Experimental and theoretical studies of acid-catalyzed oxygen-18 exchange rates of conformationally rigid ketones. Is the antiperiplanar effect important?

The relative rates for the acid-catalyzed addition of H218O to the carbonyl group of the conformationally fixed bridged biaryl ketone, 1, and several derivatives bearing methyl, chloro, and methoxy substituents in axial-like and equatorial-like orientations have been measured. The effects of axial- versus diaxiallike methyl and chloro substituents produce rate decreases which are consistent with the antiperiplanar (hyperconjugative) interaction proposed by Cieplak; however, the negligible influence of a methoxy group when antiperiplanar is not consistent. Theoretical calculations suggest an unsymmetrical structure for the transition state. On the basis of this structure, the results may be rationalized by a large steric interaction for the first axial methyl or chloro substituent (synperiplanar to the nucleophile) and a small one for the second (antiperiplanar) substituent. An axial methoxy can stabilize the transition state by hydrogen bonding when syn but can only exert the observed small steric retardation in the transition state involving antiperiplanar attack.