Catalytic Asymmetric Route to Enantioenriched Cyclic Allenes and a Nickel-catalyzed Dynamic Kinetic Resolution of Cyclic Allenes

生成对映体富集的环状八烯的催化不对称路线以及环状八烯的镍催化动态动力学拆分

基本信息

批准号：
10218217
负责人：
Rachel Knapp
金额：
$ 3.78万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2022-06-30
项目状态：
已结题

项目摘要

Highly functionalized heterocycles are important motifs in pharmaceuticals. Although there have been many noteworthy advances in synthetic organic methodologies, the efficient synthesis of enantioenriched heterocycles remains an ongoing challenge in the field. The primary goal of this proposal is to access enantioenriched compounds utilizing heterocyclic allene intermediates. Cyclic allenes have been avoided historically due to their high reactivity. However, the proposed research seeks to harness cyclic allenes for the efficient construction of complex scaffolds. Moreover, the inherent chirality of cyclic allenes opens opportunities to access enantioenriched adducts. The manipulation of heterocyclic allenes in a controlled manner would offer new tactics for the synthesis of enantioenriched, complex heterocycles. This proposal includes two strategies that utilize heterocyclic allenes to generate enantioenriched products. In Aim 1, an asymmetric, catalytic synthesis of oxacyclic allene precursors will be optimized to ultimately enable facile access to enantioenriched oxacyclic allenes. An investigation into the ability to transfer stereochemical information from the allene precursor all the way to enantioenriched cycloadducts will be described. The studies in Aim 2 will allow access to enantioenriched heterocycles via a transition metal- catalyzed dynamic kinetic resolution of heterocyclic allenes. Optimization of the transformation and exploration of the substrate scope is described. These studies would ultimately demonstrate the utility of strained cyclic allenes in asymmetric synthesis.

高功能化的杂环是药物中的重要基序。虽然有许多值得注意的合成有机方法的进步，有效地合成对映体化的综合杂环仍然是该领域的持续挑战。该提议的主要目标是访问利用杂环艾琳中间体的映体化合物。避免了循环艾伦斯从历史上看，由于它们的反应性很高。但是，拟议的研究试图利用循环艾伦斯复杂脚手架的有效构造。此外，循环艾伦的固有手性打开了机会访问对映基化的加合物。以受控方式对杂环艾伦进行操纵构成对映体，复杂的杂环的新策略。该提案包括两种利用异环艾伦来生成对映体化的策略产品。在AIM 1中，将优化氧化艾烯前体的不对称催化合成至最终使富含对映体的氧化甲烷可轻松进入。调查转移能力来自Allene前体的立体化学信息一直到对映体的环载量描述。 AIM 2中的研究将允许通过过渡金属进入对映射的杂环 - 催化的杂环艾伦的动态动力学分辨率。变换和探索的优化描述了底物范围。这些研究最终将证明循环紧张的效用不对称合成中的艾伦。