Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• to investigate the preparation and uses of new propargylic fluorides [12][13][14], which have been employed in the synthesis of fluorinated analogues of lipids [15][16] and in carbocyclic systems [17][18]. They have also been used for the preparation of several 5 and 6-membered heterocycles [19][20

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• spirocyclic carbocyclic systems [3], cyclic amino acid derivatives [4], cyclic ethers [5][6], and lactones [7][8]. In most of these examples, the reactions can be viewed as arising from an oxidation that forms an olefinic radical cation that is then rapidly trapped by a nucleophile. This triggers a cascade of

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• under these experimental conditions, although the intermediate imine was supposedly formed during the reaction but not isolated. The carbocyclic core of aurachin H Aurachin H (6) was isolated from Stigmatella aurantiaca at the same time as the aurachin series A–L [3]. Biosynthetically, it may arise from

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• synthetic chemists, thanks to their massive pharmacological potential [21][22]. For example, cispentacin ((1R,2S)-2-aminocyclopentanecarboxylic acid, 7) is a widely investigated naturally occurring carbocyclic β-amino acid with strong antifungal properties against Candida species (Figure 2) [23]. Its

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• ]. The unique structures and the highly pronounced pharmacological activity displayed by the spirooxindoles have made them attractive synthetic targets [6][7][8][9]. In various heterocyclic and carbocyclic spirooxindoles, the spiro-oxirane-oxindoles are a particular class of compounds with both spiro

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• still lacking: a treatment that can be of use on at least a semiquantitative basis with respect to both global and local reactivity, that is, substrate as well as positional selectivity, for a wider range of substrates and nucleophiles. In this study we have included both different carbocyclic and

• of carbocyclic as well as heterocyclic fluorinated substrates [4][5]. Anionic nucleophiles (anions of methanol, benzyl alcohol and hydrogen sulfide) were investigated, as well as neutral nucleophiles (amines). The accuracy was well within 1 kcal/mol and the predictions can be used in a quantitative

• ). The first series (series A) deals with the amination of nine different fluorinated heterocyclic substrates run at 25 °C. The second series (series B) with the amination of seven different carbocyclic substrates run at 80 °C. Except for the temperature, reaction series A and B were run under identical

Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• William F. Bailey Justin D. Fair Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, USA Department of Chemistry, Indiana University of Pennsylvania, Indiana, PA 15705, USA 10.3762/bjoc.9.59 Abstract The preparation of fairly strained carbocyclic ring systems by

• a variety of functionalized carbocyclic [5][6][7] and heterocyclic systems [8][9]. The bonding changes that accompany cyclization of an unsaturated organolithium indicate that the process should be energetically favorable since a σ-bond (bond energy ca. 88 kcal/mol) is generated at the expense of a

• π-bond (bond energy ca. 60 kcal/mol). As a consequence, strained carbocyclic systems may be constructed by operationally irreversible [10] intramolecular carbolithiations [11][12][13][14][15]. At the outset of our foray into this area several decades ago [16], we were initially surprised to find

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• intramolecular alkenylation on a range of other electron-rich heterocycles, including pyrroles, furans and thiophenes [63][64]. The intramolecular Pd(II)-catalyzed reaction of the 3-alkenylindoles 14 gave rise to the carbocyclic 5-membered ring-fused products 15 (Scheme 12) [65][66]. This procedure involves O2

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• -membered ring to bicyclic 3,4-diaminopyridines leads to tricyclic diaminopyridines 407, 408, and 410 and is accompanied by an increase in acetyl cation affinities above 240 kJ/mol. Annelation of a carbocyclic ring thus has a comparabel effect as already observed for DMAP (54) and its ring-extended forms

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• and Heck reactions, respectively [21]. The dienes obtained during these transformations were successfully converted in Diels–Alder reactions to afford carbocyclic chiral compounds with a sugar backbone. In 2008, Gagné introduced a Ni-mediated Negishi coupling to synthesize alkyl- and aryl-C-glycosides

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

• Subrata Kumar Chaudhuri,
• Sanchita Roy and
• Sanjay Bhar

Beilstein J. Org. Chem. 2012, 8, 323–329, doi:10.3762/bjoc.8.35

• at C4 having no partner to couple with. Thus the incorporation of bromine at C3 (Table 1, entries 2 and 4) was established. When 1b reacted with more than two equivalents of DD, the second bromine atom was incorporated in the carbocyclic ring at C8 through aromatic electrophilic substitution (Table 1

• result (Table 1, entries 10 and 11). It is important to note that the presence of an electron-donating group (–NH2) at C6, without an alkyl substituent at C4, lead to bromination of the carbocyclic ring bearing the amino group through aromatic electrophilic substitution instead of vinylic bromination

• aromatic substitutions at the more activated carbocyclic aromatic ring without vinylic bromination, regardless of the presence or absence of the alkyl substituent at C4 (Table 1, entries 13 and 14). The appearance of only one singlet around δ 7.5 (due to aromatic-H at C8) in 2kk and 2l indicated the

Synthetic approaches to multifunctional indenes

• Neus Mesquida,
• Sara López-Pérez,
• Immaculada Dinarès and
• Ermitas Alcalde

Beilstein J. Org. Chem. 2011, 7, 1739–1744, doi:10.3762/bjoc.7.204

• access to different substitution patterns, is rather cumbersome owing to the complexity of the indene chemistry, especially of those processes that could be modulated by the aromatic character of a resulting indenyl anion species. Indeed, indene is an unusually acidic nonaromatic carbocyclic system and

Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

• Paul W. Davies,
• Nicolas Martin and
• Neil Spencer

Beilstein J. Org. Chem. 2011, 7, 839–846, doi:10.3762/bjoc.7.96

• - and deuterium-labelled substrates. Keywords: 1,2-aryl shift; cycloisomerisation; gold; isotopic labelling; pyrrole; skeletal rearrangement; Introduction Gold-catalysed cycloisomerisation reactions have emerged as powerful methods to construct a diverse array of hetero- and carbocyclic motifs under

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2011, 7, 601–605, doi:10.3762/bjoc.7.70

• , intermolecular [2 + 2] cycloaddition reaction between 2,3-pentadiene and methyl propiolate [10]. In summary, there are only a few general methods to prepare carbocyclic spirooxindoles non-racemically [11][12][13][14]; we have demonstrated the first thermal, intramolecular [2 + 2] cycloaddition reaction of an

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• importantly on the way the heterocyclic components were assembled. Aromatic and non-aromatic heterocyclic rings are a predominant architectural constant of pharmaceuticals and allow for variable interactions with the biological target which are not possible using simpler carbocyclic motifs. Based on our

Highly substituted benzannulated cyclooctanol derivatives by samarium diiodide-induced cyclizations

• Jakub Saadi,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, 1229–1245, doi:10.3762/bjoc.6.141

• ]. Among these approaches to carbocyclic compounds, samarium diiodide-mediated reactions play an important role and have been described in a number of excellent review articles [19][20][21] and original publications [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. In our previous reports we have

Carbasugar analogues of galactofuranosides: α-O-linked derivatives

• Jens Frigell and
• Ian Cumpstey

Beilstein J. Org. Chem. 2010, 6, 1127–1131, doi:10.3762/bjoc.6.129

• carbocyclic ring as the β-talo epoxide 4, were opened by nitrogen nucleophiles (nucleobases [18] or azide [19][20]) with generally good regioselectivity for attack at C1. The only precedent for attack at such carbapentafuranose epoxides with an oxygen nucleophile would appear to be the acid-mediated attack of

β-Hydroxy carbocation intermediates in solvolyses of di- and tetra-hydronaphthalene substrates

• Jaya S. Kudavalli and
• Rory A. More O'Ferrall

Beilstein J. Org. Chem. 2010, 6, 1035–1042, doi:10.3762/bjoc.6.118

• the carbocyclic substrate in this case shows a rate retardation of 80,000 [16]. This value has been considered exceptionally large and an additional rate-retarding effect has been attributed to ring strain induced by the presence of oxygen in the six-membered ring of the bicyclic carbocation

A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles

• Kay M. Brummond and
• Joshua M. Osbourn

Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33

• Kay M. Brummond Joshua M. Osbourn Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, U.S.A 10.3762/bjoc.6.33 Abstract The synthesis of C3-carbocyclic spirooxindoles was realized by way of an intramolecular [2 + 2] cycloaddition reaction between a vinylidene indolin

• evidenced by baseline impurities on the TLC. However, the only discernable product in the NMR spectrum is the desired spirooxindole 10f. Conclusion We have developed a concise synthesis to C3-carbocyclic spirooxindoles. One important feature of this thermal tandem [3,3]-sigmatropic rearrangement/[2 + 2

• column. The column was eluted with hexanes (100 mL) and then with 25% ethyl acetate/hexanes. The fractions containing the desired product were concentrated under reduced pressure to provide 18 mg of spirooxindole 10a as a brown oil in 60% yield. Heterocyclic and carbocyclic spirooxindoles. Access to

Fused bicyclic piperidines and dihydropyridines by dearomatising cyclisation of the enolates of nicotinyl-substituted esters and ketones

• Heloise Brice,
• Jonathan Clayden and
• Stuart D. Hamilton

Beilstein J. Org. Chem. 2010, 6, No. 22, doi:10.3762/bjoc.6.22

• carbocyclic ring by dearomatising cyclisation The study was initiated with the synthesis of the δ-nicotinyl ketone 7 as illustrated in Scheme 2. Ethyl benzoylacetate was alkylated with 3-(3-iodopropyl)pyridine 5 and the product 6 hydrolysed and decarboxylated to yield the pyridine 7 in moderate yield. On

• corresponding 12.9 Hz coupling to the proton α to the ester group is consistent with adoption of an exo–equatorial orientation by this substituent. Formation of a tetrahydrofuran by dearomatising cyclisation Encouraged by the successful formation of carbocyclic rings in dearomatising cyclisations of nicotinyl

Ring-alkyl connecting group effect on mesogenic properties of p-carborane derivatives and their hydrocarbon analogues

• Aleksandra Jankowiak,
• Piotr Kaszynski,
• William R. Tilford,
• Kiminori Ohta,
• Adam Januszko,
• Takashi Nagamine and
• Yasuyuki Endo

Beilstein J. Org. Chem. 2009, 5, No. 83, doi:10.3762/bjoc.5.83

• B) than for carbocyclic derivatives (C and D). Analysis indicates that this effect may have quadrupolar and conformational origin. Keywords: p-carborane; liquid crystals; structure-property relationship; Introduction During the past decade, we have been investigating mesogenic derivatives of p

• exclusively the nematic phase. Similar nematic behavior is observed for carbocycles in series 17–20 with the exception of 19D, which exhibits a SmA phase in addition to a N phase. In contrast, most carbocyclic derivatives in series 14[6]–16[6] display only smectic and soft crystalline polymorphs. The bicyclo

• alkoxyphenyl group) for the carbocyclic compounds. In contrast, the difference in TNI is larger by 10 K for p-carborane A and 18 K for p-carborane B (Figure 5 and Figure 6). These results are consistent with earlier findings for pairs 1/2, 3/4, and 5/6 (Figure 5) in which a particularly large impact of the

Synthesis of chiral cyclohexanes and carbasugars by 6-exo-dig radical cyclisation reactions

• Rajeev K. Shrivastava,
• Elise Maudru,
• Gurdial Singh,
• Richard H. Wightman and
• Keith M. Morgan

Beilstein J. Org. Chem. 2008, 4, No. 43, doi:10.3762/bjoc.4.43

• of carbohydrates as precursors for highly functionalised carbocyclic rings systems has found wide utility in organic synthesis [1][2][3][4][5][6][7][8][9][10][11]. In particular there is a large amount of literature devoted to the synthesis of cyclopentanes [12][13] that employs a 5-exo-dig ring

Understanding the mechanism of Pd-catalyzed allylic substitution of the cyclic difluorinated carbonates

• Jun Xu,
• Xiao-Long Qiu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2008, 4, No. 18, doi:10.3762/bjoc.4.18

• , Shanghai 201620, China 10.3762/bjoc.4.18 Abstract We present a mechanistic investigation of Pd-catalyzed allylic substitution of cyclic gem-difluorinated carbonates 1 and 4, previously employed in the synthesis of 3',3'-difluoro-2'-hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides in 17 steps. The

• substitution features a reversal of regioselectivity caused by fluorine. Background Carbocyclic nucleosides (CNAs), in which the furanose oxygen atoms of the 4'-oxonucleosides are substituted by CH2, have received considerable attention because they exhibit greater metabolic stability toward nucleoside

• phosphorylases and higher lipophilicity, two properties that are potentially beneficial in terms of increased in vivo half life, oral efficiency and cell wall penetration [1][2]. Based on CNA skeletons, 1,2-disubstituted carbocyclic nucleosides (OTCs) recently attracted more and more attention [3][4][5][6][7][8

Allylsilanes in the synthesis of three to seven membered rings: the silylcuprate strategy

• Asunción Barbero,
• Francisco J. Pulido and
• M. Carmen Sañudo

Beilstein J. Org. Chem. 2007, 3, No. 16, doi:10.1186/1860-5397-3-16

• to a wide range of functionalised allylsilanes, which are valuable intermediates for carbocyclic annulations. Effectively, the former substrates (containing a nucleophilic allylsilane unit and an electrophilic function) undergo "intramolecular allylsilane terminated" cyclizations when treated with