EXPERIMENTAL AND THEORETICAL-STUDIES OF ACID-CATALYZED O-18 EXCHANGE-RATES OF CONFORMATIONALLY RIGID KETONES - IS THE ANTIPERIPLANAR EFFECTIMPORTANT

The relative rates for the acid-catalyzed addition of (H2O)-H-18 to th e carbonyl group of the conformationally fixed bridged biaryl ketone, 1, and several derivatives bearing methyl, chloro, and methoxy substit uents in axial-like and equatorial-like orientations have been measure d. The effects of axial-versus diaxial-like methyl and chloro substitu ents produce rate decreases which are consistent with the antiperiplan ar (hyperconjugative) interaction proposed by Cieplak; however, the ne gligible influence of a methoxy group when antiperiplanar is not consi stent. 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 met hyl or chloro substituent (synperiplanar to the nucleophile) and a sma ll one for the second (antiperiplanar) substituent. An axial methoxy c an stabilize the transition state by hydrogen bonding when syn but can only exert the observed small steric retardation in the transition st ate involving antiperiplanar attack.