New Cycloaddition Strategies for Five-Membered Ring Synthesis

该提案的总体目标是开发用于制备五元环的新的环加成技术。在Diels桤木反应和其他广泛使用的环加成方法中如此强大的简单原料类型如烯烃、炔烃和二烯烃通常不能直接联合收割机以允许奇数环的组装。本提案旨在针对目前可用的转换的这一现有限制制定若干解决方案。第一个目标涉及开发一种新的策略，该策略允许两个简单的偶数π系统在催化环加成中联合收割机以产生五元环产物，同时起始材料经历净双电子还原。其次，简单的环丙基酮和亚胺将用于开环环加成，将环丙烷中的三碳单元安装到五元环产物中。最后，将开发两个新的反应，涉及两个简单的两原子π-系统与一个碳单元或一个硅单元的环加成，以制备碳环或硅环五元环。除了新的环加成方法，该提案还将开发一种新的炔和缺电子烯烃的还原偶联程序，以解决目前可用的共轭加成程序的挑战和局限性。有了这个奖项，有机和大分子化学计划正在重新支持密歇根大学化学系的约翰蒙哥马利教授的工作。虽然已经开发了用于合成含有六元环的分子的强有力的方法，但是用于合成五元环的一般方法已经落后。蒙哥马利教授和他的学生正在发现从根本上新的环加成过程，提供访问这些较小尺寸的环，这是无处不在的化合物显示生物或药理活性，以及在各种其他学科，包括材料科学和分子电子感兴趣的许多化合物。教授蒙哥马利还将参与一个主要的多机构计划，旨在吸引和指导学生从代表性不足的群体的可行性研究。

The general goal of this proposal is to develop new cycloaddition technologies for preparing five-membered rings. The types of simple feedstocks such as alkenes, alkynes, and dienes that are so powerful in Diels Alder reactions and other widely used cycloaddition methods typically cannot directly combine to allow assembly of odd-numbered rings. This proposal aims to develop several solutions to this existing limitation of currently available transformations. The first goal involves developing a new strategy that allows two simple even-numbered pi-systems to combine in a catalytic cycloaddition to generate a five-membered ring product while the starting materials undergo a net two-electron reduction. Secondly, simple cyclopropyl ketones and imines will be used in ring-opening cycloadditions that install a three-carbon unit from the cyclopropane into a five-membered ring product. Finally, two new reactions will be developed that involve cycloaddition of two simple two-atom pi-systems with a one carbon unit or one-silicon unit to prepare carbocyclic or silacyclic five-membered rings. In addition to new cycloaddition approaches, the proposal will also develop a novel reductive coupling procedure of alkynes and electron deficient alkenes in order to address challenges and limitations of currently available conjugate addition procedures.With this award, the Organic and Macromolecular Chemistry Program is renewing support for the work of Professor John Montgomery, of the Department of Chemistry at the University of Michigan. While powerful methods have been developed for the synthesis of molecules containing six-membered rings, general approaches for the synthesis of five-membered rings have lagged behind. Professor Montgomery and his students are discovering fundamentally new cycloaddition processes affording access to these smaller-sized rings, which are ubiquitous in compounds displaying biological or pharmacological activity, as well as in numerous compounds of interest in a variety of other disciplines, including materials science and molecular electronics. Professor Montgomery will also be involved in a study of the feasibility of a major multi-institution program designed to attract and mentor students from under-represented groups.