Categories: Synthesis of O-Heterocycles > benzo-fused O-Heterocycles >
Synthesis of Benzofurans
Recent Literature
A convenient metal-free cyclization of ortho-hydroxystilbenes into
2-arylbenzofurans and 2-arylnaphthofurans is mediated by hypervalent iodine
reagents. Using stoichiometric (diacetoxyiodo)benzene in acetonitrile, desired
products can be isolated in good yields.
F. V. Singh, T. Wirth, Synthesis, 2012, 44,
1171-1177.
An iodine(III)-catalyzed oxidative cyclization of 2-hydroxystilbenes using 10
mol% (diacetoxyiodo)benzene [PhI(OAc)2] as catalyst in the presence of m-chloroperbenzoic
acid provides 2-arylbenzofurans in good to excellent yields.
F. V. Singh, S. R. Mangaonkar, Synthesis, 2018, 50,
4940-4948.
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.
Reactions of calcium carbide with salicylaldehyde p-tosylhydrazones or
2-hydroxyacetophenone p-tosylhydrazones provide methyl-substituted
benzofuran rings in good yields in the presence of cuprous chloride as catalyst.
The advantages of this method are the use of a readily available and
easy-to-handle acetylene source and a simple workup procedure.
R. Fu, Z. Li, Org. Lett.,
2018, 20, 2228-2231.
Easily prepared Palladium nanoparticles catalyze a one-pot synthesis of various
benzofurans via Sonogashira cross-coupling reactions under ambient conditions.
The catalyst can be recycled and reused without significant loss in its activity.
P. K. Mandali, D. K. Chand, Synthesis, 2015, 47,
1661-1668.
Indium(III) halides catalyze the hydroalkoxylation reaction of ortho-alkynylphenols
to afford benzo[b]furans in good yields.
L. Alonso-Marańón , M. M. Martínez , L. A. Sarandeses, E. Gómez-Bengoa, J. P.
Sestelo, J. Org. Chem., 2018, 83,
7970-7980.
An isocyanide-mediated and Pd-catalyzed 5-exo-dig reductive cyclization
of 1-(2-hydroxyphenyl)-propargyl alcohols provides 2-alkyl/benzyl benzofurans in
excellent yields. The reaction features a high substrate scope and is
insensitive to air. Further, a direct metal-free C-H functionalization (azidation,
alkoxylation, and hydroxylation) and selective oxidative cleavage of
2-benzylfurans are described.
M. Rajesh, N. Thirupathi, T. J. Reddy, S. Kanojiya, M. S. Reddy, J. Org. Chem.,
2015,
80, 12311-12320.
A nickel-catalyzed intramolecular nucleophilic addition reaction of aryl
halides to aryl ketones provides benzofuran derivatives in moderate yields. A number
of substrates bearing electron-donating or electron-withdrawing groups can be
converted.
X.-R. Zhu, C.-L. Deng, Synthesis, 2021, 53,
1842-1848.
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 domino intermolecular Sonogashira coupling of
2-(2-bromophenoxy)-1-phenylethan-1-ones/alkyl
2-(2-bromophenoxy)acetates/2-(2-bromophenoxy)acetonitrile/1-(2-bromophenoxy)propan-2-one
with terminal acetylenes followed by an intramolecular carbanion-yne cyclization
in a 5-exo-dig manner and subsequent double-bond isomerization
provide 2,3-disubstituted benzo[b]furans.
D. R. Kishore, G. Satyanarayana, J. Org. Chem., 2022, 87,
10158-10172.
An efficient palladium-catalyzed addition of arylboronic acids to aliphatic
nitriles provides a broad range of alkyl aryl ketones in good yields. It is
noteworthy that sequential addition and intramolecular annulation reactions of
2-(2-hydroxyphenyl)acetonitriles with arylboronic acids smoothly afford
2-arylbenzofurans in good yields under the standard conditions.
X. Wang, X. Wang, M. Liu, J. Ding, J. Chen, H. Wu, Synthesis, 2013, 45,
2241-2244.
A palladium-catalyzed addition of potassium aryltrifluoroborates to aliphatic
nitriles leads to a wide range of alkyl aryl ketones with good yields. The scope
of the developed approach is successfully explored toward the one-step synthesis
of 2-arylbenzo[b]furans via sequential addition and intramolecular
annulation reactions. The methodology accepted a wide range of substrates and is
applicable to library synthesis.
X. Wang, M. Liu, L. Xu, Q. Wang, J. Chen, J. Ding, H. Wu, J. Org. Chem., 2013,
78, 5273-5281.
A well-defined cationic Ru-H complex catalyzes the dehydrative C-H alkylation
reaction of phenols with alcohols to form ortho-substituted phenol
products. The reaction with diols delivers benzofuran derivatives via
dehydrative C-H alkenylation and annulation reaction. The catalytic C–H coupling
method employs cheap starting materials, exhibits a broad substrate scope, and
liberates water as the only byproduct.
D.-H. Lee, K.-H. Kwon, C. S. Yi, J. Am. Chem. Soc., 2012,
134, 6571-6574.
Benzo[b]furans were prepared in one pot based on the addition/palladium-catalyzed
C-H bond functionalization of phenols with bromoalkynes. The addition reactions
of phenols to bromoalkynes generated (Z)-2-bromovinyl phenyl ethers
exclusively. Subsequent intramolecular cyclization affords 2-substituted benzo[b]furans
in good yields through palladium-catalyzed direct C-H bond functionalizations.
S. Wang, P. Li, L. Yu, L. Wang, Org. Lett., 2011,
13, 5968-5971.
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.
NiCl2(PPh3)(IPr) catalyzes cross-coupling reactions of
2-methylsulfanylbenzofurans with alkyl Grignard reagents. The alkylation is
widely applicable, including the synthesis of a couple of protein tyrosine
phosphatase inhibitors, 3-(4-biphenylyl)-2-alkylbenzofurans.
A. Baralle, S. Otsuka, V. Guérin, K. Murakami, H. Yorimitsu, A. Osuka,
Synlett, 2015, 26, 327-330.
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.
A Pd-catalyzed O-arylation of ethyl
acetohydroximate as an hydroxylamine equivalent with aryl chlorides,
bromides, and iodides offers short reaction times and broad substrate scope. The
reaction allows
access to O-arylhydroxylamines that would be difficult to prepare.
Moreover, the O-arylated products 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.
A regioselective 5-exo-trig intramolecular oxidative cyclization of
ortho-cinnamyl phenols using [PdCl2(CH3CN)2]
as catalyst and benzoquinone as an oxidant provides functionalized 2-benzyl
benzo[b]furans. Further, a one-pot, sequential synthesis of ortho-cinnamyl
phenols, starting from readily available alcohols and phenols, followed by
Pd-catalyzed oxidative annulation, has also been developed.
M. Rehan, R. Nallagonda, B. G. Das, T. Meena, P. Ghorai, J. Org. Chem.,
2017, 82, 3411-3424.
Base-catalyzed condensation of o-hydroxyphenones with
1,1-dichloroethylene enables the preparation of highly functionalized
benzofurans via the corresponding chloromethylene furans. These labile
intermediates undergo a facile rearrangement into benzofuran carbaldehydes under
mild acidic conditions.
F. Schevenels, I. E. Markó, Org. Lett., 2012,
14, 1298-1301.
An iridium-catalyzed hydrogen transfer in the presence of p-benzoquinone
allows the synthesis of various substituted benzofurans, benzothiophenes, and
indoles from substituted benzylic alcohols.
B. Anxionnat, D. G. Pardo, G. Ricci, K. Rossen, J. Cossy, Org. Lett., 2013,
15, 3876-3879.
A synthesis of 2-carboxybenzofurans from 2-gem-dibromovinylphenols is
based on Cu-catalyzed intramolecular C-O coupling followed by Mo(CO)6-mediated
intermolecular carbonylation. This protocol provides a broad range of
functionalized benzofuran-2-carboxylic acids, esters, and amides in very good
yields under Pd- and CO gas-free conditions.
Q. Mo, N. Sun, L. Jin, B. Hu, Z. Shen, X. Hu, J. Org. Chem., 2020, 85,
11490-11500.
A cascade reaction composed of a [2+2] annulation of DMF with an aryne followed
by a trapping with a sulfur ylide enables the synthesis of a broad range of
2-aroyl benzofurans with high functional-group tolerance.
P. Gouthami, L. N. Chavan, R. Chegondi, S. Chadrasekhar, J. Org. Chem., 2018, 83,
3325-3332.
A Rh(III)-catalyzed annulation between salicylaldehydes and diazo compounds
offers good functional group tolerance, scalability, and a controllable
chemoselectivity. AgNTf2 as additive favored benzofurans via a tandem
C-H activation/decarbonylation/annulation process, while AcOH led to chromones
through a C-H activation/annulation pathway.
P. Sun, S. Gao, C. Yang, S. Guo, A. Lin, H. Yao, Org. Lett.,
2016, 18, 6464-6467.
A highly effective cocatalysis system (PdI2-thiourea and CBr4)
enables a carbonylative cyclization of a broad range of o-hydroxylarylacetylenes
to the corresponding methyl benzo[b]furan-3-carboxylates.
Y. Nan, H. Miao, Z. Yang,
Org. Lett., 2000, 2, 297-299.
A gold(I) complex catalyzes the cycloisomerization of a broad range of
2-(iodoethynyl)aryl esters to give 3-iodo-2-acyl benzofurans via a [1,2]-iodine
shift, a C-O ring-closure step, and a C-C bond-formation that installs the
ketone functionality into the new ring.
P. Fernández-Canelas, E. Rubio, J. M. González,
Org. Lett., 2019, 21, 6566-6569.
One-pot reactions of acyl chlorides, phosphorus ylides, and o-iodophenols
in the presence of a copper catalyst enable a rapid synthesis of functionalized
benzofurans.
Y. Liu, H. Wang, J.-P. Wan, J. Org. Chem.,
2014,
79, 10599-10604.
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.
An ortho-selective Sonogashira coupling of dichlorophenols and terminal
alkynes, followed by cyclization and Suzuki-Miyaura coupling in one pot enabled
the synthesis of disubstituted benzo[b]furans using a
palladium-dihydroxyterphenylphosphine (Cy-DHTP) catalyst. This protocol was also
successfully applied to the one-pot synthesis of disubstituted indoles from
dichloroaniline derivatives.
M. Yamaguchi, T. Akiyama, H. Sasou, H. Katsumata, K. Manabe, J. Org. Chem.,
2016,
81, 5450-5463.
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.
Cyclodehydration of various α-aryloxy ketones proceeded to give various
multisubstituted benzofurans by using an Ir(III) catalyst. The presence of
Cu(OAc)2 and a cationic iridium complex salt, which was prepared from
[Cp*IrCl2]2 and AgSbF6, realized an efficient
transformation at ambient temperature.
T. Shibata, Y.-k. Hashimoto, M. Otsuka, K. Tsuchikama, K. Endo, Synlett, 2011,
2075-2079.
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.
Potassium trinitromethanide can be used as a 1,1-ambiphilic synthon equivalent
for the construction of a benzofuran moiety mediated by triethylamine. The
method tolerates various functional groups. Formation of an o-quinone
methide is postulated as a key intermediate of this cascade process.
V. A. Osyanin, D. V. Osipov, M. R. Demidov, Y. N. Klimochkin, J. Org. Chem., 2014,
79, 1192-1198.
CuCl catalyzes a highly efficient electrophilic amination reaction of readily
available heteroarenes with O-benzoyl hydroxylamines via a one-pot C-H
alumination to afford various heteroaryl amines in very good yields. The
reaction can be performed in a single vessel on gram scales.
H. Yoon, Y. Lee, J. Org. Chem.,
2015,
80, 10244-10251.
Electrophilic cyclization reaction of o-anisole- and o-thioanisole-substituted
ynamides with I2, NBS and NCS gives 3-halogenated 2-amidobenzofurans
and 2-amidobenzothiophenes. Some 3-iodo-2-amidobenzofurans were further
transferred into 3-aryl-, 3-alkynyl, and 3-vinyl-2-amidobenzofurans via
Pd-catalyzed cross coupling reactions.
Y. Kong, L. Yu, L. Fu, J. Cao, G. Lai, Y. Cui, Z. Hu, G. Wang, Synthesis, 2013, 45,
1975-1982.
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.
A rhodium(III)-catalyzed cascade cyclization/electrophilic amidation using N-pivaloyloxylamides
as the electrophilic nitrogen source provides 3-amidoindoles and 3-amidofurans
under mild conditions with good functional group tolerance. The 3-amidoindoles
can be converted to several heterocycle-fused indoles.
Z. Hu, X. Tong, G. Liu, Org. Lett., 2016, 18,
2058-2061.
Gold(I) catalysis enables an efficient synthesis of N-protected pyrroles
and 5,6-dihydropyridin-3(4H)-ones from N-protected and unprotected
5-aminopent-2-yn-1-ol, respectively. Atom-economic syntheses of hydroxyalkyl
indoles and benzofurans are also described. The methods offer short reaction
time, low catalyst loading, high yield, and simple open-flask reaction
conditions.
N. Bera, B. S. Lenka, S. Bishi, S. Samanta, B. Sarkar, J. Org. Chem., 2022, 87,
9729-9754.