Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• high Tpeak but also higher ΔHdec values for the latter ones. NHIs bearing N-heterocycles with a high N/C-ratio such as triazoles show among the lowest Tpeak and the highest ΔHdec values. A comparison of NHIs with known (pseudo)cyclic benziodoxolones is made and we further correlated their thermal

• promising properties in terms of reactivity and stability. However, iodanes stabilized by nitrogen-based ligands, in particular N-heterocycles are still underexplored [22][23][24][25][26][27][28]. Recently, our groups investigated systematically cyclic and pseudocyclic N-heterocycle-stabilized iodanes (NHIs

• ). We demonstrated that the N-heterocycle significantly influences the important I–L1 bond length and subsequently has a profound impact on the reactivity of the iodane in oxygen transfer reactions [29][30]. Since the combination of a highly oxidized hypervalent iodine species with N-heterocycles with a

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• ]. Additionally, a diverse range of N-heterocycles, amides and motifs commonly encountered in medicinal chemistry were used as handles to direct C–H fluorination for the synthesis of pharmaceutical drugs (Scheme 24) [25]. Copper catalysis Despite the success of Pd-catalyzed fluorinations, the more widespread use

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• ; nucleophilic carbenes; sulfur transfer reaction; Introduction Imidazole N-oxides constitute a practically valuable class of five-membered aromatic N-heterocycles [1][2][3][4][5]. The subclass of 2-unsubstituted imidazole N-oxides 1 with diverse substituents located at N(1), C(4), and C(5) is of special

• in monomeric form in the case of sterically crowded parent amines such as 1-aminoadamantane or tert-butylamine or, alternatively, as trimeric hexahydro-1,3,5-triazines 3’ in the case of sterically less crowded amines [7]. In analogy to other azoles and in contrast to six-membered aromatic N

• -heterocycles, N-oxides 1 cannot be prepared via oxidation of the parent imidazoles by treatment with an oxidizing agent, e.g., with a percarboxylic acid [6]. Imidazole N-oxides are versatile substrates for the preparation of diverse imidazole derivatives and the most characteristic feature is their 1,3-dipolar

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• -phenylselanyl-1H-pyrazoles through reaction of α,β-alkynic hydrazones with phenylselenyl chloride [11]. In this context, pyrazoles are one of the most important N-heterocycles found in natural products including formycin, pyrazofurin and withasomnine, for example. Still, pyrazole unities are present in several

• antidepressive activity [14][15][16][17]. Moreover, they have been extensively used as synthons to prepare a wide variety of fused N-heterocycles of synthetic and pharmacological importance [18][19][20]. Thus, an effective strategy for the design and the preparation of new pharmacologically promising drugs that

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• are known to react with N-haloamines to form aziridines and other N-heterocycles. Typically, the reactions require a catalyst (e.g., Cu, I2) [17][18][27], whilst more active reagents such as chloramine-T with osmate catalysts have been used to make 1,2-aminoalcohols and diamines [28][29][30][31][32

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• enantioselectivities (Scheme 14) [44]. The reaction was also found to be compatible with aromatic N-heterocycles and alcohol nucleophiles to afford the corresponding products in moderate to good yields with high to excellent enantioselectivities [44]. The use of water as a solvent by Kobayashi and co-workers is

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• atom-economical biphenylation of N-heterocycles was developed [33]. This method involved a direct N-arylation of pyrazoles or triazoles 12 under basic conditions, followed by a ruthenium-catalysed C–H arylation with the emerging aryl iodide (Scheme 8). Due to the fact that the first step of this

• dithiocarbamates 7 and 7’ from one equivalent of diaryliodonium salt 1. Synthesis of substituted isoindolin-1-ones 9 from 2-formylbenzonitrile 8 and the postulated reaction mechanism. Domino C-/N-arylation of indoles 10. Domino modification of N-heterocycles 12 via in situ-generated directing groups. Synthesis of

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• incorporate α-methylbenzylamine-type chiral auxiliaries, which have been extensively used by Davies et al. to gain access to a wide range of chiral N-heterocycles via intermolecular aza-Michael reactions [34][47][48][49][50][51]. The starting unsaturated benzoic acids 14a–e and 15 were readily prepared via a

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• of the direct methylation of electron-deficient N-heterocycles have been reviewed [9]. In a project aimed at the synthesis of tri- and tetracylic alkaloids containing the isoquinoline scaffold, we were interested in isoquinoline building blocks which bear a methyl group at C1, since this group should

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• synthesis of 5–8 Based on the recently obtained 1,2,3-triazole-appended N-heterocycles, as promising lead compounds with efficient and selective cytostatic activities [8][9], our research groups share an interest in derivatization of target compounds by a triazole bridge [33]. Quinoline is an important

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• , Lebanon Université de Rennes 1, Institut des Sciences Chimiques de Rennes, CNRS UMR 6226, Avenue du Général Leclerc, 35042 Rennes Cedex, France 10.3762/bjoc.13.208 Abstract Using an aerobic oxidative coupling, different new imidazo[1,2-a]-N-heterocycles with gem-difluroroalkyl side chains have been

• coupling reactions as well as nucleophilic substitutions have been performed successfully in order to increase the molecular diversity. Keywords: aerobic oxidative coupling; imidazo[1,2-a]-N-heterocycles; gem-difluoroalkyl derivatives; propargylic fluorides; Introduction Nitrogen-containing heterocyclic

• fluorinated propargylic derivatives [21]. Thus, taking into account the known biological properties of the imidazo-fused N-heterocycles, we became interested in the preparation of new derivatives of this type possessing gem-difluorinated side chains as indicated in Figure 1. Such new fluorinated heterocycles

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• - and N-heterocycles The different dimers of isoprene can be transformed into a large number of derivatives such as terpene-alcohols or ethers [38]. Moreover, some isoprene dimers have been submitted to Diels–Alder reactions with olefins such as maleic acid anhydride or methacrolein to form products

• isoprene. Functionalization of the isoprene-dimer 2-TT to substituted O- and N-heterocycles. Optimization of the dimerization reaction of isoprene.a Supporting Information Supporting Information File 244: 1H NMR and 13C NMR spectra collection of the products and GC–FID analysis of the isoprene dimer’s

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

• ]. Encouraged by these results a variety of functionalized N-heterocycles were oxidatively dehydrogenated with IBX, to afford their aromatic counterpart. For example imidazoles 11, dihydroisoquinoline 12, pyridine 13, and pyrrole 14 were obtained from their corresponding heterocyclic precursors 7–10 in

• dehydrogenation of N-heterocycles [31][32][33][34]. IBX-mediated room temperature one-pot condensation–oxidative dehydrogenation of o-aminobenzylamines. Anhydrous cerium chloride-catalyzed, IBX-mediated oxidative dehydrogenation of various heterocycles at room temperature. Oxidative dehydrogenation of

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

• 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

• patterns. It is well known that they can undergo a number of cyclization reactions to produce various N-heterocycles and complex natural products. In this context we recently reviewed their role in the syntheses of pyrrole [65], pyridine [66], quinoline [67], pyrazine [68], 1,4-oxazepane, and 1,4-diazepane

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• interest of synthetic and medicinal chemists. Synthesis of various propargylamines from various salicylaldehydes under metal-catalyst-free conditions. Representative examples of bioactive compounds bearing a propargylamine moiety and synthesis of various N-heterocycles from propargylamine-containing

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• of nitrogen-containing moieties, such as amides [86][87], N-heterocycles [88][89], imines [90][91], pyridine N-oxide [92], amines [93][94], as well as a variety of others [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• cyclization, giving the tricyclic N-heterocyclic core. Very recently, Shi and co-workers reported the chiral phosphoric acid (CPA, cat. 31)-catalyzed asymmetric dearomatization reactions of tryptamines with 3-indolyl-3-hydroxyoxindoles, affording the indole-containing tricyclic N-heterocycles in a highly

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• efforts to better comprehend the scope of this catalytic system, especially on features concerning the BARF salt effect [43][44] and electronic effects on the aromatic rings of the chiral ligands [45]. In 2014, Maguire at al reported the syntheses of N-heterocycles by the enantioselective insertion of

• . Cyclopropanation/Insertion rhodium carbenoid reactions into C(sp3)–H reported by Pavlyuk and coworkers. Syntheses of N-heterocycles by RCM reported by Pavlyuk and coworkers. Acknowledgements We thank the Brazilian National Research Council (CNPq, Gran Nos. 477418/2013-9), the Brazilian Coordination for the

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• : α-lithiation; C–H functionalization; heterocycle; photoredox catalysis; piperazine; Introduction Piperazine is one of the most important saturated N-heterocycles frequently found in life-saving small-molecule pharmaceuticals [1]. In a recent statistical study done by Njardarson and co-workers

• , piperazine ranks among the top three N-heterocycles along with pyridine and piperidine in the U.S. FDA-approved pharmaceuticals [2]. Due to its broad utilization, piperazine has been considered as a privileged scaffold in drug discovery to combat various human diseases (Figure 1). For example, Imatinib (also

• , path b). Although there have been major advancements made in the field of direct sp3 C–H bond activation and functionalization adjacent to nitrogen in saturated N-heterocycles and acyclic amines [25][26][27], C–H functionalization of piperazines has been a daunting challenge. In comparison to the well

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

• been discussed. Gandelman and Jacobsen reported the first asymmetric 1,4-addition of various N-heterocycles to α,β-unsaturated imides [246]. This reaction represented a novel approach to synthesizing functionalized chiral N-heterocycles, which are studied in areas such as material science [247][248

• studies as the basis for the development of the 1,4-addition of N-heterocycles to α,β-unsaturated imides. They applied both substituted and unsubstituted purines, benzotriazole, and 5-substituted tetrazoles as nucleophiles to this reaction, which resulted in moderate to excellent yields and excellent

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• yields (up to 95%, Scheme 4). McBurney et al. prepared various N-heterocycles, using oxime carbonates as excellent precursors for the photoinduced generation of iminyl radicals, whereby at standard photolysis conditions, 3-substituted 6-methylphenanthridines were obtained in good to quantitative yields

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• Chemistry, University of Debrecen, H-4010 Debrecen, Hungary Porfirin Ltd., Mikszáth K. u. 7. III/3, 4032 Debrecen, Hungary 10.3762/bjoc.10.272 Abstract Condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties were prepared by a regio- and diastereoselective domino

• preparation of condensed O,N-heterocycles with the 1,2,8,9-tetrahydro-7bH-quinolino[1,2-d][1,4]benzoxazepine skeleton, the neuroprotective activities of which were tested against hydrogen peroxide (H2O2), Alzheimer's amyloid β-peptide fragment Aβ25–35 and oxygen–glucose deprivation (OGD)-induced neurotoxicity

• derivative afforded three condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties. trans-Diastereoselectivity of the cyclizations was determined by the correlation of 3JH,H coupling constants with the geometry of the computed conformers, while (2R,15aR) absolute

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -imidazo[1,2-b]pyrazole; isocyanide; multicomponent reaction; N-heterocycles; Introduction For the relatively rapid design and construction of a diverse, large pharmacophore library, the basic concepts of diversity-oriented synthesis and isocyanide-based multicomponent reactions, such as the Ugi four

• diversity arising from the pyrazole starting material. As far as we are aware, a one-pot two-step process involving the in situ formation of the desired amino-substituted N-heterocycles such as C4 functionalized 5-aminopyrazoles, followed by GBB-3CR has not been described to date. On the other hand, the

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• in recent years [67][68][69]. Especially one of these protocols drew our attention: The group of C. Bolm reported a facile, iron-catalyzed protocol for N-arylation of various N-heterocycles including one example on indole (phenylation in 60% yield), employing aryliodides, N,N'-dimethylethylenediamine