Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• tetrahydropyranyl rings derived from nitriles 1c and 1d, respectively, afforded tricyclic oxaspirocyclohexadienones 3c and 3d in moderate yields along with the corresponding alkenes 4c and 4d as well as p-tolunitrile (5a) (Table 2, entries 2 and 3). On the other hand, the reaction starting from carbonitrile 1e

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

• with the RCM product 78 in 71% (Scheme 15). Burnell and co-workers [20] have demonstrated the RRM of unsaturated spirocycles with two alkenyl chains by employing catalyst 2 to generate a unsaturated spiro-fused tricyclic system. In this context, the compounds 80 and 81 were subjected to RRM with

• catalyst 2 to furnish exclusively fused tricyclic systems 83a and 83b in 85% and 61% yields, respectively. Substitution on the cyclohexene system as in compound 82 did not deliver the RRM product (Scheme 16). Pyran systems Donnard and co-workers [21] have accomplished a RRM approach for assembling complex

• system such as 102. To this end, the spironorbornene 102 was subjected to a RRM sequence under the influence of catalyst 1 to deliver the RRM product 103 and the RCM product 104 in a 99:1 ratio. When norbornene derivative 102 was treated with catalyst 2 tricyclic compound 103 and spironorbornene

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1727–1731, doi:10.3762/bjoc.11.188

• with allyl bromide in the presence of NaH delivered the aromatized compound 2a in 42% yield. Then, the tricyclic compound 2a was subjected to RRM with Grubbs 1st generation (G-I) catalyst in the presence of ethylene to furnish the tetracyclic compound 1a in 75% yield (Scheme 1). The structures of

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

• dichlorobenzene at 150 °C to obtain a 3:5 mixture of the tricyclic cyclopentanones 17 and 18 (Scheme 4) [34]. Almost no regioselectivity between the 5- and 7-positions was observed. Our ongoing studies investigate the influence of bulky N-protecting groups. In the absence of the α,β-double bond, SmI2 in THF did

• Merck KGaA (Darmstadt, Germany) for chromatography materials. BASF Group (Ludwigshafen, Germany) and Honeywell Specialty Chemicals Seelze GmbH (Seelze, Germany) are thanked for the donation of solvents. Tina Bohlmann is thanked for the synthesis of tricyclic cyclopentanones 17 and 18. Wera Collisi

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• spectra, and in one case, from an X-ray crystal structure. Assorted bicyclic and tricyclic imines were formed with both spiro-rings and fused-rings and with varying ring sizes and substituents. Extending this work, we have studied radical cyclizations of several ene-sulfonamides and N-sulfonylindoles. The

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• Sambasivarao Kotha Ongolu Ravikumar Jadab Majhi Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai-400 076, India, Fax: 022-25767152 10.3762/bjoc.11.163 Abstract A tricyclic lactam is reported in a four step synthesis sequence via Beckmann rearrangement and ring

• target molecule 1 is shown in Figure 1. RRM of the tricyclic allylated compound 2 can deliver the target lactam 1. The key synthon 2 can be derived by allylation of lactam 3, which in turn can be prepared via BR starting with the known enone 4 [25][26][27], derived from dicyclopentadiene (5) [28][29][30

• ]. Results and Discussion To begin with, the oxidation of dicyclopentadiene (5) in the presence of SeO2 gave 1α-dicyclopentadienol (6), which on treatment with pyridinium chlorochromate (PCC) [31] delivered the known tricyclic enone 4. Selective reduction of enone 4 with Zn in AcOH/EtOH under reflux

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• -dimensional structure and avoid time-consuming molecular dynamic simulations, the starting model of 2 was created from the X-ray single crystal structure of tricyclic spiroketal (CSD entry: ERYTHR) [55], with replacement of the 6-hydroxy group by 6-methoxy. A two-step minimization process consisted of adding

• energy constraints to the X-ray structure followed by unconstrained minimization. Significant conformational changes were not expected due to the rigidity of the tricyclic system. A low energy conformation of 2 is presented in Figure 1. Analogous to pyranoside conformations, the highly substituted

• acid-promoted modification of 6-O-methyl-9(E)-hydroxyiminoerythronolide A into three rigid tricyclic spiroketal systems 2, 3 and 4. Compound 2 proved to be stable in non-acidic media. After acidic treatment two new dehydrated molecules are formed: compound 3 which with time spontaneously transforms

Design and synthesis of polycyclic sulfones via Diels–Alder reaction and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1373–1378, doi:10.3762/bjoc.11.148

• synthesized from the functionalized tricyclic sulfone 2 by RRM sequence. The sulfone 2 may be prepared from the dimesylate 3, which in turn, can be assembled from the known anhydride 4 via reduction followed by mesylation of the resulting diol. Compound 4 could be prepared via DA reaction starting with

• attention towards the RRM step. Initially, the diallyl sulfone 2a (~0.0141 M solution in dry CH2Cl2) was subjected to RRM using G-I catalyst in the presence of ethylene gas in refluxing CH2Cl2 to get the tetracyclic sulfone 1a, however, we isolated the tricyclic sulfone 10 in 48% yield. When the G-I

• conditions to furnish 1c. Interestingly, the tricyclic sulfone 11 was isolated in 60% along with the expected tetracyclic sulfone 1c (32%) and a minor amount of ring-opened product 12 (6%, Scheme 5). A complex mixture of products was obtained when compound 2c was exposed to the metathesis catalyst for a

Hybrid macrocycle formation and spiro annulation on cis-syn-cis-tricyclo[6.3.0.0^2,6]undeca-3,11-dione and its congeners via ring-closing metathesis

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Rashid Ali

Beilstein J. Org. Chem. 2015, 11, 1123–1128, doi:10.3762/bjoc.11.126

• new strategy based on Fischer indolization and ring-closing metathesis as the key steps. To develop a simple synthetic methodology to aza-polycycles and spiropolycycles from readily available starting materials [47][48][49][50][51][52], bicyclic, tricyclic and pentacyclic diones (1–3) were identified

• ]. Also, based on Fischer indolization and ring-closing metathesis (RCM), we have developed a new strategy to indole-based propellane derivatives [57]. Here, the tricyclic dione 2 required was prepared starting with the Cookson’s dione 4 in two steps involving flash vacuum pyrolysis (FVP) and

• hydrogenation steps (Scheme 1). A variety of synthetic transformations involving tricyclic diones 5 and 2 were reported in the literature [47]. To expand the utility of building block 2 in organic synthesis, we conceived a simple retrosynthetic approach to macrocylic aza-polyquinane 6 and spiro-polyquinane

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• –Knorr cyclization, thus affording tricyclic thieno[2,3-b]indoles. Keywords: aldol-crotonic condensation; isatin; Lawesson’s reagent; methyl ketones; Paal–Knorr reaction; thieno[2,3-b]indole; Introduction 8H-Thieno[2,3-b]indole is a fused heterocyclic system, which has attracted a considerable

• through a tandem reduction of the C=C double bond and the Paal–Knorr cyclization, thus affording tricyclic thieno[2,3-b]indoles. In its turn, the required indolin-2-ones have been prepared by a simple “aldol-crotonic” type of condensation of N-alkylated isatins with acetophenones or their heterocyclic

DBU-promoted carboxylative cyclization of o-hydroxy- and o-acetamidoacetophenone

• Wen-Zhen Zhang,
• Si Liu and
• Xiao-Bing Lu

Beilstein J. Org. Chem. 2015, 11, 906–912, doi:10.3762/bjoc.11.102

• the carboxylative cyclization reaction to furnish the tricyclic product 2h in moderate yield (Table 2, entry 8). With the successful DBU-promoted carboxylative cyclization of o-hydroxyacetophenone at hand, we then extended this strategy to o-acetamidoacetophenone to synthesize 4-hydroxy-2(1H

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• studied for the construction of heterocycles. We have reported on a highly efficient gold/silver-catalyzed intramolecular hydroamination of terminal alkynes in water for the synthesis of fused tricyclic xanthenes [34]. On the basis of this methodology, we have also afforded two fused benzimidazoles

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• striking differences regarding their reaction with water. While BIFOP–Cl is nearly completely unreactive, its oxo-derivative O–BIFOP–Cl reacts instantly with water, yielding a tricyclic hydrocarbon unit after rearrangement. The analysis of the crystal structure of O–BIFOP–Cl and BIFOP–Cl revealed that the

Copper-catalyzed cascade reactions of α,β-unsaturated esters with keto esters

• Zhengning Li,
• Chongnian Wang and
• Zengchang Li

Beilstein J. Org. Chem. 2015, 11, 213–218, doi:10.3762/bjoc.11.23

• diastereoselectivity. As expected, a cyclic β-halo-α,β unsaturated aldehyde substrate led to the respective tricyclic lactone, the core structure of strigolactone [12]. Bertrand synthesized β-carboxylic acid-γ-lactones in high yields but with low diastereoselectivity via a dialkylzinc-mediated radical addition to the

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• proved difficult to determine the cis/trans relationship in many examples due to the presence of rotameric forms, however the products of phenyl magnesiumbromide were identified to be trans presumably due to opposite face attack of intermediate 52b. Bicyclic lactams [73] and tricyclic systems [74] have

• such as the nucleobases: protected cytosine, guanine 87, adenine, and thymine to afford azanucleoside products such as 88 (Scheme 20). The use of the Shono-type electrooxidation in peptide and peptidomimetic chemistry The preparation of a bridged tricyclic analogue to induce an α-helix conformation in

• synthetically challenging aza-nucleosides employing an electrochemical step [88]. Synthesis of a bridged tricyclic diproline analogue 93 that induces α-helix conformation into linear peptides [90]. Synthesis of (i) a peptidomimetic and (ii) a functionalised peptide from silyl electroauxiliary precursors [91

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• hydroxyaryl group as well as tricyclic nitrogen-containing heterocycles derived from salicylaldehyde have been reported as anticancer [1], antihypertensive agents [2], neuropeptide Y antagonists [3], and calcium channel blockers [4]. Fused azoloazines containing carboxamide substituents also exhibit a broad

• ). Obtaining of two classes of compounds was found to originate from steric influence rendered by the alkyl moiety of the ester group in the active methylene species. Inspired by Světlik’s studies, Jing et al. [17] developed an efficient method for the synthesis of oxygen-bridged pyrimidine tricyclic

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• 14‡. Distances are shown in angstrom (italics). Synthesis of tricyclic 1,2,4-thiadiazoles 2a–c. Possible mechanistic scenarios. DMAP assisted cyclization-I and IIa. Free energies are reported in kcal mol−1 at 25 °C referenced to 8 for cyclization-I and 13 for cyclization-IIa. Free energy values

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• (b). The number given for each compound can correspondingly be found in Table 1. The compound class is indicated in parenthesis (M – acyclic monoterpenes, OM – oxygenated acyclic monoterpenes, OM1/2 – oxygenated mono/bicyclic monoterpenes, P – phenolic derivatives, S1/2/3 – mono/bi/tricyclic

• sesquiterpenes, OS2/3 – oxygenated bi/tricyclic sesquiterpenes). The score plot from the PCA analysis of the O. basilicum L. essential oil compounds nanoencapsulation in β-CD (classification as acyclic or cyclic (numbered) mono- and sesquiterpenoid hydrocarbons (M and S), or the corresponding oxygenated terpenes

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• carbon skeleton with an unprecedented 6/5/6 tricyclic ring system bearing an α,β-unsaturated spirolactone moiety in ring B, and represents a new subclass of norditerpenoid, the skeleton of which is named aspergilane. The hypothetical biosynthetic pathway for 1 was also proposed. The cytotoxic

• enone fragment. HMBC correlations from H2-8 to C-7 and C-12 secured the connectivity of the C-8 to C-7. The connectivity of C-6 to the ketone carbon C-13 through an ester linkage, which was also supported by the downfield chemical shift of C-6 (δC 88.6) completed the structure of 6/5/6 tricyclic

• Bijvoet pairs by single-crystal X-ray diffraction experiment [13]. Therefore, the absolute configurations of the chiral centers in 1 were established as 5R, 6S, 10R, 11R. This compound is structurally characterized by a new carbon skeleton with an unprecedented 6/5/6 tricyclic ring system bearing an α,β

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