Transannular Interaction in 3-Heterobicyclooctanes, Implications for the Mechanism of Biotin Action

Article abstract of DOI:10.1021/jo00268a035

endo(exo)-7-(Tosyloxy)-3-thiabicyclo<3.3.0>octane and endo(exo)-7-(tosyloxy)-3-oxabicyclo<3.3.0>octane were synyhesized from the corresponding 3-heterobicyclo<3.3.0>octan-7-ones.For exo-7-(tosyloxy)-3-thiabicyclo<3.3.0>octane, solvolysis in methanol resulted in a retention/inversion ratio of 2.3.The entropy of activation was found to be ca. -39 J/mol K in 80percent ethanol/water.The three other tosylates underwent substitution with exclusive inversion, entropies of activation ranging from -49 to -54 J/mol K.These results are interpreted in terms of a weak transannular sulfur-C7 interaction.In exo-7-(tosyloxy)-3-thiabicyclo<3.3.0>octane, anchimerically assisted displacement of the tosyloxy group gives rise to the retention product.Attempts to observe the 5-methyl-1-thioniatricyclo<3.3.0.0^3,7>octane cation by low-temperature 1H and 13C NMR failed.Coordination to the ring heteroatom instead of ionization was found upon addition of antimony pentafluoride to 3-thiabicyclo<3.3.0>octan-7-one, exo-7-chloro-7-methyl and endo-7-methoxy-7-methyl-3-thiabicyclo<3.3.0>octane, the endo-7-hydroxy-7-methyl derivative gave complex product mixtures.Alkylation of 3-thiabicyclo<3.3.0>octan-7-one with triethyloxonium tetrafluoroborate yielded exclusively the S-ethylated product. 1',3'-N-Bis(phenylsulfonyl)biotin methyl ester was found to coordinate antimony pentafluoride to the ester carbonyl group.From the whole of the data it is concluded that sulfur transannular interaction cannot play a significant role in the mechanism of biotin action.