Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• -one bis-nucleophiles. Keywords: 1,4-addition; annulation; decarboxylation; palladium; Pd-catalyzed allylation reaction; Introduction The development of new strategies for the synthesis of complex carbocyclic and heterocyclic structures remains a general topic for the synthetic chemists [1]. In the

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• are also important precursors in the synthesis of various biologically active molecules and pharmaceuticals such as antidepressants, antiviral and antibacterial drugs [4]. Cyclopropanols and their derivatives are considered to be carbocyclic homologues of enols presenting similar chemical properties

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• the other hand, the attempted N-alkylation of 8b upon MW irradiation led to the formation of a mixture of starting materials and some unidentified decomposition products. Due to the great importance of both carbocyclic and heterocyclic systems functionalized with the adamantyl group [27], different

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• allows sigmatropic rearrangements leading to odd-numbered carbocyclic derivatives [8]. In this sense, seven-membered carbocycles, namely 1,4-cycloheptadienes, can be forthrightly prepared from cis- or trans-1,2-divinylcyclopropanes through a Cope rearrangement [8][9]. The potential of this type of

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• can take part in ring-opening reactions under certain conditions. Cyclopropane derivatives, with their three-membered carbocyclic frameworks, have spurred considerable attention especially in the domain of organic and pharmaceutical synthesis because of their highly strained three-membered carbocyclic

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

• pseudorotation phase angle P adopting values of 175° (6a) and 181° (6b), respectively. The maximum puckering amplitude νmax was 43° (6a) and 40° (6b). Furthermore, the nucleobase displayed an anti orientation. The carbocyclic ring adopted a chair conformation. As a consequence, the angle γ was aligned in the

• ) surprisingly showed only one single low energy region in the Southern area of the pseudorotational cycle. The minimal energy conformer of nucleoside 7 adopted a C2’-endo furanose conformation (P = 160°) and a twist-boat orientation of the carbocyclic unit (Figure 3b). Hence, the angle γ took up a synclincal

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

• analogs as building blocks for therapeutic oligonucleotides, we investigated the bc4,3-DNA as scaffold for the modification. The idea was to place the fluorine atom next to the internucleosidic linkage. Furthermore, an additional double bond in the cyclohexane ring was expected to rigidify the carbocyclic

• the ±sc and anti range, whereas the angle ζ adopts all values between 0–360°. The reason for the flexibility of the angle ζ might lie in its compensatory nature to balance the constrained backbone angles that lay within the carbocyclic system. The DNA or RNA strand in these hybrid duplexes displayed

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• . Carbocyclic or heterocyclic fused pyridine derivatives are an important class of compounds omnipresent in natural products and biologically relevant synthetic compounds [23][24][25][26][27]. For example, imiquimod is an immune response modifier used to treat warts on the skin and certain type of skin cancer

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• of the great potential little attention has been paid [43] for exploring its application in the synthesis of complex carbocyclic ring systems, backbones of innumerable natural products. We undertook a program for the synthesis of condensed polycarbocyclic scaffolds using a metathesis of norbornene

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

• and six-membered carbocyclic ring system can be achieved in only four steps from a simple acyclic β-keto ester. Keywords: alkaloid; Danheiser annulation; decahydroquinoline; Introduction cis-Fused hydrindanes (bicyclo[4.3.0]nonanes) [1][2], scaffolds of numerous natural products, are amenable to

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• %. Further irradiation of hydrazones derived from furan-fused tricyclic diazocyclopentanediones culminates in the cycloelimination of furans to yield 2-N-(alkyl)hydrazone of cyclopentene-1,2,3-trione. By contrast, the direct photolysis of carbocyclic diazodiketones gives only Wolff rearrangement products

• compounds. The main objective of our current research was to elucidate the possibility of using carbocyclic diazodiketones in this photochemical process. For this purpose, diazocyclopentanediones 1a–g were tested in the study including unsubstituted diazocyclopentanedione 1a, tricyclic diazodiketones 1b–e

• as an argument in favor of the concerted Wolff rearrangement [11][12][13][14][15][16][17][18] in the case of these diazodiketones. Conclusion The sensitized photoexcitation of carbocyclic diazodiketones proceeds without elimination of dinitrogen. Instead, the reaction leads to the insertion of the

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

• compounds can be achieved using stoichiometric or catalytic amounts of iodine(III) reagents. According to literature reports, both heterocyclic and carbocyclic spirocyclic compounds can be achieved using these reagents [27][32]. 2. Synthesis of spirolactones 2.1. Using stoichiometric amounts of iodine(III

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• ][20][21][22][23][24][25][26][27][28]. In particular, the arylation–cyclisation reactions promoted by the highly electrophilic Cu(III)–aryl intermediates 3 can allow access to aryl-functionalised carbocyclic and heterocyclic molecules 8 with valuable functionalities [9][29][30][31][32][33][34][35][36

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• carbocyclic lignan variants related to podophyllotoxin, a pseudo-anomeric stereospecific inversion of a carbasugar was achieved in good yield in Nishimura’s group [39]. More recently, the Mitsunobu procedure was applied in the context of gold-catalyzed glycosylation in order to install a reactive anomeric

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

• well. The extension of hypervalent iodine-mediated glycosylation allowed us to couple a nucleobase with cyclic allylsilanes and glycal derivatives to yield carbocyclic nucleosides and 2’,3’-unsaturated nucleosides, respectively. In addition, the combination of hypervalent iodine and Lewis acid could be

• reaction coupled with oxidation. The concept of the oxidative glycosylation reaction was successfully applied to the synthesis of other nucleoside derivatives, including 4’-selenonucleosides and carbocyclic nucleosides. The hypervalent iodine-mediated glycosylation has also been used for oligosaccharide

• desired guanosine derivative 82 [60] (Scheme 11). As in the case of 4’-thionucleosides, the use of hypervalent iodine greatly improved the glycosylation reaction with 4-seleosugars by skipping the preparation of unstable selenoxide derivatives. Synthesis of carbocyclic nucleosides As described above, in

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• : Fulvalenes are typical cross-conjugated carbocyclic unsaturated compounds and are of theoretical and synthetic interest [59]. Several researchers have studied the synthesis of benzofulvalenes via the carbonyl group of 4,5-benzotropone (11) (Scheme 11). Halton’s group applied the Peterson olefination reaction

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• . Replacing the hemiaminal (O–C–N) connectivity of the canonical nucleosides with an O–C–C bond (Figure 3) results in a class of compounds called “C-nucleosides” [45][46][47][48][49][50][51]. Further modification to a C–C–C connectivity results in “carbocyclic C-nucleosides” (Figure 3) [52][53]. C-nucleosides

• nucleophilic substitutions to D-ribonolactone are discussed, a method that has seen wide applications. Next, we describe reports of different applications and structural variants that have expanded the diversity of the C-nucleosides. Finally, we discuss a modular synthetic approach to carbocyclic C-nucleosides

• lactol was formed, deoxygenation by BF3·OEt2 and reduction in presence of the Hantzsch ester afforded the desired β-anomer, while the use of Et3SiH gave the α-anomer [75]. Carbocyclic C-nucleosides In an attempt to synthesize carbocyclic C-nucleosides, Maier et al. found that reaction of aryl lithiums

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• arenes react well and substituted pyrroles and indoles give the corresponding sulfoxides in high yields. Less electron-rich thiophene or benzene derivatives gave low yields. Nevertheless, carbocyclic azulene afforded the respective sulfoxide in 88% yield. We propose an electrophilic aromatic substitution

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• the synthesis of 2’,3’-methano carbocyclic nucleosides via compound 24 (Scheme 5) [17]. Carbocyclic nucleosides are important synthetic targets because of their use as antiviral and antitumor agents [17]. Replacing the oxygen unit in the parent furanose ring with a methylene unit helps to stabilize

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• , we demonstrated selective constructions of six and seven-membered carbocyclic rings through the intramolecular iodoarylation of 3,3-difluoroallylic biaryls. The size selectivity in the cyclization was drastically controlled by the presence or absence of an aryl group in the 2-position of the 3,3

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• to suppress side reactions and to use a stoichiometric amount of nucleophile. Under these conditions, Michael addition reactions with nitrosoalkenes can be realized in an intramolecular fashion that opens access to complex bridged and fused carbocyclic frameworks bearing several contiguous

• and ketones including cyclic ones were successfully used as nitrosoalkenes precursors to give oximes 8 in good to high yields. The same authors used the advantage of intramolecular Michael addition of enolates to nitrosoalkenes to construct bridged and fused carbocyclic systems [27]. For example, the

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• carbocyclic five-membered ring to the 2,3-position of the bicyclic camphor-derived moiety (Scheme 2a) [20]. Reactions of 4a with halogens (e.g., bromine) or acids were even more puzzling. In addition to the annulation, an unprecedented formation of a ketone accompanied by the reduction of sulphur took place

• the C–C bond between the atoms bearing the OH and NH groups (ring enlargement). The result is an isomerisation of 4a and 4b to form tricyclic compounds 7 containing a nine-membered carbocyclic ring (Scheme 3a) [27]. Isomerisations are the best examples for a perfect “atom economy” [28][29][30] since

• similarities (shown in red in Scheme 3) but also differences to our compounds obtained by Pt(II) catalysis from, e.g., 4a. The eye-catching dimethylmethylene bridge over the largest carbocyclic ring is of course the most striking similarity, although this ring is in our compounds one-carbon unit smaller (9 vs

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• carbocyclic nucleoside methylphosphonate analogues bearing purine bases (adenine and guanine) was accomplished using bio-sourced furfuryl alcohol derivatives. All compounds were prepared using a Mitsunobu coupling between the heterocyclic base and an appropriate carbocyclic precursor. After deprotection, the

• compounds were evaluated for their activity against a large number of viruses. However, none of them showed significant antiviral activity or cytotoxicity. Keywords: analogue; antiviral; carbocyclic; nucleoside; phosphonate; Introduction Biomass is a valuable resource in search of renewable organic carbon

• some of the products have shown interesting antiviral activities. As part of our studies on carbocyclic nucleoside phosphonates [6] as potential anti-HIV agents [7][8], we envisioned to use bio-sourced racemic (+/−)-4-O-protected 2-cyclopentenone for the synthesis of hitherto unknown carbocyclic

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• . Following an optimized Schenck ene reaction procedure, N-methyl-1,2,3,6-tetrahydrophthalimide (1a) was reacted with molecular oxygen in the presence of methylene blue as sensitizer (Scheme 6). The resultant hydroperoxide motif (2a) constitutes a valuable carbocyclic building block. For reasons of

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ]. Their biosynthesis can be divided into three parts: the assembly of the PKS carbon backbone by a type II PKS including formation of the carbocyclic aromatic core, post-PKS modifications leading to the installation of the oxygen heterocycle and third, its modification by diverse tailoring enzymes [21][22