Theoretical study of solvent effect on diastereoselectivity in protonation of methyl 3-fluorobutanoate anion by ethanol: Application of the 3D-RISM theory

The H/D exchange reaction of carbonyl compounds is one of the most important reactions in synthetic organic chemistry as well as in biochemistry. In the present study, 3D-RISM theoretical model has been used to examine the high diastereoselectivity and the solvent effects in the protonation of methyl 3-fluorobutanoate anion by ethanol. The 3D-RISM analysis along the IRC coordinates clearly suggested that not only solvent molecules stabilize the reaction system throughout the entire reaction process, but also the stabilization mechanism operates so as to minimize the energy difference between the two diastereofacial processes. The energy difference between the two diastereofacial processes in the ground state carries directly through the transition state. This strongly suggested that diastereoselectivity of the protonation reaction should be determined essentially in the ground state. Confirmative evidence for this conclusion was obtained by the EFOE (exterior frontier orbital extension model) model.