Stereochemistry of conjugate halogenation of 1-phenyltricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptane

1-Phenyltricyclo[4.1.0.0^2,7]heptane reacts with N-bromo- and N-chlorosuccinimides in the presence of external nucleophiles providing products of a conjugate (electrophilic with respect to halogen) addition across the central bond C¹-C⁷ of the bicyclo[3.1. 1]heptane structure with a pronounces endo, anti-stereoselectivity. In similar reactions with N-iodosuccinimide the products obtained originated mainly from endo, syn-addition across the C¹-C⁷ bond. The reasons for differences in the selectivity of the conjugate halogenation are discussed applying the data of the quantum-chemical calculation in the basis MP2/STO 3G of the electronic and spatial structure of the reaction intermediates, norpinanyl cations of benzyl type.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 11, 2004, pp. 1647–1655.Original Russian Text Copyright © 2004 by Vasin, Semenov, Razin.     

Synthesis of 7-sulfonyl-substituted norpinan-6-ones and -thiones from 1-bromotricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptane

1-Bromotricyclo[4.1.0.0^2,7]heptane reacted with benzene- and methanesulfonyl thiocyanates in benzene at 20°C via anti addition to the central C¹–C⁷ bicyclobutane bond with formation of 6-endo-bromo-6-exo-thiocyanato-7-syn-(R-sulfonyl)bicyclo[3.1.1]heptanes. Treatment of the benzenesulfonyl thiocyanate adduct with potassium tert-butoxide in THF at 20°C gave 7-endo-(benzenesulfonyl)norpinan-6-one, whereas the reaction with 1,8-diazabicyclo[5.4.0]undec-7-ene in methylene chloride afforded 7-exo-(benzenesulfonyl)-norpinane-6-thione which was converted into 7-exo-(benzenesulfonyl)norpinan-6-one by alkaline hydrolysis.     

Chemo-, regio-, and stereoselectivity in acid-catalyzed hydromethoxylation of tricyclo[4.1.0.0<Superscript>2,7</Superscript>]hept-1-yl and 7-methyltricyclo[4.1.0.0<Superscript>2,7</Superscript>]hept-1-yl phenyl sulfones

Hydromethoxylation of tricyclo[4.1.0.0^2,7]hept-1-yl and 7-methyltricyclo[4.1.0.0^2,7]hept-1-yl phenyl sulfones with methanol at 20°C in the presence of a catalytic amount of perchloric acid is initiated by the endo attack of proton at the C¹ atom, and the subsequent cleavage of the side C¹–C² bond leads to formation of mixtures of diastereoisomeric exo-7-phenylsulfonyl-2-methoxybicyclo[4.1.0]heptanes, the endo-2 isomer prevailing. Probable factors responsible for the observed chemo-, regio-, and stereoselectivity of the addition are discussed.     

Hydrogenolysis of 7-phenyltricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptan-1-carboxylic acid. Synthesis of ketones with tricyclo[4.4.0.0<Superscript>2,7</Superscript>]decane and tricyclo[5.4.0.0<Superscript>2,8</Superscript>]undecane skeletons

Hydrogenation of 7-phenyltricyclo[4.1.0.0^2,7]heptane-1-carboxylic acid over Raney nickel occurred in the syn-stereoselective fashion to give anti-7-phenylbicyclo[3.1.1]heptane-exo-6-carboxylic acid. The latter was used to synthesize 4,5-benzotricyclo[4.4.0.0^2,7]dec-4-en-3-one and two isomeric higher homologs, 5,6-benzotricyclo[5.4.0.0^2,8]undec-5-en-3-and-4-ones.     

Stereoselectivity of halomethoxylation of 1-phenyltricyclo-[4.1.0.0<Superscript>2,7</Superscript>]heptane and methyl 7-phenyltricyclo[4.1.0.0<Superscript>2,7</Superscript>]-heptane-1-carboxylate

The stereoselectivity of halomethoxylation of 1-phenyltricyclo[4.1.0.0^2,7]heptane and methyl 7-phenyltricyclo[4.1.0.0^2,7]heptane-1-carboxylate at the central bicyclobutane C¹-C⁷ bond by the action of N-chloro-, N-bromo-, and N-iodosuccinimides in methanol depends on the halogen nature. Conjugate chlorination and bromination are characterized by pronounced anti-stereoselectivity; the contribution of syn-addition slightly increases in going from the monosubstituted tricycloheptane substrate to disubstituted. Iodomethoxylation of the latter is clearly syn-stereoselective.     

First synthesis of nitro-substituted bicyclo[1.1.0]butane derivatives and new method for generation of tricyclo[4.1.0.0<Superscript>2,7</Superscript>]hept-1(7)-ene

Successive treatment of 1-phenylsulfonyltricyclo[4.1.0.0^2,7]heptane with butyllithium and ethyl nitrate leads to the formation of 7-nitro-7′-phenylsulfonyl-1,1′-bi(tricyclo[4.1.0.0^2,7]heptane) through intermediate tricyclo[4.1.0.0^2,7]hept-1(7)-ene which is generated by 1,2-elimination of benzenesulfinic acid from the initial compound. Analogous treatment of 1-phenyltricyclo[4.1.0.0^2,7]heptane gives 1-nitro-7-phenyltricyclo[4.1.0.0^2,7]heptane.     

Regio- and stereoselective addition of methane- and bromomethanesulfonyl bromides to 1-phenylthiotricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptane

1-Phenylthiotricyclo[4.1.0.0^2,7]heptane reacted with MeSO₂Br and BrCH₂SO₂Br directly at mixing at 20°C in CH₂Cl₂ along a ionic (electrophilic with respect to bromine) mechanism affording a product of an antistereoselective addition to the central bicyclobutane C¹–C⁷ bond of the norpinane structure. The reaction product contains the exo-oriented sulfonyl group in the geminal position to the SPh substituent. The structure of the adduct with MeSO₂Br in a single crystal was determined by XRD analysis.     

Adducts of Tricyclo[4.1.0.0<Superscript>2,7</Superscript>]heptane hydrocarbons with methane- and Halomethanesulfonyl Thiocyanates and their transformations in the presence of bases (nucleophiles)

1-R-Tricyclo[4.1.0.0^2,7]heptanes (R = H, Me, Ph) take up methane- and halomethanesulfonyl thiocyanates XCH₂SO₂SCN (X = H, Cl, Br) at the central C¹–C⁷ bond in benzene at 20°C with high anti-selectivity to give bicyclo[3.1.1]heptane derivatives with the 7-endo-oriented sulfonyl group and the thiocyanato group in the geminal position with respect to the R substituent. The syn-adducts lose HSCN molecule by the action of potassium tert-butoxide in THF at 0°C or on heating in boiling aqueous dioxane containing NaOH with formation of 1-(X-methylsulfonyl)tricyclo[4.1.0.0^2,7]heptanes. Under analogous conditions the anti-adducts (X = Me) are converted into 1,2-bis(7-syn-methylsulfonyl-6-endo-R-bicyclo[3.1.1]hept-6-exo-yl)disulfanes. The anti-adduct derived from unsubstituted tricyclo[4.1.0.0^2,7]heptane and MeSO₂SCN reacted with methyllithium or phenylmagnesium bromide to produce 7-anti-methyl(phenyl)sulfanyl-6-endo-methylsulfonylbicyclo-[3.1.1]heptanes which were also obtained by photochemical addition of MeSO₂SMe(or Ph) to tricyclo-[4.1.0.0^2,7]heptane. Geometric parameters of radical intermediates in the sulfonylation of 1-R-tricyclo-[4.1.0.0^2,7]heptanes were optimized ab initio using 6-31G basis set.     

Facile conversion of [1-<Superscript>14</Superscript>C]lauronitrile to [1-<Superscript>14</Superscript>C]lauric acid under microwave irradiation

Summary A highly efficient and an optimized synthesis of [1-¹⁴C]lauric acid with high specific activity (50 mCi/mmol) is described. [1-¹⁴C]lauric acid was prepared from [1-¹⁴C]lauronitrile, in 2 minutes with a mixture of concentrated hydrochloric acid: propionic acid (1: 2 v/v) under microwave irradiation, in quantitative yield.     

<Emphasis Type="Italic">O</Emphasis>- and <Emphasis Type="Italic">N</Emphasis>-Alkylation of <Emphasis Type="Italic">N</Emphasis>-halosuccinimides in ionic reactions with 1-phenyltricyclo [4.1.0.0<Superscript>2,7</Superscript>]heptane

N-Bromo and N-chlorosuccinimides add to 1-phenyltricyclo[4.1.0.0^2,7]heptane in CH₂Cl₂ with cleavage of the C(1)-C(7) bond to give isomeric 1 : 1 Markownikoff-type endo, anti-adducts of the norpinane structure in a ∼3 :7 ratio corresponding to N and O alkylation of succinimide.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No.2, pp. 457–460, February, 2005     

Synthesis of [<Superscript>14</Superscript>C] quincetone

Summary The water-soluble fullerene derivative C₆₀(OH)_x was radiolabeled with ⁶⁷GaCl₃. The labeling yields were determined by radio-PLC. The effects of pH, reaction time, temperature and the amount of C₆₀(OH)_x on the labeling yields were studied. The stability of ⁶⁷Ga-C₆₀(OH)_x was also examined. The results showed that the labeling yields could reach 97% under the best labeling conditions and the radiochemical purity of ⁶⁷Ga-C₆₀(OH)_x solution kept at 37 °C remained at 88% after 212 hours. The biodistribution studies of ⁶⁷Ga-C₆₀(OH)_x in mice showed a high localization of ⁶⁷Ga-C₆₀(OH)_x in the bone marrow, bone, liver and spleen with slow clearance and a negligible accumulation in the blood. These data suggest that the water-soluble C₆₀(OH)_x, having the same properties as microcolloids, may be used as a carrier of drug system for lymphatic targeting.     

<Superscript>1</Superscript>H and <Superscript>13</Superscript>C NMR spectra of some drimanic sesquiterpenoids

One- and two-dimensional homo- and heteronuclear correlation proton, carbon, proton—proton, and proton—carbon NMR spectra of fifteen drimanic sesquiterpenoids: 11,12-dibromodrima-5,8-dien-7-one, drim-8-en-7-one, 11-hydroxydrim-8-en-7-one, 11,12-dihydroxydrim-8-en-7-one, 11-hydroxy-11,12-epoxydrim-8-en-7-one, 11-hydroxy-11,12-epoxydrim-8-en-7-one, 8,9-epoxydriman-7-one, 8,9-epoxydriman-7-ol, 11,12-diacetoxydrim-8-en-7-ol, drimane-7,8,11-triol, 7,8-isopropylidenedioxydriman-11-al, 9, 11-dihydroxydrim-7-en-6-one, drimane-7,8,9-triol, drimane-7,8,11-triol, and drim-8-ene-7,11,12-triol were studied. The proton and carbon chemical shifts were assigned.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2589–2594, December, 2004.     

<Superscript>18</Superscript>F- and <Superscript>11</Superscript>C-labelling of quantum dots with n.c.a. [<Superscript>18</Superscript>F]fluoroethyltosylate and [<Superscript>11</Superscript>C]methyliodide: a feasibility study

Quantum dots functionalized on the outer surface with either amino- or carboxyl functions were labelled with [¹⁸F]fluoroethyltosylate and [¹¹C]methyliodide in order to use the positron emitter-labelled fluorescence agents for multimodality imaging techniques, i.e. fluorescence imaging and positron emission tomography. ¹⁸F-Labelling of both compounds was realized with yields up to 5% as determined by size exclusion chromatography, which is twice as much as reported in literature before [1]. ¹¹C-Labelling of amino- and carboxyl-QDs proceeded with good yields (up to 45 and 35%, respectively) under optimized reaction conditions. In general for both QD-types and both labelling agents the labelling yield increased with the amount of QDs used in the reaction as well as with reaction time and reaction temperature.