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

• conjugates form layer-like structures during crystal formation via multiple hydrogen bonding interactions. This structural information indeed helps to design novel MGBs with much better binding affinity and specificity. A new family of conjugates between a Zn(II)-tach complex and (indole)2 or benzofuran

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• ) in 52% yield. For 3-aryl-2-propynoic acids bearing heteroaromatic groups, treatment of 3-(benzothiophen-2’-yl)-2-propynoic acid (1n) and 3-(benzofuran-2’-yl)-2-propynoic acid (1o) under the same procedure and conditions gave the corresponding coumarins 3An and 3Ao in moderate yields, respectively

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• derivative. 5-Benzothiophene- and 5-benzofuran-modified uracil in aegPNA exhibited a fluorescence that was marginally sensitive to the environment [195]. When incorporated into PNA, benzothiophene-uracil exhibited an increased fluorescence compared to the free nucleoside. The opposite effect was observed

• with benzofuran-uracil, and the fluorescence was almost completely quenched when G was the flanking nucleobase. Significant fluorescence enhancement with a small blue-shift of the emission maxima was observed upon duplex formation with DNA for both modified uracil derivatives. Unfortunately, the

• discrimination between complementary and mismatched duplex observed with benzothiophene-uracil was limited to sequences with flanking Cs. No discrimination was observed with benzofuran-uracil PNA unless it was used in combination with GO as a quencher for ssPNA [196]. In this respect, the thiophene-modified

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• ; spiro compounds; synthetic methods; Introduction Molecular structures based on partially or exhaustively hydrogenated indole and benzofuran cores are omnipresent in nature. Both types of ring systems are found in a variety of important biologically active natural products [1][2][3][4][5][6][7][8][9][10

• in the target-oriented synthesis of pyrrole-based natural alkaloids [34][35][36][37][38]. Herein we wish to report a new synthetic route towards spirocyclic scaffolds possessing partially hydrogenated indole or benzofuran cores. The featured approach is based on the highly efficient regiodivergent

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

• 17β-HSD1 inhibitors, displaying submicromolar IC50 values. Keywords: benzofuran; 13α-estrone; 17β-HSD1 inhibition; partial saturation; Sonogashira coupling; Introduction Synthetic modifications of the naturally occurring female prehormone estrone may lead to compounds with diverse biological

• , suppressing the conversion by less than 15%. The phenylalkynyl derivatives in the 3-OMe series 9a–e and 11a–e exerted weak inhibitions. Phenylalkenyl compounds 13 and 15 and benzofuran compounds 12 and 14 displayed weaker inhibitory activity than their alkynyl counterparts 8c and 10c. The full saturation

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted

• -pot synthesis of heterocycles derived from indole and benzofuran, convenient ortho-substituted phenylacetylenes were also tested. To our delight, the o-diethylamino-substituted derivative 6i afforded N-ethyl-2-(n-octylselanyl)-1H-indole (9) in 62% isolated yield (Scheme 4). The primary selenyl

• (Table 4, entry 10). The subsequent electrophilic addition of I2 to selenide 5q afforded 3-iodo-2-(n-octylselanyl)benzofuran (10) in excellent yield (93% isolated yield, Scheme 4). Finally, we compared our method with syntheses reported in the literature that mainly rely on commercially available

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

• Youngeun Jung Dileep Kumar Singh Ikyon Kim College of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea 10.3762/bjoc.12.266 Abstract The recognition of the local symmetric image within benzofuran-based

• 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

• (Scheme 5) [43][44]. Conclusion In summary, we have established a highly scalable and flexible synthetic route to several benzofuran-containing oligostilbenoid natural products by relying on a symmetry-breaking strategy from 3,5-dimethoxybenzyl alcohol. The relative reactivity of ester, aldehyde, and

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• target bond 3-partition dissection maps for 27 commonly found heterocyclic rings is given in the Supporting Information File 1 (see Schemes S6 to S32). These include benzimidazole, 2,3-dihydro-1H-benzo[b][1,4]diazepine, benzofuran, benzopyran, chromen-4-one, coumarin, cyclopent-2-enone, furan, Hantzsch

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

• : bromobenzofuran coupling; cross-coupling; palladium; regio-selective; triarylbismuth; Introduction The benzofuran scaffold is present in various biologically active molecules [1][2][3][4][5][6][7][8], natural products [9][10][11][12][13][14][15] and also part of various functional materials [16]. Importantly

• expected to attract easy applications in structural elaborations of medicinally important benzofuran scaffolds. Important benzofuran skeletons. X-ray structure of bis-coupling product 3.1 (CCDC-1425338) [43]. Bis- and tris-couplings. Screening for mono-arylation.a Cross-couplings of 2,3-dibromobenzofurans

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

• pharmaceutically relevant indole, benzofuran, and aza-indole scaffolds in a single operation (7a–f) [48][49][50][51][52]. Finally, with the viewpoint of generality of DMF substitution by Cyrene, the base/temperature sensitivity issue may have potential implications for further applications of Cyrene within well

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

• -borylated products using our system, as exemplified by the high yields obtained from 9 and 10 (Table 2, entries 6 and 7). Although benzofuran 11 was borylated at the 2-position successfully, the isolated yield was somewhat lower than the yield calculated from the 1H NMR data, probably because of the

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• role of the 6’-OH functionality is shown to be critical in the orchestration of the reaction process, as depicted in the proposed transition state model (Scheme 20). Cycloadditions The [4 + 2] cycloaddition of benzofuran-2(3H)-one derivatives 84 with methyl allenoate 85 to give the corresponding

• dihydropyran fused benzofuran precursors 86 using β-ICPD has been achieved by Li and Cheng and co-workers (Scheme 21a) [60][61][62][63]. A large number of computational studies were conducted to explain the enantioselection of the process, resulting in the transition state shown which depicts a critical

Efficient synthesis of π-conjugated molecules incorporating fluorinated phenylene units through palladium-catalyzed iterative C(sp²)–H bond arylations

• Fatiha Abdelmalek,
• Fazia Derridj,
• Safia Djebbar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2015, 11, 2012–2020, doi:10.3762/bjoc.11.218

• arylated in β-position instead of α-position with the classical procedure employing aryl halides as coupling partners [53][55] and benzofuran regioselectively led to C2 arylated compounds instead of the mixtures of C2 and C3 arylated products obtained with aryl bromides [56]. Moreover, these processes are

• investigation with the synthesis of a set of heteroarenes bearing a 1,2,3-trifluorobenzene motif (Scheme 1). Using our previous reaction conditions, namely 5 mol % PdCl2(CH3CN)2 in the presence of 3 equiv of Li2CO3 in dioxane at 140 °C, both 2-n-butylfuran and benzofuran reacted with 2,3,4

• contrast to these examples, when the reaction was performed with a heteroaryl bromide such as 3-bromopyridine, the two regioisomers 9a and 9b were obtained in 45:55 ratio. On the other hand, it is well known that the C–H bond at the C-3 position of the benzofuran is very reactive in palladium-catalyzed

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• )ethynyl)thiophene was also successfully converted to 2-(thiophen-2-yl)benzofuran (2j) in good yields. Subsequently, the R1 substituent of the 2-fluorophenylacetylene derivatives was varied from hydrogen to other functional groups. Substituents at the ortho position of the benzyl group did not have an

• fluoro-substituted benzofuran was obtained (Scheme 2, 2q) [34][35][36][37]. This shows the good selectivity of the current reaction system. It should be emphasized that the 1,3-bis(2-(2-fluorophenyl)ethynyl)benzene was also successfully converted to benzo[b]furan 2r in good yield. Unfortunately, when

• )ethynyl)benzene were performed, as shown in Scheme 4. In F/Br-substituted 1-bromo-2-(2-(2-fluorophenyl)ethynyl)benzene, the fluoro moiety served as leaving group and gave 2-(2-bromophenyl)benzofuran (2t) as a major product. In F/Cl-substituted 1-chloro-2-(2-(2-fluorophenyl)ethynyl)benzene was able to

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• generated 1,2-benzoquinones via sequential Michael addition/ring closure An electrochemical method for the synthesis of benzofuran and indol derivatives is based on the oxidation of catechol in presence of 1,3-dicarbonyl compounds or analogous C,H-acidic compounds 62 (Scheme 24) [69][70][71][72]. The

• model compounds via electrochemically induced Diels–Alder cycloaddition. Cycloaddition of anodically generated N-acyliminium species 58 with olefins and alkynes. Electrochemical aziridination of olefins. Proposed mechanism for the aziridination reaction. Electrochemical synthesis of benzofuran and

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• Supporting Information File 1). Aromatic protons of 10 are at 6.9–7.3 ppm and the proton on the oxazoline moiety is a singlet at 6.2 ppm. The specific aliphatic protons HA–HF of the bicyclic skeleton (Figure 1) show a similar pattern as the previously described benzofuran intermediate [41]. In the 13C NMR

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• formal [4 + 3] cycloaddition [82]. Starting from 4-methoxyphenol (90) Friedel–Crafts acylation and cyclization provided bicycle 91. Wittig olefination furnished benzofuran 92. Diazotransfer using p-ABSA yielded the crucial diazo compound 93, which was used in the following enantioselective

• cyclopropanation with the lesser substituted double bond of piperylene under Rh2(R-DOSP)4 catalysis. Cis-divinylcyclopropane intermediate 94 underwent in situ DVCPR under the reaction conditions, and rearomatization of the benzofuran moiety provided 95. Reduction of the less hindered double bond yielded tricycle

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

• = H) and furan 11g (R1 = Ph and R2 = H) were effectively transformed to the desired carbazole 12f and benzofuran 12g in 95% yields. It can be noticed that large substituents at R1 and R2 did not affect the efficiency of the reaction. The gold(I)-catalyzed cyclization of 11h (R1 = R2 = Ph) and 11i (R1

• = 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

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• . Removal of the benzyl groups, cleavage of the tert-butyl group with concomitant formation of the methoxy ester (COOt-Bu → COOMe), and global deprotection gave 187. Acid-catalyzed (Amberlyst 15) spiroannulation afforded a 1.7:1 mixture of the benzofuran and the benzopyran (90% overall conversion). For the

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

• natural product 8-methoxypsoralen (2). Findings Benzofuran (7a) is less reactive then furans and indeed no product was observed under the conditions optimized for the latter [21] at room temperature or at 60 °C using the commercially available electrophilic alkynylation reagent TIPS-EBX (8) (Table 1

• , entries 1 and 2) [24][25][26][27]. Fortunately, benzofuran (7a) was also more stable in the presence of acidic additives, and co-activation became possible, whereas Zn(OTf)2 was superior to trifluoroacetic acid (TFA) at 60 °C (Table 1, entries 3 and 4) [19][28]. No product was observed in the absence of

• method could also be successful in the case of more complex benzofuran-containing natural products and drugs. We were pleased to see that the alkynylation of 8-methoxypsoralen (2) was indeed possible. The major product 10 bearing the acetylene group at the C5’ position was obtained in 37% yield (Scheme 4

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

• procedure allows the preparation of heterocycles with good yields and is tolerant to a wide variety of functional groups. Keywords: benzofuran; bimetallic catalyst; heterogeneous catalysis; indole; water; Introduction Heterocycles are ubiquitous building blocks in natural products, bioactive compounds and

• classic for the synthesis of indole- and benzofuran-containing natural products [9][10][11][12][13] and biologically relevant agents [14][15][16][17][18]. The traditional procedure requires a homogeneous source of palladium and copper in a polar solvent (usually DMF) with an organic base such as Et3N. The

• alkynylation–cyclization sequence for indole and benzofuran syntheses. Optimization of the nitrogen protecting group. aReaction conditions: 2-iodoaniline (0.5 mmol), phenylacetylene (1 mmol), ethanolamine (1.5 mmol), Ph3P (5 mol %) and Pd–Cu/C (2 mol % Pd) were stirred in water (3 mL) at 80 °C under Ar for 20

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• azides with CO was achieved. The reaction of iodoaryl allyl azides, TTMSS and AIBN under CO pressure (80 atm) in THF at 80 °C gave the desired 4,4-spirocyclic indoline, benzofuran, and oxindole γ-lactams in moderate to good yields. Keywords: 4,4-spirocyclic indol γ-lactams; carbon monoxide; free radical

• )allyloxy)-2-iodobenzene (1d) also gave the spiro benzofuran lactam 2d in 58% yield (Table 1, entry 4). On the other hand, 2-(azidomethyl)allyl(2-iodophenyl)sulfane (1e) gave a low yield of the corresponding spiro thiobenzofuran lactam (19%, Table 1, entry 5), which may be rationalized by the less effective

• next chain reaction. Conclusion We have examined a TTMSS-mediated 5-exo radical cyclization/carbonylation/spirocyclization sequence to synthesize 4,4-spirocyclic rings. By using this protocol, indoline, benzofuran and oxindole γ-lactams can be conveniently prepared in moderate to good yields. As shown

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• spectroscopy. Iminyls with suitably placed arene or heteroarene acceptors underwent cyclisations yielding phenanthridine-type products from ortho-additions. For benzofuran and benzothiophene acceptors, spiro-cyclisation predominated at low temperatures, but thermodynamic control ensured ortho-products

• iminyl cyclisations are comparatively slow and, based on the previous product analyses, the ortho- (Ar1-6) mode predominates at room temperature and above. Spiro-cyclisations with benzofuran and benzothiophene acceptors EPR spectra from oxime carbonate 2a, containing a benzofuran acceptor, gave well

• benzofuran acceptor. Rate constants of ring-closure reactions can be determined for sterically unhindered radicals by measurements of the concentrations of the ring-open and cyclised radicals under EPR conditions [43][44][45]. Steady-state concentrations of 12a were determined in the usual way from the