Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• underwent a [4 + 2] cycloaddition reaction (reaction 1 in Scheme 1) [69][70][71][72][73][74]. This metal-catalyzed one-pot reaction not only combined the advantages of a traditional Diels–Alder reaction and the recently developed multicomponent reactions, but also meets the goal of green and sustainable

• cycloaddition between the indole-based ortho-quinodimethanes (o-QDMs, A) and dienophiles affords the final spiro compounds 1, 2, 4 and 5 as major isomers through an endo-transition state. Due to the different polarity, 3-phenacylideneoxindole and isatylidene malononitrile resulted in regioisomeric spiro

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

• 1,3-dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to the stable azomethine ylide – protonated form of Ruhemann's purple (PRP) has been developed. Both 3-substituted and 3,3-disubstituted cyclopropenes reacted with PRP, affording the corresponding bis-spirocyclic 3-azabicyclo[3.1.0]hexane

• 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

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• ; cycloaddition; debromination; Diels−Alder reaction; mechanochemistry; Introduction The complementarity of reaction conditions [1][2][3] where the reaction takes place under some, but not under other conditions, or where a chemical reaction proceeds in a different way or mechanism is a useful feature in

• envisaged that the absence of solvent under mechanochemical conditions should prevent the formation of products from tetrahydrofuran and therefore allow cycloaddition to take place. Results and Discussion Reaction optimization Anthracene addition to dibromide 10 (Scheme 1) was used as the model reaction

• could be also obtained by cycloaddition parity reversal principle [16][36], employing norbornene dibromide 11 and furan (18). Ball milling reaction without THF (neat grinding) provided 22 as the major product, together with a minor amount of dehalogenated product 40 (Scheme 2). When THF was added for

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• processes. To evaluate the scope of the disclosed reaction a set of isoxazoles 1 was prepared using approaches shown in the Scheme 3 and Scheme 4. Isoxazoles 11a–f were prepared by cycloaddition of nitrile oxides, generated from N-hydroxyimidoyl chlorides 7a–f, to propargyl halides [29], followed by the

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

• reactions (anthracene (33) and maleic anhydride (34) to the cycloaddition adduct 35 and chromene carbaldehyde 36 and enol ether 37 to the diastereomeric pyrano-chromenes 38), Alder-En reactions (oxomalonate diethyl ester (39) and β-pinene (40) to give the α-pinene derivative 41), and the thermal

• coupled with in situ generation of the azide from the corresponding bromide. The 1,2,3-triazoles are formed in up to 99% yield and in less than 10 minutes residence time, which includes azide formation prior to the cycloaddition step. Interestingly, this process could not be successfully repeated under

• conventional batch conditions. Organ's findings [49] suggest that the inductive heating technique creates local hot spots, either on the copper surface due to skin depth effects or alternatively in copper nanoparticles released into solution, likely leading to a dramatic acceleration of the cycloaddition

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

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

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• [cyclohexane-1,3'-indoline] 3a albeit with low yields (entries 4–6 in Table 1). The spiro[cyclohexane-1,3'-indoline] 3a was clearly produced by a tri(n-butyl)phosphine-catalyzed formal [4 + 2] cycloaddition reaction. This result showed that tri(n-butyl)phosphine has a higher nucleophilic catalytic ability than

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

• other hand, their specific geometry enables intriguing transformations with simultaneous involvement of the diazo function and the benzylidene fragment. DAS were first described in 2020 and were involved in a [2 + 1] cycloaddition to aldehydes to give oxiranes [1]. Later on, we developed a convenient

• 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

• ortho-methyl substituent in the benzylidene fragment. In this case, along with conventional reaction products ‒ dimer 2r and indene 3r, unexpectedly the cyclobutane 5, a product of the formal [2 + 2] cycloaddition, was isolated in low yield (Scheme 1); its structure was confirmed by single-crystal X-ray

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• ][10][11][12][13][14]. Among the known synthetic methodologies, the domino cycloaddition reaction of benzimidazolium salts with two molecules of 2-(2-oxoindolin-3-ylidene)acetates provided as an important tool for the construction of dispirooxindoles [15]. In particular, most of the dispirooxindole

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

• Agriculture, Agricultural Research Service, University of Mississippi, Mississippi 38677, USA 10.3762/bjoc.18.47 Abstract Herein we report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and

• 1,3-diketones, β-ketoesters, or β-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1–2

• prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• involved in various transformations including homo- and cross-coupling [1][2][3][4][5][6][7], addition [1][8][9], cycloaddition [1][10][11] and other reactions. Of particular synthetic value is the addition to the triple bond of bromoacetylenes to provide vinyl adducts, which can undergo numerous

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• -LED light [111]. Under these conditions, menadione (10) and terminal alkynes 66 underwent a [2 + 2] cycloaddition reaction generating compounds containing cyclobutene rings (67a–c), that are important precursors in natural products syntheses. It is important to note that the choice of the blue-LED

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• recently gained considerable attention because of its ability to store light-energy by the photo-induced intramolecular [2 + 2] cycloaddition to the metastable quadricyclane [1][2][3][4][5][6][7]. The latter may be transformed back to the starting norbornadiene in an exothermic process upon heating or

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• replacement of organic solvents. The melts are stable against air and have very low vapor pressures resembling the properties of ionic liquids. In addition, the polarity of these melts is very high [33]. Recently, we have explored several organic transformations such as coupling reaction, cycloaddition

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• phosphonium selenide catalysts which showed catalytic activity in assembly reactions [41], Michael addition reactions [41], Rauhut–Currier reactions [42], cyanosilylation reactions [43], and cycloaddition of vinylindoles through chalcogen–π bonding catalysis [44]. Our previous works demonstrated that Se···O

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

• containers. The emphasis is on those reactions that give different product distributions on the potential reactive sites inside the containers than they do outside, free in solution. Specific cases include site-selective cycloaddition and addition of arenes, reduction of epoxides, α,β-unsaturated aldehydes

• , that is, selective reactions that take place at one specific potential reactive site out of the similar others, in this review. In the following part, the literature reports will be mainly divided according to the reaction types, namely cycloaddition/addition, reduction, oxidation, and substitution

• . 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

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• 2021, Deng et al. showcased an unprecedented iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols 22 with α-imino esters 23 as azomethine ylide precursors to afford azepino[3,4,5-cd]indoles 24 in good yields and with complete regioselectivity and generally excellent

• cyclization leading to the formation of polycyclic azepino[5,4,3-cd]indoles. Synthesis of azepino[3,4,5-cd]indoles via iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides. Aldimine condensation/1,6-hydride transfer/Mannich-type cyclization cascade of

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• disclosed important discoveries with proline and imidazolidinones as ample chiral catalysts for aldol [7][8], Diels–Alder [9], dipolar cycloaddition [10], and Mannich reactions [11]. The organic chemistry community this time took a tremendous interest in this concept, which led to many valuable developments

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• sialic acid derivatives in good yields and high purity via copper-catalysed azide–alkyne cycloaddition (CuAAC, click chemistry) and evaluated their activity towards TcTS and neuraminidase. Surprisingly, the compounds showed practically no TcTS inhibition, whereas ca. 70% inhibition was observed for

• ) has also been introduced at C-2 of α-triazole-linked sialic acid derivatives modified at C-9 as ligands for the transmembrane glycoprotein CD22 [21]. In this sense, we have synthesised a small series of 1,2,3-triazole-linked sialic acid derivatives via copper-catalysed azide–alkyne cycloaddition

• broad range of substrates, solvents, and reaction conditions; all these parameters have to be carefully planned to avoid low yields or even no product formation, as previously described for compound 1 [20]. Amongst the vast number of reported procedures, the 1,3-dipolar cycloaddition was performed with

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• -oxazoles are: the 1,3-dipolar cycloaddition of alkenes and alkynes with nitrile oxides, and the reaction of a three-carbon atom component, such as a α,β-unsaturated ketone or a 1,3-diketone with hydroxylamine hydrochloride [33]. Recently, Rosa et al. reported a useful procedure for the synthesis of various

• regioisomeric 1,2-oxazole derivatives. Accordingly, the synthetic route starts from the condensation of 1,3-diketones with N,N-dimethylformamide dimethylacetal to form β-enamino ketoester. The latter undergoes a subsequent cycloaddition reaction with hydroxylamine to form regioisomerically substituted 1,2

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• . Results and Discussion Initially, we focused on the synthesis of β-lactam 2, which was prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cis,cis-1,3-cyclooctadiene, as described in the literature [26]. β-Lactam 2 was transformed into cis-amino ester 3 by cleavage of the lactam ring with

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• construction of bispirobarbiturates [30][31]. In 2019, for example, An and co-workers reported an asymmetric Michael/Mannich [3 + 2] cycloaddition reaction between N-(2,2,2-trifluoroethyl)isatin ketimines and barbiturate-based olefins (Scheme 1a) [32]. Based on the current knowledge, the construction of

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

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• -dipolar cycloaddition [16][21][22], were submitted to the reaction with benzoyl isothiocyanate in refluxing acetonitrile to obtain compounds L1, L2 and L3 in good yields [16][21]. Due to the very low biological activity of these ligands by themselves, the chelation with nickel(II) and palladium(II) was

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• well as by Sm(OTf)3-catalyzed stereoselective [3 + 2] cycloaddition of bis-silyldienediolate and imines, in turn synthesized from anthranylamides and benzaldehydes [32]. A promising approach to the synthesis of 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one derivatives substituted at the pyrrolidine

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