六价硫氟类化合物的合成与转化研究

Sulfur (VI) fluoride compounds are overlooked in history until recently Sharpless’ lab reported the sulfur (VI) fluoride exchange transformations (SuFEx). Great applications of this type of function groups therefore emerged in material science, chemical biology and synthetic chemistry. The great stability of sulfur (VI) fluorine bond is kinetic rather than thermodynamic in origin since it is thermodynamically unstable with respect to water. They are relatively unreactive towards most categories of chemical reactions (hydrolysis, reduction, nucleophilic substitution, thermolysis, etc.). When reactions do occur, they appear to react exclusively at the sulfur center. The contrast between the high kinetic stability of S(VI)-F bond and their activatable sulfur (VI) fluoride exchange (SuFEx) chemical reactivity resulting in fringe acid-base reactivity. These properties designate SuFEx reactivity as a potentially powerful, context-dependent variant of click chemistry. In contrast with traditional fluorine chemistry, this research proposal focus on the synthesis of sulfur(VI)-fluoride bonds, the activation process also mechanism, and the applications of this unique type of reactivity. The readily available industry raw materials with S(VI)-F bond are of interest to this proposal, such as RSO2F, SO2F2 (Sulfuryl fluoride), SF6 (Sulfur hexafluoride). And also several unique type of inorganic N-S(VI)-F, O-S(VI)-F molecules, such as SOF4 (Thionyl tetrafluoride) and NSF3 (Thiazyl trifluoride).

从高价主族元素氟化物反常的，动力学上的高度稳定性以及热力学上的高度反应活性出发，主要以六价硫氟类化合物（化学键）作为这一全新反应性的承载体，探索一个前所未有的思路：一个简单、高度易得、低极性的化合物中所含的亲电官能团具有广义上极高的化学稳定性，甚至在生物体中不可被轻易活化，同时可能具有狭义上极高的化学反应性：即在外加第三方的诱导因素的条件下被活化，和普通的亲核试剂进行高效的链接或者转化。与传统的氟化学不同，该研究主要关注的是无机氟化学与有机化学中间地带的交叉和再发现；杂氟键的合成和其在特定条件下的活化转化。该计划以此做为研究方向的切入点，结合几种廉价的氟化工原料进行突破，例如SF6，SO2F2等。希望合成一批有自主知识产权的新材料，例如聚硫酸酯，磺酰胺类聚合物，新的合成化学试剂（例如碳原子和杂原子的SF5化）等，乃至新类型的生物正交反应以及新结构的药物探针分子。

我们发现了一类阴离子氟盐[HF2-]（Bifluoride anion），可以作为更加高效的催化剂促进SuFEx反应，合成具有理想的聚合度以及优秀的分子量分布和优良的官能团耐受性的聚硫酸酯和聚磺酸酯类材料。该工艺在降低催化剂、聚合物提纯和副产品回收成本方面是可行的。该工艺对放大不敏感，这对其未来从实验室研究转化为工业应用至关重要。.我们报道从可得性最丰富的官能团之一——伯胺出发合成叠氮化合物。该反应仅使用一当量的氟磺酰叠氮（FSO2N3），以安全和实用的方式在96孔板上制备1200多种叠氮化合物。这种转化为CuAAC环加成反应提供了有力的工具。使用该方法大大增加了叠氮化合物和1，2，3-三唑类化合物的数量，在有机合成、药物化学、化学生物学和材料科学等领域有着广泛的应用前景。