Aim and Objective: The synthesis of bipyridines, especially 2, 2’-bipyridines, remains challenging because the catalytic cycle can be inhibited due to coordination of bipyridine to transition metal. Thus, the development of efficient methods for the synthesis of bipyridines is highly desirable. In the present work, we presented a promising approach for preparation of bipyridines via a Pd-catalyzed reductive homocoupling reaction with simple piperazine as a ligand.
Materials and Methods: Simple and inexpensive piperazine was used as a ligand for Pd-catalyzed homocoupling reaction. The combination of Pd(OAc)2 and piperazine in dimethylformamide (DMF) was observed to form an excellent catalyst and efficiently catalyzed the homocoupling of azaarenyl halides, in which DMF was used as the solvent without excess reductants although stoichiometric reductant was generally required to generate the low-oxidation-state active metal species in the catalytic cycles.
Results: In this case, good to excellent yields of bipyridines and their (hetero) aromatic analogues were obtained in the presence of 2.5 mol% of Pd(OAc)2 and 5 mol% of piperazine, using K3PO4 as a base in DMF at 140°C.
Conclusion: According to the results, piperazine as an inexpensive and efficient ligand was used in the Pd(OAc)2-catalyzed homocoupling reaction of heteroaryl and aryl halides. The coupling reaction was operationally simple and displayed good substrate compatibility.
Keywords: Piperazine, Pd-catalyzed, homocoupling reaction, bipyridines, halide azaarenes, heteroaryl, aryl halides.
(b)Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Aryl-aryl bond formation one century after the discovery of the Ullmann reaction. Chem. Rev., 2002, 102(5), 1359-1470.
(c)Balzani, V.; Campagna, S. Photochemistry and Photophysics of Coordination Compounds I, II (Topics in Current Chemistry); Springer: Verlag, Berlin, 2007, Vol. 280-281, .
(d)Hapke, M.; Brandt, L.; Lutzen, A. Versatile tools in the construction of substituted 2,2-bipyridines-cross-coupling reactions with tin, zinc and boron compounds. Chem. Soc. Rev., 2008, 37(12), 2782-2797.
(e)Zhang, F.; Duan, X-F. Facile One-Pot Direct arylation and alkylation of nitropyridine n-oxides with grignard reagents. Org. Lett., 2011, 13(22), 6102-6105.
(b)Korn, T.J.; Cahiez, G.; Knochel, P. New cobalt-catalyzed cross-coupling reactions of heterocyclic chlorides with aryl and heteroaryl magnesium halides. Synlett, 2003, 2003(12), 1892-1894.
(c)Zapf, A. Coupling of Aryl and Alkyl Halides with Organoboron Reagents Wiley-VCH: Verlag GmbH 2008, 211-229.
(d)Meijere, A.D.; Bräse, S.; Oestreich, M. Metal-Catalyzed Cross-Coupling Reactions and More; Wiley-VCH: Weinheim, 2012.
(e)Almond-Thynne, J.; Blakemore, D.C.; Pryde, D.C.; Spivey, A.C. Site-selective Suzuki–Miyaura coupling of heteroaryl halides–understanding the trends for pharmaceutically important classes. Chem. Sci., 2017, 8, 40-62.
(b)Martin, R.; Buchwald, S.L. Palladium-catalyzed suzuki−miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc. Chem. Res., 2008, 41(11), 1461-1473.
(c)Birkholz, M-N.; Freixa, Z.; van Leeuwen, P.W.N.M. Bite angle effects of diphosphines in C-C and C-X bond forming cross coupling reactions. Chem. Soc. Rev., 2009, 38(4), 1099-1118.
(b)Marion, N.; Nolan, S.P. Well-defined n-heterocyclic carbenes−palladium(II) precatalysts for cross-coupling reactions. Acc. Chem. Res., 2008, 41(11), 1440-1449.
(b)Serrano, J.L.; García, L.; Pérez, J.; Pérez, E.; García, J.; Sánchez, G.; Sehnal, P.; De Ornellas, S.; Williams, T.J.; Fairlamb, I.J.S. Synthesis and characterization of imine-palladacycles containing imidate “pseudohalide” ligands: efficient suzuki–miyaura cross-coupling precatalysts and their activation to give Pd0Ln species (L = Phosphine). Organometallics, 2011, 30(19), 5095-5109.
(c)Mandegani, Z.; Asadi, M.; Asadi, Z. Nano tetraimine Pd(0) complex as an efficient catalyst for phosphine-free Suzuki reaction in water and copper-free Sonogashira reaction under aerobic conditions. Appl. Organomet. Chem., 2016, 30(8), 657-663.
(b)Li, J-H.; Liang, Y.; Wang, D-P.; Liu, W-J.; Xie, Y-X.; Yin, D-L. Efficient stille cross-coupling reaction catalyzed by the Pd(OAc)2/dabco catalytic system. J. Org. Chem., 2005, 70(7), 2832-2834.
(c)Kylmälä, T.; Kuuloja, N.; Xu, Y.; Rissanen, K.; Franzén, R. Synthesis of chlorinated biphenyls by Suzuki cross-coupling using diamine or diimine-palladium complexes. Eur. J. Org. Chem., 2008, 2008(23), 4019-4024.
(d)Bowser, A.K.; Anderson-Wile, A.M.; Johnston, D.H.; Wile, B.M. Diamine bis(phenolate) and pendant amine bis(phenolate) ligands: catalytic activity for the room temperature palladium-catalyzed Suzuki–Miyauracoupling reaction. Appl. Organomet. Chem., 2016, 30(1), 32-39.
(b)Gu, P.; Xu, Q.; Shi, M. Synthesis of Novel N-heterocyclic carbene-oxazoline palladium complexes and their applications in Suzuki–Miyaura cross-coupling reaction. Synlett, 2013, 24(10), 1255-1259.
(b)Saikia, B.; Boruah, P.R.; Ali, A.A.; Sarma, D. Simple and efficient phosphine-free Pd(OAc)2 catalyzed urea accelerated Suzuki–Miyaura cross-coupling reactions in iPrOH–H2O at room temperature. Tetrahedron Lett., 2015, 56(4), 633-635.
(b)Ma, N.; Duan, Z.; Wu, Y. DAB-Cy as an inexpensive and effective ligand for palladium-catalyzed homocoupling reaction of aryl halides. J. Organomet. Chem., 2006, 691(26), 5697-5700.
(c)Ratniyom, J.; Chaiprasert, T.; Pramjit, S.; Yotphan, S.; Sangtrirutnugul, P.; Srisuratsiri, P.; Kongsaeree, P.; Kiatisevi, S. Air-stable imidazole-imine palladium complexes for Suzuki–Miyaura coupling: Toward an efficient, green synthesis of biaryl compounds. J. Organomet. Chem., 2014, 752, 161-170.
(b)Moore, L.R.; Vicic, D.A. A heterogeneous-catalyst-based, microwave-assisted protocol for the synthesis of 2,2′-bipyridines. Chem. Asian J., 2008, 3(6), 1046-1049.
(c)Liao, L-Y.; Kong, X-R.; Duan, X-F. Reductive Couplings of 2-halopyridines without external ligand: phosphine-free nickel-catalyzed synthesis of symmetrical and unsymmetrical 2, 2′-bipyridines. J. Org. Chem., 2014, 79(2), 777-782.
(b)Baumann, C.G.; De Ornellas, S.; Reeds, J.P.; Storr, T.E.; Williams, T.J.; Fairlamb, I.J.S. Formation and propagation of well-defined Pd nanoparticles (PdNPs) during C–H bond functionalization of heteroarenes: are nanoparticles a moribund form of Pd or an active catalytic species? Tetrahedron, 2014, 70(36), 6174-6187.
(c)Reay, A.J.; Fairlamb, I.J.S. Catalytic C-H bond functionalisation chemistry: the case for quasi-heterogeneous catalysis. Chem. Commun., 2015, 51(91), 16289-16307.
(b)Li, J-H.; Hu, X-C.; Liang, Y.; Xie, Y-X. PEG-400 promoted Pd(OAc)2/DABCO-catalyzed cross-coupling reactions in aqueous media. Tetrahedron, 2006, 62(1), 31-38.
(c)Durand, J.; Milani, B. The role of nitrogen-donor ligands in the palladium-catalyzed polyketones synthesis. Coord. Chem. Rev., 2006, 250(3-4), 542-560.
(d)Truong, T.; Nguyen, C.K.; Tran, T.V.; Nguyen, T.T.; Phan, N.T.S. Nickel-catalyzed oxidative coupling of alkynes and arylboronic acids using the metal-organic framework Ni2(BDC)2(DABCO) as an efficient heterogeneous catalyst. Catal. Sci. Technol., 2014, 4(5), 1276-1285.
(b)Lin, Y-S.; Yamamoto, A. Studies relevant to palladium-catalyzed carbonylation processes. mechanisms of formation of esters and amides from benzylpalladium and (phenylacetyl)palladium complexes on reactions with alcohols and amines. Organometallics, 1998, 17(16), 3466-3478.
(c)Qi, C.; Sun, X.; Lu, C.; Yang, J.; Du, Y.; Wu, H.; Zhang, X-M. Palladium catalyzed reductive homocoupling reactions of aromatic halides in dimethyl sulfoxide (DMSO) solution. J. Organomet. Chem., 2009, 694(18), 2912-2916.
(d)Zeng, M.; Du, Y.; Qi, C.; Zuo, S.; Li, X.; Shao, L.; Zhang, X-M. An efficient and recyclable heterogeneous palladium catalyst utilizing naturally abundant pearl shell waste. Green Chem., 2011, 13(2), 350-356.
(e)Willcox, D.; Chappell, B.G.N.; Hogg, K.F.; Calleja, J.; Smalley, A.P.; Gaunt, M.J. A general catalytic β-C–H carbonylation of aliphatic amines to β-lactams. Science, 2016, 354(6314), 851-857.
(b)Jutand, A.; Mosleh, A. Nickel- and palladium-catalyzed homocoupling of aryl triflates. scope, limitation, and mechanistic aspects. J. Org. Chem., 1997, 62(2), 261-274.