3-azabicyclo -nonane

The mercuration-demercuration reaction of cw,cw-l,5-cyclooctadiene (3) has been widely studied in order to get some insight into the synthesis of 9-oxa and 9-azabicyclo-nonane derivatives. However, the results of the reaction have often been the subject of some controversy since the ratio of the two isomeric bicyclo[3.3.1]- [199 and 201] and [4.2.1]- [198 and 200] nonanes, after reduction (equation 166), strongly depended on the reaction conditions of the mercuration step168,169. 

Azabicyclo[4.2.l]nona-2,4-diene-9-carboxylic acid, 7-0X0-ethyl ester synthesis, 7, 524 Azabi cyclononadienones synthesis, 7, 524 1 -Azabi cyclo[5.2.0]nonane nomenclature, 7, 342... 

A kinetic study of the mercuric acetate oxidation of l-alkyl-3,5-dimethyl-piperidines (81) and 3-alkyl-3-azabicyclo[3.3.1]nonanes (82) was made to evaluate the effect of the N-alkyl group on the rate of oxidation and to contrast these two ring systems (70). The maximum factor in the piperidine... 

Bohlmann et al. (118-121) observed that an infrared absorption band between 2700-2800 cm is characteristic of a piperidine derivative possessing at least two axial carbon-hydrogen bonds in antiperiplanar position to the free-electron pair on the nitrogen atom. The possibility of forming an enamine by dehydrogenation can be determined by this test. Compounds which do not fulfill this condition cannot usually be dehydrogenated (50, 122,123). Thus, for example, yohimbine can be dehydrogenated by mercuric acetate,whereas reserpine or pseudoyohimbine do not react (124). The quinolizidine (125) enamines (Scheme 4), l-azabicyclo(4,3,0)-nonane, l-azabicyclo(5,3,0)decane, l-azabicyclo(5,4,0)undecane, and l-azabicyclo(5,5,0)dodecane have been prepared in this manner (112,126). 

Trimethyl-9-azabicyclo[3.3.1 ] nonan-30i-ol Methyl 0i,ai-di(2-thienyl)glycollate... 

A mixture of 1.0 g of 6,6,9-trimethyl-9-azabicyclo[3.3.1 ] nonan-3/3-ol, methyl 0i,0i-di-(2-thienyD-glycollate and 30 mg of metallic sodium is heated at 80°C to 90°C for about 2 hours under reduced pressure. After cooling, ether is added to the reaction mixture. The mixture is extracted with 10% hydrochloric acid. The aqueous layer is alkalified with sodium carbonate and reextracted with ethyl acetate. The extract is washed with water, dried and concentrated to dryness. The residue thus obtained is treated with hydrogen chloride by conventional manner. 2.0 g of the 0i,0i-di-(2-thienyl)glycollate of 6,6,9-trimethyl-9-azabicyclo-(3.3.1 ] nonan-3/3-ol hydrochloride are obtained. Yield 83%. 

C3SH52N2O10S 18409-40-0) see Atropine methonitrate e/ido-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine (C9H1JN2 76272-56-5) see Granisetron methyl azidoacetate... 

The pyrrolizidines and indolizidines are a group of alkaloids that are characterized by the presence of the basic azabicyclo[3.3.0]octane and azabicyclo[4.3.0]nonane frameworks, respectively. These alkaloids exhibit remarkably diverse types of biological activity and have been reported to act as antitumor, hypotensive, anti-inflammatory, carcinogenic, or hepatoxic agents. Various pyrrolizidines and indolizidines have been prepared by 1,3-dipolar cycloaddition.115 Synthesis of these is described in the section 8.2 discussing cycloaddition. 

A wide variety of other photocyclizations have been reported, but only a few of these have any general application. The unsaturated amine 366 undergoes cyclization in cyclohexane to give the 7-azabicyclo[4.3.0]nonan-2-one 367.303 The formation of pyrrolidine derivatives by photocyclization has also been observed in JV-alkyl-2-allylanilines,304 and imidazoles have been obtained by irradiation of 2-amino-1-dialkylaminoanthraquinones.30 5... 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

The reaction of LTMP at 80° with 2,2,6,6-tetramethylcyclohexane (3) to give 4 evidently involves transfer of a 3-methyl of LTMP, since 6 is also formed during the reaction. The minor carbinol (5) of this reaction can be formed in quantitative yield when N-lithio-9-azabicyclo[3.3.1]nonane (7) is used as the base. This base lacks both p-hydrogens and p-methyl groups, but evidently can metalate a methyl group of 3 to form the anion b. The same paper also presents evidence for bridgehead metalation by LTMP. 

Finally, it must be mentioned that phenylselenation of some diolefins may provide a suitable method for the construction of heterocycles containing two phenylseleno groups. For instance, 3 reacts142 with lV-(phenylseleno)phthalimide (NPSP) in the presence of cyanamide (FENCN) to give the regioisomeric 9-azabicyclo[3.3.1]- and 9-azabicyclo [4.2.1]-nonanes, 173 and 174, as the result of a combined process of inter- and intramolecular nucleophilic addition of cyanamide (equation 140). 

Analogously, mixtures of A-alkoxycarbonyl- and iV-tosyl-9-azabicyclo 3.3.11- and [4.2.1]nonanes were obtained by reaction of 3 with carbamates or p-toluenesufonamide in the presence of mercury(II) nitrate followed by in situ demercuration with sodium borohydride (equation 168)171,172. 

Recently, Sugimoto et al. presented a strategy toward the synthesis of tricyclic lactones containing a 2-azabicyclo[3.3.1]nonane skeleton via tandem intra-... 

The derivatives of 2-azabicyclo[3.3.1]nonanes (morphane) (41) can also be used to build the framework of alkaloids with the azocino[4,3-l7]indole fragment. 7-(2-Nitrophenyl)-substituted azabicyclononanone 42 obtained from N-benzylpiperidone-4 (seven stages, total yield (10%)) under the conditions of reductive cyclization has been converted into N-benzylhexahydroazocino [4,3-1 ]-indole 43 (Scheme 10 88T2087). 

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