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

• available starting materials, good functional group tolerance, and mild, transition-metal-free conditions. NHC-catalyzed radical approach furnishes access to substituted 3,4-dihydro-2H-pyrroles 18, in good yields (Scheme 7) [57]. A novel strategy was discovered for 1,2-dicarbonylation of vinyl arenes 11

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• demonstrated an Fe-catalyzed dearomatization of β-2-furyl ketone oxime acetates, yielding functionalized pyrroles [18]. Herein, we report our investigation of the Fe-catalyzed spirocyclization of β-3-indolyl ketone oxime acetates. Results and Discussion Our study commenced with the synthesis of key propan-1

• resulted in extensive decomposition and tarring, a common issue with α-unsubstituted pyrroles under acidic conditions. These results indicate that substrates featuring strongly electron-withdrawing groups or acid-sensitive motifs are not compatible with the developed protocol. Next, we synthesized the

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

• benzamides with terminal alkynes, 5-exo-dig aza-cyclization of 2-alkynylbenzamides as well as reductive cascade annulation of o-alkynylbenzamides. Pyrroles and imidazoles were formed efficiently via electrochemical annulation of alkynes with enamides and tandem Michael addition/azidation/cyclization of

• reactions of alkynes towards five-membered rings are classified and presented in detail. Based on different types of five-membered rings, electrochemical construction of indoles, isoindolinones, indolizines, oxazoles, imidazoles, pyrroles, imidazoles and 1,2,3-triazoles are summarized and the possible

• imidazoles, (d) construction of pyrroles, imidazoles and 1,2,3-triazoles. Literature on the electrochemical formation of five-membered rings from alkynes in this review was collected up to June 2025. We apologize to the authors if their contributions were not involved here due to the limitations of the

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

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• method for the synthesis of 3-arylbenzo[4,5]thieno[3,2-b]pyrroles has been developed via pyrrole ring annulation to the aromatic benzo[b]thiophene system, using 3-arylazirines as a N‒C=C synthon. The reaction is catalyzed by Ni(hfacac)2 and proceeds through the azirine ring opening across the N=C3 bond

• reagents for the preparation of 3-aryl-substituted benzo[4,5]thieno[3,2-b]pyrroles by the annulation of the 1H-pyrrole ring to the benzo[b]thiophene system (Scheme 1, reaction 6). The behavior of indoles as aza-analogs of the benzo[b]thiophenes under the identified catalytic annulation conditions is also

• for the synthesis of benzo[4,5]thieno[3,2-b]pyrroles are lacking and obtaining their derivatives remains challenging [24][25], the reaction we discovered could significantly facilitate access to compounds of this type. To test the generality and usefulness of the reaction, we investigated a variety of

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• regioselectivity of the Friedel–Crafts alkylation to the para-position, forming exclusively (or significant amounts of) 3,3-diaryloxetanes. In 2017, Vanderwal and co-workers published a novel, facile synthesis of furans 181 and pyrroles 185 from 3-(2-oxoalkylidene)oxetanes 179, precursors which are readily

• equivalents of the amine and longer reaction times were found necessary to transform the undesired adducts 183 (X = NHR3) to the pyrroles and hence obtain higher yields. Two years later, Sun and co-workers reported a convenient and highly efficient synthesis of 2-oxazolines 187 which applied mild conditions

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• reaction between the anhydride and the amine suggested the subsequent reaction with the ketone to give an imine intermediate XXIV. This latter can undergo intramolecular nucleophilic attack affording the quinazolinone derivative 26 (Scheme 20) [37]. Polysubstituted pyrroles 27 were obtained in a cascade

• -dihydroquinazolin-4(1H)-one derivatives 26. Synthesis of polysubstituted pyrroles 27. Enantioselective synthesis of polysubstituted pyrrolidines 30 directed by the copper complex 29. Synthesis of 4,5-dihydropyrazoles 31. Synthesis of 2 arylisoindolinones 32. Synthesis of imidazo[1,2-a]pyridines 33. Synthesis of

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

• axially chiral pyrroles and indoles 44 are obtained (Scheme 14). Zhu and co-workers developed a method for the atroposelective formation of arenes 48 by an NHC-catalyzed formal (4 + 2) cycloaddition [34]. The triazolium pre-catalyst (R,S)-C11 was the most efficient in providing a range of biaryls in high

• indoles 96 or pyrroles 99 and 1,4 diketones 97, respectively, the authors were able to achieve very good to near-perfect yields with consistently high enantioselectivities. Configurational stabilities of the products 98 and 100 were explored in toluene at 110 °C. Rotational barriers were calculated to be

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• Mandeep K. Chahal School of Chemistry and Forensic Science, University of Kent, Canterbury, CT2 7NH, UK 10.3762/bjoc.20.257 Abstract This review provides an overview of recent progress made in the field of catalysis using metal-free tetrapyrrolic macrocycles, focusing on calix[4]pyrroles

• , porphyrins and corroles, which are structurally related to porphyrins. Calix[4]pyrroles are versatile receptors in supramolecular chemistry while porphyrins are considered as ‘pigment of life’ due to their role in vital biological processes. Beyond their natural functions, synthetic porphyrins have been

• two macrocycles as metal-free catalysts. Keywords: calix[4]pyrroles; electrocatalysis; free-base porphyrins; organocatalysis; photocatalysis; tetrapyrrolic macrocycles; Introduction Tetrapyrrolic macrocycles are a class of cyclic compounds that contain four pyrrolic units in their ring. Examples of

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• great attention in biomedical applications, clinical diagnostics, and conjugate materials. Keywords: cyclic imines; dibenzothiazepine; dibenzoxazepine; isocyanides; multicomponent reactions; pyrrole; triazolobenzodiazepine; Introduction Pyrroles and their derivatives are important N-heterocyclic

• compounds with antibiotic, antiviral, and anticancer properties that are found in many drugs and natural products [1][2][3][4][5][6]. Pyrroles' biological properties manifest when they are fused to other heterocycles [7][8][9][10][11][12]. Among them, seven-membered heterocycles of the benzodiazepine

• electrophilic sites simultaneously in their structure, these zwitterions are able to participate in various cyclization processes, especially for the synthesis of pyrroles [37][38][39][40]. For example, Li et al. developed a one-pot four-component reaction (4-CR) of malononitrile, aldehydes, and isocyanides

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• related to yne-allylic substitutions. Review Copper-catalyzed yne-allylic substitutions affording 1,3- and 1,4-enynes In 2022, Fang et al. [62] realized the copper-catalyzed yne-allylic substitution involving stabilized “soft” nucleophiles for the first time. Indoles and pyrroles with various substituents

• yielded mono yne-allylic substituted products (Scheme 15, 3a–w), but while pyrroles were used as nucleophiles, double yne-allylic substituted products can be obtained with high dr and ee values (Scheme 16, 15a–c). They also demonstrated the importance of terminal alkyne through control experiments and

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• -dihydro-1H-pyrroles using aryldiazonium salts and (S)-PyraBox, followed by sequential Jones oxidation. They showcased their methodology by preparing both (R)-rolipram and (R)-baclofen hydrochloride. Tóth et al. reported the design and synthesis of new analogues of HeE1-2Tyr, a nonnucleoside SARS-CoV-2

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• reported herein may impact the synthesis of other macrocyclic arene species, e.g., calix[n]arenes, calix[4]pyrroles, pillar[n]arenes, and cucurbit[n]urils [90][91][92]. Perspective Supramolecular chemistry is a mature field that has crossed boundaries into many other scientific areas. However, the work

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• structures were elucidated by 1D and 2D NMR spectroscopic analyses, HRESIMS, and chemical derivatization. The absolute configurations of compounds 2 and 3 were predicted by comparison of experimental and calculated specific rotation data. Compounds 1–5 are the first examples of natural pyrroles substituted

• many marine natural products [6][7], pyrroles substituted with long hydrocarbon chains (pyrrole lipids) are seldomly isolated, and their presence is limited to certain marine organisms [8]. A series of 3-alkylpyrrole-2-carbaldehydes/carboxylic acid/methylcarboxylate was reported from the marine sponge

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• computationally, identifying key interactions to understand TAAR1 agonism. Pyrroles: New histamine-related compounds were synthesized and evaluated towards activation of human carbonic anhydrase isoforms (hCA), aiming at potency and selectivity enhancement by Chiaramonte et al. [41]. Among them, a discrete set of

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• together with genes encoding the production of polybrominated pyrroles [138][139][140]. The Microbulbifer BGCs lack genes for brominated pyrrole biosynthesis and polybrominated pyrroles have not been reported to be produced by Microbulbifer bacteria. Future studies looking at the evolutionary relationship

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• of efforts to developing efficient thio/selenocyanation approaches [33][34][35][36][37][38][39][40][41]. Specifically, a plethora of synthetic strategies have been reported for the thiocyanation of heteroaromatic compounds including arenes, indoles, carbazoles, pyrroles, and imidazopyridines [42][43

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• % of Mn4 and 1.1–1.5 equiv of t-BuOK in 1,4-dioxane at 120 °C for 20 h, affording good to excellent yields of the substituted pyrimidines (Scheme 68). The same group disclosed an efficient synthesis of substituted pyrroles from aminoalcohols and secondary alcohols using Mn4 under mild conditions [95

• ]. A variety of amino alcohols and alcohols were investigated with Mn4 (0.5 mol %) and t-BuOK (1.5 equiv) in 2-MeTHF under reflux conditions and the corresponding pyrroles were isolated with up to 93% yield (Scheme 69). Notably, the same pincer ligand-supported Co and Fe complexes showed no activity in

• pyrrole synthesis under the same reaction conditions. In 2019, Rueping, El-Sepelgy and co-workers achieved the sustainable multicomponent synthesis of pyrroles from readily available substrates catalyzed by manganese-pincer complex Mn12 [96]. The use of 2 mol % of Mn12 in combination with a catalytic

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• herein an enantioselective palladium-catalyzed Heck–Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation

• -pyrroles posed some challenges due to substrate instability and undesirable side reactions. In 2003, we reported the Heck–Matsuda arylation of N-protected 2,5-dihydro-1H-pyrroles [10] to obtain 4-aryl-γ-lactams in a racemic manner [11], thus demonstrating the feasibility of this transformation. The γ

• -lactam ring is a privileged scaffold widely present in drugs and natural products [12][13][14], as shown in Scheme 1. Herein, we report the effective desymmetrization strategy of N-protected 2,5-dihydro-1H-pyrroles using aryldiazonium salts and the chiral N,N-ligand (S)-PyraBox (Scheme 2). The obtained

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• can be found in bioactive molecules and have been tested in structure–activity relationship studies (Scheme 1A) [8][9][10]. Moreover, transformations have been developed to exploit the two functional groups simultaneously, for example through their intramolecular cyclization to form pyrroles in the

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• guests with an anion-binding stimulus. This system could further be tuned and adapted by increasing the macrocycle size or by modifying the TTF groups. Indeed, the authors later reported the allosterically regulated complexation of Li+ encapsulated C60 (Li+@C60) in TTF-calix[4]pyrroles and benzoTTF-calix

• [4]pyrroles [73]. The electrochemical properties of the host–guest system are modulated by a thermally induced electron transfer (ET) that generates the charge separation state [PrS-TTF-C4P•+/Li+@C60•−]. This behavior was first reported with Cl− as an allosteric regulator but was then described with

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• electrophilic enough to activate alkenes toward the attack of pyrroles [34][35]. Gold-catalyzed reactions are known to be sensitive to subtle anion and media effects [48], and within the binary of rate determining π-activation versus protodeauration, trends do not always provide obvious conclusions. The unique

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• -thiolated pyrroles 61 and pyrrolines 62 from propargylic tosylamides 60 and N-thiosuccinimides 1 was described by Gao′s group (Scheme 25) [61]. When AlCl3 as the Lewis acid catalyst and nitromethane as the solvent were used, a series of 3-thiolated pyrrole products 61 were detected, and 3-thiolated

• pyrrolines 62 were obtained by changing the reaction solvent to MeCN. Also, organic fluorophore compounds such as benzothienopyrrole and bis-thiolated boron dipyrromethene can be achieved from 3-thiolated pyrroles. Mechanistic studies showed that the oxidative species HNO and HCHO were generated through a

• -workers demonstrated bisulfenylation/cyclization of homopropargylic azides 82 with N-thiosuccinimides 1 in the presence of AlCl3 as the catalyst, 3,4-bisthiolated pyrroles 83 were obtained as the desired products in moderate to high yields (Scheme 34) [66]. The reaction involves the Lewis acid-catalyzed

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• 44, from which reductive elimination of iodobenzene would generate 40. In 2021, Sen and Gremaud disclosed a blue LED-mediated formal C–H insertion reaction between iodonium ylides (e.g., 31) and pyrroles (e.g., 45), indoles and furans, producing malonate-substituted heterocycles 46 (Scheme 9) [126

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• ). Notably, the protocol was also applicable to 4-iodotoluene as a moderately deactivated aryl iodide and the C(sp2)–I bond cleavage occurred chemoselectively in the presence of a C(sp2)–Br bond. N-Methylpyrrole and various other substituted pyrroles could be applied as trapping agents for electron-poor aryl

• pyrroles was applicable to electron-poor aryl halides including various heterocyclic halides, affording their products in poor to excellent yields (4–92%) (Figure 9A). Regarding the unsatisfactory results, the coupled products of the strongly deactivated 4-bromoanisole (Epred = −2.75 V vs SCE) and 4

• , several polyhalogenated aromatics could be chemoselectively engaged at one C–X bond, even for 1-bromo-4-iodobenzene (1f). Apart from N-methylpyrrole, other substituted pyrroles, thiazine (4o), pyrazine (4p) and electron-rich benzenes (4q) were found to be suitable trapping reagents with varying efficiency