Categories: Synthesis of S-Heterocycles >
Synthesis of thiophenes and benzothiophenes
Name Reactions
Paal-Knorr Thiophene Synthesis
Recent Literature

Copper-catalyzed tandem S-alkenylation of potassium sulfide with
1,4-diiodo-1,3-dienes enables an efficient synthetic approach to variously
substituted thiophenes.
W. You, X. Yan, Q. Liao, C. Xi, Org. Lett., 2010,
12, 3930-3933.

An efficient one-step method for the synthesis of highly substituted
thiophenes from thiomorpholides and α-haloketones was developed. The
mechanism is discussed.
F. Matloubi Moghaddam, H. Zali Bionee, Tetrahedron, 2004, 60,
6085-6089.

An efficient and highly versatile microwave-assisted Paal-Knorr condensation
of various 1,4-diketones gave furans, pyrroles and thiophenes in good yields.
In addition, transformations of the methoxycarbonyl moiety, such as Curtius
rearrangement, hydrolysis to carboxylic acid, or the conversion into amine
by reaction with a primary amine in the presence of Me3Al, are
described.
G. Minetto, L. F. Raveglia, A. Sega, M. Taddei, Eur. J. Org. Chem., 2005,
5277-5288.

Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, and N,N'-acylhydrazines
with the use of a fluorous Lawesson's reagent leads to thioamides, thiophenes,
1,3-thiazoles, and 1,3,4-thiadiazoles in high yields. The isolation of the final products is achieved in most cases by a
simple filtration.
Z. Kaleta, B. T Makowski, T. Soos, R. Dembinski, Org. Lett.,
2006, 8, 1625-1628.

4-dimethylaminopyridine (DMAP) promotes an efficient and experimentally rapid
protocol for the synthesis of 2,3-dicarboalkoxy-4-aroyl/heteroaroyl/alkanoyl
thiophenes in high yields via 1-2 (C-S) and 3-4 (C-C) bond connections in only
3-5 min in DCM at room temperature. This method allows a clean and general
synthesis of previously inaccessible and synthetically demanding thiophenes.
G. C. Nandi, S. Samai, M. S. Singh, J. Org. Chem., 2011,
76, 8009-8014.

An efficient one-pot procedure allows the synthesis of various functionalized
2-aminothiophene scaffolds catalyzed by L-proline in high yields under mild
conditions. Low catalyst loading, simple procedure, and high yields are the
important attributes of this methodology.
T. Wang, X.-G. Huang, J. Liu, B. Li, J.-J. Wu, K.-X. Chen, W.-L. Zhu, X.-Y. Xu,
B.-B. Zeng, Synlett, 2010,
1351-1354.

A palladium-catalyzed C-H arylation of electron-enriched heteroarenes with aryl
bromides and aryl chlorides proceeds in the presence of LiO-t-Bu as a
base. Differently substituted 2,5-diarylthiazole can be obtained with the same
catalyst system by switching the solvent and the amount of base.
S. Tamba, Y. Okubo, S. Tanaka, D. Monguchi, A. Mori, J. Org. Chem., 2010,
75, 6998-7001.

In the presence of CuI and TMEDA, a thiolation annulation reaction of 2-bromo
alkynylbenzenes with sodium sulfide delivers various 2-substituted benzo[b]thiophenes
in good yields.
L.-L. Sun, C.-L. Deng, R.-Y. Tang, X.-G. Zhang, J. Org. Chem., 2011,
76, 7546-7550.

Thiourea can be used as a cheap and easy to handle dihydrosulfide surrogate in
C-S bond formation/cross-coupling/cyclization domino reactions. Structurally
important biarylthioether, benzo[b]thiophenes, and thieno[3,2-b]thiophene
scaffolds are provided in high yield.
M. Kuhn, F. C. Falk, J. Paradies, Org. Lett., 2011,
13, 4100-4103.

A gold-catalyzed carbothiolation provided an atom-economic way of
synthesizing sulfur-containing heterocycles such as 2,3-disubstituted
benzothiophenes.
I. Nakamura, T. Sato, Y. Yamamoto, Angew. Chem. Int. Ed., 2006, 45, 4473-4475.

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.

Conditions for the palladium-catalyzed direct arylation of a wide range of
heterocycles with aryl bromides employ a stoichiometric ratio of both coupling
partners, as well as a substoichiometric quantity of pivalic acid, which results
in significantly faster reactions. An evaluation of the influence of the nature
of the aryl halide has also been carried out.
B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou, J. Org. Chem., 2009,
74, 1826-1834.

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.

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.

