Theoretical Studies On The Mechanisms Of Asymmetric Reactions Catalyzed By Chiral Tertiary Amine-Thioureas Or Rhodium

Organocatalysis and metal-catalysis are the two most important methods in the field of catalytic asymmetric synthesis. More and more chiral compounds are synthesized by catalytic methods in industry. Thus, studies on catalytic asymmetric synthesis including experimental studies and theoretical investigations are of great significance. In this thesis, the mechanisms of the two kinds of reactions have been investigated by the density functional theory(DFT). The main contents of this thesis contain two parts as follows:1. Computational studies have been performed to elucidate the activation mechanism of the Michael addition reactions containing bifunctional tertiary amine–thioureas and isatylidene malononitriles by density functional theory(DFT) calculations at the B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level of theory. Results showed a difference of 6.47 kcal/mol between M1-O and M1-N, which suggests that M1-O is more stable energetically. This activation model accelerates the nucleophilic attack of dimethyl phosphite on isatylidene malononitrile. Besides, when isocyanoacetate acts as the nucleophile, the same activation model is also observed. As a result, it is the carbonyl group of isatylidene malononitriles, instead of the malononitrile moiety, that plays a dominating role in the activation of the electrophile by the catalysts. The predicted mechanism also successfully explains the experimentally observed enantioselectivity.2. The origin of the enantio- and regio-selectivity of ring opening reaction of oxabicyclic alkenes catalyzed by rhodium/Josiphos was investigated computationally. Density functional theory(DFT) calculations at the level of M06-2X/6-311+G(d,p)-LANL2DZ//M06-2X/6-31G(d)-LANL2 DZ predict a 98% ee for the enantioselectivity and only the 1,2-trans product as one regio- and diastereomer, in excellent agreement with experimental results. We have found that the solvent tetrahydrofuran(THF) plays a key role in assisting nucleophilic attack. Orbital composition analysis of the LUMO and the NPA atomic charges calculations were conducted to probe the origins of the regioselectivity. The orbital composition analysis reveals two potential electrophilic sites of the Rh–π-allyl intermediate M3 and the NPA atomic charges demonstrate that Cα carry more positive charges than Cγ, which suggests that Cα is the electrophilic site.