RUI: Accessing Asymmetric Carbon Atoms by Samarium(II)-Water Allylic Benzoate Reductions

化学部的化学合成项目支持Gregory O'Neil教授的项目。奥尼尔教授是西华盛顿大学化学系的教员。他正在开发一种新的反应，这种反应可以使碳原子的一个镜像超越另一个镜像。许多重要的分子（如药用天然产物）和材料作为单一镜像存在，其活性与该特定镜像直接相关。因此，控制碳原子镜像形成的方法对于构建具有正确生物活性的分子至关重要。因此，O-Neil教授和他的团队正在利用钐(II)-水复合物的独特化学特性来实现这一目标。选择这些反应是因为钐（II）很容易获得，而且在水中进行反应的能力避免了特殊的处理或设备要求。因此，化学很容易被其他人采用，非常适合在主要的本科机构进行研究，并且与有机实验入门课程相兼容。此外，学生参与者正在学习各种研究方法，包括有机合成和先进的分析技术。他们通过参加专业会议和使用标准（例如科学论文和海报）和不太传统的渠道（例如播客、视频、杂志文章）传播结果而融入科学界。奥尼尔教授的团队有能力为在科学领域代表性不足的学生提供这种体验。生成具有绝对立体控制的立体碳的能力是许多引人注目的合成目标的要求。本项目的目的是研究sm2 (H2O)n在烯丙基苯甲酸盐还原中的应用。这种结合为不对称碳原子的合成提供了一种高度通用和易于使用的方法。这些反应具有潜在的强大功能，因为它们为现有的挑战提供了解决方案，不需要使用专门的试剂，易于执行，并且具有广泛的底物范围和官能团耐受性。这些方法能够生成其他方法难以构建的不对称碳原子，它们一致且可预测地导致立体选择性，可通过启动底物结构来控制，并且独立于新形成的立体碳上的基团，它们可以直接使用现成的试剂/底物和水进行（因此允许功能基团（例如-OH）通常不耐受）。它们是由一个立体分化基团控制的这个基团可以被合并到最终目标中或者作为手性辅助物被循环利用。该项目的更广泛影响和教育内容包括开发和实施一个为期4天的本科实验室实验，该实验教授立体化学相关概念和确定异构体比例所需的方法。这项工作还将创建一个包含各种手性醛的光学活性数据的存储库，供其他团体使用。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。

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Gregory O'Neil. Professor O'Neil is a faculty member in the Department of Chemistry at Western Washington University. He is developing new reactions that allow access to one mirror image of a carbon atom over another. Many important molecules (e.g. medicinal natural products) and materials exist as a single mirror image with their activity directly related to that specific mirror image. Hence, methods to control which mirror image of a carbon atom is formed are essential for the construction of molecules that have the correct biological activity. Accordingly, Professor O-Neil and his group are harnessing the unique chemistry of samarium(II)-water complexes to achieve this goal. The reactions were chosen because samarium(II) is readily available, and the ability to perform the reactions in water obviates special handling or equipment requirements. Thus, the chemistry is readily adoptable by others, well suited for research at a primarily undergraduate institution, and compatible with incorporation into an Introductory Organic Laboratory course. In addition, student participants are learning a variety of research methods including organic synthesis and advanced analytical techniques. They become integrated into the scientific community through attendance at professional meetings and dissemination of results using both standard (e.g. scientific papers and posters) and less traditional outlets (e.g. podcasts, videos, magazine articles). Professor O'Neil's group is well positioned to provide this experience for students underrepresented in science.The ability to generate stereogenic carbons with absolute stereocontrol is a requirement for many compelling synthetic targets. The goal of this project is to investigate the use of SmI2(H2O)n for allylic benzoate reductions. The combination leads a highly versatile and accessible method for the synthesis of asymmetric carbon atoms. The reactions are potentially powerful because they provide a solution to an existing challenge that does not require the use of specialized reagents, is easy to execute, and has a broad substrate scope and functional group tolerance. The methods are capable of generating asymmetric carbon atoms that can be difficult to construct with other methods, they consistently and predictably lead to stereoselectivities that are controllable by starting substrate structure and independent of the groups attached to the newly formed stereogenic carbon, they are straightforward to conduct using readily available reagents/substrates and with water (thereby allowing for functional groups (e.g. -OH) often not tolerated), and they are controlled by a stereo-differentiating group that can either be incorporated into the final target or be recycled as a chiral auxiliary. Broader impacts and educational components of the project include the development and implementation of a 4-day undergraduate laboratory experiment that teaches concepts related to stereochemistry and the methods needed for isomer ratio determination. This work will also create a repository with optical activity data for various chiral aldehydes available for use by other groups.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.