Categories: C-C Bond Formation > Arenes > Biaryls >
Synthesis of heterobiaryls
Recent Literature
A wide range of aryl boronic 1,1,2,2-tetraethylethylene glycol esters [ArB(Epin)s]
were readily synthesized. ArB(Epin) derivatives are easily purified on silica
gel and isolated in excellent yields. Suzuki-Miyaura couplings of ArB(Epin)
derivatives provided higher yields of the desired biaryl products than those
obtained using the corresponding aryl boronic acids or pinacol esters.
N. Oka, T. Yamada, H. Sajiki, S. Akai, T. Ikawa, Org. Lett.,
2022, 24, 3510-3514.
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 versatile microwave-assisted procedure for the palladium-catalyzed direct
arylation of heterocycles by aryl bromides and heteroaryl bromides features
short coupling times (10–60 min) and low catalyst loadings and allows the
successful arylation of previously unreactive heterocyclic substrates.
M. Baghbanzadeh, C.Pilger, C. O. Kappe, J. Org. Chem., 2011,
76, 8138-8142.
Low-toxicity chromium(II) chloride catalyzes very fast coupling reactions of
various (hetero)arylmagnesium reagents with N-heterocyclic halides,
aromatic halogenated ketones or imines, and alkenyl iodides at room temperature.
Remarkably, much lower amounts of homo-coupling side products are obtained
compared to related iron, cobalt, or manganese cross-couplings.
A. K. Steib, O. M. Kuzmina, S. Fernandez, D. Flubacher, P. Knochel, J. Am. Chem. Soc., 2013,
135, 15346-15349.
A highly electron-rich Pd complex efficiently catalyzes a direct arylation of
heteroaromatics with unreactive and sterically hindered aryl chlorides.
D. Ghosh, H. M. Lee, Org. Lett., 2012,
14, 5534-5537.
Pinacol boronate esters that are analogous to unstable boronic acids are
formed in high yield by iridium-catalyzed C-H borylation of heteroarenes and
fluoroarenes. These boronates are stable in the solid state or in solution and
can be generated and used in situ for the palladium-catalyzed synthesis of
biaryls and heterobiaryls from arenes and haloarenes.
D. W. Robbins, J. F. Hartwig, Org. Lett., 2012,
14, 4266-4269.
An efficient palladium-catalyzed direct arylation of 2-furaldehyde with aryl
halides provides a range of 5-aryl-2-formylfuran derivatives in good yields
under mild conditions.
M. S. McClure, B. Glover, E. McSorley, A. Millar, M. H. Osterhout, F. Roschangar,
Org. Lett., 2001, 3, 1677-1680.
N-Protected (1H-tetrazol-5-yl)zinc pivalates are storable solids
with appreciably air and moisture stability. They are obtained in high yields by
deprotonation using the mixed zinc-magnesium base TMPZnClˇMg(OPiv)2.
Subsequent cross-couplings and copper-catalyzed electrophilic aminations using
hydroxylamine benzoates give access to functionalized 1H-tetrazoles.
C. P. Tüllmann, S. Steiner, P. Knochel, Synthesis, 2020, 52,
2357-2363.
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. Besseličvre, 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 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.
A Suzuki-Miyaura cross-coupling of tetrabutylammonium 2-pyridyltriolborate salts
with various aryl and heteroaryl chlorides produces the corresponding desired
coupling products with good to excellent yields in the presence of catalytic
amounts of PdCl2dcpp and CuI/MeNHCH2CH2OH in
anhydrous DMF without bases. Tetrabutylammonium 2-pyridyltriolborate salts are
more reactive than the corresponding lithium salts.
S. Sakashita, M. Takizawa, J. Sugai, H. Ito, Y. Yamamoto, Org. Lett., 2013,
15, 4308-4311.
Low loadings of (IPr)Ni(allyl)Cl catalyzes the cross-coupling reactions of
heteroaromatic chlorides with aryl Grignard reagents to afford products in
excellent yields. This nickel-based catalytic system also promotes the
activation of the CAr-O bond of anisoles in the Kumada-Tamao-Corriu
reaction under fairly mild conditions.
M. J. Iglesias, A. Prueto, M. C. Nicasio, Org. Lett., 2012,
14, 4318-4321.
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.
An efficient, palladium-catalyzed Hiyama cross-coupling reaction of
aryltrifluorosilanes with aryl chlorides enables the preparation of various
functionalized biaryl derivatives in good to excellent yields. The scope of this
reaction has also been extended to heteroaryl chlorides, affording the
corresponding heterobiaryl compounds in high yields.
G. A. Molander, L. Iannazzo, J. Org. Chem., 2011,
76, 9102-9108.
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 well-defined NHC-Pd(II)-Im complex enables a facile and alternative
methodology for the direct C-H bond arylation of (benz)imidazoles with (hetero)aryl
chlorides. Various activated, unactivated, and deactivated (hetero)aryl
chlorides were used as arylating reagents to yield 2-(hetero)aryl (benz)imidazoles
in good yields.
Z.-S. Gu, W.-X. Chen, L-X. Shao, J. Org. Chem., 2014,
79, 5806-5811.
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.
The use of Cu(OAc)2 enables a dehydrogenative cross-coupling between
two heteroarenes via disproportionation of the copper mediator. This synthetic
protocol provides a concise and "green" access to unsymmetrical biheteroarenes
bearing structural motifs of substantial utility in organic synthesis.
Z. F. Mao, Z. Wang, Z. Q. Xu, F. Huang, Z. K. Yu, R. Wang, Org. Lett., 2012,
14, 3854-3857.
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.