Theoretical Study On The Mechanism Of Organic Additives In Proline - Catalyzed Asymmetric Reaction

In recent years, organocatalysis has attracted extensive attention in various fields.Especially, it was found that water, acid, base and other small molecule additives would play a crucial role on product stereoselectivity in the organocatalytic process. In this paper, density functional theory is used to give theoretical support for above mentioned experimental phenomena.First, quantum mechanical calculations have been performed to study the equilibrium and relative stability among iminium ion, oxazolidine, and enamine in the proline-catalyzed reactions under base-free and base-present conditions. The results confirmed that the tautomeric equilibrium among these species can be tuned by the basic additives.Second, three effective stereodetermining transition state models are used to explain the reversal of enantioselectivity at the present of DBU in amination with propanal as reactants and examined at the SMD/mPW1K/6-31+G** computational level.Calculations give the reason is DBU can alter the asymmetric induction strategy in the stereodetermining step. The activation strain analysis has been employed to explain the stereoselectivity associated with different models.Third, the reverse diastereoselectivities in the cyclic and acyclic ?- and ?- amino acids-promoted Mannich reactions have been satisfactorily explained by the the SMD/M06-2X/6-31G** computational level. The activation strain analysis has been used to account for the selectivity-switching for these selected bifunctional catalysts.Lastly, the reverse stereoselectivities in proline-catalyzed aldol reaction induced by two kinds of TBD-derived guanidinium salt with anion(BPh4-and BF4-) are explained by the MPW1K/6-31G* computational level.