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

• motif of bromine atoms pointing towards the phenyl rings is visible in this structure and seems to be a staple of this series (Figure 3B). Secondly, the edge-on interaction in this structure has changed, where the pyrrole moiety is pointing towards the face of the porphyrin macrocycle as seen in Figure

• this case, is the marked decrease in the CaCmCa of 2° seen in compound 3. Generally, all atom displacements (Δ24, ΔN, ΔCa, ΔCb, and ΔCm) [20] show a significant increase along with the pyrrole tilt angle which are moderately increasing when substituting a bromine atom for an iodine atom. This, however

• . This is seen as a general decrease in the bond lengths, bond angles, and core size, corresponding to a significant increase in atom displacement and pyrrole tilt angles. This is essentially due to the ruffling caused by inserting a nickel(II) center [20][29][30][31] and is reflected in the NSD by a

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

• the high nucleophilicity of the amino group in the substrate 23 to control the regioselectivity of the reaction (Scheme 9). 3 Indoles Indoles have a bicyclic structure consisting of a six-membered benzene ring fused with a five-membered nitrogen-containing pyrrole ring. Figure 3 depicts some of the

• 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

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• 60 and Umemoto reagent 20 as substrates as well as N-methylmorpholine (NMM) as organic base additive at room temperature (Scheme 21). The highly functionalized indole, pyrrole, benzofuran, and electron-rich benzene containing CF3 can be given in good yield. Given the redox potential of NMM and

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• -iodoaniline (12) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-[tris(1-methylethyl)silyl]-1H-pyrrole (13) according to Pratt’s conditions (Scheme 3) [29]. Subsequently, to remove the triisopropylsilyl (TIPS) protecting group, compound 14 was treated with tetra-n-butylammonium fluoride (TBAF) in THF

• -iodo-5-methoxyaniline (24), was synthesized according to the procedure previously reported by Wetzel and co-workers [31]. The Suzuki–Miyaura coupling of 2-iodoaniline derivative 24 and pyrrole-3-boronic acid pinacol ester 13 was carried out in the presence of Pd(OAc)2 and SPhos, followed by the

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• ], and self-assembled supramolecular architectures [48]. On the other hand, many natural compounds that contain a pyrrole core, such as bilirubin, hemoglobin, chlorophyll a, and vitamin B12, are very important for life. In addition to being common in natural products and biological systems, the active

• ingredient of many top-selling drugs such as atorvastatin, sunitinib, and ketorolac, contains a pyrrole unit (Figure 1) [49]. Due to these unique features, the synthesis of new dihydropyridazines, pyridazines, and pyrroles, which have the potential to be used in many applications, is very important. inverse

• ring contraction under reductive conditions in presence of zinc dust in acetic acid according to the Boger procedure, which is a highly reliable synthetic approach [66][67][68]. For pyrrole conversions, methoxycarbonyl- and 2-pyridylpyridazine derivatives 4a and 4b were used. When

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• -disubstituted pyrroles (minor products). The observed selectivities in the case of the reactions with aliphatic alkynes were high. Keywords: pyrrole; transannulation; rhodium carbene; triazole; Introduction Pyrroles are known to be important structural moieties appearing in natural products, synthetic drugs

• , agrochemicals, and functional materials (polymers, dyes, films, etc.) (Figure 1) [1][2][3][4]. Numerous methods exist for pyrrole synthesis, including the classical and industrially important condensation approaches, such as the Hantzsch, Huisgen, and Paal–Knorr processes [5]. However, the direct modification

• than the nitrile group and again the 3,4-disubstituted pyrrole 4 regioisomer dominated over the 2,4-disubstitued pyrrole 4’ (Scheme 4). To demonstrate the compatibility of the formed N-perfluoroalkylpyrroles with the conditions of pyrrole derivatization by metalation in position two and reaction with

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• which heterol rings were set as central aromatic rings (Ar1) (Scheme 3, route a and Scheme 6b). As in the original strategy (Scheme 3, route a), coupling of 3,4-dibromofuran (13a), 3,4-dibromothiophene (13b), and 3,4-dibromo(N-tosyl)pyrrole (13c) with phenylboronic acid ester 3 bearing an acetal moiety

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• ratio suggests here that the positive charge is highly delocalized in the pyrrole ring and should be regarded as a pyrrolium ion 60’ rather than an α-(trifluoromethyl)carbenium ion 60 (Scheme 16). Similarly, trifluoromethyl-substituted indolium ions were invoked as intermediates in the recently reported

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• operations overall from methyl N-Boc-prolinate. The key step proceeds in each case via N,O-diacylation, then selective oxidative hydrolysis of the intermediate bicyclic pyrrole and establishes a precedent for the synthesis of related C(7a)-hydroxylated pyrrolizidines. Keywords: acyloxypyrroles; bacterial

• pyridine as a scavenger for the liberated HCl, gave solutions of crude diacylated product 18 in acceptable purity after simple filtration as work-up. It was reasoned that the activation of the electron-rich pyrrole (with generic electrophile X2 as shown) would hasten cleavage of the ester and that

• pyrrole 18, and the appearance of new resonances at 3.21 (ddd, J = 11.5, 9.0, 2.5 Hz, 1H) and 3.64 (dt, J = 11.5, 8.5 Hz, 1H) ppm that correspond visually with those reported for the diastereotopic CH2N protons in legonmycin A. HRMS (ESI+) analysis of material isolated from this NMR experiment showed m/z

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• by the two attached fluorine atoms. The nucleophilic attack of the nitrile, followed by cyclization and aromatization could then give the pyrrole derivatives 142. Later, Xiao et al. performed another ring-opening reaction of gem-difluorocyclopropyl ketones 143, this time mediated by BX3 (X = F, Cl

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• applied in aqueous solution, with the Schmuck binding motif – the guanidiniocarbonyl‐pyrrole zwitterion binding motif – representing a most versatile binding motif with potential from nanostructure design to biomedicine [22][23][24][25]. In addition, it is desirable to establish general concepts that do

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• , 64293 Darmstadt, Germany 10.3762/bjoc.17.11 Abstract We report novel supramolecular polymers, which possess a reversed viscosity/temperature profile. To this end, we developed a series of ditopic monomers featuring two self-complementary binding sites, either the guanidiniocarbonyl pyrrole carboxylic

• acid (GCP) or the aminopyridine carbonyl pyrrole carboxylic acid (ACP). At low temperatures, small cyclic structures are formed. However, at elevated temperatures, a ring–chain transformation leads to the formation of a supramolecular polymer. We demonstrate that this effect is dependent on the

• VII system requires a BU with strong dimerization tendency and a LU with precoordinating properties. For our purpose, we initially employed the guanidiniocarbonyl pyrrole (GCP) motif as a binding unit [19]. The GCP unit is a self-complementary zwitterion, which forms dimers with high association

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• embrace: π-deficient pyrazine ring of one enantiomer of 10a is located over the π-excessive pyrrole ring of another enantiomer (Figure 2a and Figure 2b). An intermolecular distance between the centroids of these rings was found to be equal to 3.74 Å making the π overlapping possible. In the case of

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• . The shapes and geometries of anions are widely different, and therefore the design of corresponding tailor-made receptors is based mostly on more directional interactions, such as hydrogen bonds. Indeed, an incredible number of neutral receptors bearing amide, sulfonamide, urea, thiourea, pyrrole, or

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• -bromoacetaldehyde acetal by using aluminum(III) chloride as a Lewis acid catalyst through [1 + 2 + 2] annulation. This new versatile methodology provides a wide scope for the synthesis of different functional N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds, which can be further derived to access multisubstituted

• pyrrole-3-carboxamides. In the presence of 1.2 equiv of KI, a polysubstituted pyrazolo[3,4-b]pyridine derivative was also successfully synthesized. Keywords: acid catalyst; [1 + 2 + 2] annulation; KI; pyrazolo[3,4-b]pyridine; pyrroles; Introduction Among nitrogen-containing heterocycles, pyrroles have

• garnered significant attention in the literature because of their presence in various natural products [1][2][3][4] and pharmaceutically relevant drugs [5][6]. Accordingly, numerous synthetic methods to construct pyrrole skeletons were reported, including the classical Hantzsch [7][8] and the Paal–Knorr

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• the results from density functional theory (DFT) calculations. Keywords: GCI; GCP; guanidiniocarbonyl indole; guanidiniocarbonyl pyrrole; UVRR; Raman spectroscopy; resonance Raman; Introduction Supramolecular ligands are capable to selectively bind to peptides and proteins via reversible non

• -covalent interactions namely hydrogen bonds, van der Waals, and/or hydrophobic interactions [1][2][3][4][5]. In this context, Schmuck and co-workers have introduced a class of synthetic receptors based on the guanidiniocarbonyl pyrrole (GCP) moiety (cf. Figure 1 top right) as a carboxylate binding site

• supramolecular ligands: guanidiniocarbonyl pyrrole (GCP) and guanidiniocarbonyl indole (GCI). The latter class of artificial carboxylate receptors is a potential next generation binder based on the GCI motif which maintains the good carboxylate binding properties of GCP. GCI comprises an indole ring instead of a

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• . AuNP-based probes for inorganic anions, for example, can serve to monitor the water quality [14][15]. An example is the probe for halides that was described by the Sessler group. It comprised AuNPs with immobilized calix[4]pyrrole residues that are known to interact with chloride and fluoride. The

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• . 250, 64293 Darmstadt, Germany 10.3762/bjoc.16.214 Abstract The synthesis and optoelectronic properties of novel S,N-heterotetracenes consisting of fused heterocyclic thiophene and pyrrole rings are presented. Tetracyclic and benzannulated derivatives with a varying number and sequence of sulfur and

• nitrogen heteroatoms were synthesized in multistep synthetic routes. A Buchwald–Hartwig amination of brominated precursors, thermolysis of azide precursors, and a Cadogan reaction of nitro-substituted precursors were successfully applied to eventually build-up pyrrole rings to stable and soluble fused

• ]. The series of thienoacenes consisting of only fused thiophene rings has been synthesized up to an octamer, whereby the longer members in the series quickly lose solubility [4][5][6]. The implementation of pyrrole rings into the fused ladder-type structure leads to the class of S,N-heteroacenes

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• efficiencies were calculated based on the shift of the pyrrole protons relative to an independently synthesized fivefold coordinated Ni-porphyrin, which was used as a reference for a completely coordinated 5-coordinate Ni-porphyrin [13] (Table 1). Since coordination and decoordination is fast on the NMR time

• scale, the average pyrrole shift is a very accurate indicator of the proportion of species with and without a coordinating axial ligand (100% coordination (paramagnetic) 48.9 ppm and 0% coordination (diamagnetic) 9.1 ppm in acetone-d6). It should be noted that the cis/trans ratio does not necessarily

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• with small molecules, in a green and scalable process. Results and Discussion The boron dipyrromethene dye 1 bearing a phenylboronic acid moiety (PBA) at the meso position of the BODIPY core (Scheme 1) was prepared in four synthetic steps starting from 4-formylbenzeneboronic acid (2) and pyrrole (3

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• naphthalene diimde analogue (NDI) equipped at the imide positions with two guanidinio-carbonyl-pyrrole (GCP) pendant arms interacted significantly stronger with ds-DNA at pH 5 than at pH 7, due to reversible protonation of the GCP arms. This was consequence of a pH-switchable threading intercalation into ds

• the DNA/RNA conjugate NDI-GCP2 showed also aggregation along the ds-polynucleotide and AFM and DLS demonstrated that NDI-GCP2 has pronounced ds-DNA condensation ability. Keywords: AFM; circular dichroism; DNA/RNA recognition; fluorescence; guanidinio-carbonyl-pyrrole; naphthalene diimide

• spectroscopy methods (FDCD, CPL), the sensitivity of response is approaching the classical fluorimetric probes [14]. Our systematic work on aryl-guanidiniocarbonyl-pyrrole (GCP) derivatives characterised the GCP moiety as very useful building block in the design of new small molecules targeting DNA/RNA. The

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• coordination. On this account, isomerization and coordination were investigated separately by 1H NMR spectroscopy. The protons meta to the azo group in the azopyridine unit (H-11) are responsive to the configuration of the azo group (cis or trans) and the chemical shifts of the pyrrole protons of the porphyrin

• signals (1H NMR, 600 MHz, THF-d8, 300 K) of the pyrrole protons in the PSS at 530 nm and 435 nm. Coordination/decoordination is fast on the NMR timescale and signal averages for the pyrrole protons are observed. 50.40 ppm corresponds to 100% coordinated (paramagnetic) Ni-porphyrin and 10.83 ppm is the

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• )pyrrole (GCP) cation 1 as a synthetic analogue of the guanidinium cations, somehow a “super-guanidinium” conceived to drive “arginine magic” [20][21] to the extreme (Figure 1) [23]. The power of the Schmuck cation to bind carboxylate and phosphate anions in competitive water has several origins [22

• binding is further enhanced by the addition of hydrogen-bonding interactions between the amide NH moiety in position 5 of the pyrrole ring or the pyrrole NH group and the oxoanion (Figure 1, blue part). Thirdly, the rigid and planar conformation of the GCP moiety is beneficial to bind planar anions such

• cations (6: KD = 20 mM, Figure 2). The amide NH unit in position 5 of the pyrrole ring is crucial for this binding affinity, which even exceeds the effect of the pyrrole NH moiety (4 and 5 vs 7: KD = 7.7 mM). In addition, the size and electronic structure of the pyrrole core are also important for this

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• superstructures [11]. The rings should be of remarkable size for accommodating even small anions, such as acetate. In many cases the receptor is formally a macrocycle, but the anion is bound on its “surface”, not inside the ring [10][12]. A well-known example is the calix[4]pyrrole family, which emerged as an

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• to afford intermediate isoindole 4a [2][3][4][5][6]. Then, the addition of water to the sterically less-hindered site of the latter compound followed by ring opening resulted in the rearranged aldehyde 2a [1]. As regards the formation of dimer-like product 3a, the tendency of pyrrole [7][8], indole