Towards Catalytic, Asymmetric (4+3)-Cycloadditions

通过这个奖项，化学系的化学合成计划支持密苏里-哥伦比亚大学的Michael Harmata教授开发(4+3)-环加成化学的研究。在这样的环加成反应中，两个分子片段，一个四碳片段(二烯)和一个三碳片段(烯丙基阳离子)在一个反应中连接。其主要特征是生成具有正电荷的烯丙基阳离子，并与也是手性的配对(带负电荷的)阴离子配对。手性是任何不能叠加在其镜像上的对象的条件。例如，左手和右手是镜像，但不能重叠。这种手性可以用来在(4+3)-环加成反应产物的形成中诱导手性。这一点意义重大，因为生命的分子以及许多药物都是手性的，不是以右手分子和左手分子的混合物形式出现，而是以右手或左手分子的形式出现。这通常被称为不对称。不对称反应的发展，只产生右手或左手产物，是目前科学和化学工业中非常感兴趣的事情。Harmata教授将把这个项目的研究和教育部分整合到一个新的中学生推广计划中。通过一系列旨在强调日常经验和化学进步之间的联系的研讨会，该计划为中学生提供基于发现的体验，通过实验捕捉STEM领域的创造力。哈马塔教授与当地学区和特许学校建立了合作伙伴关系，以触及在科学界代表性较低的贫困社区。该计划通过为中学生提供讨论科学观察的机会，同时与大学生互动，促进在STEM领域追求高等教育。这一概念将通过染色过程来展示，在染色过程中，带电染料将选择性地对相反带电的织物进行染色。程序将由中学教师制定，他们将在夏季测试和提炼4H成员的想法，然后在学年将教学技术传回课堂。目标教室尤其是那些在STEM计划中暴露在农村或以其他方式得不到充分服务的教室。科学计划将包括使用手性磷酸从烯丙醇中产生烯丙基阳离子，手性磷酸已被设计为与烯丙基阳离子配对。这些物种预计将以非对映选择性的方式与二烯反应，导致环加合物的净对映体选择性。这将为七元碳环的对映选择性合成提供新的方法学。一些筛选也将作为反应发展过程的一部分进行。我们将考察分子间和分子内的反应。将寻求优化方案，以最大限度地提高对映体的选择性。

With this award, the Chemical Synthesis Program in the Chemistry Division is supporting the research of Professor Michael Harmata at the University of Missouri-Columbia to develop (4+3)-cycloaddition chemistry. In such cycloadditions, two molecular fragments, a four-carbon piece (the diene) and a three-carbon piece (the allylic cation)are joined in a single reaction. The key feature is the generation of the allylic cation, which possesses a positive charge, and is paired with a partner (negatively-charged) anion that is also chiral. Chirality is the condition of any object that cannot be superimposed on its mirror image. For example, left and right hands are mirror images, but cannot be superimposed. The idea is that this chirality can be used to induce chirality in the formation of the products of the (4+3)-cycloaddition reaction. This is significant because the molecules of life, as well as many drugs are chiral and occur not as mixtures of right and left handed molecules, but as either right or left. This is generally known as asymmetry. The development of reactions that are asymmetric, producing only right or left handed products, is of great current interest across science and the chemical industry. Professor Harmata will integrate the research and educational components of this project within a new outreach program for middle school students. Through a series of workshops aimed at highlighting the connections between everyday experience and chemistry advances, this program provides middle school students with a discovery-based experience that captures the creativity of the STEM fields through experiments. Professor Harmata has established partnerships with local school districts and charter schools to reach an underprivileged community, which is underrepresented in the sciences. The program promotes the pursuit of higher education in the STEM fields by providing an opportunity for middle-school students to discuss scientific observations while interacting with college students. This concept will be demonstrated through the process of dyeing, in which charged dyes will selectively dye oppositely charge fabrics. Procedures will be developed by middle school teachers who will test and refine the ideas on 4H members during the summers and then transfer the teaching technology back to their classrooms during academic years. Targets classrooms are particularly those that are rural or otherwise underserved in the context of exposure to STEM programs.The scientific program will consist of the generation of allylic cations from allylic alcohols using chiral phosphoric acids that have been designed to ion pair with allylic cations. These species are anticipated to react with dienes in a diastereoselective fashion, resulting in a net enantioselectivity in the cycloadducts. This will provide new methodology for the enantioselective synthesis of seven-membered carbocyclic rings. Some screening will also be conducted as part of the reaction development process. Both inter- and intramolecular reactions will be examined. Optimization protocols will be pursued in an effort to maximize enantioselectivity.