1-Azabicyclo alkanes

The stereochemical aspect of these cyclizations has been investigated. They have been found to be non-stereoselectives.342 On the contrary, diastereoselective 1-azabicyclo-alkanes have been prepared in the same way, the stereochemistry being dependent upon the size of the ring formed, namely, 1,5-cis and 1,6-trans.343 This methodology has been applied to the synthesis of ( )-isoretronecanol, ( )-epilupinine344 and retronecanol.345... 

In comparison to other 1-azabicyclo-alkanes quinuclidine is characterized by high symmetry and by insignificant strain in the cyclic system. 

In an investigation of the intramolecular Schmidt reaction of alkyl azides for the synthesis of benzo-fused l-azabicyclo[m.n.O]alkanes, the perhydrobenzo[/]pyrrolo[l,2-a] azepine 29 was prepared in 72% yield . 

Versions of these aminocyclopropanations of terminal alkenes can also be applied intramolecularly. Terminally ethenyl-substituted N,N-dialkylcarboxamides such as 67 yield l-(dialkylamino)bicyclo[n.l.O]alkanes such as 68, while (w-alkenylamino)carboxa-mides such as 69 and 71 lead to 1 -alkyl-2-azabicyclo u.l.0]alkanes such as 70 and 72 (Scheme 11.20) [86,118], and N-allylamino acid N,N-dialkylamides furnish bicyclic diamines (see below). 

The Rh-BIPHEPHOS-catalyzed cyclohydrocarbonylation has also been successfully applied to the rapid synthesis of a variety of l-azabicyclo[X.Y.O]alkane amino acids, which serve as conformationally restricted dipeptide surrogates for enzyme inhibitors and receptor antagonists, directly from dehydrodipeptide substrates (Scheme Reaction... 

Conveniently N-protected 2,2/-bis(trimethylsilylmethyl)pyrrolidine, -piperidine and -azepane were prepared and reacted with phenylvinylsulfone in the presence of silver fluoride (2 equiv.). The X-azabicyclo[m.2.1]alkane framework in each case is obtained in good to excellent yields. Being very efficient, this technique provides a new strategy to synthesize tropinone, an important member of the tropane class of alkaloids.451... 

The use of another type of bis(trimethylsilylmethyl)amine leads to the synthesis of l-azabicyclo[m.3.0]alkanes also present in the skeleton of a number of alkaloids as trachelanthamidine, isoretronecanol, and tashiramine.447 451... 

Pandey, G. and Devi Reddy, G. (1992) Stereoselectivity in the cyclisation of photoinduced electron transfer (PET) generated cyclic a-amino radicals first general stereoselective entry to 1-azabicyclo (m n o) alkane systems. Tetrahedron Letters, 33, 6533-6536. 

Bicyclic aziridines 17 with a l-azabicyclo[n.l, 0]alkane framework can also be subjected to ring opening with either hydrogen fluoride or the hydrogen fluoride-pyridine complex to give 3-fluoro-l-azacycloalkanes 18. ° ° ... 

Glushkov VA, Stryapunina OG, Dolzhenko AV et al (2009) Synthesis and antiaggregant and antihypotensive activity of benzo-annelated azabicyclo[m.n.0]alkanes. Pharm Chem J 43 245-248... 

Gillaizeau-Gauthier, I., Royer, I, and Husson, H.-P. 2002. Toward an asymmetric general access to azabicyclo[w.2.1]alkanes according to the CN(i ,S) method. EurJ Org Chem 1484-1489. 

Pandey, G., Laha, J.K., and Lakshmaiah, G. 2002. Stereoselective construction of X-azabicyclo[ i.2.1]alkanes by [3+2]-cycloaddition of non-stabilized cyclic azomethine ylides synthesis of enantiopure constrained amino acids and formal total synthesis of optically active epibatidine. Tetrahedron 58, 3525-3534. 

Gosselin, E, and Lubell, W.D.. An olefination entry for the synthesis of enantiopure a,co-diaminodi-carboxylates and azabicyclo[X.Y.0]alkane amino acids. 7. Org. Chem.. 63. 7463. 1998. 

Pearson, W. H. Fang, W. Synthesis ot Benzo-Fused 1-Azabicyclo[/n.n.0)alkanes via the Schmidt Reaction A Formal Synthesis of Gephyrotoxin J. Org. Chem. 2000, 65, 7165-7174. 

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