Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• gem-difluoroalkenes with organic azides in morpholine as a solvent to construct fully decorated morpholine-substituted 1,2,3-triazoles. Mechanistic studies revealed the formation of an addition–elimination intermediate of morpholine and gem-difluoroalkenes prior to the triazolization reaction via two

• ; gem-difluoroalkenes; organic azides; Introduction gem-Difluoroalkenes and their synthetic preparations soared in the last decade, driven by the high demand for carbonyl mimics in medicinal chemistry and drug discovery [1]. Although a wide array of functionalization strategies for gem-difluoroalkenes

• reactions with azoles and amines (Figure 1B) are also well-precedented [10]. Herein, we address a critical gap in the literature and report the discovery of a cycloaddition of gem-difluoroalkenes and organic azides mediated by a base and with morpholine as a solvent. The cycloaddition adducts, 1,4,5

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• the Nobel Prize in 2022 to M. Meldal, K. B. Sharpless and C. R. Bertozzi did not come as a surprise. In most cases the (3 + 2) cycloadditions were performed with isolated (and purified) organic azides, but it was early found that one-pot processes generating the potentially hazardous azides [22] in

• nucleophilic substitutions employing sodium azide and organic substrates with potential leaving groups have been reported. The resulting organic azides were trapped in situ by a suitable alkyne to give the 1,2,3-triazoles [26][27][28][29][30][31][32][33][34][35][36]. Fairly recent review articles summarize

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• ) azide complex, reducing the iron catalyst back to the starting Fe(II) state. Organic azides can be formed in moderate to high enantioselectivity using this approach; however, the scope is largely limited to benzylic products, a result in line with Groves’ finding that benzylic acid substrates perform

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• operationally simple fluorination strategy suitable for bioactive structural motifs. Manganese-catalyzed late-stage C–H azidation In organic synthesis, organic azides are of considerable significance in the fields of medicinal chemistry, chemical biology, and nanotechnology as they can participate in elegant

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• environmental catalysis area. A metal-free protocol has been developed for the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles 3 from the reaction between α-bromo-β-alkylacroleins and α-bromo-β-phenylacroleins 1 and organic azides 2 in chloroform at room temperature (Scheme 2). A low to moderate yield of

• 48 with organic azides was studied by Smirnov et al. The alkynes 48 were subjected to the action of MeMgCl in THF and then, the desired aryl azides were added into the solution, followed by the addition of N-halosuccinimide to give chloro-, bromo-, and iodotriazoles 50 (Scheme 17) [47]. It was found

• found to be efficient for a practical pathway to 5‐alkynyl-1,2,3-triazoles 69 from organic azides 67, alkynes 66, and 1-bromoalkynes 68. To test the scope of this reaction, a number of alkyl- and (hetero)aryl-substituted alkynes as well as (alkyl)aryl azides have been used in this reaction, affording 5

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• could generate some risks, due to the explosive nature of organic azides, and possible overpressure issues caused by nitrogen generation at high temperatures. Consequently, scalability and control of this processes represents a real challenge. The exploitation of microfluidic technologies has therefore

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

• two-component or three-component “click” reactions. In the two-component reaction, acetylene compounds and organic azides were stirred in dimethylformamide or in a mixture of t-BuOH/H2O, 3:1, v/v as the solvent using diethylisopropylamine and SiO2–Cu. In the three-component example, acetylene species

• nitride-supported copper nanoparticles was disclosed by Islam and co-workers (Scheme 18) [79][80]. The nanocatalyst 87 was successfully used as a high-performance photoreactor promoting “click” reactions of alkynes with organic azides under light irradiation in the absence of basic condition. In the first

• laponite® discs was to prevent their aggregation. Moreover, the catalytic activity of the nanocomposite 136 was explored in 1,3-dipolar cycloadditions of alkynes with in situ-generated organic azides. The reactions proceeded well in an aqueous medium at 70 °C with 0.004 g of the catalyst (Scheme 30). In

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• from alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes is reported. The alkyl carboxylic acids is for the first time being used as the alkyl azide precursors in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ

• ], derived from the Huisgen’s 1,3-dipolar cycloaddition of azides and alkynes [22], has conceivably emerged as the premier example of click chemistry. Generally, organic azides are used as the azido source in most of the CuAAC reactions (Scheme 1a) [23]. However, the organic azides with low molecular weight

• are considered to be unstable moieties that can decompose spontaneously, with which the reactions are difficult or dangerous to handle [16]. Thus, a one-pot two-step process for the in situ generation of organic azides is highly required. A frequently used method to in situ generate organic azides is

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• intermediate 3-nitro-2H-chromenes with organic azides in a one-pot two-step sequence. The triazolochromenes were formed with complete regioselectivity and new biologically relevant structures were synthesized via extension of the developed procedure and via postfunctionalization. The mechanochemical synthesis

• nitroacetate and organic azides, in which the synthesis of both triazolocoumarin regioisomers was accomplished [33]. Interestingly, the expected regioisomer was not observed in the case of the in situ formed 3-nitrocoumarins. Hence, in our continued exploration towards novel multicomponent reactions for the

• assembly of triazole-fused (hetero)cycles [24][33][34][35][36][37][38][39][40][41][42], we opted to develop a new one-pot two-step three-component reaction starting from salicylaldehydes, nitroalkenes and organic azides, without isolation of the intermediate 3-nitrochromenes, in a regioselective manner and

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• (CuAAC) reaction [28]. An alternative way is the functionalization of calix[4]arenes by terminal alkynyl groups. However, in this case further transformations by CuAAC reactions are limited mainly due to the fact that low molecular weight organic azides, especially containing less than 3 carbon atoms are

[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

• , in deuteric solvent hydrolyzed to give 3-deutero pyrazole. However, Fokin et al. has recently [123] revealed that monomeric copper acetylide complexes are not reactive toward organic azides in analogous copper-catalyzed alkyne–azide cycloaddition (CuAAC) and the catalysis by an external Cu(I) salt is

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• carbonyl compounds could successfully generate an enamine or an enolate, and these species react as dipolarophiles with organic azides in organocatalyzed 1,3-dipolar cycloadditions. Our research group has demonstrated β-enamine–azide cycloaddition reactions for the synthesis of selenium-functionalized

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• -deficient alkene led to the intermediate bromoisoxazoline from which, by loss of HBr, a 3,5-disubstituted isoxazole derivative is formed as major regioisomer [34]. Based on the copper(I)-catalyzed click reactions of organic azides with terminal acetylenes [35], different copper(I)-catalyzed synthetic

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• radioactive peaks on a radio-TLC using a radio-TLC scanner (Fuji, BAS2000). [18F]Fluoride was produced using the PET cyclotron Cyclone 18/9 (IBA). [18O]H2O was irradiated with protons (18 MeV, 30 µA) exploiting the 18O(p,n)18F nuclear reaction. CAUTION! Hazard warning for organic azides: risk of explosion by

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• ] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. Keywords

• alkyne, an organic azide, and an H-phosphate in the presence of CuCl2 (10 mol %) and triethylamine (2 equiv) afforded the desired 1,2,3-triazolyl-5-phosphonates [23]. Fokin et al. carried out the reaction of ethynylbismuthane with organic azides using CuOTf (5 mol %) and isolated 5-bismuthano-1,2,3

• been no reports concerning the synthesis of 1,4,5-trisubstituted 5-stibano-1,2,3-triazoles. Herein, we report a novel CuAAC of a simple alkynylstibane, (phenylethynyl)di-p-tolylstibane, with organic azides to form fully substituted 5-organostibano-1,2,3-triazoles. Results and Discussion We initially

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• with different or same azides that require the deprotection of the second reactive site to liberate another alkyne moiety. In 2007, Monkowius et al. reported that the 4,4'-bitriazoles 3 could be synthesized by the two-fold click reaction between 1,3-butadiyne and substituted organic azides [17], and

• low yield when the alkynes or azides were linked directly with a hindered group or an aromatic moiety. In 2012, Xu and co-workers disclosed that both the secondary and primary amine-functionalized polysiloxanes were good ligands for the copper-catalyzed Huisgen reaction of organic azides and alkynes

• -developed, and three main methods are reported: (1) the one-pot CuAAC reactions of the terminal dialkynes with two equiv of the organic azides, providing the corresponding bistriazoles, which is the most popular method for the synthesis of bistriazoles with dialkyne spacers. (2) The second protocol is the

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• . Alternate organic azides were synthesized according to known methods [39][40][41]. 4-Methylbenzyl azide forms triazole 6g in a comparable yield to 6a, but electron-poor 4-(trifluoromethyl)benzyl azide forms triazole 6h in lower yield. Aryl and alkyl azides display parallel reactivity in the formation of

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• organic azides. This kind of decarboxylative CuAAC reaction has not been further investigated. Transition metal-mediated C–H bond activation has become a hot topic in recent years [7][8][9][10][11]. Formally, it requires insertion of a transition metal (usually Pd, Ru, Rh or Ir) across a strong C–H bond

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• onto polymers from a single monomer via convenient ‘click’ chemistry with organic azides. The incorporation of various pendant functional groups could effectively tailor the physicochemical properties of polylactide. The reported synthesis of 1 started from propargyl bromide and ethyl glyoxylate

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• various interesting applications in organic chemistry [9][10][11] as well as material science [12][13][14][15] and drug discovery [16][17][18]. Organic azides in general are popular in recent times because of their use as synthons in Cu(I)-catalyzed “click chemistry” [19]. It is also well known that

Synthesis of chiral N-phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via Co(II)-based metalloradical catalysis

• Jingran Tao,
• Li-Mei Jin and
• X. Peter Zhang

Beilstein J. Org. Chem. 2014, 10, 1282–1289, doi:10.3762/bjoc.10.129

• chiral catalysts, such as Mn, Fe, Cu, Rh, Ru and Co complexes, have been demonstrated as effective catalysts in asymmetric olefin aziridination with various nitrene sources, including the widely used iminoiodanes and their in situ variants, chloramine-T, bromamine-T, tosyloxycarbamates and organic azides

• [9][10][11][12][13][14][15]. Among them, the organic azides have recently emerged as attractive alternative nitrene sources for metal-catalyzed aziridination because of many advantages such as ease of preparation, structural diversity, and N2 gas as the only byproduct [13][14][15]. While sulfonyl and

• aryl azides have been effectively employed for metal-catalyzed asymmetric aziridination [16][17][18][19], the catalytic system based on other types of azides, such as phosphoryl azides, remains underdeveloped. Phosphoryl azides, a family of common organic azides that can be directly synthesized from

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

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

• 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

• emerged [59]. The main driving forces behind these CF methodologies are the safety aspects associated with the handling of azides and the inherent scalability of flow processing. Moreover, when organic azides are formed in situ, operational safety can be further improved [55][57]. We envisioned that it