Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• fluorination strategies by using Selectfluor as an electrophilic source of fluorine [24][25][26][27][28][29][30][31] can provide a powerful tool for building up nitrogen heterocycle derivatives. Fluorinated pyrrolidines [32] and fluorinated pyrazoles [33] have been synthesized from 1,ω-N-protected aminoalkynes

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

• [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

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• , the copper-catalyzed N-arylation has been extensively utilized for C–N coupling, especially for the arylation of N-containing heterocycles such as indoles, imidazoles, indazoles, pyrroles, pyrazoles and triazoles [25][26][27][28] to construct more fused heterocycles. In recent years, several

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• . [47] have demonstrated that ethynyl ketones can be generated in flow by the palladium-catalysed acylation of terminal alkynes and further transformed in a continuous process to pyrazoles by cyclocondensation with hydrazines using a commercially available conductive heating modular flow reactor. Given

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• photolysis technique was used for the generation of DRc–g from the corresponding azoalkanes AZc–g (Scheme 2). Results and Discussion Synthesis of AZc–g and their steady-state photolyses. The precursor azoalkanes AZc–g were prepared in an analogous method to the synthesis of AZa,b [28] (Scheme 3). Pyrazoles

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• of adenosine and, thus, has been incorporated in various compounds impairing protein kinases and ATPases [7][8][9]. Moreover, a large variety of additional fused pyrazoles exhibit interesting biological activities, such as, pyrazolo[1,5-a]quinolones [10], pyrazolo[4,3-c]quinolones [11], pyrazolo[5,1

• -a]isoquinolines [12], and thieno[2,3-c]pyrazoles [13]. In view of these facts as well as due to our continuing interest in the exploration of useful but unused chemical space, which has become a paradigm of contemporary medicinal chemistry [14], we have devoted some effort to the construction of

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• ], and moreover, pyrazolidines can also be oxidized to afford pyrazolines [8][9][10][11][12] and pyrazoles [13][14][15]. The pyrazolidine structural unit is commonly constructed by [3 + 2] cycloaddition reactions using hydrazones [16][17][18][19][20][21][22][23] or azomethine amines [24][25][26][27] as

Chemistry of polyhalogenated nitrobutadienes, 10: Synthesis of highly functionalized heterocycles with a rigid 6-amino-3-azabicyclo[3.1.0]hexane moiety

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Armin de Meijere and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2012, 8, 621–628, doi:10.3762/bjoc.8.69

• chlorides result in the formation of the enamines 11, 12, 13, 16, 25, the amidine 6, and the amides 20, 21, respectively. In the following, cyclization to the highly functionalized pyrazoles 27, 28, pyrimidine 26 and pyridopyrimidine 24 succeeded. Deprotection of 21, 12 and 28 proved to be only partially

• 75–90% yield (Scheme 6). A conceivable mechanism for the cascade reaction that leads to the pyrazoles 27 and 28 is presented in Scheme 7. Initially, the trichlorobutene I is formed upon addition of the arylhydrazine to the nitro-substituted butadiene 25. Subsequent elimination of benzotriazole

• results in the diaminobutadiene II, which tautomerizes to the stable amidine III. The pyrazoline IV is then formed by an intramolecular SNVin reaction. Finally, HCl elimination affords the pyrazoles 27, 28. The stimulus to investigate such compounds originated from the known pharmacological activities of

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• recently reported to afford the corresponding pyrazolo[1,5-a]-quinazolin-6-one derivatives [21]. Although it is well established that 5-amino-pyrazoles have nonequivalent nucleophilic reaction centres in the aminopyrazole scaffold (N1, C4, NH2), which can lead to the formation of several different

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• % yield). Keywords: [3 + 2] cycloaddition; isoindoles; nitrile imines; pyrazoles; sydnones; Introduction Sydnones belong to the group of five-membered heterocyclic compounds referred to as being "mesoionic" and have been widely studied since their discovery [1][2][3][4][5]. They can be represented as

Efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles from 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes

• Yiwen Yang,
• Chunxiang Kuang,
• Hui Jin,
• Qing Yang and
• Zhongkui Zhang

Beilstein J. Org. Chem. 2011, 7, 1656–1662, doi:10.3762/bjoc.7.195

• , Fudan University, Handan Road 220, Shanghai 200433, China 10.3762/bjoc.7.195 Abstract An efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles was achieved. The synthesis involves the [3 + 2] dipolar cycloaddition of 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes. The process proceeds smoothly in

• moderate to excellent yields. 1,3-Diaryl-4-halo-1H-pyrazoles are found to be important intermediates that can easily be converted into 1,2,5-triaryl-substituted pyrazoles via Pd-catalyzed C–H bond activation. Keywords: C–H bond activation; cycloaddition; dihaloalkenes; pyrazole; sydnones; Introduction

• Over the past decade, pyrazoles as key motifs in biologically active compounds have received increasing attention from the synthetic community. Diazoles can be employed as a central building block in the synthesis of compound libraries in the pharmaceutical [1] and agrochemical [2] industries. Pyrazole

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• , only a very few applications based on these potentially very useful functional groups have been reported to date. Lately, Yu et al. [2] disclosed the synthesis of pyrazoles, while Chiba et al. employed vinyl azides for the Mn(III)-mediated synthesis of different azaheterocycles [3][4]. Furthermore

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• pyrazoles in a consecutive fashion from terminal alkynes, acid chlorides, and hydrazine derivatives. Classical approaches to these valuable compounds are notably based on the cyclocondensation of hydrazine derivatives with 1,3-disubstituted three-carbon units, including α,β-unsaturated ketones, and

• presence of Et3N and catalytic amounts of PdCl2(PPh3)2 and CuI. The resulting ynones 27 were then treated in situ with diversely substituted hydrazine derivatives to produce, upon microwave heating, a series of pyrazoles 28–30 (Scheme 15). As previously established for this type of cycloaddition, one of

• . Synthesis of masked 3-aminoindan-1-ones. Synthesis of homoallylic amines and α-aminoesters. Preparation of 1,2-dihydroisoquinolin-1-ylphosphonates. Pyrazole elaboration by cycloaddition of hydrazines with alkynones generated in situ. An alternative approach to pyrazoles involving hydrazine cycloaddition

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• by our smooth glyoxylation–alkynylation sequences with a variety of unfunctionalized π-nucleophiles, such as pyrazoles, thiophenes, furans, and even the hydrocarbon azulene (1a) [53], we decided to perform optimization studies of the glyoxylation–decarbonylative alkynylation with guaiazulene (1b), a

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• . Pyrazoles are also useful intermediates for many industrial products and it is, therefore, not surprising that many synthetic methods have been developed for the preparation of such heterocyclic systems, for example, through 1,3-dipolar cyclo-additions of diazo compounds and the direct condensation of 1,3

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

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• , respectively, with tert-butyl cyanoacetate (14), as illustrated in Scheme 5 [36]. Baraldi et al. [37] utilized this method for the regioselective synthesis of 2-alkyl- or 2-aryl-3-aminothieno[3,4-c]pyrazoles 19. Several alkyl- or arylhydrazine hydrochlorides on condensation with 4-cyano-3

• -component, two-step “catch and release” solid-phase synthesis of 3,4,5-trisubstituted pyrazoles was reported which involved a base-promoted condensation of a 2-sulfonyl- or a 2-carbonyl-acetonitrile derivative (29 or 33) with an isothiocyanate and in situ immobilization of the resulting thiolate anion (30

• or 34) on Merrifield resin in the first step. Reaction of the resin-bound sulfonyl intermediate 31 with hydrazine, followed by release from the resin and intramolecular cyclization, afforded 4-arylsulfonyl-3,5-diamino-1H-pyrazoles 32. Reaction of the resin-bound carbonyl intermediate 35 with

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• resulted in good yields [4][26]. Copper-diamine-catalysed N-arylation facilitated the arylation of pyrroles, pyrazoles, indazoles, imidazoles, triazoles, benzimidazoles and indoles [27][28][29]. Besides aryl halides as the aryl donor, arylsiloxanes [30], arylstannanes [31], iodonium salts [32], aryl lead

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