Presidential Young Investigator: Application of Group Transfer from Metals to Olefins

埃里克·N·雅各布森博士是由有机合成计划资助的总统青年研究员。他将研究用于有机合成的对映选择性催化剂的开发。非官能化烯烃的氧化将是他将探索的第一个反应。基团转移到前手性烯烃的表面选择性可以通过纯非键相互作用或通过底物预配位限制非对映过渡态的自由度来控制。基于这两个原则正在开发催化系统。设计了一系列手性锰络合物，用于催化高达33%对映体过量的碘代芳烃环氧化分离的和未官能化的烯烃。这些络合物的配体很容易通过手性二胺与水杨醛驱动剂的缩合而制备，从而允许它们的空间和电子性质的系统变化。目前的努力是调整反应中心周围的空间环境，以便将对映体选择性提高到综合有用的水平，并使用观察到的立体化学偏好来绘制烯烃接近中间金属氧物种的轨迹。迄今制备的六种催化剂的结果以及对最有效体系的晶体结构的检查，使人们得以开发出从锰到烯烃的氧原子转移的详细过渡结构。这个模型现在正在通过金属、配体和底物的系统变化来改进；对立体化学具有预测价值的过渡结构的阐明也将提供对氧原子从金属到烯烃转移的一般问题的机械洞察，这是广泛的实验室、工业和生物过程中的重要一步。

Dr. Eric N. Jacobsen is being funded by the Organic Synthesis Program as a Presidential Young Investigator. He will be studying the development of enantioselective catalysts for organic synthesis. The oxidation of unfunctionalized olefins will be the first reaction that he will explore. Facial selectivity in group transfer to a prochiral olefin can be controlled by purely non-bonded interactions or by constraining the degrees of freedom in diastereometric transition states through substrate pre-coordination. Catalytic systems are being developed based on both principles. A series of chiral manganese complexes have been designed which catalyze epoxidation of isolated and unfunctionalized olefins by iodosoarenes with up to 33% enantiomeric excess. The ligands for these complexes are readily prepared by condensation of chiral diamines with salicylaldehyde drivatives, permitting systematic variation of their steric and electronic properties. Current efforts are directed toward tuning the steric environment surrounding the reactive site in order to increase enantioselectivity to synthetically useful levels and to use observed stereochemical preferences to map out the trajectory of olefin approach to the intermediate metal oxo species. The results with six catalysts prepared to date and examination of a crystal structure of the most effective system have allowed a detailed transition structure for oxygen-atom-transfer from manganese to olefin to be developed. This model is now being refined by systematic variation of metal, ligand, and substrate; the elucidation of a transition structure which holds predictive value with regard to stereochemistry will also provide mechanistic insight into the general question of oxygen-atom transfer from metals to olefins, an important step in a wide range of laboratory, industrial, and biological processes.