Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• previously been a challenging transformation due to the propensity of these systems to produce non-cyclized hydroarylation products due to an unproductive rhodium 1,4-migration on heteroaromatic moieties. The use of benzothiophene, benzofurans, and benzopyrrole boronate esters in this investigation prevented

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• heteroarenes such as thiophenes, benzofurans, furans, and indoles were found suitable substrates and afforded the desired products with high chemo- and site-selectivity. A possible mechanism for the reaction was also described. The first step of the catalytic cycle involves the formation of a cationic complex

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

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

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• using nonprecious Fe and Cu catalysis have been described by Sutherland and co-workers in 2020 (Scheme 32B and C) [165]. Benzofurans are important scaffolds present in several bioactive compounds, such as balsaminone A (91, antipruritic activity), xylarianaphthol-1 (92, anticancer activity), and

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

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

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

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

• light (Scheme 21) [66]. However, benzofurans and, most importantly, indoles are also accessible through this cascade. The authors demonstrated the synthesis of an array of different, potentially drug-like compounds. The authors also showed the accessibility of their starting materials by synthesising

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• significant antibacterial activity against Gram-positive bacterial strains [50]. Several other distamycin analogs were synthesized by replacing one or more pyrrole rings with other heterocycles such as pyrazoles [51], benzofurans [52], thiazoles, thiophenes, imidazole and oxazoles [53] in order to establish a

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• phenylacetylenes using Pd(PPh3)4 as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the

• . There are literature reports about similar transition-metal-catalyzed cyclizations of o-alkynylphenols to construct benzofurans [34][35]. These heterocycles are important structural units in a variety of biologically active natural or synthetic compounds [36][37]. Full hydrogenation of the 2- or 4

• , furnishing alkenes or benzofurans depending on the nature of the substituent at C-3. Full hydrogenations of certain phenethynyl derivatives were also achieved. The newly-synthesized potent 17β-HSD1 inhibitors may serve as suitable tools for ligand-based enzyme studies. Further derivatizations of our

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• ][30]. Although the Ugi-4CR generates linear α-acylamino-amides, a wide range of heterocycles are accessible through the combination with other transformations (post-transformation strategy) [31]. For example, the Ugi/Diels–Alder process leads to the formation of benzofurans and indoles [32] as well as

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• in the synthesis of alkyl aryl ethers and benzofurans, which often possess interesting biological activities. In 2011, the Zhang and Ma group screened a series of 2-heteroarylpyridines and found another N,N-bidentate ligand, 5-bromo-2-(1H-imidazol-2-yl)pyridine (L6), and succeeded to synthesize

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• in the literature [4][5][6][7][8][9][10]. In connection with our research on benzofurans [11][12], our laboratory has been involved in the synthesis of these benzofuran-containing natural products for the last several years [13][14][15]. For example, we have reported a concise total synthesis of

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• , 2,3-disubstituted benzofurans are biologically important (Figure 1a–d) and a few reports about their isolation and synthetic methods are available [17][18][19]. Substituted benzofurans serve as antitumor agents [20], protein tyrosine phosphatase-1B inhibitors [21], antimycobacterial agents [22] and as

• ambipolar materials (CZBDF, Figure 1c) [16]. To note, synthetic functionalization under transition-metal-catalyzed conditions allows the preparation of multi-substituted benzofurans in a facile manner [23][24][25][26][27][28]. Langer et al. reported the site-selective Suzuki–Miyaura reaction of 2,3

• known facile coupling nature of aryl bromide [42] and its presence as part of the substrate, we obtained high regio-selective couplings with polyhalogenated benzofurans. The corresponding coupling products 2.22–2.27 were obtained in high yields (Table 2, entries 22–27). It is to be mentioned at this

Scope and limitations of a DMF bio-alternative within Sonogashira cross-coupling and Cacchi-type annulation

• Kirsty L. Wilson,
• Alan R. Kennedy,
• Jane Murray,
• Ben Greatrex,
• Craig Jamieson and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2016, 12, 2005–2011, doi:10.3762/bjoc.12.187

• alternative to DMF, Cyrene. In addition, we have shown the capacity for extension of the utility of this new solvent towards enabling the cascade synthesis of functionalised indoles and benzofurans via a Cacchi-type annulation. Perhaps more importantly, we have documented some of the limitations of the use of

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• oxidation of catechol in the presence of 4-hydroxycoumarin was reported by Tabaković et al. (Scheme 25, left) [69]. Using an undivided cell, an aqueous sodium acetate electrolyte and a graphite anode, the product was obtained in 95% yield. In a similar fashion, benzofurans of type 68 and 69 were synthesized

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• chromophores, benzoin, pHP, and now 1,4-hydroxynaphthylacetyl substrates cleanly undergo rearrangements that shift the absorption chromophore. Benzoins form benzofurans that, in fact, exacerbate the problem of light competition and fluorescence. Only pHP and 1,4-substituted naphthylacetyl 14 generate a less

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

• Yifan Li Jerome Waser Laboratory of Catalysis and Organic Synthesis, Ecole Polytechnique Fédérale de Lausanne, EPFL SB ISIC LCSO, BCH4306, 1015 Lausanne, Switzerland 10.3762/bjoc.9.204 Abstract The direct alkynylation of benzofurans was achieved for the first time using the hypervalent iodine

• reagent 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one (TIPS-EBX) based on the cooperative effect between a gold catalyst and a zinc Lewis acid. High selectivity was observed for C2-alkynylation of benzofurans substituted with alkyl, aryl, halogen and ether groups. The reaction was also

• successful in the case of the more complex drug 8-methoxypsoralen (8-MOP). Keywords: alkynylation; benzofurans; cooperative catalysis; direct functionalization; gold catalysis; hypervalent iodine; Introduction Benzofurans are important heterocycles frequently encountered in both bioactive compounds and

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• /bjoc.9.160 Abstract This paper describes the preparation of indoles, azaindoles and benzofurans in pure water by using a new heterogeneous Pd–Cu/C catalyst through a cascade Sonogashira alkynylation–cyclization sequence. Details of the optimization studies and the substrate scope are discussed. This

• materials. Amongst the variety of heterocycles, indoles and benzofurans have emerged as privileged structures, especially in medicinal chemistry [1]. This great interest stimulated organic chemists to design efficient and diverse synthetic accesses, abundantly reviewed in the past few years [2][3][4][5][6

• ][7]. A detailed survey of the recent literature revealed that both indoles and benzofurans can be attained by a cascade Sonogashira alkynylation–cyclization sequence (Scheme 1). Many efficient catalytic systems have been reported since the pioneering studies of Yamanaka [8] and this approach is now a

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• ]. Benzofurans Replacement of the nitrogen of the benzoxazole backbone with carbon affords the benzofuran backbone of compounds 121–126 (Figure 4), which has also been successfully employed for radioimaging of Aβ plaques. The [11C]-labeled benzofuran 121 was prepared via Wittig reaction between the

• changed to a secondary methylamino or hydroxy moiety with little effect on binding affinity for synthetic Aβ1-40, as all compounds had a Ki ≤ 8 nM (Table 10). While the [125I]-labeled benzofurans in this series showed good brain uptake in normal mice, their washout was rather slow indicating nonspecific

• binding in vivo. Several [18F]-labeled benzofurans have been employed with success for Aβ imaging. [18F]FPYBF-1 (123a), which has a N,N-dimethyl-2-aminopyridine group attached to the benzofuran core, was synthesized via Suzuki coupling between 5-methoxybenzofuran-2-boronic acid (130) and 2-amino-5

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• , efficiently leading to a variety of functionalized 2-arylpyridines [17]. More recently, this nickel-catalyzed reaction provided a convenient and mild method for a one-pot synthesis of substituted benzofurans, chromans and indoles by carbonickelation of alkynes [18]. We finally decided to extend the scope of

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• synthesis of chiral aromatics and heteroaromatics, such as isoquinolines or benzofurans, though lower yields and ee were obtained [15]. On the other hand, α-aryl O-(α-arylalkenyl) carbamates (α-carbamoyloxy-substituted styrenes) such as 14 undergo facile intermolecular carbolithiation reactions, via

• using (−)-sparteine (L1) as chiral ligand, and diisopropyl ether as solvent (Scheme 17). The resulting organolithium can be trapped with several external electrophiles [50]. The presence of a substituent at the 6-position of the aromatic ring (R1 ≠ H) is necessary to obtain the benzofurans 48. Otherwise

A novel and facile synthesis of 3-(2-benzofuroyl)- and 3,6-bis(2-benzofuroyl)carbazole derivatives

• Wentao Gao,
• Meiru Zheng and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 1533–1540, doi:10.3762/bjoc.7.180

• (0.5 equiv) as catalyst in the presence of K2CO3 as base in refluxing CH3CN for 10 h, the desired benzofurans 3a were obtained, but the attempt was still plagued by low yield. In this reaction the use of 0.5 equivalents of PEG-400 was found most suitable with 1 and 2a to provide a maximum yield of 3a

First synthesis of 2-(benzofuran-2-yl)-6,7-methylene dioxyquinoline-3-carboxylic acid derivatives

• Wentao Gao,
• Jia Liu,
• Yun Jiang and
• Yang Li

Beilstein J. Org. Chem. 2011, 7, 210–217, doi:10.3762/bjoc.7.28

• construction of the benzofuran moiety from intermediate 5. For the construction of 2-substituted benzofurans, the most widely used approach involves the palladium-catalyzed heteroannulation of 2-halophenols with a terminal alkyne via a tandem Sonogashira coupling-5-endo-dig-cyclization, largely based on the

• methods of Larock and his co-workers [31][32][33][34]. Recently, others less popular approaches for the synthesis of 2-substituted benzofurans have included p-toluenesulfonic acid-mediated cyclization of o-(1-alkynyl)anisoles to obtain 2-arylsubstituted benzofurans [35], rearrangement and cyclization