3.7- Diazabicyclo nonan-9-ones

The final step to 46 is cyclocondensation of 3,7-diazabicyclo[3.3.1]nonane (51), bispidine70, with formaldehyde. There are two different approaches to 51 (i) a pyridine is converted to a piperidine and (ii) the double Mannich or Robinson-Schopf condensation of ketone 52 with formaldehyde and primary amines affords 1,5-disubstituted 3,7-dazabicyclo[3.3.1]nonan-9-one (53), bispidone, from which 5,7-disubstituted l,3-diazaadamantan-6-one (61) is derived. Route (i) is adopted by Galinovsky and Langer,71 Stetter and... 

A similar vinylogous Mannich reaction has been used by Martin in the total syntheses of the heteroyohimboid alkaloids (—)-ajmalicine and (—)-tetrahydroalstonine <1995JOC3236>. An attempted synthesis of an opioid analgesic 2,4-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-one-l,5-dicarboxylate (piperidone) by a double Mannich reaction of oxoglutarate, 2 equiv of phenylacetaldehyde, and methylamine did not give the expected product but instead gave rise to an unexpected [l,6]naphthyridine derivative (Scheme 57) <1998PHA442>. 

Beckmann rearrangement of quinuclidin-3-one oxime (103) in the presence of polyphosphoric acid or oleum proceeds with quinuelidine ring expansion and the formation of 3-oxo-l,4-diazabicyclo[3.2.2]-nonane (146).m,m... 

Selenium 3,7-diazabicyclo-[3.3.1]nonan-9-one derivatives have also been prepared by the author (2) as illustrated in Eq. 2 ... 

Gonzales Trigo. G.. Galvez Ruano, E., and Mcnendez Aguirre. C.. Spiro heterocyclic derivatives. XV. Some N-methyl-N -alkyl (or aralkyl) -3.7-diazabicyelo 0. 3.3.1 nonan-9-ones and. some, spiro-5 -hydanioin derivatives of 3,7-diazabicyclo(3.3.l Inonanes. An. Quim.. 75, 894, 1979 Chem Ahstr., 93. 26411, 1980. 

Paquette, L. A., Wise, L. D. Unsaturated heterocyclic systems. XI. The Hofmann elimination of 9-methyl-3,9-diazabicyclo[4.2.1]nonan-4-one methiodide. Nature of the product and mechanism. J. Org. Chem. 1965, 30, 228-231. 

The diazabicyclononanone (3,7-diazabicyclo[3.3.1]nonan-9-one) skeleton is placed in a relatively new class [23-25], having two positively charged groups, which is also common to peptides (Fig. 6). Diazabicyclononanones include HZ1, 3FLB, and HZ2 [23, 53], the last of which exhibits the next highest K-selectivity (p/K > 66.7) after... 

Ac AIBN 9-BBN Bn Boc Bu Bz CAN Cbz CD CSA DABCO DAST DBN DBU DCC DDQ DEAD DHP DIAD DIBAL-H DMAP DME DMF DMP DMSO DNB EE Ee Eq Et Fmoc GLC HLADH HMDS HMPA HOBt HPLC Im acetyl 2,2/-azobisisobutyronitrile 9-borabicyclo[3.3.1]nonane benzyl f-butoxycarbonyl butyl benzoyl ceric ammonium nitrate benzyloxycarbonyl circular dichroism camphorsulfonic acid 1.4- diazabicyclo[2.2.2]octane A,A-Diethylaminosulfur trifluoride 1.5- diazabicyclo[4.3.0]non-5-ene l,8-diazabicyclo[5.4.0]undec-7-ene A,A -dicyclohexylcarbodiimide 2.3- dichloro-5,6-dicyano-1,4-benzoquinone diethyl azodicarboxylate 3.4- dihydro-2//-pyrane diisopropyl azodicarboxylate diisobutylaluminum hydride 4-A,A -dimethylaminopyridine 1,2-dimethoxyethane A,A -dimethylformamide Dess -Martin periodinane [1,1,1 -tris(acetyloxy)-1,1 -dihydro-1,2-benziodoxol-3-( IH) -one] dimethyl sulfoxide 3.5- dinitrobenzoyl 2-ethoxyethyl enantiomeric excess molar equivalent ethyl 9-fluorenylmethoxycarbonyl gas-liquid chromatography horse liver alcohol dehydrogenase 1,1,1,3,3,3 -hexamethyldisilazane hexamethylphosphoric triamide 1 -hydroxybenzotriazole high-performance liquid chromatography 1-imidazolyl or imidazole... 

A flattened CC conformation has been assigned for the 3,7-diazabicyclo[3.3.1]nonan-9-ones 156-159 in (CD3)2SO and in CDC13 on the basis of H-and 13C-NMR, IR, and Raman spectral data (111,114). H-and 13C-NMR studies of compounds 156 and 160-162 in CDC13 solution have confirmed for 156 and shown for 160-162 a flattened chair-chair conformation with the N-substituents in the equatorial position. Additionally, an increase in distortion of the A-alkylpiperidine ring was observed as the size of the JV-substituent was increased (115). 

X-ray studies of a series of 1,5-diphenyl /V,/V -disubstituted derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one have shown that their conformation depends on whether the lone-pair electron density is delocalized away from the... 

Hydrogen exchange alpha to a carbonyl group has been observed in the pyrolysis of 9-methyl-3,9-diazabicyclo-[4,2,l]nonan-4-one methiodide in the presence of hydroxide ion at 150°C . This is not surprising in view of the ketonic function, but as to whether the carbanion is involved in elimination (23) remains unsolved. 

A soln. of 7-dimethylamino-5,6,7,8-tetrahydro-2(lH)-azocinone in anhydrous ether treated dropwise with a slight excess of an 1 1 ethanolic perchloric acid soln., cooled, the supernatant soln. decanted, ethanol added, and warmed 30 sec. on a steam bath 9-methyl-3,9-diazabicyclo [4.2.1] nonan-4-one metho-perchlorate. Y 97.5%. F. e. s. L. A. Paquette and L. D. Wise, Am. Soc. 87, 1561 (1965). 

Cl i,H32Cl0N4Ni2, Bis-N-methyl-N -diazabicyclo[2.2.2]octonium di-M" chloro-hexachlorodinickelatedi), 35B, 878 Cl5H1iN, [2.2](2,6)Pyridinoparacyclophane-1,9-diene, 40B, 287 Cl5H1gBrN02, 9-Benzoyl-3a-bromo-9-azabicyclo[3.3.1]nonan-2-one, 37B,... 

Swal997 Swayze, E.E., The Solid-Phase Synthesis of Trisubsti-tuted l,4-Diazabicyclo[4.3.0]nonan-2-one. Scaffolds On Bead Monitoring of Heterocycle Forming Reactions Using N NMR, Tetrahedron Lett., 38 (1997) 8643-8646. 

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