New Cycloaddition Strategies for Five-Membered Ring Synthesis

这项建议的总体目标是开发新的环加成技术来制备五元环。在Diels Alder反应和其他广泛使用的环加成方法中非常有效的简单原料类型，如烯烃、炔烃和二烯，通常不能直接结合以允许组装奇数环。这项提议旨在为现有可用转换的这一现有限制制定几个解决方案。第一个目标涉及开发一种新的策略，允许两个简单的偶数pi体系在催化环加成反应中结合，生成五元环产品，同时起始材料进行净两电子还原。其次，简单的环丙基酮和亚胺将用于开环加成反应，即从环丙烷安装一个三碳单元到一个五元环产品中。最后，将开发两个新的反应，涉及两个简单的两原子pi系统与一个碳单元或一个硅单元的环加成，以合成碳环或硅环五元环。除了新的环加成方法，该提案还将开发一种新的炔烃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限制。有了这个奖项，有机和高分子化学计划再次支持密歇根大学化学系约翰·蒙哥马利教授的工作。虽然已经开发出强大的方法来合成含有六元环的分子，但合成五元环的一般方法一直落后。蒙哥马利教授和他的学生正在发现从根本上说新的环加成过程，这些过程提供了获得这些较小尺寸环的途径，这些环普遍存在于具有生物活性或药理活性的化合物中，以及许多其他学科感兴趣的化合物中，包括材料科学和分子电子学。蒙哥马利教授还将参与一项关于一个大型多机构项目的可行性研究，该项目旨在吸引和指导代表人数不足的群体的学生。

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.