Improving Efficiency in Organic Synthesis via Catalytic Reactions

点击翻译按钮获取中文摘要

The future of organic synthesis requires chemists to discover and develop new reactions and new strategies in order to address the pressing issues of identifying new medicinal agents, agrochemicals and materials while at the same time producing less waste and finding more efficient ways of making the end products. Our research addresses two significant and enduring problems associated with improving efficiency in organic synthesis. We seek to identify new chemical transformations that have the potential to change how we make a product of interest by expanding the repertoire of chemical reactions that are available to the community. Ideally new reactions are simple combinations of the reacting partners so as to minimize waste. Reactions need to be scalable, simple and practical if they are to be widely adopted. In addition we are identifying new strategies to streamline the ways synthesis is conducted in the laboratory so as to reduce the waste associated with operations in a synthetic sequence. We have had success in both these areas for the past decade and have recently made several discoveries that have propelled our work in new and exciting directions. A typical synthetic sequence involves mixing all reagents in a solvent, an extractive work-up and purification of the products (chromatography, distillation, crystallization). This sequence is repeated over and over. At each step there is a considerable amount of waste, often far exceeding the amount of actual product isolated. In contrast Nature has all of the necessary reaction components, catalysts and other ingredients present at the outset and each reaction is conducted in the presence of the all other agents. Typically the catalysts are highly evolved to be very selective for a single substrate and so a clearly defined pathway is observed. Chemists seek a broad substrate scope yet have the high selectivity that Nature achieves. Our studies are designed to show that metal catalyzed reactions developed over the past 40 years can co-exist within a single flask and thereby achieve a sequence of chemical reactions with all the catalysts and substrates present at the outset. Success is measured by avoiding work-up and purification after each step and instead a single work-up and purification is done at the end of the entire sequence. Rather than synergistic catalysis we seek "independent sequential catalysis" where each metal (and its associated ligand) preforms the desired reaction while leaving other reagents and products untouched. These studies tackle fundamental questions including metal-ligand binding when multiple metals and ligands are present (thermodynamic stability) as well as the reactivity of each metal-ligand complex (kinetic reactivity) if more than one species is formed. Our goal is to make molecules of interest to the broader chemical community and show that there are simpler ways to make a desired target of interest.