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

• chemical space with the aim of finding new biologically active structures. Modern chemistry offers several approaches, for instance, diversity oriented synthesis (DOS) for the generation of diverse compound libraries [6][7][8]. From this point of view, multicomponent reactions (MCRs), including isocyanide

• -pyrazole-4-carboxamide and 3-amino-5-methylisoxazole as an amine component in isocyanide-based multicomponent reactions was studied. Particularly, 5-amino-N-aryl-1H-pyrazole-4-carboxamide reacted as 1,3-binucleophile with aromatic aldehydes and alkylisocyanides with the formation of 3-(alkylamino)-N,2

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

• clinical trials [14]. Multicomponent reactions (MCRs) [15][16][17][18][19], comprising three or more components, provide straightforward approaches to a wide range of heterocycles through the formation of various bonds in a one-pot process. These reactions not only greatly accelerate chemical syntheses [20

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• -tetrafluorocyclohexane aldehydes 4 were used successfully in Ugi multicomponent reactions [11][12]. In this paper we report the preparation of amines of this series starting from a Birch reduction on benzonitrile, and with a similar methyl iodide quench, to generate amines 5, which are stable to hydrogen fluoride

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• cyanoacetates (α-cyanoesters). These compounds are particularly versatile reagents in organic synthesis including multicomponent reactions [109][110][111][112][113]. However, like decarboxylation for related malonic ester or acetoacetates, an easy access to the removal of the cyano group should encourage future

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

• ; multicomponent reactions; Passerini reaction; tandem reactions; Introduction Multicomponent reactions (MCRs) are fascinating straightforward reactions for the preparation of diversely substituted products starting from three or more precursor molecules, forming products containing atoms/moieties of all

• Passerini or Ugi reactions in a sequential one-pot procedure [32]. Furthermore, up to eight components were reacted by the combination of three multicomponent reactions [33]. In 2010, the Ugi reaction and the Ugi–Smiles reaction were combined by Westermann et al. [34]. In addition, the Ugi reaction was used

• first reaction step, different 3,4-dihydropyrimidin-2(1H)-one acids were synthesized, isolated and fully characterized. These products were subsequently used in a Passerini reaction utilizing a dichloromethane/dimethyl sulfoxide solvent mixture. By variation of the components in both multicomponent

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

• reaction for the construction of acyclic acylhydrazino-peptomers. The consecutive multicomponent reactions produced a variety of acylhydrazino-peptomers in moderate to excellent yields (47–90%). These compounds are multifunctional intermediates that can be further functionalized to obtain new

• 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

• , pyrazole, and the Biginelli adduct as target ring systems with a view to discover new and greener strategies for their construction using multicomponent reactions. The application of the method is also extended to various heterocycles found in many natural products and pharmaceuticals. Keywords: atom

• greenness” as a core principle based on reaction design was applied to a database of named organic reactions [10] and multicomponent reactions (MCRs) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49

• the total number of possible 2-, 3-, and 4-partitions. These correspond to all possible 2-, 3-, and 4-component coupling assemblages. The 3- and 4-component couplings are commonly referred to as multicomponent reactions (MCRs). Next, we list and draw out each of these partitions in the form of target

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• cycloaddition one of the most valuable means of combinatorial chemistry. Such multicomponent reactions are characterized by productivity, operational simplicity, and efficiency [9][10][11][12][13]. A highly interesting class of heterocycles which is accessible through 1,3-dipolar cycloaddition reactions are

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

Thiophene-forming one-pot synthesis of three thienyl-bridged oligophenothiazines and their electronic properties

• Dominik Urselmann,
• Konstantin Deilhof,
• Bernhard Mayer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2016, 12, 2055–2064, doi:10.3762/bjoc.12.194

• ; copper; cyclic voltammetry; DFT; microwave-assisted synthesis; multicomponent reactions; palladium; phenothiazines; thiophenes; Introduction Oligothiophenes [1][2][3][4][5][6][7][8] have adopted a dominating role among functional π-electron systems [9]. In particular, they have received attention as

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• a diversity of multicomponent reactions, which includes trapping of onium ylides by different electrophiles, such as activated С=С, С=O, C=N and other bonds [9]. A plethora of works aimed at realization of this “metal–carbene” methodology appeared in the last few years. Thus a diastereoselective

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• . Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step. Keywords: α-ketoamides; aziridines; multicomponent reactions; nitrogen heterocycles; one-pot reactions; peptide mimics; vicinal tricarbonyl compounds; Introduction Aziridine

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

• Multicomponent reactions (MCRs) have attracted considerable attention in organic and medicinal chemistry due to their high efficiency, simple operability, atom economy and unmatched versatility [1][2][3][4][5][6]. Especially, these reactions serve as an ideal synthetic tool for the assembly of structurally

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

• Mohammad Haji Chemistry Department, Science and Research Branch, Islamic Azad University, Tehran, Iran 10.3762/bjoc.12.121 Abstract Multicomponent reactions (MCRs) are one of the most important processes for the preparation of highly functionalized organic compounds in modern synthetic chemistry

• . As shown in this review, they play an important role in organophosphorus chemistry where phosphorus reagents are used as substrates for the synthesis of a wide range of phosphorylated heterocycles. In this article, an overview about multicomponent reactions used for the synthesis of heterocyclic

• compounds bearing a phosphonate group on the ring is given. Keywords: multicomponent reactions; organophosphorus chemistry; phosphorus reagents; phosphorylated heterocycles; Introduction Heterocyclic rings are found in many naturally occurring compounds and they compose the core structures of many

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

• already been reported in preliminary form [31]. Homoallylic amines of type 12 may be efficiently obtained through multicomponent reactions. These involve the nucleophilic allylation of imines which may be generated in situ by the condensation of an amine and a carbonyl compound. As shown in Scheme 2, two

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• , allowing the introduction of five diversity inputs. Keywords: aminoalcohols; isocyanides; multicomponent reactions; peptidomimetics; Ugi reaction; Findings Isocyanide-based multicomponent reactions [1][2][3], such as the Ugi reaction, were demonstrated to be very useful in the rapid assembly of complex

• is considered excellent for isocyanide-based multicomponent reactions, due to the very low steric biases of isocyanides. We then moved on to establish the scope of the method, varying the Boc-protected aminoalcohol, the carboxylic acid and the isocyanide (see Table 2). For a comparison, we performed

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• ], multicomponent reactions [8], ring-closing metathesis approaches [9][10], tandem reactions of 1,3-dicarbonyl compounds [11][12] and cyclocondenzation reactions of salicylic aldehydes with α,β-unsaturated carbonyl compounds [13][14][15]. The utility of some of these methods are limited by drawbacks such as

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• ; copper catalysis; multicomponent reactions; tetrasubstituted carbon; triazole; Introduction 1,2,3-Triazoles demonstrate wide spread application in biological systems and drug development [1][2][3][4][5][6][7][8][9][10][11][12]. Copper-catalyzed azide–alkyne cycloadditions (CuAAC) regioselectively

• ]. The lengthy synthesis of tetrasubstituted propargylamine precursors limits the exploration of such alpha-tetrasubstitued triazoles. The vast majority of three-component couplings produce trisubstituted propargylamines. Copper remains the most popular catalyst for these multicomponent reactions

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

• : aminoalcohols; free-radical addition; imine; multicomponent reaction; titanium salts; Introduction Multicomponent reactions (MCRs) represent a green approach towards the synthesis of polyfunctionalized molecules by promoting multiple bond-forming mechanisms in a one-pot synthesis [1][2][3][4][5][6][7

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

• -libraries of homo- and heterodimers verified by ESI-MS and HPLC. In a preliminary evaluation, some compounds display moderate activity against the Gram-positive bacterium Bacillus subtilis. Keywords: antibacterial; combinatorial; diynes; homodimerization; multicomponent reactions; peptoids; Ugi reaction

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• spectrum of biological activity [5][6], which led to choose acetoacetamides as perspective methylene-active compounds for further studies of multicomponent reactions. The interactions of 3-oxobutanamides with aldehydes and a number of aminoazoles, namely 3-amino-1,2,4-triazoles [7][8][9][10][11], 5

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• hypervalent iodine reagents [9][10][11][12], and homogeneously or heterogeneously catalyzed multicomponent reactions [13][14]. Moreover, radical cyclizations predominantly conducted using Bu3SnH in the presence of azobisisobutyronitrile (AIBN) play a crucial role [15][16]. However, all these methods require

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

• efficient and practical synthetic procedures have emerged for the synthesis of versatile spirooxindole-fused heterocycles [5][6][7][8][9]. In recent years, because of the emphasis on the development of green and sustainable chemistry, multicomponent reactions have been developed as efficient and potent

• tools for the preparation of structurally diverse molecules. Practically, multicomponent reactions based on the versatile reactivity of isatins and their 3-methylene derivatives have emerged in large numbers and become the new efficient protocols for the synthesis of various spirooxindoles [10][11][12

• [indoline-3,4'-pyrano[2,3-c]pyrazoles] have been developed very recently by several groups [25][26][27]. Against this background and in continuation of our efforts toward the development of practical multicomponent reactions based on the reactivity of isatin and its derivatives [28][29][30][31][32][33][34

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

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

• methods provide amidines in acceptable yields, they suffer from limitations such as limited structural diversity of the final products. Since multicomponent reactions (MCRs) are expected to provide a rich structural diversity, much attention was paid on the development of multicomponent-coupling

• strategies for the synthesis of amidines. The Ugi reaction is probably one of the best multicomponent reactions to provide huge structural diversification of the products [12]. Thus, several modifications of the Ugi reaction were explored recently. As depicted in Figure 1, diamides, α-amino amides, and α