Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones

• Xiaochen Du,
• Jianjun Huang,
• Anton A. Nechaev,
• Ruwei Yao,
• Jing Gong,
• Erik V. Van der Eycken,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234

• address this issue by employing propargylamides 7 obtained by a four-component Ugi reaction of propiolic acids 3, aldehydes 4, isocyanides 5 and 3,5-dimethoxyaniline (6a) (Scheme 2). We anticipated that the resulting adducts 7 would readily produce 2-quinolones 8 bearing a branched substituent on the

• -oriented approach towards 2-quinolones bearing a branched substituent on the nitrogen atom. The strategy relies on the application of a four-component Ugi reaction followed by a gold-catalyzed intramolecular alkyne hydroarylation. The developed process has a broad scope and simple reaction settings

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• reductant, carboxyzincation and the four-component coupling reaction between alkyne, acrylates, CO2, and zinc occur efficiently. Rh complexes also catalyze the carboxylation of arylboronic esters, C(sp2)–H carboxylation of aromatic compounds, and hydrocarboxylation of styrene derivatives. The Rh-catalyzed

• carboxylation of allylarenes when a suitable ligand is used. In the presence of zinc powder, the Co-catalyzed carboxyzincation of alkynes and the four-component coupling reaction between alkyne, acrylates, CO2, and zinc proceed in an efficient manner. Visible-light-driven hydrocarboxylation reactions are shown

• , thereby giving the carboxyzincated product and regenerating Co(I) species A (step c). We also achieved the four-component coupling of alkynes 16, acrylates 18, CO2, and Zn metal, as depicted in Scheme 18 [40]. As a model reaction, the reaction using diphenylacetylene (16h), butyl acrylate (18a), CO2, and

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

• spirocyclic oxindole γ-lactams). There have been other groups in the past, including our own research group, who have reported on post-modified Ugi-four-component synthetic strategies (Scheme 1) towards the synthesis of 2-oxindoles and spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones and spiro[indoline-3,2

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

• )-diones 4. Modified sequence for the synthesis of acceptor-substituted 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones 4. Pseudo four-component synthesis of (E)-2,9-diphenyl-3-(phenylimino)-2,3-dihydro-1H-benzo[f]isoindol-1-one (5). Synthesis of 6-phenyl-12H-benzo[f]benzo[4,5]imidazo[2,1-a]isoindol-12-one (6

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• oligosaccharides including those containing both 1,2-cis and 1,2-trans linkages, branching sequences and sulfate esters. For example, a four component preactivation-based one-pot synthesis was designed to synthesize Globo-H, an important tumor-associated carbohydrate antigen (Scheme 18) [60]. Globo-H

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

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• found in natural and pharmaceutical products. Results and Discussion Multicomponent motifs to build single rings In this section we consider the partitioning of 3- to 12-membered monocyclic rings according to two-, three-, and four-component couplings since these ring sizes and partitions have immediate

• circle, its algebraic representation is indistinguishable from its ring dissection map representation. where r is the ring size (4, 6, 8, …). where r is the ring size (3, 5, 7, …). (iii) four-component couplings Equation 4 and Equation 5 give the relationships for the number of unique four-partitions of

• heterocyclic ring that contains only one nitrogen atom instead of two. Scheme 12 shows a novel [2 + 2 + 1 + 1] four-component strategy by Orru [193][194]. Since the Biginelli adduct is an even-membered ring with alternating nucleophilic and electrophilic centres, all but two of the cited examples do not

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• and have inspired the development of new multicomponent coupling reactions. Isocyanide-based multicomponent couplings [1], led by the foundational Ugi four-component coupling [2][3], have been used extensively for the synthesis of natural products and the preparation of diverse heterocyclic scaffolds

• reactants for the four-component Ugi–Smiles coupling [21]. A notable exception is one reported example of 2-furaldehyde participating in a Ti(O-iPr)4-catalyzed modified Ugi–Smiles reaction that used an isocyanide as an amine equivalent [22]. We recently reported a successful tandem Ugi–Smiles intramolecular

• , initial studies evaluated only amines that included an available alkene for participation in a tandem US-IMDA reaction. However, these amine components provided access to uncyclized Ugi–Smiles adducts, demonstrating the first successful four-component Ugi–Smiles reactions with a furyl-substituted aldehyde

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

• )phosphonates. Synthesis of phosphonodihydropyrans via a domino Knoevenagel/hetero-Diels–Alder process. Multicomponent synthesis of phosphonodihydrothiopyrans via a domino Knoevenagel/hetero-Diels–Alder process. One-pot four-component synthesis of 1,2-dihydroisoquinolin-1-ylphosphonates under multicatalytic

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• such procedures were evaluated within the preliminary study. The first protocol that we analyzed was reported by the group of Tian. It involves a four-component coupling of aldehyde 10 with CbzCl for activation of the nitrogen source, HMDS and allyltrimethylsilane (11) in the presence of catalytic

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

A convenient four-component one-pot strategy toward the synthesis of pyrazolo[3,4-d]pyrimidines

• Mingxing Liu,
• Jiarong Li,
• Hongxin Chai,
• Kai Zhang,
• Deli Yang,
• Qi Zhang and
• Daxin Shi

Beilstein J. Org. Chem. 2015, 11, 2125–2131, doi:10.3762/bjoc.11.229

• -6-(2-nitrophenyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine was determined by single crystal X-ray diffraction. Keywords: four-component; one-pot; pyrazolo[3,4-d]pyrimidine; sodium alkoxide; Introduction Heterocycles containing a pyrimidine ring are extensively present in natural products and are very

• ]. The differences between their and our strategy are that we developed a four-component combined reaction to synthesize pyrazolo[3,4-d]pyrimidines, the catalyst that we use is different, the universality of the substrates are very broad and the substrates are more readily available. Results and

• disclosed an efficient one-pot four-component synthesis of pyrazolo[3,4-d]pyrimidines. The simplicity of execution, readily available substrates and the potentially important use of the products make this synthetic protocol attractive for academic research and practical applications. Further studies towards

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

• -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

• -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

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• aldehyde), an amine, an isocyanide, and a carboxylic acid (Scheme 13) [77][78]. The Ugi MCRs involving a nucleoside as the substrate bearing the formyl, amino, or isocyano group have been reported. The four-component Ugi reaction employing 3',5'-di-O-acetyl-5-formyl-2'-deoxyuridine (14) as the key

• its epimer (Scheme 21) [87]. After completion of the synthesis of the urea dipeptide 53 bearing the cyclic moiety found in muraymycin D2, the four-component condensation was performed similarly as in [86] to yield the protected product 54 as a 1:1 diastereomeric mixture. Functional group manipulation

• purine nucleoside (i.e., adenosine) was modified (Scheme 25). Tungstophosphoric acid (H3PW12O40) was employed as a catalyst (2 mol %). Hybrids 71 originated from the pseudo-four component cascade employing two equivalents of barbituric acid. The authors demonstrated that the method was applicable with

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• diversity by a one-pot operation, we attempted to realize a four-component (4CR) version. An equimolar mixture of isatin and (S)-phenyl ethylamine was reacted with 2a (2 equiv) and 3a (2 equiv) in methanol in the presence of MgSO4 as a dehydrating agent to promote the formation of the ketimine

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

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• these results obtained in the liquid phase, Hall and co-workers also examined the suitability of a solid-phase strategy. Finally, due to problems of purity encountered with an N-arylmaleidobenzoic acid-functionalized resin [70], or availability of the supported aldehyde partner, a four-component variant