Mechanistic Studies and Method Development in Asymmetric Organocatalysis

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Chiral compounds, which exist as a pair of non-superimposable mirror images (called enantiomers), are the building blocks of all life. Living organisms are comprised of chiral molecules and are therefore sensitive to the chirality of the compounds with which they interact. As a result, chiral compounds are widely used in the manufacturing of pharmaceuticals, agrochemicals, fragrances, flavourings, cosmetics and fine chemicals. The global Chiral Chemicals market was valued at $53,930 million USD in 2020 and is expected to reach $101,350 million USD by the end of 2027, according to the Global Industry Research Report. It is well established that the different enantiomers of a compound can have vastly different biological activities. Many of the chiral compounds produced industrially are required in an enantiomerically pure form (only one of the two enantiomers), as regulatory agencies have recognized that each enantiomer of a compound can have different effects when interacting with biological systems, including the human body. It is an ongoing and pressing challenge to develop robust and reliable processes that produce a single enantiomer of a compound to satisfy the demand for enantiopure chiral chemicals. Asymmetric organocatalysis has emerged as a powerful synthetic methodology that has provided access to a variety of previously unachievable enantioselective transformations, resulting in a diverse array of enantioenriched chiral compounds. Asymmetric organocatalysis employs chiral organic molecules, largely derived from amino acids, to activate another molecule and promote the formation of new bonds in a stereoselective manner. The impact of this work has led to its global recognition as a key synthetic methodology and the awarding of the 2021 Nobel Prize to the founders of the field. The Davis group is working at the forefronts of organocatalysis to develop new catalysts and reactions that will expand the types of enantioselective reactions that can be performed and increase the number of chiral molecules that can be created with this catalytic method. We are focused on addressing standing issues in the field including the development of catalysts that promote photochemical reactions and the installation of new bonds further from the catalyst. We will then apply these methods in the synthesis of biologically significant compounds, demonstrating the strength of these catalytic methods in converting cheap achiral starting materials into high value, industrially relevant enantioenriched chiral compounds. This work will generate catalytic methods that will aid in addressing the current needs of the chiral chemical industry and will produce researchers that are uniquely trained to address the future challenges facing this rapidly growing area of the economy.