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 controlle d diacetalation of rac-threitol with alkylaldehydes provided bicyclic, cis- tetraoxadecalin (TOD) ("66") and bi(dioxolanyl) (BDO) ("55") products, show n to be formed in acid-concentration and temperature-dependent ratio. The c onfigurational and conformational isomeric diacetals obtained in four such reactions of substituted aldehydes (RCHO, R = CH3, CH2Cl, CH2Br, CO2CH3) wi th rac-threitol were isolated and characterized. A variable acid-concentrat ion analysis of the equilibrium mixture of products in one such case (R = C H2Br) was performed and provided equilibrium constants and, hence, free-ene rgy differences among these products and their relatively stable protonated intermediates. The latter were rationalized by the unusually high proton-a ffinity calculated for the cis-TOD ("66") form.