One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• to use 1 mmol of 5a with 10 mol % Pd(OAc)2 and 20 mol % PPh3, 2 equiv of K2CO3 in 3 mL CH3CN at 105 °C for 3 h under N2 atmosphere which afforded product 6a in 70% yield (Table 1, entry 3). The combination of an initial multicomponent reaction with post-condensation reactions in one-pot is a good

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• multicomponent reaction protocol. Keywords: carboamination; diazo chemistry; palladium catalysis; radical-polar crossover; three-component reaction; Introduction Since the discovery of the existence of non-canonical amino acids (AAs) in organisms, such structural motifs have attracted considerable attention

• diverse derivatizations further highlight the practical utility of this MCR protocol. Background (a and b) and proposed carboamination MCR with diazo esters (c). a) Selected bioactive γ- and ε-amino acid derivatives. b) Multicomponent reaction strategies with diazo compounds. c) Our design: a radical MCR

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• formation, essential for the GBB-3CR mechanism. Moderate yields were obtained with the use of 2-aminothiazole derivatives (4yy–aaa). These lower yields did not change using MeOH as a solvent or increasing the amount of HPW used. The use of aliphatic aldehydes in the GBB multicomponent reaction for the

• synthesis of imidazo[1,2-a]pyridines is not as usual, given that Schiff bases from aliphatic aldehydes are found to be less stable and readily polymerize in comparison to stable Schiff bases of aromatic aldehydes. Nonetheless, our protocol for the HPW-catalyzed GBB multicomponent reaction proved to be very

• imidazo[1,2-a]pyridine core [13]. Examples of application of HPW as catalyst in the synthesis of heterocyclic compounds through multicomponent reaction approaches. a) Reported phosphomolybdic acid-catalyzed synthesis of imidazo[1,2-a]pyridines via GBB-3CR. b) Attempts to reproduce the results reported in

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain 10.3762/bjoc.20.21 Abstract An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper

• General procedure for copper-catalyzed multicomponent reaction of β-amino esters Into a flask were added amines 1 (0.4 mmol), acids 3 (0.1 mmol), CuI (20 mol %), and CH3CN (2 mL). Then, the mixture was stirred at room temperature under a nitrogen atmosphere and t-BuONO (0.4 mmol) was added dropwise

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• -type AMYs in multicomponent, one-pot, and stepwise reactions for the synthesis of diverse heterocycles related to some bioactive compounds and natural products. Keywords: [3 + 2] cycloaddition; decarboxylation; 1,3-dipolar; double cycloaddition; one-pot synthesis; multicomponent reaction; semi

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

• generated via an azide–alkyne cycloaddition or a multicomponent reaction between carbonyls and azides [17]. α-Trifluoromethyl (α-CF3) carbonyls were recently utilized to generate NH-1,2,3-triazoles and fully substituted 1,2,3-triazoles [28][29]. However, there are no reports of a formal [3 + 2

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• enantioselectivity. Keywords: acetaldehyde; acetaldehyde dimethyl acetal; cascade reaction; multicomponent reaction; organocatalysis; Introduction Multicomponent reactions (MCRs) are chemical processes that involve three or more compounds, in which the product contains all the atoms of the reagents, except for

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• substituent. A plausible reaction mechanism is proposed to explain the formation of the different spirooxindoles. Keywords: cascade reaction; dimedone; isatin; 3-methyleneoxindole; multicomponent reaction; spirooxindole; Introduction Spirooxindole is one important privileged structural skeleton and is found

• -phenacylideneoxindoles resulted in the two different novel dispirooxindole skeletons. Conclusion In summary, we have investigated the base-promoted multicomponent reaction of 3-methyleneoxindoles, dimedone, isatins and ammonium acetate. The reaction showed very interesting molecular diversity and diastereoselectivity

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• –Bienaymé reaction; imidazo[1,2-a]pyridine; isocyanide; multicomponent reaction; peptidomimetic; Ugi reaction; Introduction The use of isocyanide multicomponent reactions (IMCR) to prepare biologically active compounds is one of the most promising tools in modern organic and medicinal chemistry. Therefore

• attention to another isocyanide multicomponent reaction – the Ugi reaction [21], which is one of the most important methods for the synthesis not only of peptidomimetics but also of other types of complex organic compounds. The presence of several diversity points and modification of starting components for

• , chloroform and some other typical solvents). Therefore, it was not surprising to us that the usual stirring of the starting materials in methanol at 50 °C was not successful for this multicomponent reaction. Increasing the temperature to 75 °C also did not give any positive results. Therefore, we tried to

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• products. Keywords: amino acids; asymmetric catalysis; multicomponent reaction; palladium catalysis; Petasis reaction; sulfonamides; Introduction α-Amino acids play a crucial role in every aspect of our human life [1]. They are important synthetic intermediates in the chemical industry and used for the

• imine species provide a very flexible approach to the arylglycine scaffold [2][9]. The Petasis borono-Mannich reaction constitutes a prominent example for such an imine-based multicomponent reaction (Scheme 1a). The reaction of glyoxylic acid, an amine component and an arylboronic acid offers a highly

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• . through a multicomponent reaction system [57]. The authors provided a series of substituted derivatives through Pd/Rh-catalysed domino coupling. The reaction proceeded via a Suzuki coupling, followed by an in situ Buchwald–Hartwig amination. The authors reported moderate to good yields in a series with

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

• summarized so that the chemists, researchers, and pharmaceutical industries find its effectiveness in near future for the synthesis of potent, novel, and non-toxic drug molecules. Keywords: functionalization; imidazole N-oxide; mechanistic insights; multicomponent reaction; nucleophilic substitution

• tosyl halogenides. Solvent-free chlorination reaction of imidazole N-oxides. Multicomponent reaction of imidazole N-oxides 28 with Meldrum’s acid (26) and aldehydes. Multicomponent reaction of imidazole N-oxides with CH-acids and aldehydes. Reaction conditions: aThe mixture of 2-unsbstituted imidazole 1

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

• prolonging the reaction time could not increase the yield of the product 3a. Therefore, the functionalized 5-hydroxy-cyclopent-1-ene derivatives can be conveniently prepared in satisfactory yield in very simple reaction conditions. It should be pointed that a similar triethylamine-promoted multicomponent

• reaction of phenacyl bromide, malononitrile, dialkyl but-2-ynedioate, and triphenylphosphine has been already reported, in which diethyl 3-phenyl-5,5-dicyanocyclopent-2-ene-1,2-dicarboxylates were produced by further elimination of a hydroxy group [30]. In the present reaction, the hydroxy group is still

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

• . Synthesis of 3,3'-(arylmethylene)bis(2-methyl-1H-indole). Reaction conditions: 2-methylindole (1.0 mmol), aromatic aldehyde (0.5 mmol), CuSO4 (0.1 mmol), toluene (6.0 mL), 110 °C, 3 h. Isolated yields are shown. Proposed reaction mechanism for the multicomponent reaction. Optimization of reaction

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines under mild reaction conditions is still of high demand in the discovery of biologically active compounds. The Passerini reaction is an isocyanide-based multicomponent reaction, which has been used in preparing various α-acyloxy adducts starting

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

• synthesize tetrahydrobenzo[a]xanthene-11-ones 184 and diazabenzo[a]anthracene-9,11-dione derivatives 185 in good yields via a multicomponent reaction (Scheme 42) [76]. This methodology was based on the cyclocondensation of aromatic aldehydes 180, β-naphthol (181), and cyclic 1,3-dicarbonyl compounds 182 or

• -workers [77] provided better results. In a related approach, Estévez-Braun and co-workers synthesized dibenzo[a,h]anthracene-12,13-diones 188 from 2-hydroxy-1,4-naphthoquinone (186), β-naphthol (181), and aromatic aldehydes 187 through a multicomponent reaction that used InCl3 as catalyst under solvent

Correction: One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2021, 17, 2026–2027, doi:10.3762/bjoc.17.130

• 10.3762/bjoc.17.130 Keywords: antiproliferative activity; 1,2-dihydropyridines; green Hantzsch synthesis; heterogeneous catalysis; one-pot multicomponent reaction; The authors noticed that the E-factor (E) was calculated using a wrong Equation 2 in the original publication: The correct Equation 2 should

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• multicomponent reaction (IMCR) [31]. The enantioenriched hemiacetals 5 were obtained using the Jørgensen catalyst 7 as previously described by Rueping et al. [32]. This approach enables the rapid assembly of complex natural product hybrids 6 including up to four different molecular fragments, such as

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

• economic perspective due to increased amounts of waste generation, toxic solvents, and no real-time control of pollution generated, etc. [4]. Therefore, in this connection, the multicomponent reaction (MCR) is one such approach where three or more reactants combine to form a single product retaining the

• majority of the atoms of the starting materials. The ability of forming multiple bonds in one-pot via a multicomponent reaction provides a novel and sustainable method in drug discovery [4]. In the recent years, these reactions have emerged as a promising strategy following green chemistry principles such

• ] tailored a microwave-assisted multicomponent reaction for fast and efficient generation of diastereoselective dibenzo[c,e]azepinones. The protocol utilized substituted 2'-formylbiphenyl-2-carboxylic acid 19, benzylamines 20, and isocyanides 21 in TFE and Na2SO4 as drying agent for the construction of

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• 22 can be afforded easily (Scheme 7). This procedure offers a novel cyclization method with bifunctionalization, causing a multicomponent reaction of vinylaniline, halide, and sulfonylate to give corresponding indole derivatives. Furthermore, a wide variety of applicable substrates and good

• successfully applied to the gram scale, providing a step towards assorted aryl sulfide structural units with medicinal value. In 2019, Yang and colleagues [52] developed a method for preparing S-aryl dithiocarbamates 135 by a multicomponent reaction of an EDA complex under visible-light irradiation (Scheme 47

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• Schwartz’s reagent-mediated reductive amide functionalization followed by a variant of the Ugi–azide multicomponent reaction. The anomeric configurations of two products were unambiguously confirmed by X-ray analysis. This work also describes examples of interesting further transformations of the title

• one-pot Mannich/Michael sequence leading to oligocyclic compounds [24], and employment in subsequent Joulié–Ugi multicomponent reactions [25]. This work is an extension of these efforts and seeks to investigate the possibility of incorporating the Ugi–azide multicomponent reaction in this workflow. A

• first example of using Schwartz’s reagent-mediated partial reduction of lactams and the Ugi–azide multicomponent reaction in a tandem process. Yields of the described products are moderate to good, a satisfying result for such a multistep process. We have shown that such a reaction does not necessarily

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• commonly used methods to prepare these compounds include the Cu-catalyzed multicomponent reaction of alkynes, sulfonyl azides and amines [23][24][25][26][27][28][29][30][31], the reaction of thioacetamide derivatives and cyclic thioamides with sulfonyl azides [22][32][33], the chlorophosphite-mediated

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• reactivity of aliphatic aldehydes, the reaction in Scheme 6 should be a wise choice for the synthesis of products similar in type to 5a. This point deserves further investigation. Conclusion In summary, an efficient and practical one-pot multicomponent reaction of (hetero)arylamines with α-bromoacetaldehyde

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• oxidizing agents [7][17][18]. One of the greatest limitations of this synthesis is however the fact that the dihydropyridines that are obtained are usually the 1,4-symmetrical ones. This multicomponent reaction has been thought to have one of the most complex mechanisms since various routes might take place

• find a green catalyst that could provide a wide substrate scope for the Hantzsch synthesis of 1,2-dihydropyridines in a short reaction time. In order to achieve a green method, apart from utilizing a multicomponent reaction as a route providing a high atom economy, heterogeneous catalysis should be

• preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range. Keywords: antiproliferative activity; 1,2-dihydropyridines; green Hantzsch synthesis; heterogeneous catalysis; one-pot multicomponent