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

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• -carbaldehyde (2p) was used. In this case, we observed abundant tarring and decomposition of the reaction mixture, which is probably due to the acidophobic nature of monosubstituted pyrroles. Surprisingly, the reaction of 4-(methylthio)benzaldehyde (2h) with 2-(5-methylfuran-2-yl)ethylamine (1a) under the

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• refluxing acetonitrile gave unique 2-azabicyclo[4.2.0]octa-3,7-dienes as major products and 1,3a,4,6a-tetrahydrocyclopenta[b]pyrroles as minor products via further rearrangement. Keywords: 1,4-dihydropyridine; electron-withdrawing alkyne; formal [2 + 2] cycloaddition; Huisgen's 1,4-dipole; isoquinoline

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• -functionalization of the indole (Scheme 2) [25]. In 2018, Lin and co-workers deployed pyrroles 9 in an aza-Friedel–Crafts reaction with trifluoromethyldihydrobenzoazepinoindoles 8 to achieve the aromatic electrophilic substitution at the C2 position of the pyrrole ring. A further extension of the scope of this

• . Stereoselectivity in the products 10/11 was achieved by using the chiral spirocyclic phosphoric acid catalyst P3 which, through H-bonding interactions with the nucleophile and the electrophile, forces the nucleophile to approach the C=N plane from the Re face. In general, enantiocontrol with pyrroles was better

• than with indoles (Scheme 3) [26]. In 2018, Kim and co-workers developed an aza-Friedel–Crafts protocol involving pyrroles 9 as the π-nucleophile in combination with cyclic N-sulfimines 12. The chiral phosphoric acid P4 was used to catalyze the introduction of a pyrrole-substituted aza-quaternary

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• well-known method for synthesizing a large number of N-substituted pyrroles. In recent years, due to global warming and environmental concern, research laboratories and pharmaceutical industries around the world are searching for more environmentally friendly reaction conditions for synthesizing

• compounds. As a result, this review describes the use of various eco-friendly greener protocols to synthesize N-substituted pyrroles. This synthesis involves the reaction of various aliphatic/aromatic primary amines, and sulfonyl primary amines with 2,5-dimethoxytetrahydrofuran in the presence of numerous

• many natural products [1][2][3] and biologically active molecules [4][5][6][7]. Pyrroles are a significant class of five-membered aromatic nitrogen-containing heterocyclic skeletons that have attracted much attention due to their broad spectrum of biological activity, such as anticancer [8][9][10

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• 1-(2-thiophenyl)pyrroles (Scheme 4). It includes intramolecular cationic π-cyclizations in 3-hydroxy-2-(2-sulfanylphenyl)-2,3-dihydro-1H-isoindol-1-ones (Scheme 4, entry 14) [9] and intramolecular cyclizations of 1-(2-(methylsulfinyl)phenyl)-1H-pyrroles under «interrupted Pummerer rearrangement

• reaction in 1-(2-bromophenyl)-5-(butylsulfanyl)pyrrolidin-2-one. Approach to PBTAs via intramolecular cyclizations of 1-(2-thiophenyl)pyrroles. A new approach to PBTAs via nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines. Reaction of APBTT 1a with methanol (2a). Derivatization of

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• )pyrroles [15]. The CsF-promoted nucleophilic addition of isocyanides to bromoacetylenes furnished the functionalized bromovinyl amides followed by Pd-catalyzed formation of 5-iminopyrrolone [16]. Sequential nucleophilic addition/intramolecular cyclization of amidine with bromoacetylenes led to imidazoles

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• to the synthesis of calix[4]pyrroles. In the presence of 5 mol % selenide catalyst, calix[4]pyrrole products were obtained in moderate to good yields at room temperature. The experimental results showed that both bidentate and monodentate catalysts were catalytically active in the condensation

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• controlling cell fate. Keywords: cells; enzyme; N-terminal; peptides; pyrroles; self-assembly; Introduction Biomacromolecular assemblies have received considerable attention recently in the field of biomaterials [1][2][3][4][5][6][7], among which peptides are of particular interest because of their unique

• shown nucleobases, as the heteroaromatic groups, are able to act as the N-capping group for EISA of phosphopeptides [67]. In this study, we chose to examine a different type of heteroaromatic group, pyrroles, because pyrrole is adaptable for solid-phase synthesis [68] so that it is feasible to conjugate

• multiple pyrroles to phosphopeptides. In addition, pyrrole has yet to be incorporated in peptides for EISA, though oligomeric pyrroles have been extensively explored for binding nucleic acids [68]. Based on a naphthyl-capped phosphopeptide (Nap-ffpy, 1), we conjugated heteroaromatic dipyrrole or tripyrrole

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

• methodology was extended to the carbosilylation of olefins with carbon nucleophiles 108 including indoles, pyrroles, and 1,3-dicarbonyls. The scope of the reaction was broad and could tolerate a variety of functional groups; however, electron-deficient alkenes afforded the products in slightly diminished

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

• combination of acidic α-carbon atoms, isocyano groups, and sulfonyl moieties [18]. In general, TosMIC undergoes base-mediated 1,3-dipolar cycloadditions with activated alkenes to provide pyrroles as products [18] (Scheme 1A). Recently, alternative functionalizations using TosMIC as a tosyl source of

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• of prolinol silyl ether (cat. 120) and benzoic acid (A1) catalysts to bring about reaction between 3-formyl-substituted indoles or pyrroles 118 and diverse electrophiles, including carbonyls, imines and other Michael acceptors (Scheme 5) [69]. The reaction with secondary amines occurred via the

• . Asymmetric synthesis of chiral N-functionalized heteroarenes. Asymmetric cascade aza-Michael−aldol reactions of α,β-unsaturated ketones with pyrroles. Intramolecular aza-Michael addition of conjugated ketones. Intramolecular enantioselective aza-Michael addition. Asymmetric aza-Michael addition of 4

• chiral N-triflylphosphoramide. Aza-Michael addition of primary amines to β-trifluromethyl-β-phenylnitroolefin catalyzed nitrogen heterocyclic carbene. Asymmetric aza-Michael additions of pyrroles to protected (E)-4-hydroxybut-2-enals. Asymmetric aza-Michael addition of purine bases to aliphatic α,β

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• heteroarenes were much poorer, with pyrroles and thiophenes giving yields of ≈20% or less and benzofuran and benzothiophene failing to produce any product. Interestingly, a cyclopentanone-derived substrate (120) failed to yield the corresponding α-amino cyclohexanone 121 under the standard conditions used for

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• enaminones as both nucleophiles and electrophiles have frequently been exploited in the synthesis of heterocyclic products, including pyrroles and related systems [22][23][24][25][26][27][28]. Nonetheless, encouraged by the ease of access to pyrrole-containing products of type 12 and their potential

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

• functionalized pyridines and pyrroles. Review Synthesis of pyridines via tandem annulation of 1,3-enynes In 2015, Reddy and co-workers reported the synthesis of substituted pyridines via Lewis acid-mediated aza-annulation of 2-en-4-ynyl azides 1 (Scheme 1) [49]. They discovered that Ag-mediated intramolecular

• also found that the aza-annulation could be carried out under iodine-mediated electrophilic annulation reaction conditions to give 5-iodo-3,6-disubstituted pyridines 3 as the major products, occasionally with a small amount of 2-acylated pyrroles 4. The proposed mechanism for the Ag-catalyzed aza

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• ][4][5][6][7][8][9][10][11][12][13]. Pyrroles with vicinal o-bromophenyl and heteroaryl substituents, which are readily accessible via reactions of the corresponding 2H-azirines and phenacylcycloiminium ylides [14][15][16][17][18][19], are excellent precursors for various fused aza-heteroaromatics via

• -bromophenyl-substituted pyrroles into 7-oxa-2a1-azabenzo[b]-cyclopenta[pq]pleiadenes [30]. However, an attempt to use AIBN/Bu3SnH for the cyclization of pyrrole 1a to compound 3a only led to a tarring of the reaction mixture, regardless of the temperature (70–110 °C, MeCN) and the protocol for mixing the

• parameters are drawn at 50% probability level. Molecular structure of compound 17a, displacement parameters are drawn at 50% probability level. Retrosynthetic analysis of heterocycles A and B. Free-radical cyclization of N-protected and N-unprotected pyrroles 1a and 2. Synthesis of 2H-pyrido[2,1-a]pyrrolo

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• substituted pyrrole-2-aldehydes to 5-azaindole transformation during a base-catalyzed imination reaction [31]. However, we envisioned that our methodology might be strategically applied towards the synthesis of substituted γ-carbolines as a C-3 nucleophilic attack is more favored in indoles than in pyrroles

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

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

• irradiation under solvent-free conditions. The library of compounds proved to be active as xanthine oxidase inhibitors with the most potent molecule showcasing IC50 = 4 μM (Scheme 21). 5 Pyrroles Pyrroles are five-membered heterocycles consisting of four carbon atoms and a nitrogen atom. The pyrrole ring is

• found to be abundant in a plethora of lead molecules and marketed drugs like atorvastatin (57), elopiprazole (58), isamoltane (59) and tolmetin (60, Figure 5) [59][60]. The diverse pharmacological activities of pyrroles enlivened Kumar and co-workers [61] to report a facile and eco-friendly microwave

• -assisted four-component reaction involving chromene-aldehyde (61), amines 32, acyclic 1,3-diketones 54 and nitromethane using silica-gel-supported polyphoshoric acid as catalyst under neat conditions for the synthesis of tetra-substituted pyrroles 62. A comparative study of the protocol employing the