EXPERIMENTAL AND AM1 CALCULATIONAL STUDIES OF THE DEPROTONATION OF BICYCLO[2.2.2]OCTANE-2,5-DIONE AND BICYCLO[2.2.2]OCTANE-2,6-DIONE - A STUDY OF HOMOCONJUGATION, INDUCTIVE, AND STERIC EFFECTS ON THE RATES ANDDIASTEREO-SELECTIVITIES OF ALPHA-ENOLIZATION

The kinetics of NaOD-catalyzed H/D exchange (enolization) at C3 alpha to the carbonyl group of bicyclo[2.2.2]octane-2,5-dione (1) and bicycl o[2.2.2]octane-2,6-dione (2) have been studied in 60:40 (v/v) dioxane- D2O at 25.O degrees C. The second-order rate constants for exchange ar e (9.7 +/- 1.5) x 10(-1) and (3.4 +/- 1.2) x 10(-5) L mol(-1) s-1 for 1 and 2, respectively. Thus, 1, exchanges 76 times faster than bicyclo [2.2.2]octan-2-one (3) (k = (1.27 +/- 0.02) x 10(-2) L mol(-1) s(-1)), but the 2,6-dione 2 unexpectedly is much less reactive (2.7 x 10(-3)) than the monoketone. Unlike the large exo selectivity of 658 observed in the case of bicyclo[2.2.1]heptan-2-one, small and opposite selecti vities, exo (1.2) for 1 and endo (2.1) for 2, are found for the isomer ic [2.2.2] ketones. The results indicate that the incipient enolate of 1 is stabilized by a polar effect of the beta carbonyl group at C5, n ot by homoconjugation. The source of the surprising low reactivity of 2 is unknown at this stage. The small diastereoselectivities, exo (1.2 ) for 1 and endo (2.1) for 2, correlate with relative energies of the diastereomeric pyramidal enolates calculated with AM1.