Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• involves several steps: the 1,3-dipolar cycloaddition of ozone to the double bond to form unstable 1,2,3-trioxolane 164 (so-called molozonide) that is followed by its decomposition to a peroxycarbenium ion and a carbonyl compound (Criegee intermediates). The 1,3-dipolar cycloaddition of the intermediates

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

• formation of these compounds can be rationalized by pathways presented in Scheme 2 [4][22]. 1) Pathway A implies the initial 1,3-dipolar cycloaddition between the diazo compound 2 and the С=S bond of thioketone 1 giving rise to 1,3,4-thiadiazoline 10. The latter is usually an unstable intermediate species

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• but-2-ynedioate and phenyl azide at 100 °C in a sealed tube and suggested that regioisomeric triazoles were formed [1]. However, it was only in the 1960s that Huisgen recognized this type of reaction for its generality, scope and mechanism [2][3][4][5], and coined the term 1,3-dipolar cycloaddition

• a factor of up to 107 in comparison to Huisgen’s uncatalyzed procedure [13][14]. Since Meldal and Sharpless had first reported this copper-catalyzed variant of Huisgen’s 1,3-dipolar cycloaddition, a myriad of protocols employing different catalyst systems has been described. It is essential for the

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• , Universidad del País Vasco, Apdo. 1072, E-20018 San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 10.3762/bjoc.9.280 Abstract The 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(Sa

• : asymmetric catalysis; DFT; 1,3-dipolar cycloaddition; gold catalysis; NICS; NTR; oxazolones; prolines; Introduction The synthesis of α-amino acids employing an α-amino carbonyl template constitutes the most straightforward route to introduce the α-side chain [1]. As a valid example, oxazol-5-(4H)-ones

• electrophilic alkenes have not been exploited. Toste´s group published an efficient 1,3-dipolar cycloaddition (1,3-DC) between alanine, phenylalanine and allylglycine derived azlactones with maleimides and acrylates employing dimetallic (S)-Cy-Segphos(AuOBz)2 complex 1 as a catalyst (2 mol %) in the absence of

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• is the first example of six-armed carbohydrate-substituted triptycenes, which appear as promising candidates for the development of new supramolecular systems with specific properties. Results and Discussion The Huisgen 1,3-dipolar cycloaddition reaction, which represents the key step of click

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• reacted with olefins (such as styrene, allyl derivatives, etc.) through a 1,3-dipolar cycloaddition to give the desired product. Therefore, the development of a straightforward and mild general procedure to access these valuable derivatives remains of great importance. In the present work, we describe a

• unreactive towards trifluoroacetonitrile oxide 4. 1,3-Dipolar cycloaddition reactions have been studied from the theoretical standpoint since the 1970’s onwards [36][37] with an ever-increasing accuracy as computational methods evolved [38]. Assuming that the above-mentioned transformations occur via a

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

• reviewed the synthesis of 1,2,4-oxadiazoles [33]. He pointed out that two general methods dominate the practical preparation (≈95%): (a) The condensation of amidoximes with carboxylic acid derivatives. (b) The dipolar cycloaddition of nitrile oxides to nitriles. The general approach for the synthesis of

• (interplanar angles 22° and 9°). Three of the four NH hydrogens are involved in hydrogen bonds, leading to ribbons of H-bonded rings parallel to the a axis. Following the second route, the 1,3-dipolar cycloaddition, with the purpose of increasing the yield of compound 1, we used p-toluenesulfonic acid (PTSA

• complex as a leaving group, giving rise to the formation of the nitrile oxide. The 1,2,4-oxadiazole moiety is established by the 1,3-dipolar cycloaddition of nitrile oxide to the 4-aminobenzonitrile. However, the Lewis acid might also be involved in the formation of the heterocycle via a Lewis acid

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• . This transformation proceeds via a 1,3-dipolar cycloaddition between the in situ formed azomethinylide 15 and the benzoquinone 16 to directly give 17 (Scheme 1). Spontaneous oxidation of the so-obtained cyclization adduct generates isoindole 18. Isoindoles have also found application as dyes. Pigment

• % overall yield. Two years later, a more concise and efficient access to (±)-nominine (225), featuring a oxidoisoquinolinium-1,3-dipolar cycloaddition and a dienamine-Diels–Alder reaction, was accomplished by Gin (Scheme 31) [178]. Coupling of 235 and 236, both synthesized within three steps from simple

• -dipolar cycloaddition. Carrying out the reaction at 180 °C in tetrahydrofuran provided a separable mixture of pyrrolidine isomers 241 and 242 (1:3.6). The undesired cycloadduct 242 could be equilibrated to 241 due to the reversibility of the reaction. Conversion to the β,γ-cyclohexenone 243 was

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• that when tetrahydroisoquinolines (e.g., 41 and 45) were substituted with a methylene group attached to one or two esters, the initially formed iminium ions were readily converted to azomethine ylides. They subsequently underwent 1,3-dipolar cycloaddition with a range of dipolarophiles to form fused

• loss of a proton. 1,3-Dipolar cycloaddition of 50 with a dipolarophile 46 furnishes fused pyrrolidine 51 that is further oxidized to pyrrole 52. The Zhu group discovered that the use of α-ketoester 53 as a pronucleophile to intercept the iminium ion of 13 triggered a new cascade reaction en route to

• oxidized to nitrone 64. Finally, an intramolecular 1,3-dipolar cycloaddition of 64 furnishes isoxazolidine 55. Tetrahydroisoquinolines are arguably the most exploited amines in visible light photoredox catalysis. However, efforts towards expanding the scope of amines have been recently reported. Li [82

AgOTf-catalyzed one-pot reactions of 2-alkynylbenzaldoximes with α,β-unsaturated carbonyl compounds

• Qiuping Ding,
• Dan Wang,
• Puying Luo,
• Meiling Liu,
• Shouzhi Pu and
• Liyun Zhou

Beilstein J. Org. Chem. 2013, 9, 1949–1956, doi:10.3762/bjoc.9.231

• /Pd-catalyzed direct arylation of 2-alkynylbenzaldoximes [41]. Inspired by the key contributions from the groups of Wu [36][37][38][39] and Deng [40], we envisioned that 1-alkylated isoquinolines could be generated in a one-pot AgOTf-catalyzed cyclization/1,3-dipolar cycloaddition/rearrangement or

• a 1,3-dipolar cycloaddition with α,β-unsaturated carbonyl compound 2 leading to 2,10b-dihydro-1H-isoxazolo[3,2-a]isoquinoline intermediate B [44][45], which may then suffer a rearrangement or fragmentation resulting in compound 3 (Scheme 1) [35][36][38][42]. To demonstrate the feasibility of this

[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

• nitrile ylide formation and the 1,3-dipolar cycloaddition. We initially chose to photolyze methyl 4-(1-azidovinyl)benzoate (1a) in the presence of acrylonitrile (4a) (Table 2). A solution of 1a and 4a in the respective solvent was passed through the photochemical flow-reactor with 5.5 mL volume and a

• presence of a tenfold access of 4a provided the cycloaddition product 5a in 96% yield as a single regioisomer (Table 2, entry 8). Remarkably, after removal of the solvent under reduced pressure it was not necessary to further purify the product. Next the scope of the photo-induced 1,3-dipolar cycloaddition

• 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

The rapid generation of isothiocyanates in flow

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 1613–1619, doi:10.3762/bjoc.9.184

• chemical transformation which typically eliminates the requirements for any conventional work-up or purification of the reaction stream. Keywords: chloroxime; dipolar cycloaddition; flow chemistry; flow synthesis; immobilised reagents; isothiocyanate; nitrile oxide; Introduction Flow based chemical

• ], both reagents causing safety concerns due to the formation of toxic, malodorous and/or extremely corrosive byproducts (Scheme 1a). An underutilised alternative sequence is the 1,3-dipolar cycloaddition reaction between a nitrile oxide and a thiourea compound which initially generates an unstable 1,4,2

• purification of reaction sequences [40][41][42][43][44]. In addition they have been successfully utilised in order to render dipolar cycloaddition reactions involving azomethine ylides [45][46] as well as nitrile oxides [47][48] more practical for generating important heterocyclic scaffolds such as

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• acid derivatives in a simple and efficient continuous-flow procedure is reported. The 1,3-dipolar cycloaddition reactions were performed with copper powder as a readily accessible Cu(I) source. Initially, high reaction rates were achieved under high-pressure/high-temperature conditions. Subsequently

• applications in numerous other areas of modern chemical sciences, such as bioconjugation [13], supramolecular chemistry, [14] and polymer sciences [15]. Probably the most useful and powerful procedure for the synthesis of 1,2,3-triazoles is the Huisgen 1,3-dipolar cycloaddition of organic azides with

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• -broadening in the NMR spectra was found to depend on the presence of substitution next to the inverting nitrogen center. Keywords: DFT calculations; dipolar addition; fluxional behavior; sulfones; VT NMR; Introduction The 1,3-dipolar cycloaddition [1][2][3] represents a powerful methodology for the

• referenced to the carbon resonances of the solvent (CDCl3: δ 77.00). TLC plates were visualized by exposure to KMnO4 stain. Accurate masses were obtained using an orbitrap MS. Infrared spectra were collected using an FT IR spectrometer. General procedure for the dipolar cycloaddition. The vinyl sulfone (0.5

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• Abstract A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide–internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the

• methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields. Keywords: 2-alkynylindoles; azides; 1,3-dipolar cycloaddition; domino reaction

• ; indolodiazepinotriazoles; Introduction The intermolecular Huisgen azide–alkyne 1,3-dipolar cycloaddition reaction [1][2][3][4][5][6] for the synthesis of 1,2,3-triazoles in both aqueous [7][8][9][10] and organic solvents under either metal-catalyzed [11][12][13] or metal-free conditions [14][15][16] has received

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• alternatively pursued a copper-free approach that relied on the oxanorbornadiene strategy of Rutjes [24][25][26][27][28]. This type of specific conjugation most likely proceeds by a 1,3-dipolar cycloaddition/retro-Diels–Alder cascade. By incubating oxanorbornadiene functionalized membranes 7b with cRGD

• ). Absorption maxima of fluorescein were located at 457 nm and 481 nm, which can be ascribed to the presence of two isomeric forms (lacton versus carboxylate) of fluorescein [31]. These measurements clearly revealed the successful covalent functionalization of TPX with fluorescein by 1,3-dipolar cycloaddition

• ) of the TPX membrane with an increased factor for the absorption intensity of about 65 compared to 8c. This remarkable result may be rationalized if one assumes that copper is not ideally distributed during the course of the 1,3-dipolar cycloaddition reaction, as the presence of the heterogeneous TPX

Asymmetric synthesis of γ-chloro-α,β-diamino- and β,γ-aziridino-α-aminoacylpyrrolidines and -piperidines via stereoselective Mannich-type additions of N-(diphenylmethylene)glycinamides across α-chloro-N-sulfinylimines

• Gert Callebaut,
• Sven Mangelinckx,
• Pieter Van der Veken,
• Karl W. Törnroos,
• Koen Augustyns and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2012, 8, 2124–2131, doi:10.3762/bjoc.8.239

• , comparable non-halogenated trans-imidazolidines were already synthesized by 1,3-dipolar cycloaddition of N-benzylidene glycine ester enolates across N-sulfinylaldimines in the presence of a Lewis acid [43]. The trans-stereochemistry of imidazolidine 12b was ensured by the vicinal coupling constant 3JH4-H5

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

• Rutjes [68] as well as Sharpless [69] elegantly devised alternative approaches exploiting 1-haloalkynes [70], we became interested in exploring a single [71][72][73] inexpensive copper catalyst for one-pot reaction sequences comprising a 1,3-dipolar cycloaddition along with an intramolecular C–H bond

• sequential synthesis of 1,4-dihydrochromeno[3,4-d][1,2,3]triazole (4b, Scheme 2). We were delighted to observe that the desired reaction sequence consisting of a copper-catalyzed 1,3-dipolar cycloaddition and an intramolecular C–H bond arylation converted alkyne 1a to the desired product 4b with high

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

• – Huisgen 1,3-dipolar cycloaddition of solid-phase-immobilized azides with terminal alkynes by copper(I) catalysis: An azide-functionalized Wang resin 7 or 9 (1 equiv) was preswollen in dimethylformamide (1.5 mL/100 mg resin) for 2 h at room temperature. The copper(I) catalyst was prepared in situ by using

• steps with water, dimethylformamide, methanol and dichloromethane (each solvent 3 × 2 mL/100 mg resin) were carried out. GP 3 – Huisgen 1,3-dipolar cycloaddition of solid-phase-immobilized azides with terminal or internal alkynes by ruthenium(II) catalysis: The azide functionalized Wang resin (1 equiv

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• (Scheme 3). According to the previously reported protocol [22], Ugi reaction employing allylamine (31) and stepwise installation of a diazoimide group provided 35 in good yield. Upon treatment of 35 with Rh2(OAc)4 in benzene under reflux, 1,3-dipolar cycloaddition of the ylide intermediate with the

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• high yield and purity. Click reactions generally involve a Cu(I)-catalyzed version of the Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides (CuAAC), to regioselectively yield 1,4-disubstituted 1H-1,2,3-triazoles [11][12]. In the meanwhile, this type of click reaction has become very

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• dipolarophiles to yield aryl isoxazolines with the boronate ester function intact and available for subsequent reaction. Keywords: dipolar cycloaddition; heterocycle; nitrile oxide; hypervalent iodine oxidation; pinacol boronic acid esters; Introduction Metal-mediated coupling reactions to form carbon–carbon

• bonds, and 1,3-dipolar cycloaddition reactions to construct five-membered heterocycles are both powerful tools for assembling organic molecules. Used in combination, these tools offer great flexibility for strategies such as diversity-oriented synthesis [1], solution-phase combinatorial libraries [2

• convenient substrate would be the arylboronate nitrile oxide 1, which would undergo 1,3-dipolar cycloaddition to give isoxazolines 2. This latter compound could in turn be coupled with heterocycles or aryl groups to give insecticidal [5] derivatives of type 3 (Scheme 1). The utility of arylboronic acids and

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

• rise to an annelated bicyclic substructure. In contrast, in our case as well as in [29], the olefinic dipolarophile is found as a substituent at a remote ring position of the cyclic carbonyl ylide, such that the intramolecular 1,3-dipolar cycloaddition generates a bridged oxabicyclo[3.2.1]octane

Aldol elaboration of 4,5,6,7-tetrahydroisoxazolo[4,3-c]pyridin-4-ones, masked precursors to acylpyridones

• Raymond C. F. Jones,
• Abdul K. Choudhury,
• James N. Iley,
• Mark E. Light,
• Georgia Loizou and
• Terence A. Pillainayagam

Beilstein J. Org. Chem. 2012, 8, 308–312, doi:10.3762/bjoc.8.33

• genetic techniques, and been shown to involve conversion from an acyltetramic acid by oxidative ring expansion [7][8]. During a programme of synthesis towards metabolites containing the enolised heterocyclic tricarbonyl motif 3 [9][10][11][12][13][14][15][16], we have reported nitrile oxide dipolar

• -cycloaddition strategies to access the isoxazolo[4,3-c]pyridin-4-one 4 as 2nd-generation masked nonpolar scaffolds for the 3-acyl-4-hydroxypyridin-2-one nucleus [12]; our 1st-generation approach had employed the [4,5-c] isomer 5 [13][14][15]. We have recently reported on elaboration of isoxazolopyridone 4 at C

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

• Iain Coldham,
• Adam J. M. Burrell,
• Hélène D. S. Guerrand,
• Luke Watson,
• Nathaniel G. Martin and
• Niall Oram

Beilstein J. Org. Chem. 2012, 8, 107–111, doi:10.3762/bjoc.8.11

• sequence involving condensation to an intermediate imine, then cyclization and formation of an intermediate azomethine ylide and then intramolecular dipolar cycloaddition. The fused tricyclic products are formed with complete or very high stereochemical control. The hydroxymethyl group was converted into

• ; dipolar cycloaddition; heterocycle; tricyclic; Introduction Cascade reaction sequences [1] provide a rapid and efficient means to build complexity in organic chemistry. One such sequence involves a cyclization followed by in situ intramolecular cycloaddition to give three new rings in a single

• transformation [2][3][4][5][6][7][8]. We have been studying the intramolecular dipolar cycloaddition of azomethine ylides in synthesis [9][10][11][12][13][14][15][16] and were able to show that the azomethine ylide could be prepared in situ by a cyclization step [17][18]; for example, by heating the aldehyde 1