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

• catalyst when products were obtained with excellent enantioselectivity (92% ee) (Scheme 46). 2.3 [3 + 2] Cycloaddition reactions In a [3 + 2] cycloaddition reaction, a three atoms dipolar moiety (1,3-dipole) adds across two atoms of an alkene or alkyne (1,3-dipolarophile) (Scheme 47). It is also known as

• -donors on the catalytic activity of NHC–Cu(I) complexes for azide–alkyne [3 + 2] cycloaddition reactions [67]. They determined binding constants of four NHC–CuCl complexes with two N-donors, which revealed that addition of phenanthroline to the NHC–CuCl enhanced the catalytic activity manifold. In fact

• explored the application of a thiazolylidene-based Cu(I) complex as catalyst for [3 + 2] cycloaddition reactions. They prepared an ethylene-linked bisthiazol-2-ylidene dicopper(I) complex 136 which showed high catalytic activity (Scheme 53). The activity increased upon addition of acetic acid, particularly

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• cycloaddition reactions that occur without transition metal catalysts, the unexpected initiation of single electron transfer (SET) processes or photochemical transformations, and even proton transfers that appear to defy pKa limitations. The reaction pathways followed by iodonium ylides and Lewis basic reaction

• was presumed to play a central role in these metal-free processes. Various cycloaddition reactions of iodonium ylides that were typically associated with metallocarbene-mediated processes were also operative in the absence of catalysts. The mild reaction conditions precluded researchers from proposing

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• ; isoquinolino[1,2-f][1,6]naphthyridine; Introduction Among various well-known cycloaddition reactions such as the 1,3-dipolar cycloaddition reaction, Diels–Alder reaction, and the Povarov reaction, the cycloaddition reaction of Huisgen 1,4-dipoles with activated alkenes received increasing attention [1][2][3

• act as activated alkene to take part in various cycloaddition reactions [35][36][37][38][39][40]. For example, Lavilla and co-workers developed a Sc(OTf)3-catalyzed three-component reaction of 5,6-unsubstituted 1,4-dihydropyridines, arylamines and ethyl glyoxylate for the preparation of various pyrido

• , 1040, 914, 854, 769, 704 cm−1; HRESIMS (m/z): [M + Na]+ calcd for C29H30NaN2O8, 557.1894; found, 557.1891. Single crystal structure of the compound 4k. Single crystal structure of compound 5a. Single crystal structure of compound 6f. Various cycloaddition reactions of 5,6-unsymmetric 1,4

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• -benzothiazol-2-yl(diazo)acetates (Scheme 1, entry 3) [12], dearomative [3 + 2] cycloaddition reactions of benzothiazoles with cyclopropanes (Scheme 1, entry 4) [13][14][15], multicomponent reactions (MCRs) of benzothiazoles, isocyanides and 2-methylidenemalonates (Scheme 1, entry 5) [16], 1,3-dipolar

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• target diazo reagent 5, which contains both a trifluoromethyl and a difluoromethylphosphonate moiety, was isolated as a stable, non-volatile liquid (Scheme 2). To highlight the synthetic utility of the novel carbene precursor 5, subsequent [2 + 1] cycloaddition reactions with selected terminal aromatic

• diastereoisomer adopts trans configuration (Figure 1). Furthermore, terminal aliphatic alkenes as well as N-Boc-allylamine were subjected to [2 + 1] cycloaddition reactions with the carbene precursor 5. The results are summarized in Scheme 4. As observed, the procedure was successful with a series of terminal

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• ; Introduction Transannular cycloaddition reactions (TCRs) are useful for the synthesis of complex natural products and other biologically active compounds with high efficiency and stereoselectivity [1][2][3][4]. There are several different ways in which TCRs can occur, depending on the nature of the starting

• and co-workers demonstrated for transannular Diels–Alder cycloaddition reactions of symmetrically tethered large systems (10–18-membered rings) [29]. In this context, we have recently reported the transannular enantioselective (3 + 2) cycloaddition of cycloalkenone hydrazones under Brønsted acid

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• cation in (3 + 2) cycloadditions: 5,6-dihydro-1,4-dithiin-2-methanol as a stabilized allyl cation Allyl cations are versatile electrophiles for the allylation of various nucleophiles, but can also act as C3-π-systems in a range of cycloaddition reactions (Scheme 13) [84][85][86][87][88]. When combined

• with dienes, a swift (4 + 3) cycloaddition can happen, which is isoelectronic to a Diels–Alder reaction, and amounts to a homo-Diels–Alder reaction (Scheme 13a) [89][90]. Cycloaddition reactions of ‘naked’ unsubstituted allyl cations are usually not synthetically useful, as they lead to a mixture of

• untapped potential in this area of research, and expect the utility of these building blocks to grow in the coming years. In particular, the recently established options to elaborate and functionalize 1,4-dithianes using mild transition-metal-catalyzed couplings, and their use in cycloaddition reactions

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• on the success of the catalytic aza-Nazarov reaction. Keywords: α-methylene-γ-lactam; aza-Nazarov reaction; β-silicon effect; heterocycles; intramolecular cyclization; Introduction The rapid construction of aliphatic heterocycles from acyclic building blocks via cyclization or cycloaddition

• reactions constitutes one of the main pillars of organic synthesis [1]. In this respect, the all-carbon Nazarov cyclization of divinyl ketones represents a direct method for the synthesis of five-membered carbocycles [2][3][4][5][6][7][8][9]. Variants of the Nazarov cyclization with substrates bearing one

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• , such as aldol reactions, Michael reactions, cycloaddition reactions, etc. Organophotoredox catalysis has emerged recently as another important catalysis type which has gained much attention and has been quite well-reviewed. At the same time, there are a significant number of other processes, especially

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• the past years are discussed. This review contains cycloaddition reactions, nucleophilic halogenation reactions, metal-free coupling reactions, formation of N-heterocyclic carbenes, and multicomponent reactions, mainly three-component reactions. The mentioned methodologies have been performed by

• more research using imidazole N-oxides as precursors to make this research field flourishing in near future. Review Cycloaddition reactions In 2020, Anton V. Kutasevich et al. unfolded a very interesting deoxygenative reaction procedure where 2-unsubstituted imidazole N-oxides reacted with ethyl

• of ethyl 2-cyano-2-(1,3-dihydro-2H-imidazole-2-ylidene)acetate derivatives via [3 + 2] cycloaddition reactions. C–H/C–Li coupling reaction of 2H-imidazole 1-oxides with pentafluorophenyllithium. Transition-metal-free coupling reaction of 2H-imidazole 1-oxides with polyphenols. Reaction conditions: 1

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• compounds to molecules containing an enone fragment. Cycloaddition reactions involving diazo and enone moieties are usually carried out using transition-metal catalysis [18][19][20], with catalyst-free reactions being carried out only with the participation of reactive unsubstituted diazomethane [21][22][23

• formal [4 + 1] cycloaddition (Scheme 1). Results and Discussion FPDs are highly reactive compounds [25][26] containing an highly electrophilic enone fragment which facilitates the course of cycloaddition and nucleophilic addition reactions. In recent years, some types of cycloaddition reactions were

• investigated for FPDs: the [4 + 2] cycloaddition with alkenes resulting in pyran-annulated products [27][28][29][30][31][32][33][34] and the [3 + 2] cycloaddition with nitrones resulting in isoxazole-annulated products [35][36][37] (Scheme 2). However, formal [4 + 1] cycloaddition reactions for FPDs remain to

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• advantages over the related enol silyl ethers [24][25]: they are more stable towards acidic conditions, their electronic character contributes to high regioselectivity in cycloaddition reactions, and they can be converted to many other functions, including their hydrolysis to ketones [26]. In the other hand

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• ]+ calcd for C39H39NaN3O12, 764.2431; found, 764.2413. Single crystal structure of compound 3k. Single crystal structure of compound 4a. Single crystal structure of compound 4c. Single crystal structure of compound 5. Representative cycloaddition reactions of phenacylmalononitriles. Proposed reaction

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• cycloadducts in moderate to good yields with high diastereofacial selectivity. Moreover, several unstable 1,2-disubstituted cyclopropenes were successfully trapped by the stable 1,3-dipole under mild conditions. The mechanism of the cycloaddition reactions of cyclopropenes with PRP has been thoroughly studied

• using density functional theory (DFT) methods at the M11/cc-pVDZ level of theory. The cycloaddition reactions have been found to be HOMOcyclopropene–LUMOylide controlled while the transition-state energies for the reaction of 3-methyl-3-phenylcyclopropene with PRP are fully consistent with the

• [15]. In our recent studies, great attention was paid to developing methods for the synthesis of spiro[3-azabicyclo[3.1.0]hexanes] based on 1,3-dipolar cycloaddition reactions involving azomethine ylides and cyclopropene dipolarophiles, and also the in vitro activity of some synthesized compounds has

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• compounds (aldehydes and ketones) enable to obtain the products of formal [5 + 2] cycloaddition reactions ‒ 2-benzazepines [8] and 2-benzoxepines [9][10]. When studying the Rh(II)-catalyzed reaction of DAS with ketones [10], we attempted to involve poorly reactive fluorenone in the reaction. To our surprise

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• polarity on the keto–enol equilibrium of the 1,3-diketones, which influences the results of the [3 + 2] cycloaddition reactions under mild basic conditions, via nuclear magnetic resonance (NMR) spectroscopy. The 1H NMR spectra of 1-phenyl-1,3-butanedione (2a) in CDCl3 and in methanol-d4 indicated that 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

• . Review Cycloaddition/addition Cycloaddition reactions have long been applied to molecular container-mediated enzyme-mimicking transformations [27][31][32][33], and the Fujita group has done pioneering research works in this direction [27][34]. In 2006, the authors reported unique Diels–Alder reactions of

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• cycloaddition reactions and also serves as a precursor for the generation of important functional groups like amines, aldehydes, ketones and carboxylic acids. Even though the nitrile functional group is prevalent in the transformation into different functional groups, the synthetic approaches that incorporate

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• ], rhodium-mediated alkyne [2 + 2 + 2] cycloaddition reactions [3], and the palladium-catalysed aerobic domino Suzuki coupling/Michael addition reaction [4]. The most attractive and common strategies to phenanthridines rely on intramolecular cyclizations of various ortho-functionalized biaryl precursors

(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

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• substituents on the benzaldeydes 169 [72]. Cycloaddition reactions In 2014, Gao, Li, and their co-workers published a facile strategy to synthesize polysubstituted aromatic compounds from the reaction of quinones or maleimides with β-enamino esters (Scheme 39) [73]. They synthesized anthraquinone derivatives

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

• ] and batteries [174]. Due to its accessibility, it is well explored in catalysis for many fields, such as cycloaddition reactions [175], polymerization [176], and C–C cross-coupling methods [177]. Several biologically active compounds have been obtained through cobalt catalysis [178][179][180

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

• decrease in the yield [47]. Some research groups have utilized strain-promoted azide–alkyne cycloaddition reactions (SPAAC) on side chains to afford polymer-based prodrugs. Generally, a range of key strained cyclooctyne derivatives 52 could be reacted with aliphatic azides 51 via this strategy to give

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• fluorine-containing organic molecules combined with the 1,4-quinone moiety can be considered as a challenging problem of current organic synthesis. Thus, the main goal of the present study was to check the course of [3 + 2]-cycloaddition reactions of electron-deficient CF3-substituted nitrile imines 7 with