The synthesis of novel benzomorphan analogues: a new intramolecular acid-catalysed aldol route to benzannelated bicyclo[3.3.1]nonane derivatives. X-Ray molecular structure of 8-hydroxy-1-methoxytricyclo[7.3.1.02,7]trideca-2,4,6-trien-10-one

Abstract

Novel benzomorphan analogues are described in which the piperidine ring is replaced by an aminocyclohexane ring. The key synthetic intermediate, benzannelated bicyclo[3.3.1]nonane derivative (12), is prepared by an efficient three-step synthetic route based on the addition of 2-lithiobenzaldehyde ethylene acetal to cyclohexane-1,4-dione monoethylene acetal followed by methylation, acid-catalysed deprotection, and in situ intramolecular aldol condensation. The stereospecificity of the aldol cyclisation to give intermediate (12) is noteworthy. Preliminary studies of the synthetic potential of the methodology for the preparation of derivatives with varying oxidation and substitution patterns are also described.