Synthesis of benzothiophenes
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 highly efficient synthesis of benzothiophenes from easily available o-halovinylbenzenes and potassium sulfide tolerates a wide range of functionalities and provides various 2-substituted benzo[b]thiophenes in high yields in the absence of a transition-metal catalyst.
X. Zhang, W. Zeng, Y. Yang. H. Huang, Y. Liang, Synlett, 2013, 24, 1687-1688.
A photocatalytic radical annulation process of o-methylthio-arenediazonium salts with alkynes yields substituted benzothiophenes regioselectively. Green light irradiation of eosin Y initiates the photoredox catalysis. The scope of the reaction was investigated by using various substituted diazonium salts and different alkynes.
D. P. Hari, T. Hering, B. König, Org. Lett., 2012, 14, 5334-5337.
In the presence of CuI and 1,10-phen, and n-Pr3N as the base, (2-iodobenzyl)triphenylphosphonium bromide and (2-iodophenylimino)triphenylphosphorane reacted efficiently with thiocarboxylic acids to give benzo[b]thiophenes and benzothiazoles in good yields via sequential Ullmann-type C-S bond coupling and subsequent Wittig reaction.
H. Yu, M. Zhang, Y. Li, J. Org. Chem., 2013, 78, 8898-8899.
Iodine-catalyzed cascade reactions of substituted thiophenols with alkynes under metal- and solvent-free conditions enable the synthesis of benzothiophene derivatives in good yields. Such an efficient, economical, and green transformation should provide an attractive approach to various benzothiophenes.
K. Yan, S. Yang, M. Zhang, W. Wei, Y. Liu, L. Tian, H. Wang, Synlett, 2015, 26, 1890-1894.
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.
α-C-H functionalization using Cu(OAc)2 as catalyst and xanthate as sulfur source enables an efficient synthesis of 2-acylbenzo[b]thiophenes from easily accessible 2-iodochalcones. Less reactive 2-bromochalcones also yielded the corresponding 2-acylbenzothiophenes in good yield. The reaction proceeds via in situ incorporation of sulfur followed by copper-catalyzed cyclization.
S. Sangeetha, G. Sekar, Org. Lett., 2017, 19, 1670-1673.
The reaction of 2-nitrochalcones with elemental sulfur provides a wide range of 2-benzoylbenzothiophenes in the presence of DIPEA as sulfur activator.
T. B: Nguyen, P. Retailleau, Org. Lett., 2017, 19, 4858-4860.
A tandem base-mediated condensation of o-iodoarylacetonitriles/acetates/ketones with (hetero)aryldithioesters and an intramolecular C-S bond formation provides diversely substituted benzothiophenes and heterofused thiophenes in excellent yields.
Y. Kumar, H. Ila, Org. Lett., 2021, 23, 1698-1702.
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.
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.
The use of a stable dimethyl(thiodimethyl)sulfonium tetrafluoroborate salt enables an electrophilic cyclization o-alkynyl thioanisoles to provide 2,3-disubstituted benzo[b]thiophenes with a valuable thiomethyl group at position 3 in excellent yields. The reaction utilizes moderate reaction conditions while tolerating various functionalities.
Z. Alikhani, A. G. Albertson, C. A. Walter, P. J. Masih, T. Kesharwani, J. Org. Chem., 2022, 87, 6312-6320.
A practical and efficient electrochemical method enables a green synthesis of C-3-sulfonated benzothiophenes in good yields from 2-alkynylthioanisoles and sodium sulfinates under oxidant- and catalyst-free conditions. Preliminary mechanistic studies indicated a tandem radical addition-cyclization pathway. Moreover, the protocol is easy to scale up.
D. Zhang, J. Cai, J. Du, X. Wang, W. He, Z. Yang, C. Liu, Z. Fang, K. Guo, J. Org. Chem., 2021, 86, 2593-2601.