Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• DHPMs becomes an urgent and paramount task. In connection with this, multicomponent Biginelli and Biginelli-like reactions of aldehydes, urea/thiourea, and enolizable carbonyls revealed as very efficient tools to prepare DHPMs [3]. Although the Biginelli reaction was firstly discovered over a century

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• multicomponent reaction of rare-earth metal amides [28], the reaction of CO2 with propargylamines or aziridines [29][30] and the cycloaddition reaction of epoxides with isocyanates [31][32]. On the other hand, for the synthesis of five-membered cyclic carbonates, the cycloaddition of CO2 to epoxides, the

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• structures of 1,3,5-triazine-2,4-dithione derivatives were characterized by spectroscopic techniques as well as by single crystal X-ray diffraction. Keywords: aldehydes; multicomponent reactions; nitrogen heterocycles; thiourea; triazinethiones; Introduction The construction of nitrogen-containing

• benign methodologies for the generation of structurally diverse triazinethione derivatives is still challenging in organic synthetic chemistry and medicinal chemistry. Multicomponent reactions (MCRs) gained much interest among synthetic organic chemists as well as in combinatorial chemistry and drug

• discovery as versatile tools for the construction of different biologically active compounds by combining three or more starting materials into a single product in one convergent chemical step [19][20][21][22][23]. Among multicomponent reactions, aldehydes have emerged as one of the most useful class of

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• ]isoquinolines. The multicomponent reaction was combined with one-pot reactions to make a synthetic method with good pot, atom and step economy. MeCN was used as a preferable green solvent for the reactions. Keywords: [3 + 2] cycloaddition; Heck reaction; hexahydropyrrolo[2,1-a]isoquinoline; one-pot reactions

• ]isoquinolines and related ring systems [11][12][13][14][15], while medicinal chemists have also been interested in making related compounds for biological screening and drug development [16][17]. Multicomponent reactions (MCRs) have been developed as highly efficient tools for assembling heterocyclic scaffolds

• via sequential 1,3-dipolar cycloaddition, N-allylation, and intramolecular Heck cyclization reactions [50][51][52][53][54] (Scheme 2, K). Both stabilized and non-stabilized azomethine ylides could be used for the initial [3 + 2] cycloaddition. A multicomponent reaction was combined with one-pot

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• 53a–h [48]. The free amino acid 53i was prepared by the same protocol [49] (Scheme 12). 2,5-Difluorophenylalanines with either R or S configuration were synthesized also via the Erlenmeyer azalactone method. The synthesis started with the multicomponent reaction of aldehyde 55, acetylglycine 51a and

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• –84% yields (Scheme 59) [97]. The Ugi-type multicomponent reactions between imines, carboxylic acids, and isocyanides, and Mannich-type reactions between iminium and carbonyl groups have found many applications in organic synthesis [108]. Che’s group employed the methodology of oxidation of an amine

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis (RCM) [67][68]. Starting from 3-cyanocyclohex-2-enone, the authors obtained a versatile intermediate able to provide the appropriate dienyne precursors (A–C, Scheme 4) by multicomponent Grignard addition-alkylations. Through divergent cyclizations involving a chemoselective enyne metathesis

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• has the potential to produce a large number of tetramic acid analogues, which cannot be easily accessed by the classic synthetic methods. Keywords: Dieckmann cyclization; multicomponent reactions; nitrogen heterocycles; one-pot reaction; Ugi reaction; Introduction Nitrogen-containing heterocycles

• medicinal chemistry. Multicomponent reactions (MCRs) [22][23][24] are emerging tools for assembling complex molecules in a rapid and efficient manner. The four-component Ugi reaction followed by a suitable post modification of [25][26] has become a popular research field for diversity-oriented synthesis [27

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• Tianjin University, Fuzhou 350207, China 10.3762/bjoc.16.60 Abstract A diastereo- and enantioselective approach to access chiral CF2-functionalized aziridines from difluorodiazoethyl phenyl sulfone (PhSO2CF2CHN2) and in situ-formed aldimines is described. This multicomponent reaction is enabled by a

• in situ-generated aldimines and our recently developed difluorodiazo reagent PhSO2CF2CHN2 acting as the difluorinated nucleophile [32][33][34][35], providing access to a variety of chiral CF2-fuctionalized aziridines under mild conditions (Scheme 1b). The key to this multicomponent transformation

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

• reactions, Ugi–Smiles reactions, Mizoroki–Heck reactions, aldol reactions, oxidation and dehydration reactions, Mannich reactions, and multicomponent reactions. Because of the mentioned reasons as well as due to the low toxicity of silica nanoparticles, they are often a good option [24]. For this review

• heterogeneous nanocatalyst in “click” reactions for the multicomponent synthesis of triazole products in water with ultrasound irradiation and 0.017 mol % catalyst loading. As such, a series of aryl/alkyl-substituted oxiranes was treated with sodium azide and nonactivated terminal alkynes, giving 1,2,3-triazole

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines. Keywords: 5-amino-1H-pyrazole-4-carbonitrile; 3-amino-1,2,4-triazole; 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines; heterocycle; multicomponent reaction; ultrasonication; Introduction Tetrahydropyrimidines are heterocycles of high pharmacological

• α,β-unsaturated ketones [8][9][10][11] or via their multicomponent analogues. On the other hand, multicomponent reactions (MCRs) directly leading to tetrahydroazolopyrimidine heterocyclic systems have also been published [4][5][16][17][18][19][20][21][22][23][24]. In particular, multicomponent

• via similar MCRs when using salicylic aldehydes, allowing further intermolecular cyclization [23][24]. One of the promising reagents for the synthesis of diverse types of azoloazines by multicomponent and sequential reactions is pyruvic acid, along with its derivatives (Scheme 2). The selectivity of

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

• , Viale Morgagni 85, 50134 Florence, Italy 10.3762/bjoc.16.23 Abstract The Cu-catalyzed multicomponent ketone–amine–alkyne (KA2) reaction was combined with a Pauson–Khand cycloaddition to give access of unprecedented constrained spirocyclic pyrrolocyclopentenone derivatives following a DOS couple-pair

• ; 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

• generate the maximum diversity and complexity from simple starting materials applying divergent synthetic strategies, such as the use of complexity-generating reactions and the build/couple/pair approach [17][18]. The application of multicomponent approaches has proven to be very useful as starting points

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• molecular aggregation in the solid state causes fluorescence quenching [16]. In recent years, we have coined diversity-oriented syntheses of functional chromophores by multicomponent strategies [17][18], opening accesses to substance libraries for systematic studies of structure–property relationships on

• fluorophores [19], in particular on aggregation-induced emissive polar dyes [20]. Conceptually, many of these consecutive multicomponent syntheses rely on transition-metal-catalyzed heterocyclic syntheses [21]. By virtue of catalytic generation of alkynones [22] we have recently disclosed consecutive

• alkynylation–Michael addition–cyclocondensation (AMAC) multicomponent syntheses of α-pyrones [23]. While most α-pyrones neither fluoresce in solution nor in the solid state specific substitution patterns have been identified for fluorophore design for this heterocyclic family. Tominaga and co-workers

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• to the N–O· group. Keywords: domino reactions; EPR; nitroxide; spin relaxation; Introduction Domino reactions have attracted much attention as an approach for the synthesis of complex molecules in a few steps [1]. The utility of multicomponent reactions involving amines, activated olefins and

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• . Keywords: C–H activation; cyclization; isoquinolone; multicomponent reaction; tetrazole; Introduction Pyridones and isoquinolones are relevant heterocyclic scaffolds present in numerous bioactive compounds and natural products [1][2][3][4]. Similarly, molecules containing a tetrazole ring exhibit a wide

• comprises an initial Ugi-azide-4CR followed by a cyclization step, involving some of the reactive functionalities previously installed in the multicomponent process [20][21][22][23][24][25][26]. However, the interplay between the multicomponent synthesis of tetrazoles and metal-catalyzed cyclization

• /pyridone hybrids by means of a reaction sequence comprising an Ugi-azide-4CR and a Rh(III)-catalyzed annulation as key steps (Scheme 1D). Results and Discussion In previous works, our group has described a variety of synthetic approaches that combine the diversity-generating character of multicomponent

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• was assayed with 1,1-diphenyl-2-picrylhydrazyl. Keywords: 5-aminotetrazole; antioxidant activity; 1,3-dicarbonyl compounds; multicomponent synthesis; tetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines and their partially hydrogenated derivatives are known for their interesting

• multicomponent approach to minimize the number of reaction steps according to green chemistry principles as well. Based on our recent research [26][27][28], where water proved to be an effective solvent for the multicomponent synthesis of low-molecular-mass dihydroazolopyrimidines, we decided to use water also

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• inert C–H bonds, alkyl bromides and -triflates: In a 2012 study, Lectka’s group [67] disclosed the catalytic fluorination of a series of aliphatic, benzylic, and allylic substrates with moderate yields. In this case, the authors employed a multicomponent catalytic system, involving Selectfluor, the

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• developed for the synthesis of bile acid-based macrocycles, using macrolactamization, ring-closing metathesis and Ugi-multicomponent macrocyclization. Developing more efficacious and economical methods for the construction of these macrocycles is still in demand due to the disadvantages of the

Multicomponent reactions III

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1974–1975, doi:10.3762/bjoc.15.192

• Thomas J. J. Muller Heinrich-Heine Universität Düsseldorf, Institut für Organische Chemie und Makromolekulare Chemie, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.15.192 Keywords: MCR; multicomponent reactions; In times of steadily increasing relevance of sustainability and

• environmental concern, the concept of multicomponent reactions (MCRs) [1] has become a particularly powerful principle of synthetic design, combining synthetic efficiency with conceptual efficacy. The importance of rapid lead finding and identification has demanded novel ways of synthetic approaches, ultimately

• issue on multicomponent reactions proceeds the previously released issues from 2011 and 2014 [5][6]. Moreover, by the majority of the contributing authors it also becomes a vivid testimony of last year's 7th International Conference on Multicomponent Chemistry and Related Reactions that was held in

Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• threaded through one γ-CD [34]. More recently, Yang and co-workers have described a rotaxane-based host that detects tryptophan which binds to the γ-CD cavity of the rotaxane [35]. As part of our program in the synthesis and application of complex, multicomponent interlocked molecules [37][38][39], we are

• complex, multicomponent rotaxane, catenane and other mechanically interlocked architectures and the potential applications thereof. LC–MS analysis of the reaction mixture of the [n]rotaxane synthesis in the presence of (a) 0.5; (b) 5; (c) 10; (d) 20; and (e) 50 equiv of γ-CD. Partial 1H NMR spectra (500

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• functionalities, have the potential for further elaboration. Keywords: CO; multicomponent reaction; radicals; sulfonyl oxime ethers; xanthogenates; Introduction Multicomponent reactions constitute a powerful and highly efficient tool in organic synthesis to build up intricate compounds from simple molecules in

• a single operation [1][2][3][4][5]. Needless to say, the contribution by radical chemistry is not trivial [5][6][7]. While alkenes and alkynes have served as efficient radical donor/acceptor type C2 synthons in multicomponent radical reactions, CO and isonitriles were shown to react as donor

• /acceptor type C1 synthons [6][7][8][9][10][11][12][13][14][15]. In this context, sulfonyl oxime ethers are powerful acceptors of type C1 synthon [8][16][17], which terminates the multicomponent reaction by a β-scission of RSO2 radicals [18][19][20]. Recently, one of us reported on a three-component radical

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

• Gagandeep Kour Reen Ashok Kumar Pratibha Sharma School of Chemical Sciences, Devi Ahilya University, Indore, (M. P.), India 10.3762/bjoc.15.165 Abstract A comprehensive account of recent advances in the synthesis of imidazopyridines, assisted through transition-metal-catalyzed multicomponent

• development and (ii) for the modifications needed thereof in the R&D sector. Keywords: C–H activation/functionalization; coupling reactions; imidazopyridines; multicomponent reactions; transition metal catalysis; Introduction The structural diversity and biological importance of nitrogen-containing

• organic reactions. In the syntheses of IPs, various forms of copper viz., salts, complexes, MOFs, oxides, and nanoparticles (NPs) have been used as the catalytic system in both multicomponent reactions (MCRs) as well as derivatization methodologies. The role of palladium in synthetic chemistry Pd

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• Andras Gyorgy Nemeth Gyorgy Miklos Keseru Peter Abranyi-Balogh Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Organic Chemistry, Medicinal Chemistry Research Group, 1519 Budapest, POB 286, Hungary 10.3762/bjoc.15.155 Abstract A new multicomponent reaction has

• ; multicomponent reaction; one-pot; thiocarbamate; Introduction O-Thiocarbamates belong to a class of important biologically active molecules, used mainly as fungicides [1][2][3] in agricultural and pharmaceutical fields. In particular, recently antitumor [4], anesthetic [5] and enzyme inhibitory effects were

• yield [70]. In certain cases, sulfur can be trapped by in situ generated carbenes to afford O-thiocarbamates [71][72]. Thioureas and S-thiocarbamates are also accessible through multicomponent reactions starting from isocyanides and sulfur [73][74][75]. The cumbersome synthesis of isothiocyanates from

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• nanoreactor which is a single molecule as catalyst in the earliest steps of the mechanistic pathway (Figure 6). This multicomponent reaction is expected to comprise a series of condensations and subsequent ring-closure cascade reactions (Scheme 3). To demonstrate the mechanistic pathway, dimedone (2), isatin

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• synthesis, notably multicomponent reactions (MCRs). An algorithm has been developed to precisely evaluate even highly complex syntheses with regards to their synthesis efficiency Effsyn as a tool for strict compliance with green chemistry requirements, and for economic progress. The mathematical operations

• are highly suitable for electronic data processing (EDP). This algorithm is also suitable as a basis for fair cost assessment of complex chemical syntheses. Keywords: efficiency; efficiency algorithm; multicomponent; overall yield; synthesis algorithm; synthesis efficiency; synthesis evaluation

• synthesis steps yn (Equation 1). An extreme example for the impact of the overall yield is the tropinone synthesis by Willstätter (yoa = 0.75%) [7][8] compared to the Robinson–Schöpf synthesis (yoa = 90%) [9][10]) using a double Mannich reaction, a multicomponent reaction (MCR) [11][12][13]. The Mannich-3CR