Mechanistic Studies of Halenium-Alkene Additions for Chemical Catalysis

该奖项由化学系化学催化计划资助，授予密歇根州立大学Babak Borhan教授，使不对称卤代官能化的机械分析和发现成为可能。通过探索这些过程的机理细微差别，这项研究将加速设计和发现新的卤化反应、改进的催化剂和通往复杂结构的有效途径。该项目将有机合成、光谱技术、同位素分析和量子化学模型结合在一起，为博士生提供了一个在分析、有机化学和物理化学领域接受培训的绝佳机会。与不同背景的PI合作，进行这项研究的化学研究生、本科生(UG)和暑期高中生(HS)除了必须掌握多种实验室技术外，还学习批判性思维和沟通技能。Borhan教授的发现是有机催化剂(DHQD)2PHAL促进卤素手性传递到烯烃和相关底物，打开了反应的大门，这些反应在一般性和实用性上类似于最近的不对称环氧化、二羟基化和氢化，这些都是有机合成的里程碑式工具。这些新颖的立体控制的卤化反应使人们能够快速获得具有生物和药物重要性的复杂结构。机理研究使用动力学分析；溶剂效应调查；同位素标记以追踪立体化学并通过动力学同位素效应确定关键的速率和产物决定步骤；设计和合成电子可调节的底物和卤化剂；多核和多维核磁共振技术用于探测分子相互作用；以及详细的量子化学模拟以指导和解释实验。分子建模和机理探索也得益于詹姆斯·杰克逊教授的参与，他是一名物理有机化学家，在计算、催化和绿色化学领域具有丰富的经验，是这项拨款的合作伙伴。

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.