Efficient Synthesis of a New Family of 2,6-Disulfanyl-9-selenabicyclo[3.3.1]nonanes

The efficient synthesis of a new family of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes in high yields has been developed based on 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion generated from bis-isothiouronium salt of 2,6-dibromo-9-selenabicyclo[3.3.1]nonane. The derivatives of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonane containing alkyl, allyl and benzyl moieties have been prepared in 90–99% yields by nucleophilic substitution of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion with alkyl, allyl and benzyl halides. The reaction of nucleophilic addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to alkyl propiolates afforded 2,6-di(vinylsulfanyl)-9-selenabicyclo[3.3.1]nonanes. The conditions for regio- and stereoselective addition of 9-selenabicyclo[3.3.1]nonane-2,6-dithiolate anion to a triple bond of alkyl propiolates have been found. To date, not a single representative of 2,6-disulfanyl-9-selenabicyclo[3.3.1]nonanes has been described in the literature.     

Synthesis and properties of 3-substituted 3-azabicyclo-[3.3.1]nonan-9-amines

Catalytic hydrogenation of 3-benzyl- and 3-tert-butoxycarbonyl-3-azabicyclo[3.3.1]nonan-9-one oximes over Raney nickel gave the corresponding 3-substituted 3-azabicyclo[3.3.1]nonan-9-amines which were converted into amides via reactions with acetyl and chloroacetyl chlorides and maleic and succinic anhydrides, into Schiff bases by condensation with benzaldehyde and 4-chlorobenzaldehyde, and into isothiocyanates by treatment with thiophosgene in the presence of K₂CO₃. 3-Benzyl- and 3-tert-butoxycarbonyl-3-azabicyclo-[3.3.1]nonan-9-yl isothiocyanates readily reacted with methanol, aniline, and sodium azide to produce methyl thiocarbamate, thiourea, and dihydrotetrazole-5-thione derivatives having a 3-azabicyclo[3.3.1]nonane fragment.     

Reactions of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with nitrogen-containing nucleophiles

Condensation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with hydroxylamine and hydrazine hydrate gave the corresponding oximes, hydrazones, and azines. Reductive amination of the title compounds in the presence of sodium triacetoxyhydridoborate led to the formation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-amines which were converted into the corresponding dihydrochlorides by treatment with dry hydrogen chloride. Treatment of 3-tert-butoxycarbonyl derivatives with HCl under analogous conditions was accompanied by elimination of the tert-butoxycarbonyl group to produce 3-azabicyclo[3.3.1]nonan-9-amine dihydrochlorides.     

Substituted 9-Oxabicyclo[4.2.1]- and 9-Oxabicyclo[3.3.1]nonanes (Part II)

The preparation, isolation, structure determination, and some reactions of the two stereoisomers of 2-iodo-9-oxabicyclo[4.2.1]nonane ( 9 and 10 ) and of 2-iodo-9-oxabicyclo[3.3.1]-nonane ( 11 and 12 ), respectively, are described. Iodine cleavage of the [4.2.1]-iodomercuri compound 3 yielded the iodides 9, 10 , and 11 , and iododemercuration of the [3.3.1]-iodomercuri compound 6 afforded the iodo compounds 9, 11 , and 12 , respectively. Direct treatment of 4-cycloocten-1-ol ( 1 ) with iodine in chloroform resulted in the exclusive formation of the two endo-iodides 9 and 11 . Raney nickel treatment as well as lithium aluminium hydride reduction of each índividual iodo compound 9, 10, 11 , and 12 gave the corresponding unsubstituted 9-oxabicyclononane ( 4 or 8 , respectively) with the unaltered skeleton. No rearrangement products could be observed. An oxonium ion is involved as an intermediate in the reaction of the endo-iodides 9 and 11 with silver acetate leading to an identical mixture of the two acetates 15 and 16 as well as in the isomerization of 9 to 11 .     

2-Oxo-9C(3)-hydroxy- und 2-Oxo-9C(7)-hydroxy-bicyclo[3.3.1]nonan

A synthesis of the two C(9) epimers 14 and 15 of 2-oxo-9-hydroxy-bicyclo[3.3.1]nonane is described starting from the two C(2) epimers 3 and 4 of 2-hydroxy-9-oxo-bicyclo[3.3.1]nonane.     

Oxymercuration. Substituted 9-oxabicyclo[4.2.1]- and 9- oxabicyclo[3.3.1]nonanes

Oxymercuration of cis, cis-1, 5-cyclooctadiene ( 1 ), followed by treatment with potassium iodide and subsequent reaction with iodine, leads to six isomeric diiodides which represent the three possible stereoisomers 2 , 3 , and 4 of 2, 5-diiodo-9-oxabicyclo[4.2.1]nonane as well as 5 , 6 , and 7 of 2, 6-diiodo-9-oxabicyclo[3.3.1]nonane. The isolation, structure determination and some reactions of these diiodo compounds 2 – 7 are described.     

Several transformations of 3-benzyl-9-carbethoxymethyl-3,9-diazabicyclo[3.3.1]nonane

The transformations of 3-benzyl-9-carbethoxymethyl-3,9-diazabicyclo[3.3.1]nonane (I) were studied. The dichloride of 9-(-chloroethyl)-3,9-diazabicyclo[3.3.1]nonane, which is readily cyclized in the basic form to 3,9-diazatricyclo[3.3.1.2^3,9]undecane (V), was synthesized by reduction of I with LiAlH₄ and debenzylation with subsequent replacement of the hydroxy group, in the alcohol formed, by chlorine. An unusual cleavage of the carboxymethyl residue to form the nitrogen-unsubstituted dichloride of 3,9-diazabicyclo[3.3.1]nonane (XI) occurs on treatment with thionyl chloride of the acid obtained by saponification and debenzylation of I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1372–1375, October, 1970.     

The synthesis of 7-hydroxy-3, 9-diazabicyclo[3.3.1]nonane

7-Hydroxy-3, 9-diazabicyclo[3.3.1]nonane is synthesized, starting from the dimethyl ester of the 4-hydroxypiperidine-2, 6-dicarboxylic acid, by preparing the N-benzyl derivative and cyclizing the latter with benzylamine to the benzylimide of the 1-benzyl-4-hydroxypiperidine-2, 6-dicarboxylic acid. On reduction of the given imide with lithium aluminum hydride and catalytic hydrogenolysis of the benzyl groups, the final 7-hydroxy-3,9-diazabicyclo[3.3.1]nonane is obtained, the three-dimensional structure of which (chair-chair type) is proved by comparison of its methyl derivative with a known compound of demonstrated three-dimensional structure.     

Synthesis and study on 2,4,6,8-tetraaryl- 3,7-diazabicyclo[3.3.1]nonanes and their derivatives

1-Carbethoxy-2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1] nonan-9-ones (1, 2) were synthesized and their 1H and 13C NMR data are reported. Chemical shifts and spectral assignments for 2,4,6,8-tetrakis(4-chlorophenyl)-3,7-diazabicyclo[3.3.1]nonan-9-one (3), 2,4,6,8-tetraphenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one (4) and 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonanes (5-7) are also included.     

Bicyclo[3.3.1]nonane and its derivatives—IV : Reactions of some carbonyl derivatives of bicyclo[3.3.1]nonane with diazomethane

The reaction of bicyclo[3.3.1]nonane-2,6-dione with diazomethane in situ does not lead to the homologous bicyclo[4.3.1]decane-2,7-dione, but mainly to tricyclo[4.4.0.0^2,9]decan-9-ol-5-one. The structure of the latter was confirmed by the proton NMR spectra measured with an addition of Eu(DPM)₃, A mixture of tricyclo[4,4.0.0^2,9]decan-9-ol-5-one and bicyclo[4.3.1]decane-2,7-dione results when solutions of diazomethane are used. The reaction of bicyclo[3.3.1]nonane-2,6-dione monoethyleneacetal with diazomethane in situ yields predominantly bicyclo[4.3.1]decane-2,7-dione. Under the same conditions bicyclo[3.3.1]nonan-2-one gives with diazomethane in situ only bicyclo[4.3.1]decan-2-one.     

Substituierte 9-Oxabicyclo[4.2.1]- und 9-Oxabicyclo[3.3.1]nonane IV. endo,endo-2,5-Dihydroxy-9-oxabicyclo[4.2.1]nonan,endo, endo-, endo,exo- und exo,exo-2,6-Dihydroxy sowie endo,exo-2,7-Dihydroxy-9-oxabicyclo[3.3.1]nonan; Darstellung und Umwandlungsprodukte

The synthesis of the following compounds and reaction products thereof are described: endo, endo-2,5-dihydroxy-9-oxabicyclo[4.2.1]nonane ( 3–5 ), epimeric 2,6-dihydroxy-9-oxabicyclo[3.3.1]nonanes (endo, endo: 6–8 , exo, exo: 29–32 , and endo, exo: 43–45 ), and endo, exo 2,7-dihydroxy-9-oxabicyclo[3.3.1]nonane ( 46–50 ).     

9-BBN还原1,7-辛二烯-3-醇的研究

本文报道了用9-BBN与1,7-辛二烯-3-醇进行硼氢化反应的结果。这个反应的区域选择性极低,除生成1-辛烯-3-醇(47％)外,同时还生成了7-辛烯-3-醇(41％)和辛醇-3(12％)。     

Facile and convenient synthesis of B-amino-9-borabicyclo[3.3.1]nonanes. Aminoboration of lsocyanates

The reaction of 9-borabicyclo[3.3.1]nonane (9-BBN) with aliphatic and aromatic primary and secondary amines in tetrahydrofuran (THF) at 65°C proceeds rapidly and quantitatively with evolution of hydrogen and the formation of the corresponding B-amino-9-borabicyclo[3.3.1] nonane (B-amino-9-BBN). Simple evaporation of THF from the reaction mixture gives the B-amino-9-BBN derivatives in high yield and purity. These B-amino-9-BBN derivatives are reactive towards alkyl and aryl isocyanates. Consequently, the aminoboration of various isocyanates has been studied using B-phenylamino-9-BBN. Thus, two equivalents of isocyanates react with one equivalent of B-phenylamino-9-BBN to afford, following the hydrolysis of the intermediate with ethanolamine, N, N'-disubstituted-N -(phenylamido)-ureas in excellent yields. A plausible mechanism for this aminoboration reaction of isocyanates is also presented.     

Synthesis and structure of new 3,7-diazabicyclo[3.3.1]nonane derivatives

Aminomethylation of triethylammonium 4-aryl-3,5-dicyano-6-oxo-1,4,5,6-tetrahydropyridin-2-olates and their sulfur and selenium analogs, as well as the structure of formed products, were studied in details. The reaction is of general character and leads to the formation of 7-substituted 9-aryl-2,4-dioxo-, 9-aryl-4-oxo-2-thioxo-, 9-aryl-4-oxo-2-selenoxo-3,7-diazabicyclo[3.3.1]nonane derivatives or their salts. The structures of ethyl 9-(2-chlorophenyl)-5-cyano-7-(4-methylphenyl)-2-oxo-4-thioxo-3,7-diazabicyclo[3.3.1]nonane-1-carboxylate (as a complex with N-methylmorpholine) and triethylammonium salt of 7-benzyl-4-oxo-2-selenoxo-9-(2-thienyl)-3,7-diazabicyclo[3.3.1]nonane-1,5-dicarbonitrile were studied by X-ray crystallography.     

3,7-disubstituted bicyclo [3.3.1] nonanes—II : Synthesis and conformation of some 3,7-disubstituted 9-oxobicyclo [3.3.1] nonanes

Condensation of pyrrolidine enamines of 4-alkylcyclohexanones with methyl α-(bromomethyl)acrylate affords methyl 7β- and 7α-alkyl-9-oxobicyclo [3.3.1] nonane-3α-carboxylates in a ratio of 3:2. The mechanism of the annelation reaction is discussed. The conformations of the reaction products and their epimers have been studied by means of PMR spectroscopy.     

Synthesis and structure of 7-alkoxyalkyl-3-thia-7-zabicyclo[3.3.1]nonan-9-ones and several of their derivatives

New 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ones were synthesized by the double Mannich cyclization of tetrahydrothiopyran-4-one with suitable alkoxyalkylamines and paraformaldehyde in acetous methanol. Wolff-Kishner decarbonylation of these bicyclic ketones gave 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonanes. The reduction of 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ones by alkali metal hydride complexes leads to a mixture of two stereoisomeric secondary alcohols, which are epimers at C₍₉₎. Active analgesic, antiarrhythmic, and antibacterial compounds were found among these products. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 585–592, April, 2006.     

Synthesis,structural and conformational study of some amides derived from 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide

A series of 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carbonitrile and 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide N-substituted have been synthesized and studied by ¹ H and ¹³C nmr spectroscopy and the crystal structure of 3,7-dimethyl-9-benzylamino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide dihydrochloride ( IVb· 2HCl) has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform, dimethyl sulfoxide-d₆ and methanol-d₄ the same preferred flattened chair-chair conformation with the methyl groups in equatorial position. The carboxamido group lies in a plane nearly perpendicular to the bispidine skeleton. The conformation and protonation sites of IVb· 2HCl in the crystal state and in deuterium oxide solution are discussed.     

Synthèse facile de dérivés du diphényl-2,4-aza-3-bicyclo[3.3.1]nonane et du diphényl-7,8-aza-8-bicyclo[4.3.1]décane

Facile synthesis of derivatives of 2,4-diphenyl-3-azabicyclo[3.3.1]nonane and 7,9-diphenyl-8-azabicyclo[4.3.1]decane The facile synthesis of hydantoins, cyanhydrins and aminonitriles derived from 2,4-diphenyl-3-azabicyclo[3.3.1]nonanone and 7,9-diphenyl-8-azabicyclo[4.3.1]decanone is described. Configurations at C(9) or C(10) of the new compounds wth pharmaceutical and synthetical utility is deduced from their spectral properties.     

Synthesis of 2,6-Dibromo-9-selenabicyclo[3.3.1]nonane-Based Pyridinium Salts Containing Acetal Groups

Russian Journal of Organic Chemistry - An efficient one-pot procedure has been developed for the synthesis of previously unknown 1,1′-(9-selenabicyclo[3.3.1]nonane-2,6-diyl)dipyridinium...     

5-Hydroxy-1-phosphabicyclo[3.3.1]nonan

5-Hydroxy-1-phosphabicyclo[3.3.1]nonane A new approach to 1-phosphabicyclo[3.3.1]nonane compounds involves free-radical cyclization of 4-trimethylsilyloxy-4-phosphinomethyl-hepta-1.6-diene synthesized by the reaction of 2.2-diallyl-oxirane with KPH₂ followed by trimethylsilylation. Trimethylsilyl groups are easily cleaved in boiling methanol forming 5-hydroxy-1-phosphabicyclo[3.3.1]nonanes. Silylated and desilylated bicyclic compounds are characterized by n.m.r. and i.r. data.