Diverse Behaviour of C-3 Enolates Derived from Configurationally Isomeric Trimethyl 1-Methylcyclohexane-1,2,3-Tricarboxylates

Configurational relationships among three, A, B and C, of the four possible isomers of trimethyl 1-methylcyclohexane-1,2,3-tricarboxylate imply that A and C should form a common C-3 enolate. While methylation of tritylsodium-formed A C-3 enolate gives one of the two possible meso forms and B C-3 enolate gives the racemic product, C does not form an enolate. ¹H NMR-assigned preferred conformations of A and B show that their C-3 enolates form Na⁺ complexes stabilized by the C-1 syn, axial ester group, while the C-1 methyl in C hinders removal of the C-3 proton, thus preventing enolate formation. Early treatment of A enolate with methyl iodide leads to one of two possible meso methylated products, while late treatment gives the racemic form, also a product of B methylation. A gradual rise in C/A ratio is seen on protonating A enolate, though only a ring flip is involved, this phenomenon is attributed to the intervention of a slow Na⁺ deand re-complexation process. A unified explanation emerges under the premise that while the methylating agent approaches the enolate from the non-hindered face anti to Na⁺, the proton is guided by Na⁺ towards syn approach.