Solvent and temperature effect in aldol condensation between the lithium enolate of tert-butyl acetate and 2-phenyl propanal: enthalpy and entropy contribution

An analysis of nucleophilic addition of the lithium enolate of tert-butyl acetate and 2-phenyl propanal in two different solvents, such as THF and n-hexane, revealed the great importance of solvent effect in determining the stereoselectivity. In particular, temperature-dependent measurements of diastereomeric ratio allow the evaluation of diastereoselectivity in terms of differential enthalpy and entropy of activation for this reaction. Either in THF or n-hexane we obtained a predominance of the anti isomer in all temperature ranges, but in THF the diastereoselection is controlled by the differential activation enthalpy, whereas in n-hexane it is the sole differential activation entropy that accounts for the anti predominance.