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

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• reported for the first time by Ivar Ugi in 1959. This Ugi four-component reaction (U-4CR) furnishes α-acylamino amides 11 by combining oxo-substrates, carboxylic acids, amines and isocyanides in one-pot and like the Passerini reaction a wide variety of substrates is tolerated. In contrast to the Passerini

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• Hong Gao Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.330 Abstract The four-component reaction of 2-aminobenzothiazole, aromatic aldehydes, acetylenedicarboxylate and piperidine or pyrrolidine in ethanol afforded the

• synthesis of a versatile heterocyclic system, herein we wish to report the interesting results of the four-component reaction of secondary cyclic amines, acetylenedicarboxylate, 2-aminobenzothiazole and aromatic aldehydes and the efficient synthesis of the complex 2-pyrrolidinones containing both

• give the polyfunctionalized 2-pyrrolidinone 1b–1f (Table 1, entries 2–6) in 53–72% yields, respectively. The four-component reaction containing diethyl acetylenedicarboxylate also successfully afforded the expected 2-pyrrolidinone 1g in 63% (Table 1, entry 7). In view of the success of the above

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• , Department of Chemistry, University of Delhi, Delhi-110 007, India Chemistry Building-4.20b, School of Chemistry, The University of Manchester, Manchester M13 9PL, UK 10.3762/bjoc.9.246 Abstract An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces

• ][39][40][41][42][43]. We have recently reported a post-Ugi gold-catalyzed intramolecular domino cyclization sequence which produces spiroindolines (Scheme 1) [44]. The first step in this sequence is an Ugi four-component reaction (Ugi-4CR) [4][5] with 2-alkynoic acid as an alkyne source. The second

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• arylamines and other primary amines. Keywords: 1,4-dihydropyridine; electron-deficient alkyne; four-component reaction; isatin; one-pot reaction; spiro compound; Introduction β-Enaminones and β-enamino esters represent important synthetic building blocks for the development of versatile carbon–carbon bond

• functionalized spiro[indole-3,4’-pyridines] via the four-component reaction prompted us to study the reaction scope further [25]. Another widely used electron-deficient alkyne reagent, methyl propiolate, was utilized to replace dimethyl acetylenedicarboxylate as one component. The addition reaction of aniline to

• very clear. Conclusion In summary, we have successfully developed a one-pot four-component reaction of arylamines, methyl propiolate, isatin and malononitrile or ethyl cyanoacetate with triethylamine as base catalyst. This reaction can proceed smoothly under mild conditions to afford the functionalized

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• allylmagnesiation of alkynyl sulfone. Copper-catalyzed four-component reaction of alkynyl sulfoxide with alkylzinc reagent, diiodomethane, and benzaldehyde. Rhodium-catalyzed reaction of aryl alkynyl ketones with arylzinc reagents. Allylmagnesiation of propargyl alcohol, which provides the anti-addition product

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• ] derivatives in moderate yields (Scheme 1a) [15]. In order to explore the generality of this four-component reaction, the reactivity of the other cyclic 1,3-diketones was also investigated. In an exploratory experiment, the four-component reaction of p-methoxyaniline, dimethyl acetylenedicarboxylate, 1-benzyl

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• strategies and affords the optically active natural product in 20% overall yield over six steps. A more economical approach with only four steps leads to the similarly active racemate by utilizing a Ugi four-component reaction (Ugi-4CR) as the key transformation. A small library of viridic acid analogues is

• a bidirectional sequence from the least- to the most-reactive amine (NMe-Val < H-Ant-OBn < H-Gly) to yield the protected tetrapeptide 2 (Scheme 1a). Alternatively, a multicomponent (MCR) approach based on a Ugi four-component reaction (Ugi-4CR) of dipeptide 3, isobutyraldehyde, methylamine and

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• another allenic unit. After a new transmetalation step with the boronic acid, the active catalytic species can be released and entered into a new catalytic cycle (Scheme 13). Imine as a nucleophilic partner A tandem four-component reaction allowing access to 1,2-dihydroisoquinolin-1-ylphosphonates 26 was

• -dihaloarene partner and the corresponding polysubstituted indoles were isolated in good yields as single regioisomers (Scheme 23). Based on this concept, Alper and coworkers reported the synthesis of isoindolin-1-one derivatives 53 through a four-component reaction starting from ortho-dihaloarenes and

• stereoselectivity. A four-component reaction was further developed through an in situ post C–B arylation by adding a second aryl iodide, with Cs2CO3 and water, to the newly formed alkenylboronate 78. The subsequent Suzuki–Miyaura coupling led to the formation of 2,3-diarylated amines 79 and the best results were

Novel synthesis of pseudopeptides bearing a difluoromethyl group by Ugi reaction and desulfanylation

• Jingjing Wu,
• Hui Li and
• Song Cao

Beilstein J. Org. Chem. 2011, 7, 1070–1074, doi:10.3762/bjoc.7.123

• triglyceride transfer protein (MTP) and useful for the treatment of obesity and atherosclerosis (Figure 1) [20]. Among the protocols for the preparation of pseudopeptide derivatives, the Ugi four-component reaction offers significant advantages over conventional linear-step synthesis [21]. Various fluorinated

• building blocks have been used in the Ugi four-component reaction to construct a fluorinated compound library [22][23][24][25]. Our group has always been interested in developing efficient methods for the preparation of difluoromethyl-containing compounds through multicomponent reactions [26][27][28][29

Synthesis of dihydrophenanthridines by a sequence of Ugi-4CR and palladium- catalyzed intramolecular C-H functionalization

• Florence Bonnaterre,
• Michèle Bois-Choussy and
• Jieping Zhu

Beilstein J. Org. Chem. 2008, 4, No. 10, doi:10.3762/bjoc.4.10

• . Introduction Multicomponent reactions (MCRs) offer a unique way to generate efficiently libraries of complex molecules with high degree of diversity [1][2]. Among them, the Ugi four component reaction (Ugi-4CR) is without doubt one of the most powerful transformations that has been extensively investigated for

• Scheme 1. The Ugi four-component reaction between an o-iodobenzaldehyde 2, an aniline 3, an isocyanide 4 and a carboxylic acid 5 should afford an α-acetamido-α-phenylacetamide 6, which upon palladium-catalyzed C-H activation process should provide dihydrophenanthridine 1 [15][16][17][18][19][20][21

• developed an efficient palladium-catalyzed intramolecular CH-arylation reaction leading, under ligandless conditions, to dihydrophenanthridines in good to excellent yields. In combination with the Ugi four-component reaction, this medicinally important heterocycle can be easily prepared in two steps from