On five- vs six-membered diacetal formation from threitol and the intermediacy of unusually stable protonated species

The long known, but hitherto poorly understood, thermodynamically controlled diacetalation of rac-threitol with alkylaldehydes provided bicyclic, cis-tetraoxadecalin (TOD) ('66') and bi(dioxolanyl) (BDO) ('55') products, shown to be formed in acid-concentration and temperature-dependent ratio. The configurational and conformational isomeric diacetals obtained in four such reactions of substituted aldehydes (RCHO, R = CH₃, CH₂Cl, CH₂Br, CO₂CH₃) with rac-threitol were isolated and characterized. A variable acid- concentration analysis of the equilibrium mixture of products in one such case (R = CH₂Br) was performed and provided equilibrium constants and, hence, free-energy differences among these products and their relatively stable protonated intermediates. The latter were rationalized by the unusually high proton-affinity calculated for the cis-TOD ('66') form.