Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• multicomponent one-pot (3 + 2) cycloaddition reactions involving azomethine ylides from isatins and amino acids [21][35]. The main feature of this review is that we have attempted to consider all currently known systems for generating azomethine ylides based on carbonyl compounds and amino acid derivatives (or

• of regio- and endo-stereoselective spiro- and dispiro-derivatives of azabicyclo[3.2.0]heptane 151 and 152 is due to orbital control along with second orbital interactions [101]. In 2015, Wu and co-workers described a multicomponent synthesis of various spiro[indole-pyrrolizine], spiro[indole

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• possible to use an ester group for the cleavage of 3-sulfonylpyrrolidines, it required a longer reaction time and provided a slightly lower overall product yield (77%) compared to the use of the benzoyl group. With an optimized synthetic route in hand – comprising a multicomponent reaction of ketosulfone

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• direct access to scarcely explored open-chain quinolinone esters, expanding the medicinal chemistry toolbox with promising scaffolds for drug discovery. Keywords: antibacterial activity; 4-hydroxyquinolin-2(1H)-one; ʟ-proline catalysis; Meldrum’s acid; Michael addition; multicomponent reaction

• ; Introduction Contemporary organic chemistry focuses on the development of universal, efficient, and environmentally benign synthetic methods that address the challenges of constructing complex molecular architectures [1][2][3]. Among these, multicomponent reactions (MCRs) have emerged as powerful tools

• -hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylpropanoic acid have not, to the best of our knowledge, been previously described. Structurally related compounds, such as 4-aryl-4,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5(3H)-diones, have been reported only in a few cases, typically via multicomponent

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• multicomponent reagent system (Scheme 20A). In an effort to render the transformation more environmentally benign, benzoyl chloride was replaced with triphosgene [73] [bis(trichloromethyl) carbonate, BTC], a putative “greener” surrogate [74]. Nevertheless, the high vapor pressure and associated safety concerns

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• -component cyclization; Introduction The modern strategy of organic synthesis is aimed at conforming to the "green chemistry" principles based on PASE (pot, atom, step, economic) methods. These principles serve as the foundation for multicomponent processes that allow various structurally complex molecules

• to be obtained in one stage using commercially available reagents [1][2][3]. Their ambident properties make 3-oxo esters convenient reagents for the use in multicomponent syntheses, with the Hantzsch [4][5] and Biginelli [6][7][8] reactions being the best known. In the transformations, 3-oxo esters

• starting substrates in multicomponent syntheses [17][18][19]; at the same time, they often show extraordinary reactivity. For example, the introduction of polyfluoroalkyl-3-oxo esters into the aforementioned Hantzsch and Biginelli reactions leads to the hydrated heterocycles, which can provide insight into

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• to replace AcOH by ethanol (Table 1, entry 10), however, the use of ethanol with piperidine was controversial. We found out that, during the reaction with benzaldehyde (1a) and rhodanine (2a), a multicomponent reaction was taking place by a substitution process, leading directly to 2-amino-5

• states: protonated, deprotonated, and neutral. Multicomponent reaction of benzaldehyde, rhodanine, and piperidine in ethanol leading directly to a 2-amino-5-benzylidenethiazol-4-one. Substrate scope of the EDA-catalyzed Knoevenagel condensation reactions using a range of aromatic/heteroaromatic aldehydes

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• -dicarbonyl compounds 23 in good yields. This system showed broad synthetic scope and excellent functional group tolerance of this multicomponent borylacylation, using NHC (20 mol %) and photocatalyst (2 mol %), in K2CO3 (20 mol %) under mild conditions, further highlighting the utility and versatility of

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• applications must persist. In the modern world, one of the main goals of an increasing number of chemists interested in the design and synthesis of versatile organic molecules is to develop atom-efficient, multicomponent, low-cost, and environmentally benign synthetic strategies for these molecules. In the

• purification techniques [62][63][64]. Synthesis of pyrrolo-isoxazolidines utilizing nitrosoarenes via the multicomponent strategy is indeed feasible [65][66]. In a similar manner, Chakraborty obtained diastereomer products, primarily in cis configuration, from the cycloaddition reaction of a fluoro or a furyl

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• piperazinone ring. Keywords: benzodiazepine; click reaction; multicomponent reaction; one-pot; piperazinone; polycyclic; triazole; tetrazole; Ugi–azide reaction; Introduction Triazole, tetrazole, and benzodiazepine are privileged heterocyclic rings commonly found in drug molecules and functional materials [1

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• mediator and proceeding in aqueous solution with pleasure yields, was a simple, convenient, powerful, environmentally benign and sustainable electrooxidative approach towards indolizine. Construction of oxazoles and imidazoles Without any additional oxidants and catalysts, an electrochemical multicomponent

• and reductive cascade annulation of o-alkynylbenzamides. An electrochemical intramolecular 1,2-amino oxygenation of alkynes provided indolizines in reasonable yields. The electrochemical multicomponent reaction was also developed for the construction of oxazole. Pyrrole could be prepared by

• cascade annulation of o-alkynylbenzamide. Electrochemical intramolecular 1,2-amino oxygenation of alkyne. Electrochemical multicomponent reaction of nitrile, (thio)xanthene, terminal alkyne and water. Electrochemical aminotrifluoromethylation/cyclization of alkynes. Electrochemical cyclization of o

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• at illustrating how the chemistry of biobased carbonyl platform molecules with backbones from C2 to C6 offers opportunities to reach all kinds of chemical architectures, sometimes even complex ones benefiting from the ability of the carbonyl group to be involved in multicomponent reactions. Keywords

• : aldehydes; biobased chemistry; biomass; carbonyl; fine chemicals; ketones; multicomponent; platforms; sustainability; Introduction Shifting towards sustainable practices in the chemical industry relies on continued advancement of green chemistry sciences which aim to minimize the global environmental

• ). The obtained hydrocarbons exhibited higher density (0.78–0.88 g/cm3) and higher net heat of combustion (44.0–46.0 MJ/kg) than some commonly commercial fuels [194]. Multicomponent reactions involving the reactivity of furfural are also noteworthy. A Ugi four-component polymerization was developed to

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• National Academy of Sciences of Ukraine, Nauky Av. 60, 61072 Kharkiv, Ukraine, Faculty of Chemistry, V. N. Karazin Kharkiv National University, Svobody Sq. 4, 61077 Kharkiv, Ukraine 10.3762/bjoc.21.163 Keywords: multicomponent reactions; The synthesis of complex molecules is a cornerstone of modern

• optimization of promising lead structures has therefore inspired the development of powerful synthetic strategies. A glance at Web of Science reveals that one-pot methods and multicomponent reactions (MCRs) [1] have attracted steadily increasing attention within the scientific community over the past 25 years

• (Figure 1). According to a quick Web of Science [2] keyword search of "multicomponent reaction" and "one-pot reaction" (Figure 1A) and "multicomponent reaction" (Figure 1B) filtered by publication year, the impressive sum of 136,658 publications on multicomponent (Figure 1A) and one-pot reactions and

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• , 61072, Kharkiv, Ukraine Enamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine Faculty of Chemistry, V. N. Karazin Kharkiv National University, Svobody sq., 4, 61022, Kharkiv, Ukraine 10.3762/bjoc.21.158 Abstract Switchable multicomponent reactions involving 3-substituted-5-amino-1,2,4

• multicomponent reaction of the same starting materials led to the formation of only tetrahydrotriazolopyrimidine derivatives. Keywords: 5-amino-1,2,4-triazole; heterocyclization; multicomponent reaction; salicylaldehyde; ultrasonication; Introduction Multicomponent reactions (MCRs) are a powerful tool for the

• concept of multicomponent-switched reactions [6] allows to tune the selectivity of MCRs and direct them into several different pathways. That is why the study of multicomponent heterocyclizations of aromatic aldehydes, compounds with an active methylene group and aminoazoles, for example with 3-amino

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• substituted 3-(3-oxo-3,4-dihydroquinoxalin-2-yl)propanoic acids containing a pharmacophore quinoxalinone moiety. The tandem Ugi/aza-Wittig combination was also carried out in a one-pot procedure without isolation of the intermediate. Keywords: α-ketoglutaric acid; aza-Wittig reaction; multicomponent reaction

• ; quinoxalinone derivative; Ugi reaction; Introduction Multicomponent reactions are powerful tools in organic chemistry that enable the synthesis of structurally complex and multifunctional compounds from three or more starting materials in a single synthetic step. They are widely used in drug discovery because

• , unlike conventional linear synthesis strategies, they enable the preparation of libraries of organic compounds in higher yields and with significantly less time, resources, and chemical waste [1][2][3][4][5]. The Ugi reaction, discovered in 1959 by Ivar Karl Ugi [6], is one of the classic multicomponent

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• strategies have been explored in recent decades for the synthesis of structurally diverse quinolines. Among them, transition-metal-catalyzed multicomponent reactions (MCRs) have emerged as particularly effective for constructing complex quinoline-based heterocycles [26][27][28]. Catalytic pathways such as

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• become a hot topic in synthetic organic chemistry. Isocyanides (also termed isonitriles) are a class of highly versatile building blocks in organic synthesis, participating in a wide range of transformations including multicomponent reactions (e.g., the well-known Passerini and Ugi reactions) [13][14][15

• substrates under the standard conditions (Scheme 4b). On one hand, such findings demonstrated that the second cyclization determines enantioselectivity; on the other hand, it provided a practical way to the preparation of unsymmetrical pyrido[6]helicenes 26. Isocyanide-based multicomponent reactions Except

• for Pd-catalyzed isocyanide insertion reactions, organocatalytic isocyanide-based multicomponent reactions have been explored for the synthesis of axially chiral compounds. In 2024, Yang and co-workers reported a catalytic asymmetric version of the Groebke–Blackburn–Bienaymé reaction [32][33][34

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• benzamides from isonitriles as well as in multicomponent reactions with isonitriles in general. Only a few examples of photochemical cascade arylation–cyclizations of isonitriles with diaryliodonium salts have been published [31][32][33]. To bridge this gap, we propose a photoredox-mediated strategy for the

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• substitution pattern on the regioselectivity and stereoselectivity of the reactions. A Review article by Papis and co-workers discusses various copper(II) triflate-catalyzed multicomponent reaction types [2]. Therein, the synthesis of cyclic and acyclic compounds, as well as three-component and four-component

• reactions, are separately debated. In addition, mechanistic insights into the reaction of heteropolycyclic systems, cycloadditions, and aza-Diels–Alder reactions are provided. This is important because multicomponent, one-pot reactions have gained interest as potentially more economic, efficient, and

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• , or selenium enables spectral tuning across the visible to near-infrared range, improved photostability, and dual-state emissive behavior. In parallel, significant progress in synthetic methodologies – including enantioselective catalysis, electrochemical cyclizations, and multicomponent reaction

• , enantioselective synthetic approach toward azahelicenes via a chiral phosphoric acid-catalyzed multicomponent Povarov reaction or oxidative aromatization [32]. Among the synthesized compounds, compound 19 displayed dual absorption bands at 260 and 325 nm and emission peaks at 420 and 440 nm, which red-shifted to

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• –Bienaymé (GBB); imidazopyridine; intramolecular Diels–Alder (IMDA); isoquinolinone; multicomponent reaction (MCR); re-aromatization; Introduction Multicomponent reactions (MCRs) have intrinsic green chemistry advantages of synthetic efficiency and operational simplicity. Performing post-condensational

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• ) [131]. In addition, a gram scale operation has been successfully demonstrated. In addition, Hu and co-workers (2020) studied a catalyst-free multicomponent coupling reaction of benzynes derived from alkyne 349, cyclopropenone 309, and sulfoxides to give the corresponding o-(methylthio)phenyl acrylates

• affording cinnamamide (99) in excellent yield. The reaction proceeds via the decarboxylated amide–copper complex 359 (Scheme 79B) [134] and could be scaled-up to a gram scale reaction. Cinnamic acid derivatives could also be accessed via multicomponent reactions. For example, Jana and Ghosh (2019) utilized

• Meldrum’s acid (361), aldehyde 360, and an amine to prepare the corresponding cinnamamides 362–364, natural products of the piperamide family. The multicomponent reaction involves consecutive acetone and CO2 release via 365 and 366 (Scheme 80A) [135]. A multigram scale operation has been achieved smoothly

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• Isatin is a well-known natural indole derivative. Due to the broad biological activities of its derivatives, extensive research has been conducted on their synthesis. Furthermore, the isatin framework is a versatile starting material for various transformations, including multicomponent reactions and the

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• procedures and harsh reaction conditions, resulting in limited substituent and scaffold diversity [18][19]. In this regard, multicomponent reactions (MCRs) have gained increasing attention for their operational simplicity, efficiency, robustness, atom economy, and potential for diversity-oriented synthesis

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• remains a formidable challenge, primarily due to the inherent ring strain and the difficulties associated with achieving high diastereoselectivity during cyclization [4]. Recently, Chen and co-workers developed a chiral phosphoric acid (CPA)-catalyzed multicomponent reaction of anilines, aldehydes, and

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• /bjoc.21.45 Abstract Formaldehyde emerges as a cornerstone in multicomponent reactions, mainly prized for its robust reactivity. Yet, alongside these beneficial traits, this highly reactive C1-building block raises concerns, primarily regarding its toxicity. One notable issue is the challenge of

• controlling the formation of undesired byproducts during its reactions. This review explores alternative C1-building blocks that serve as surrogates for formaldehyde, aiming to mitigate some of the challenges associated with its use in multicomponent reactions. By identifying these alternatives, toxicity

• concerns and improved reaction control can be addressed, paving the way for more efficient and sustainable synthetic methodologies. Keywords: cascade reactions; formaldehyde surrogates; green chemistry; heterocycles; multicomponent reactions; Introduction Organic chemistry is a mature discipline that has