Development of Asymmetric Oxidation Reactions Catalyzed by Guanidinium-bisurea Bifunctional Organocatalysts Utilizing Computational Methods

Organocatalysis has become widely used since the early 2000s as a third type of catalysis in addition to the two types of catalysis, metals and enzymes, and the Nobel Prize in Chemistry was awarded in 2021 for its pioneering achievements. In organocatalytic reactions, stereoselectivity is often controlled by the cooperative action of weak interactions such as hydrogen bonding and dispersion interactions, and it is extremely difficult to elucidate the stereocontrol mechanism from experimental perspectives. On the other hand, recent advances in computational chemistry have made it possible to deeply understand transition state and clarify important roles in controlling the stereoselectivities in organocatalytic reactions. Furthermore, the findings computationally revealed can provide guidelines for the design of new reactions and catalytic structures. Herein, we describe asymmetric oxidation reactions using conformationally flexible bifunctional guanidine-bisurea organocatalysts developed by us and theoretical analysis of the transition states of these reactions. We also discuss the development of novel catalytic reactions and catalyst designs based on the obtained transition state models.