New Cycloaddition Strategies for Five-Membered Ring Synthesis

本提案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如此强大的简单原料类型，如烯烃，炔烃和二烯，通常不能直接组合以允许奇数环的组装。本建议旨在开发几种解决方案，以解决当前可用转换的现有限制。第一个目标是开发一种新策略，允许两个简单的偶数pi系统在催化环加成中结合，生成五元环产物，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品中。最后，将开发两个新的反应，涉及两个简单的两原子pi-体系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外，该提案还将开发一种新的炔和缺电子烯烃的还原偶联过程，以解决当前可用的共轭加成过程的挑战和局限性。有了这个奖项，有机和大分子化学项目再次支持了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却落后了。蒙哥马利教授和他的学生们正在发现新的环加成过程，为这些小尺寸的环提供了途径，这些小尺寸的环在具有生物或药理活性的化合物中无处不在，也在许多其他学科中感兴趣的化合物中，包括材料科学和分子电子学。Montgomery教授还将参与一项可行性研究，研究一个主要的多机构方案，旨在吸引和指导来自代表性不足群体的学生。

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.