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

• cycloaddition is presented in Scheme 3. The base (DBU) abstracts the acidic proton of furo[3,2-h]quinolinium 9a to generate the 1,3-dipole I. The Cu(II)–phenanthroline system activates the maleimide dipolarophile via coordination with the carbonyl group to undergo a [3 + 2] cycloaddition with the 1,3-dipole to

• synthesized (Scheme 5) from phenanthroline (11) and 2′-bromoacetophenones 8a and 8d, under basic alumina/microwave (180 W) conditions. These were then subjected to the optimized [3 + 2] cycloaddition protocol with different N-phenylmaleimide dipolarophiles 4a–c, which eventually produced similar cycloadducts

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

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

• transformation, i.e., [3 + 2] cycloaddition (Scheme 9). Another application of an A3-MCR for the improvement of molecular complexity was published by Kokezu and Srinivas [39]. The authors suggested a straightforward AuBr3-catalyzed route to 2-, 3-, or 5-propargylamine substituted indoles 9. The reactions were

• reaction involving nitriles 52 as pro-nucleophiles (Scheme 28) [71]. Wu and co-workers successfully employed the isoquinolinium-2-ylamides 43 as an ylidic species in two-component tandem [3 + 2]-cycloaddition reactions with a series of substrates including dimethyl acetylenedicarboxylate [72

• isoquinolinium-2-ylamide 43 undergoes a [3 + 2]-cycloaddition reaction with carbodiimide 54. Further intramolecular rearrangement yields the desired 1-(isoquinolin-1-yl)guanidine 55. Moreover, isoquinolinium-2-ylamides 43 can participate as 1,3-dipoles in [3 + 2]-cycloaddition reactions with in situ generated

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• compounds. Preliminary experiments, however, showed that under standard conditions, a cycloaddition of diazodimedone and dimethyl diazomalonate with thiobenzophenone did not occur [5][6]. On the other hand, recent studies showed that the [3 + 2]-cycloaddition of this thioketone with many diazodicarbonyl

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• carbolactonization of terminal alkenes with arylboronic acids. Synthesis of tricyclic indolines via gold-catalyzed formal [3 + 2] cycloaddition. Gold(I) catalyzed aminoarylation of terminal alkenes in presence of Selectfluor [dppm = bis(diphenylphosphino)methane]. Mechanistic investigation on the aminoarylation of

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• catalyzed [3 + 2] cycloaddition reaction. Unfortunately, the yield for this reaction was very low (<20%). In order to obtain compound 1 by the 1,3 dipolar cycloaddition route we changed the protocol. We synthesized the nitro derivative 2 (3-tert-butyl-5-(4-nitrophenyl)-1,2,4-oxadiazole) in situ by using the

[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

• with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• -diamines [19]. Herein, we report the reactivity and diastereoselectivity of 5a–c as heterodienes in a multicomponent [4 + 2]/[3 + 2] cycloaddition with ethyl vinyl ether (EVE) and selected electron-deficient alkenes in the presence of LiCl or LiClO4 as promoters. A study on the solvent effect was also

• route led to the obtainment of a great number of new chiral aminated nitroso acetals (7, 9–13) and the feasible synthesis of the pyrrolizidin-3-one scaffold. The good reactivity and diastereoselectivity of the new chiral-γ-aminated nitroalkenes 5a–c in multicomponent [4 + 2]/[3 + 2] cycloaddition

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3-nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields. Keywords: amino

• -derivatives 10b,c (Table 1, entries 11 and 12) or the triazole derivative 11a (Table 1, entry 13) when THF or CH3CN were used as solvents, respectively. The formation of chiral 1,2,3-triazole derivative 11a was proposed to be by way of a [3 + 2]-cycloaddition with the azide group acting as 1,3-dipolarophile

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• (Figure 5), and they have investigated their catalytic activities in asymmetric alkylation reactions for producing enantiomerically enriched amino acids. The synthesis of these quaternary ammonium ions follows a diversity-oriented approach wherein the tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition 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

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• -homolysine side chain to an azide [12][13][14] employing the Wong azidation [15] enables Huisgen [3 + 2]-cycloaddition [16] as an orthogonal coupling method. In order to build up the peptide sequence in the presence of Fmoc, Cbz and the azide, an acid-labile protecting group was required for temporary

• 4 from methanol. Functionalization of the β-tripeptide template The cyclic β-tripeptide template 4 has the potential for orthogonal functionalization at the side chains with up to three different moieties, by successive amide-bond formation and by employing the Huisgen [3 + 2]-cycloaddition

• reported, as well as the functionalization with the nucleobase recognition units thymine-1-yl acetic acid (6) and (N4-benzyloxycarbonyl)cytosine-1-yl acetic acid (7) (Figure 3). In all cases, the template contains a third option for functionalization by covalent attachment of molecules through [3+2

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• -metal (or "Roper-type") carbenes with significant π backbonding, consistent with Roper's predicted patterns of reactivity for metal–carbon double bonds [75]. These Roper-type carbenes also reacted with organic azides and nitrous oxide via an apparent [3 + 2] cycloaddition [76][77], leading to oxygen

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• intermolecular [3 + 2] cycloaddition of MBH carbonates with methyleneindolinones to afford the corresponding spirocyclopentaneoxindoles in good yields and high ee values in 2011 [49]. Moreover, Lu and co-workers have recently explored a series of thiourea-phosphine catalysts derived from L-threonine, which are

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• example of a more complex alkyne. The azide–alkyne [3 + 2] cycloaddition was catalyzed with copper(II) sulfate pentahydrate and L-ascorbic acid in DMF overnight at room temperature. A solution of EDTA was added to remove the remaining copper cations from the resin. Resin cleavage under acidic conditions

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• explanation for the observed binding affinities. Results and Discussion Synthesis of glycoclusters The Cu(I)-catalyzed [49][50] Huisgen [3 + 2] cycloaddition [51] of azides and alkynes (CuAAC) is a frequently used method for the covalent attachment of carbohydrate epitopes to azide- or alkyne-presenting

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• rearrangement. The short-lived carbonyl ylides derived from methionine and S-benzylcysteine formed head-to-tail dimers by a [3 + 3]-cycloaddition and could be trapped with external dipolarophiles, while the S-allyl derivative 14c yielded the pentacyclic compound 17 by an intramolecular [3 + 2]-cycloaddition

• tetrahydrothiophene 16 (31% yield, two diastereomers), and carbonyl ylide 14c is trapped by an intramolecular [3 + 2]-cycloaddition to give the pentacyclic compound 17 (35% yield). The regioselectivity of the latter reaction was established by NMR studies: after assignment of proton resonances from HMBC spectra, a

• NOESY NMR experiment indicated the correlation shown in Scheme 6. Intramolecular [3 + 2]-cycloaddition reactions of a carbonyl ylide with a nonactivated but suitably positioned olefinic bond have been known for some time [3][27][28][29][30][31][32][33][34][35] and can be used for the construction of

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

• , namely, trans–cis and cis–trans isomerization of the stilbene moiety, and photolysis of the sydnone ring resulting in the formation of the nitrile imine intermediate. The nitrile imine species is, in intramolecular dipolar [3 + 2] cycloaddition, trapped by the cis- or trans-double bond of the stilbene

• proton C with tolyl (H-10) and H-5 protons was seen. In order to explain the diverse structures (14 and 15) and their formation mechanism, we analysed the possible ways of intramolecular [3 + 2] cycloaddition relating to the arrangement of the sydnone ring towards the cis and trans double bond (Figure 5

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

• Pyrazolidinones were prepared in a two-step sequence starting from α-hydrazonocarboxylic acids. After a four-component Ugi coupling, the resulting hydrazone was engaged in a copper triggered [3 + 2] cycloaddition/aerobic oxidation cascade. Keywords: aerobic oxidation; copper(II); [3 + 2] cycloaddition; hydrazone

• pyrazolidinone under oxidative conditions from simple hydrazone derivatives (Scheme 1) [13]. The cascade features a [3 + 2] cycloaddition coupled with an aerobic oxidation of the resulting pyrazolidine. A further oxidative coupling may be observed according to the substitution pattern of the starting acyl

• possible Ugi pathways to introduce an alkene moiety that is prone to undergo an intramolecular [3 + 2] cycloaddition with a hydrazone, we selected the Ugi coupling between α-hydrazonocarboxylic acids and allylamine as the most straightforward path. There are several reports on the use of hydrazones in Ugi

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• aforementioned mechanistic pathway [26]. According to the theoretical data, the formal (4 + 2) cycloaddition would indeed comprise a two-step process consisting of a dipolar (3 + 2) cycloaddition of the carbonyl ylide I to afford a carbene species III [27][28], followed by a 1,2-alkyl migration to yield the

• , when PtCl2 (under an atmosphere of CO) is used, the major products are 2,3-indoline-fused cyclopentenes 44, which arise from a formal (3 + 2) cycloaddition (lower arrow) [86]. Thus, the appropriate choice of a Pt or Au catalyst determines whether the allenyl intermediate 42 participates as a 2C- or as

• derived from DTBM-Segphos or, as recently demonstrated, with gold complexes derived from chiral phosphoramidites [88][89]. Also in 2007, L. Zhang and co-workers reported another formal intramolecular cycloaddition between alkenes and allenes, in particular a (3 + 2) cycloaddition between allenyl MOM

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

• proved to be less successful for more complex pyrroles of which atorvastatin was an example (Scheme 1). In order to prepare the 5-isopropylpyrrole derivative 16 a more efficient [3 + 2] cycloaddition of an acetylene component with an amido acid 13 was developed. Unfortunately, reacting ethyl

• product 16 albeit in only moderate yield (Scheme 3). By modification of the coupling partners a more defined dipolar [3 + 2] cycloaddition between N,3-diphenylpropynamide (22) and an in situ generated mesoionic species 21 furnished the desired product 23 regiospecifically [4] (Scheme 4). A further

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• isoxazole (7a), 5-methylisoxazole (7b), 3,5-dimethylisoxazole (7d) and 3,4,5-trimethylisoxazole (7e) were synthesized by reaction of the corresponding carbonyl compounds with hydroxylamine, while 3-methylisoxazole (7c) was obtained by the [3 + 2]-cycloaddition of acrylonitrile with the trimethylsilylester

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• , diastereoselective sequence of two [3 + 2] cycloaddition reactions promoted by triflic acid where the large 1,3-diol protecting group – the 1,1,3,3-tetraisopropoxydisiloxanylidene group (TIPDS) – plays a crucial role in facial discrimination. Results and Discussion Our approach to the preparation of enantiomerically

• ) HF·pyridine, THF, 0 °C to rt, 1 h. Substrate-controlled double [3 + 2] cycloaddition. Supporting Information Supporting Information File 184: Experimental procedures, 1H and 13C NMR spectra. Acknowledgments Funding provided by the National Science Foundation (CHE-0848856) is gratefully acknowledged. H.M. is

A surprising new route to 4-nitro-3-phenylisoxazole

• Henning Hopf,
• Aboul-fetouh E. Mourad and
• Peter G. Jones

Beilstein J. Org. Chem. 2010, 6, No. 68, doi:10.3762/bjoc.6.68

• obtained in 40% yield. Keywords: cinnamyl alcohol; furoxan derivatives; isoxazole derivatives; X-ray diffraction; Introduction The isoxazole ring system, which can be easily obtained by [3 + 2] cycloaddition of nitric oxides to alkynes, is of interest since it forms a part of various biodynamic agents

Bioorthogonal metabolic glycoengineering of human larynx carcinoma (HEp-2) cells targeting sialic acid

• Arne Homann,
• Riaz-ul Qamar,
• Sevnur Serim,
• Petra Dersch and
• Jürgen Seibel

Beilstein J. Org. Chem. 2010, 6, No. 24, doi:10.3762/bjoc.6.24

• ), followed by N-acylation with the activated ester 7 led to the alkyne 8 in a yield of 75% based on D-arabinose. A [3+2] cycloaddition reaction between N-tert-butyl nitrone 9 and 8 and subsequent base-catalyzed ring-opening and hydrolysis afforded N-(1-oxohex-5-ynyl)neuraminic acid (Neu5Hex, 3) in 38% yield