One-Carbon Bridge Stereocontrol in Robinson Annulations Leading to Bicyclo[3.3.1]nonanes

The one-carbon bridge stereochemistry of bicyclo[3.3.1]nonane products formed in the Robinson annulation reactions of 2-substituted cyclohex-2-enones was investigated. In contrast to previous reports, it was found that the major diastereomer formed places the one-carbon bridge substituent anti to the β-keto ester/amide unit introduced in the Robinson annulation. This stereoselectivity appears to be kinetically controlled. In the case of a β-keto amide product derived from carvone, it was demonstrated, through base-catalyzed epimerization, that thermodynamic control favors the syn isomer.