Categories: C-C Bond Formation > Arenes > Biaryls >

Synthesis of heterobiaryls

Recent Literature

Highly stable and active Pd-phosphine catalysts have been found for the Suzuki-Miyaura coupling of pyridine, pyrrole, and indole boronic acids. These complexes are not inhibited by the presence of highly basic aminopyridines or aminopyrimidines.
K. L. Billingsley, K. W. Anderson, S. L. Buchwald, Angew. Chem. Int. Ed., 2006, 45, 3484-3488.

Pd-catalyzed couplings of several (hetero)aromatic halides with (hetero)aromatic boronic acids can be conducted under mild conditions in pure water using commercially available Pd catalysts and PTS, a nanomicelle-forming amphiphile.
B. H. Lipshutz, A. R. Abela, Org. Lett., 2008, 10, 5329-5332.

A new method for a direct, copper-catalyzed arylation of heterocycle C-H bonds by aryl iodides allows the conversion of electron-rich five-membered heterocycles and electron-poor pyridine oxides. The best results are obtained by using a combination of lithium tert-butoxide as base and copper iodide as catalyst.
H.-Q. Do, O. Daugulis, J. Am. Chem. Soc., 2007, 129, 12404-12405.

Pd(PPh₃)₄ efficiently catalyses both direct arylation and alkenylation of oxazoles. The method is regio- and stereospecific with respect to bromoalkenes and tolerates a wide range of functional groups.
F. Besselièvre, S. Lebrequier, F. Mahuteau-Betzer, S. Piguel, Synthesis, 2009, 3511-3512.

A straightforward route allows the synthesis of 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics.
C. Verrier, T. Martin, C. Hoarau, F. Marsais, J. Org. Chem., 2008, 73, 7383-7386.

A new catalyst system for the Pd-catalyzed cross-coupling of organozinc reagents with aryl halides permits efficient preparation of hindered biaryls, functions effectively at low levels of catalyst, and tolerates a wide range of functional groups and heterocyclic substrates.
J. E. Milne, S. L. Buchwald, J. Am. Chem. Soc., 2004, 126, 13028-13032.

New air-stable PdCl₂{PR₂(Ph-R')}₂ complexes, readily prepared from commercial reagents, exhibit unique efficiency as catalysts for the Suzuki-Miyaura coupling reactions of a variety of heteroatom-substituted heteroaryl chlorides with a diverse range of aryl/heteroaryl boronic acids.
A. S. Guram, X. Wang, E. E. Bunel, M. M. Faul, R. D. Larsen, M. J. Martinelli, J. Org. Chem., 2007, 72, 5104-5112.

New air-stable palladium phosphine complexes represent simple, general, and efficient catalysts for the Suzuki-Miyaura cross-coupling of aryl halides including five-membered heteroaryl halides and heteroatom-substituted six-membered heteroaryl chlorides with a various arylboronic acids.
A. S. Guram, A. O. King, J. G. Allen, X. Wang, L. B. Schenkel, J. Chan, E. E. Bunel, M. M. Faul, R. D. Larsen, M. J. Martinelli, P. J. Reider, Org. Lett., 2006, 8, 1787-1789.

The use of Pd₂(dba)₃ and X-Phos as a ligand enables a mild Negishi cross-coupling of 2-heterocyclic organozinc reagents and aryl chlorides providing 2-aryl-substituted pyridines and thiophenes in high yields. An efficient method to generate the organozinc reagents at room temperature is also demonstrated.
M. R. Luzung, J. S. Patel, J. Yin, J. Org. Chem., 2010, 75, 8330-8332.

Suzuki reactions of electron-deficient 2-heterocyclic boronates generally give low conversions and remain challenging. A successful copper(I) facilitated Suzuki coupling of 2-heterocyclic boronates is broad in scope and affords greatly enhanced yields of these notoriously difficult couplings. Furthermore, mechanistic investigations suggest a possible role of copper in the catalytic cycle.
J. Z. Deng, D. V. Paone, A. T. Ginnetti, H. Kurihara, S. D. Dreher, S. A. Weissman, S. R. Stauffer, C. S. Burgey, Org. Lett., 2009, 11, 345-347.

Air-stable and easily accessible PinP(O)H enables highly efficient palladium-catalyzed Kumada cross-coupling reactions of aryl tosylates. The in situ generated catalyst proved applicable not only to electron-rich and electron-poor carbocyclic tosylates but also to heterocyclic tosylates, such as pyridine and quinoline derivatives.
L. Ackermann, A. Althammer, Org. Lett., 2006, 8, 3457-3460.

C-C Coupling Reactions of Aryl Bromides and Arylsiloxanes in Water Catalyzed by Palladium Complexes of Phosphanes Modified with Crown Ethers
I. Gordillo, E. de Jesús, C. López-Mardomingo, Org. Lett., 2006, 8, 3517-3520.

A range of biaryl compounds can be efficiently prepared in high yields by a palladium-catalyzed cross-coupling reaction between ortho-substituted triarylindium reagents and aryl halides. The triarylindium reagents are prepared by directed ortho-lithiation and transmetallation to indium from the corresponding benzene derivatives.
M. A. Pena, J. P. Sestelo, L. A. Sarandeses, J. Org. Chem., 2007, 72, 1271-1275.

A highly efficient method for the synthesis of multisubstituted 1,2,3-triazoles via a direct Pd-catalyzed C-5 arylation has been developed.
S. Chuprakov, N. Chernyak, A. S. Dudnik, V. Gevorgyan, Org. Lett., 2007, 9, 2333-2336.

The use of nontoxic polyethylene glycol (PEG) as solvent and MesCO₂H as cocatalyst enabled user-friendly palladium(0)-catalyzed C-H bond functionalizations under air in the absence of phosphine ligands. Direct arylations of 1,2,3-triazoles gave substituted triazoles in good yields. Recycling of the catalytic system led to a slight decrease of activity.
L. Ackermann, R. Vicente, Org. Lett., 2009, 11, 4922-4925.

Cascade reactions starting from isocyanides allow a straightforward synthesis of five-membered ring heterocycles. Addition of sodium azide on isocyanide dibromides followed by electrocyclization and a Suzuki coupling affords tetrazoles scaffolds, whereas addition of tetrazoles on isocyanide dibromides followed by Huisgen rearrangement and a Suzuki coupling gives triazoles scaffolds.
L. El Kaim, L. Grimaud, P. Patil, Org. Lett., 2011, 13, 1261-1263.

An efficient, practical, and highly regioselective direct palladium-catalyzed C-3 arylation of electron-rich free (NH)-indoles with various aryl bromides under ligandless conditions in refluxing toluene in the presence of K₂CO₃ as the base can be run outside a glovebox without purification of solvent and reagents.
F. Bellina, F. Benelli, R. Rossi, J. Org. Chem., 2008, 73, 5529-5535.

A mild, Pd(OAc)₂-catalyzed regioselective cross-coupling between indoles and potassium aryltrifluoroarylborates gives 2-aryl indoles in moderate yields in the presence of Cu(OAc)₂ in acetic acid at room temperature.
J. Zhao, Y. Zhang, K. Cheng, J. Org. Chem., 2008, 73, 7428-7431.

An efficient and mild Negishi cross-coupling strategy for substituted 2,2′-bipyridines uses tetrakis(triphenylphosphine)palladium(0) as a simple, commercially available, and relatively inexpensive catalyst for both 2-bromo- and 2-chloropyridines.
U. Kiehne, J. Bunzen, H. Staats, A. Lützen, Synthesis, 2007, 1061-1069.

Various 5-substituted 2,2-bipyridines have been synthesized from substituted 2-chloropyridines through a modified Negishi cross-coupling reaction.
A. Lützen, M. Hapke, Eur. J. Org. Chem., 2002, 2292-2297.

Thiophene was regioselectively deprotonated by treatment with Bu₃MgLi in THF at room temperature. The lithium arylmagnesate formed was either trapped with electrophiles or cross-coupled in a ‘one-pot’ procedure with aryl halides under palladium catalysis.
O. Bayh, H. Awad, F. Mongin, C. Hoarau, F. Trécourt, G. Quéquiner, F. Marsais, F. Blanco, B. Abarca, R. Ballesteros, Tetrahedron, 2005, 61, 4779-4784.