3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• reaction, in which 2H-azirines act as the annulation reagent. Keywords: annulation; azirines; benzothiophenes; indoles; nickel catalysis; Introduction 2H-Azirines represent a valuable class of nitrogen heterocycles that are widely used as versatile building blocks in organic synthesis. In particular, the

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• stimuli-responsive chiral electrochromic materials. In the same year, You’s group developed a transition-metal-catalyzed C–H/C–H-type regioselective C3-arylation of benzothiophenes using molecular oxygen as the oxidant [79]. This strategy afforded the TADF-active compound 64a, which exhibits efficient

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• reaction of 2-fluorobenzothiophene (4) with 2a, increasing the amount of Ni(cod)2 to 20 mol % without adding extra cod yielded 48% of the desired product 5 (Scheme 3). This result indicates that the reaction is applicable to benzothiophenes as well as benzofurans. Moreover, we successfully introduced two

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• heterocycles, namely benzofurans, benzothiophenes, isocoumarins, chromones, benzopyrans, 1,2-dihydronaphthaIenes, coumarins, and coumestan including some physiologically active heterocyclic natural products like flavones [84]. In the presence of Hg(OAc)2 in acetic acid, simple cyclization of ortho-substituted

• arylacetylenes 93, 95, and 97 yielded benzofurans 94, benzothiophenes 96, and indoles 98, respectively. When the carbonyl group was introduced between an aryl and a methoxy group (99) then six-membered isocoumarin ring 100 was formed, and when a carbonyl group was introduced in between an aryl and an alkyne

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• ]. This approach allowed the synthesis of alkylated benzofurans and benzothiophenes (Scheme 27). Investigations of the substrate scope revealed that both electron-donating and electron-withdrawing group substituents at the aromatic portions of the imine substrate could afford the aromatic heterocycle in

• benzothiophenes in good yield (72m). The use of olefins bearing leaving groups such as halides also afforded cyclic products (Scheme 27; 72o and 72p). Mechanistically, the alkylated heteroaromatic compounds were obtained after protonation/isomerization of the aza-enolate intermediate formed in this type of

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• incorporation of sulfur to generate multifunctional β-carboline-linked benzothiophenones in good to excellent yields. The synthetic strategy could also be extended towards the synthesis of β-carboline-linked benzothiophenes. Moreover, the afforded products emerged as promising fluorophores and displayed

• synthesis of benzothiophenes, however, these methods rely on the use of organosulfur-based substrates [38][39][40][41]. Moreover, these methods are associated with some limitations such as using costly metal catalysts, air-sensitive starting materials, malodorous sulfides or thiols, low yields, and

• -nitrochalcone 1bA and elemental sulfur by testing different activators (Table 1). Recent findings revealed that a combination of an aliphatic amine with DMSO activated elemental sulfur for an electrophilic addition to generate thioaurones and benzothiophenes [59]. At 70 °C, the use of DIPEA in combination with

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• heterocycle. This intermediate was then trifluoromethylselenylated by [(bpy)CuSeCF3]2. While benzofurans and benzothiophenes were prepared in moderate to good yields, only marginal yields were obtained with indole derivatives (up to 25%). Finally, the reactions could easily be scaled up to a gram scale. The

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• with mono- (Th1) and bithiophene (Th2) units attached to positions 6 and 6′ (Sy = symmetric) or only to position 6 (As = asymmetric). “Oxidized” compounds have highly fluorescent closed forms emitting in the visible region (yellow to red). The dyes with nonoxidized benzothiophenes possess fluorescent

• of the ester groups was performed only for nonoxidized benzothiophenes, as shown for compound SyTh2 in Scheme 4. Diarylethenes with “oxidized” benzothiophene units and perfluorocyclopentene rings react with aqueous or alcoholic solutions of strong bases [5][10][15]. Under these conditions

• the location of the absorption band in the CF. If we compare the absorption spectra of SyOTh1 and AsOTh2, we see that the most red-shifted bands have very similar positions. This is a remarkable feature, as both compounds consist of the same parts: two oxidized benzothiophenes and, in total, two

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• , benzothiophenes and benzimidazoles seen in many drugs. In another demonstration of the value of diazonium salts, the König group have published a protocol for the synthesis of substituted benzothiophenes using Eosin Y photocatalysis, starting from o-methylthioarenediazonium salts and substituted alkynes (Scheme

•  20) [65]. The scope of the substrates demonstrated is quite broad, with substituted aromatic and aliphatic alkynes being used and a variety of substituents tolerated on the diazonium salt starting material. Terminal alkynes selectively formed 2-substituted benzothiophenes, whereas the

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• metal-free method for the synthesis of benzothiophenes via a photocatalyzed tandem addition/cyclization reaction (Scheme 11) [41]. Aryl thiols were coupled with dimethyl acetylenedicarboxylate, applying 9-mesityl-10-methylacridinium perchlorate (Acr+-Mes ClO4−) as organic photocatalyst and benzoic acid

• production could only be achieved by careful selection and adjustment of the type and amount of basic additives. The scope of this method includes electron-rich and electron-deficient 2-aryl-substituted benzothiophenes. However, strongly electron-donating methoxy or electron-withdrawing trifluoromethyl

• groups decreased the yield of the reaction. A series of 2-alkylsubstituted benzothiophenes were prepared and the method was applied for the synthesis of antitumor agents. In the same year, the group of Singh published two similar, but metal-free procedures. In the first report a new photocatalyzed

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• in natural products and pharmacologically active compounds, thus economic and efficient methods to construct heterocycles are always highly desirable [1][2][3][4][5][6]. Benzothiophenes are important heterocycles that are one of the key motifs of anti-inflammatory, anti-estrogenic and anti-HIV drugs

• (Figure 1) [7][8][9]. Moreover, benzothiophenes have extensive applications in materials science. Besides the traditional methods of transition metal-catalyzed cyclization of alkyne substrates [10][11][12], the synthesis of benzothiophenes via metal-free conditions has recently aroused much attention [13

• -pot process. Based on our understanding of organosulfur chemistry [20][21][22], we report herein a simple, metal-free method for the formation of benzothiophenes using an intramolecular addition of a sulfur atom (originated from a sulfide) to the electron-deficient allene moiety generated in situ by a

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• intramolecular fashion, with the nucleophilic group appropriately displayed by one of the reagents. By inspection of the literature data, we were surprised to find only one example where benzothiophenes were obtained by reacting o-methylthioarenediazonium salts with alkynes under green light irradiation [4]. We

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• the corresponding 2-borylated products 4-B, 5-B, 6-B and 7-B, respectively (Table 2, entries 1–4). When 1,4-dimethylindole (8) was used, 2-borylated product 8-B was formed exclusively with no borylation occurring at the benzylic position (Table 2, entry 5) [8][35][36]. Benzothiophenes readily gave 2

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• various applications of eosin Y to visible light-driven syntheses of biaryls [15], stilbenes [16], benzothiophenes [17], α-phenylketones [18], phenanthrenes [19], arylsulfides [20] and arylboron pinacolates [21] (Scheme 1). Numerous mechanistic studies have been performed at reactions with organometallic

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• 11d (R1 = H and R2 = Me) were converted to benzothiophenes 12c and 12d in 82% and 95% yield, respectively. The synthesis of substituted hydrindene 12e was also achieved in 85% yield from monosubstituted enyne 11e (R1 = Ph, R2 = H). Substituted enynes bearing heterocycles such as indole 11f (R1 and R2

• = Ph and R2 = Me) provided the corresponding benzothiophenes 12h and 12i in 91% and 87% yield, respectively. Conclusion In summary, we have developed a mild and efficient gold(I)-catalyzed 5-exo-dig polycyclization cascade to prepare an array of substituted aromatic compounds such as benzofuran

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

•  1, entry 7). Importantly, in contrast to our previous work with benzothiophenes [19], high selectivity for C2 alkynylation was observed. The scope of the reaction was then investigated (Scheme 2). Substitution by diverse functional groups was first examined on the C5 position. An electron-rich

Extending the utility of [Pd(NHC)(cinnamyl)Cl] precatalysts: Direct arylation of heterocycles

• Anthony R. Martin,
• Anthony Chartoire,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2012, 8, 1637–1643, doi:10.3762/bjoc.8.187

• arylation of various benzothiophenes, thiophene and imidazopyridine. C–H functionalization of such heterocycles was performed in moderate to good yields by using only 0.1–0.01 mol % of precatalyst. This study highlights the fact that [Pd(NHC)(cin)Cl] complexes are multipurpose precatalysts as they may be

Transition- metal/Lewis acid free synthesis of acyl benzothiophenes via C-C bond forming reaction

• Sarbani Pal,
• Mohammad Ashrafuddin Khan,
• P. Bindu and
• P. K. Dubey

Beilstein J. Org. Chem. 2007, 3, No. 35, doi:10.1186/1860-5397-3-35

• - and 3-acyl substituted benzothiophenes has been described via environmentally benign acylation of benzothiophene with in situ generated acyl trifluoroacetates. Both aliphatic and aromatic carboxylic acids participated in trifluoroacetic anhydride/phosphoric acid mediated C-C bond forming reactions

• under solvent-free conditions affording acyl benzothiophenes in good overall yields. Background Benzothiophene derivatives possessing an acyl group as one of the substituents on the five-membered ring are of immense medicinal value because of their promising pharmacological properties. For example

• known for the synthesis of acyl benzothiophenes [13][14][15][16][17][18][19][20] many of them however, are only suitable for the preparation of certain specific compounds, namely, acetyl, propanoyl and benzoyl derivatives. Some of these syntheses require complicated reaction conditions e.g. the use of