On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes.
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.
Gregersen
Anette
A
Department of Chemistry, University of Aarhus, Denmark.
Pedersen
Christian Marcus
CM
Jensen
Henrik Helligso
HH
Bols
Mikael
M
D000588:Amines / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D004583:Electrons; D006536:Heptanes / Q000138:chemical synthesis / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry*; D015394:Molecular Structure
D000588:Amines; D001372:Aza Compounds; D006536:Heptanes; D006878:Hydroxides