Conceptual development: modulating and utilizing intrinsic reactivity

Obiettivo

"This project focuses on fundamental principles of organic reactivity. Achieving broad manipulable selectivity in catalysis is often hindered by limited understanding of the mechanistic generality across various systems. This concept-driven project will offer a new way of thinking, starting by revealing whether each selectivity pattern is incidental on its own or systematic across a family of reactions. Between competing pathways at the transition state (TS), a very under-explored aspect is that each pathway has a distinct sensitivity to changes in the kinetic-thermodynamic relationship—how much can a given change in reaction free energy impact reaction rates. Adjusting the thermodynamic driving force can alter the differences in energy discrimination at the TS between competing paths, thereby increasing and even switching selectivity. The difference in this sensitivity between competing pathways is crucial in determining how responsive the selectivity is to thermodynamic changes. This sensitivity has not been treated as an adjustable variable in targeted modulation, nor has it been utilized as a design principle in catalytic reactions. This project aims to develop a framework that systematically modulates such sensitivity. We work in both directions, simultaneously instantiating the overarching concepts with concrete examples of common organic reactions and deriving rational reaction designs from them, converging the two into a cohesive framework. The focused conceptual framework is relevant in a virtually unlimited number of chemical systems, which offers a ""deductive"" complementarity to many other research programs. The understanding gained could fundamentally alter strategies for selectivity manipulation in small-molecule catalysis and guide practical advancements in areas such as copolymerization. Though conceptually ambitious, the project uses established standard physical organic approaches, making it methodologically highly feasible.

"