Direct arylation and Suzuki-Miyaura coupling of imidazo[1,2-a]pyridines catalyzed by (SIPr)Pd(allyl)Cl complex under microwave-irradiation

Authors

  • Abdelmoula El Abbouchi Euromed Research Center, Euromed Faculty of Engineering, Euromed University of Fes (UEMF), Route de Meknes, 30000 Fés
  • Jamal Koubachi Faculté Polydisciplinaire de Taroudant, Université Ibn Zohr d'Agadir, B.P 271, 83000 Taroudant
  • Nabil El Brahmi
  • Said El Kazzouli

DOI:

https://doi.org/10.13171/mjc1911271124sek

Abstract

A short and practical arylation of imidazo[1,2-a]pyridine and imidazole derivatives with aryl halides or aryl boronic acids as coupling partners was successfully carried out using phosphine-free (SIPr)Pd(allyl)Cl as the catalyst [SIPr: (N,N’-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene)] ((SIPr)Pd(allyl)Cl complex). 3,6-disubstituted imidazo[1,2-a]pyridine and 5-substituted imidazole compounds were obtained in good to excellent yields in only 1h under microwave-assisted C-H arylation and Suzuki-Miyaura coupling reaction conditions.

Author Biographies

Abdelmoula El Abbouchi, Euromed Research Center, Euromed Faculty of Engineering, Euromed University of Fes (UEMF), Route de Meknes, 30000 Fés

Euromed Faculty of Engineering

Jamal Koubachi, Faculté Polydisciplinaire de Taroudant, Université Ibn Zohr d'Agadir, B.P 271, 83000 Taroudant

Faculté Polydisciplinaire de Taroudant

Nabil El Brahmi

Euromed Research Center, Euromed Faculty of Engineering, Euromed University of Fes (UEMF), Route de Meknes, 30000 Fés

References

- (a) M. Gerlach, C. Maul, WO 01/27119; (b) B. Sundermann, C. Maul, H.-H. Hennies, J. Schneider, WO 02/30428; (c) S. T. Hodgson, US005538970; (d) H. Nagaya, Y. Kawano, T. Kashihara, WO 01/34152; (e) K. Fuchs, M. Romig, K. Mendla, H. Briem, K. Fechteler, WO02/14313; (k) A. P. Thomas, G. A. Breault, J. F. Beattie, P. J. Jewsbury, WO 01/14375.

- M. Hayakawa, H. Kaizawa, K. Kawaguchi, N. Ishikawa, T. Koizumi, T. Ohishi, M. Yamano, M. Okada, M. Ohta, S. Tsukamoto, F. I. Raynaud, M. D. Waterfield, P. Parker, P. Workman, Synthesis and biological evaluation of imidazo[1,2-a] pyridine derivatives as novel PI3 kinase p110α inhibitors. Bioorg. Med. Chem., 2007, 15, 403-412.

- G. Trapani, M. Franco, A. Latrofa, L. Ricciardi, A. Carotti, M. Serra, E. Sanna, G. Biggio, G. Liso, Novel 2-Phenylimidazo[1,2-a] pyridine Derivatives as Potent and Selective Ligands for Peripheral Benzodiazepine Receptors: Synthesis, Binding Affinity, and in Vivo Studies. J. Med. Chem., 1999, 42, 3934-3941.

- R. Ducray, I. Simpson, F. H. Jung, J. W. M. Nissink, P. W. Kenny, M. Fitzek, G. E. Walker, L. T. Ward, K. Hudson, Discovery of novel imidazo[1,2-a] pyridines as inhibitors of the insulin-like growth factor-1 receptor tyrosine kinase. Bioorg. Med. Chem. Lett., 2011, 21, 4698-4701.

- L. Almirante, L. Polo, A. Mugnaini, E. Provinciali, P. Rugarli, A. Biancotti, A. Gamba, W. Murmann, Derivatives of Imidazole. I. Synthesis and Reactions of Imidazo[1,2-α] pyridines with Analgesic, Anti-inflammatory, Antipyretic, and Anticonvulsant Activity. J. Med. Chem., 1965, 8, 305-312.

- G. Guillaumet, S. Berteina-Raboin, S. El Kazzouli, P. Delagrange, D.-H. Caignard, PCT, Int. Appl., WO 2006027474, 2006. Chem. Abstract.,2006, 144, 254132.

- (a) M. Lhassani, O. Chavignon, J. M. Chezal, J. C. Teulade, J. P. Chapat, R. Snoeck, G. Andrei, J. Balzarini, E. De Clercq, A. Gueiffier, Synthesis and antiviral activity of imidazo[1,2-a] pyridines. J. Med. Chem., 1999, 34, 271-274. (b) k. S. Gudmundsson, J. C. Drach, L. B. Townsend, Synthesis of Imidazo[1,2-a] pyridine C-Nucleosides with an Unexpected Site of Ribosylation, J. Org. Chem., 1997, 62, 3453-3459. (c) C. Hamdouchi, J. de Blas, M. del Prado, J. Gruber, B. A. Heinz,

L. Vance, 2-Amino-3-substituted-6-[(E)-1-phenyl-2-(N-methyl carbam-oyl) vinyl]imidazo[1,2-a]pyridines as a Novel Class of Inhibitors of Human Rhinovirus: Stereospecific Synthesis and Antiviral Activity. J. Med. Chem., 1999, 42, 50-59. (d) K. S. Gudmundsson, J. D. Williams, J. C. Drach, L. B. Townsend, Synthesis and Antiviral Activity of Novel Erythrofuranosyl Imidazo[1,2-a] pyridine C-Nucleosides Constructed via Palladium Coupling of Iodoimidazo[1,2-a] pyridines and Dihydrofuran. J. Med. Chem., 2003, 46, 1449-1455.

- J. J. Kaminsky, A. M. Doweyko, Antiulcer Agents. 6. Analysis of the in Vitro Biochemical and in Vivo Gastric Antisecretory Activity of Substituted Imidazo[1,2-a] pyridines and Related Analogues Using Comparative Molecular Field Analysis and Hypothetical Active Site Lattice Methodologies. J. Med. Chem., 1999, 40, 427-436;

- Y. Rival, G. Grassy, G. Michael, Synthesis and Antibacterial Activity of Some Imidazo[1,2-α] pyrimidine Derivatives. Chem. Pharm. Bull., 1992, 40, 1170-1176;

- P. J. Beeswick, I. B. Campbell, A. Naylor, PCT. Int. Appl. WO 9631 509, 1996; Chem. Abst., 1997,126, 8117.

- (a) G. Trapani, M. Franco, A. Latrofa, L. Ricciardi, A. Carotti, M. Serra, E. Sanna, G. Biggio, G. Liso, Novel 2-Phenylimidazo

,2-a] pyridine Derivatives as Potent and Selective Ligands for Peripheral Benzodiazepine Receptors: Synthesis, Binding Affinity, and in Vivo Studies. J. Med. Chem., 1999, 42,

-3941. (b) G. Trapani, M. Franco, L. Ricciardi, A. Latrofa, G. Genchi, E. Sanna, F. Tuveri, E. Gagetti, G. Biggio, G. Liso, Synthesis and Binding Affinity of 2-Phenylimidazo[1,2-a] pyridine Derivatives for both Central and Peripheral Benzodiazepine Receptors. A New Series of High-Affinity and Selective Ligands for the Peripheral Type. J. Med. Chem., 1997, 40, 3109-3118.

- P. J. Sanfilippo, M. Urbanski, J. B. Press, B. Dubinsky, J. B. Jr. Moore, Regiospecific synthesis of 3-substituted imidazo[1,2-a] pyridines, imidazo[1,2-a] pyrimidines, and imidazo[1,2-c] pyrimidine. J. Med. Chem., 1991, 34, 2060-2067.

- K. Fuchs, M. Romig, K. Mendla, H. Briem,

K. Fechteler, WO 14 131, 2002, Chem. Abstr., 2002, 136, 183824r.

- Z. P. Zhuang, M. P. Kung, A. Wilson, C. W. Lee, K. Plössl, C. Hou, D.M. Holtzman, H. F. Kung, Structure−Activity Relation ship of Imidazo[1,2-a]pyridines as Ligands for Detecting β-Amyloid Plaques in the Brain. J. Med. Chem., 2003, 46, 237-243.

- H. Franke, J. Geisler, U. Hartfiel, W. Franke,

G. Dorfmeister, M. Ganzer, G. Johahann, R. Rees, Ger. Offen. DE. 4 120 108, 1991; Chem. Abstr., 1992, 118, 213075v.

- K. F. Byth, J. D. Culshaw, S. Green, S. Oakes, A. P. Thomas, Imidazo[1,2-a] pyridines. Part 2: SAR and optimisation of a potent and selective class of cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 2245-2248.

- A. C. Humphries, E. Gancia, M. T. Gilligan, S. Goodacre, D. Hallett, K. J. Merchant, S. R. Thomas, 8-Fluoroimidazo[1,2-a] pyridine: Synthesis, physicochemical properties and evaluation as a bioisosteric replacement for imidazo[1,2-a] pyrimidine in an allosteric modulator ligand of the GABAA receptor. Bioorg. Med. Chem. Lett., 2006, 16, 1518-1522.

- Y. Abe, H. Kayakiri, S. Satoh, T. Inoue, Y. Sawada, K. H. Imai, A Novel Class of Orally Active Non-Peptide Bradykinin B2 Receptor Antagonists. 1. Construction of the Basic Framework. J. Med. Chem., 1998, 41, 564-578.

- (a) T. Okubo, R. Yoshikawa, S. Chaki, S. Okuyamac, A. Nakazato, Design, synthesis and structure–affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands. Bioorg. Med. Chem., 2004, 12, 423-438; (b) S. Z. Langer, S. Arbilla, J. Benavides, B. Scatton, Zolpidem and Alpidem: Two imidazopyridines with selectivity for ω_1-and ω_3-receptor subtypes. Adv. Biochem. Psychopharmacol., 1990, 46, 61-72.

- (a) K. J. Holm, K. L. Goa, Zolpidem. Drugs. 2000, 59, 865-889; (b) N. Hsua, S. K. Jha, T. Coleman, M. Frank, Paradoxical effects of the hypnotic Zolpidem in the neonatal ferret. Behav. Brain Res., 2009, 201, 233-236;

- (a) K. Mizushige, T. Ueda, K. Yukiiri, H. Suzuki, Olprinone: a phosphodiesterase III inhibitor with positive inotropic and vasodilator effects. Cardiovasc. Drug Rev., 2002, 20,

-174; (b) T. Ueda, K. Mizushige, K. Yukiiri, T. Takahashi, M. Kohno, Improvement of cerebral blood flow by olprinone, a phosphodiesterase-3 inhibitor, in mild heart failure. CerebroVasc. Dis., 2003, 16, 396-401; (c) K. Ochiai, S. Takita, A. Kojima, T. Eiraku, N. Ando, K. Iwase, T. Kishi, A. Ohinata, Y. Yageta, T. Yasue, D. R. Adams, Y. Kohno, Phosphodiesterase inhibitors. Part 4: Design, synthesis and structure-activity relationships of dual PDE3/4-inhibitory fused bicyclic heteroaromatic-4,4-dimethylpyrazolones. Bioorg. Med. Chem. Lett., 2012, 22, 5833-5838.

- J. Koubachi, S. El Kazzouli, M. Bousmina, G. Guillaumet, Functionalization of Imidazo[1,2‐a] pyridines by Means of Metal‐Catalyzed Cross‐Coupling Reactions. Eur. J. Org. Chem. 2014, 5119-5138.

- (a) S. El Kazzouli, J. Koubachi, N. El Brahmi, G. Guillaumet, Advances in direct C–H arylation of 5, 5-6, 5-and 6, 6-fused-heterocycles containing heteroatoms (N, O, S). RSC Adv., 2015, 5, 15292-15367; (b) U. Sharma, A. Modak, S. Maity, A. Maji, D. Maiti, Direct Arylation via C–H Activation, RSC Catalysis Series No. 21, From the book: New Trends in Cross-Coupling: Theory and Applications, ed. by T. J. Colacot, 2014, 551- 609.

- D. Enders, O. Niemeier, A. Henseler, Organocatalysis by N-heterocyclic carbenes. Chem. Rev., 2007, 107, 5606-5655.

- (a) N-Heterocyclic Carbenes: Effective Tools for Organometallic Synthesis-Wiley-VCH, 568 pages, September 2014, ed. byS. P. Nolan, ISBN: 978-3-527-33490-2, Print ISBN: 978-3-527-33490-2, ePDF ISBN: 978-3-527-67125-0; (b) A. Charroire, and P. S. Nolan, Advances in C–C and C–X Coupling Using Palladium–N-Heterocyclic Carbene (Pd–NHC) Complexes, RSC Catalysis Series No. 21, From the book: New Trends in Cross-Coupling: Theory and Applications, ed. byT. J. Colacot, 2014, 139,

(c) S. Díez-González, N. Marion, S. P. Nolan, N-heterocyclic carbenes in late transition metal catalysis. Chem. Rev., 2009, 109, 3612-3676.

- (a) X.-B. Lan, F.-M. Chen, B.-B. Ma, D.-S. Shen, F.-S. Liu, Pd-PEPPSI Complexes Bearing Bulky [(1,2-Di-(tert-butyl) acenaphthyl] (DtBu-An) on N-Heterocarbene Backbones: Highly Efficient for Suzuki–Miyaura Cross-Coupling under Aerobic Conditions. Organometallics, 2016, 35, 3852-3860; (b) P. Yin, M. Y. Wong, J. Thamb, T.-P Loh, Nucleoside analogs as a rich source of antiviral agents active against arthropod-borne flaviviruses. Org. Chem. Front., 2014, 1, 1266-1269; (c) M. J. Cawley, F. G. N. Cloke, R. J. Fitzmaurice, S. E. Pearson, J. S. Scott, S.Caddick, Development of a practical Buchwald–Hartwig amine arylation protocol using a conveniently prepared (NHC) Pd(R-allyl)Cl catalyst. Org. Biomol. Chem., 2008, 6, 2820-2825; (d) O. Navarro, Marion, J. Mei, S. P. Nolan, Rapid room temperature Buchwald–Hartwig and Suzuki–Miyaura couplings of heteroaromatic compounds employing low catalyst loadings. Chem. Eur. J., 2006, 12, 5142-5148;(e) N. Marion, O. Navarro, J. Mei, E. D. Stevens, N. M. Scott, S. P. Nolan, Modified (NHC)Pd(allyl)Cl (NHC= N-Heterocyclic Carbene) Complexes for Room-Temperature Suzuki−Miyaura and Buchwald−Hartwig Reactions. J. Am. Chem. Soc., 2006, 128, 4101-4111; (f) O. Navarro, H. Kaur, P. Mahjoor, S. P. Nolan, Cross-Coupling and Dehalogenation Reactions Catalyzed by (N-Heterocyclic carbene)Pd(allyl)Cl Complexes. J. Org. Chem., 2004,69, 3173-3180; (g) L. J. Gooßen, J. Paetzold, O. Briel, A. Rivas-Nass, R. Karch, B. Kayserc, Buchwald-Hartwig Aminations of Aryl Chlorides: A Practical Protocol Based on Commercially Available Pd(0)-NHC Catalysts. Synlett., 2005, 36, 275-278; (h) R. Singh, S. P. Nolan, An efficient and mild protocol for the

α-arylation of ketones mediated by an (imidazol-2-ylidene) palladium(acetate) system. J. Organomet. Chem., 2005, 690, 5832-5840; (i) O. Navarro, N. Marion, N. M. Scott, J. Gonzalez, D. Amoroso, A. Bell, S. P. Nolan, Synthesis of novel (NHC)Pd(acac)Cl complexes (acac= acetyl acetonate) and their activity in cross-coupling reactions. Tetrahedron, 2005,61, 9716-9722; (j) O. Navarro, N. Marion, Y. Oonishi, R. A. Kelly, S. P. Nolan, Suzuki−Miyaura, α-Ketone Arylation and Dehalogenation Reactions Catalyzed by a Versatile N-Heterocyclic Carbene−Palladacycle Complex. J. Org. Chem., 2006,71, 685-692; (k) K. Matsubara, H. Okazaki, M. J. Senju, Polycondensation of haloarylketones catalyzed by palladium compounds bearing N-heterocyclic carbene (NHC) ligands. J. Organomet. Chem. 2006, 691, 3693-3699.

- (a) P. V. Kumar, W.-S. Lin, J.-S. Shen, D. Nandi, H. M. Lee, Direct C5-arylation reaction between imidazoles and aryl chlorides catalyzed by palladium complexes with phosphines and N-heterocyclic carbenes. Organometallics. 2011, 30,5160-5169; (b)

S. Demir, I. Özdemir, H. Arslan, D. J. VanDerveer, Butylene linked palladium N-heterocyclic carbene complexes: Synthesis and catalytic properties. J. Organomet. Chem., 2011, 696,2589-2593; (c) B. B. Touré, B. S. Lane, D. Sames, Catalytic C− H arylation of SEM-protected azoles with palladium complexes of NHCs and phosphines. Org. Lett., 2006, 8,1979-1982; (d) I. Ozdemir, Y. Gök, Ö. Özeroğlu, M. Kaloğlu, H. Doucet, C. Bruneau, N‐Heterocyclic Carbenes: Useful Ligands for the Palladium‐Catalysed Direct C5 Arylation of Heteroaromatics with Aryl Bromides or Electron‐Deficient Aryl Chlorides. Eur. J. Inorg. Chem., 2010,1798-1805; (e) A. R. Martin, A. Chartoire, A. M. Z. Slawin, S. P. Nolan, Extending the utility of [Pd (NHC)(cinnamyl) Cl] precatalysts: Direct arylation of heterocycles. Beilstein J. Org. Chem., 2012, 8, 1637-1643; (f) M. Lesieur, F. Lazreg, C. S. Cazin, A cooperative Pd–Cu system for direct C–H bond arylation. J. Chem. Commun., 2014, 50, 8927-8929; (g) D. Ghosh, H. M. Lee, Efficient Pd-catalyzed direct arylations of heterocycles with unreactive and hindered aryl chlorides. Org. Lett., 2012, 14, 5534-5537.

- (a) J. Koubachi, N. El Brahmi, G. Guillaumet, S. El Kazzouli, Oxidative alkenylation of fused bicyclic heterocycles. Eur. J. Org. Chem., 2019, 2568-2586. (b) S. Faarasse, S. El Kazzouli, F. Suzenet, G. Guillaumet, Palladium-Catalyzed C3-Arylations of 1H- and 2H-Pyrazolo[4,3-b] pyridines on Water. J. Org. Chem., 2018, 83, 12847-12854. (c) S. Faarasse, S. ElKazzouli, M. Naas, J. Jouha, F. Suzenet, G. Guillaumet, “On Water” Direct C-3 Arylation of 2H-Pyrazolo[3,4-b] pyridines. J. Org. Chem., 2017, 82, 12300-12306. (d) M. Naas, S. El Kazzouli, E. M.Essassi, M. Bousmina, G.Guillaumet, Palladium-catalyzed oxidative direct C3-and C7-alkenylations of indazoles: Application to the synthesis of Gamendazole. Org. Lett., 2015, 17, 4320-4323.

- (a) S. El Kazzouli, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, Solid-phase synthesis of imidazo[1,2-a] pyridines and imidazo[1,2-a] pyrimidines. Tetrahedron Lett., 2003, 44, 6265-6267; (b) S. El Kazzouli, A. Berthault, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, Solution and solid phase functionalization of imidazo[1,2-a] pyridines. Lett. Org. Chem., 2005, 2, 184-187.

- (a) J. Koubachi, S. El Kazzouli, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, Regioselective palladium-catalyzed arylation and heteroarylation of imidazo[1,2-a] pyridines. Synlett., 2006, 19, 3237-3242; (b) J. Koubachi, S. El Kazzouli, S. Berteina-Raboin,

A. Mouaddib, G. Guillaumet, Synthesis of Polysubstituted Imidazo[1,2-a] pyridines via Microwave-Assisted One-Pot Cyclization/Suzuki Coupling/Palladium-Catalyzed Heteroarylation. J. Org. Chem., 2007, 72, 7650-7655; (c) J. Koubachi, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, Intramolecular arylation reactions: first efficient synthesis of novel fused pyridoimidazo-quinolinones or pyridoimidazo-azepinones libraries. Tetrahedron, 2010, 66, 1937-1946.

- (a) J. Koubachi, S. El Kazzouli, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, New and efficient palladium (0)-mediated microwave-assisted direct C3 alkenylation of imidazo[1,2-a] pyridines. Synthesis, 2008, 16,2537-2542; (b) J. Koubachi, S. Berteina-Raboin, A. Mouaddib,

G. Guillaumet, Pd/Cu-Catalyzed Oxidative C-H Alkenylation of Imidazo[1,2-a] pyridines, Synthesis, 2009, 2, 271-276.

- (a) J. Koubachi, S. El Kazzouli, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, Efficient microwave-assisted Suzuki-Miyaura cross-coupling reaction of 6-haloimidazo[1,2-a] pyridines. J. Mar. Chim. Heterocycl., 7, 2008, 1-9; (b) A. El Akkaoui, J. Koubachi, S. Berteina-Raboin, A. Mouaddib, G. Guillaumet, Pd-catalyzed regiocontrolled Sonogashira and Suzuki cross-coupling reaction of 3, 6-dihalogenoimidazo [1,2-a] pyridines: One-pot double-coupling approach. Tetrahedron, 2011, 67, 7128-7138.

- M. S. Viciu, R. F. Germaneau, O. Navarro-Fernandez, E. D. Stevens, S. P. Nolan, Activation and reactivity of (NHC) Pd (allyl) Cl (NHC= N-heterocyclic carbene) complexes in cross-coupling reactions. Organometallics, 2002, 21, 5470-5472.

- M. S. Viciu, R. F. Germaneau, S. P. Nolan, Well-defined, air-stable (NHC) Pd (Allyl) Cl (NHC= N-heterocyclic carbene) catalysts for the arylation of ketones. Org. Lett., 2002, 4, 4053-4056.

- Q-X. Liu, B-Y. He, P-C. Qian, L-X Shao,

N-Heterocyclic carbene–palladium (ii)–1-methylimidazole complex catalyzed direct C–H bond arylation of imidazo[1,2-a] pyridines with aryl chlorides. Org. Biomol. Chem., 2017, 15, 1151-1154.

- D. Nandi, S. S. Siwal, K. Mallick. Mono Arylation of Imidazo[1,2-a] pyridine and 1,2-dimethyl Imidazole: Application of Carbon Nitride Supported Palladium Catalyst. ChemistrySelect 2017, 2, 1747–1752.

- S. K. Rasheed, D. N. Rao, P. Das, Copper-catalyzed inter-and intramolecular C–N bond formation: synthesis of benzimidazole-fused heterocycles. J. Org. Chem., 2015, 80, 9321-9327.

- F-M. Chen, F-D. Huang, X-Y. Yao, T. Li, F-S, Liu, Direct C–H heteroarylation by an acenaphthyl-based α-diimine palladium complex: improvement of the reaction efficiency for bi (hetero) aryls under aerobic conditions. Org. Chem. Front. 2017, 4, 2336-2342.

- X.-X. He, Y. Li, B.-B. Ma, Z. Ke, F.-S, Liu, Sterically Encumbered Tetraarylimidazolium Carbene Pd-PEPPSI Complexes: Highly Efficient Direct Arylation of Imidazoles with Aryl Bromides under Aerobic Conditions. Organometallics, 2016, 35, 2655-2663.

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Published

2019-11-27

Issue

Vol. 9 No. 5 (2019)

Section

Organic Chemistry

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