Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• . Gorelsky calculated that the Gibbs free energies of activation for the cleavage of C–H bonds at C5-position of thiophene or pyrrole derivatives, for reaction which proceed via concerted metallation–deprotonation [38][39][40], are higher than that of thiazoles (see bottom of Scheme 2) [42]. We assume that

• -heteroarylated selenophene with regeneration of the Pd(0) species. Conclusion In summary, the reactivity of 2-bromoselenophenes was investigated and revealed that the C2-heteroarylation of 2-bromoselenophene in high yields is only possible with specific heteroarenes such as thiazoles and imidazopyridines

• , whereas thiophene or pyrroles gave the desired products in low yields. Conversely, 2,5-dibromoselenophene was successfully coupled with both thiazoles and thiophenes in the presence of phosphine-free Pd(OAc)2 catalyst precursor and KOAc as inexpensive base, affording the desired 2,5-diheteroarylated

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• and amides have been developed, controlled by the reagents employed. With the Brønsted base KOt-Bu and CBrCl3 as radical initiator, benzo[d]imidazo[2,1-b]thiazoles are synthesized via attack at the α-carbon and keto carbon of the β-ketoester moiety. In contrast, switching to the Lewis acid catalyst

• bromination of the α-carbon using CBrCl3 as the Br source. This in situ halogenation strategy has been employed for the synthesis of quinoxalines [23], oxazoles [24][25], pyrido[1,2-a]benzimidazoles [26], imidazo[1,2-a]pyridines [27][28][29][30], thiazoles [31][32] and benzothiazoles [33][34]. With weak

• wastes. Here we describe the extension of this α-bromination shuttle system to 2-aminobenzothiazoles as substrates to synthesize benzo[d]imidazo[2,1-b]thiazoles. The benzo[d]imidazo[2,1-b]thiazole backbone is found in many bioactive molecules and pharmaceutical compounds as evident by its use as

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• an important class of compounds [1]. A large variety of such compounds are discovered so far and their therapeutic potential in diverse disease models has been thoroughly investigated [2]. For example thiazoles and oxazoles are found in various bioactive natural products, organic dyes and

• temperature. DDQ also induced oxidative dehydrogenation in 2-thiazolidines 27 and 2-oxazolidines 28 at room temperature in the presence of 4 Å molecular sieves with dichloromethane as solvent to generate diversely substituted 2-thiazoles 29 and 2-oxazoles 30 (Scheme 7) [41]. The putative mechanism initiated

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• cyclizations [69][70]. There are examples of using aminoazoles as an amine component in GBB-3CR (Scheme 1). They mostly involve different substituted 3-amino-1,2,4-triazoles [71][72][73][74][75] and 2-amino(benzo)thiazoles [71][72][76][77][78][79][80][81][82][83][84][85][86][87][88]. Several publications deal

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• S. Arshadi E. Vessally L. Edjlali R. Hosseinzadeh-Khanmiri E. Ghorbani-Kalhor Department of Chemistry, Payame Noor University, Tehran, Iran Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, Iran 10.3762/bjoc.13.61 Abstract Thiazoles and their hydrogenated analogues are not

• biologically important compounds. Keywords: 6-endo-dig cyclization; 5-exo-dig cyclization; N-heterocycles; N-propargylamines; thiazoles; Introduction Thiazoles are an important class of azole compounds that have attracted considerable attention due to the fact that they exhibit a wide variety of

• kinase activity [10][11][12][13][14] (Figure 1). This compound class is also a crucial part of many natural products such as vitamin B1 (thiamine), epothilone, dolastatin, and many more (Figure 2) [15][16][17][18][19][20][21][22][23][24]. Moreover, thiazoles are widely applied as pesticides and dyes [25

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• pathways but is found across proteins of all sizes so will not be discussed here. Review Thiazole and oxazoles Thiazoles and oxazoles are found in a huge number of bacterial RiPPs, which are often loosely defined as thiazole/oxazole-modified microcins [24] (TOMMs), although these can be subdivided more

• residue required for AviCys formation derives from cysteine rather than serine. Pyridine and piperidine formation in thiopeptides Thiopeptides are a widespread bacterial RiPP family that are characterised by multiple thiazoles, dehydrated residues and a central substituted pyridine, dehydropiperidine or

• actively transcribed thiopeptide gene clusters in human microbiota from every body site assessed [6]. Thiazoles in thiopeptides are introduced by a BCD-protein system described previously, while threonine and serine residues are dehydrated by lantibiotic-like dehydratases. The formation of core pyridine

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• preventing the catalyst deactivation. In 2013, Moss generalized the method to the formation of azepines fused with a variety of heteroaromatics including pyrimidines, pyridines, thiazoles and pyrrazoles [59]. Interestingly, most of the heteroaryls possess a chlorine substituent but no explanation was given

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

• biological functions of halogenated heteroarenes [57], the synthesis of haloheteroarenes via the corresponding arene C–H halogenations also gained extensive attention. In 2009, Pike and co-workers [58] reported the synthesis of halogenated 1,3-thiazoles using copper(II) halide as a catalyst. As shown in

• Scheme 17, the catalysis of copper(II) halides allowed selective halogenation of 2-amino-1,3-thiazoles 47 to give 5-halo-2-amino-1,3-thiazoles 48, 2,5-dihalo-2-amino-1,3-thiazoles 49 or 2-halo-1,3-thiazoles 50 according to the difference on reaction conditions such as temperature, catalyst species etc

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• . The N-(2-keto)amide skeleton is of particular interest, as it serves as a synthetic precursor for various small heterocyclic compounds such as imidazoles, oxazoles and thiazoles [7][8][9]. Azirine, the smallest nitrogen-containing unsaturated three-membered heterocyclic system, is well known as a

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

Thiazole-induced rigidification in substituted dithieno-tetrathiafulvalene: the effect of planarisation on charge transport properties

• Rupert G. D. Taylor,
• Joseph Cameron,
• Iain A. Wright,
• Neil Thomson,
• Olena Avramchenko,
• Alexander L. Kanibolotsky,
• Anto R. Inigo,
• Tell Tuttle and
• Peter J. Skabara

Beilstein J. Org. Chem. 2015, 11, 1148–1154, doi:10.3762/bjoc.11.129

• demonstrated that the substitution of thiophene units for thiazoles was found to increase the observed charge transport, which is attributed to induced planarity through S–N interactions of adjacent thiazole nitrogen atoms and TTF sulfur atoms and better packing in the bulk. Keywords: non-covalent

Thiazole formation through a modified Gewald reaction

• Carl J. Mallia,
• Lukas Englert,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 875–883, doi:10.3762/bjoc.11.98

• The synthesis of thiazoles and thiophenes starting from nitriles, via a modified Gewald reaction has been studied for a number of different substrates. 1,4-Dithiane-2,5-diol was used as the aldehyde precursor to give either 2-substituted thiazoles or 2-substituted aminothiophenes depending on the

• substitution of the α-carbon to the cyano group. Keywords: design of experiment (DOE); 1,4-dithiane-2,5-diol; Gewald reaction; thiazole; thiophene; Introduction Thiazoles are privileged motifs which are encountered in many naturally occurring bioactive compounds and pharmaceuticals with indications in a

• number of therapeutic areas including anticancer, antifungal, antibacterial, anti-inflammatory and as antidepressants (Figure 1) [1]. Several protocols have already been described for the synthesis of substituted thiazoles and benzothiazoles [2][3][4][5][6][7][8][9][10][11]. The current first choice

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

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• also used for probing in life science comprises the heterocyclic thiazoles. This structural element can be found in commercial products, such as thiazole orange, SYBR® Green I or TOTO®, which are, e.g., used for DNA labeling. In these compounds the thiazole ring is part of a benzothiazole. We set out

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , oxazoles, thiazoles and triazoles incorporated into peptide structures will be described. Pyrrolidines 2-substituted pyrrolidine-based dipeptide mimics were obtained from an Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization as described by Banfi et al. [51] . Herein, the Ugi reaction provided a small

• expected compound 109 (Scheme 34). Thiazoles In several natural products, the thiazole ring can be found as a backbone linker, probably resulting from easy cyclization/oxidation of cysteine residues. These compounds show interesting antifungal and antibiotic [95][96], algicidal [97], and antitumor [98][99

• ] biological activities. In addition, thiazole-based pharmaceuticals are also used as anti-prion agents (neurodegenerative disorders) [100]. Dömling and co-workers were the first that reported an Ugi-based synthesis of 2,4-disubstituted thiazoles (Scheme 35) [101][102]. The procedure involved a condensation of

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

• ]thiazoles, imidazoles and polyfluorobenzenes (same system but di-tert-butyl peroxide as oxidant instead of air, Table 21); the nature of the copper(II) salt, the base and the oxidant had to be reassessed for the reaction of indoles (Cu(OH)2/1,10-phenanthroline/KF/Ag2CO3). Interestingly, the results obtained

• [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

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• ., ring contraction and fusion products. A plausible mechanism was proposed for the formation of the products. Keywords: anthracene-1,4-diones; 1H-carbazole-6,11-diones; fused thiazoles; fusion reaction; heterocycles; naphthoquinones; ring contraction; sulfur–nitrogen; Introduction The 1,4

• that the most reliable route would be a reaction of sulfur monochloride with dialkylamino derivatives 3 and 4 (Scheme 1). According to the classification of the synthesis of sulfur-containing heterocycles from organic substrates and S2Cl2, thiazoles 1 and 2 should be generated from the four-member

• this paper we report a study of a reaction between dialkylaminonaphtho- and anthraquinones and sulfur monochloride in the presence of tertiary amines, a selective synthesis of fused thiazoles, and some of their chemical transformations. Results and Discussion We examined in detail the reaction of 2

Imidazole as a parent π-conjugated backbone in charge-transfer chromophores

• Jiří Kulhánek and
• Filip Bureš

Beilstein J. Org. Chem. 2012, 8, 25–49, doi:10.3762/bjoc.8.4

• thiazoles were synthesized, and their properties were compared within the individual series of substituents as well as across the three heterocyclic rings (Figure 3, Table 1). These A-π-IM-(π-D)2 systems possess exceptional thermal stabilities, respectable dipole moments, and significant nonlinearities. It

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• to the preparation of two potential inhibitors of vascular endothelial growth factor receptor-2 (Scheme 5) [38][39]. In 1998, Miura reported the first study of Pd(0)-catalyzed direct arylation of imidazoles, oxazoles and thiazoles with iodo- and bromobenzene [40]. It was notably shown that the use of

• the reactivity at the C2 position significantly. Tamagnan further reported the first example of Pd(0)/Cu(I)-catalyzed direct arylation of benzoxazole (Scheme 7) [41]. Interestingly, Bellina and Rossi reported the Pd(0)/Cu(I)-catalyzed direct arylation of indoles, imidazoles, oxazoles and thiazoles

• , thiazoles and oxazoles, using phosphate or carbonate bases (Scheme 13) [55]. The same year, Doucet demonstrated the high efficiency of PdCl(dppb)(C3H5) precatalyst in Pd(0)-catalyzed direct arylation of thiazoles and oxazoles with arylbromides (Scheme 13) [56]. Notably under these two protocols, oxazole was

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• were purified and unequivocally characterized by NMR and HPLC methods. Taking into account that the oxidation of thiazolidines to thiazoles with MnO2 (25 equiv) in toluene (55 °C) in the presence of pyridine (1.25 equiv) is a clean and efficient method [35], a first experiment was set up to test these

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• activation [83][84] (Scheme 17). Similarly, some five membered heterocycles with two heteroatoms [N-Ac- and N-(SO2Alk)-thiazoles, 1-Me-2-SCH2CF3- and 1,2-Me2-imidazoles] undergo single trifluoromethylsulfanylation on heating (60 °C) with CF3SCl in a pyridine-chloroform mixture [83]. Interestingly, unlike 1,2

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

• compared to nonactin (1 × 10−6 M) [128] in an ISE sensor format. This design was primarily based on size-fit factors. In addition, the aromatic units increase rigidity and the thiazoles provide hydrogen bonding sites. Campayo et al. examined acyclic compounds containing the 1,3-bis(6-oxopyridazin-1-yl

ADDP and PS-PPh₃: an efficient Mitsunobu protocol for the preparation of pyridine ether PPAR agonists

• Paul S. Humphries,
• Quyen-Quyen T. Do and
• David M. Wilhite

Beilstein J. Org. Chem. 2006, 2, No. 21, doi:10.1186/1860-5397-2-21

• . As expected, oxazoles, thiazoles, pyrazoles, and pyridines are tolerated in this chemistry. In a limited number of cases, functionality (e.g. basic amines, benzimidazoles, indoles, etc.) caused no reaction to occur and only recovered starting materials were isolated (data not shown). We then shifted