Enantioselective Pd-Catalyzed Reactions Enabled by Imidazole-based Chiral Biaryl Ligands

在化学系化学合成项目的支持下，佛罗里达大学的Aaron Aponick教授将研究新的钯催化反应，旨在改善用于农业、清洁能源技术和人类健康的化合物的制造。该研究的一个突出特点是，它将能够产生所谓的“光学活性形式”的产物，其中分子的“对映体结构”（大约相当于手性的概念）占主导地位。该项目更广泛的影响将扩展到为学生提供实践培训，为现代劳动力做好准备。此外，将通过“化学日，分子狂热”的教育活动，对科学、技术、工程、数学（STEM）领域的公众进行宣传。总的来说，这个活动很受孩子们的欢迎，也促进了与公众的互动。许多具有不同社会经济背景的游客参与其中。钯催化烯烃反应一直被认为是制备原料和精细化学品的良好起点。许多这样的转变涉及核化反应；然而，反应参数的细微变化会影响反应机理，使得设计可靠的对映选择工艺变得困难。该资助项目通过在对映选择性内1,2-烯烃双官能化反应中利用Pd（II）•StackPhos配合物来解决碳官能化的挑战。在这里，催化剂通过识别特定的烯烃面来控制产物的立体化学构型，从而导致净对映选择性烯烃功能化反应。该研究的一个关键目标是确定在合成和反加成反应中表现出高水平立体选择性的催化剂。机械探针将被用来收集关于加法模式的信息。进一步的研究旨在形成碳环的反应，主要是通过内模环化和补充目前更发达的外模环化。额外的工作将扩展到迄今为止所研究的各种转化，以涵盖可能导致有用的对映体富集产物的替代底物。该项目的成功实现将对过渡金属催化领域产生重大影响，为对映选择性内1,2双官能化反应提供必要因素的基本理解。预计这些发现将使这一战略在学术和工业实验室的一系列合成应用中得到广泛应用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support of the Chemical Synthesis program in the Division of Chemistry, Professor Aaron Aponick of the University of Florida will study new palladium-catalyzed reactions designed to improve the manufacture of chemical compounds used in agriculture, clean energy technologies, and human health. A prominent feature of the research is that it will enable the generation of products in a so-called 'optically active form' in which one 'enantiomeric configuration' (approximately equivalent to the concept of handedness) of the molecule predominates. The broader impacts of the project will extend to providing hands-on training for students, preparing them for the modern workforce. In addition, public outreach in science, technology, engineering, and mathematics (STEM) will be achieved through an educational event called "Chemistry Day at the Mall, Molecular Mania." This event is popular with children and fosters interactions with the public, in general. Many visitors with diverse socioeconomic backgrounds participate.Palladium-catalyzed reactions of olefins have long been recognized as excellent starting points for the preparation of feedstock and fine chemicals. Many such transformations involve a nucleopalladation reaction; however, subtle changes in reaction parameters impact reaction mechanism making it difficult to design reliable enantioselective processes. The funded project specifically addresses challenges in carbofunctionalization by the utilization of Pd(II)•StackPhos complexes in enantioselective endo-1,2-alkene difunctionalization reactions. Herein, the catalyst controls the stereochemical configuration of products by recognizing a specific olefin pi-face, leading to net enantioselective olefin functionalization reactions. A key goal of the research is to identify catalysts that exhibit high levels of stereoselectivity for both syn- and anti-addition reactions. Mechanistic probes will be used to glean information in regard to the mode of addition. Further studies are aimed at carbocycle-forming reactions, primarily through the endo-mode cyclization and complementing the more highly developed exo-mode cyclizations currently available. Additional work will expand on the kinds of transformations hitherto investigated to encompass alternative substrates that may also lead to useful enantioenriched products. Successful realization of the goals of the funded project will have a significant impact on the field of transition metal-mediated catalysis by providing a fundamental understanding of the factors necessary for enantioselective endo-1,2-difunctionalization reactions. It is anticipated that the findings will enable widespread deployment of this strategy across a range of synthetic applications in both academic and industrial laboratories.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.