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

• substitution on cyclopentanone gives C1'–OH carbocyclic C-nucleosides. B. Synthesis of cyclopentanone from norbornadiene and substituents that facilitate carbocyclic C-nucleoside syntheses. Synthesis of carbocyclic C-nucleosides via Suzuki coupling [53]. A. Synthesis of OTf-cyclopentene that enable Suzuki

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• , cispentacin) are relevant antifungal agents [19]. Therefore we have selected some five and six-membered alicyclic dihydroxylated β-amino ester stereo- and regioisomers as model compounds [23][24][25][26], derived from cyclopentene or cyclohexene β-amino acids. These were used in order to evaluate their

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• cyclopentene moieties should always have more positive 3J NMR coupling constants for the cis than for the trans arrangement: Unrecognized exceptions might misguide one to wrong stereochemical assignments and thence to erroneous mechanistic conclusions. We show here that two structurally innocent-looking 2,3

• envelope shape (expected puckering ca. 22–33°) of the cyclopentene parts of 1 (lines 2 and 3 of Scheme 1): the distance between two vicinal, sp3-positioned protons in indanes clearly must be substantially longer for the pseudodiaxial (2ax-H,3ax-H) trans than for the pseudoaxial/pseudoequatorial (2ax-H,3eq

• the generated portion of 4 together with remnant n-BuLi, so that a very rapid Br/Li interchange reaction of 4 with n-BuLi will produce 1,1-dimethyl-2-lithioindene, whose protolysis forms 1,1-dimethylindene (2). Conclusion Cis/trans differentiation in the saturated part of cyclopentene moieties should

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• is the case for carbene 19, since the alkyl bridge locks its conformation in such a way that prevents an activating alignment, and the oxygen acts as an inductive electron-withdrawing group. The alkene in the cyclopentene of 20 was oxidatively cleaved, and then an aldol condensation gave the

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• yields than aryl and acyl groups. Other olefins such tert-butylethylene and cyclopentene can be used as well, but the yields were significantly lower (cf. 63 and 64). The scope of the directing 2-pyridinyl group can be expanded to electron-withdrawing groups such as ester and trifluoromethyl, while

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• -sulfonylimines proceeded in an unexpected [3 + 2] annulation mode to afford a cyclopentene ring with an all-carbon quaternary center (Scheme 1) [48]. In recent years our group has developed a family of amino acid-derived bifunctional phosphines and has intensively investigated related asymmetric transformations

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• of cyclopentene anellation by cyclization of aryl-substituted allyl cations. High yields were reported by Alvarez-Manzaneda et al. in the course of their total synthesis of taiwaniaquinone H. They induced the cyclization by treatment of arylvinylcarbinols with the mild Lewis acid SnCl4, which were

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• – 1.0 mM, 0.60 mL, 0.6 μmol) in a NMR tube. The substrate conversion was monitored at 20 °C via 1H NMR spectroscopy by integration of the sufficiently separated multiplet signals at δ 2.78 ppm (m, allyl-CH2, DEDAM) and 3.13 ppm (m, ring-CH2, cyclopentene derivative). General procedure for the RCM of

• with ethyl vinyl ether, dried under vacuum, and the monomer conversion was monitored via 1H NMR spectroscopy (300.1 MHz, 20 °C, D2O) by integration of the signals δ 2.58 (DAMA-CH2) and δ 2.98 ppm (cyclopentene-CH2). The aliquots taken after 60 min indicated the same conversion level as those taken

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• RRM with E-selectivity at the macrocyclic double bond. Along similar lines, compound 65f was treated with catalyst 1 in refluxing toluene followed by treatment with catalyst 2 to deliver desmethylmanshurolide 67 in 44% yield (Scheme 11). Cyclopentene systems In RRM with cyclopentene systems, the

• and Li [17] disclosed a highly distereoselective RRM approach starting with cyclopentene derivatives. In this regard, the cyclopentene derivative 72 was treated with the catalyst 2 in the presence of ethylene (24) to generate the required cyclohexene-based product 73. The total synthesis of

• , when the cyclopentene derivative 74 gave 75 and 76 (1:5, 75%) with catalyst 1; whereas, the catalyst 2 produced 75 and 76 in 85% yield (12:1). Here, they have shown the thermodynamically favored RRM leads to the formation of 75, while kinetically favored RCM gave the product 76 (Scheme 14). Cyclohexene

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• ]. Treatment of indole 14 with SmI2 afforded the cyclic bisindole 15 and, after silica column chromatography, its elimination product cyclopentene 16. On the TLC only the tertiary alcohol 15 and full consumption of the starting material were observed. Product 15 was converted quantitatively to cyclopentene 16

• between the two β-carbons. When the enone unit was connected to the indole 6-position via the carbonyl moiety, a deconjugated cyclopentene (16) became accessible. In the absence of the α,β-double bond as in the natural product verticillatine B (20), SmI2 in THF was not able to induce a dimerization and no

• . Meyer–Schuster rearrangement of 13 and SmI2-mediated reductive [3 + 2] cycloaddition, followed by elimination to cyclopentene 16. Selected NOESY correlations for compound 15 are given. Nazarov-type cyclization of 14 to cyclopentanones 17 and 18; synthesis of verticillatine B (20). Synthesis and X-ray

Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

• Thibault E. Schmid,
• Florian Modicom,
• Adrien Dumas,
• Etienne Borré,
• Loic Toupet,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 1541–1546, doi:10.3762/bjoc.11.169

• hand, we then briefly investigated the scope of metathesis transformations using 1 mol % of 4a in dichloromethane at 25 °C, using hydrochloric acid as activator (Table 1). Both substrates 6 and the tosylamine 8 were efficiently converted to the desired cyclopentene products that were isolated in 97 and

Thermal properties of ruthenium alkylidene-polymerized dicyclopentadiene

• Yuval Vidavsky,
• Yotam Navon,
• Yakov Ginzburg,
• Moshe Gottlieb and
• N. Gabriel Lemcoff

Beilstein J. Org. Chem. 2015, 11, 1469–1474, doi:10.3762/bjoc.11.159

• be disrupted first to afford a linear polymer, followed by the ring opening of the less reactive cyclopentene double bond to effectively cross-link the chains (Scheme 1). Notably, with tungsten and molybdenum initiators the linear polymer may be isolated [20][21]; unlike the case with ruthenium

• attributable to further polymerization of unreacted cyclopentene bonds and free monomer. Resting temperature effect. Blue columns: resting at room temperature. Orange columns: resting at −5 °C. Gray columns: resting at −196 °C. Time elapsed between measurements was 1 week. Top: Sample after 1 week with ethyl

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• , we then tested the scope of the reaction using different cyclic ketones. Thus, the reaction of the azido alcohol (±)-3 with cyclobutanone and cyclopentanone afforded the corresponding cyclopentene-substituted lactams (±)-7 and (±)-8 in good yields. The 2D NMR analysis and HMBC correlations for one of

• the products (±)-8 are shown in Scheme 4 and confirmed the 1,2-substitution in the cyclopentene ring of the product. Similarly, lactam (±)-9 was prepared from 4-pyranone with (±)-3 and obtained in moderate yield. To further broaden the scope of this method, the reaction was also performed with

• symmetrical ketone 6,6-dimethyl-bicyclo[3.1.0]hexan-3-one [39] with (±)-3 resulted in compound (±)-10 in 40% yield. Since all synthesized compounds contain a 1,2-substituted cyclopentene ring in their structures, it is suggested that the starting 1,3-azido alcohol 3 undergoes a 1,3-shift to give the

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• cleavage of carbobicycle-fused 2-isoxazolines converts both exo- and endo stereoisomers of 8 into the corresponding single isomer of cyclopentene 9 (Table 1) [20]. Since then, we have been interested in the outcomes of cleavage reactions of 2-isoxazolines fused to heterobicyclic compounds 10 or 11, which

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• mild conditions, providing a variety of functionalized cyclopentenes, cyclopentenylphosphonates, spirooxindoles, heterocyclic spiranes, cyclopentene-fused chromanones, and dihydroquinolinones enantioselectively (Schemes 10–17) [38][39][46][47][48]. These products can be quite biologically active and

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• from (1R,2S)-ephedrine, to α-substituted cyclopentenones. The required precursor for the synthesis of methyl jasmonate (11), 2-(2-pentynyl)-2-cyclopentene-1-one (148) was prepared by a known sequence [115] starting from 1,3-cyclohexanedione (145) (Scheme 18). Addition to 1-bromo-2-pentyne (146

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• triflates was also observed, suggesting the reaction is also sensitive to sterics (Table 4, entries 9 and 10). We also tested all new ligands L1–L6 in the asymmetric Heck arylation of cyclopentene (Table 5). Initial experiments conducted under the conditions optimized for arylation of dihydrofuran 1

• provided no reaction with cyclopentene 21. Additional optimization revealed that reasonable reaction rates can be achieved only in the presence of Pd(dba)2 catalyst and proton sponge. It should be mentioned that employment of Pd2(dba)3·CHCl3 catalyst in place of Pd(dba)2 provided no reaction. Generally

• dihydrofuran with aryl tiflates. Evaluation of Ligands L1–L6 in the intermolecular asymmetric Heck reaction of phenyl triflate (2a) with cyclopentene (19). Supporting Information Supporting Information File 446: Detailed experimental procedures of chiral ligands L2, L5, and L6. Acknowledgements Financial

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• diastereospecific available [30] (Figure 4). The process started with a Wohl–Ziegler allylic bromination of cyclopentene. The volatile and unstable allylic halide 10 was immediately reacted with excess N,N-dibenzylamine and the resulting allylic amine 11 was obtained in good yield over two steps. Next, we

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• expansion [11][12] as a special case of the DVCPR is not part of this review. The related vinylcylopropane–cyclopentene rearrangement has been reviewed elsewhere [13][14]. Review Mechanistic considerations Transition state. Although the cis-divinylcyclopropane rearrangement is in fact a tethered version of

• vetiver oil were synthesized starting from cyclopentene derivative 60 [61]. This rather simple starting material was elaborated to advanced bicyclic 61 in only seven steps. This time the group of Piers used a cis-divinylcyclopropane, which underwent smooth DVCPR during distillation at 110 °C to yield

• –cyclopentene rearrangement [13][14] has been shown to be the major competing side reaction in this case. Nitrogen variants Three different approaches can be used to incorporate nitrogen into the DVCPR. The cis-divinylaziridine rearrangement (311 to 312, see Scheme 38) after rhodium-catalyzed aziridine

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

• Sylvestre Bachollet,
• Kimitada Terao,
• Shin Aida,
• Yasuhiro Nishiyama,
• Kiyomi Kakiuchi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2013, 9, 2015–2021, doi:10.3762/bjoc.9.237

• , Takayama-cho, Ikoma, Nara 630-0101, Japan 10.3762/bjoc.9.237 Abstract [2 + 2]-Cycloadditions of cyclopentene and 2,3-dimethylbut-2-ene to furanone were investigated under continuous-flow conditions. Irradiations were conducted in a FEP-microcapillary module which was placed in a Rayonet chamber

• amber flask. Irradiation conditions and light penetration Model irradiations using furanone 1 and cyclopentene (2) in acetonitrile were performed under batch conditions to establish the most suitable reaction conditions (Scheme 1; R = R′ = H, R″ = –(CH2)3–). Upon direct irradiation with UVC light in a

• smaller diameter, the light transmission in the microcapillary was still superior with 53%, compared to 0.3% in the test tube. [2 + 2]-Cycloadditions with cyclopentene The photoaddition of cyclopentene (2) to 1 was subsequently investigated in detail under batch and microflow conditions (Scheme 2, Table 1

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• the enantioselective desymmetrization of meso-epoxides. Organocatalyzed enantioselective ring-opening of epoxides in early stage In 1981, Andrews [78] and co-workers have found that the ring-opening of cyclohexene and cyclopentene oxides with silicon halides was facilitated by the addition of

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• cyclopentene did not participate in the metathesis reaction, and the bridged macrocycle 53 was obtained in low yield. We have previously observed the formation of macrocyclic metathesis products in similar metathesis cascade reactions [14]. The formation of the cyclopropanes 46 and 47 as byproducts in the

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• ) [26]. Asymmetric induction can be achieved in [2 + 2] cycloadditions through the use of a chiral auxilliary. The [2 + 2] reaction shown in Scheme 3 employed a chiral ester function to direct the facial selectivity of the addition of the enone to cyclopentene. Diastereoselectivity was found to be

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• dihydronepetalactones [1], this key intermediate could be obtained via a highly diastereoselective transfer hydrogenation of the known [19] trisubstituted cyclopentene 7 with ammonium formate over palladium [1][14][15]. Starting from the aldehyde 8, the relative configuration of which had been confirmed by NOE

• that along with other iridoids 18 and 19 are also components of the essential oil of some plant species [36]. A related cyclopentene derivative is chrysomelidial (21), a relatively widespread defense compound in larvae of phytophagous leaf beetles Chrysomelidae [37][38], which has been found in other

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• trans-fused dihydronepetalactones were synthesized. Key compounds were pure stereoisomers of 1-acetoxymethyl-2-methyl-5-(2-hydroxy-1-methylethyl)-1-cyclopentene. The stereogenic center of limonene was retained at position 4a of the target compounds and used to stereoselectively control the introduction

• . Route to stereochemically pure trans-fused dihydronepetalactones from (R)-limonene Due to the shortcomings of the route described above, we designed an improved strategy towards trans-fused dihydronepetalactones. Starting from 1-formyl-2-methyl-5-(1-methylethenyl)-1-cyclopentene (15) as the key

• the key intermediate 16 – which shows two differentiated primary alcohol functions – started from enantiomerically pure (R)-limonene (14, Scheme 2). Ozonolysis followed by reductive workup with dimethyl sulfide produced (3R)-3-(1-methylethenyl-6-oxoheptanal), which yielded the formyl cyclopentene 15