Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• + 2] cycloaddition of azides with alkynes as will be discussed later. Jin Zhang et al. used the same base, namely KOt-Bu in the presence of CuCl to obtain the thiazolylidene–Cu(I) complex 20 (Scheme 10) [23]. In 2012, Zhu and co-workers synthesized NHC–CuCl complexes using alkali carbonates (Na2CO3

• yield by reacting [Cu(CH3CN)4]BF4 with 2 equiv of benzimidazolium salt 38 in the presence of NaOt-Bu (Scheme 14) [28]. The catalytic activity of the complex 39 was studied in the [3 + 2] cycloaddition of azides with alkynes [28]. Coyle et al. reported the synthesis of a series of NHC and ADC (acyclic

• which showed that all complexes adopted a slightly distorted linear geometry. Furthermore, abnormal-NHC and triazolylidene-based Cu(I) complexes exhibited an outstanding catalytic property towards the [3 + 2] cycloaddition of alkynes with azides. Recently, we have reported the synthesis of NHC

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

• carbohydrate mimetics, but the reductive cleavage of the 1,2-oxazine rings to aminopyran moieties did not proceed cleanly with these compounds. Keywords: alkynes; azides; copper catalysis; nucleophilic substitution; 1,2-oxazines; Introduction The concept of click reactions [1][2], in particular, the

• ]). Mechanistic aspects of the CuAAC have been studied in detail [16][17]. Whereas the traditional 1,3-dipolar cycloaddition (Huisgen reaction) [18][19][20] of azides and alkynes requires often – but not always – relatively harsh conditions and proceeds with moderate regioselectivity only [21], the copper

• 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

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

• of recent interest, with exciting preliminary decarboxylative azidation results obtained under thermal conditions by Hongli Bao and co-workers [44]. An asymmetric iron (NON) pincer catalyst IV was employed to decarboxylate benzylic peroxyesters and form enantiomerically enriched benzylic azides. An

• ) 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

• azides for a wide range of both activated (benzylic) and unactivated carboxylic acids. Control reactions support the intermediacy of alkyl radicals and the absence of carbocation rearrangements in a variety of probe substrates disfavor the reaction proceeding via RPC. Intriguingly, no additional oxidant

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• protocol is appropriate for both ketosulfonyl reagents and α-sulfonyl-substituted alkyl acetates providing the target quinoline derivatives in good to excellent yields. Keywords: aza-Wittig reaction; azides; cyclocondensation; quinolones; sulfonamides; Introduction The quinoline scaffold has a wide

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• connect a porphyrin with a chromophoric group. Among these, the copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction [1][2] of azides with terminal alkynes is a popular and well established process to link a porphyrin with other moieties via 1,2,3-triazole group [3] (Figure 1). The term “click

• and benzyl azides 150a–c. Furthermore, the metal-porphyrin conjugates 152a–c and 153a,b were obtained in good yields from the corresponding free-base porphyrins 151a–c by the reaction with zinc acetate and copper acetate, respectively. The authors revealed that these compounds can self-assemble into

• ) with azides 169a–c in the presence of CuI and DIPEA in toluene under microwave conditions. Further, three triazole-meso-porphyrins 171a–c were prepared using a slightly modified Adler–Longo procedure. Also, the corresponding zinc derivatives 172a–c of these free-base porphyrins were synthesized in

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• conversion of cholesterol 1 into diene 9, bromide 4, and azides 5 and 6. Manipulations for bromination and azidation of cholesterol. Supporting Information Supporting Information File 75: X-ray crystallography and NMR spectra. Supporting Information File 76: Crystallographic information files for compounds

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• -azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate with Zn/NH4Cl and debenzylation resulted in the target aziridinecyclooctanediol. Keywords: aminocyclitols; aminocyclooctanetriol; azides; aziridines; aziridinecyclooctanediol; Introduction Aziridines are the smallest nitrogen-containing heterocycles

• . This difference is due to the occurrence of dynamic balance when the system is heated. A general and versatile method for the synthesis of azides involves the reaction of a mesylate with sodium azide. Therefore, the dimesylate 8 was first reacted with an excess of sodium azide in DMF at 105 °C to give

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• method to synthesize 1,2-azaphospholidine 2-oxide derivatives 13. Arylphosphinyl azides generate arylphosphinyl nitrenes under photoirradiation. The phosphinyl nitrenes underwent an intramolecular insertion into the ortho C–H bond of the aryl group accompanied with the Curtius-like rearrangement as well

• [24]. Both monomesityl and dimesitylphosphinyl azides 14 generated 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 15 in 31% and 20%, respectively, via an intramolecular nitrene C–H insertion, for dimesitylphosphinyl azide (14b), with 51% yield of phosphonamidate 16 as byproduct. Bis(2,4,6

• ). Synthesis of 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 from N-aryl-2-chloromethylphenyl(methyl)phosphinamides 12. Synthesis of 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides from alkylarylphosphinyl or diarylphosphinyl azides via an intramolecular nitrene C–H insertion. Synthesis of 3

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

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• reactors (Scheme 12, case A). There, it performs a second role by also becoming a source for a copper catalyst, either by being released into solution or by acting as a surface-active species capable of promoting "click" reactions between alkynes and azides [76][77][78][79][80][81]. The process can be

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• )-52/(S)-53 were mixed with the dialkynylated amine 54 to give the pseudorotaxanes based on ammonium–phosphate interactions. Subsequent stoppering with bulky azides 55a/b gave rotaxanes (S)-56a/b and (S)-57a/b in yields of 28–58%. These catalysts differ in the length of the axle (n = 0 or 1, for a or b

• ]. Macrocycle (S)-61, featuring two iodotriazole units, was reacted with bis-iodoalkyne 62 and azides 63a/b in order to establish the mechanical bond in an active metal template approach (using the conformational flexibility of the iodotriazole groups for copper N-ligation). Subsequent N-methylation of the

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , azides, halides and alkenes, oxidation of remote C–H bonds and alkenes, and substitution reactions involving ring-opening cyclization of epoxides, nucleophilic substitution of allylic chlorides, and hydrolysis reactions. The product selectivity is interpreted as the consequence of the space shape and

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• synthesis of chain extended azides 149 and γ-azido chloroalkanes 150 in good yield (Scheme 31) [125]. The electronic nature of the alkene had no clear effect on the reactivity of the system; however, no product was detected when unactivated alkenes like when cyclohexene was used. This strategy was also

• utility of their reaction, the authors studied the one-pot conversion of the vinyl azides to 2H-azirines 161. The carboazidation reaction for the aryl alkynes was completed in a comparable amount of time. A myriad of different functionalized π-systems was tolerated by the reaction, demonstrating its

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• . Intramolecular Schmidt reaction of alkyl azides and ketones, which follows the first pathway in the mechanism, found especially broad application in the synthesis of different lactams [23][24]. Serious drawbacks of the Schmidt reaction for tetrazole synthesis are the need for a large excess of the hazardous

• reported Lewis acid-mediated enone reactions with alkyl azides yielding enaminones [48]. Similarly, as with ketone, reactivity of the enone derivative 4 with HN3 in the presence of BF3⋅OEt2 (Table 2, entry 1) was examined. It was shown that a longer time is needed to achieve conversion, and the yield was

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• [Cu(dap)2Cl] and visible light are necessary for this transformation. In 2013, Ollivier and co-workers [45] successfully applied the same strategy to the allylation of diphenyliodonium 2. In 2017, Liu’s group [46] reported the copper salt-catalyzed cyclization of vinyl azides 3 with ammonium

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• condensation of α-halogenated carbonyl compounds, β-dicarbonyl compounds and amines; and iv) the latest developed multicomponent tandem reactions and transition metal-catalyzed coupling reactions [30][31][32][33][34][35][36][37][38][39]. Recently, substantial achievements have been made using azides as a

• functionalized pyridines and pyrroles. Review Synthesis of pyridines via tandem annulation of 1,3-enynes In 2015, Reddy and co-workers reported the synthesis of substituted pyridines via Lewis acid-mediated aza-annulation of 2-en-4-ynyl azides 1 (Scheme 1) [49]. They discovered that Ag-mediated intramolecular

• annulation of 2-en-4-ynyl azides 1 could provide the corresponding 3,6-disubstituted pyridines 2 in 60–88% yield in the presence of TFA (2.0 equiv). The reaction substrates, 2-en-4-ynyl azides 1, derived from MBH acetates of acetylenic aldehydes, could tolerate various substituted aryl, indolyl, and alkyl

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• cycloaddition reactions via the copper-catalyzed 1,3-dipolar cycloaddition reaction (CuAAC) of the azides 5 and 9 with suitably functionalized acetylenes 6a–j, using sodium ascorbate and copper sulfate in ACN/H2O 2:1 under microwave irradiation were carried out to obtain the 1,4-regioisomers of the final

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

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

• industry. The current review aims to cover a wide literature survey of numerous synthetic strategies. Recent reports (2017–2021) in the field of 1,4,5-trisubstituted 1,2,3-triazoles are emphasized in this current review. Keywords: azides; Click reaction; [3 + 2]‐cycloaddition; fully functionalized 1,2,3

• applications of these five-membered N-heterocycles are the result of both their easy synthetic procedures and ring functionalization [9][31][32]. Typically, 1,2,3-triazole derivatives are prepared via a 1,3-dipolar cycloaddition reaction between azides and alkynes [33]. It is worth noting that the metal

• 1,2,3-triazoles through multicomponent reactions and the relevant mechanistic aspects have been surveyed by Chen, Ren, et al. [27]. The 1,3-dipolar cycloaddition reaction between azides and alkynes is the most efficient pathway for the preparation of disubstituted 1,2,3-triazole derivatives. The copper

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• azides and alkynes [14][15]. However, the formation of the nitrogenated azoles by the classical Huisgen methodology is slow due to its high activation energies and also lack of regiochemical control, in general, leading to a mixture of 1,4- and 1,5-regioisomers of 1,2,3-triazoles. Later, Sharpless and

• alternative approach for the synthesis of such triazole moiety 3a is the [3 + 2] cycloaddition between alkynes and the corresponding azides. However, the major disadvantage of such a strategy is the use of 3-azidoenone which is difficult to handle owing to its explosive nature. Therefore, our method provides

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• modifications were introduced into the DNA backbone using the Staudinger reaction between the 3’,5’-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to