Controlled and Efficient Synthesis of Quinoline Derivatives from Morita–Baylis–Hillman Adducts by Palladium-Catalyzed Heck Reaction and Cyclization

Abstract

An efficient synthesis of 2,3-disubstituted quinoline derivatives from easily accessible (het)aryl-substituted Morita–Baylis–Hillman (MBH) adducts was achieved by an approach involving a palladium-catalyzed Heck reaction and cyclization. This strategy converts the MBH adducts into α-benzyl β-keto ester derivatives that can cyclize into the corresponding quinolines in good yields.

Key words

quinolines - cyclizations - catalysis - palladium - Heck reactions - tandem reactions

• References and Notes

• 1a Zhang X, Shetty AS, Jenekhe SA. Macromolecules 1999; 32: 7422
• 1b Lam P.-l, Kan C.-w, Yuen MC.-w, Cheung S.-y, Gambari R, Lam K.-h, Tang JC.-o, Chuia C.-h. Color. Technol. 2012; 128: 192
• 1c Nolan EM, Jaworski J, Okamoto K.-I, Hayashi Y, Sheng M, Lippard SJ. J. Am. Chem. Soc. 2005; 127: 16812
• 1d Rose MJ, Fry NL, Marlow R, Hinck L, Mascharak PK. J. Am. Chem. Soc. 2008; 130: 8834
• 2a Bilker O, Lindo V, Panico M, Etiene AE, Paxton T, Dell A, Rogers M, Sinden RE, Morris HR. Nature 1998; 392: 289
• 2b Edmont D, Rocher R, Plisson C, Chenault J. Bioorg. Med. Chem. Lett. 2000; 10: 1831
• 2c Chen Y.-L, Fang K.-C, Sheu J.-Y, Hsu S.-L, Tzeng C.-C. J. Med. Chem. 2001; 44: 2374
• 2d Waters NC, Dow GS, Kozar MP. Expert Opin. Ther. Pat. 2004; 14: 1125
• 2e Michael JP. Nat. Prod. Rep. 1997; 14: 605
• 3a Zhao P, Yan X, Yin H, Xi C. Org. Lett. 2014; 16: 1120
• 3b Fu Y.-h, Di Y.-t, He H.-p, Li S.-l, Zhang Y, Hao X.-j. J. Nat. Prod. 2014; 77: 57
• 3c Ren X, Wen P, Shi X, Wang Y, Li J, Yang S, Yan H, Huang G. Org. Lett. 2013; 15: 5194
• 3d Beesu M, Malladi SS, Fox LM, Jones CD, Dixit A, David SA. J. Med. Chem. 2014; 57: 7325
• 3e Nobuhide M, Yoshinobu Y, Hiroshi I, Yoshio O, Tamejiro H. Tetrahedron Lett. 1993; 24: 8263
• 3f Trécourt F, Mongin F, Mallet M, Quéguiner G. Synth. Commun. 1995; 25: 4011
• 4 Larock RC, Kuo M.-Y. Tetrahedron Lett. 1991; 32: 569
• 5a Ramesh C, Lei P.-M, Kavala V, Kuo C.-W, Yao C.-F. Molecules 2012; 17: 5081
• 5b Korivi RP, Cheng C.-H. J. Org. Chem. 2006; 71: 7079
• 5c McNaughton BR, Miller BL. Org. Lett. 2003; 5: 4257
• 5d Kim SC, Gowrisankar S, Kim JN. Bull. Korean Chem. Soc. 2005; 26: 1001
• 6a Basavaiah D, Muthukumaran K. Tetrahedron 1998; 54: 4943
• 6b Sundar N, Bhat SV. Synth. Commun. 1998; 28: 2311
• 6c Kumareswaran R, Vankar YD. Synth. Commun. 1998; 28: 2291
• 6d Kabalka GW, Venkataiah B, Dong G. Org. Lett. 2003; 5: 3803
• 6e Kim JM, Kim KH, Kim TH, Kim JN. Tetrahedron Lett. 2008; 49: 3248
• 7 Perez R, Veronese D, Coelho F, Antunes OA. C. Tetrahedron Lett. 2006; 47: 1325
• 8 Gowrisankar S, Lee HS, Kim JM, Kim JN. Tetrahedron Lett. 2008; 49: 1670
• 9a Ribière P, Declerck V, Nédellec Y, Yadav-Bhatnagar N, Martinez J, Lamaty F. Tetrahedron 2006; 62: 10456
• 9b Declerck V, Ribière P, Nédellec Y, Allouchi H, Martinez J, Lamaty F. Eur. J. Org. Chem. 2007; 201
• 9c Vasudevan A, Tseng P.-S, Djuric SW. Tetrahedron Lett. 2006; 47: 8591
• 10a Lee HS, Kim JM, Kim JN. Tetrahedron Lett. 2007; 48: 4119
• 10b Kudryavtsev KV, Ivantcova PM, Churakov AV, Vasin VA. Tetrahedron Lett. 2012; 53: 4300
• 10c Because of the large difference in the pK _a values of DABCO (pK _a = 8.8) and DBU (pK _a = 12), one-pot tandem cyclization and aromatization resulted in decomposition of the starting materials.
• 11 1,4-Dihydroquinolines 3 and Quinolines 4; General Procedure A mixture of 2-iodoaniline (2a; 2.1 equiv), Pd (OAc)₂ (10 mol%), DABCO (0.6 equiv), and TBAB (2.1 equiv.) in MeCN (2 mL) was refluxed under argon. After 15 min, the MBH adduct 1 (100 mg) was added. When the reaction was complete (TLC), the mixture was allowed to cool to r.t. and filtered through a Celite pad. The resulting mixture of compounds 3 and 4 was subjected to aromatization with DBU and purified by column chromatography (silica gel) to give the quinoline 4. Methyl 2-(4-Chlorophenyl)-1,4-dihydroquinoline-3-carboxylate (3a) + Methyl 2-(4-Chlorophenyl)quinoline-3-carboxylate Yellow oil; yield: 110 mg (84%); IR (CH₂Cl₂): 3389, 3096, 1728, 1622, 1593, 1485, 1366, 755cm^–1; ¹H NMR (500.1 MHz, CDCl₃): δ = 3.50 (s, 3 H), 3.78 (s, 3 H), 3.91 (s, 2 H), 5.77 (br s, 1 H), 6.57 (m, 1 H), 6.94 (m, 1 H), 6.96 (m, 2 H), 7.08 (m, 2 H), 7.38 (m, 2 H), 7.45 (m, 2 H), 7.58 (m, 2 H), 7.62 (t, J = 7.0 Hz, 1 H), 7.83 (m, 1 H), 7.92 (d, J = 8 Hz, 1 H), 8.16 (d, J = 8.5 Hz, 1 H), 8.65 (s, 1 H); ¹³C NMR (125.7 MHz, CDCl): δ = 27.94, 50.87, 52.53, 95.58, 114.31, 121.38, 123.34, 124.61, 125.88, 127.08, 127.52, 128.30 (2 C), 128.43 (2 C), 128.59 (2 C), 129.09 (2 C), 129.31 (2 C), 129.53 (2 C), 130.01, 131.88, 134.81, 134.90, 136.62, 139.04, 139.58, 148.45, 156.89, 167.57, 168.00; FAB: m/z [M + 1]⁺ calcd for C₁₇H₁₂ClNO₂: 297.06; found: 298.31: m/z [M + 1]⁺ calcd for C₁₇H₁₄ClNO₂: 299.07; found: 300.28. Methyl 2-Pyridin-2-ylquinoline-3-carboxylate (4l) Pale-yellow solid; yield: 101 mg (74%); mp 109–110 °C; IR (KBr): 2932, 1718, 1625, 1598, 1488 cm^–1; ¹H NMR (300.1 MHz, CDCl₃): δ = 3.93 (s, 3 H), 6.49 (m, 1 H), 6.77 (m, 1 H), 7.14 (t, J = 8.0 Hz, 1 H), 7.23 (t, J = 7.5 Hz, 1 H), 7.50 (m, 1 H), 7.83 (m, 2 H), 8.13 (m, 1 H), 8.47 (s, 1 H); ¹³C NMR (125.7 MHz, CDCl₃): δ = 52.46, 120.09, 122.19, 122.45, 122.90, 124.52, 125.97, 126.99, 127.47, 127.84, 128.67, 130.31, 130.77, 135.61, 144.18, 166.47; FAB: m/z [M⁺] calcd for C₁₆H₁₂N₂O₂: 264.09; found: 264.45. Methyl 2-(2-Thienyl)quinoline-3-carboxylate (4n) Pale-yellow oil; yield: 71 mg (52%); IR (KBr): 2932, 1722, 1624, 1585, 1492 cm^–1. ¹H NMR (300.1 MHz, CDCl₃): δ = 3.92 (s, 3 H), 7.12 (m, 1 H), 7.26 (s, 1 H), 7.40 (m, 1 H), 7.48 (d, J = 8.5 Hz, 1 H), 7.57 (d, J = 7.5 Hz, 1 H), 7.78 (m, 1 H), 8.12 (m, 1 H), 8.45 (s, 1 H); ¹³C NMR (125.7 MHz, CDCl₃): δ = 52.08, 99.39, 99.89, 107.19, 110.43, 115.44, 116.74, 118.95, 126.88, 128.08, 139.39, 142.39, 147.42, 154.11, 166.48; FAB: m/z [M⁺] calcd for C₁₅H₁₁NO₂S: 269.05; found: 269.37.
• 12 Usually, short-lived H–Pd–I species undergo immediate reductive elimination with a base, but MBH adducts with electron-donating substituents can undergo coupling with H–Pd–I, presumably under the influence of the +I effect of the electron-donating group.
• 13 Ma G.-N, Jiang J.-J, Shi M, Wei Y. Chem. Commun. 2009; 5496