Introduction of an isoxazoline unit to the β-position of porphyrin via regioselective 1,3-dipolar cycloaddition reaction

• Xiujun Liu,
• Xiang Ma and
• Yaqing Feng

Beilstein J. Org. Chem. 2019, 15, 1434–1440, doi:10.3762/bjoc.15.143

• four pyrrole rings with respect to the porphyrin mean plane, which are more twisted than that in normal Zn-porphyrin [49]. The lengths of Zn–N bonds range from 2.041 Å to 2.073 Å. The new formed five-membered isoxazoline ring is almost vertical (with a dihedral angle of 82.7°) to the mean plane of the

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• of 0.49 V, is much easier to oxidize due to the electron-rich character of the pyrrole ring [47]. The HOMO energy levels were determined from the onset of the oxidation wave and accordingly gradually decreased from 1 to 4 (−5.92 eV to −5.80 eV) (Table 4, Figure 7). Due to the absence of reduction

Extending mechanochemical porphyrin synthesis to bulkier aromatics: tetramesitylporphyrin

• Qiwen Su and
• Tamara D. Hamilton

Beilstein J. Org. Chem. 2019, 15, 1149–1153, doi:10.3762/bjoc.15.111

• mechanochemical condensation with pyrrole to give meso-tetrakis[2,4,6-(trimethyl)phenyl]porphyrin (TMP) after oxidation in solution. Yields are similar to those obtained using high-temperature porphyrin synthesis, although they remain significantly lower than some optimized room-temperature, solution-based

• materials, namely: pyrrole and an aldehyde (Scheme 1). Porphyrin synthesis is interesting to study as a mechanochemical reaction because it involves the combination of reactive molecules under appropriate conditions to give a very stable, aromatic product. Furthermore, depending on the nature of the

• work on mechanochemical porphyrin synthesis has demonstrated that it is possible to synthesize tetraphenylporphyrin (TPP) by grinding benzaldehyde and pyrrole (two liquids) in the presence of an acid catalyst, followed by oxidation with DDQ in minimal amounts of solvent [19]. TPP was produced in a

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• (Scheme 4). In this case, copper catalyst and alkynes are also used but, unlike the above method, alkynes 18 are monosubstituted. The third component is an indole or pyrrole derivative 19 and the result of the reaction is a 3,3-disubstituted isoindolinone derivative 20, which contains a newly formed

• quaternary centre [79]. The reaction takes places in water, even in the presence of air, and with nanodomain cuprous oxide as an inexpensive and reusable catalyst. The scope includes aryl, alkyl and carboxyl groups at 2- and 3-positions of the lactam ring. Pyrrole reacts across the 2-carbon while indole

• similar way to that described in Scheme 3. In this case, the coupled alkyne moiety is again activated by Cu(I) and then base-promoted cyclization occurs. A new copper complex formation with the alkene analogue to 13 (see Scheme 3) facilitates the aromatic nucleophilic substitution by indole or pyrrole

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• compounds of both natural and synthetic origin, containing in their structure pyrrole and imidazole rings, display a wide set of pharmacologically significant activities. The most important natural sources of such systems are marine sponges. Since the 70's of 20th century up to date more than 150

• derivatives containing pyrrole and 2-aminoimidazole fragments in their structure were found among the metabolites of these marine organisms [1]. This group of compounds is characterized by an exceptional molecular diversity. The main structural types of these substances are shown in Figure 1. The metabolites

• . are a source of alkaloids with core structures containing simultaneously pyrrole carboxamide and 2-aminoimidazole moieties such as the simple achiral compound oroidine (V) and spatially organized molecules in a complex manner with a large number of chiral centres like (−)-palau’amine (VI) [3

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• , who treated pivalonitrile (1) with lithiated methoxyallene 2 and isolated the expected primary addition product 3 [21]. This intermediate was subjected to different cyclization conditions (Scheme 1) and the desired pyrrole derivative 4 was produced under specific conditions employing silver nitrate as

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• approaches towards this tempting scaffold are reported in the literature. They can be divided into two groups: oxidation of pyrrolo[3,2-c]pyridines [13][15][16] and annulation of pyridine by a pyrrole-2,3-dione moiety (cyclization of 2-(4-((alkoxycarbonyl)amino)pyridin-3-yl)-2-oxoacetates [11], interaction

• of 5-azaisatoic anhydride with cyanides followed by hydrolysis [10], Scheme 1). Herein, we report a distinct synthetic approach to 5-azaisatins via annulation of pyrrole-2,3-dione by a pyridine ring based on an unprecedented interaction of 1H-pyrrole-2,3-diones with thioacetamide (Scheme 1). Results

• '-pyrroles] 3. It could be either a molecule of the spiro[thiazolo-5,2'-pyrrole] 3 or a molecule of the PBT 2. To determine the most possible one, we investigated the effect of the ratio of the reagents. When we used excessive amounts of thioacetamide (fivefold excess to PBT 2a), a significant decrease in

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• nucleophiles was tested under selected conditions. Thus, employment of pyrrole as a nucleophile gave product 7a in 43% yield, and N-methylpyrrole facilitated desired compound 7b in 23% yield (Scheme 4). Isomeric 5-, 6- and 7-azaindoles were found to be appropriate nucleophiles too, producing the corresponding

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• , triazolo[1,2-a]indazoletrione derivatives, tetrasubstituted imidazole derivatives, aromatic/aliphatic sulfide derivatives, and N-substituted pyrrole derivatives. These catalysts were used in cellulose hydrolysis, cellobiose hydrolysis, production of fatty acid ethyl ester, the transesterification of

• derivatives. The synthetic route for MWCNT-SO3H and its catalytic application for the synthesis of N-substituted pyrrole derivatives. The sulfonic acid-functionalized polymers (P-SO3H) covalently

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• (diols). Seleno-Pummerer reactions of 3-selanylmethylpyrroles also proceeded via in situ generation of selenoxides, followed by a treatment with TBAH. Keywords: hydroamination; Pummerer reaction; pyrrole; pyrroloazepine; 1,7-sulfur shift; Introduction Pyrrolo- and indoloazepine skeletons are chemical

• radical cyclisations [28] and the 1,7-electrocyclisation of azomethine ylides or ring expansion sequences [29]), most of these approaches are ineffective for synthesising pyrrolo[3,2-c]azepines. Recently, Echavarren and Beller reported a novel Au- or Pt-catalysed cycloisomerisation reaction of pyrrole-2

• determined by analysing the single-crystal X-ray diffraction spectrum of the corresponding sulfone of 4a; the structure was a pyrrole bearing both 3-sulfanylmethyl and 4-allylaminomethyl groups (see Supporting Information File 1). To develop a useful Pummerer reaction procedure, we selected allylamine

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• -methoxyphenyl) disulfide was employed as the thiolating agent (3h). With symmetrical arenes, diarylation was observed. The initially formed mono-arylated product is more reactive than the starting material and reacts to the diarylthiol product. When 1-phenyl-1H-pyrrole-2,5-dione was employed as the arene, the

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• reported in the literature [7]. Besides the classical calixarene phenolic subunits linked by methylene groups, “calixarenes” incorporating other subunits include, but are not limited to, resorcinol [8], hydroquinone [9], naphthols [10], pyrrole [11], heteroaromatics [12] and triptycene [13] in their cavity

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• in the presence of CoCp*(CO)I2 and AgNTf2 (Scheme 38) [98]. The reaction tolerated various pyrimidine containing arenes, such as indole, phenyl, and pyrrole with different ketenimines to form enaminylation products 61. Subsequently, the hydroarylation products 61 were further converted into bioactive

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• aminated pyrrole adducts. Somewhat surprisingly, no reaction was observed between onchidal and n-pentanethiol. Structurally simplified n-pentyl 11–13 and cyclohexylmethyl 15–17 analogues of onchidal were prepared and demonstrated similar amine-selective reactivity. Onchidal and analogues reacted with the

• model protein lysozyme, forming covalent adducts and leading to protein cross-linking. These results provide preliminary evidence supporting the molecular mechanism of biological activity exhibited by onchidal. Keywords: dialdehyde; lysozyme; mollusc; onchidal; pyrrole; Introduction More than 80

• binneyi) also exhibit biological properties including feeding deterrence, antibacterial and anticholinesterase activities. Chemical reactivity studies using polygodial (1), scalaradial (2) and caulerpenyne (3) have demonstrated evidence of pyrrole formation upon reaction with primary amines, with

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• ). The reaction uses 2H-azirines and aldehydes to access the functionalised heterocycles [61]. Unlike the pyrrole-forming reaction, this protocol requires an oxidising agent, DDQ, for the desired oxazole to be obtained. This means that access to the corresponding 2,5-oxazolines is also possible

Synthesis and characterization of π–extended “earring” subporphyrins

• Haiyan Guan,
• Mingbo Zhou,
• Bangshao Yin,
• Ling Xu and
• Jianxin Song

Beilstein J. Org. Chem. 2018, 14, 1956–1960, doi:10.3762/bjoc.14.170

• subporphyrin moiety are not ideally coplanar. This feature can be proved by the dihedral angles of two adjacent pyrrole units in the tripyrrin moiety, which are as large as 15.8(1)° and 16.1(1)°, respectively. We assume that the twisted structure results from the strain transmitted from the subporphyrin moiety

• of which are shorter than that of 3. This contraction is probably due to a slight mismatch of the radii between the Pd center and the cavity. In addition, this mismatch also leads to a further twist of the pyrrole units in the tripyrrin moiety. The dihedral angles of two adjacent pyrrole units in the

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• introduction of the iodobenzoic acid motif onto the pyrrole ring. 5-Aroyloxy-γ-lactams 4 can be isolated with yields in the 56–96% range, however, the reaction requires 2.5 equivalents of the λ5-iodane reagent, a result that supports its limited efficiency in terms of atom economy (Scheme 3) [31]. λ3-Iodane

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• significant antibacterial activity against Gram-positive bacterial strains [50]. Several other distamycin analogs were synthesized by replacing one or more pyrrole rings with other heterocycles such as pyrazoles [51], benzofurans [52], thiazoles, thiophenes, imidazole and oxazoles [53] in order to establish a

• structure–activity relationship. It has been observed that the number and position of pyrrole rings are crucial for antileukemic activity. The presence of pyrrole rings close to the alkylating BAM moiety is responsible for better cytotoxic activity both in vitro and in vivo, whereas a pyrazole ring in close

• lipophilicity [53]. These structural analogs comprise of branched N-alkyl- and N-cycloalkylpyrroles to test the conformational flexibility towards DNA binding. Hydrophobic N-terminal amides and substituted thiazole replacing pyrrole were installed in order to impart more lipophilicity. All these compounds were

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China 10.3762/bjoc.14.75 Abstract A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily

• substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research. Keywords: azomethine ylides; 1,3-dipolar cycloaddition; one-pot synthesis; polysubstituted pyrroles; pyrrolo[3,4-c]pyrrole-1,3-diones

• ; Introduction Pyrroles are an important class of five-membered nitrogen containing heterocycles which are widely used in numerous medically relevant fields. Pyrrolo[3,4-c]pyrrole-1,3-diones and highly substituted pyrroles with amide groups are important frameworks of pyrrole compounds that play important roles

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• Amarendar Reddy Maddirala Peter R. Andreana Department of Chemistry and Biochemistry and School of Green Chemistry and Engineering, University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA 10.3762/bjoc.14.74 Abstract The synthesis of spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones and

• synthetic method for these molecules that allows for structural diversity is also important but not necessarily trivial. For these and other reasons, we became interested in synthesizing spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-dione and spiro[indoline-3,2'-pyrrolidine]-2,5'-dione scaffolds (a class of

• spirocyclic oxindole γ-lactams). There have been other groups in the past, including our own research group, who have reported on post-modified Ugi-four-component synthetic strategies (Scheme 1) towards the synthesis of 2-oxindoles and spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones and spiro[indoline-3,2

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• photosensitive dyes. Keywords: benzyne; cycloaddition; diaryliodonium salts; N-phenylamine; pyrrole; Introduction Pyrrole is a very useful heterocyclic substrate to produce structural attributes of valuable chemicals, functional materials and pharmaceuticals [1][2][3][4][5]. Recently, arylation of pyrrole

• derivatives with diaryliodonium salts for pyrrole–aryl coupling products is generating tremendous academic interest in organic synthesis. In 2012, the Zhang and Yu group reported that sodium hydroxide promoted direct arylation of unprotected pyrroles with diaryliodonium salts at the temperature of 80 °C, the

• coupling products were obtained in moderate to good yields (Scheme 1a) [6]. Later in 2013, Xue and Xiao et al. developed a method of photoredox catalysis in the presence of [Ru(bpy)3]2+ with visible light for the coupling reaction of arenes with unprotected or N-substituted pyrroles, pyrrole substrates

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• ]. Several methods use prerequisite quinoline derivatives for the construction of the pyrrole ring of quindoline. 2-(2-Aminophenyl)-3-bromoquinoline cyclized to quindoline by reacting with pyridinium hydrochloride (d) [14]. Insertion of nitrene generated from 2-(2-nitrophenyl)quinoline by triethylphosphite

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• conditions and Cu(OH)2 and Ag2CO3 were the best catalyst and oxidant, respectively. The electron density of the pyrrole ring had impact on the efficiency. N-Tosylindole and indole bearing the CO2Me group on C3 position were nearly unreactive. A plausible mechanism was proposed based on preliminary

Reactivity of bromoselenophenes in palladium-catalyzed direct arylations

• Aymen Skhiri,
• Ridha Ben Salem,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2017, 13, 2862–2868, doi:10.3762/bjoc.13.278

• allowed the coupling of several heteroaromatics such as thiazole, pyrrole, furan or imidazole derivatives with aryl bromides [36]. 2-Bromoselenophene, which was easily prepared by reaction of selenophene with N-bromosuccinimide [37], and 2-ethyl-4-methylthiazole were employed as model substrates for our

• . Gorelsky calculated that the Gibbs free energies of activation for the cleavage of C–H bonds at C5-position of thiophene or pyrrole derivatives, for reaction which proceed via concerted metallation–deprotonation [38][39][40], are higher than that of thiazoles (see bottom of Scheme 2) [42]. We assume that

• , due to these higher energies of activation for reactions with thiophene or pyrrole, larger amounts of selenophene oligomers were formed in the presence of these less reactive heteroarenes. Then, the reactivity of imidazo[1,2-a]pyridine, which contains a very reactive C–H bond at C3-position was

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• -trifluoromethylsulfenylation did not occur with 3-substituted substrates. Other azaarenes, such as pyrrole derivatives, as well as enamines or silyl enol ethers were also compatible with these conditions, and furnished the corresponding products in moderate to good yields. The key step of the reaction comprises the formation

• trifluoromethylsulfenylated analogue (Scheme 33). Yi and co-workers reported that the reaction could also be performed in acetonitrile at 90 °C, with diethyl phosphite as the reducing agent (Scheme 34) [43]. These modifications allowed to get improved yields for the trifluoromethylsulfenylation of indole and pyrrole

• of CF3SO2Cl and tricyclohexylphosphine, the trifluoromethylsulfinylation of various indole and pyrrole derivatives featuring diverse functional groups, as well as other azaarenes could be achieved in low to excellent yields (Scheme 38a). Generally, indole derivatives provided better results than