Synthesis, structural and crystallographic study of some carbamates derived from 9-methyl-9-azabicyclo[3.3.1]nonan-3α-ol

A series of benzimidazole, thiazole and benzothiazole carbamates derived from 9-methyl-9-azabicyclo[3.3.1]nonan-3α-ol was synthesized and studied by ¹H, ¹³C, 2D NMR and IR spectroscopy. To assist in the interpretation of the spectroscopic data, the crystal structure of 3 (9-methyl-9-azabicyclo[3.3.1]nonan-3α-yl 2-amino-1H-benzimidazole-1-carboxilate) was determined by X-ray diffraction. It has been found that 1-carbamates and 2-carbamates can be obtained in the case of the benzimidazole derivatives. The benzimidazole-1-carbamates are obtained in higher yields (41, 38%) than the benzimidazole-2-carbamates (3, 9%). The compounds studied displayed in CDCl₃ solution a preferred chair–boat conformation with the substituted ring in a distorted boat form and the N–CH₃ substituent in an axial position with respect to the chair piperidine ring. This conformation is similar to that determined by X-Ray diffraction for compound 3.     

Conformational analysis of 3-borabicyclo[3.3.1]nonane derivatives

Conformations of 3-borabicyclo[3.3.1]nonane derivatives have been studied by means of ¹H and ¹³C NMR spectroscopy. With the aid of the coupling constants ³J(HH) and ¹³C chemical shifts it has been shown that all the derivatives of 3-borabicyclo[3.3.1]nonane with the trigonal boron atom studied are in a flattened double-chair conformation. In 3-borabicyclo[3.3.1]nonane derivatives with the tetra-coordinated boron atom and substituents at the 7α-position, the chair-boat conformation predominates, the boat conformation being characteristic of the cyclohexane ring; exceptions are the compounds with the internal donor—acceptor bond between the boron atom an 7α-substituent.     

Synthesis and x-ray diffraction analysis of (endo-7-methyl-3-borabicyclo [3.3.1] nonyl-3)-8-hydroxyquinolinate

Conclusions (endo-7-Methyl-3-borabicyclo[3.3.1]nonyl-3)-8-hydroxyquinolinate has been synthesized, and it has been established that its bicyclononane ring structure exists in the chair-boat conformation. The cyclohexane ring has the boat form. The B-O bond of the hydroxyquinoline fragment is fixed in the endo position.DeceasedTranslated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1645–1649, July, 1986.     

Unique stereochemistry of 3-borabicyclo[3.3.1]nonane derivatives

The conformational equilibrium in solution was examined by NMR spectroscopy for a series of 7-phenyl-3-borabicyclo[3.3.1]nonane derivatives containing various substituents at the boron atom. The structures of these derivatives were studied in the crystalline state (X-ray diffraction analysis) and by quantum-chemical calculations (B3Pw91/6-31G*). The B...Ph transannular interactions corresponding to charge transfer from the system of the phenyl group to the vacant p-orbital of the B atom were demonstrated to be responsible for unique stability of the chair-chair conformation of these derivatives.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1884–1896, September, 2004.     

Crystal and molecular structure of 6,6-dimethyl-cis-2,4-diphenyl-3-aza-7-oxabicyclo[3.3.1]nonan-9-one

A method is presented for synthesizing 6,6-dimethyl-2,4-diphenyl-3-aza-7-oxabicyclo[3.3.1]nonan-9-one. The x-ray structure shows that the compound in the crystal exists in the chair-boat conformation with the piperidine ring in the boat form. The two phenyl substituents in the 2- and 4-positions are responsible for such a conformation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1400–1402, October, 1990.     

Chair-boat equilibria in bicyclo[3.3.1]nonane and some 3- and 3,7-substituted derivatives: Thermodynamic parameters and geometry of the conformers as obtained by molecular mechanics

ΔG-Values for conformational equilibria in 3,7-substituted bicyclo[3.3.1]nonanes have been obtained by means of epimerisation experiments (cc α bc) and by variable temperature ¹³C NMR (bc α bb). The results of these experiments fit well with those of molecular mechanics using the Schleyer force field. In bicyclo[3.3.1]nonane and 3β-substituted derivatives the cc conformation predominates; however, the bulky 3β-substituent t-butyl, is found to have a destabilizing effect. A 3α-substituent forces the substituted wing into the boat conformation. For the 3α,7α-substituted derivatives the conformational preferences depend on the size of the substituents: for 3α-methyl-7α-t-butylbicyclo[3.3.1]nonane the cb and t-bb conformers are of approximately equal enthalpy. The geometries, obtained by the calculations, show that the conformers of bicyclo[3.3.1]nonane (cc, bc and t-bb) are all distinctly flattened. The boat wings of bc conformers are not twisted to any extent. The t-bb is the most stable bb conformation. The influence of substitution at positions 3 or 7 is discussed in detail; in general, a bulky substituent such as t-butyl, affects the geometry of both wings of the ring system. The calculated geometries are in good agreement with the conclusions of previous ¹H NMR investigations.     

The gas-phase conformation of 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane

The gas-phase conformation of the title compound (1) is discussed in reference to its photoelectron spectrum. The experimental lone-pair/lone-pair splitting (0.51 eV), when compared with that of similar diamines and with the results of three sets of MO calculations (MINDO/3, MNDO and STO-3G), leads to the conclusion that 1 exists in the chair-chair conformation. A remarkable sensitivity of the calculations to slight changes in the geometry is noted, and it is suggested that calculations of this type must include geometry-optimization. The question of through-space vs through-bond inteaction of the nitrogen lone pairs was explored by performing MNDO calculations in which the N-N resonance integrals were set to zero. These calculations indicate that in the chair-chair conformation the N-N interaction is mainly through-space. The ¹³CNMR and Ni(acac)₂-induced ¹³C shifts of 1 are discussed.     

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.     

Synthesis and conformational analysis of exo-and endo-7-substituted-3-azabicyclo[3.3.1]nonanes

The synthesis of some 7-substituted-3-azabicyclo[3.3.1]nonanes is described. Routes followed were the debenzoylation of the 7-benzoyl derivative 7 and the decarboxylation of the 7-carboxy compounds 21 and 27. The so-obtained 7-oxo-N-tosyl-3-azabicyclo[3.3.1]nonanes 8and 11 show an extremely low reactivity towards a series of nucleophilic reagents. From analysis of the ¹H NMR spectral data of a series of derivatives, the twin-chain conformation for the 7-exo compounds and the chair-boat conformation for the 7-endo compounds is indicated.     

Molecular and crystal structure of 5,7-diphenyl-7-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine

The molecular and crystal structures of 5,7-diphenyl-7-methyi-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine have been studied by X-ray structural methods. The crystal is monoclinic,a=16.112(3),b=13.489(3),c=14.480(3)Å, =101.62(2)°,Z=8, space groupC2/c,R=0.071. The presence of short intermolecular contacts indicates considerable steric strain in the molecule. The dihydropyrimidine ring exists in an unevenly planar boat conformation. Increasing the steric strain of the dihydrocycle leads to a twisted conformation.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1912–1914, November, 1993.     

On the conformation of 6-ketononanolide and 1,4-cyclohexanedione in solution by dipole moment studies

The dipole moments of 6-ketononanolide (1) and its 2,4,7 and 8-Me derivatives (2–5) are found to be 1·8 – 1·9±0·2 D. Utilizing the known solid-state geometry of 1, a dipole moment of 1·6 D is calculated by the INDO quantum mechanical method. Thus the conformation of 1 in solution does not differ much from its solid-state conformation which is diamond-lattice derived with the CO groups 174° apart and in “Type III” positions. However, the IR spectrum of 1 in solution shows differences from that in the solid state (Nujol or KBr).The dipole moment of 1,4-cyclohexanedione (10) is calculated to be 1·2 D for the experimental 156° twist boat conformation (found in the solid-state). This is in excellent agreement with the experimental value found by several groups. 1,6-Cyclodecanedione (6), however, is found to have an experimental dipole moment of 0·7 D, as contrasted with a calculated value of 0 D for 180° opposed carbonyls.     

Organoboron compounds : CCCXCIX. The matteson-pasto rearrangement in the series of 3-borabicyclo[3.3.1]nonane compounds

Bromination of 3-isopropyl-7-methyl- and 3-isopropyl-7-bromomethyl-3-borabicyclo[3.3.1]nonane leads to corresponding 3-(2-bromo-2-propyl) derivatives, which, on treatment with alcohols or pyridine as well as on heating, undergo the Matteson-Pasto rearrangement to convert into 3-X-4,4,8-trimethyl- and 3-X-4,4-dimethyl-8-bromomethyl-3-borabicyclo[4.3.1]decane (X = Br, OR). Interaction between triethylamine and 3-(2-bromo-2-propyl)-7-methyl-3-borabicyclo[3.3.1]nonane is accompanied by dehydrobromination leading to 3-isopropenyl-7-methyl-3-borabicyclo[3.3.1]nonane. Carbonylation of 3,4,4,8-tetramethyl-3-borabicyclo[4.3.1]decane at 140°C is accompanied by migration of two alkyl groups from the boron to the carbon atom, and subsequent oxidation with H₂O₂ produces 1-(2-hydroxy-2-methyl-1-propyl)-3-acetonyl-5-methyl-cyclohexane. Under more forcing conditions (180-195°C), the third alkyl group also migrates to give, after oxidation, a mixture of isomeric 3,4,4,8-tetramethylbicyclo[4.3.1]decan-3-ols. 3-n-Butoxy-4,4-dimethyl-8-bromomethyl-3-borabicyclo[4.3.1]decane, on treatment with Lì, undergoes cyclization to afford 4,4-dimethyl-3-borahomoadamantane, carbonylation and subsequent oxidation of which gave 4,4-dimethylhomoadamantan-3-ol.     

Study of the Steric Structure of 7-Alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ones and Their Derivatives Using 1H NMR Spectroscopy

Using the ¹H NMR spectroscopic method it has been shown that 7-alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonan-9-ones and 7-alkoxyalkyl-3-oxa-7-azabicyclo[3.3.1]nonanes exist in deuterochloroform solution in a double chair conformation. 7-(3-Butoxypropyl)-3-oxa-7-azabicyclo[3.3.1]nonan-9-ol is a 1:1 mixture of the two stereoisomeric alcohols. One of them exists in a double chair conformation having an equatorial hydroxyl group with relation to the piperidine ring and the other in a chair-boat conformation having an axial hydroxyl group which involves an intramolecular hydrogen bond with the unshared electron pair of the nitrogen atom.     

Chiral azole derivatives. Part 5: Synthesis of enantiomerically pure 1-[α-(benzofuran-2-yl)arylmethyl]-1H-1,2,4-triazoles, antifungal and antiaromatase agents

Racemic and enantiopure benzofuranmethanamines 5a–c have been reacted with N-Boc-3-(4-cyanophenyl)oxaziridine to give N-Boc-hydrazines 7a–c, which have in turn been transformed by deprotection and cyclisation into triazoles 4a–c, potent antiaromatase agents, in good overall yield and with high enantiomeric excess.     

Assymetric syntheses of the ladybug alkaloid adaline and 1-methyl-9-azabicyclo [3.3.1]nonan-3-one

The double Michael addition of benzylamine to 3-alkyl-2,7-cyclooctadienones, followed by hydrogenolysis, affords bridgehead substituted 9-azabicyclo[3.3.1]nonan-3-ones. Use of (+)-α-methylbenzylamine in the addition leads to mixtures of diastereomeric adducts in unequal amounts. Although the degree of asymmetric induction is low (10–20% ee), the diastereonomers can be easily separated, affording pure enantiomeric forms of the ladybug alkaloid adaline 1 and the Euphorbia alkaloid 3.     

New strategy to the synthesis of (N → B) phenyl[N-alkyliminodiacetate-O,O′,N]boranes: The crystal structure of (N → B) phenyl[N-benzyliminodiacetate-O,O′,N]borane, (N → B)phenyl[N-(4-methyl)benzyliminodiacetate-O,O′,N]borane and (N → B) phenyl[N-phenacyliminodiacetate-O,O′,N]borane

A new, mild and friendly method for the synthesis of (N → B) phenyl[N-alkyliminodiacetate-O,O′,N]boranes 2–7 is reported. All compounds were identified by ¹H, ¹¹B, ¹³C NMR and their high resolution mass spectra (HRMS) are reported. The structure of the compounds 2, 4 and 5 were established by single crystal X-ray. Compounds 2 and 4 crystallized with two independent molecules 2A, 2B and 4A, 4B, respectively in the asymmetric unit. These molecular structures established the bicyclic structure showing a N → B bond length of 1.666 (2) Å for 2A, 1.675 (2) Å for 2B, 1.675 (3) Å for 4A, 1.663 (3) Å for 4B and 1.679 (2) Å for 5, as well as different torsion angles of the junction, 28.70 (2)° (C11–B1–N6–C17) for 2A, 21.50 (2)° (C11a–B1a–N6a–C17a) for 2B, 25.76 (0.26)° (C11–B1–N6–C17) for 4A, 21.96 (0.28)° (C11a–B1a–N6a–C17a) for 4B and −29.22 (0.20)° (C5–N1–B1–C13) for 5.     

Structures and conformations of 1-aryl-1,4-dihydro-3(2H)-isoquinolinones

The X-ray crystal structures of series of 1-aryl-1,4-dihydro-3(2H)-isoquinolinones (1-7) have been determined. Lactame heterocyclic ring possesses more or less deformed boat conformation in all examined structures. The aryl substituent adopts the equatorial position in the structures 1-3 and the axial one in 5-7. In the structure of 4, due to extremely flattened heterocyclic ring, aryl substituent location can be named as bisectional. In all solved structures the molecules are joined into the dimers via two N-H?O hydrogen bonds. At the same time, ¹H NMR studies in DMSO-d₆ solutions were accomplished and profound analysis of ²J, ³J, and ⁵J coupling constants have shown that in isoquinolinone system the heterocyclic ring adopts the boat conformation in all investigated compounds. The stereochemical orientations of the phenyl ring at C1 do not depend on the nature of the substituent but, exclusively, on the mode of substitution. However, three forms of undulated laktam heterocyclic ring conformation in respect of 1-aryl substituent positions were confirmed by calculation (conformational analysis).     

Selective reduction of tertiary alkyl,benzyl, and allyl halides to hydrocarbons using lithium 9,9-di-n-butyl-9-borabicyclo[3.3.1]nonanate

The title 9-borabicyclo[3.3.1]nonane(9-BBN) ate complex (1) brings about selective removal of tertiary alkyl, benzyl and allyl halides to give the corresponding hydrocarbons in excellent yields without concomitant attack on secondary, primary and aryl derivatives. The reduction of cis- and trans - 4 - t - butyl - 1 - methylcyclohexyl chlorides (2) with 1 gives 4 - t - butyl - 1 - methylcyclohexanes (3) with partial inversion of configuration in cyclohexane, while that in benzene gives thermodynamically stable trans-3 predominantly. The reactions of 1,1 - dimethyl - 5 - hexenyl chloride (4) and 1,7,7 - trimethylbicyclo[2.2.1]hept - 2 - yl chloride (8) with 1 proceed with the rearrangements characteristic to a carbonium ion intermediate. The reduction of 1 - ethyl - 1 - methylpentyl chloride with 1 follows a second-order rate equation.     

Conformational and configurational studies on 3-azabicyclo[3.3.1]nonane (3-abn) derivatives and related systems employing carbon-13 NMR spectroscopy

The ¹³C nmr spectra of 4 cis-2,4-diphenyl-3-azabicyclo[3.3.1]nonanes, 11 cis-2,4-diaryl-3-azabicyclo[3.3.1]-nonan-9-ones, 26 cis-2,4-diaryl-3-azabicyclo[3.3.1]-nonan-9-ols or acetates thereof, 5 cis-2,4-diaryl-3-azabi-cyclo[4.3.1]decan-10-ones or -10-ols and 5 cis-2,4-diphenyl-3-aza-7-thiabicyclo[3.3.1]nonan-9-ones, -9-ols or 9-yl acetates have been recorded. Except for the 7-thia compounds, which appear to exist mainly in the configuration and conformation with the nitrogen-containing ring in the boat form, these compounds seem to exist overwhelmingly in chair-chair conformations. The configuration of the 9-ols and their acetates (syn or anti to the nitrogen-containing ring) has been deduced from the spectra. In a number of cases, the structures assigned differ from those earlier postulated. Broadening of one set of aryl signals (probably those due to the ortho carbons) in the case of N-methyl (but not N-H) compounds without ortho substituents is ascribed to restricted phenyl rotation.     

Structural properties of five- and six-layered [3.3]metacyclophanes

We performed X-ray structural analyses of the five- and six-layered [3.3]metacyclophanes (MCPs) 1 and 2 and the six-layered [3.3]MCP tetraone 3. In the solid state, the MCP moieties of 1, 2, and 3 adopt different conformations from those of the free MCPs in solution. In the five-layered [3.3]MCP 1, all the [3.3]MCP moieties adopt anti (chair/boat) conformations. In the six-layered [3.3]MCP 2, two three-layered [3.3]MCPs are connected by a [3.3]MCP in the anti conformation with completely parallel benzene rings. In the six-layered [3.3]MCP tetraone 3, the outer [3.3]MCP moieties and diones adopt general syn and anti geometries, respectively. However, the inner [3.3]MCP moiety adopts an anti geometry. Based on density functional theory (DFT) calculations, the most stable conformers of 1, 2, and 3 are syn (chair/chair) in the [3.3]MCP moieties and anti (twist boat/twist boat) in the dione moieties.