Abstract
Two stereoisomeric 2,3,5,6-tetrahydroxyazabicyclo[2.2.1]heptanes were synthesised and their base strengths determined. The 2,3,5,6-exo-isomer 1 and the 2,3-exo-5,6-endo-isomer 2 were prepared from the Diels-Alder adduct of Boc-pyrrole and tosylacetylene by a route involving osmium catalyzed dihydroxylation and protection, tosyl group reduction and repeated dihydroxylation. Deprotection gave 1, while 2 was obtained by conversion of the diol into the ditriflate, followed by nucleophilic inversion with KNO(2) and deprotection. Synthesis of the 2,3,5,6-endo-isomer by a similar strategy was attempted but failed. The pK(a) of 1 and 2 was determined to be 7.0 and 6.4 respectively. This means that the change in base strength as a result of stereoisomerism of an OH is smaller in the [2.2.1]-azabicyclic system than in the piperidines. This is explained by a difference in charge-dipole interactions in the two systems.
| Original language | English |
|---|---|
| Journal | Organic & Biomolecular Chemistry |
| Volume | 3 |
| Issue number | 8 |
| Pages (from-to) | 1514-1519 |
| Number of pages | 6 |
| ISSN | 1477-0520 |
| DOIs | |
| Publication status | Published - 2005 |
| Externally published | Yes |
Keywords
- Amines
- Aza Compounds
- Cyclization
- Electrons
- Heptanes
- Hydroxides
- Molecular Structure