Fluoroamination of Allylsilanes

含氟砌块在生命科学中的地位越来越重要，代表着一类高价值的化合物。在这方面，含氟含氮杂环是制药和农化工业的主要目标。考虑到这些化合物的可及性较差，我们建议探索新的合成方法来获得氟化吡咯烷。鉴于大量的文献关于亲电诱导的环化反应，一个非常吸引人的途径是通过亲电氟化反应使带有亲核氨基的烯烃得到含氟氮杂环化合物。然而，这条路线目前是不可能的，因为未活化的烯烃不与现有的[易于处理]亲电氟化N-F试剂反应。在这项提议中，我们提出了两种解决方案，基于使用硅基暂时激活烯烃进行亲电氟化。第一种方法的特点是各种烯丙基硅烷的关键亲电氟环化反应，这些硅烷含有一个待定的亲核对甲苯磺化氨基。这个反应产生硅化的氟化吡咯烷，在氧化裂解时释放出所需的氟化吡咯烷。该路线的优点是可以根据烯丙基硅烷的E/Z几何构型对目标的立体化学进行调制。第二种溶液的特点是烯丙基氟化物的同步选择性碘胺化反应，该反应也含有待定的亲核N-甲苯磺酰基团。我们计划发展的化学将受到挑战，合成氟化的吡咯里西啶和其他生物相关的目标，由于进一步的氨基功能操作。

Fluorinated building blocks are becoming more and more important in the life sciences, and therefore represent a class of high-value compounds. In this context, fluorinated nitrogen-containing heterocycles are key targets for the pharma- and agrochemical industry. Considering the poor accessibility of these compounds, we propose to explore new synthetic methodologies to access fluorinated pyrrolidines. In the light of the abundant literature on electrophile-induced cyclisations, a very attractive route to access fluoro nitrogen-containing heterocycles is the electrophilic fluorocyclisation of alkenes bearing a pending nucleophilic amino group. However, this route is currently not possible because unactivated alkenes do not react with existing [easy to handle] electrophilic fluorinating N-F reagents. In this proposal,we propose two solutions to this problem based on the use of a silyl group to temporarily activate the alkene toward electrophilic fluorination. The first approach features a key electrophilic fluorocyclisation of various allylsilanes bearing a pending nucleophilic tosylated amino group. This reaction generates silylated fluoropyrrolidines which upon oxidative cleavage release the desired fluorinated pyrrolidines. This route presents the advantage to allow for modulation of the stereochemistry of the targets as a function of the E/Z geometry of the allylsilanes. The second solution features a syn selective iodoamination of allylic fluorides also bearing pending nucleophilic N-tosyl groups. The chemistry we propose to develop will be challenged with the synthesis of fluorinated pyrrolizidines and other biologically relevant targets, resulting from further functional manipulation of the amino group.