Design and synthesis of novel bis-annulated caged polycycles via ring-closing metathesis: pushpakenediol

• Sambasivarao Kotha and
• Mirtunjay Kumar Dipak

Beilstein J. Org. Chem. 2014, 10, 2664–2670, doi:10.3762/bjoc.10.280

• -diallylpentacyclo[5.4.0.02,6.03,10.05,9]undeca-8,11-dione (20) Tricyclic dione 19 (125 mg, 0.49 mmol) was dissolved in dry ethyl acetate (500 mL) and irradiated in a Pyrex immersion well by a 125 W lamp (homemade) for 1.5 h under nitrogen at rt. After completion of the reaction (TLC monitoring), the solvent was

• ; found, 309.1862 [M + H]+. Selected theoretically interesting molecules. Retrosynthetic approach toward bis-annulated PCUD. (a) Optimized structure of 22 (b) Ancient flying machine “Pushpak Viman”. The synthesis of diallylated tricyclic diene 19. The synthesis of diallylated pentacyclic dione 20. The

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• the nine-membered ring led to tricyclic compound 45. The pyrrole ring of 45 was formed by intramolecular condensation of cinnamyl amide 46, which is prepared via union of quaternary piperidinone 47 and cinnamyl electrophile 48. We envisioned that our allylic alkylation of lactam enolates would furnish

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• ring-opening to 11 during the solvent evaporation after the irradiation and therefore the identification of this compound had to be done immediately after the work-up procedure. The formation of tricyclic formamido derivative rel-(9S)-11 can be explained by the addition of water to the exo-double bond

• -vinylnaphtho[2,1-b]thiophene [6] occured, respectively. During chromatography on silica gel the tricyclic formiato derivative rel-(9S)-12 is formed from 8 (Scheme 5). In the 1H NMR spectrum the main diastereomer rel-(9S)-12a shows the signal of the formiato proton in the low field at 8.2 ppm. The signals from

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• indolenium salt more likely to accept the migrating alkyl group at the C2-position that is in equilibrium with the corresponding tricyclic pyrroloindolines. Indeed, the reaction between 3-benzylindole (1a) and methyl 2-phthalimidoacrylate (2b) gave only 48% yield of the desired rearranged product (3j) (Table

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

• carbapenem-resistant enterobacteriaceae such as Klebsiella pneumoniae [90][91]. In the 1990’s, scientists at GlaxoWellcome developed sanfetrinem (113), a member of a novel class of tricyclic β-lactam antibiotics known as trinems [92][93]. Eventually the development of sanfetrinem was stopped in 2009 after

• tricyclic intermediate 121. Cleavage of the TBS ethers and hydrogenolysis of the benzyl ester in presence of amidine 122 yielded trinem 23a as its amidinium salt 123. Trinem 123 exhibited antibacterial activity against a variety of strains, with MIC’s of 1.0 μg/mL against Staphylococcus aureus 853E and 0.1

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• functionalized with an alkyne group by a Cu(I) azide–alkyne cycloaddition (CuAAC) reaction. Then, the mimetic 6 with a butyne group at the anomeric position, which is required for the conjugation to the glycodendron 7 (Scheme 1), was also prepared as already reported [33]. The synthesis of the tricyclic spiro

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• major reaction products were obtained in combined yields of 30–67%. One product resulted from aminomethyl radical addition, the other product was a tricyclic compound, which is likely formed by attack of the intermediately formed α-carbonyl radical at the phenyl ring. For five-membered α,β-unsaturated

• tricyclic product 4 employing 4,4’-bis(dimethylamino)benzophenone (3) as the catalyst [38]. In this case, the amine was used in large excess (15 equiv) and the chiral menthyl group was derived from (−)-menthol. It was later found that the reaction proceeds with a higher yield (73%) if acetone was employed

• = phenylpyridyl; bpy = 2,2’-bipyridine) and [Ir(ppy)2(dtbbpy)]BF4 (7) (dtbbpy = 4,4’-di-tert-butyl-2,2’-bipyridine) gave the best results while other iridium catalysts turned out to be inferior. Remarkably, the desired tricyclic product 10 was isolated as the only product while the direct addition product 11 was

Cuevaenes C–E: Three new triene carboxylic derivatives from Streptomyces sp. LZ35ΔgdmAI

• Jing-Jing Deng,
• Chun-Hua Lu,
• Yao-Yao Li,
• Shan-Ren Li and
• Yue-Mao Shen

Beilstein J. Org. Chem. 2014, 10, 858–862, doi:10.3762/bjoc.10.82

• activity against Gram-positive bacteria [1]. JBIR-23 and JBIR-24, novel anti-malignant pleural mesothelioma (MPM) agents, were isolated from Streptomyces sp. AK-AB27 six years ago [2]. All of these natural products have a tricyclic core and a polyene side chain with an enolmethyl ether inside. This type of

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• -[4,5]deca-6,9-diene-3,8-diones (171) via a 5-exo-Michael addition, whereas DCM as solvent induced an intramolecular thiophene Diels–Alder reaction yielding tricyclic lactam 173. In an alternative approach an Ugi-protocol employing a resin-bound carbonate-based convertible isocyanide 174 (CCI) was

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• corresponding tricyclic naphthalene fused pyrazoles 15 (Scheme 12, path A). Moreover, in a subsequent work, the authors applied the same strategy to obtain pyrazolo[4,3-b]indoles 16, a new class of CK2 inhibitors [42]. These products were obtained starting from properly substituted dihydropyrazoles 13 in which

• different reaction mechanism and allows for the synthesis of tricyclic H-pyrazolo[5,1-a]isoquinoline 48 (Scheme 25). With these results in hand, a MCR involving 2-alkynylbenzaldehydes 25, tosylhydrazide (41), methanol and α,β-unsaturated aldehydes or ketones 49 was set up to synthesize a library of 24 H

• (enamines and carbanions) or be involved in cycloaddition reactions affording tricyclic compounds by cascade processes. An unprecedented, co-catalyzed reaction involving enamines 51 as nucleophilic partners, also yields the H-pyrazolo[5,1-a]isoquinoline nucleus 48, in the presence of silver triflate and

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• thus be tricyclic. The NMR data and a DEPT experiment (Table 1) indicated the presence of an olefinic methine group [δH 6.03 (br s), δC 124.1], two aliphatic methine groups [δH 2.47 (m), δC 43.1; δH 2.45 (m), δC 35.4], five methylene groups [δH 2.33 (m), 2.68 (m), δC 33.8; δH 1.87 (m), 2.03 (m), δC

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• boronated dienes 6, which were not isolated, but directly used in a one-pot Diels–Alder reaction/allylboration sequence. This efficiently generated, in high yields, tricyclic structures 7 with control of four stereogenic centers created (Scheme 8). In the presence of Grubbs II catalyst, a skeletal isomer 8

• -phenylmaleimide furnished the single tricyclic compound 37 (Scheme 26). The initial boronic ester group of 38, the direct precursor of 32, can be also converted into a trifluoroborate substituent by treatment with KHF2 in MeOH/H2O to increase the reactivity of the dienyl moiety towards electron-poor dienophiles

• . Tandem aza-[4 + 2]-cycloaddition/allylboration/retrosulfinyl-ene sequence. Boronated heterodendralene 32 in [4 + 2]-cycloadditions. Synthesis of tricyclic imides derivatives. Synthesis of 37 via a HDA/allylboration/DA sequence. Diels–Alder/allylboration sequence. Acknowledgements L.E. thanks the Durham

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• hydroxy substituents of 24 with TBS-groups, a Staudinger reaction was performed, which furnished bicyclic 1,2-oxazine derivative 25 with a primary amino group in 80% yield (over two steps). Next we wanted to synthesize the unexpectedly formed unique tricyclic 1,2-oxazine 20 with higher efficacy. After

• isolated in 63% and 88% yield, respectively. Gratifyingly, the unique tricyclic 1,2-oxazine 20 was very efficiently converted into bicyclic aminooxepane derivative 28 (96% yield) without formation of side products. The irreproducible results with 14 and 15 are probably due to the formation of side products

• , EtOH, 0 °C, 4 h; c) TBAF (1 M THF), THF, 0 °C → rt, 3 d. [TBAI = tetra-n-butylammonium iodide] Synthesis of tricyclic compound 20, bicyclic azide 24 and bicyclic amine 25. Conditions: a) MsCl, Et3N, CH2Cl2, 0 °C → rt, 5 h; b) NaBH4, EtOH, 0 °C, 6 to 16 h; c) NaN3, DMF, reflux, 16 to 46 h; d) Et3N, DMF

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

• (DMAPP) through 28 to yield 29, (Scheme 6) [40][41][42] the spiro-oxindole 30 was synthesized. The system underwent a cis-aryl-vinyl-cyclopropane rearrangement [43] to give 31 followed by rearomatization in 4–12 hours at room temperature yielding tricycle 32. The formation of the obtained tricyclic

• the cytotoxic sesquiterpenoid quadrone (55) from Aspergillus terreus [52][53] started from tricyclic ketone 52 [54], which was converted into tricycle 53 in 12 steps. Trans-divinylcyclopropane 53 underwent the desired DVCPR after trans-cis-isomerization of the vinyl moiety at 175 °C, forming bridged

• 96, for which the yield and enantioselectivity was determined starting from 93. Standard functional group interconversion first provided exo-methylene 97, followed by ruthenium-catalyzed oxidative cleavage of the installed exo-methylene moiety [94] to give tricyclic ketone 98, which can be converted

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• the 13C NMR spectra (102.3–105.3 ppm; Table 3) similarly to the compounds 9a,c described in literature [7]. The tricyclic analogue 3g obtained from diazodimedone (2g) and thioketone 1a showed the absorption signal of the C(2)-atom at lower field (106.8 ppm) most likely due to the stronger deshielding

• contrast, tricyclic derivative 3g displays a chemical shift of C(5) at a lower field (166.6 ppm), most likely due to the similar reasons as for deshielding effect observed for the atom C(2). However, in the case of С(5) this effect is considerably stronger, since this atom is a vinylogue of the C=O group

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• propellane derivatives involves a Weiss–Cook condensation, a Fischer indole cyclization, and a ring-closing metathesis as key steps. Keywords: allylation; indole derivatives; propellanes; ring-closing metathesis; Weiss–Cook condensation; Introduction Propellanes are tricyclic systems conjoined with carbon

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• pyrimidine moiety is an important pharmacophore [1]. Especially, the fused bi- or tricyclic heterocyles containing a pyrimidine motif have received considerable interest in the design and discovery of new compounds for pharmaceutical and herbicidal applications [2][3]. For example, the pyrrolo[2,3-d

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• hydroamination intermediate affording tricyclic 3-benzazepines 129 (Scheme 32c). In the same field, Zhang reported the carboamination, carboalkoxylation and carbolactonization of terminal alkenes with arylboronic acids. Under best conditions, oxidative gold catalysis provided expedient access to various

• on the efficiency of gold catalysis in the functionalization of C–H bonds [77]. In particular, N-aryl-N’-allylureas 136 were selectively transformed into tricyclic indolines 137 in good yields. The reaction preceeded through the regioselective 5-exo anti-aminoauration of the C–C double bond (139

• carbolactonization of terminal alkenes with arylboronic acids. Synthesis of tricyclic indolines via gold-catalyzed formal [3 + 2] cycloaddition. Gold(I) catalyzed aminoarylation of terminal alkenes in presence of Selectfluor [dppm = bis(diphenylphosphino)methane]. Mechanistic investigation on the aminoarylation of

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• agreement with the experimental results (Table 2, entry 1). The complete reaction path of the cycloaddition process is shown in Scheme 4. We do not study computationaly the second synthetic step, namely the ring-opening of the tricyclic-cycloadduct, because that step has no relevance in the stereochemical

Direct electrophilic N-trifluoromethylthiolation of amines with trifluoromethanesulfenamide

• Sébastien Alazet,
• Kevin Ollivier and
• Thierry Billard

Beilstein J. Org. Chem. 2013, 9, 2354–2357, doi:10.3762/bjoc.9.270

• bis-amines can also be trifluoromethylthiolated, with the most nucleophile atom as a target (Figure 2). In this case, 2.1 equiv of BuLi are required and reaction times are loner (20 h). This new method was applied to synthesize a trifluoromethylthio analog (3l) of the well-known tricyclic

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• of platelet activating factor (PAF) and of histamine used in the treatment of allergies. This compound consists of a highly functional tricyclic core with an unsaturated linkage to a pendant piperidine ring. The picoline derivative 1.23 is first treated with two equivalents of n-butyllithium (n-BuLi

• substituted Grignard reagent 1.26. A Friedel–Crafts type acylation promoted by either triflic acid or polyphosphoric acid (PPA) furnishes the tricyclic structure 1.28 which upon N-demethylation affords clarinex (1.22). One of the top-selling classes of pharmaceuticals containing the pyridine ring are the

• (D)-(+)-O,O-dibenzoyltartaric acid was reported to separate the enantiomers [61]. By analogy to moxifloxacin the synthesis of levofloxacin (1.103) can be accomplished using an intramolecular double SNAr reaction sequence converting the tetrafluoroarene 1.116 into the required tricyclic

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• % yield when heated at 150 °C, presumably through strained tricyclic transition state 27a [1]. In contrast, nitronic ester 26b fails to undergo rearrangement presumably owing to the requirement that the nitro and phenyl groups be cis in the product. The rearrangement of nitronic ester 7 to give nitro

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• provided the depicted endo-diastereomer in good yield. Exchange of the N-benzyl for a Boc-protecting group and cleavage of the silyl enol ether gave the corresponding ketone, which was first converted to an enol-triflate and then to the tricyclic alkene 73. At this stage, the syntheses of cytochalasin B

Cyclization of substitued 2-(2-fluorophenylazo)azines to azino[1,2-c]benzo[d][1,2,4]triazinium derivatives

• Aleksandra Jankowiak,
• Emilia Obijalska and
• Piotr Kaszynski

Beilstein J. Org. Chem. 2013, 9, 1873–1880, doi:10.3762/bjoc.9.219

• computational results. Keywords: DFT; heterocycles; mechanism; synthesis; Introduction Derivatives of benzo[c]quinolizinium [1][2][3][4] (I, X = Y = CH, Figure 1) and its di-aza analogue pyrido[2,1-c]benzo[d][1,2,4]triazinium (I, X = Y = N) belong to a class of tricyclic cations featuring general structure I

• substituents at the benzene ring were prepared by acid-catalyzed photoinduced cyclization of phenylazopyridines [5]. Recently, we demonstrated an efficient alternative method for the formation of 1a and other parent tricyclic azinium cations of general structure I (A = B = H) by light-induced intramolecular