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

• homopropargylic azide was formed using pyrrole 1e it could not be isolated due to its instability. No conversion was observed when the transformation was attempted directly on the indole scaffold 1f. Only a small amount of product was formed using styrene 1g bearing an extra α-phenyl substituent. A slightly

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• transformation of the five-membered pyrrole ring in compound 2 to the six-membered ring in compound 1 is particularly intriguing. For this transformation, three hypotheses are considered. One suggests that the methyl modification at the oxygen atom of the succinimide ring occurs first, which is then followed by

• from the known brocaeloid D by the addition of a methyl group, and there is a change in the relative stereochemistry at C2 and C3. In addition, the conversion of the five-membered pyrrole ring in compound 2 to the six-membered piperidine ring in compound 1 is intriguing. Although there have been many

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

• -responsive switchable tweezers are based on an H-bonding motif that can establish recognition interactions with the anionic species. One of the first examples was developed by Sessler, Jeppesen, and co-workers with a calix[4]pyrrole switching unit [68]. Calix[4]pyrrole tweezers 33 are functionalized by four

• tetrathiafulvalene (TTF) arms, adopting a 1,3-alternate conformation by default with two cavities for binding electron-poor guests between the TTFs (Figure 18). The authors demonstrated complexation with 1,3,5-trinitrobenzene and other electron-poor guests such as TCNQ. The N–H protons of the pyrrole subunits can

• -conformation calix[4]pyrrole and the electron-donating nature of TTFs allow the complexation of electron-poor C60 guests [71]. A 2:1 complexation of C60 by TTF-functionalized calix[4]pyrrole 33 was observed for the Cl− bound cone conformation with each calix[4]pyrrole entrapping C60 on one side. The complex

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• substituted at positions 2 and 5 with 1,8-dibromonaphthalene using 5 mol % PdCl(C3H5)(dppb) catalyst with KOPiv as the base in DMA (Scheme 3). From 2,5-dimethylthiophene or 1,2,5-trimethylpyrrole, the desired acenaphtho[1,2-c]thiophene 16 and acenaphtho[1,2-c]pyrrole and 17 were obtained in 60% and 56% yield

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• unambiguously established based on COSY, HSQC, and HMBC NMR-spectroscopic data. Further, the 15N NMR spectrum of 5a confirmed the typical pyrrole-like character of the N(12) atom as well as the pyridine-like character of the N(7) and N(14) atoms (Figure S31, Supporting Information File 1) [21][22]. The

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• 52% (3p) yields, respectively. If the chains did not involve a carbonyl group, the yields were much lower (3q, 25%; 3s, 29%, and 3t, 29%). When a pyrrole ring was used instead of indole, the reaction proceeded but gave the product in low yield (3r). We did not explore the reaction with a primary

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• pyrrole unit to one of the dithiole rings of an IF-TTF, allowing for dimerization of extended TTFs via the nitrogen atom by different linkers [14]. Donor–acceptor chromophores can be obtained by replacing one of the dithiafulvene (DTF) rings of the IF-TTF by an electron acceptor. Cyclic and acyclic

• explore further annellation of dihydropyrrole and pyrrole units at the DTF moiety of an IF-DTF. A phosphite-mediated coupling of either 1,3-dithiole-2-thione 2, 7, or 8 with IF dione 1 afforded IF-DTFs 9–11, as shown in Scheme 1. Compound 11 was also obtained from building block 4 via the pyrrolo

• -annelated IF-DTF 12 by removal of the tosyl (Ts) group under alkaline conditions, followed by nucleophilic substitution to incorporate the hexyl chain on the pyrrole. Furthermore, treatment of the IF-DTF ketone 4 with Lawesson’s reagent (using a recently established protocol [20]) yielded the large dimer 13

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• product 6b in high yield. The reaction with methyl pyrrole-2-carboxylate resulted in the isolation of only the C–H insertion product 9c in low yield. Similar reaction progress was observed in the case with imidazole, the product N–H insertion was observed only in trace amounts (according to NMR data of

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• been reported involving the use of A3-bilanes [30][31] or dipyrromethane–dicarbinols [32], the modification of A4-porphyrins [33], or the reaction of pyrrole with different aldehydes [34]. In the present work, the applied synthetic method provided the A3B-porphyrins in a single-step reaction from

•  1). In our previous works, we have shown that the reaction of pyrrole with N-tosylimines leads to pyrrole sulfonamides as the main products [35]. In another work, in the synthesis of dipyrromethane structures, we have proven the formation of azafulvene intermediates by Cu(OTf)2-appended elimination

• were between 7–18%. Synthesis of tripyrrane 5 5,10-Bis(4-trifluoromethylphenyl)tripyrromethane (5) was obtained as side product of dipyrromethane synthesis by the condensation of pyrrole and 4-(trifluoromethyl)benzaldehyde. A typical procedure involves 4-(trifluoromethyl)benzaldehyde (28.7 mmol) and

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• commercially available. Regarding the molecular design and their properties, porphyrins and crown ethers are like water and fire – they constitute the opposite elements (Figure 1). Porphyrins are built of four pyrrole rings, two of which are considered amine-like due to the presence of NH groups, whereas the

• greater detail in the next sections. In 1977 Chang provided the first example of a capped (strapped) β-pyrrole appended crown ether porphyrin. This result laid the foundation for future work on capped porphyrins [38]. The later contributions to the porphyrin macrocycle incorporating the crown ether motif

• macrocycle with a crown ether segment attached through the β-positions of the two pyrrole rings located oppositely to each other, hovering above the porphyrin plane [40]. The initiation of these research topics was crucial for the search of simple chemical models for haemoglobins and cytochromes, as well as

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• . Surprisingly, 2-naphthaldehyde was found to be less reactive and needed a reaction time of 24 h to obtain product 3g with 85% yield. Heterocyclic aldehydes gave also good results as shown with pyrrole-2-carboxaldehyde that allowed formation of product 3h in 86% yield. Rhodanine-3-acetic acid also allowed

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

• the HNO species, the pyrroline structure could oxidize and aromatize to the pyrrole ring 61 (Scheme 26). In 2021, Anbarasan and co-workers were able to obtain a diverse range of sulfenylated products 64 in a Co-catalyzed C2-sulfenylation and C2,C3-disulfenylation of indole derivatives with N

• acid organocatalysts were evaluated for sulfenylation on C3, or C2 position of N-heterocycles 115, including indoles, peptides, pyrrole, and 1-methyl-1H-pyrrolo[2,3-b]pyridine. The authors hypothesized a mechanism for the activation of N-sulfanylsuccinimides 1 or 14 by conjugate Lewis base Brønsted

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione

• ][59][60][61][62], we investigated the base-promoted annulation reaction of dimedone adducts of 3-methyleneoxindoles, with isatin and ammonium acetate. It was unexpectedly found that novel dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] were

• the three-component reaction. To our surprise, instead of the above mentioned dispiro[indoline-3,2'-quinoline-3',3''-indolines] 3a–m, the novel dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives 4a–i were obtained in high yields. The results are summarized in Table 3. The structural analysis

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

• studies revealed that the C2–H bond of pyrrole did not participate in the rate-determining step. This led the authors to propose a multi-step reaction mechanism, where irradiation of an initial halogen-bonded EDA complex 47 led directly to iodocyclobutane 48 (Figure 10). Reductive elimination of

• . Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation. Mechanistic proposal for the X–H insertion reactions of iodonium ylides. Calculated reaction coordinate for the radiofluorination of iodonium ylide 60. Difference in Gibbs activation energy for ortho- or para-anisyl

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

• , or it is trapped with pyrrole derivatives 3 in a C–C bond formation to afford arylated products 4. Based on the ultrashort lifetime of *PDI•− (τ = 145 ps), the notion of its photochemistry has attracted skepticism and it has been suggested decomposition products of *PDI•− may instead serve as

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

• developed method include the impossibility of using aliphatic aldehydes (for example, 2-phenylacetaldehyde (2o)), that is also explained by an insufficient stabilization of the resulting cation and the impossibility of cyclization. We also did not detect the formation of the target product when 1H-pyrrole-2

• . The reversibility of the acid hydrolysis is quite typical for furans and is more pronounced for di- and polysubstituted furans, due to the higher stability of the latter [49][50][51]. 3-(2-Oxopropyl)piperidin-4-one 5a could be involved into the Paal–Knorr pyrrole synthesis in a one-pot manner. Thus

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

• ]pyrrole derivatives 6e, 6f, 6i, 6k, 6l, and 6m were isolated in 23–39% yield from the reaction mixture. In other cases, the corresponding 1,3a,4,6a-tetrahydrocyclopenta[b]pyrrole derivatives could not be isolated due to too low yields. By analyzing the chemical structures of the 1,3a,4,6a

• -tetrahydrocyclopenta[b]pyrrole derivatives 6, it was found that the 1,4-dihydropyridinyl ring of the substrate was converted to a fused pyrrole ring, which might be a result from a rearrangement process of the formed 2-azabicyclo[4.2.0]octa-3,7-diene-7,8-dicarboxylates 5a–o at elevated temperature. The chemical

• cyclobutenyl ring and the 1,4-dihydropyridyl ring exist on the fused position. The two protons at the bridged position and the phenyl group are cis-configured. From Figure 3 (compound 6f), it can be seen that the fused pyrrole ring and the cyclopentyl ring are butterfly shaped. The unusual feature is that the

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

• process was achieved through the C3–H functionalization of indole derivatives 4. The nucleophile favors the attack at the imine carbon included in the seven-membered ring of compound 8 to generate an aza-quaternary stereocenter containing trifluoromethyl, pyrrole/indole, and benzoazepinoindole moieties

• 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

• Dileep Kumar Singh Rajesh Kumar Department of Chemistry, Bipin Bihari College, Affiliated to Bundelkhand University, Jhansi-284001, Uttar Pradesh, India P.G. Department of Chemistry, R. D. S. College, B. R. A. Bihar University, Muzaffarpur-842002, Bihar, India 10.3762/bjoc.19.71 Abstract Pyrrole

• is an important aromatic heterocyclic scaffold found in many natural products and predominantly used in pharmaceuticals. Continuous efforts are being made to design and synthesize various pyrrole derivatives using different synthetic procedures. Among them, the Clauson–Kaas reaction is a very old and

• acid catalysts and transition metal catalysts. The goal of this review is to summarize the synthesis of various N-substituted pyrrole derivatives using a modified Clauson–Kaas reaction under diverse conventional and greener reaction conditions. Keywords: catalyst; Clauson–Kaas pyrrole synthesis; 2,5

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• as a result of ESIPT-induced reactions (Scheme 1A and B). At the same time, both directions of phototransformation are realized for terarylenes with furan, pyrrole, and oxazolone-bridge fragments (Scheme 1C). However, the suppression of the ESIPT process in such systems makes it possible to perform

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• at 90 °C) [36]. It is now well-documented that the incorporation of heteroatoms into the graphene materials or NG molecules can effectively tune their electronic and optical properties. Examples in Scheme 3 show the nitrogen-doped, seco-HBC-based chiral NGs. By introducing a pyrrole ring, Jux and co

• -workers reported pyrrole-containing helical NGs 19 and 20. The precursors 17 and 18 were synthesized from pyrrole-containing alkynes and tetracyclone 2 through a typical Diels–Alder reaction. The pair of enantiomers of these aza-[5]helicenes was confirmed by the X-ray crystal structure of racemic

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

• targeted cancer therapy development. Keywords: 1,4-benzothiazine; 1,3-benzothiazole; 1H-pyrrole-2,3-diones; nitrogen heterocycle; sulfur heterocycle; Introduction Pyrrolo[2,1-b][1,3]benzothiazole (PBTA) is an angularly fused sulfur and nitrogen-containing heterocyclic scaffold. Its derivatives are

• to the PBTA scaffold is an annulation of benzothiazoles with a pyrrole moiety (Scheme 1). It includes intramolecular cyclizations of benzothiazoles bearing a 3'-chloro substituent at C2 position (Scheme 1, entries 1 and 2) [5][6][7], intramolecular catalytic carbene cascade reactions of propargyl 1,3

•  4). Results and Discussion It is known that [e]-fused 1H-pyrrole-2,3-diones (FPDs) (Figure 2) are versatile synthetic platforms enabling the synthesis of numerous heterocyclic species [33][34][35][36]. They are polyelectrophilic compounds, bearing five electrophilic centers, whose reactivity

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• fluorescence response. Compounds that consisted of pyrrole-guanidine attached to larger aryl moieties (pyrene and phenanthridine) bind to the human DPP III enzyme [17]. Pyrene–cyanine conjugates connected with a rigid triazole-peptide linker were designed and synthesized in our group and showed a strong pyrene

• –pyrrole conjugates towards single stranded RNA systems [19][52]. To confirm that the described clustering analysis elucidated the most representative structures of each conjugate at both experimental pH values, we proceeded by calculating energies of the excited states responsible for the experimental UV

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• multisubstituted pyrrole derivatives (Scheme 1a) [16][17][18][19]. Another seminal work in this field was the aza-Nazarov cyclization of N-acyliminium salts 1 reported by Klumpp and co-workers in 2007 (Scheme 1b) [20]. This reaction was promoted with the use of superstoichiometric amounts of TfOH

• pyrrole-fused heterocyclic tricycles [33]. The involvement of Nazarov and in particular aza-Nazarov reactions in the cyclization of alkynes that go through metal carbene intermediates has recently been reviewed by Gao and co-workers [34]. In 2019, we reported a highly effective aza-Nazarov cyclization for