Sulfonimidamides: New Frontiers in Stereochemistry and Functionality

在化学系化学合成项目的支持下，加州大学戴维斯分校的Jared T. Shaw教授正在研究磺胺酰胺（SIAs）合成新方法的发展。SIAs是自然界中不存在的有机分子，因此相对未被探索。它们表现出手性，即以“右手”或“左手”构型存在的能力。这种性质使它们成为研究的有趣分子，因为它们的反应性和独特的性质，它们有望赋予新的药物、材料和其他有用的应用。资助的研究包括研究如何使用新的催化方法选择性地使这些分子具有单手性或主要是一种对映体结构，这些方法将优化效率并检查应用的广度。此外，该项目将研究硫中心的手性或“手性”如何影响与SIA相邻的新键的形成，这将使合成新的、复杂的SIA成为可能，而这些SIA迄今尚未被接触或探索过。这些相关研究将为未来在工程和医学上的应用奠定基础，有可能为发现和应用开辟新的前景。在进行科学实验的同时，该项目将包括每月一次的科学咖啡馆，提供一个方便（而且有趣！）的活动，让科学家在校外的场所向公众交流他们的工作。这项工作的更广泛的影响集中在使新分子的发现有利于社会，以及来自加州大学戴维斯分校的科学的公众讨论，以及它如何有利于国家，社区和社会。受资助的研究重点是开发与磺胺酰胺（SIAs）有关的新合成方法。有机化学中这一未被充分开发的官能团为从潜在的新药物先导化合物到新材料和催化剂的发现提供了肥沃的土壤。本研究考察了几种新的催化、对映选择性合成SIAs的方法，包括目前在专利文献之外未知的这些分子的环状版本。这些催化方法包括使用过渡金属配合物的动态动力学分解（DKR）以及新的基于磷的S=O键到S=N键的转化。此外，硫基手性对产生新的立体中心的亲核加成反应的影响将被研究。虽然以前的方法使用s -手性化合物，如亚砜酰亚胺作为手性助剂，但本研究旨在制造具有多个相邻碳立体中心的结构新颖的SIAs作为有用的靶分子。总的来说，这个项目旨在在如何在有机化学中制造新的官能团以及该官能团如何影响相邻碳原子的反应性方面迈出垂直的一步。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 the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Jared T. Shaw of the University of California, Davis is studying the development of new methods for the synthesis of sulfonimidamides (SIAs). SIAs are organic molecules that do not occur in nature and, as such, are relatively unexplored. They exhibit chirality, i.e. the ability to exist in a “right-” or “left”-handed configuration. This property makes them interesting molecules to study both for their reactivity and for the unique properties that they are expected to impart to new drugs, materials, and other useful applications. The funded research includes investigations into how to make these molecules selectively of one handedness or of largely one enantiomeric configuration using new catalytic methods that will be optimized for efficiency and examined for breadth of application. In addition, this project will examines how this chirality or “handedness”at a sulfur center can influence the formation of new bonds adjacent to the SIA, which will enable the synthesis of new, complex SIAs that have been not been accessed or explored heretofore. These related studies will lay the groundwork for future applications in engineering and medicine that have the potential to open up new vistas for discovery and application. In parallel to the scientific experiments, this project will involve a monthly science café that provides an accessible (and fun!) event where scientists communicate their work to the general public at an off-campus venue. The broader impacts of this work center on enabling the discovery of new molecules to benefit society as well as the public discussion of science from across UC Davis and how it benefits the state, community, and society.The funded research centers on the development of new synthetic methods related to sulfonimidamides (SIAs). This underexplored functional group in organic chemistry provides fertile ground for the discovery from potentially new pharmaceutical lead compounds to new materials and catalysts. This research examines several new catalytic, enantioselective methods for the synthesis of SIAs, including cyclic versions of these molecules that are currently unknown outside of patent literature. These catalytic methods include dynamic kinetic resolution (DKR) using transition metal complexes as well as new phosphorous-based conversion of S=O bonds to S=N bonds. In addition, the impact of sulfur-based chirality on nucleophilic addition reactions that generate new stereogenic centers will be examined. Although previous methods used S-chiral compounds, e.g. sulfinimides, as chiral auxiliaries, this work seeks to make structurally novel SIAs with multiple adjacent carbon stereogenic centers as useful target molecules. Collectively this project aims to take a vertical step in the knowledge of how to make a new functional group in organic chemistry and how that functional group influences the reactivity of adjacent carbon atoms.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.