New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• ]. Continuing our interest in the synthesis of N-heterocycles via the aza-Wittig reaction and multicomponent reactions [36][37][38], we wish to report herein a facile synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• ], disulfide- [13], thioether- [14][15][16][17][18][19][20], triazole- [21][22], oxime- [23] and hydrazone formation [24] as well as multicomponent reactions such as the Ugi- or Petasis reaction [25][26][27][28][29][30][31][32]. The content of helicity can moreover be changed by the introduction of a photo

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• ; cyclization; multicomponent reactions; synthetic methods; tetrahydroisoquinoline; Introduction The tetrahydroisoquinoline moiety is the key structure in large number of natural and synthetic biologically important molecules. Among them, isoquinoline alkaloids constitute a large family of natural products

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• (diphenylphosphino)ethane (DPPE) as ligand improved the yield of the anthraquinones. Representative examples included anthraquinones 179a and 179b obtained from terminal alkynes and 179c and 179d from internal alkynes [75]. Multicomponent reactions In 2009, Singh and co-workers reported a solvent-free methodology to

• multicomponent reactions employing 2-hydroxy-1,4-naphthoquinone (186), β-naphthol (181), and aromatic aldehydes. Synthesis of substituted anthraquinones catalyzed by an AlCl3/MeSO3H system. Palladium(II)-catalyzed/visible light-mediated synthesis of anthraquinones. [4 + 2] Anionic annulation reaction for the

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• 1,2,3-triazoles through multicomponent reactions and the relevant mechanistic aspects have been surveyed by Chen, Ren, et al. [27]. The 1,3-dipolar cycloaddition reaction between azides and alkynes is the most efficient pathway for the preparation of disubstituted 1,2,3-triazole derivatives. The copper

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• Shivani Gulati Stephy Elza John Nagula Shankaraiah Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India 10.3762/bjoc.17.71 Abstract Microwave-assisted (MWA) multicomponent reactions (MCRs) have successfully emerged as one

• -MCRs and their mechanistic insights over the past decade and shed light on its advantage over the conventional approach. Keywords: cycloaddition; Knoevenagel condensation; Michael addition; microwave; multicomponent reactions; Introduction Recently, organic chemists are focussed to develop

• capacity and modes to achieve the uphill task easily [19]. The contemporary organic chemistry procedure involving microwave heating has paved way for the molecular diversity that helps in reducing the time required for the drug discovery process. As multicomponent reactions and microwave reactions hold

Effective microwave-assisted approach to 1,2,3-triazolobenzodiazepinones via tandem Ugi reaction/catalyst-free intramolecular azide–alkyne cycloaddition

• Maryna O. Mazur,
• Oleksii S. Zhelavskyi,
• Eugene M. Zviagin,
• Svitlana V. Shishkina,
• Vladimir I. Musatov,
• Maksim A. Kolosov,
• Elena H. Shvets,
• Anna Yu. Andryushchenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2021, 17, 678–687, doi:10.3762/bjoc.17.57

• harder while the microwave-assisted catalyst-free conditions were effective for both terminal and non-terminal alkynes. Keywords: click chemistry; microwave chemistry; multicomponent reactions; triazolobenzodiazepines; Ugi reaction; Introduction Benzannulated heterocycles are among the most important

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• phthalazinone derivatives 5 and 6 (Scheme 1, route B). In the literature, the number of reported synthetic methods for 4-aminophthalazin-1(2H)-ones is limited to a few examples and they usually involve two main approaches: 1) the application of multicomponent reactions starting from, e.g., the available o

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• -generator and blowing agent [1][2]. Moreover, it is a useful building block in organic synthesis, including various multicomponent reactions opening the way to diverse fused heterocycles [3]. Salts with anionic tetrazole, i.e., aminotetrazolates 2, and cationic ones, i.e., aminotetrazolium salts 3, are

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• one-pot Mannich/Michael sequence leading to oligocyclic compounds [24], and employment in subsequent Joulié–Ugi multicomponent reactions [25]. This work is an extension of these efforts and seeks to investigate the possibility of incorporating the Ugi–azide multicomponent reaction in this workflow. A

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• pyrrole syntheses [9][10][11], which have been developed to harvest the pyrrole frameworks. In the past few years, the interest in developing new methods to synthesize this heterocyclic motif has rapidly grown; transition metal-catalyzed cyclization [12][13][14] and multicomponent reactions [15][16][17

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• reaction; Introduction A multicomponent approach towards the synthesis of the desired product offers a number of advantages over a stepwise method. Such advantages include the development of a design that is: cheaper, simpler, economical, and environmentally friendly [1][2]. Multicomponent reactions are

• not new to research. The pioneer multicomponent reactions are the Hantzsch (1882), Biginelli (1891), Mannich (1912), Passerini (1921), and Ugi (1959) reactions [3]. The significance of such a phenomenal approach for the synthesis of novel compounds first began as a way of increasing the chemical

• under argon, they obtained a mixture of the two regioisomers (1,4-DHP/1,2-DHP 32:68), proving further the complexity of this reaction [19]. Therefore, continuing our studies for the development and application of environmentally friendly methodologies for multicomponent reactions [20], we attempted to

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position. Keywords: cinchona alkaloids; electrophilic fluorination; enantioselective synthesis; 2-oxo-aldehydes; Ugi reaction; Introduction Multicomponent reactions (MCRs) [1][2][3][4][5][6

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• the broad tunability of their physicochemical properties and the ability to act not only as solvents but also as catalysts and reagents, DESs have progressively replaced toxic and volatile organic solvents (VOCs) in countless heterocyclodehydration processes and multicomponent reactions (MCRs) [1][2

Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation

• Kumar Godugu,
• Venkata Divya Sri Yadala,
• Mohammad Khaja Mohinuddin Pinjari,
• Trivikram Reddy Gundala,
• Lakshmi Reddy Sanapareddy and
• Chinna Gangi Reddy Nallagondu

Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156

• –proline, trimethylsilyl chloride (TMSCl), Amberlite® IR-120, indion 190, trifluoroethanol, YCl3, HClO4–SiO2, MMZY zeolite, Er(OTf)3, etc. [22][23][24][25][26][27][28][29][30]. Developments in already established multicomponent reactions (MCRs) are interesting topics in organic synthesis. For instance, the

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• structures of 1,3,5-triazine-2,4-dithione derivatives were characterized by spectroscopic techniques as well as by single crystal X-ray diffraction. Keywords: aldehydes; multicomponent reactions; nitrogen heterocycles; thiourea; triazinethiones; Introduction The construction of nitrogen-containing

• benign methodologies for the generation of structurally diverse triazinethione derivatives is still challenging in organic synthetic chemistry and medicinal chemistry. Multicomponent reactions (MCRs) gained much interest among synthetic organic chemists as well as in combinatorial chemistry and drug

• discovery as versatile tools for the construction of different biologically active compounds by combining three or more starting materials into a single product in one convergent chemical step [19][20][21][22][23]. Among multicomponent reactions, aldehydes have emerged as one of the most useful class of

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• ]isoquinolines and related ring systems [11][12][13][14][15], while medicinal chemists have also been interested in making related compounds for biological screening and drug development [16][17]. Multicomponent reactions (MCRs) have been developed as highly efficient tools for assembling heterocyclic scaffolds

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• –84% yields (Scheme 59) [97]. The Ugi-type multicomponent reactions between imines, carboxylic acids, and isocyanides, and Mannich-type reactions between iminium and carbonyl groups have found many applications in organic synthesis [108]. Che’s group employed the methodology of oxidation of an amine

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

• has the potential to produce a large number of tetramic acid analogues, which cannot be easily accessed by the classic synthetic methods. Keywords: Dieckmann cyclization; multicomponent reactions; nitrogen heterocycles; one-pot reaction; Ugi reaction; Introduction Nitrogen-containing heterocycles

• medicinal chemistry. Multicomponent reactions (MCRs) [22][23][24] are emerging tools for assembling complex molecules in a rapid and efficient manner. The four-component Ugi reaction followed by a suitable post modification of [25][26] has become a popular research field for diversity-oriented synthesis [27

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• reactions, Ugi–Smiles reactions, Mizoroki–Heck reactions, aldol reactions, oxidation and dehydration reactions, Mannich reactions, and multicomponent reactions. Because of the mentioned reasons as well as due to the low toxicity of silica nanoparticles, they are often a good option [24]. For this review

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

• α,β-unsaturated ketones [8][9][10][11] or via their multicomponent analogues. On the other hand, multicomponent reactions (MCRs) directly leading to tetrahydroazolopyrimidine heterocyclic systems have also been published [4][5][16][17][18][19][20][21][22][23][24]. In particular, multicomponent

• . Therefore, the present work is devoted to the study of multicomponent reactions involving 3-amino-1,2,4-triazole or 5-aminopyrazoles, aromatic aldehydes, and pyruvic acid or its esters under ultrasonication. Results and Discussion It was discovered that MCRs involving 3-amino-1,2,4-triazole or 5-amino-1H

• reactions involving pyruvic acids (pyruvates) and different α-aminoazoles. Synthesis of 4-arylamino-substituted tetrahydroquinolines. Ultrasound-assisted multicomponent reactions of 3-amino-1,2,4-triazole or 5-amino-1H-pyrazole-4-carbonitrile, aldehydes, and pyruvic acid/ethyl pyruvate. Synthesis of 3-cyano

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• ; chemoinformatics; Cu-catalysis; cycloadditions; molecular scaffolds; multicomponent reactions; Introduction The screening of small molecule libraries is a well-established approach in early-stage drug discovery to identify hit candidates for the development of drug leads. The application of unconventional

• reference set of brand-name blockbuster drugs (orange squares). Synthetic strategies for accessing pyrrolocyclopentenone derivatives, including the novel couple/pair approach that combines the KA2 and PK multicomponent reactions. L.A. = Lewis acid; PK = Pauson–Khand. Couple/pair approach using combined KA2

• and Pauson–Khand multicomponent reactions. Follow-up chemistry on compound 5 taking advantage of the enone chemistry. Reaction conditions. (i) NaBH4 (2 equiv), CeCl3.7H2O (2 equiv), DMC/MeOH 1:1 (20 mL/mmol), 25 °C, 1 h; (ii) m-CPBA (1 equiv), DCM (6.5 mL/mmol), 0 °C, 4 h; (iii) EtMgBr 3 M in Et2O (5

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• to the N–O· group. Keywords: domino reactions; EPR; nitroxide; spin relaxation; Introduction Domino reactions have attracted much attention as an approach for the synthesis of complex molecules in a few steps [1]. The utility of multicomponent reactions involving amines, activated olefins and

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

• tetrazole ring takes part in the catalytic reaction mechanism by chelating Rh(III) upon activation of the amide ortho-position. This work illustrates the synthetic potential of combining isocyanide-based multicomponent reactions with metal-catalyzed transformations to generate structural diversity and

• /pyridone hybrids by means of a reaction sequence comprising an Ugi-azide-4CR and a Rh(III)-catalyzed annulation as key steps (Scheme 1D). Results and Discussion In previous works, our group has described a variety of synthetic approaches that combine the diversity-generating character of multicomponent

• reactions (MCRs) with the large synthetic scope of metal-catalyzed cyclization protocols [49][50][51][52][53][54]. In this sense, we envisioned that the application of modern Ru(II) or Rh(III)-catalyzed annulations on Ugi-azide-4CR-derived scaffolds could be a promising strategy to generate novel hybrid