Control of stereoselective protonation of enols1,2

A decalyl framework with a siloxy enolic moiety and proximate proton transferring groups was synthesized. On enolate generation with fluoride two competitive reaction modes were possible: (a) intermolecular protonation, and (b) intramolecular proton transfer by the proximate group. Control of the protonation stereochemistry proved possible by varying the proximate group and by changing the acidity of the medium. With the groups -CH2OH, -CH=O, and -CH2OCH2OCH3 as the proximate groups, only intermolecular proton transfer was observed with no dependence on acidity. In contrast, with -COO- and COOH, only intramolecular protonation resulted but again with no dependence on acidity of the medium. In contrast, with -CH2NH2 as the proximate group, intramolecular proton transfer predominated with a dependence on the effective pH of the medium. A kinetic analysis provided a linear-log relationship of the ratio of the two stereoisomers with the medium acidity. The analysis revealed that two acetic acid molecules are involved in providing the proton to the enolate moiety. A theoretical analysis was developed paralleling the experimental results. In the ketonization transition state, the hybridization was shown to be close to sp2 hybridized at the alpha-enolate carbon.