Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• . Polycyclic aromatic hydrocarbon frameworks (naphthalene and anthracene rings) as well as a representative heterocyclic ring (furan) may be incorporated into the 4H-chromene skeleton product by using chalcones (7c, 7d, and 7e, respectively) functionalized with these moieties. Disappointingly, attempts to

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• and Suzuki reaction conditions. To this end, 2-(tributylstannyl)furan was coupled with 6-chloropurine nucleoside 26 by Stille cross coupling [47][48] catalyzed by bis(triphenylphosphine)palladium(II) chloride in DMF (Method I) (Scheme 3). The resulting 6-aryl compound 30 was obtained in 91% yield and

• deprotected with a saturated solution of ammonia in methanol to give the desired analogue 5 with furan-2-yl substituent at position 6 of the purine base. Considering the possible toxicity of organostannyl reagents, we then utilized various organoboronic acids for Suzuki cross couplings [49][50][51] to

• and deprotection of 2,6-dichloropurine 42 was achieved with a saturated solution of ammonia in methanol to furnish 2-chloro-3’-deoxy-3’-fluoroadenosine (16). The 2,6-dichloro-intermediate 42 was coupled with 2-(tributylstannyl)furan catalyzed by bis(triphenylphosphine)palladium(II) chloride in DMF to

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• conditions, providing the desired products 20 and 21 in 59% and 88% yield, respectively. Additionally, heterocyclic acids, such as thiophene- and furan-3-carboxylic acid were well tolerated, providing the amides 22 and 23 in acceptable yields. Gratifyingly, aliphatic carboxylic acids, such as

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• , I) and a proper additive promoted smoothly the synthesis of various o-haloaryl-2-carboxamides 11. This synthetic protocol tolerated not only carbon aryls, but also various heteroaryls such as thiophene, furan and pyridine in the amide component. Interestingly, in an earlier example studying the

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

• palladium-catalyzed direct arylation conditions, namely the C–H bond at the ortho position to the fluorine atom and the C–H bonds at C3 or C4 positions of the (benzo)furan (Scheme 2). We decided to employ the reaction conditions that we had previously described for both direct arylations of fluorobenzenes

• [46][59][60] and C3-arylation of furans [61][62] (i.e., 2 mol % PdCl(C3H5)(dppb) as catalyst associated to KOAc as base in DMA). We were pleased to find that 2-butyl-5-(2,3,4-trifluorophenyl)furan (1) was preferentially arylated on the electron-deficient ring whichever the aryl bromide was. For

• 68% yield. Using the more challenging substrate 2-butyl-5-(2,4-difluorophenyl)furan (19) with 4-bromobenzonitrile, a mixture of three regioisomers was formed in a 61:32:7 ratio. Only the major regioisomer 27, in which the arylation happend at the C–H bond flanked by the two fluorine atoms, has been

Chiral Cu(II)-catalyzed enantioselective β-borylation of α,β-unsaturated nitriles in water

• Lei Zhu,
• Taku Kitanosono,
• Pengyu Xu and
• Shū Kobayashi

Beilstein J. Org. Chem. 2015, 11, 2007–2011, doi:10.3762/bjoc.11.217

• also reacted with the diboron reagent to give the desired products in good to high yields with good to high enantioselectivities. No significant deterioration of chiral induction was observed upon changing the electronic nature of the double bonds. Meanwhile, heterocyclic substrate 1e, bearing a furan

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• reaction may be improved by using neat reaction conditions. Experimental A mixture of 1 and 2 (1.6:1) is readily available from the Diels–Alder reaction of furan and acrylonitrile according to the literature procedure [28][29]. The pure isomers were isolated by column chromatography. The 1H and 13C NMR

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• furan ring, respectively (Scheme 9) [70]. Analogues (50–55) shown in Scheme 10 are based on the meridine (56) structure but contain a pyridophenanthrolinone scaffold instead of a benzopyridophenanthrolinone as the natural product. In addition they have a tetracyclic core instead of being pentacyclic

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• synthesis of polyunsaturated [10]paracyclophane annulated by two azulene rings by using the McMurry reaction [100][101]. The bis(trimethylsilyl)enol ether 74 was reacted with 3-methoxycarbonyl-2H-cyclohepta[b]furan-2-one (75) in refluxing decaline to generate the 1,4-diazulenobenzene derivative 76. Double

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• naphthoquinones (Figure 1) such as naphtho[2,3-b]furan [5][6][7][8][9][10][11][12][13][14], naphtho-pyran [15][16][17][18], benzo[f]indole [19][20][21][22][23][24], benzo[g]quinolone [25], benzo[b]carbazole [26], naphtho[2,3-b]thiophene [27][28][29][30][31][32][33] and naphtho[2,3-b]]oxazole [34] have been

• pyrrole-, furan- and thiophene-fused naphthoquinones [36]. For several years, our group has been interested in developing new synthetic methods for the preparation of heterocycle-fused 1,4-naphthoquinones or heterocycle-tethered 1,4-naphthoquinones. 1,3-Quinazolines are nitrogenated heterocycles that are

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• examined. In the course of these studies, numerous scaffolds were synthesized, including a furan, a cyclopentenone, an acyclic enone and even a naphthalenone. The diversity of these structural motifs lies in novel cascades of reactions originating from a common carbocationic manifold. Keywords

• improved the yield to 44% (which is superior to the overall yield of the previous three steps synthesis). Along with cyclopentenone 4, we observed the formation of furan 13 (27% isolated yield). The proposed mechanism for this reaction is shown in Scheme 4. Both 4 and 13 are expected to arise through the

• intermediate 12 that undergoes an oxo-cyclization to afford an oxonium en route to furan 13 (pathway B). Alternatively, intermediate 12 may result from the allylic [1,3]-transposition of a perrhenate ester [10]. Replacement of the highly electron-donating 2,4,6-trimethoxyphenyl group by a 4-chlorophenyl

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• products. The PhSe+ cation could interact with the 1,1-disubstituted double bond and nucleophilic attack could lead to oxiran- or oxetan-type products. On the other hand, the interaction of the PhSe+ ion with the 1,2-disubstituted double bond would lead to the furan-type products 3 or alternatively to

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

• Fatma Belkessam,
• Aidene Mohand,
• Jean-François Soulé,
• Abdelhamid Elias and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 2912–2919, doi:10.3762/bjoc.10.309

• et al. [38]. A fluorescent π-conjugate thiophene derivative bearing spiro[fluorene-9,4’-[4H]indeno[1,2-b]furan] substituents at C2 and C5 has been prepared in 46% yield by this reaction using Pd(OAc)2 (5 mol %) associated to PPh3 (10 mol %) as catalytic system [39]. A pyrrole derivative was coupled

• degradation products. The use of 6 equiv of thiophene allowed the formation of 2,2':5',2"-terthiophene (7) in 85% yield. The reactivity of three furan derivatives was also studied using PdCl(C3H5)(dppb) as the catalyst. From 2-n-butylfuran, 8 was obtained in 79% yield, whereas 2-acetylfuran and methyl 2

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

• reaction and its application in the synthesis of benzo[b]furan and benzo[b]thiophene derivatives is presented starting from readily available 2-fluorophenylacetylene derivatives. The key annulation step involves the hydration of the C–F bond of 2-fluorophenylacetylene derivatives followed by an

• intramolecular annulation to afford benzo[b]furan and benzo[b]thiophene derivatives. Moreover, structurally important 2,2'-bisbenzofuran scaffolds are provided in good yields. Keywords: annulation; benzo[b]furan; C–F activation; copper-promoted; heterocycle; Introduction The development of general and

• efficient methodologies for the synthesis of complex heterocycle skeletons has received much attention in the past decades. Among the most ubiquitous heterocyclic moieties in natural and bioactive products are the benzo[b]furan and benzo[b]thiophene units [1][2][3][4][5][6][7][8]. Despite the existence of

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• Amjid Iqbal El-Habib Sahraoui Finian J. Leeper University of Cambridge, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, U.K. 10.3762/bjoc.10.270 Abstract An analogue of thiamine having a furan ring in place of the thiazolium ring has been synthesised by a short and efficient route

• , involving gold(I)-catalysed cyclisation of an alkynyl alcohol to form the furan ring. The furan analogue of thiamine diphosphate (ThDP) was also made and tested for binding to and inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis (overexpressed in E. coli with a N-terminal His-tag). It is a

• very strong inhibitor, with a Ki value of 32.5 pM. It was also shown that the furan analogue of thiamine can be functionalised at the C-2 position, which will allow access to mimics of reaction intermediates of various ThDP-dependent enzymes. Keywords: furan synthesis; gold-catalysed cyclisation

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• sesterterpenoid bearing a furan unit and an eight-membered lactone tethered by a non-conjugated triene chain (Figure 1). Although the proposed structure of compound 1 is unusual, given that a number of compounds isolated from sponges of the same species have a steroid-like structure [7][8][9], the structure does

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

• formation of the photoproducts 8 and 10 can be explained by intramolecular cycloaddition and formation of resonance stabilized biradicals A/A’ followed by the 1,6-ring closure (Scheme 4). An 1,3-H shift, as in furan and thiophene derivatives [6], and rearomatization to fused oxazole derivatives B/B’ is not

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

• F1, but-3-yn-2-one reacted with a series of N-protected isatins in ethyl ether at −20 °C to afford enantioenriched spiro[furan-2,3´-indoline]-2´,4(5H)-diones with good to excellent ee's, albeit moderate yields. 2.7 [4 + 2] Annulations of allenes with activated imines Compared with phosphine-catalyzed

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• with the furan compound 52 (Table 1, entry 4). The furan derivative 52 in this reaction was probably formed through a monocyclisation, followed by β-H−-elimination and aromatisation. In the case of substrate 13 having an unprotected α-hydroxy group, the reaction provided only a mixture of unidentified

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• -substituted tryptophan was observed (Table 2, entry 6). For indoles containing 3-heterobenzyl substituents, the results were conflicting. Whereas 3-(furan-2-ylmethyl)indole (1g) did not react under the usual reaction conditions (Table 2, entry 7), bis(indol-3-yl)methane (1h) provided the desired product in an

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• and subsequent hydrogenation and reductive 6-deoxygenation [21][22]. Successful de novo approaches [14] to both enantiomers of amicetose include an Achmatowicz rearrangement–hydrogenation sequence, starting from enantiomerically pure 2-(1-hydroxyethyl)furan [23][24][25], a sequence comprising

• product 8 to a fully protected acyclic cinerulose derivative. We are aware of only one previous de novo synthesis of DL-cinerulose, which used an Achmatowicz rearrangement of 2-(1-hydroxyethyl)furan [45]. Results and Discussion The three second generation catalysts A [46], B [47][48] and C [49][50] were

• benzoylation in pyridine resulted exclusively in the formation of furan 10 (Table 2, entry 1). We reasoned that pyridine initiates an E/Z-isomerization of the enal through nucleophilic attack at the β-position, followed by lactol formation, benzoylation of the lactol and finally elimination of benzoic acid

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• reactions to the parent furan-2(5H)-one (9) and was conducted with a set of eight visible light lamps (Osram L 8W/640 cool white) [48]. A screen of potential catalysts (see Supporting Information File 2 for further details) in CH2Cl2 as the solvent (c = 0.1 M) revealed that [Ir(ppy)2(bpy)]BF4 (ppy

• the fact that oxidation of the putative intermediate B is required, which seems to occur at the expense of the substrate. If a suitable compound was found to adapt the role of an ancillary oxidant, yields could possibly be improved. PET-catalyzed addition of N,N-dimethylaniline (1) to furan-2(5H)-one

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• procedures involved the use of the Diels–Alder reaction on a furan ring to synthesize isoindoloquinoline derivatives [22][23][24][25]. Reaction of methallylmagnesium chloride with furyl aldimines produced furan-substituted N-aryl homoallylamines which reacted with maleic anhydride to undergo amide formation

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• ]. In particular, unsubstituted acylketenes, the reactivity of which towards azirines is until now unknown, cannot be generated from diazo compounds. An alternative source of acylketenes can be furan-2,3-diones, which have been used in reactions with nucleophiles and various cycloadditions [30][31][32

• ]. Aiming to broaden the scope of the reaction of acylketenes with 2H-azirines we tried to use furan-2,3-diones instead of diazo compounds as the source of ketenes. Results and Discussion Unexpectedly, with a new source of acylketenes in addition to predictable products (derivatives of 5,7-dioxa-1

• -azabicyclo[4.4.1]undeca-3,8-diene) derivatives of 4,11-dioxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-5,12-diene, a new heterocyclic system, were formed. Boiling a benzene solution of furan-2,3-dione 1a and azirine 2a (1:1) for 0.5 h gave a mixture of compounds 3a–5a, which were isolated by column

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• -position (2d, 2g, 2o) are well tolerated. Polar substituents like alcohols (2k) can also be employed in the sequence. From the literature it is known that the naturally occurring compound 2h [16][17] and 2,5-bis(3,4,5-trimethoxyphenyl)furan (2g) are highly biological active [39]. Compound 2k is

• in a one-pot fashion, which opens a ready access to biologically active furan derivatives. In addition the investigation of the photophysical properties of these compounds reveals an intense blue luminescence in solution approaching unity for the fluorescence quantum yield Φf of distinct derivatives