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Synthesis of Benzofurans

Recent Literature

Substituted benzofurans were synthesized from their corresponding substituted 1-allyl-2-allyloxybenzenes using ruthenium-catalyzed C- and O-allyl isomerization followed by ring-closing metathesis.
W. A. L. van Otterlo, G. L. Morgans, L. G. Madeley, S. Kuzvidza, S. S. Moleele, N. Thornton, C. B. de Koning, Tetrahedron, 2005, 61, 7746-7755.

An effective, Ru-catalyzed cycloisomerization of benzannulated homo- and bis-homopropargylic alcohols affords benzofurans and isochromenes chemo- and regioselectively (5-, and 6-endo cyclizations). The presence of an amine/ammonium base-acid pair is crucial for the catalytic cycle.
A. Varela-Fernández, C. González-Rodríguez, J. A. Varela, L. Castedo, Carlos Saá, Org. Lett., 2009, 11, 5350-5353.

Alkali-metal salts of a large number of electron-rich, electron-poor, and sterically hindered aryl- and heteroarylsilanols undergo efficient cross-coupling with a wide range of aromatic bromides and chlorides under mild conditions. The critical feature for the success of these coupling reactions and their considerable scope is the use of bis(tri-tert-butylphosphine)palladium.
S. E. Denmark, R. C. Smith, W.-T. T. Chang, J. M. Muhuhi, J. Am. Chem. Soc., 2009, 131, 3104-3118.

A ligand-free CuBr-catalyzed coupling/cyclization of terminal alkynes with N-tosylhydrazones derived from o-hydroxy- or o-aminobenzaldehydes enables the synthesis of benzofurans or indoles. A wide range of functional groups tolerate the reaction conditions.
L. Zhou, Y. Shi, Q. Xiao, Y. Liu, F. Ye, Y. Zhang, J. Wang, Org. Lett., 2011, 13, 968-971.

Reaction of O-arylhydroxylamine hydrochlorides with either cyclic or acyclic ketones in the presence of methanesulfonic acid leads directly to the benzofuran derivative via a proposed one-pot condensation-rearrangement-cyclisation reaction sequence in good to excellent yields.
F. Contiero, K. M. Jones, E. A. Matts, A. Porzelle, N. C. O. Tomkinson, Synlett, 2009, 3003-3006.

Hydroxyterphenylphosphine is an effective ligand for a Pd-catalized one-pot benzo[b]furan synthesis from 2-chlorophenols and alkynes.
J.-R. Wang, K. Manabe, J. Org. Chem., 2010, 75, 5340-5342.

Addition of a range of Grignard reagents to 1-(2-hydroxyphenyl)-2-chloroethanones generates alkoxide intermediates, which can form either 2-substituted benzo[b]furans via a [1,2]-aryl migration or 3-substituted benzo[b]furans via a direct cyclization and dehydration sequence. A temperature-dependent [1,2]-aryl migration mechanism for the formation of 2-substituted benzo[b]furan is proposed.
T. Pei, C.-y. Chen, L. DiMichele, I. W. Davies, Org. Lett., 2010, 12, 4972-4975.

An efficient Pd catalyst allows the O-arylation of ethyl acetohydroximate as an efficient hydroxylamine equivalent with aryl chlorides, bromides, and iodides. Short reaction times and broad substrate scope allow access to O-arylhydroxylamines that would be difficult to prepare. Moreover, the O-arylated products so formed can be directly transformed into substituted benzofurans in a single operation.
T. J. Maimone, S. L. Buchwald, J. Am. Chem. Soc., 2010, 132, 9990-9991.

A one-pot synthesis of benzofurans which utilizes a palladium-catalyzed enolate arylation demonstrates broad substrate scope and provides differentially substituted benzofurans in moderate yields. The utility of the method is further demonstrated by the synthesis of the natural product eupomatenoid 6 in three steps.
C. Eidamshaus, J. D. Burch, Org. Lett., 2008, 10, 4211-4214.

An effective and mild microwave-assisted route to 2-substituted benzofurans directly from carboxylic acids allows the preparation of α-alkyl-2-benzofuranmethanamines from N-protected α-amino acids without racemization in good yields.
L. De Luca, G. Giacomelli, G. Nieddu, J. Org. Chem., 2007, 72, 3955-3957.

TFAA induces a [3,3]-sigmatropic rearrangement of N-trifluoroacetyl-ene-hydroxylamines for the synthesis of dihydrobenzofurans, whereas reactions with TFAT-DMAP gives benzofurans. The synthetic utility is demonstrated by the short synthesis of natural benzofurans without protection of the hydroxy group.
N. Takeda, O. Miyata, T. Naito, Eur. J. Org. Chem., 2007, 1491-1509.

Copper-TMEDA catalyzes the transformation of readily available ketone derivatives into the corresponding benzo[b]furans in good to excellent yields. The sustainable protocol uses water as the solvent without organic cosolvents, and one example of catalyst reutilization is also presented.
M. Carril, R. SanMartin, I. Tellitu, E. Dominguez, Org. Lett., 2006, 8, 1467-1470.

An efficient CuI-catalyzed ring closure of 2-haloaromatic ketones gives a wide variety of benzo[b]furans.
C.-Y. Chen, P. G. Dormer, J. Org. Chem., 2005, 70, 6964-6967.

An efficient, indirect anti-Markovnikov hydration of unsymmetrically substituted terminal and internal alkynes is based on TiCl₄-catalyzed hydroamination reactions. Its application to ortho-alkynylhaloarenes, followed by a copper-catalyzed O-arylation, provides substituted benzo[b]furans.
L. Ackermann, L. T. Kaspar, J. Org. Chem., 2007, 72, 6149-6153.

In the presence of palladium(II) acetate and copper(I) iodide, unsymmetrical buta-1,3-diynes were selectively obtained from the reaction of (E)-1,2-diiodoalkenes with terminal alkynes in moderate to good yields at room temperature. Using the same conditions, the coupling of 2-ethynylphenol with (E)-1,2-diiodoalkenes followed by a cyclization at 100°C gives ethynylbenzofurans.
Y. Liang, L.-M. Tao, Y.-H. Zhang, J.-H. Li, Synthesis, 2008, 3988-3994.

Zn(OTf)₂ catalyzed the cyclization of propargyl alcohols with anilines and phenols in toluene at 100°C without additive and gave various indole and benzofuran products with different structures. The cyclization of propargyl alcohols and amides gave oxazoles. Mechanisms for the different substituation patterns are discussed.
M. P. Kumar, R.-S. Liu, J. Org. Chem., 2006, 71, 4951-4955.

A simple and highly efficient protodecarboxylation of various heteroaromatic carboxylic acids is catalyzed by Ag₂CO₃ and AcOH in DMSO. This methodology enables also a selective monoprotodecarboxylation of several aromatic dicarboxylic acids.
P. Lu, C. Sanchez, J. Cornella, I. Larrosa, Org. Lett., 2009, 11, 5710-5713.

A convenient high-yielding, efficient, selective and simple one-pot procedure for the synthesis of 3-ethoxycarbonylbenzofurans from commercially available salicylaldehydes and ethyl diazoacetate has been developed.
M. E. Dudley, M. M. Morshed, M. M. Hossain, Synthesis, 2006, 1711-1714.

CuI-catalyzed coupling of 1-bromo-2-iodobenzenes with β-keto esters in THF at 100°C provides 2,3-disubstituted benzofurans. This domino transformation involves an intermolecular C-C bond formation and a subsequent intramolecular C-O bond formation process.
B. Lu, B. Wang, Y. Zhang, D. Ma, J. Org. Chem., 2007, 72, 5337-5341.

The Pt-catalyzed cyclization of o-alkynylphenyl acetals produces 3-(-alkoxyalkyl)benzofurans in good to high yields. The mechanism is discussed.
I. Nakamura, Y. Mizushima, Y. Yamamoto, J. Am. Chem. Soc., 2005, 127, 15022-15023.

A one-pot method for the preparation of alkyl aryl ethers from aryl halides and the preparation of substituted benzofurans via a Pd-catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl alkynes are described.
K. W. Anderson, T. Ikawa, R. E. Tundel, S. L. Buchwald, J. Am. Chem. Soc., 2006, 128, 10694-10695.

2,3-Disubstituted benzo[b]furans are readily prepared under very mild reaction conditions by the Sonogashira coupling of various o-iodoanisoles and terminal alkynes, followed by an electrophilic cyclization. Aryl- and vinylic-substituted alkynes give cyclization products in excellent yields.
D. Yue, T. Yao, R. C. Larock, J. Org. Chem., 2005, 70, 10292-10296.

A room temperature copper-catalyzed annulative amination of ortho-alkynylphenols with O-acylated hydroxylamines as electrophilic amination reagents proceeds efficiently to provide the corresponding 3-aminobenzofurans of biological and pharmaceutical interest.
K. Hirano, T. Satoh, M. Miura, Org. Lett., 2011, 13, 2395-2397.