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

• ] where fundamental organic reactions are combined in one-pot sequences [25][26][27][28][29]. Multicomponent reactions (MCR) take advantage of creating and transforming reactive functionalities in the same reaction vessel without intermediary work-up [30]. Syntheses of functional chromophores by MCR [31

• ][32] have indeed become a powerful tool in synthetic chemistry for convergently approaching substance libraries of luminescent molecules. In particular, blue-emissive heterocyclic chromophores, intensively requested in illumination research, are equally accessible by MCR strategies [33]. Cyclic imides

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• for dye complexation, K11, and the corresponding ΔH and TΔS were derived from the UV–vis data as described in the Results and Discussion section. Rheology Rheological measurements were carried out with a Physica MCR 501 (Anton Parr GmbH) stress-controlled rheometer with a 25 mm cone and plate geometry

A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy

• Taofeng Shao,
• Zhiming Gong,
• Tianyi Su,
• Wei Hao and
• Chao Che

Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82

• attracted broad attention in the field of organic synthesis [40][41][42]. In order to expand the structural diversity of GBB products, further investigation of GBB-based synthetic strategies remains highly desirable. In continuation of our research on the development of MCR strategies for the rapid library

• isoquinoline-containing derivatives. GBB-based MCR strategy for the imidazo[1,2-a]pyridine-fused isoquinoline derivatives. Optimization of the cyclization reaction conditions.a Substrate scope for the syntheses of compounds 4 and 6.a Supporting Information Supporting Information File 174: Characterization

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• -dimethylaminobenzoate. FTIR spectra were measured using an iS10 FTIR spectrometer (Thermo Scientific). Viscosity was measured on an Anton Paar Physica MCR 300 equipped with CP 50-1 plate–plate geometry at a shear stress τ of 5 Pa and 25 data points from 0.72 to 1450 rad were taken and averaged. Refractive indices (RI

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• scale. This calculation (MCR-ALS, multivariate curve resolution – alternating least squares) gives the concentration profiles of the components and also the spectra of pure components. From Figure 3, it can be seen that the addition reaction was complete after 3.5 h. Finally, the characteristic IR

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• in the construction of functionalized spiro compounds. We report herein the facile synthesis of novel spiropyrrolidine compounds through a one-pot three-component reaction involving N-substituted vinylindole/indazole, ninhydrin and sarcosine/L-proline. The present multicomponent reaction (MCR) leads

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

• hydrazino-Ugi reaction (or a classical Ugi reaction). The hydrazides 3a–c used in the first MCR were prepared by the reaction of glycine-derived esters 2, 5 and 7 with hydrazine monohydrate (hydrazinolysis), following a known procedure [63][64] (Scheme 2). The obtained hydrazides were then reacted with

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

• integer partitioning algorithm to monocyclic rings. Supporting Information File 367: Excel file of an MCR database of literature routes to various heterocycles. Supporting Information File 368: Excel file of statistics AE(min) and probability of intrinsic greenness for heterocyclic MCRs. Acknowledgements

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• ; tetrahydroquinazoline; Introduction The synthesis of new molecules with potential biological activity through pot, atom and step-economic (PASE) reactions is an attractive green organic technique [1][2][3][4][5]. By the combination of multicomponent reactions (MCR) [6][7][8][9][10][11] with stepwise one-pot reactions

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• scaffolds can be constructed in great diversity by a multicomponent reaction of amidines, aldehydes and isocyanides. This MCR, a variant of the Ugi reaction [24][25], was discovered independently by three groups and is known as the Groebke–Blackburn–Bienaymé (GBB) reaction [26][27][28][29]. The reaction

• development of new GBB-based methods for the efficient synthesis of novel polycyclic fused imidazo[1,2-a]pyridines is highly desirable. In an earlier study, we have developed a GBB/lactamization MCR strategy, which provided the rapid access to isoquinolinone-fused imidazo[1,2-a]pyridines with potent and

• selective CDK2 inhibition properties [34][35]. As a continuing effort, we report herein our recent efforts in the development of a GBB-based MCR method for the one-pot synthesis of diverse quinazolin-2-one fused imidazo[1,2-a]pyridines (Scheme 1). Parts of the work have been disclosed in a previous patent

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

• . Some of these post-MCR transformations are: intramolecular cycloaddition reactions, Knoevenagel condensations, metathesis reactions, aza-Wittig reactions, Mitsunobu reactions, etc. [21]. Up to now, two review articles have been reported on azaheterocyclic phosphonates [22][23], but no overview article

• about the multicomponent synthesis of phosphono-substituted heterocycles has been reported so far. This review focuses on general multicomponent reactions as well as on modified MCR towards heterocyclic phosphonates. It is organized by the reaction types and covers literature published up to September

• irradiation. Thus, the development of novel MCR based on phosphorous reagents would allow the synthesis of macrocyclic and medium or large-sized heterocyclic systems, substances which are currently underrepresented in the literature. Further, the design of new biocompatible scaffolds such as β-lactams and

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• approach. In fact, our procedure requires neither the preformation of imines nor anhydrous media, due to the coordinating effect of titanium salts, which promote the one-pot synthesis of amino derivatives according to a classical MCR. The basic approach consists of the simple mixing of an aniline, an

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

• . In addition, HPLC analyses revealed that an adjacent stereocenter (Table 1, entry 8, 7h/8h) does not racemize under the reaction conditions of both the MCR and the Glaser coupling. Due to the high selectivity and high conversions found in the Glaser coupling step, our attention turned toward the

• activity of the active ligand moieties. Conclusion In summary, a reliable sequential U-4CR/Glaser coupling approach towards the synthesis of 1,3-diyne-linked peptoids was developed. The strategy resulted in a library consisting of ten homodimers in good yields. The post-MCR copper-catalysed homocoupling

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• is attached either to the carbamate or amide (Figure 5) [69][70][71] (using a platinum anode and tungsten cathode electrochemical set-up) [69] or the use of Cu-PyBox chiral ligand systems [72]. The cation pool method can be adapted to a multicomponent reaction (MCR) when an N-acyliminium ion is

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

• -withdrawing substituents as in 2e–g resulted in decreased yields. α-Methylcinnamaldehyde (2i) as an uncommon isocyanide-based MCR component was successfully subjected to the GBB reaction, leading to the formation of the corresponding bicycles 38–41 in yields of 26–67%. All the reactions except those based on

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• part of our ongoing interest towards the synthesis of new molecular libraries [21][22][23][24], we were interested in developing a one-pot MCR strategy for the synthesis of amidines. Results and Discussion To check the feasibility of the iodine-catalyzed amidine synthesis through the modified Ugi

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• afforded the corresponding pyrazolo[4,3-c]pyridine 5-oxides 7a–c by a regioselective 6-endo-dig cyclisation [30] in high yields. Moreover, we tested an alternative approach to access compounds 7 through multicomponent reactions (MCR). Attempts to react chloroaldehyde 2 with hydroxylamine hydrochloride and

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

• employment of MCRs in the synthesis of nucleoside analogs. The references were selected in accordance with the definition of a MCR given by Ugi et al.: “a multicomponent reaction comprises reactions with more than two starting materials participating in the reaction and, at the same time, the atoms of these

• educts contribute the majority of the novel skeleton of the product” [44]. In this review, we understand educts as compounds that contribute carbon atoms to the MCR product [45]. By the analogy to nucleosides included in the DNA/RNA nucleic acids, this review is limited to MCRs involving furanosyl

• carbon atom. Conclusion In this comprehensive review application of multicomponent reactions (MCRs) in nucleoside chemistry has been presented. In recent years, growing interest in the construction of novel nucleoside scaffolds by MCR has been observed. This conclusion is supported by the fact that 23

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• (Scheme 1, path C) as a multicomponent reaction (MCR). The utility and importance of MCRs have been recognized by chemists [20][21][22][23]. Several MCRs are now well-established reactions, such as Ugi [24], Passerini [25], Van Leusen [26], Strecker [27], Hantzsch [28], and Biginelli [29][30][31]. However

• % yield upon stirring at rt and microwave irradiation, respectively (path B). However, in the MCR approach (Scheme 1, path C) the desired product was obtained in a good yield. The reaction proceeded smoothly in the presence of CuSO4.5H2O and D-glucose under microwave irradiation for 15 min and gave the

• desired compound in 80% yield. Surprisingly, under conventional heating with this MCR approach no product formation was observed, even after an extended period of time (24 h) with heating under reflux . In order to optimize the reaction conditions for this protocol, we screened several organic solvents

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

• cyclic constrained peptidomimetics, the acyclic products have to be cyclized via additional cyclization strategies. This is possible via incorporation of bifunctional substrates into the initial IMCR. Examples of such bifunctional groups are N-protected amino acids, convertible isocyanides or MCR

• . Besides saving time and reagents, another major advantage of these reactions is the ability to combine commercially available or readily accessible starting materials with a variety of functionalities in one-step. Further, MCR-based strategies can cover a broader range of chemical space because a large

• . the incorporation of bifunctional substrates or by activation of functionalized substrates in the initial MCR [19]. The Passerini reaction The first isocyanide-based MCR was described by Mario Passerini in 1921 and named after him. The Passerini reaction is a three-component reaction (3-CR) and

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• recently, silver–NHC complexes were found to be valuable catalysts for this MCR. Their first application was reported by Wang and co-workers in 2008 [12], who developed a polystyrene-supported NHC–Ag(I) complex as an efficient catalyst for the A3-coupling under solvent-free conditions, at room temperature

• without a significant loss of its catalytic activity. Similar PS–NHC–silver complexes were recently prepared via click-chemistry, and their aptitude to catalyze A3-coupling was verified [13]. The suitability of NHC–Ag(I) complexes as catalysts for A3-coupling MCR was confirmed, and independently developed

• an effective KA2-MCR, that is, the substitution of aldehyde partners with less reactive ketones. This issue was partially solved by Ji and co-workers, who found with AuBr3 (4 mol %), no-solvent and 60 °C the best conditions to react alkyl ketones, secondary amines and aryl/alkylacetylenes to give the

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• reactions [2], especially the intramolecular Mitsunobu reaction of alcohols with phenols or sulfonamides. By exploiting a single post-MCR transformation (the Mitsunobu reaction) it is possible to obtain several diverse heterocyclic scaffolds by installing the two additional groups in any of the four

Multicomponent reactions II

• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 115–116, doi:10.3762/bjoc.10.7

• Thomas J. J. Muller Heinrich-Heine-Universität Düsseldorf, Institut für Makromolekulare Chemie und Organische Chemie, Lehrstuhl für Organische Chemie, Universitätsstr. 1, 40225 Düsseldorf, Germany 10.3762/bjoc.10.7 Keywords: multicomponent; The concept of multicomponent reactions (MCR) [1] has

• addition, a lot of syntheses of heterocycles from the early days are MCR, and these reaction sequences paved the way to a multitude of applications. Moreover, Ugi's groundbreaking developments in isonitrile-based chemistry and his conclusions demonstrated that MCR are not only highly practicable in the

• light of approaching the ideal synthesis [3][4] as one-pot methodologies, but rely on a reactivity based concept [5]. The perpetual generation of reactive functionalities and reactivity is the underlying general principle. Therefore, MCR are intriguing for industrial applications. But they are also

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• imines with isocyanides is mainly focused on to the well-known Ugi multicomponent reaction (MCR) [1]. This fundamental process features the participation of a carboxylic acid group which attacks the intermediate nitrilium ion thus leading, after the Mumm rearrangement, to α-amidoamides. However, the

• . Compounds 4 and 5 could not be detected (Scheme 2). When the process was run as a true MCR (mixing the amine, the aldehyde and two equivalents of isocyanide 2a), the adduct 3a was produced in trace amounts and the main product was the α-amino-amidine 4, in good agreement with previous reports [5][6][7][8

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265