Base-induced isomerisation of epoxide 13 gives an azanortricyclanol 17 which is a precursor for a novel free-radical induced rearrangement to 6-substituted 2-azabicyclo[2.2. I]hept-5-enes 28-31. Compound 31 undergoes selective exo-face hydrogenation to give the 6-substituted 2-azabicyclo[2.2. I]heptane 33 (structure confirmed by X-ray crystallographic analysis). Deprotection of 33 gives epibatidine analogue 2 which has been shown to bind with high affinity at rat brain nicotinic acetylcholine receptors.
|Number of pages||9|
|Journal||Journal of the Chemical Society: Perkin Transactions 1|
|Publication status||Published - 2001|
Hodgson, D. M., Maxwell, C. R., Wisedale, R., Matthews, I. R., Carpenter, K. J., Dickenson, A. H., & Wonnacott, S. (2001). 6-Substituted 2-azabicyclo[2.2.1]hept-5-enes by nitrogen-directed radical rearrangement: Synthesis of an epibatidine analogue with high binding affinity at the nicotinic acetylcholine receptor. Journal of the Chemical Society: Perkin Transactions 1, (23), 3150-3158. https://doi.org/10.1039/b107414h