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

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• the above catalytic system. To the best of our knowledge, this is the first report of the application of this catalyst for the regioselective 1,3-dipolar cycloaddition reaction, involving azomethine ylides derived from structurally complex quinoline-based N-heterocycles. Results and Discussion Our

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

• new key intermediates encompass the structural motif C=N+–N−, a very useful framework for further functionalizations. Wu and co-workers widely used preformed N’-(2-alkynylbenzylidene)hydrazides 42 in two component reactions involving 43 as an intermediate for the construction of N-heterocycles

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• powerful tools for the assembly of small-molecule libraries [1][2]. MCRs leading to functionalized N-heterocycles [3][4][5][6][7] have long been known before the general concept of MCRs was introduced, e.g. the Hantzsch dihydropyridine synthesis [8] or the Biginelli reaction [9] leading to

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• Xiang-Guo Hu Luke Hunter School of Chemistry, The University of New South Wales, Sydney NSW 2052, Australia 10.3762/bjoc.9.306 Abstract The stereoselective incorporation of fluorine atoms into N-heterocycles can lead to dramatic changes in the molecules’ physical and chemical properties. These

• changes can be rationally exploited for the benefit of diverse fields such as medicinal chemistry and organocatalysis. This brief review will examine some of the effects that fluorine substitution can have in N-heterocycles, including changes to the molecules’ stability, their conformational behaviour

• , their hydrogen bonding ability, and their basicity. Finally, some methods for the synthesis of stereoselectively fluorinated N-heterocycles will also be reviewed. Keywords: conformation; fluorine; N-heterocycles; iminosugars; medicinal chemistry; organo-fluorine; Review 1. Introduction A cursory

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• to perform many transformations that are hardly possible under thermal conditions. This includes photocatalytic reactions that have seen an immense interest lately [1]. Nitrile ylides 3 are 1,3-dipoles that have served for the preparation of different five-membered N-heterocycles in 1,3-dipolar

• further generalization of this flow protocol along with telescoping it with vinyl azide formation. Formation of azirines 2 from vinyl azides 1, photoinduced ring-opening to the nitrile ylides 3, and 1,3-dipolar cycloaddition to the pentacyclic N-heterocycles 5. Solid-phase assisted synthesis of vinyl

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• synthesis; catalysis; enones; intramolecular aza-[3 + 3] annulation; N-heterocycles; natural product; vinylogous amides; Introduction Throughout the past decade, we have been developing an aza-[3 + 3] annulation reaction as a general and unified strategy in alkaloid synthesis [1][2][3][4][5][6][7][8][9][10

Interplay of ortho- with spiro-cyclisation during iminyl radical closures onto arenes and heteroarenes

• Roy T. McBurney and
• John C. Walton

Beilstein J. Org. Chem. 2013, 9, 1083–1092, doi:10.3762/bjoc.9.120

• (R)=N• closures are well documented. Forrester and co-workers were probably the first to utilise iminyl radicals synthetically. They obtained iminyls by persulfate oxidation of imino-oxyacetic acids in aqueous solvents and prepared azines [6], N-heterocycles [7][8], and other derivatives [9]. This

Synthesis of phenanthridines via palladium-catalyzed picolinamide-directed sequential C–H functionalization

• Ryan Pearson,
• Shuyu Zhang,
• Gang He,
• Nicola Edwards and
• Gong Chen

Beilstein J. Org. Chem. 2013, 9, 891–899, doi:10.3762/bjoc.9.102

• [26]. In 2012, our laboratory [28] as well as that of Daugulis [27] independently reported that picolinamide substrates can undergo intramolecular dehydrogenative C–H amination reactions to afford medium-sized N-heterocycles under the catalysis of Pd(OAc)2 with PhI(OAc)2 oxidant. These discoveries led

New simple synthesis of ring-fused 4-alkyl-4H-3,1-benzothiazine-2-thiones: Direct formation from carbon disulfide and (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles

• Qiuping Ding,
• Yuqing Lin,
• Guangni Ding,
• Fumin Liao,
• Xiaoyan Sang and
• Yi-Yuan Peng

Beilstein J. Org. Chem. 2013, 9, 460–466, doi:10.3762/bjoc.9.49

• (Scheme 1) [9]. Promoted by these results, we envisioned that (E)-3-(2-aminoaryl)acrylates or (E)-3-(2-aminoaryl)acrylonitriles could also be utilized as starting substrates for the synthesis of N-heterocycles. Therefore, we focused on the o-amino-α,β-unsaturated compound 1 (Scheme 2), which would be

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• aldehyde and aniline derivatives) with alkenes have become efficient strategies for the generation of N-heterocycles [9][10][11]. In these reactions the alkene must be electron-rich, which means that functional groups attached to the alkene should be able to donate electrons. Among the electron-rich

Asymmetric Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene

• Magnus Rueping and
• Sadiya Raja

Beilstein J. Org. Chem. 2012, 8, 1819–1824, doi:10.3762/bjoc.8.208

• construction of optically active, nitrogen-containing, six-membered rings, such as tetrahydroquinolines and piperidines. N-heterocycles are found in a wide range of natural products and many biologically active compounds [1][2][3][4]. To date, most aza-asymmetric Diels–Alder reactions have been catalyzed by

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• - and step-economical access to annulated carbo- as well as O- and N-heterocycles. Finally, we found that the catalytic system also proved to be applicable to the one-pot copper-catalyzed direct arylation of various azoles 5 through N–H/C–H bond cleavages with aryl iodides 6 as the organic electrophiles

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• diastereoselectivity [9]. We previously reported on the unusually diverse synthetic potential of carbohydrate-derived 1,2-oxazines allowing the smooth and flexible preparation of various highly functionalised compounds, including de novo syntheses of carbohydrates and their mimetics, as well as N-heterocycles [10][11

• as well as additional spots seen on TLC of the crude reaction mixtures support this assumption, but none of these possible by-products could be isolated. With respect to the enormous importance of polyhydroxylated N-heterocycles as carbohydrate-mimicking glycosidase inhibitors [41][42][43][44][45

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

• glyoxylation of electron rich N-heterocycles, such as indoles and pyrroles, leads to the formation of glyoxylyl chlorides, which can be reacted without isolation by decarbonylative Sonogashira coupling to form the desired ynones. So far, only one example of the synthesis of azulenylynones has been described

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• approach to other N-heterocycles [52]. Thus, the benzene ring was substituted by a cis-alkene, and a gold-catalyzed synthesis of 5,6-dihydro-8H-indolizin-7-ones 21 from N-(pent-2-en-4-ynyl)-β-lactams 20 was developed (Scheme 11). Pt(II) and Pt(IV) also catalyzed this reaction, albeit less efficiently. In