Synthesis and stereochemistry of some multi methyl-substituted 1,3-dioxanes

Several multimethyl-substituted 1,3-dioxanes [trans-2,4,4,6-tetramethyl (1), r-2,4,4,c-5,t-6-pentamethyl- (2), r-2,4,4,t-5,t-6-pentamethyl (3) and trans-2,4,4,5,5,6-hexamethyl-1,3-dioxanes (4)] with 2,6-trans-disubstitution has been prepared via the Grignard reaction of the corresponding axial 2-methoxy-1,3-dioxanes. Inspection of their C-13 NMR chemical shifts in respect of different substituent effects showed that 1 and 3 attain exclusively the 1,4-twist form whereas 2 and 4 still favor clearly the chair form due to the very strong steric interaction caused by the pseudo axial methyl groups at position 5. We also manage to equilibrate 1 and its cis-epimer (5) although less than 1% of 4 was present at equilibrium. Thus only -Delta G degrees = 12.9 +/- 0.5 kJ mol(-1) could be given and it compares well with some literature values. Since the conformational energy of 4-axial methyl group in 5 is 12.2 kJ mol(-1) the Delta H(1,4-CT) is equal to 25 kJ mol(-1) again in good agreement with an earlier estimate.