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 and diastereoselectivities of α enolization

• Published in: Canadian journal of chemistry 1995-03, Vol.73 (3), p.460-463
• Main Authors: Werstiuk, Nick Henry, Roy, Chandra Deo
• Format: Article
• Language: English
• ISSN: 0008-4042; 1480-3291
• DOI: 10.1139/v95-060

The kinetics of NaOD-catalyzed H/D exchange (enolization) at C3 α to the carbonyl group of bicyclo[2.2.2]octane-2,5-dione ( 1 ) and bicyclo[2.2.2]octane-2,6-dione ( 2 ) have been studied in 60:40 (v/v) dioxane-D 2 O at 25.0 °C. The second-order rate constants for exchange are (9.7 ± 1.5) × 10 −1 and (3.4 ± 1.2) × 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) × 10 −2  L mol −1 s −1 ), but the 2,6-dione 2 unexpectedly is much less reactive (2.7 × 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 selectivities, exo (1.2) for 1 and endo (2.1) for 2 , are found for the isomeric [2.2.2] ketones. The results indicate that the incipient enolate of 1 is stabilized by a polar effect of the β carbonyl group at C5, not 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. Keywords: enolization, bicyclo[2.2.2]octane-2,5-dione, bicyclo[2.2.2]octane-2,6-dione, AM1, thermodynamic acidities.