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.     

The Mannich-type interaction of sulfur-containing CH acids with formaldehyde and primary amines

One-pot reactions of dimethyl sulfonyldiacetate and N-methyl-2r,6c-di(methoxycarbonyl)-3t,5t-diphenyltetrahydro-1,4-thiazine 1,1-dioxide with formaldehyde and primary amines lead to derivatives of 9-thia-3,7-diazabicyclo[3.3.1]nonane 9,9-dioxide resulted from decarboxylation of the ester groups at the positions 1 and 5. The effects of the reaction conditions and structure of the starting reagents on the yields of 9-thia-3,7-diazabicyclo[3.3.1]nonane 9,9-dioxides were studied.     

Synthesis and transformations of polyhedral compounds. Synthesis of 2-[quinolin-3(2)-yl]-1,3-diazaadamantanes

A number of new 1,3-diazaadamantane derivatives containing quinoline fragments on C² have been synthesized by condensation of 1,5-dialkyl-3,7-diazabicyclo[3.3.1]nonan-9-one, 1,5-dimethyl-3,7-diazabicyclo-[3.3.1]nonan-9-ol, and 1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane with 2-oxo-1,2-dihydroquinoline-3-carbaldehyde, 2-chloro- and 2-iodoquinoline-3-carbaldehyde, and quinoline-2-carbaldehyde.     

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.     

Heteroadamantanes and their derivatives. 9. Synthesis of 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonane and derived 2,2-disubstituted 5,7-dinitro-1,3-diazaadamantanes

Heating 1,5-dinitro-3,7-di(tert-butyl)-3,7-diazabicyclo[3.3.1]-nonane with concentrated hydrobromic acid gives 1,5-dinitro-3,7-diazabicyclo[3.3.1]nonane. Cyclization of the latter with various aldehydes and ketones gave a series of 2,2-disubstituted 5,7-dinitro-1,3-diazaadamantanes. The behavior of the synthesized compounds under electron impact has been studied.For Communication 8 see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 538–542, April, 1990.     

A combined experimental and computational study on the sulfoxidation by high-valent iron bispidine complexes

Iron-bispidine complexes are efficient catalysts for the oxidation of thioanisole to phenylmethylsulfoxide with iodosylbenzene as oxidant. With the tetradentate bispidine ligand L(1) (L(1) = 2,4-pyridyl-3,7-diazabicyclo[3.3.1]nonane)) the catalytic efficiency is smaller than with the pentadentate bispidine ligand L(2) (L(2) = 2,4-pyridyl-7-(pyridine-2-ylmethyl)-3,7-diazabicyclo[3.3.1]nonane)). Based on the redox potentials (iron complexes with L(1) are stronger oxidants than with L(2)) and known efficiencies in catalytic olefin oxidation and C-H activation reactions, the expectations were different. A DFT-based analysis is used to explain the apparent contradiction, and this is based on differences in the electronic ground states of the ferryl complexes as well as in the oxygen transfer transition states.     

Synthesis,crystal and molecular structure of 3,7-ditosyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonane

3,7-Ditosyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonane has been found to adopt a chair–chair conformation in the crystalline state in contrast to 3,7-ditosyl-1,5-diphenyl-3,7-diazabicyclo[3.3.1]nonan-9-one, which had been previously found to exist in a chair-boat conformation.     

Synthesis of novel piperazine based building blocks: 3,7,9-triazabicyclo[3.3.1]nonane, 3,6,8-triazabicyclo[3.2.2]nonane, 3-oxa-7,9-diazabicyclo[3.3.1]nonane and 3-oxa-6,8-diazabicyclo[3.2.2]nonane

The preparation of four novel bridged piperazine building blocks is described: 3,7,9-triazabicyclo[3.3.1]nonane 1, 3-oxa-7,9-diazabicyclo[3.3.1]nonane 2, 3,6,8-triazabicyclo[3.2.2]nonane 3 and 3-oxa-6,8-diazabicyclo[3.2.2]nonane 4. The scaffold of 1 was synthesized from N,N′-dibromobenzenesulfonamide and ethyl acrylate. Compound 2 may be prepared from identical starting materials or alternatively from α,α′-diglycerol. Compounds 3 and 4 were identified as side products from possible aziridinium intermediates.     

The "hockey sticks" effect revisited: the conformational and electronic properties of 3,7-dithia-1,5-diazabicyclo[3.3.1]nonane from the QTAIM perspective

The conformational effects in bicyclo[3.3.1]nonanes, while thoroughly studied, have not yet received the full theoretical explanation. R. F. W. Bader's quantum theory of atoms in molecules presents unique opportunities for studying the stereoelectronic interactions (SEI) and weak intramolecular bonding leading to these effects. Here, we report the study of 3,7-dithia-1,5-diazabicyclo[3.3.1]nonane by means of the topological analysis of the calculated (MP2(full)/6-311++G**) and experimental (X-ray derived) charge density to reveal the origins of the so-called "hockey sticks" effect observed in similar compounds. A new explanation of the relative stability of bicyclo[3.3.1]nonane conformers based on the analysis of the QTAIM atomic energies is given. The H···H and S···S interactions in bicyclo[3.3.1]nonane and its dithia derivatives are shown to be significant factors contributing to the differences in the relative stability of the conformers.     

Cyclopalladate complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane

Russian Chemical Bulletin - A new (C,N,N)-pincer cyclopalladate unsymmetrical complex of 3-benzyl-7-methyl-3,7-diazabicyclo[3.3.1]nonane (3-benzyl-7-methylbispidine) was synthesized and...     

First asymmetric synthesis of a C2-symmetric 2-endo,6-endo-disubstituted bispidine

The enantioselective synthesis of a C₂-symmetric 2-endo,6-endo-disubstituted bispidine (3,7-diazabicyclo[3.3.1]nonane) has been accomplished for the first time. The key step was a Michael addition of the protected β-amino ester methyl (R)-3-{N-benzyl-N-[(S)-1-phenylethyl]amino}-3-phenylpropionate to its α-methylene derivative delivering an anti,anti-configured α,α′-methylene-bridged bis(β-amino ester) as the major diastereomer. Deprotection, reduction and cyclisation furnished (1R,2R,5R,6R)-2,6-diphenyl-3,7-bis((S)-1-phenylethyl)-3,7-diazabicyclo[3.3.1]nonane in six steps and 15% overall yield.     

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.     

Synthesis and Reactions of Polyhedral Compounds. 27. Development of a Synthetic Route for 2- Spiro-substituted 6-Hydroxy-5,7-dimethyl-1,3-diazaadamantanes

Alternative methods for the synthesis of 2-spiro-substituted 6-hydroxy-5,7-dimethyl-1,3-diazaadamantanes have been developed. These are the reduction of the ketone group to hydroxyl in the corresponding 6-oxo-1,3-diazaadamantanes and the condensation of 9-hydroxy-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonane (obtained by different routes from 5,7-dimethyl-6-oxo-1,3-diazaadamantane) in reaction with cyclic ketones.     

Amine-mediated tandem conjugative isomerization-bridging Michael addition: concise synthesis of 1-azabicyclo[3.3.1]nonanes

To reach densely functionalized 1-azabicyclo[3.3.1]nonane frameworks synthesis, a stereocontrolled bridging Michael addition involving an unexplored C-5/C-6 disconnection strategy was studied. 1-Azabicyclo[3.3.1]nonane scaffolds have been diastereoselectively elaborated in fairly good yields by two concise pathways implying pyrrolidine derivative organocatalyst or enantiopure 1-phenylethylamine.     

A practical synthesis of (+/-)-alpha-isosparteine from a tetraoxobispidine core

[reaction: see text] The title alkaloid was synthesized in racemic form from 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (7) by a regioselective diallylation reaction followed by double ring-closing olefin metathesis and exhaustive reduction. Tetraoxobispidine 7 was itself prepared in three simple operations from dimethyl malonate. The entire sequence to alpha-isosparteine was conducted on a multigram scale and proceeded without recourse to chromatography.     

New construction of the bicyclo[3.3.1]nonane system via Lewis acid promoted regioselective ring-opening reaction of the tricyclo[4.4.0.0]dec-2-ene derivative

A new access to the bicyclo[3.3.1]nonane system, which is a common structure in a number of polyisoprenylated phloroglucinol derivatives (phloroglucins), has been developed via the Lewis acid promoted regioselective ring-opening reaction of the cyclopropane, a tricyclo[4.4.0.0^5,7]dec-2-ene derivative.     

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.     

Synthesis and conversions of polyhedral compounds. 25. Synthesis and convepsions of certain oxindole derivatives of 1,3-diazaadamantane and 3,7-diazabicyclo[3.3.1]nonane

By the reaction of 1,5-dimethyl-9-oxo-3,7-diazabicyclo[3.3.1]nonane with isatin and a number of its derivatives, spiro(1,3-diazaadamantane-2,3′-oxindoles) have been synthesized. In the case of 5-bromoisatin, either 3-(3-hydroxyoxindolyl)-3,7-diazabicyclo[3.3.1]nonane or the corresponding spirane is obtained, depending on the temperature. The interaction of these products with acetic anhydride has been studied. For communication 24, see [1]. A. L. Mndzhoyan Institute of Fine Organic Chemistry, Academy of Sciences of the Republic of Armenia, Erevan 375014. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1490–1493, November, 1997.     

13C and1H NMR spectra and structure of 2-aryl-1,3-dibenzoyl-1,3-diazabicyclo[3.3.1]nonanes

Conclusion ¹³C and¹H NMR spectroscopy was used to determine the structures of 2-aryl-1,3-dibenzoyl-1, 3-diazabicyclo[3.3.1]nonanes and 2-aryl-1-benzyl-3-benzoyl-1,3-diazabicyclo[3.3.1]nonane. These compounds were found to exist predominantly in the boat-chair conformation (boat for the diaza ring), while the 2-aryl substituents occupy the exo or endo position.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1023–1028, May, 1988.     

Synthetic studies on phloroglucins: a new approach to the bicyclo[3.3.1]nonane system via the regioselective ring-opening of the methoxycyclopropane

A new synthetic approach to the bicyclo[3.3.1]nonane system, a common structure in a number of polyisoprenylated phloroglucinol derivatives (phloroglucins), has been developed. The key step in our approach is a ‘one-pot’ procedure of two successive reactions, the intramolecular cyclopropanation reaction which affords the tricyclo[4.4.0.0^5,7]dec-2-ene derivative and its methoxy group directed regioselective ring-opening reaction mediated by ZnCl₂, producing the desired bicyclo[3.3.1]nonane as the sole product.