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

• [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

• -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

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

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

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

• 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

• -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

• 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

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

• 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 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

• -oxopropanenitriles 3 were synthesized from the reaction of indoles 1 and 2-cyanoacetic acid (2) in acetic anhydride under heating conditions (Scheme 1) [73]. Subsequently the one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitrile (3a), 4-chlorobenzaldehyde (4f), cyclododecanone (5a) and ammonium

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• economical, simple and generate ample molecular diversity with the ease of using readily available starting materials. Developing new, post-modified Ugi-four-component reaction (Ugi-4CR) transformations in domino cyclization [12][13][14][15] sequences are very important for achieving unprecedented chemical

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -isomer in slightly higher amounts than the trans-isomer. A four-component reaction having ethyl acetoacetate (81) as fourth component resulted in the formation of the same pyrazolo[3,4-b]pyridine derivative 95 showing no involvement of any additional fourth component (Scheme 27). Dandia et al. [76] also

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• bearing 1,5-disubstituted tetrazoles. Our strategy was accomplished in only three steps: first, a one-pot hydrazino-Ugi-azide four-component reaction; second a hydrazinolysis and finally an additional hydrazino-Ugi-azide reaction. This sequence provides the title compounds in moderate to excellent yields

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• varying the reaction conditions the potential of the sequence can be extended. An increase of the T3P® concentration to 2.0 equiv leads to the regioselective formation of (E)-2,9-diphenyl-3-(phenylimino)-2,3-dihydro-1H-benzo[f]isoindol-1-one (5) in 15% yield in the sense of a pseudo four-component

• reaction (Scheme 6). The increased amount of the condensation agent T3P® obviously enables further activation of the initially formed 1H-benzo[f]isoindole-1,3(2H)-dione by electrophilic attack on the sterically easier accessible carbonyl group. As a consequence the imine condensation proceeds also with

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• amine component in Ugi and Groebke–Blackburn–Bienaymé multicomponent reactions. The first example of an application of aminoazoles in an Ugi four-component reaction was discovered and novel features of a Groebke–Blackburn–Bienaymé cyclocondensation are established and discussed. The heterocycles

• -based MCRs as the Ugi four-component reaction (Ugi-4CR) and the Groebke–Blackburn–Bienaymé reaction (GBB-3CR) in combination with post-cyclizations are powerful tools to access diversity as well as complexity in a one-pot procedure; in this way they largely cover the available chemical space [9][10][11

• -diaryl-1H-imidazo[1,2-b]pyrazole-7-carboxamides (Groebke–Blackburn–Bienaymé reaction). In contrast, 3-amino-5-methylisoxazole acted as a primary amine in Ugi four-component reaction with aromatic aldehydes, phenylpropiolic acid and tert-butylisocyanide giving N-(1-arylethyl-2-(tert-butylamino)-2-oxo)-N

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• dihydropyridine synthesis (1882), the Biginelli dihydropyrimidone synthesis (1891), the Mannich reaction (1912), the Passerini three-component reaction (1921) and the Ugi four-component reaction (1959) [9]. In this work, we used Biginelli and Passerini reactions to synthesize highly functionalized compounds

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• for the synthesis of acylhydrazino-peptomers, a new class of peptidomimetics. The key idea in this approach is based on a simple route using a one-pot hydrazino-Ugi four-component reaction followed by a hydrazinolysis or hydrolysis reaction and subsequent hydrazino-Ugi reaction or classical Ugi

• difficult sequences [48]. It is therefore important to have alternative methods for the fast and easy construction of such important compounds. In this sense, the Ugi four-component reaction (U-4CR) has proven to be a robust and versatile method for the synthesis of peptoids and peptide-peptoid hybrids

• multicomponent reactions (Scheme 1): the hydrazino-Ugi four-component reaction (HU-4CR) and the classical Ugi reaction (U-4CR). The strategy was based on the formation of an acylhydrazino-peptomer via an initial hydrazino-Ugi reaction followed by a hydrazinolysis reaction (or ester hydrolysis) and a subsequent

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• phosphite. When butanediones 128 with a larger substituent than Me were used, only monophosphonates 129 were obtained. The second method comprises a one-pot four-component reaction of diamines 130, ketones 131 and phosphites 132 in the presence of FeCl3 as a catalyst to give benzodiazepinylphosphonates 133

• four-component reaction through a methyleneaziridine ring-opening process has been developed for the synthesis of α-aminophosphonates [76]. Thus, the one-pot reaction between methyleneaziridines 173, Grignard reagents 174, alkyl halides 175 and dialkyl phosphonates in the presence of CuI afforded

• -component reaction for the synthesis of 1,5-benzodiazepin-2-ylphosphonates. Synthesis of indole bisphosphonates through a modified Kabachnik–Fields reaction. Synthesis of heterocyclic bisphosphonates via Kabachnik–Fields reaction of triethyl orthoformate. A domino Knoevenagel/phospha-Michael process for the

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• urea dipeptide 27 [96][97]. Starting from the uridine derivative 28 used in the synthesis of (+)-caprazol, Ichikawa and Matsuda built up muraymycin D2 and its epimer (Scheme 4). They used an Ugi four-component reaction with an isonitrile derivative 29 obtained from the uridine-derived core structure 28

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• synthesized through an Ugi four-component reaction (U-4CR) followed by a copper-catalysed alkyne homocoupling (Glaser reaction). The short and chemoselective reaction sequence allows generating diverse (pseudo) dimeric peptoids. A combinatorial version allows the one-pot preparation of, e.g., six-compound

• which are able to mimic peptide structures [7][8][9]. In addition to the mimetic function, these compounds also possess an enhanced resistance to proteolytic enzymes. The fastest method for synthesizing peptoids is the Ugi four-component reaction (U-4CR) [10][11][12]. In combination with other protocols

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• Chao Wang Yan-Hong Jiang Chao-Guo Yan College of Chemistry & Chemical Engineering Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.10.281 Abstract The one-pot four-component reaction of benzohydrazide (2-picolinohydrazide), acetylenedicarboxylate, isatins and malononitrile (ethyl

• reactions [19][20][21]. Recently, we and Perumal have demonstrated that the four-component reaction of arylamine, acetylenedicarboxylate, isatin and malononitrile can afford the spiro[indoline-3,4’-pyridine] derivatives in satisfactory yields [22][23][24]. We envisioned that functionalized spiro[indoline

• -3,4’-pyridine] derivatives can be synthesized by employing other nitrogen-containing nucleophiles such as hydrazine and imines in the similar four-component reactions. In fact, the four-component reaction of hydrazine, acetylenedicarboxylate, isatin and malononitrile for the formation of spiro

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -component reaction (U-4CR), can be adopted. The sequential combination of four species (amines, aldehydes, isocyanides and carboxylic acids) in a single-pot synthetic operation permits access to bisamide peptidomimetics through a highly electrophilic nitrilium intermediate [1][2][3][4]. Modification of the

• -imidazo[1,2-b]pyrazole; isocyanide; multicomponent reaction; N-heterocycles; Introduction For the relatively rapid design and construction of a diverse, large pharmacophore library, the basic concepts of diversity-oriented synthesis and isocyanide-based multicomponent reactions, such as the Ugi four

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• the Ugi four-component reaction (U-4CR) [8][9][10][11][12][13][14]. It has been demonstrated that the combination of multicomponent reactions with the use of microwave irradiation is able to efficiently produce complex molecules with a reduced number of steps and short reaction times [15][16][17][18

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• Strukturchemie, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.10.100 Abstract Phenothiazinyl and carbazolyl-donor moieties can be covalently coupled to an anthraquinone acceptor unit through an Ugi four-component reaction in a rapid, highly convergent fashion and with moderate to good yields

• rigid Do–Acc dyads [55]. Nevertheless, a modular and rapid access by multicomponent reactions to these types of functional targets has never been explored prior to our recent studies [56]. For instance, the Ugi four-component reaction (Ugi 4CR) [57][58][59][60] establishes the chemically robust α

• directed towards multicomponent syntheses of more complex light harvesting and charge separation systems are currently underway. Experimental Synthesis of compounds 8 and 10 via Ugi four-component reaction (General Procedure) in a manner similar to [56]) In a 25 mL Schlenk tube 0.50 mmol of the donor