Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• = 24 kHz (at 298 K). A similar exchange process was observed in the four-component rotors [90] developed along two orthogonal self-sorting motifs (HETPYP = Npy → [Cu(phenAr2)]+ and NDABCO → ZnPor interactions). Again, the synthetic approach is a straightforward multicomponent self-sorting assembly

• , thermodynamic stabilization quantitatively drives the reaction to the hetero-assembly 59, simply by mixing the components in the correct stoichiometric ratio (Figure 13). Various nanorotor assemblies are possible by this approach. The dynamics of the four-component rotor 59 = [Cu2(55)(57)(60)]2+ cannot be

• ) through nanomechanical motion. Recently, the suitability of the four-component rotors to act as catalysts in various click reactions was investigated having a look at nanorotors [Cu2(55)(60)(X)]2+ (with X = 62, 63 or 64), revealing an unexpected correlation between their rotational speed and catalytic

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

• a four-component radical dual difunctionalization and ordered assembly of two chemically distinct alkenes 114/115, aldehyde 65, and tert-butyl peroxide (Scheme 23) [108]. In order to selectively couple one alkene to another, without the formation of oligomers, the authors utilized the different

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• mechanistically similar to the Hantzsch pyridine synthesis is the Guareschi type-IV pyridine synthesis, first reported in 1897 [7] and involving the four-component condensation of ammonia, a carbonyl derivative, and two molecules of a cyanoacetic ester. The reaction affords 3,5-dicyanoglutarimides, known as

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

• exploring the MC-MWA reactions Jiang and co-workers [41] designed a microwave facilitated regioselective four-component domino reaction employing naphthyl- or anthracenylamine 10, aldehydes 5 and 2-hydroxy-1,4-naphthoquinone (11) in acetic acid for the construction of dibenzo[a,h]acridine-12,13(7H,14H

• azepinone 22 and exemplified a modified Ugi reaction (four-component reaction). The aldehyde and acid component of the Ugi reaction was functionalized on the same biaryl ring employing a Suzuki–Miyaura coupling. The authors advocated the use of microwave as it consistently increased the yield from 49% to 82

• ). Similarly, the same group extended the work by illustrating [51] a three and four-component microwave-assisted base and catalyst-free reaction for the synthesis of substituted spirooxindoles 40. The three-component reaction involved the reaction between substituted isatin 35, but-2-ynedioates 39 and amino

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• to a large number of diverse heterocyclic compounds [10][11]. Over the past decade, several cases of using an Ugi four-component reaction (Ugi-4CR) in combination with intramolecular azide–alkyne cycloaddition (IAAC) for the synthesis of 1,2,3-triazolobenzodiazepines were reported [3][7][12][13][14

• conclusion, we have advanced the creation of a convenient tandem approach to potentially biologically active 1,2,3-triazolobenzodiazepinones. The developed synthetic procedure includes a four-component Ugi reaction followed by microwave-assisted intramolecular azide–alkyne cycloaddition and allows to build a

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• phosphonylation of hydroxy esters 2 with N-protected aminoalkylphosphonochloridates 3 (method I), reactions of N-protected aminoalkylphosphonic monoesters 4 with hydroxy esters 2 (method II) or with 1-(alkoxycarbonyl)alkyl halides or sulfonates 5 (method III), pseudo-four-component condensations (method IV), and

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• release of DABCO using a double self-sorting protocol [54]. Schmittel and co-workers reported on the three-component rectangle [Cu4(16)2(17)2]4+ (SelfSORT-I) that rearranged into the four-component sandwich complex [Cu2(16)(17)(18)]2+ (Figure 8) upon the addition of DABCO (SelfSORT-II). A full

• -assemble the four-component rotor [Cu2(79)(80)(18)]2+ that itself triggered the catalysis of a click reaction (81 + 46 → 82) as shown in Figure 22. In conclusion, the output of the AND gate regulated both the assembly of the multicomponent machinery and the catalytic output. Conclusion In conclusion, the

• . Some selected self-sorting outcomes and their qualitative and quantitative assessment. Illustration of an integrative vs a non-integrative self-sorting. The pH-driven four-component 2-fold completive self-sorting based on host–guest chemistry. (a) The monomers 5 and 6 and their H-bonding array. (b) The

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• -component Passerini [19][20][21][22] and four-component Ugi [23][24] reactions that rely on the ability of organic isocyanides to participate in the nucleophilic attack onto the carbonyl or imine group are among the most studied MCRs. Accordingly, a wide range of post-MCR transformations have been

• ], no general asymmetric protocol for the four-component mode has been developed until very recently. In 2018, Houk, Tan and co-workers described an efficient enantioselective procedure operating in the presence of catalytic amounts of chiral phosphoric acids (Table 2) [57]. Two synthetic protocols have

• structure of (S)-12e (slow enantiomer). Post-transformations of 2-oxo-aldehyde-derived Ugi adducts 8. Synthesis of 2-oxo-aldehyde-derived Ugi adducts. Asymmetric protocols for Passerini three-component reaction (P-3CR). Asymmetric protocols for Ugi four-component reaction (U-4CR) by Houk, Tan and co-workers

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• palladium-catalyzed regioselective cascade cyclization of propargylamides/coupling with ArB(OH)2 in dioxane/water, to give trisubstituted arylidene-isoquinolinones [44] was published. However, the Ugi four-component reaction used to construct the starting building blocks was limited to the preparation of

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

• 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

• [35][36][37]. These new processes improved the overall efficiency with shorter reaction times and lower costs of synthetic preparations, and minimized the amount of waste generated. In recent years, we used the Ugi four-component reaction as a main tool to generate nitrogen-containing heterocycles [38

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

• Republic 10.3762/bjoc.16.27 Abstract Four-component reactions of 3-amino-1,2,4-triazole or 5-amino-1H-pyrazole-4-carbonitrile with aromatic aldehydes and pyruvic acid or its esters under ultrasonication were studied. Unusual for such a reaction type, a cascade of elementary stages led to the formation of

• -pyrazole-4-carbonitrile with aromatic aldehydes and pyruvic acid or its esters under ultrasonication led to the formation of 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines 4a–u (Scheme 4) containing an azolylamino substituent in the 7-position via an unusual pseudo four-component reaction, rather than two

• -aminopyrazoles bearing an electron-withdrawing substituent in the 4-position, such as a carbonitrile group, often behave similar to 3-amino-1,2,4-triazole; therefore, we studied the latter under the same reaction conditions. We showed that the pseudo four-component heterocyclization of two equivalents of 3-amino

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

• in DOS [19][20][21][22], such as the exploitation of the Petasis three-component [23][24][25][26][27][28][29] and the Ugi four-component reactions [30][31][32][33], showing interesting properties for the generation of compounds characterized by high stereochemical and skeletal diversity. Although not

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

• substituent in the 3-position [29]. Most syntheses generating 1H-pyridines make use of ethyl cyanoactate as a starting material. It can react with itself and forms a dimer by selfcondensation, catalyzed by transition metals [30][31]. Intrigued by the unusual pseudo-four-component AMAC synthesis we

• -pyrones from acid chlorides, terminal alkynes and dialkyl malonates. Consecutive pseudo-four-component alkynylation–Michael addition–cyclocondensation (AMAC) synthesis of 1H-pyridines 5a and an aniline derivative. Consecutive pseudo-four-component alkynylation–Michael addition–cyclocondensation (AMAC

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

• prospect of the tetrazole hybridization strategy in drug discovery. Among the most versatile methods for obtaining tetrazoles are the Ugi-azide four-component reaction (Ugi-azide-4CR) [14][15][16] and the 1,3-dipolar cycloaddition of azides with (acyl)cyanides [17][18]. The Ugi-azide-4CR enables the

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

• , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, Talence, 33405 Cedex, France 10.3762/bjoc.15.176 Abstract Four-component coupling reactions between xanthogenates, alkenes, CO, and sulfonyl oxime ethers were studied. In the presence of hexabutylditin, working as a propagating

• radical reagent, the chain reaction proceeds, as expected, taking into account reagents polarities, affording the corresponding functionalized α-keto oximes. Although yields are modest, this rare one-pot four-component process is easy to carry out and the resulting compounds, bearing multiple

• and two radical C1 synthons, CO and sulfonyl oxime ethers, is known to be feasible [23][24][25], we were tempted to explore a novel class of four-component radical reaction [26][27][28] incorporating a xanthogenate, an alkene, CO, and a sulfonyl oxime ether (Scheme 1, reaction 2). This paper reports

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

Selective detection of DABCO using a supramolecular interconversion as fluorescence reporter

• Indrajit Paul,
• Debabrata Samanta,
• Sudhakar Gaikwad and
• Michael Schmittel

Beilstein J. Org. Chem. 2019, 15, 1371–1378, doi:10.3762/bjoc.15.137

• -component rectangle [Cu4(1)2(2)2]4+ and the four-component sandwich complex [Cu2(1)(2)(4)]2+ is triggered by inclusion and release of DABCO (4). The fully reversible and clean switching between two multicomponent supramolecular architectures can be monitored by fluorescence changes at the zinc porphyrin

• was demonstrated to be reversible after removing the guest. This compilation of remarkable results already indicates that guest-induced supramolecular transformations are not yet explored to their full potential. Herein, we will present the formation of self-assembled three to four-component

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• -type condensation of aminopyrazoles, aldehydes and pyruvic acid [45][46] with the isocyanide-based four-component Ugi reaction. As we have shown before [47][48] the application of the CBD strategy to multicomponent Doebner-type condensations involving aminoazoles allowed the synthesis of several

• the Ugi four-component reaction to create 3 additional points of diversity. However, due to the low solubility of the pyrazolopyridine acids 4a,b under the literature standard reaction conditions for the Ugi transformation (stirring in methanol at rt and similar procedures) the reaction did not take

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• intermediate was far away from the chiral steroidal nucleus. A better stereoselectivity was reported by Bruttomesso et al. in their work on the Ugi four-component reaction (Ugi-4CR) with a steroidal aldehyde, in which the carbonyl group was directly linked at the steroidal framework [16]. As shown in Scheme 2

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• synthesis of prolyl pseudo-peptides having a furan ring handle, which could be subsequently incorporated into PFA during the polymerization process. Results and Discussion To this end, a solution-phase multicomponent procedure based on the Ugi four-component reaction (Ugi-4CR) [14], was employed to

• system producing γ-nitroaldehyde 5 with PFA-supported catalyst 3 packed in a microreactor. Schematic synthesis of polyfurfulyl alcohol (PFA) incorporating a prolyl peptide catalyst. AA: Amino acid. Utilization of the Ugi four-component reaction (Ugi-4CR) for the synthesis of prolyl pseudo-peptide

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• CO (23). Proposed mechanism for the palladium-catalysed synthesis of isoindoloquinazolinones 57. Four-component reaction of 2-vinylbenzoic acids 67, aryldioazonium tetrafluoroborates 68, DABCO·(SO2)2 (69) and nitriles 70. Plausible mechanism for the formation of isoindolinones 71. Three-component

• furnishes an acylpalladium complex 65, which, after elimination of hydrogen bromide and subsequent reductive elimination of palladium from intermediate 66, affords 57 with regeneration of Pd(0). 2-Vinylbenzoic acids 67 are also appropriate substrates for the preparation of isoindolinones 71 through a four

• -component reaction with aryldiazonium tetrafluoroborates 68, DABCO·(SO2)2 (69) and nitriles 70 under Ru(IV) photocatalysis with visible light and in the presence of a Lewis acid (Scheme 21) [101]. Up to 24 isoindolinone derivatives were obtained, bearing a wide variety of aryl moieties at the sulfonyl group

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• (Scheme 5) [23]. The synthetic strategy was based on a four-component Ugi reaction (U-4CR) followed by a three-component Ugi reaction (U-3CR). The first step involved the reaction of ammonium chloride or tritylamine, with oxo components, isocyanide, and sodium azide or TMS azide followed by acid treatment

• the first example in which the Ugi reactions were used in the construction and cyclization of peptoids in a combined fashion. The methodology was based on two consecutive four-component Ugi reactions for the construction of the acyclic precursors 84 and 89, followed by a final intramolecular Ugi

• of nonsymmetric cryptands by two sequential double Ugi-4CR-based macrocyclizations (Scheme 28). The approach also relies on MiBs strategy [45]. The main focus was on the use of the Ugi four-component reaction (Ugi-4CR) due to the tremendous capability of this process to generate molecular complexity

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• prominent and studied MCRs is the Ugi reaction. The Ugi four-component condensation reaction (U-4CC) between an aldehyde, an amine, a carboxylic acid and an isocyanide provides a rapid preparation of α-aminoacyl amide or pseudo-peptide derivatives. These biologically active peptide-like molecules can be

• for Ugi reactions because it has two functional groups in its structure. By the way, using bifunctional chemicals in Ugi four-component condensation reaction (4CC) converts it to an Ugi three-component condensation reaction (3CC) and this is identified as an Ugi-4-centre-3-component reaction (U-4C-3CR

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia 10.3762/bjoc.14.269 Abstract The one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitriles, aromatic aldehydes, cycloalkanones and ammonium acetate occurred via a six-step tandem Knoevenagel

• four-component reaction of cyclic/acyclic ketones, malononitrile, aromatic aldehyde and ammonium acetate affording 2-amino-3-cyanopyridine derivatives have been explored extensively [45][46][47][48][49][50][51][52][53][54][55]. However, syntheses of pyridine scaffolds bearing an indole side chain have

• ]. Recently we reported the synthesis of pyridine/benzo-fused cyclododecanes through a four-component tandem reaction [70]. In continuation we herein report the synthesis of novel indole substituted cycloalkyl[b]pyridine-3-carbonitriles from a one-pot six-step tandem protocol involving 3-(1H-indol-3-yl)-3

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• synthesis of tetrahydrobenzo[a]xanthenone derivatives 48a and the four component synthesis of tetrahydrobenzo[a]acridinone derivatives 48b were performed with good to excellent yields under solvent-free conditions at 75–85 °C within short reaction times using the higher acidic/stable ILs containing