The Preparation and Utility of Pentafluorosulfanyl Substituted Aliphatic Compounds

在化学中很少有机会探索一个新的官能团的化学性质。五氟磺胺基（SF5）是近100年来为数不多的新官能团之一，有可能对生命科学和材料化学产生重大影响。SF5基团对受体呈硫结合氟的方形金字塔状，但占据的体积略小于叔丁基。碳- sf5键的大偶极矩导致底物分子的远距离静电相互作用。作为大量生物相关分子的核心组成部分，快速、经济地合成含羰基化合物的脂肪族SF5具有不可估量的价值。阐明了含sf5的环和无环醛、酮和氧羰基离子与亲核试剂的立体化学反应。五氟磺化的空间效应和静电相互作用均可用于由含sf5的构建块合成碳水化合物、氨基酸和叠氮二酮。更广泛的影响。具有重要经济和社会意义的许多有机氟化合物的利用受到代谢和环境限制的困扰。这些新的含sf5分子的现成可用性可以成为取代在环境中持续存在并对人类和动物产生不利影响的三氟甲基化农用化学品的第一步。作为药物制剂的替代品，SF5基团易于代谢为无免疫或酶毒性的物质，可能扩大抗疟疾或抗焦虑药物的用途。该计划培养下一代的学生在基础合成氟化学和物理有机化学。学生将利用多维核磁共振方法和从头计算技术。参与这个跨学科项目的学生将准备加入其他具有多学科背景和研究和解决问题经验的科学家和工程师。在过去的三年里，PI指导了9名来自历史上代表性不足的群体的学生。到目前为止，这些学生中有五人继续在研究生院学习。一种新的官能团的发展及其在合成中的应用可以对几乎所有有机化学领域产生影响，并为我们的工业提供一种独特的美国技术。所提出的研究成果显然对药物化学和材料科学的新构建模块的开发具有直接的适用性，并且有可能阐明控制合成不对称的新策略，这是21世纪制备方法的基本要求。

Rarely in chemistry does the opportunity to explore the chemistry of a new functional group appear. The pentafluorosulfanyl (SF5) group, one of the few new functional groups of the last 100 years, has the potential to dramatically impact both life sciences and materials chemistry. The SF5 group presents a square pyramid of sulfur-bound fluorines to receptors yet occupies a volume somewhat less than the tert-butyl group. The large dipole moment in the carbon-SF5 bond results in long range electrostatic interactions of the substrate molecule. As the core building blocks of an enormous number of biologically relevant molecules, the synthesis of aliphatic SF5 containing carbonyl compounds quickly and economically is invaluable. The stereochemistry of reactions of cyclic and acyclic SF5-containing aldehydes, ketones and oxocarbenium ions with nucleophiles will be elucidated. Both the steric effects and electrostatic interactions of pentafluorosulfanylation can be employed in the synthesis of carbohydrates, amino acids and azetidinones from SF5-containing building blocks. The broader impact. Of vital economic and social importance, the utility of many organofluorine compounds is plagued by both metabolic and environmental limitations. The ready availability of these new SF5-containing molecules can be the first step in replacing trifluoromethylated agrichemicals that persist in the environment with adverse effects on both humans and animals. As replacements in pharmaceutical agents, facile SF5 group metabolism to substances that are not immunologically or enzymatically toxic may expand the utility of anti-malarial or anxiolytic drugs. The proposed program trains the next generation of students in basic synthetic fluorochemical and physical organic chemistry. Students will utilize multi-dimensional NMR methods and ab initio computational techniques. Students engaged in this cross-disciplinary project will be prepared to join other scientists and engineers with multidisciplinary backgrounds and experience in research and problem-solving. Within the last three years, PI has mentored nine students from historically under represented groups. Of these students, to date, five have continued their studies in graduate school. The development of a new functional group and its applications in synthesis can have an impact on nearly all areas of organic chemistry and offers a uniquely American technology to our industries. The product of the proposed research clearly has direct applicability to the development of new building blocks for medicinal chemistry and materials science as well as the potential to illustrate new strategies for the control of asymmetry in synthesis, a basic requirement of 21st century preparative methods.