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

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• gained from the first total synthesis of (−)-curvulamine (171) [91], Maimone’s group leveraged their plan for accessing several members of this class (Scheme 14). The challenge this group had to address in this particular case was the high acid sensitivity and oxidative fragility of pyrrole intermediates

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• , Perm 614990, Russian Federation 10.3762/bjoc.18.162 Abstract There has been developed an easy synthetic approach to spiro[dihydrofuran-2,3'-oxindoles] via a highly diastereoselective formal [4 + 1] cycloaddition reaction of [e]-fused 1H-pyrrole-2,3-diones with diazooxindoles. The described novel

• heterocyclic systems are heteroanalogues of antimicrobial and antibiofilm fungal metabolites. The developed reaction represents the first example of involving 1H-pyrrole-2,3-diones fused at the [e]-side in a [4 + 1] annulation reaction. Keywords: [4 + 1] annulation; catalyst-free; diazooxindole; 1H-pyrrole

• ] (Scheme 1). Thus, in the present work, we report a simple, catalyst-free diastereoselective method for the synthesis of dihydrofurans spiro-annulated with an oxindole moiety for the first time. The essence of the method is the use of [e]-fused 1H-pyrrole-2,3-diones (FPDs) as the enone component in a

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• of novel supramolecular catalysts. In their contribution Wang and co-workers [17] reported an interesting example of chalcogen bonding catalysis approach for the synthesis of calix[4]pyrrole macrocycles. The Se···O=C chalcogen bonding interactions between a selenide-based catalyst and the carbonyl

• -substrate catalyzed the macrocyclization with pyrrole. Interestingly, only 5 mol % of catalyst loadings were necessary in order to promote the condensation processes, and calix[4]pyrrole derivatives were obtained in moderate to high yields. Mild reaction conditions were employed, thus highlighting the

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• during the reaction, and the formation of the bridged species is thermodynamically favored, except in the case of 5-methylfurfural and pyrrole-2-carboxaldehyde. This is the first report detailing this type of aldol/Michael cascade involving oxa-Michael initiation. Keywords: cascade reactions; green

• adducts from these aldehydes and the reduced ketone 12 are known [14]. The reactions of cinnamaldehyde, propanal, and pyrrole carboxaldehyde with 1 also failed to yield bridged species, and the complex mixtures that resulted from these reactions were not further examined. Mechanistically, the reaction is

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• Baris Temelli Pinar Kapci Hacettepe University, Department of Chemistry, Beytepe Campus, 06800, Ankara, Turkey 10.3762/bjoc.18.145 Abstract A copper triflate-mediated approach to access copper complexes of pyrrole-substituted corroles from the reaction of 1,9-diformyldipyrromethanes and an excess

• amount of pyrrole is presented for the first time. This procedure is a simple and efficient way for the preparation of corroles with a polymerizable substituent on meso-positions. Keywords: corrole; dipyrromethane; macrocycles; metal triflates; pyrrole; Introduction Corroles, a member of contracted

• several methods including; (i) the condensation of pyrrole or dipyrromethanes with aldehydes [14][15][16], (ii) the reaction of 2,2’-bipyrrole with dipyrromethane-1,9-dicarbinols [17][18], (iii) the condensation of bipyrrole-5,5’-dicarbinols with dipyrromethanes [19], (iv) the reaction of dipyrromethane

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• prediction of two C2 related, dominating binding sites on 14-3-3ζ that may bind to two of the supramolecular ligand molecules. Keywords: AIE luminophores; fluorescence emission; guanidiniocarbonyl-pyrrole; ligand binding; 14-3-3 protein; Introduction The 14-3-3 protein family was one of the first

• option to modulate, inhibit, or stabilize protein–protein interactions (PPI) is the use of specific supramolecular ligands [7][8]. One well-known example of efficient protein binders is the so-called guanidiniocarbonyl-pyrrole (GCP) developed 20 years ago by Schmuck et al. [9]. These compounds are known

• -anions [11]. The guanidiniocarbonyl-pyrrole (GCP) is able to bind oxo-anions even in aqueous solvents with competing ions and salts. Schmuck et al. also discovered that an additional positive charge increases the binding affinity to oxo-anions [10]. These unique properties make the GCP oxo-anion binder

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• Palau’amine (45), a dimeric pyrrole-imidazole-bisguanidine alkaloid, was first isolated from the marine sponge Stylotella aurantium in 1993 [16][17]. It received considerable attention from the synthetic community because of its broad range of biological activities and complex structure. In an early endeavour

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

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

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• phenacylmalononitriles and allenoates for the tunable synthesis of multifunctionalized cyclopentene carboxamides and cyclopentenols [33] (reaction 3 in Scheme 1). Recently, Zhang and Ban reported a NaHCO3-promoted reaction of phenacylmalononitriles and N-alkylmaleimides to give the novel cyclopenta[c]pyrrole-4

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

• study, we used 1-methyl-4-(methylsulfanyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbonitrile (1) with a methylsulfanyl group as a good leaving group. As shown in Scheme 1, the one-pot reaction of 1 with 2-aminopyridine (2a) proceeded by refluxing in ethanol for 2 h to produce the ring-fused pyridine

• 5 of the pyridine ring (Table 1). On the other hand, the reaction of 1 with 5-bromo-2-aminopyridine (2c) afforded an N-methyl-4-((pyridin-2-yl)amino)-substitued maleimide, 4-((5-bromopyridin-2-yl)amino)-1-methyl-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbonitrile (4a), based on an A–D–A system

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

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

• ]pyrrole derivatives. The Se···O bonding interactions between selenide catalysts and ketones gave rise to the catalytic activity in the condensation reactions between pyrrole and ketones, leading to the generation of calix[4]pyrrole derivatives in moderate to high yields. This chalcogen bonding catalysis

• . Keywords: calix[4]pyrrole; chalcogen bonding; ketones; Se···O bonding interactions; supramolecular catalysis; Introduction Noncovalent catalysis has been established as one of the fundamental concepts in organic synthesis that enables achieving numerous chemical transformations [1]. Among these

• ]. Despite these significant advances, catalysis with chalcogen bonding interactions is still in its infancy and the development of new types of reactions is highly desirable. Calix[4]pyrrole derivatives have been widely used as transition metal ligands and functional materials [50][51][52][53]. Thus far

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

• Qiuxin Zhang Weiyi Tan Bing Xu Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA 10.3762/bjoc.18.17 Abstract Here we report the synthesis and effect on the cell viability of pyrrole-conjugated phosphopeptides. Encouraged by the selective inhibition of cancer

• 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

• radical across the alkene to afford the benzylic radical. Oxidation of the corresponding radical affords the benzylic carbocation which is attacked by the indole nucleophile. The authors applied the reaction methodology to pyrrole as a substrate; however, only one example was given in a 50% yield. Further

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• [13], as well as Ir-catalyzed intramolecular dehydrative cross-coupling of 2-(pyrrolidine-1-yl)benzamide [14]. Another approach to compounds of type 1 that relies on a cascade formation of the pyrimidine and pyrrole rings have found much wider application (see Scheme 1B). One of its variations

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• the base (dr 93:7) but unfortunately with a comparable enantioselectivity (Table 3, entry 2). When the excess of butanal (6a) was reduced from 3 to 1.5 equivalents, the yield again decreased (Table 3, cf. entries 2 and 7). The Michael addition of aldehyde 6a to nitroalkene 7a with K2CO3 and pyrrole

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

• subsequently deprotonates pyrrole to provide the stronger nucleophilic pyrrolide anion [27]. Similarly, Liu et al. accomplished an asymmetric intramolecular aza-Michael addition of various enone carbamates 10 using a chiral cinchona-based primary-tertiary diamine as catalyst to obtain 2-substituted piperidines

• , i.e., to assist in 1,3-prototropic shift. 2.2 Catalysis by chiral pyrrolidine derivatives Chiral pyrrolidine derivatives, such as (S)-proline are widely used as organocatalysts [54][64]. Lee et al. synthesized bromopyrrole alkaloids 107 via aza-Michael addition of 4,5-dibromo-1H-pyrrole-2-carbonitrile

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

• temperature and microwave power, although requiring much longer time. A possible mechanism for the cyclization is presented, and further functionalization of the newly created pyrrole ring in the dihydropyrrolizine core is described. Keywords: dihydropyrrolizines; enaminones; microwaves; silica gel

• 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

• the expected pyrrolizinone 13a/13a', but the 2,3-dihydro-1H-pyrrolizine ester 19a. The expected signals for the ethyl ester were apparent in the 1H NMR spectrum, the lone pyrrole hydrogen appeared as a singlet at δ 5.95, and the ester carbonyl group occurred at δ 161.4 in the 13C NMR spectrum. In

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

• structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly

• introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles. Keywords: 1,3-enyne; functionalization; pyridine; pyrrole; tandem annulation; Introduction The pyridine moiety is an important class of six-membered N-heterocycles that is widely found

• pyridine derivatives have been developed through the intramolecular or intermolecular tandem addition annulation/functionalization of alkynes with some N-containing compounds, such as nitriles, oximes, and imines [15][16][17][18][19]. The pyrrole structural motif is also an invaluable five-membered N

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• . Based on this concept, the applicability of N-acyliminium chlorides in thiourea-catalyzed anion-binding reactions was further explored. In 2008, an intramolecular asymmetric Pictet–Spengler-type cyclization reaction with pyrrole derivatives 13 was reported. The authors were not only able to control the

• enantioselectivity, but this system also allowed the control over regioselectivity (C2 vs C4 cyclization) through alteration of the N-substituent of the pyrrole substrate and the acylating reagent (Scheme 4a) [34]. This example showcases that next to the counterion, the acylating group can have a major influence on

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• -decyltetradecyl)-6,6’-di(thiophen-2-yl)-[2,2’-biazulene]-1,1’3,3’-tetracarboxdiimide (TBAzDI) 79 to make these polymers was synthesized as shown in the Scheme 16. The monomer 79 was reacted with N-dodecylthieno[3,4-c]pyrrole-4,6-dione (TPD, 80) and 1,2,4,5-tetrafluorobenzene (TFB, 82) via a palladium-catalyzed

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• heterocycles, because of its diverse presence in bioactive molecules [1][2][3][4][5][6][7][8], coupled with the distinct nucleophilic chemistry revolving its aromatic benzo-fused pyrrole system as encountered throughout the bibliography [9][10][11][12][13][14][15]. It is therefore obvious that a non-metal

• a concise account of the same, although preparations of ionic bis(indolyl) metal salts will not be considered [24][25][26][27][28][29][30][31][32][33]. Review The pyrrole C2 and C3 linkages By virtue of the two available sites in its pyrrole substructure, two indoles can be attached to a central

• the indoles are less studied compared to the same through their pyrrole counterpart. The corresponding compounds are investigated for boron, nitrogen, oxygen, sulfur, and selenium as the central connecting atom. Boranes The indole alkaloid dragmacidin D is a marine secondary metabolite which was