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

化学部化学合成计划支持格雷戈里·奥尼尔教授的项目。奥尼尔教授是西华盛顿大学化学系的一名教员。他正在开发新的反应，使人们能够看到碳原子在另一个原子上的镜像。许多重要的分子(如药用天然产物)和材料以单一镜像的形式存在，它们的活性与该特定镜像直接相关。因此，控制碳原子形成哪个镜像的方法对于构建具有正确生物活性的分子是至关重要的。因此，O-Neil教授和他的团队正在利用Sm(II)-水络合物的独特化学作用来实现这一目标。之所以选择这些反应，是因为Sm(II)很容易获得，而且能够在水中进行反应，因此不需要特殊的处理或设备要求。因此，化学很容易被其他人采用，非常适合在主要是本科生的机构进行研究，并与有机实验室入门课程兼容。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利用标准渠道(如科学论文和海报)和非传统渠道(如播客、视频、杂志文章)传播成果，融入科学界。奥尼尔教授的团队处于有利地位，可以为科学界代表性不足的学生提供这种体验。具有绝对立体控制的生成立体碳的能力是许多引人注目的合成靶点的要求。本项目的目标是研究SmI2(H2O)n在烯丙基苯甲酸酯还原中的应用。这种组合导致了一种高度通用和易获得的不对称碳原子的合成方法。这些反应是潜在的强大的，因为它们提供了一种解决现有挑战的方案，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。该方法能够产生用其他方法难以构建的不对称碳原子，它们一致且可预测地产生立体选择性，该立体选择性可通过起始底物结构来控制并且独立于连接到新形成的立体碳的基团，它们可以直接使用现成的试剂/底物和水(从而允许官能团(例如，-OH)通常不被容忍)进行，并且它们由立体分化基团控制，该立体区别基团可以结合到最终目标中或作为手性辅助回收。该项目更广泛的影响和教育内容包括开发和实施为期4天的本科生实验室实验，教授与立体化学有关的概念和确定同分异构体比率所需的方法。这项工作还将创建一个储存库，其中包含各种手性醛的光学活性数据，可供其他组织使用。该奖项反映了NSF的法定使命，并已通过使用基金会的智力优势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.