The dimerization and photochemical rearrangement of pentacyclo-[5.4.0.0.0.0]undecane-8-thione

Pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one 1 is readily sulfurated into pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8-thione 2 with Lawesson’s reagent in dry THF. Upon standing at ambient temperature the thione 2 formed the corresponding thio-dimer 3 within 10 days. When the thio-dimer 3 was exposed to oxygen and ultraviolet light an unexpected photochemical oxidation and rearrangement took place to form the stable disulfenate 5.     

Diels–Alder reactivity of 2-(bromomethyl)-1,4-quinone and 2-bromo-5-(bromomethyl)-1,4-quinone with cyclopentadiene and the synthesis of new substituted pentacyclic systems

Photochemical synthesis of the novel compounds 3-bromotetracyclo [5.3.1.0^2,6.0^4,8] undec-10(12)-ene-9,11-dione, 1-(bromomethyl)pentacyclo [5.4.0.0^2,6.0^3,10.0^5,9]undeca-8,11-dione and 1-bromo-9-(bromomethyl)pentacyclo [5.4.0.0^2,6.0^3,10.0^5,9]undeca-8,11-dione is described.     

Selective reductive dimerization of homocubane series oximes

The mixture of di- and monoethylene ketals obtained by the reaction of 1,9-dibromopentacyc lo[5.4.0.0^2,6.0^3,10.0^5,9]-undeca-8,11-dione followed by hydrolysis and ring contraction by Faworsky method was converted into a mixture of ethylene ketals of 7-bromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one-4- and 5-bromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decan-6-one-8-carboxylic acid where the carboxy group was replaced by bromine along the procedure of Hunsdiecker-Borodine-Cristol. 6-Ethylene ketal of the pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8] decan-6-one obtained by the debromination of ethylene ketals of 4,7- and 5,8-dibromopentacyclo[5.3.0.0^2,5.0^3,9.0^4,8] decan-6-one was hydrolyzed to ketone whose oxime was selectively reduced on a platinum catalyst into the di-6-pentacyclo[5.3.0.0^2,5.0^3,9.0^4,8]decylamine. The reaction of reductive dimerization was also characteristic of pentacyclo[4.3.0.0^2,5.0^3,8.0^4,7]-nonan-9-one and pentacyclo[6.3.0.0^2,6.0^3,10.0^5,9]undecan-4-one oximes, whereas the composition of the reduction products of pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan-8-one oxime depended on the amount of the catalyst.     

Reactions of Polycyclic Ketones with Dimethoxycarbene; a Convenient Route for a ‘One‐Pot’ Preparation of Some α‐Hydroxycarboxylic Acid Esters

Polycyclic ‘cage’ ketones, such as pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecan‐8‐one ( 10 ), pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane‐8,11‐dione ( 11 ), and adamantan‐2‐one ( 16 ) were treated with the nucleophilic dimethoxycarbene (DMC; 1 ), which was generated thermally from 2,5‐dihydro‐2,2‐dimethoxy‐5,5‐dimethyl‐1,3,4‐oxadiazole ( 4a ) in boiling toluene. In this ‘one‐pot’ procedure, the α‐hydroxycarboxylic acid ester 12 or a corresponding derivative 15 or 17 was obtained (Schemes 4–7). Additionally, ‘cage’ thione 21 was treated with DMC under the same conditions yielding dimethoxythiirane 22 (Scheme 8). Subsequent hydrolysis or desulfurization (followed by hydrolysis on silica gel) of 22 gave α‐mercaptocarboxylate 25 and the corresponding desulfurized ester 24 , respectively. In all cases, the addition of DMC occurred stereoselectively, and the addition from the exo‐face is postulated to explain the structures of the isolated products.     

Synthesis of hexacyclo[7.4.0.02,8.03,7.06,11]Tridecane-10,13-dione(“homosecohexaprismane-10,13-dione”)

HEXACYCLO[7.4.0.0^2,8.0^3,7.0^6,11]tridecane-10,13-dione (“homosecohexaprismane-10,13-dione”, 8) has been prepared via a six-step sequence that results in homologation of two of the cyclopentane rings in pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]-undecane-8,11-dione, 1. The structure of 8 has been established unequivocally via single crystal X-ray structural analysis.     

Base-promoted rearrangement of cage α-haloketones—II : 12-oxa-3,5,9,10-tetrachlorohexacyclo[5.4.1.02,6.03,10.05,9.08,11]-dodecane-4-one

A synthesis of 12-oxa-3,5,9,10-tetrachlorohexacyclo[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-4-one (6) from 4,4-dimethoxy-2,3,5,6-tetrachloropentacyclo [[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8,11-dione (1) is described. Reaction of 6 with sodium hydroxide in refluxing benzene, toluene, or tetrahydrofuran affords 11-oxa-3,4,5-exo-6-tetrachloropentacyclo [[6.2.1.0^2,7.0^4,10.0^5,9]undecane-endo-3-carboxylic acid (7a, 80·2% yield). The corresponding reaction of 6 with refluxing aqueous sodium hydroxide solution affords 4,12-dioxa-8,11-dichlorohexacyclo-[5.4.1.0^2,6.0^3,10.0^5,9.0^8,11]dodecane-1-carboxylic acid (8a, 66·5% yield). A mechanism which accounts for the formation of 7a and 8a from 6 is presented.     

Synthesis of novel highly functionalized biologically active polycyclic caged amides

The synthesis of novel polycyclic amides has been achieved through the reaction of bishalomethyl pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane diones with acyclic and cyclic secondary amines in the presence of an ionic liquid. Three of the compounds prepared have been found to possess antituberculosis activity.     

Preparation and complete 1 H and 13C assignment of some pentacyclo[5.4.0.02,6.03,10.05,9]undecane‐8,11‐dione (PCUD) derivatives

The preparation of a number of alkyl and alkoxy derivatives of pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane‐8,11‐dione derivatives utilising a cheap, practical, low energy, ‘green’, single‐pass continuous flow photochemical reactor is reported. Their ¹ H and ¹³C NMR spectra are fully assigned, revealing some general characteristics not previously reported for this class of compound, which should aid the assignment and prediction of the NMR spectra of PCUD derivatives. Copyright © 2012 John Wiley & Sons, Ltd.     

Structural studies of phosphor-1,1-diselenoato Mn(I) and Re(I) complexes

Mononuclear complexes of the type, M(CO)₄[Se₂P(OR)₂] (M = Mn, R = ⁱPr, 1a; Et, 1b; M = Re, R = ⁱPr, 3a; Et, 3b) can be prepared from either [-Se(Se)P(OⁱPr)₂]₂ (A) or [Se{-Se(Se)P(OEt)₂}₂] (B) with M(CO)₅Br. O,O′-dialkyl diselenophosphate ([(RO)₂PSe₂]^-, abbreviated as dsep) ligands generated from A and B act as a chelating ligand in these complexes. Upon refluxing in acetonitrile, these mononuclear complexes yield dinuclear complexes with a general formula of [M₂(CO)₆{Se₂P(OR)₂}₂] (M = Mn, R = ⁱPr, 2a; Et, 2b; M = Re, R = ⁱPr, 4a; Et, 4b). Dsep ligands display a triconnective, bimetallic bonding mode in the dinuclear compounds and this kind of connective pattern has never been identified in any phosphor-1,1-diselenoato metal complexes. Compounds 2b, 3b, and 4 are structurally characterized. Compounds 2b and 3b display weak, secondary Se?Se interactions in their lattices.     

Penicillones A and B, two novel polyketides with tricyclo [5.3.1.0] undecane skeleton, from a marine-derived fungus Penicillium terrestre

Two novel polyketides, penicillones A (1) and B (2), with tricyclo [5.3.1.0^3,8] undecane skeleton, were isolated from Penicillium terrestre. Their structures and relative stereochemistries were determined on the basis of spectroscopic methods. The absolute configuration of 2 was established by the modified Mosher’s method, while that of 1 was deduced from the similar CD absorptions of 1 and 2. Compound 1 showed weak cytotoxicities against P338 and A-549 cell lines, while 2 was inactive against P388.     

Synthesis and characterization of some novel cadmium(II) complexes with 3-hydroxypicolinic acid (3-OHpicH): Crystal and molecular structures of [CdI(3-OHpic)(3-OHpicH)(H2O)]2, [Cd(3-OHpic)2(H2O)2] and [Cd(3-OHpic)2]n

Cadmium(II) complexes of 3-hydroxypicolinic acid, namely [CdI(3-OHpic)(3-OHpicH)(H₂O)]₂ (1), [Cd(3-OHpic)₂(H₂O)₂] (2) and [Cd(3-OHpic)₂]_n (3) were prepared and characterized by spectroscopic methods (IR, NMR) and their molecular and crystal structures were determined by X-ray crystal structure analysis. Complexes 1 and 2 were prepared in similar reaction conditions using different cadmium(II) salts: cadmium(II) iodide and cadmium(II) acetate dihydrate, respectively, while 3 was prepared by recrystallization of 2 from N,N-dimethylformamide solution. Various coordination modes of 3-OHpicH in 1–3 were established in the solid state: bidentate N,O-chelated mode in 1 and 2, monodentate mode through the carboxylate O atom from zwitterionic ligand in 1 and bidentate N,O-chelated and bridging mode in 3. In the DMF solution of all prepared complexes, only monodentate mode of 3-OHpicH binding to cadmium(II) through the carboxylate O atom was established by ¹H, ¹³C, ¹⁵N and ¹¹³Cd NMR spectroscopy.     

Quantum chemistry studies on the Ru-M interactions and the P NMR in [Ru(CO)3(Ph2Ppy)2(MCl2)] (M = Zn, Cd, Hg)

To study the Ru-M interactions and their effects on ³¹P NMR, complexes [Ru(CO)₃(Ph₂Ppy)₂] (py = pyridine) (1) and [Ru(CO)₃(Ph₂Ppy)₂MCl₂] (M = Zn, 2; Cd, 3; Hg, 4) were calculated by density functional theory (DFT) PBE0 method. Moreover, the PBE0-GIAO method was employed to calculate the ³¹P chemical shifts in complexes. The calculated ³¹P chemical shifts in 1-3 follow 2 > 3 > 1 which are consistent to experimental results, proving that PBE0-GIAO method adopted in this study is reasonable. This method is employed to predict the ³¹P chemical shift in designed complex 4. Compared with 1, the ³¹P chemical shifts in 2-4 vary resulting from adjacent Ru-M interactions. The Ru → M or Ru ← M charge-transfer interactions in 2-4 are revealed by second-order perturbation theory. The strength order of Ru → M interactions is the same as that of the P-Ru → M delocalization with Zn > Cd > Hg, which coincides with the order of ³¹P NMR chemical shifts. The interaction of Ru → M, corresponding to the delocalization from 4d orbital of Ru to s valence orbital of M²⁺, results in the delocalization of P-Ru → M, which decreases the electron density of P nucleus and causes the downfield ³¹P chemical shifts. Except 2, the back-donation effect of Ru ← M, arising from the delocalization from s valence orbital of M²⁺ to the valence orbital of Ru, is against the P-Ru → M delocalization and results in the upfield ³¹P chemical shifts in 4. Meanwhile, the binding energies indicate that complex 4 is stable and can be synthesized experimentally. However, as complex [Ru(CO)₃(Ph₂Ppy)₂HgCl]⁺5 is more stable than 4, the reaction of 1 with HgCl₂ only gave 5 experimentally.     

Preparation of the novel fluorine-18-labeled VIP analog for PET imaging studies using two different synthesis methods

Vasoactive intestinal peptide (VIP) receptors are expressed on various tumor cells in much higher density than somatostatin receptors, which provides the basis for radiolabeling VIP as tumor diagnostic agent. However, fast proteolytic degradation of VIP in vivo limits its clinical application. With the aim to develop and evaluate new ligands for depicting the VIP receptors with positron emission tomography (PET), the structure modified [R^8,15,21, L¹⁷]-VIP analog was radiolabeled with ¹⁸F using two different methods. With the first method, N-4-[¹⁸F]fluorobenzoyl-[R^8,15,21, L¹⁷]-VIP ([¹⁸F]FB-[R^8,15,21, L¹⁷]-VIP 7) was produced in a decay-corrected radiochemical yield (RCY) of 33.6 ± 3%, a specific radioactivity of 255 GBq/μmol (n = 5) within 100 min in four steps. Similarly, N-4-[¹⁸F](fluoromethyl)-benzoyl-[R^8,15,21, L¹⁷]-VIP ([¹⁸F]FMB-[R^8,15,21, L¹⁷]-VIP 8) was synthesized in a RCY of 34.85 ± 5%, a specific radioactivity of 180 GBq/μmol (n = 5) within 60 min in only one step. The two products 7 and 8 were both shown good stability in HSA. Moreover, the low bone uptakes of 7 and 8 in vivo of mice showed good defluorination stability.     

Synthesis and chemistry of tricyclic cyclopropene-tricyclo[3.2.2.0]nona-2(4),6-diene

The 1,2-bridged tricyclic cyclopropene, tricyclo[3.2.2.0^2,4]nona-2(4),6-diene (1), has been synthesized by the elimination of 2-bromo-4-chlorotricyclo[3.2.2.0^2,4]-non-6-ene (5). Cyclopropene 1 will undergo different isomerizations in ether solution and in neat conditions. Compound 1 rearranged to an anti-Bredt compound 4 via diradical mechanism in ether and tricyclic compound 6 via vinyl carbene mechanism in neat conditions. Compound 1 can be trapped with DPIBF at different temperatures yielding different results: the exo-endo adduct 2 (exo-addition from the view of the cyclopropene and endo-addition from the view of bicyclo[2.2.2]octene) is a sole product at 0°C by slowly addition of methyllithium, and the exo-endo adduct 2, endo-endo adduct 9, anti-Bredt adduct 3, and styrene 8 are isolated at ether refluxing temperature. Styrene 8 is proposed to be formed from endo-endo adduct 9 by diradical mechanism. The chemistry of exo-endo adduct 2 and endo-endo adduct 9 is as well studied. The exo-endo adduct 2 undergoes hydration in trifluoroacetic acid to generate 1,3-cis-diol 11 followed by eliminations of water and formaldehyde to give naphthalene 12. The endo-endo adduct 9 reacts with water in tetrahydrofuran-containing silica gel to yield 1,4-cis-diol 10. Both 9 and 10 react with trifluoroacetic acid to form trans-3-hydroxy trifluoroacetate 13. Compound 13 will undergo hydrolysis and isomerization to generate 1,3-cis-diol 11 in trifluoroacetic acid.     

Synthesis and X-ray diffraction analysis/crystal structure of new germatranes containing methyl substituents in three five-membered chelating rings

Three monomeric germatranes, 1-isopropoxy-3,3,7,7,10,10-hexamethyl-2,8,9-trioxa-5-aza-1-germatricyclo[3.3.3.0^1,5]undecane (1), 1-isopropoxy-3,3,7,7-tetramethyl-2,8,9-trioxa-5-aza-1-germatricyclo[3.3.3.0^1,5]undecane (2), and 1-isopropoxy-3,3-dimethyl-2,8,9-trioxa-5-aza-1-germatricyclo[3.3.3.0^1,5]undecane (3) have been synthesized by the reaction of Ge(O-i-Pr)₄ in refluxing toluene with corresponding triethanolamines, (HOCH₂CH₂)_nN(CH₂CMe₂OH)_3−n (n = 0, L1H₃; n = 1, L2H₃; n = 2, L3H₃), where the number of CMe₂ groups adjacent to a OH functionality varied from 3 (L1H₃) to 2 (L2H₃), and to 1 (L3H₃). These germatranes 1-3 have been characterized by solution ¹H and ¹³C{¹H} NMR and the solid state structure of 2 has been determined by single crystal X-ray diffraction.     

Dimethylthallium(III) complexes with picolinic acid and its hydroxyl derivatives

The reaction of dimethylthallium(III) hydroxide with picolinic acid (Hpic), 3-hydroxypicolinic acid (H₂3hpic) and 6-hydroxypicolinic acid (H₂6hpic) in an aqueous/methanol mixture afforded the complexes [TlMe₂(pic)] (1), [TlMe₂(H3hpic)] (2) and [TlMe₂(H6hpic)] (3), respectively. Complex 3′, [NaTlMe₂(6hpic)₂]_n, was obtained as a minor product from a methanolic solution of 3. Compounds 1–3 were characterized by IR and Raman spectroscopy and, in the cases of 1, 2 and 3′, by single-crystal X-ray diffraction. Complex 3′ is the first example of an H6hpic⁻ heterobimetallic compound to be isolated. The ¹H and ¹³C NMR spectra of 1 and 2 are also discussed.     

Synthesis,structural characterization and reactivity of copper(I)-nitrile complexes: Crystal and molecular structure of [Cu(BzCN)4][BF4]

Complexes of general formula [CuL₄][BF₄] (L = benzonitrile – PhCN 2 or phenylacetonitrile – BzCN 3) have been prepared and structurally characterized by NMR spectroscopy and X-ray crystallography. Their structure and reactivity have been compared to the well known [Cu(MeCN)₄][BF₄] (1). The ⁶³Cu line width and the ⁶³Cu chemical shift have been evaluated by varying the temperature and the concentration of the complex 2 in benzonitrile solutions. The phenylacetonitrile solutions of the complex 3 give extremely broad signals which are beyond detection. Accordingly, compound 3 has been studied by ⁶³Cu MAS NMR spectroscopy. The solution NMR data are consistent to the prevalence of dynamic equilibrium between tetra- and low-coordinated species in both complexes. The X-ray structure of 3 revealed that the copper(I) atom sits in a slightly distorted tetrahedral geometry, surrounded by four BzCN ligands.     

Synthesis and structure of halogen derivatives of 9-dimethylsulfonium-7,8-dicarba-nido-undecaborane [9-Me2S-7,8-C2B9H11]

Halogenation of 9-dimethylsulfonium-7,8-dicarba-nido-undecaborane [9-SMe₂-7,8-C₂B₉H₁₁] with N-chlorosuccinimide, bromine and iodine gave the expected corresponding halogen derivatives [9-SMe₂-11-X-7,8-C₂B₉H₁₀], where X = Cl (1), Br (2), I (3). In the bromination reaction, [9-SMe₂-6-Br-7,8-C₂B₉H₁₀] (4) was isolated as a minor product being the first example of substitution at a “lower” belt of the 7,8-dicarba-nido-undecaborate cage. The use of excess of bromine resulted in dibromo derivative [9-SMe₂-6,11-Br₂-7,8-C₂B₉H₉] (5). Structures of the compounds prepared were determined using ¹¹B-¹¹B COSY NMR spectroscopy (for all halogen derivatives) and single crystal X-ray diffraction (for compounds 2, 3, and 5).     

Unambiguous structure elucidation of the reaction products of 3-acyl-4-methoxy-1-methylquinolinones with hydroxylamine via NMR spectroscopy

Reaction of 3-acyl-4-methoxy-1-methylquinolinones 2a,b with hydroxylamine has been investigated under different experimental conditions. Whereas compound 2a gives rise selectively and exclusively to the regioisomeric isoxazolo[4,5-c]- or isoxazolo[4,3-c]quinolin-4(5H)one (compound 3a or 4a, respectively), reaction of 2b always led to a mixture of the required isoxazole together with the oxazole derivative. Structural elucidation of all products has been independently achieved by multinuclear (¹³C and ¹⁵N) magnetic resonance spectroscopy.     

Microwave-assisted methods for the synthesis of pentacyclo[5.4.0.0.0.0]undecylamines

Efficient methodologies for the preparation of pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane (PCU) amine derivatives are described via microwave-assisted synthesis. The obtained results revealed that microwave-assisted synthetic procedures under controlled conditions (power, temperature and time) are very convenient, high yielding, efficient and low-cost methods for the preparation of PCU amine derivatives. The new methods show several advantages including operational simplicity, good performance, significant reduction in reaction time, less by-product formation and easier purification.