron SJ, Kozmin SA. Chem. Biol. 2011; 18: 222
• 8b d’Angelo J, Cave C, Desmaele D, Gassama A, Thominiaux C, Riche C. Heterocycles 1998; 47: 725
• 8c Cave C, Gassama A, Mahuteau J, d’Angelo J, Riche C. Tetrahedron Lett. 1997; 38: 4773
• 8d Von Dobeneck H, Brunner E, Bunke H, Metzner G, Schmidt R, Weil E, Sonnenbichler J. Liebigs Ann. Chem. 1981; 410
• 9a Alizadeh A, Rezvanian A. Helv. Chim. Acta 2012; 95: 858
• 9b Chakrabarti S, Panda K, Misra NC, Ila H, Junjappa H. Synlett 2005; 1437
• 9c Abelman MM, Curtis JK, James DR. Tetrahedron Lett. 2003; 44: 6527
• 9d Hadden M, Nieuwenhuyzen M, Potts D, Stevenson PJ. J. Chem. Soc., Perkin Trans. 1 1998; 3437
• 10 Paulvannan K, Chen T. J. Org. Chem. 2000; 65: 6160
• 11a Lyutenko NV, Gerus II. Tetrahedron Lett. 2013; 54: 4091
• 11b Ali A, Winzenberg KN. Aust. J. Chem. 2005; 58: 870
• 11c Cimarelli C, Palmieri G. Tetrahedron 1998; 54: 915
• 11d Lyubchanskaya VM, Sarkisova LS, Alekseev LM, Granik VG. Pharm. Chem. J. 1994; 28: 70
• 12a Müller TJ. J. Synthesis 2012; 44: 159
• 12b Müller TJ. J. Top. Heterocycl. Chem. 2010; 25: 25
• 12c Willy B, Müller TJ. J. Curr. Org. Chem. 2009; 13: 1777
• 12d Willy B, Müller TJ. J. ARKIVOC 2008; (i): 195 ; http://www.arkat-usa.org/home
• 12e D’Souza DM, Müller TJ. J. Chem. Soc. Rev. 2007; 36: 1095
• 12f Müller TJ. J. Targets Heterocycl. Syst. 2006; 10: 54
• 13a Nordmann J, Breuer N, Müller TJ. J. Eur. J. Org. Chem. 2013; 4303
• 13b Nordmann J, Müller TJ. J. Org. Biomol. Chem. 2013; 11: 6556
• 14a Sarma R, Prajapati D. Chem. Commun. 2011; 47: 9525
• 14b Tsuchimoto T, Hatanaka K, Shirakawa E, Kawakami Y. Chem. Commun. 2003; 2454
• 14c Chauhan KK, Frost CG. J. Chem. Soc., Perkin Trans. 1 2000; 3015
• 15a Susanti D, Koh F, Kusuma JA, Kothandaraman P, Chan PW. H. J. Org. Chem. 2012; 77: 7166
• 15b Zhang Y, Donahue JP, Li C.-J. Org. Lett. 2007; 9: 627
• 15c Agarwal S, Knölker H.-J. Org. Biomol. Chem. 2004; 2: 3060
• 16a Luo Y, Li Z, Li C.-J. Org. Lett. 2005; 7: 2675
• 16b Müller TE. Tetrahedron Lett. 1998; 39: 5961
• 17a Bhanushali MJ, Nandurkar NS, Bhor MD, Bhanage BM. Catal. Commun. 2008; 9: 425
• 17b Das B, Chowdhury N. J. Mol. Catal. A: Chem. 2007; 263: 212
• 18a Rosenfeld DC, Shekhar S, Takemiya A, Utsunomiya M, Hartwig JF. Org. Lett. 2006; 8: 4179
• 18b Wabnitz TC, Spencer JB. Org. Lett. 2003; 5: 2141
• 19a Liu J.-R, Fang S, Ding M.-P, Chen Z.-C, Zhou J.-J, Sun F, Jiang B, Huang J. J. Neurol. Sci. 2010; 292: 111
• 19b Hotchkiss JA, Andrus AK, Johnson KA, Krieger SM, Woolhiser MR, Maurissen JP. Food Chem. Toxicol. 2010; 48: 470
• 19c Nagano K, Umeda Y, Senoh H, Gotoh K, Arito H, Yamamoto S, Matsushima T. J. Occup. Health 2006; 48: 424