β-epimerization and γ-hydrogen abstraction via homoenolate ions

Our objective was to study homoenolate ion formation in ketones with enolizable as well as homoenolizable centers, and in other systems having special structural features. Our substrates were camphor, exo- and endo-isocamphanone, 1-acetoxytricyclane, 2,2,4,4-tetramethylcyclobutanone, norbornan-7-one, cyclodecanone, 2,2,10,10-tetramethylcyclodecanone, cyclododecanone, and 2,2,12-trimethylcyclododecanone. At 185-250°C in KO-t-Bu/t-BuOH for prolonged periods camphor, exo-isocamphanone, and endo-isocamphanone are interconvertible, and the camphor skeleton is favored. The exo ⇌ endo isomerization in the isocamphanones illustrates epimerization at a homoenolic site. The tertiary exo-H in endo-isocamphanone is abstracted and recaptured more readily than is the endo-H in exo-isocamphanone. The homoenolate ion liberated from 1-acetoxytricyclane at room temperature partitions differently in proton capture than does the homoenolate generated from the isocamphanones at 185-250°C. In deuterated medium at high temperature camphor incorporated label at sites other than at C-3 (enolic) and C-6 (homoenolic) as evidenced by species containing d₅ and d₆. Camphor-10-d₁ was synthesized and was shown to lose some of its deuterium when homoenolized in nondeuterated medium, thus establishing that hydrogens at C-10 are exchangeable. After an exchange of camphor in t-BuOD ¹H NMR studies showed that label is incorporated at C-8 and C-10 to comparable extents. Exchange at C-8 reveals that rigid C-H orientation is not a requirement for γ-hydrogen abstraction. D assay of mass spectral fragment ions confirmed that camphor exchanges at C-6, C-8, and C-10 in addition to the enolic site C-3. Exchange at C-6 in camphor proved more difficult than at C-6 in camphenilone, probably because camphor has competitive enolization as well as steric hindrance by methyl groups. At 185°C in KO-t-Bu/t-BuOD, 2,2,4,4-tetramethylcyclobutanone exchanges at the methylene and at the methyl positions, but much of the ketone is cleaved to 2,2,4-trimethylpentanoic acid. When similarly treated, norbornan-7-one undergoes α-bridgehead exchange but no homoenolic exchange; most of the ketone is cleaved to cyclohexanecarboxylic acid. Cyclodecanone and cyclododecanone undergo enolic exchange (and some loss, probably by aldol condensations) but there is no homoenolic exchange or product that would indicate transannular interactions in these medium-ring ketones. Cyclodecanone was tetramethylated by repeated alkylations with NaNH₂/CH₃I, but cyclododecanone could only be trimethylated. These methylated ketones incorporated deuterium slightly at homoenolic sites.