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.

高度功能化的杂环是药物中的重要基序。虽然已经有在有机合成方法学、对映体富集的有效合成等方面取得了许多值得注意的进展杂环化合物仍然是该领域持续的挑战。该提案的主要目标是访问利用杂环丙二烯中间体的对映体富集化合物。避免了环状丙二烯历史上由于其高反应性。然而，拟议的研究旨在利用环状丙二烯高效建造复杂的脚手架。此外，环丙二烯固有的手性带来了机会获得对映体富集的加合物。以受控方式操纵杂环丙二烯将提供合成对映体丰富的复杂杂环的新策略。该提案包括两种利用杂环丙二烯生成对映体富集的策略产品。在目标 1 中，将优化氧杂环丙二烯前体的不对称催化合成，以最终能够轻松获得对映体富集的氧杂环丙二烯。转移能力调查从丙二烯前体一直到对映体富集的环加合物的立体化学信息将被描述的。目标 2 中的研究将允许通过过渡金属-获得对映体富集的杂环。杂环丙二烯的催化动态动力学拆分。优化转型探索描述了底物范围。这些研究最终将证明应变循环的实用性不对称合成中的丙二烯。