Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• presence of Lewis acids is a common synthetic strategy for making pyrans and furans. Hemiacetals are also biosynthesis intermediates where they are transformed into individually functionalised heterocycles or acetals. In many cases, these hemiacetals are also appropriately activated to react further

• building block [34][35][36]. 1.1.3 Epoxide opening: The nucleophilic opening of epoxides is probably the most abundant type of reaction leading to furans and pyrans. It, for example, plays an important role in the biosynthesis of ionophoric terrestrial and marine polyethers (see chapter 1.3). In this

• experiments to be much more susceptible to nucleophilic attack than the respective 3,4-saturated analogues and that 6-endo-tet attack can override the 5-exo-tet cyclisation, which is favoured according to Baldwin’s rules [51][52]. 1.2 Furans 1.2.1 oxa-Michael addition: Similar to the PS domains described in

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• dihydrofurans could be easily converted into furans using DDQ in a one-pot process. In addition to α-bromo esters and ketones, Lei and co-workers have also recently shown that benzylic halides could undergo radical alkenylation via copper catalysis [39]. By exploiting the propensity of benzyl halides to form

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

• equiv of CuI and PivOH, the EWG-functionalized o-arylphenols 37 underwent simultaneous C–H iodination and intramolecular C–H o-arylation by heating in DMSO at 140 °C, which led to the production of iodinated dibenzo[b,d]furans in either the form of 38 or 39 depending on the position of the EWG. The CuI

• . CuI-mediated synthesis of iododibenzo[b,d]furans via C–H functionalization. Cu-Mn spinel oxide-catalyzed phenol and heteroarene halogenation. Copper-catalyzed halogenations of 2-amino-1,3thiazoles. Copper-mediated chlorination and bromination of indolizines. Copper-catalyzed three-component synthesis

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

• involved in palladium-catalyzed direct arylations with a set of heteroarenes (e.g., thiophenes, thiazoles, furans). Then, the resulting heteroarylated polyfluorobenzenes were arylated using PdCl(C3H5)(dppb) catalyst in the presence of KOAc as the base in DMA at 150 °C using a wide range of aryl bromides as

• -catalyzed direct arylation using aryl bromides as coupling partners. Indeed, the regioselectivity of such reaction with these coupling partners needs to be investigated (Schemes 2–4). (2,3,4-Trifluorophenyl)furans 1 and 2 have two and three C–H bonds, respectively, which are susceptible to react under

• [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

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

• : carbocationic rearrangement; cyclopentenones; furans; propargyl alcohols; Introduction In the course of our medicinal program on a new class of anticancer agents [1][2][3], we developed a novel synthesis of cyclopentenones substituted by three different aryl groups (Scheme 1) [4]. This approach combines a

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• are based on using functionalized indoles, thiophenes, furans or chromone precursors, which require several steps to be prepared. Results and Discussion In this paper we wish to report a convenient, short and robust approach to 8-alkyl-2-(het)arylthieno[2,3-b]indoles from 1-alkylisatins and the

Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

• Almaz Zagidullin,
• Vasili Miluykov,
• Elena Oshchepkova,
• Artem Tufatullin,
• Olga Kataeva and
• Oleg Sinyashin

Beilstein J. Org. Chem. 2015, 11, 169–173, doi:10.3762/bjoc.11.17

• significant interest for the preparation of highly effective catalysts, materials for light-emitting diodes and nonlinear optics [3][4]. In contrast to furans, thiophenes and pyrroles, phospholes display cycloaddition and complexation reactions and can be used as starting materials for caged phosphines

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

• –2 mol % palladium catalysts, the target 2,5-diheteroarylated thiophenes were obtained in moderate to good yields and with a wide variety of heteroarenes such as thiazoles, thiophenes, furans, pyrroles, pyrazoles or isoxazoles. Moreover, sequential heteroarylation reactions allow the access to 2,5

• promotes the 2,5-diheteroarylation of 2,5-dibromothiophene in the presence of a variety of heteroarenes such as thiophenes, furans, pyrroles, pyrazoles or isoxazoles as the coupling partners. The sequential diheteroarylation of 2,5-dibromothiophene was also found to be possible to afford 2,5

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

• established methods for the synthesis of benzo[b]furan and benzo[b]thiophene derivatives, the development of more convenient methods is of significant importance [9][10][11][12][13][14]. Commonly, the preparation of 2-substituted benzo[b]furans involves the usage of 2-halophenols as reaction precursors

• eliminated these problems to a large extent [25][26][27][28][29]. Nevertheless, the direct synthesis of benzo[b]furans from 2-haloalkynylbenzenes and the usage of 2-fluorophenylacetylene derivatives as substrates continues to represent a challenge. Indeed, Tsuji and co-workers have developed a transition

• metal-free process for the synthesis of benzo[b]furans from 2-fluorophenylacetylene derivatives. But the reaction requires conditions with a high reaction temperature for satisfactory yields. Unfortunately, only benzo[b]furans were obtained in this reaction [30]. Typically, the aryl halides used in the

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

• planned synthesis was the formation of the furan ring. Homogeneous gold-catalysed reactions have been used recently in the synthesis of furans from alkynes [13][14][15][16][17][18][19][20]. The ease with which alkynes, allenes and alkenes can be activated by Au(I) catalysts to form carbon–carbon and

• dehydrative cyclisation reaction of alkynyl alcohols catalysed by simple gold(I) salts [31]. The reaction proceeds rapidly under mild, open flask conditions to provide aromatic heterocycles such as furans, pyrroles and thiophenes in high yield with low catalyst loadings (Scheme 2). Following this synthetic

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

• ]. Various methodologies and new synthetic approaches for their preparation and reactivity have been reviewed [3]. Continuing our long-standing interest for photochemical intramolecular cycloaddition reactions of various β-heteroaryl-o-divinylbenzenes, furans [4][5][6], thiophenes [6][7][8], pyroles [9][10

A tandem Mannich addition–palladium catalyzed ring-closing route toward 4-substituted-3(2H)-furanones

• Jubi John,
• Eliza Târcoveanu,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 1462–1470, doi:10.3762/bjoc.10.150

• [19][20][21][22][23][24][25][26]. Synthetic routes for the preparation of these compounds involve transformations of substituted α-hydroxy-1,3-diketones [15][17], substituted furans [27][28][29], cyclization of allenic hydroxyketones [30], transition metal-catalyzed strategies (Au [31][32][33], Pt [34

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• -terminated SAMs [33], by Diels–Alder reaction of cyclopentadienes and furans on maleimide-terminated SAMs [34], by thiol–ene click reaction of functionalized thiols on alkene-terminated SAMs [35] as well as by strain promoted cycloadditions on azide- and nitriloxide-terminated SAMs [36] using μCP. Homogenous

Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins

• G. Gangadhararao,
• Ramesh Kotikalapudi,
• M. Nagarjuna Reddy and
• K. C. Kumara Swamy

Beilstein J. Org. Chem. 2014, 10, 996–1005, doi:10.3762/bjoc.10.99

• series include phosphonobenzofurans/indenones [21][22], -pyrazoles [23], -chromenes/thiochromenes [24][25], -pyrroles [26], multiply substituted furans [27], indolopyran-1-ones [28], N-hydroxyindolinones [29], and oxindoles [30]. In the reaction shown in Scheme 1a, for the formation of the

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

• interesting due to their bright blue luminescence with remarkably high quantum yields. The electronic structure of the title compounds is additionally studied with DFT computations. Keywords: C–C coupling; copper; DFT; fluorescence; furans; mircowave-assisted synthesis; multicomponent reactions; palladium

• furans have remained rare [12][13], although furans are ubiquitous in nature [14]. In particular, 2,5-di(hetero)arylfurans are structural units with pronounced biological activities [15] and besides in natural products [16][17] they are also present in potential pharmaceuticals for the treatment of human

• African trypanosomiasis [18][19][20], and against human renal cancer cells [21][22][23]. Furthermore, 2,5-di(hetero)arylfurans have been reported as photonic chromophores [24]. However, the electronic and photophysical properties of 2,5-di(hetero)aryl furans have only been occasionally studied [25][26][27

One-pot three-component synthesis and photophysical characteristics of novel triene merocyanines

• Christian Muschelknautz,
• Robin Visse,
• Jan Nordmann and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 599–612, doi:10.3762/bjoc.10.51

• convergent strategies paved the way to luminescent push–pull dienes 1–4 with conformationally flexible and fixed acceptor units (Figure 1) [30][31][32], pyrazoles [33][34], benzodiazepines [35], furans and pyrroles [36][37] by consecutive multicomponent reactions and to highly emissive spirocycles [38][39

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• heterocyclic scaffolds were recently reported by the research groups of Liu and Fujii/Ohno. The Liu group developed a smart approach to furans starting from arylglyoxals 11, secondary amines and arylacetylenes in methanol under a nitrogen atmosphere [40]. In this reaction, the best catalyst was AuBr3 (5 mol

• attack of the oxygen nucleophile to the Au-activated triple bond. Aromatization and protodeauration closed the catalytic cycle to give furans 12 and to regenerate the catalyst (Scheme 11). A conceptually similar approach – and a comparable mechanism – was proposed by Ohno and Fujii for the synthesis of

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• , in an additional step, was reported to effect cyclodehydration of diols to furans and pyrans [47][48] (for recent examples for cyclodehydration protocols see [49][50]). Thereby, the volatile products were separated from O=P(OEt)3 through distillation. After our initial short communication [51] about

• very good yields (>80%) to pyrrolidines, piperidines and furans 13a,b and 13d–h. The established cyclodehydration procedure only had to be slightly modified regarding the work up: As most of the products 13a,b and 13d–h are volatile, the crude reaction mixture was concentrated under reduced pressure

• was re-isolated (probably originating from hydrolysis of the corresponding phosphate of alcohol 12c). The α-aryl furans 13d–f were formed in excellent yields (83–92%, Table 3, entries 5–7). Interestingly, the cyclodehydration of rac-12f was also mediated by P(OiPr)3 and P(OPh)3 in 67% and 83% yield

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• -subsituted alkenes were sometimes obtained along with the desired addition products (Scheme 9). Afterwards, N. Kamigata et al. applied this system to arenes [99] and heteroarenes (furans, pyrroles and thiophenes) [102][103][104] and gave a full account of this work (Scheme 9) [101]. Monosubstituted benzenes

• [114] as well as of various arenes and heteroarenes (pyridines, pyrimidines, pyrazines, quinolines, pyrroles, thiophenes, furans, pyrazoles, imidazoles, thiazoles, oxazoles, thiadiazoles, triazoles) [115]. The yields were low to excellent, depending on the substrate (Scheme 12 and Figure 20). Iron(II

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• -acyloxyalkynyl ketones were efficiently converted into highly substituted furans with 2.5 mol % of triflimide (triphenylphosphine)gold(I) as a catalyst in dichloroethane at 70 °C. Keywords: alkynyl ketones; cycloisomerization; furans; gold-catalysis; 1,2-migration; Introduction Furans are an important class of

• aromatic compounds. They are found in many natural products, in pharmaceutical and agrochemical compounds as well as in flavor and fragrance industries [1]. Furans are also routinely used as building blocks in organic synthesis [2][3]. Therefore, a large number of synthetic methods has been developed to

• catalysts with their carbophilic character have emerged as a new tool for furan preparation. As summarized in Scheme 1, furans could now be obtained by either gold(I) or gold(III) catalysis from various types of substrates such as allenyl ketones [8][9][10][11][12][13][14], enynes or diynes [15][16][17

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

• knowledge, the direct alkynylation of benzofurans is still an unknown process. Since 2009, our group has developed a mild gold-catalyzed [14][15][16][17] method for the alkynylation of electron-rich aryls such as indoles and pyrroles [18], thiophenes [19], anilines [20] and furans [21]. Key for success was

• 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

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

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

• intramolecular alkenylation on a range of other electron-rich heterocycles, including pyrroles, furans and thiophenes [63][64]. The intramolecular Pd(II)-catalyzed reaction of the 3-alkenylindoles 14 gave rise to the carbocyclic 5-membered ring-fused products 15 (Scheme 12) [65][66]. This procedure involves O2

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• oligosaccharides and lectins, by synthetic carbohydrate analogues [10][11][12][13]. Based on Schmidt’s imidate strategy [14], we have developed a method for the synthesis of a library of saccharide-mimetics containing furans. Furan, especially as its bis-hydroxymethylated derivative, was chosen as a core molecule

• [17]. Molecular dynamics simulations have shown that furans with two saccharides bound to hydroxymethyl groups show a nearly perfect alignment with each of the three terminal saccharides in Lewisy [15], another member of the Lewis histo blood group family, which is involved in tumor cell adhesion [18

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• -substituted benzyloxytetrahydropyrans and furans were synthesised and incubated with resting cell suspensions of R. rhodochrous. Our aim in this study was to establish whether the organism is capable of catalysing the hydroxylation of this panel of compounds and to investigate whether these hydroxylations