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

• (Table 2). The corresponding bicyclic amine 10a was obtained by the prolonged treatment of the product 4a with catalytic amounts of TFA in acetonitrile followed by the addition of an aqueous solution of NH3. The structures of cyclized products 9 and 10 were confirmed by spectral methods. The signals of

• allows to classify them as compounds of the same type containing a fused aminoimidazo[1,2-c]pyrrole moiety. Finally, the structure of azomethines 16 was confirmed by X-ray diffraction data of the sample compound 16a (Figure 5). All atoms of the bicyclic fragment lie in the plane within 0.01 Å. The

• structures of spiroxindoles 19 and 20 were confirmed by X-ray diffraction data of the sample compound 19a (Figure 7). Compound 19a exists in the crystal phase as solvate with dimethylformamide and water in a 1:1:1 ratio. The spiro-joined bicyclic fragments are turned relatively to each other in such a way

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• for the rate enhancement under ball-milling conditions. As another highly reactive organic catalyst, 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was investigated next. The bicyclic guanidine base TBD has shown better efficiencies than DBU in many chemical transformations including the polymerization of

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• post-multicomponent reactions, diversities of bicyclic drug-like heterocyclic compounds can be obtained [26]. Results and Discussion In continuation of our interest on the synthesis of novel pseudo-peptides [27][28][29] via multicomponent reactions, herein we investigate the Ugi-4C-3CR of levulinic

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• Iteng Ng-Choi Angel Oliveras Lidia Feliu Marta Planas LIPPSO, Departament de Química, University of Girona, Maria Aurèlia Capmany 69, Girona 17003, Spain 10.3762/bjoc.15.72 Abstract A methodology for the solid-phase synthesis of biaryl bicyclic peptides containing a Phe-Phe, a Phe-Tyr or a Tyr

• resulting biaryl monocyclic peptidyl resin leading to the formation of the expected biaryl bicyclic peptide. This study provides the first solid-phase synthesis of this type of bicyclic compounds being amenable to prepare a diversity of synthetic or natural biaryl bicyclic peptides. Keywords: borylation

• ; cross-coupling; cyclization; macrocycles; solid-phase synthesis; Introduction Monocyclic and bicyclic peptides are acquiring a relevant interest in current drug discovery. They display improved biological properties over their acyclic counterparts and, at the same time, they are suitable to modulate

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• synthetic methods has been developed for the construction of carbon–heteroatom bonds using these types of catalysts. For example, the gold(I) catalyst [(Ph3PAu)3O]BF4 was applied in the regioselective intramolecular cyclization of alkynols to construct bicyclic ethers [37], while the silver(I) catalyst

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• proceeded smoothly at room temperature, affording the corresponding bicyclic cyclopropane ring-fused lactones and lactams in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). After screening of various catalysts, the Ru(II)-Amm-Pheox complex having an ammonium group proved to be

• amide derivatives, prepared from the corresponding allylic alcohols by the Fukuyama method [50] were investigated as shown in Scheme 1. The catalytic system was applicable to a wide variety of substrates, which reacted smoothly to give the corresponding bicyclic products. For example, diazo Weinreb

• amide derivatives bearing electron-donating or electron-withdrawing groups at the ortho, meta, or para positions could be converted to the corresponding bicyclic products in excellent yields (up to 99%) and enantioselectivities (up to 98% ee, Scheme 1, 2g−m). A diazo compound with two chlorine

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• equimolar amounts of easily separable cycloadducts 75 and 76 (Scheme 19) [81]. The bicyclic framework in the latter compound was first reduced and the hydroxy group was protected as acetate. Then the oxidative cleavage of the C=C bond gave diacid 77 (readily purified as dimethyl ester 78) which is a

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• -DNA (6’-diF-bc4,3-DNA). The difluorinated thymidine phosphoramidite building block was synthesized starting from an already known gem-difluorinated tricyclic glycal. This tricyclic siloxydifluorocyclopropane was converted into the [4.3.0]bicyclic nucleoside via cyclopropane ring-opening through the

• addition of an electrophilic iodine during the nucleosidation step followed by reduction. The gem-difluorinated bicyclic nucleoside was then converted into the corresponding phosphoramidite building block which was incorporated into oligonucleotides. Thermal denaturation experiments of these

• gem-difluorinated bicyclic nucleoside 6 as the main side product. Since nucleoside 6 possessed the desired stereochemistry at the 1’- and the 5’-positions, we investigated the mechanism of its formation in more detail to be able to increase its yield. To determine in which of the two steps the

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• formation of the enamine I seems plausible. It is an electron-rich dienophile which could undergo a [4 + 2] cycloaddition with the electron-poor aryl-substituted tetrazine 2 in a Diels–Alder reaction with inverse electron demand. The bicyclic Diels–Alder intermediate II then might undergo a retro-Diels

• theoretical methods [52]. Their results are in agreement with the catalytic cycle presented in Scheme 1. However, the question is raised whether the bicyclic Diels–Alder species II is a real intermediate or rather a transition state of a concerted formation of the dihydropyridazine intermediate III directly

• than the intensity of product 3 and declines very slowly as the reaction progresses (Figure 3b). However, no signals for the intermediates I1 (enamine) and II1 (bicyclic Diels–Alder intermediate) were found. Intermediate I1 (m/z 156) has been observed before by Marquez et al. in ESIMS experiments of an

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• unsaturated 6’-fluoro[4.3.0]bicyclo nucleotides (6’F-bc4,3-DNA). Two 6’F-bc4,3 phosphoramidite building blocks (T and C) were synthesized starting from a previously described [3.3.0]bicyclic sugar. The conversion of this sugar to a gem-difluorinated tricyclic intermediate via difluorocarbene addition followed

• duplexes. Results and Discussion Synthesis of the phosphoramidite building blocks Our strategy for the construction of the two phosphoramidite building blocks 10 and 16 envisaged as a key step the formation of a [4.3.0]bicyclic fluoroenone from a tricyclic siloxydifluorocyclopropane through a ring

• enlargement via selective cyclopropane ring opening [46][47][48][49]. Consequently, the synthesis started from the previously described bicyclic silyl enol ethers 1α/β (Scheme 1) [50][51]. The two anomers of 1 were individually transformed into the trimethylsilyl (TMS)-protected sugars 2α/β by adapting and

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• Orgánica, Facultad de Farmàcia, Universidad de Valencia, Av. Vicente Andrés Estellés, s/n 46100 Valencia, Spain 10.3762/bjoc.14.247 Abstract Ring-opening metathesis (ROM) of various unsaturated, constrained bicyclic ring systems has been investigated with the use of commercial ruthenium-based catalysts

• . Starting from various cyclodienes, the corresponding derived bicyclic lactone, lactam, and isoxazoline derivatives were submitted to ROM under ethenolysis. These functionalized, strained bicyclic systems afforded novel highly-functionalized diolefinated heterocyclic scaffolds in ROM reactions with

• structurally restricted cycloalkene β-amino acids or unsaturated bicyclic β-lactams, followed by cross-coupling metathesis (CM) of the newly created C–C double bonds (Scheme 1). Our current goal was to expand the study of the ROM protocol of functionalized strained ring systems to the investigation of

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• ), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain 10.3762/bjoc.14.237 Abstract A straightforward synthetic entry to functionalized hydrindane compounds based on a rapid assembly of the core nucleus by a Danheiser cycloaddition is reported. Valuable bicyclic building blocks containing the fused five

• have been used to build the hydrindane bicyclic system, but incorporating a different functionalization pattern in the cyclic compounds. Proposed here is a new methodological approach to functionalized 3a-substituted hydrindane synthesis based on a Danheiser annulation involving a [3 + 2] cycloaddition

• assemble the 6,5-bicyclic nucleus of hydrindane compounds, expanding the usefulness of the versatile decahydroquinoline building block 1. Although the compounds were prepared in racemic form, optically active substances are also accessible from enantiopure 1 [23]. The overall sequence shows the potential

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• an [8.4.0] bicyclic skeleton (1, Figure 1). In many cases, an additional oxygen bridge is present between positions 4 and 7, or 2 and 9, but there are also interesting eunicellanes without oxygen bridge, the majority of which has been isolated from marine corals. These comprise the solenopodins A–D

• of bicyclic diterpenoids sharing the eunicellane skeleton. Closure of the ten-membered ring by pinacol cyclization proved to be possible, if the six-membered ring is either aromatic or a 1,3-cyclohexadiene, but failed for systems with two sp3 centers as bridgeheads. The ten-membered ring of benzene

• beginning, and of precursors in which one of the centers will be sp2- and the other sp3-hybridized. Examples of the latter have already been obtained in form of allenes 32 and 34 that will now have to be elaborated further. Bicyclic eunicellane-type diterpenes. Synthetic eunicellane-type compounds with

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• manipulation involved the treatment of 4a with PhMgBr, converting the lactone moiety into the corresponding aromatic ketone. Product 8a formed in 71% yield without diastereoisomeric loss. Finally, LiAlH4 reduction of 4a furnished the bicyclic 1,3-diol 9a in quantitative yield, again without the need of

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• first metathesis step does not require a syn relationship (per VIII), the same possibility can be entertained for the second (see IX). This would lead to an isomeric bicyclic compound with "crossed chains". We have sought to access such species by conducting metatheses of substrates of the types in

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

• and co-workers developed a cobalt-catalyzed hydroarylation of 2-vinyloxiranes with indoles 7 to form C2-allylated products 46, albeit in low stereoselectivity (Scheme 29b) [83]. Similarly, Cheng et al. reported a hydroarylation reaction of arenes 7 with a bicyclic alkene to form ring-opening products

• form bicyclic cobaltacycle H1. After the reversible coordination of arene 55 with H1 to generate intermediate H2, ortho C–H cobaltation provides complex H3, which changed into product 56 and Co(I) catalyst by reductive elimination of H3. 5. Hydroarylation of C=X (X = N, O) bonds 5.1 Low-valent cobalt

Selective formation of a zwitterion adduct and bicarbonate salt in the efficient CO₂ fixation by N-benzyl cyclic guanidine under dry and wet conditions

• Yoshiaki Yoshida,
• Naoto Aoyagi and
• Takeshi Endo

Beilstein J. Org. Chem. 2018, 14, 2204–2211, doi:10.3762/bjoc.14.194

• particular, CO2 capture–release behaviors of bicyclic and six-membered cyclic amidine derivatives have been well studied compared to that of five-membered derivatives, because the high ring strain of five-membered cyclic amidine derivatives was unfavorable for the binding between CO2 and the amidine moiety

• guanidine derivative and CO2 was isolated and characterized for the first time, although there were a few reports about the bicyclic guanidine derivatives such as TBD. Results and Discussion CO2 fixation behavior of N-benzyl cyclic guanidine depending on dry and wet conditions First, CO2 fixation by N

An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change

• Tomoki Ogoshi,
• Tomohiro Akutsu and
• Tada-aki Yamagishi

Beilstein J. Org. Chem. 2018, 14, 1937–1943, doi:10.3762/bjoc.14.167

• /hydrophilic ratio in a molecule largely affects its assembled properties in aqueous media. In this study, we synthesized a new bicyclic compound which could dynamically change its hydrophobic/hydrophilic ratio by chemical stimulus. The bicyclic compound consisted of amphiphilic pillar[5]arene and hydrophobic

• alkyl chain rings, and formed a self-inclusion structure in aqueous media, which was assigned as a pseudo[1]catenane structure. The hydrophobic chain ring was hidden inside the pillar[5]arene cavity in the pseudo[1]catenane structure, thus the bicyclic compound was soluble in water at 20 °C with a

• aggregation of the hydrophobic alkyl chain rings, which induced insolubilization of the bicyclic compound in aqueous media at 20 °C and a decrease in its clouding point. Keywords: amphiphilic molecules; host–guest complexes; lower critical solution temperature; pillar[n]arenes; pseudo[1]catenane

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• , we wish to describe the synthesis of unprecedented tricyclic heterocycles, i.e., 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral free base derivatives 13 via the cationic [3+ + 2]-cycloaddition/rearrangement reactions using the bicyclic 4-acetoxy-4-azo

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• of DMAP base. The spirocyclization reactions were performed in MeOH for 2 h at 0 °C and spirocyclic products 56 were isolated in good yields (Scheme 18). Additionally, fused bicyclic compounds 57 were also observed in few reactions in traces. The structure of the spiro β-lactam was confirmed by

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• -thiosugar derivatives. We thus developed the first synthetic route accessing the 4-thiosugar derivative by way of bicyclic intermediate 8 from diacetoneglucose (5). Construction of the bicyclic ring of 8 was achieved by consecutive inter-/intramolecular SN2 reactions of the dimesylate derivative 7 obtained

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• correspond to two rings, which constitutes a fused bicyclic structure as suggested by the number of available aromatic carbons (eleven). A 4-quinolone substructure was indicated by a peak-splitting at the 340–320 nm region in the UV spectrum (328 and 322 nm) [13]. Indeed, 1H NMR resonances at the down field

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• coligand, their uranyl-(salen) derivatives 106a,b have been employed as models of the oxo-Mn(V)–(salen) oxidant species. The reactions were highly efficient in terms of productivity (up to 96% yield) and enantioselectivity (up to 93% ee) when rigid bicyclic alkenes such as 1,2-dihydronaphthalene and

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• bicyclic intermediate via a concerted [3 + 2]-cycloaddition followed by its very fast decomposition (extrusion of CO2) via a retro-Diels–Alder [4 + 2]-cycloaddition. The almost spontaneous extrusion of CO2 is caused by an energetically favorable aromatization occurring in this step leading to the formation

• (80 °C) caused a decrease in the total yield by approximately 50%, with slightly increased selectivity (from 4.96 to 6.56). Lowering of the yield with increasing pressure confirms the reversibility of the first step (see Scheme 5) because of retardation of CO2 cleavage from the bicyclic intermediate

• . Such reversibility was also suggested by Harrity et al. [92] on the basis of quantum calculations. While the formation of the bicyclic intermediate was calculated to be only slightly exergonic (−3.3 kcal·mol−1) the overall reaction is highly exothermic (−108.2 kcal·mol−1). These results show that minor

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• . Herein, we report such a strategy for the simple synthesis of functionalized pyrazolo[1,5-a]pyrimidinones that employs a one-pot microwave-assisted approach. Findings A number of synthetic approaches have been developed for the synthesis of privileged nitrogen-fused bicyclic systems such as the pyrazolo

• the development of novel biologically active compounds based on the pyrazolopyrimidinone scaffold, we sought to develop a simple one-pot synthesis of the nitrogen-fused bicyclic system. In order to establish reaction conditions for this one-pot synthesis, we began by seeking general reaction