Mechanistic Studies of Halenium-Alkene Additions for Chemical Catalysis

该奖项由密歇根州立大学化学系化学催化项目资助，使不对称卤代官能化的机理分析和发现成为可能。通过探索这些过程的机理细微差别，这项研究将加快设计和发现新的卤化反应，改进的催化剂和复杂结构的有效途径。该项目的有机合成，光谱技术，同位素分析和量子化学模型的跨学科组合为博士生提供了一个极好的机会，在分析，有机和物理化学的接口进行培训。与背景非常不同的PI一起工作，化学研究生，本科生（UG）和暑期高中（HS）的学生学习批判性思维和沟通技巧，除了他们必须掌握的多种实验室技术外，Borhan教授发现有机催化剂（DHQD）2 PHAL促进了卤素到烯烃和相关底物的手性传递，这为在一般性和实用性上类似于最近的不对称的反应打开了大门。环氧化、二羟基化和氢化，有机合成的标志性工具。这些新的立体控制的卤环化提供了快速获得复杂的结构的生物和药物的重要性。机理研究采用动力学分析;溶剂效应调查;同位素标记，以跟踪立体化学并通过动力学同位素效应识别关键速率和产物决定步骤;电子可调节底物和卤化剂的设计和合成;多核和多维NMR技术来探测分子相互作用;以及详细的量子化学模拟来指导和解释实验。分子建模和机理探索也受益于詹姆斯杰克逊教授的参与，他是一位物理有机化学家，在计算，催化和绿色化学领域拥有丰富的经验，他是该基金的共同PI。

This award, funded by the Chemistry Division Chemical Catalysis program in the Division of Chemistry to Professor Babak Borhan at Michigan State University, enables mechanistic analysis and discovery of asymmetric halofunctionalizations. By probing the mechanistic nuances of these processes, this research will expedite design and discovery of new halogenation reactions, improved catalysts, and efficient routes to complex structures. The project's interdisciplinary combination of organic syntheses, spectroscopic techniques, isotopic analyses, and quantum chemical models offers an excellent opportunity for doctoral students to be trained at the interface of analytical, organic, and physical chemistry. Working with PIs of very different backgrounds, the chemistry graduate, undergraduate (UG), and summer high school (HS) students who perform the research learn critical thinking and communications skills, besides the multiple lab techniques they must master.Professor Borhan's discovery that organocatalyst (DHQD)2PHAL promotes chiral delivery of halogens to alkenes and related substrates opens the door to reactions analogous in generality and utility to recent asymmetric epoxidations, dihydroxylations, and hydrogenations, landmark tools of organic synthesis. These novel stereocontrolled halocyclizations give rapid access to complex structures of biological and pharmaceutical importance. Mechanistic studies employ kinetic analyses; solvent effect surveys; isotopic labeling both to trace stereochemistry and to identify key rate- and product-determining steps via kinetic isotope effects; design and synthesis of electronically adjustable substrates and halogenating agents; multinuclear and multidimensional NMR techniques to probe molecular interactions; and detailed quantum chemical simulations to guide and interpret experiments. Molecular modeling and mechanistic explorations also benefit from the involvement of Professor James Jackson, a physical organic chemist with substantial experience in computational, catalytic, and green chemistry areas, who serves as a Co-PI on this grant.