2004

AlkaloidsU 0600 Stereoselective Synthesis of Conformationally Constrained Tropane Analogues:

6-Chloro-2,5-diazatetracyclo[8.5.0.02,13.04,9]pentadeca-4,6,8-triene-11-one and 6-Chloro-2,7-diazatetracyclo[8.5.0.02,13.04,9]pentadeca-4,6,8-triene-11-one. — Two conformationally constrained homologues of epibatidine, title compound (VII) and its 2,7-diaza isomer, are synthesized employing a palladium-catalyzed intramolecular α-arylation to generate the tricyclic compounds. The α-arylation reaction proceeds regioselectively and the reversed regioselectivity observed for (VI) in the intramolec-ular C—C coupling reaction is likely due to the thermodynamic preference of the sys-tem to form the 6-membered ring of (VII) over the less stable 7-membered ring. The constrained derivatives display very poor binding affinity for neuronal nicotinic acetyl-choline receptors which may be due to the conformational or substituent effects intro-duced by the carbonyl group. — (CHENG, J.; XU, L.; STEVENS, E. D.; TRUDELL*, M. L.; IZENWASSER, S.; WADE, D.; J. Heterocycl. Chem. 41 (2004) 4, 569-574; Dep. Chem., Univ. New Orleans, New Orleans, LA 70148, USA; Eng.) —H. Hoennerscheid

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