Catalysis in Dynamic Systems: Control within Molecular Reaction Networks

Life as we know it is based on complex networks of biochemical reactions that constantly interact within large dynamic systems. The field of systems chemistry uses chemical models to study how reaction networks – and thereby life – function on a molecular level. This thesis focuses on different aspects of catalysis in dynamic systems of interconnected reversible reactions. Using the reversible imine bond as the primary tool, such dynamic systems have both been used for catalyst screening and to achieve emergent systemic behavior. First, constitutional dynamic chemistry was used to discover catalysts within large mixtures. A method based on dynamic deconvolution was used to identify a bifunctional organocatalyst for the Morita-Baylis-Hillman (MBH) reaction from a mixture of 16 candidates. A second method involved amplification of an organometallic intermediate from a dynamic system and was used to discover directing group/metal combinations for C-H functionalization of aldehydes. Subsequently, the consequences of integrating the catalyst itself into a dynamic system were investigated. Here, dynamic covalent catalysts formed reaction networks with programmable systemic properties. Using the MBH reaction and dynamic imine exchange, catalysts capable of self-resolution, feedback regulation and error-correction were constructed. Finally, selective catalyst systems for activation of new reversible covalent behavior for imines were developed. H-bond catalysis was used to facilitate imine exchange under mild conditions, and transamination was introduced as a dynamic covalent linkage that could change the directionality of the imine bond. The research in this thesis should both be applicable for catalyst discovery within synthetic organic chemistry, for understanding connectivity in chemical and biological systems as well as for studies of the origin of life on earth and the evolution of simple molecules into advanced systems with emergent functionality.QC 20170216