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

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• redox properties similar to those of squaraine derivatives, enabling key transformations such as the cyclization of anilines with maleimides and the reduction of Umemoto salts for trifluoromethylation of alkenes. With an excited-state reduction potential around 0.80 V, 46 demonstrates the capability to

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• spectroscopy techniques. In order to show the universality of the substitution reaction, MBH maleimides of isatins 4 were also employed in the reaction. In the absence of any base as promoter, the reaction of MBH maleimides of isatins with various aromatic amines in toluene at 65 °C gave the expected

• promoter is needed in the reaction, which is assumed to be due to the much higher reactivity of MBH maleimides of isatins compared to the above-mentioned MBH nitriles and formats of isatins. The single crystal structures of the compounds 5a and 5j were successfully determined (Figure 1 and Figure 2). From

• and were fully characterized via various spectroscopy methods. The further annulation reaction did not proceed under the reaction conditions. The similar reaction of triphenylphosphine and MBH maleimides of isatins also resulted in the corresponding triphenylphosphaneylidenes 6e and 6f in satisfactory

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• benzofuran-3-carbaldehydes 50 (Scheme 16). Another demonstration of the atroposelective formation of compounds with a C–N stereogenic axis was developed by Jindal, Mukherjee, Biju, and co-workers [36]. The authors developed an NHC-catalyzed desymmetrization of N-aryl maleimides 53, which afforded a range of

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• maleimides or N-arylitaconimides. The mechanism of the studied processes was postulated basing on experimental data, HPLC–MS analysis of reaction mixtures, and quantum chemical calculations. Molecular docking results of the obtained imidazo[1,2-a]pyrimidines, when compared with voriconazole, a drug already

• in clinical use, suggest that they may possess antifungal activity against Candida albicans. Keywords: 2-aminoimidazole; antimycotic activity; imidazo[1,2-a]pyrimidine; molecular docking; N-arylitaconimides; N-substituted maleimides; recyclization; Introduction Nitrogen-containing heterocyclic

• ]pyrimidines using readily available derivatives of azaheterocycles as starting materials. As the last ones, we chose the reaction between 2-aminoimidazole and N-arylitaconimides or N-substituted maleimides, which can be analyzed by both classical synthetic and quantum DFT methods. The second problem solved in

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• nitroalkenes or guanidine-mediated addition of bisthiomalonates to maleimides, cyclic enones, and acyclic 1,4-dicarbonylbutenes, albeit at low temperatures and with relatively long reaction times, further limited to a narrow scope of thioesters (Scheme 1) [31]. Recently, we described a cinchona-squaramide

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• determined that a ratio of 1:1 MeOH/H2O should be used as this solubilized the chemical probe most efficiently. Additionally, others have previously noted that polar solvents tend to benefit Diels–Alder reactions between furoic acids and maleimides [19][23]. Next, we looked at how different additives would

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• trifluoromethyl acylhydrazones as 1,3-dipolar agents to react with β-nitrostyrenes [114], maleates [115], cyclopentadiene [116] and maleimides [117] for the synthesis of CF3-substituted pyrazolidine derivatives. These reactions were conducted under basic conditions and in the presence of Cu(OTf)2 (Scheme 19a). As

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• ketones can result in a different kind of AMYs to address the issue. The reaction of trifluoromethyl ketones with glycine or α-substituted amino acids generated stabilized AMY 8 which underwent cycloaddition with maleimides to give 2-CF3-substituted pyrrolidines 9 in 50–76% yield (Scheme 5) [65]. Both the

• each of arylaldehydes and N-substituted maleimides was carried out in EtOH as a protic solvent at 90 °C for 3 h to afford pyrrolizidines 10 in 73–93% yield with greater than 9:1 dr (Scheme 6). The scope of the reaction could be readily extended for α-substituted amino acids, such as alanine, leucine

• adducts from the first cycloaddition generate the same products 10 or 11 (Scheme 8). We also evaluated the double cycloadditions in two operational steps by using two different sets of aldehydes and maleimides to afford products 13a–d in 45–60% yields with 2:1 to 3:1 dr (Scheme 9). The low

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• + 26), respectively, were successfully employed as visible-light photocatalysts for a cross-coupling cyclization of N,N-dimethylaniline (27) and N-alkyl/aryl maleimides 28 (Figure 6). Notably, the systems showed much higher catalytic activity compared to similar reactions with the dye or cages alone

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• . pyrido[1,2-a]pyrrolo[3,4-d]pyrimidines 3a,b and N-methyl-4-((pyridin-2-yl)amino)maleimides 4a–e, were selectively prepared by a one-pot reaction between a functionalized maleimide and 2-aminopyridines with electron-donating or electron-withdrawing groups at position 5 and were investigated

• clinical applications such as cell imaging and cell sorting. To develop low-molecular-weight AIEE-based luminogens, we have synthesized a series of fluorescent compounds by the reaction of nucleophilic maleimides with 2-aminopyridines. This resulted in the development of a novel method to obtain

• heterocyclic compounds, such as ring-fused pyridines (pyrido[1,2-a]pyrrolo[3,4-d]pyrimidines) and secondary aminopyridines (N-methyl-4-((pyridin-2-yl)amino)-substituted maleimides), by changing the substituents at position 5 of the 2-aminopyridine. Interestingly, among these pyridine derivatives, secondary

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• electron-withdrawing substituents on the oxime; however, the reaction required highly activated alkenes to proceed. 1,2-Disubstituted alkenes were tolerated and were diastereoselective for the anti-addition product. When maleimides 171 were used as the 2-carbon coupling partner, a [5 + 1] annulation was

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• Ren-Jie Fang Chen Yan Jing Sun Ying Han Chao-Guo Yan College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.17.159 Abstract The p-TsOH-catalyzed Diels–Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two

• efficient domino reactions for the synthesis of biologically important carbazole derivatives [48][49][50][51][52][53], herein we wish to report the DDQ-mediated dehydrogenative Diels–Alder reaction of 3-(indol-3-yl)maleimides and benzoyl-substituted 3-ethylindoles with readily available chalcones for the

• )maleimides and in situ-generated indole-chalcones with dienophilic chalcones. This one-pot two-step reaction successfully provided the polyfunctionalized carbazole derivatives in an extremely simple and highly efficient fashion. This protocol has the advantages of using readily available starting reagents

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

• substituents on the benzaldeydes 169 [72]. Cycloaddition reactions In 2014, Gao, Li, and their co-workers published a facile strategy to synthesize polysubstituted aromatic compounds from the reaction of quinones or maleimides with β-enamino esters (Scheme 39) [73]. They synthesized anthraquinone derivatives

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• RNA in a highly selective and efficient way. The more traditional strategies rely on reaction of isothiocyanates or NHS esters with aliphatic amines [13][14], or on addition of thiols to the α,β-unsaturated carbonyl face of maleimides [15]. Over the past years, the copper catalyzed alkyne–azide

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• -Maleimides 8a and 8b with a methyl and an ethyl residue showed higher yields and a lower induction in comparison to the benzyl derivative 8e with 43% ee and 39% ee (Table 1). The poorest result was obtained by using dienophile 8c with a tert-butyl substituent (82% yield, 18% ee). This maleimide gave the

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• - and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels–Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels–Alder cycloaddition with maleimides to furnish octahydropyrrolo

• annulation process through a Pd- or Ni-catalyzed coupling starting from the N-functionalized indoles 5 [11][19][21][28][29][30]. On the other hand, the formation of pyrrolo[3,4-e]indoles 9/10 can be achieved via a Diels–Alder cyloaddition of 2-vinylpyrroles 8 with maleimides 7 [31][32][33][34][35]. This is a

• propargyl bromide (14f) to generate pyrroles 8i,j, respectively, in high yields. The synthesis of octahydropyrrolo[3,4-e]indoles 9/10 was achieved through a Diels–Alder reaction between the 2-vinylpyrroles 8a–j and 16a,b and maleimides 7a–c under thermal conditions (Scheme 3). N-Unsubstituted 2

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• the C=C double bond of maleimides was reported [96]. The iminoxyl radicals were detected by EPR spectroscopy, but the non-radical mechanism (copper-catalyzed Michael addition) can not be excluded completely. Application of the oxime radicals in organic synthesis: intramolecular reactions There are two

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

• Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot N-allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-a

• related to natural products [18][19][20]. Among the well-established MCRs, three-component 1,3-dipolar cycloadditions of benzaldehydes, maleimides, and amino esters have been developed for making N-containing 5-membered heterocycles (Scheme 1) [21][22]. The [3 + 2] cycloadditions of maleimides with

• with 2-bromobenzaldehydes 3 and maleimides 4 (Scheme 3) [30][37]. The cycloaddition reactions were diastereoselective (>20:1 dr for adducts 5 and >6:1 dr for adducts 6). The major diastereomers of 5 and 6 were isolated for following N-allylation and intramolecular Heck reactions. Adduct 5a generated

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

• of these protocols, as demonstrated by the nonmetallated TPP which did not work. The tetrahydroquinoline products were obtained in up to 1.1 gram-scale, after 20 h under blue LED irradiation (18 W), for both N-alkyl/aryl maleimides (57–92% yields) and the p-substituted N,N-dimethylanilines (78–97

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• under air, N,N-dialkylated aniline derivatives were reacted with various N-substituted maleimides and benzylidenemalonitrile to provide polysubstituted tetrahydroquinolines in moderate to good yields. When N-aryltetrahydroisoquinoline was used instead of N,N-dialkylated anilines, octahydroisoquinolo[2,1

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• ][20] compared to 2, so a simple one-step route can be used to install the maleimides. It is this functionality that allows coupling (often called "tethering", symbolized as "t" for tetherable in Scheme 1) of the probe with mutant proteins. In our case, we developed a three-step route to install the

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• . Maleimides are considered as a biologically important scaffold that possess almost all types of biological activities including antibacterial and antifungal activity [24], anticancer activity [25], cox-2 inhibitor and anti-inflammatory, antidiabetic activity [26] and photodynamic activity [27]. Attaching of

• -propargylmaleimide [44] was carried out successfully in CH2Cl2 and the fluorinated porphyrin–triazole–maleimide conjugates 7a and 7b were obtained in 54–58% yield. In these conjugates the tetrafluorophenyl units of the porphyrin macrocycle where separated from maleimides with 1,2,3-triazole spacer groups. Removal of

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• reaction. This was demonstrated in a study by Gugelchuck et al. [71], where the reaction rate of various p-substituted 6-phenylpentafulvenes with maleimides was investigated. Substituents of an electron-donating nature (e.g., H, halogens) generally increased the reaction rate through stabilisation of the

• dependent mostly on its substituents (e.g., EWG or EDG) relative to the other reactants [6][42][45][67][103][153][230]. Maleimides (including maleic anhydride) [55][71][92][96][150][176][177][179][180][181][182][183][184][186][192][229][231], dimethyl acetylenedicarboxylate (DMAD) and p-benzoquinone [60

• the yield of the Diels–Alder adduct [227]. Of particular interest is the reaction between 6-aminofulvenes and maleic anhydride. As previously reported, a fulvene reacting with maleimides (including maleic anhydride) generally results in a [4 + 2] cycloaddition (Scheme 14, reaction pathway (i)) [55][96