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

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

• (9) and diphenyl-1,3,4-oxadiazole (10); and thioflavin-T analogues such as benzothiazole (11), benzoxazole (12), benzofuran (13), imidazopyridine (14), and benzimidazole (15); as well as quinoline (16) and naphthalene (17) derivatives (Figure 1B). In this review, we provide an overview of these AD

• ]. 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

• 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

• a benzofuran or an indole core. Our first study involved the cyclization of allyl moieties such as allyl ether 1a or N-allyl protected anilines 1b–c, easily prepared by quantitative allylation of o-iodophenol and o-iodoanilines using allyl bromide in DMF (Scheme 1). Following the protocol optimized

• cyclohexenyl series, we were pleased to observe that ether 6a affords only the benzofuran 10a, but the conversion is limited (30% of the starting material 6a is recovered) and the yield modest (36% isolated, 51% based on recovered material, Scheme 5). Interestingly, the intracyclic character of the double bond

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• indole, furan, and benzofuran rings (Scheme 2) [48]. Working with indole and methyl acrylates in the presence of Pd(OAc)2 and 1,4-benzoquinone in catalytic quantity with tert-butyl hydroperoxide as oxidant, 3-alkenyl-substituted products were obtained. The synthetic value of the direct catalytic C–H

• 6-membered ring, once again producing vinyl-substituted products. An analogous process for the direct intramolecular C–H functionalization of inactive alkenyl aryl ethers, giving benzofuran and dihydrobenzofuran derivatives, was successfully developed [67]. Both possible mechanistic pathways based

Asymmetric total synthesis of smyrindiol employing an organocatalytic aldol key step

• Dieter Enders,
• Jeanne Fronert,
• Tom Bisschops and
• Florian Boeck

Beilstein J. Org. Chem. 2012, 8, 1112–1117, doi:10.3762/bjoc.8.123

• benzofuran system; thus, for further modifications it was protected as acetonide 16 in a moderate yield (66%) using 2,2-dimethoxypropane under PPTA catalysis. As we turned towards the Sonogashira reaction of the iodide 16 with a propiolic acid derivative, we found that the allyl protecting group was cleaved

• protected ketoaldehyde 8 (PG = TBS) in the proline catalyzed aldol reaction led to complete condensation to the corresponding benzofuran. Propiolic acid esters are known to be problematic substrates for Sonogashira reactions, due to side reactions [15]. For this reason, we used an orthoester, which coupled

Synthesis, solid-state fluorescence properties, and computational analysis of novel 2-aminobenzo[4,5]thieno[3,2-d]pyrimidine 5,5-dioxides

• Kenichirou Yokota,
• Masayori Hagimori,
• Naoko Mizuyama,
• Yasuhisa Nishimura,
• Hiroshi Fujito,
• Yasuhiro Shigemitsu and
• Yoshinori Tominaga

Beilstein J. Org. Chem. 2012, 8, 266–274, doi:10.3762/bjoc.8.28

• derivative 3g was obtained from 1a with (S)-methylisothiourea sulfate (2b) in 87% yield (Scheme 2). Fused pyrimidine derivatives 6 and 7 containing the electron-rich heterocycles benzothiophene or benzofuran were prepared by the reaction of ketene dithioacetal 1b or 1c with guanidine carbonate (2a) in 74

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

• substituted with a carbazole unit. Hence the synthesis of such compounds is desirable [29][30]. On the other hand, the benzofuran derivatives are an important class of heterocyclic compounds that are known to possess important biological properties [31][32][33]. Especially, recent studies have shown that some

• an attractive idea to construct new prototypes combining both the carbazole ring system and benzofuran framework in the same molecule. Such compounds are not only synthetically challenging but may also be vitally important for pharmacological studies or in the realization of new medicinal properties

• of 3-chloroacetyl-9-ethyl-9H-carbazole (1) with a variety of salicylaldehydes 2a–k is summarized in Scheme 1. The Rap–Stoermer reaction was normally performed in alcoholic medium but often produced poor to moderate yields of benzofuran products [47][48]. Considering this fact, we conducted our own

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• diiodohydrobenzoin 12 in Cu-catalyzed C–N cross-coupling reactions [33] led only to the formation of cis-4b,9b-dihydrobenzofuro[3,2-b]benzofuran (24) [34]. Consequently, the diol 12 was converted to the corresponding acetonide 25 or methyl ether 26 prior to cross-coupling. In this manner, the diphenylhydrobenzoin

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• ) is zincated without reacting with the nitro group, leading to the nitro-substituted zinc reagent 53. After allylation, the benzofuran 54 is obtained in 80% yield. The polyfunctional pyridine 55 is zincated with TMP2Zn·2MgCl2·2LiCl (42) leading to the zinc reagent 56. Subsequent allylation furnishes

• the trisubstituted pyridine 57 in 80% yield (Scheme 9) [28]. In some cases, the zincation using TMP2Zn·2MgCl2·2LiCl (42) is slow and requires long reaction times. This is the case for benzofuran (58), which requires 9 days at 25 °C for a complete zincation in position 2 leading to 59. The reaction

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• compound [22][23]. In particular, several benzo[b]furan derivatives with oxygen-bearing substituents, such as hydroxy, or alkoxy, at the benzene moiety are known to be biologically active compounds [24][25][26][27][28] (Figure 1). Among the various approaches developed for the synthesis of the benzofuran

• B gave rise to better selectivities and yields of the desired alkynes 5–7 (Table 2, entries 4,6,10,12,16 and 18). According to our retrosynthetic analysis (Scheme 1), the final step to achieve the benzofuran derivatives should be the incorporation of the hydroxy group followed by in situ

• aryl bromides instead of aryl chlorides. In addition, we also observed better yields for the corresponding benzofuran derivatives 9 (Table 3, entries 5–9) derived from the starting o-alkynylhalobenzene derivatives 6, bearing the two methoxy groups in a 3,5-relationship relative to the halide. Moreover