A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• protecting groups [12]. Later, ruthenium complexes-catalyzed alkyne–azide cycloadditions (RuAACs) regioselectively produced the opposite form of the disubstituted triazoles. Thus, a wide range of azides was reacted with diverse nonactivated terminal alkyne substrates using ruthenium complexes to generate

• 100 °C for one day, cooled, and filtered. The material Pd–Cu@rGO (78), as heterogeneous nanocatalyst, was prepared by anchoring Pd(OAc)2 on Cu@rGO in toluene via pyrolysis. The catalyst was highly active in one-pot condensations of alkyl/aryl-substituted triazole heterocycles with cycloadditions and

• , copper nanoparticles-decorated three-dimensional graphene (3D graphene/Cu nanocomposite 87) was reported as a catalyst to perform Huisgen 1,3‐dipolar cycloadditions. Therein, the GO material was mixed with EDA to produce a stable suspension that was transferred to a teflon‐lined autoclave. After heating

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• ; chemoinformatics; Cu-catalysis; cycloadditions; molecular scaffolds; multicomponent reactions; Introduction The screening of small molecule libraries is a well-established approach in early-stage drug discovery to identify hit candidates for the development of drug leads. The application of unconventional

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• ]. Following this invention, many derivatives were produced to find new viable targets. These studies mostly focused on Diels–Alder cycloadditions to create structures that resemble terpenoids readily available from easily accessible and affordable starting materials like myrcene (1). One of the newly found

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• . Tables providing comprehensive directories of fulvene cycloaddition chemistry are provided, including fulvene intramolecular and intermolecular cycloadditions complete with reactant partners and their resulting cyclic adducts, which provide a useful reference source for synthetic chemists working with

• , this can result in a bathochromic shift [2][42]. Consideration of frontier molecular orbital theory allows the electronic nature and general reactivity patterns of fulvenes to be interpreted. Fulvene cycloadditions The multiple cycloaddition pathways observed for fulvenes provides access to a diverse

• fulvene to function as a 6π component in reactions with electron-deficient dienes (Scheme 5b) and fulvenes acting as dipolarophiles have been reported for enantioselective [6 + 3] and [3 + 2] cycloadditions [83][84][105]. In general, reactions with electron-rich alkenes will take place preferentially at

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

• electrophilicity made lanthanides a catalyst of choice. Lanthanum complexes are widely used in synthetic chemistry for cycloadditions, reductions, benzimidazole syntheses, Biginelli reactions, hydrophosphinations of unsaturated substrates, double hydrophosphinylations of unactivated nitriles, Grignard additions, C

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• transient carbocations in reactions taking place in one kinetic step including asynchronous concerted cycloadditions [36] and SN2-type reactions [37]. Moreover, the real existence of transient carbocations – which are not energy minima – predicted computationally has also been recently proven experimentally

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• example for an application in biochemistry, Figure 1 shows a compound with cyclooctyne and maleimide as functional units. It was used as a "turn-on" fluorescence probe for cross-linking proteins [13]. The highly reactive cyclooctyne residue undergoes 1,3-dipolar cycloadditions with organoazides (copper

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• -terminal groups of the peptide and their putative target. This method has been used for the macrocyclization of peptides through, for example, copper-catalyzed azide–alkyne cycloadditions [14], ring-closing olefin metathesis [13] or the formation of an aryl–aryl bond between the side chain of two aromatic

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

• reactivity analogous to aldonitrones, which enables their conversion via [3 + 2]-cycloadditions with dipolarophiles such as activated ethylenes [8][9], activated acetylenes [10][11] or isocyanates [11][12]. The initially formed [3 + 2]-cycloadducts undergo spontaneous secondary conversions leading to re

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• cycloadditions varied from 51% to 76% in the case of pyrrolidinyl purines 7a–f and from 53% to 86% for piperidinyl purines 8a–f (Table 1 and Table 2). To gain an insight into the structure–photophysical properties relationship of the newly obtained structures, various EDG and EWG at the para-position of the

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• diastereoselectivities of 1,3-dipolar cycloadditions which allow to control stereochemistries at C3 and C5 [79][80]. To illustrate this concept the E/Z mixture of nitrone 70 was reacted with acrylamide 71 prepared from (2S)-bornane-10,2-sultam to afford mainly (20:1) the isoxazolidine (3S,5S)-72 easily separable from

• obtained after cleavage of 84 under basic conditions. From pyroglutamic acid In case of low availability of selected stereoisomers of 4-hydroxyprolines asymmetric syntheses of enantiomeric 4-hydroxypyroglutamates have been elaborated employing 1,3-dipolar cycloadditions of homochiral nitrones and acrylates

Unnatural α-amino ethyl esters from diethyl malonate or ethyl β-bromo-α-hydroxyiminocarboxylate

• Eloi P. Coutant,
• Vincent Hervin,
• Glwadys Gagnot,
• Candice Ford,
• Racha Baatallah and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2853–2860, doi:10.3762/bjoc.14.264

• modifications of some of the intermediates – using Suzuki–Miyaura coupling or cycloadditions – before undertaking the oximation step – provided accesses to further α-amino esters. Moreover, other pathways to α-hydroxyimino esters were explored including an attempt to improve the cycloadditions between ethyl β

• -bromo-α-hydroxyiminocarboxylate and various alkylfuranes. Keywords: α-amino ester; α-hydroxyimino ester; [2 + 4] cycloadditions; [2 + 3] cycloadditions; Knoevenagel; nitrosoacrylate; Suzuki–Miyaura; Introduction Our current work on the chemistry of imidazo[1,2-a]pyrazin-3(7H)-one luciferins [1] has

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• [2 + 3] cycloadditions, one leading to a spiroacetal, which led to the undesired ethyl 5-(benzamidomethyl)isoxazole-3-carboxylate. The addition of ethyl nitroacetate on a 5-methylene-4,5-dihydrooxazole using cerium(IV) ammonium nitrate was also explored and the synthesis of other oxazole-bearing α

• reduction of 13 using zinc and hydrochloric acid gave the target α-amino ester 14 in an 85% yield. To avoid the recourse to more rare and/or expensive heterocyclic aldehydes, we also tried synthetic approaches based on [2 + 3] cycloadditions. As depicted in Scheme 3, the carbon dioxide-producing reaction

• , toluene, dimethylformamide, or acetonitrile) [26][27]. As for a related report [28] describing [2 + 3] cycloadditions between chlorooxime 26 and other methylene-bearing compounds, its reaction with compound 25 gave the spiroacetal 27. However, in the present case this cycloadduct was only detectable by 1H

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• ][30][31][32], for example, has served enormously to the advances in both the preparation and application of 1,2,3-triazoles. In addition, the discovery of other metal-catalyzed alkyne–azide cycloadditions (MAAC) providing 1,2,3-triazoles with diverse substitution patterns triggers the continuous

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• complex helps the CBAAC by avoiding any cycloadditions outside of the CB[6] cavity and that CBAAC can be an efficient strategy for catenane synthesis. Cat-1 and its interlocked nature were further characterized by MS2, 1H and 13C NMR spectroscopy. The PF6− salt of Cat-1 was isolated in 69% yield as a

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• regioselective manner [16][20]. In cycloaddition chemistry, 1,4-quinones are applied widely both as dipolarophiles and dienophiles. In the case of [3 + 2] cycloadditions, reactions can occur chemoselectively with either the C=O or the C=C unit [21][22][23]. On the other hand, reactions with diverse 1,3-dienes

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• examples found for [3 + 2]-cycloadditions between sydnones and symmetrical non-cyclic alkynes including conditions used for the synthesis, are presented in Table 1. Extraordinarily good dipolarophiles – e.g., cycloalkynes – containing a very reactive “bent” triple bond such as in bicyclo[6.1.0]non-4-yne-9

• of the stable pyrazole ring. Both reaction steps are also compatible with Woodward–Hoffmann rules, taking into account orbital symmetry considerations [56]. Three types of [3 + 2]-cycloadditions (labelled I–III) are known from the literature [57] each differing in the frontier molecular orbital

• energy gap), for type III (LUMO-controlled) combining a low-lying dipole LUMO and a dipolarophile HOMO where substituent effects are completely opposite. For type II cycloadditions in which two-way interactions between the dipole HOMO and the dipolarophile LUMO or the dipole LUMO and the dipolarophile

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• , azomethine ylide) as the key substrate for 1,3-dipolar cycloadditions, the reaction conditions were very different exemplified by the wide range of reaction times from 0.3 h to 120 h, and the variable yields from 68% to 100% in different solvents. In order to establish the optimal experimental conditions

• yield (64%, Table 2, entry 1). The annulation process did not occur without the catalyst (Table 2, entry 2). Since most of the 1,3-dipolar cycloadditions are known to work best in nonpolar solvents, toluene instead of CH2Cl2 was selected as the reaction solvent. Unfortunately, toluene was not a good

Stepwise radical cation Diels–Alder reaction via multiple pathways

• Ryo Shimizu,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 704–708, doi:10.3762/bjoc.14.59

• been developing oxidative SET-triggered cycloadditions of enol ethers by electrocatalysis [26][27][28][29][30][31][32] in lithium perchlorate/nitromethane electrolyte solution [33]. The reactions involve a radical cation chain process and are complete using a catalytic amount of electricity. During the

• effective for this class. Furthermore, the radical cation Diels–Alder reaction of the aryl vinyl ether is found to proceed via multiple unique pathways, including direct and indirect manners. Our findings described herein are beneficial to design novel SET-triggered cycloadditions, which are under

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• luminescence quenching experiments [19]. With such an understanding in hand, radical ion chain processes could be further optimized to realize greener transformations. We have been developing anodic cycloadditions [20][21][22][23][24][25] enabled by lithium perchlorate/nitromethane electrolyte solution [26

• ], some of which were achieved with a catalytic amount of electricity. Such electrocatalytic cycloadditions should involve radical cation chain processes, meaning that the reaction is not only triggered by an oxidative SET at the surface of the electrode but also by an intermolecular SET process in bulk

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• polyheterocycles formed was also described. The [4 + 2] cycloadditions between cyclic imines and o-QMs derived from Mannich bases could also be successfully applied in the syntheses of natural alkaloid-like compounds 47. Osyanin et al. reported the preparation of rutaecarpine and evodiamine, the 14-oxa analogues

• indication that the application of this highly-reactive intermediate has made the modified Mannich reaction to be a hot topic again in organic chemistry. This review presents a wide range of applications including cycloadditions and the synthesis of bifunctional amino- or amidonaphthols that can later be

• intermediate 3. Asymmetric syntheses of triarylmethanes starting from diarylmethylamines. Proposed mechanism for the formation of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyrans 32. Cycloadditions of isoflavonoid-derived o-QMs and various dienophiles. [4 + 2] Cycloaddition reactions between

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• cycloadditions of azomethine ylides with pentafluoro-λ6-sulfanyl-substituted acrylic esters and amides [28]. A couple of years ago, we became interested in SF5-substituted ester enolates as reaction intermediates. Thus, in 2016 we reported a highly anti-selective aldol addition of SF5-substituted acetic ester

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• products under thermal conditions to afford arylamines [22]. Inspired by the pioneering work of Stuart and Wang [12][13], herein we reported the usage of diaryliodonium salts as aryne precursor for Diels–Alder cycloadditions of N-arylpyrroles (Scheme 1d). Results and Discussion We initially started the

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• ], and cycloadditions using nitrile oxides to provide 15 and 16 [7]. In the literature, there are also many examples of the cleavage of the C–O bond of 3-aza-2-oxabicyclic alkenes 1 (Scheme 3). This includes the use of protic acid [8], using metal catalysts such as Pd [9], Fe or Cu [10], In [11

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• (mp 20 °C) with a yield of 66%. The solid compound can be stored for up to 8 months at −15 °C without decomposition (polymerization). Conclusion Isobenzofuran (1) is one of the most reactive dienes in Diels–Alder reactions and other cycloadditions. For practical applications it has been generated and