Fluoroamination of Allylsilanes

烯丙基硅烷的氟胺化

• 批准号: EP/F019467/1
• 负责人: Veronique Gouverneur
• 金额: $ 15.39万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FF019467%2F1
• 关键词: Fluoroamination; Allylsilanes

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.

在生命科学中，氟化的构件变得越来越重要，因此代表了一类高价值化合物。在这种情况下，氟化氮的杂环是药物和农业化学工业的关键目标。考虑到这些化合物的可及性不佳，我们建议探索新的合成方法，以获取氟吡咯烷。鉴于有关电力诱导的环球化的丰富文献，进入含氟氮的杂环的非常有吸引力的途径是带有一个悬而未决的核氨基氨基烷基的烷烃的亲电荧光细胞化。但是，目前不可能进行此途径，因为未活化的烷烃与现有的[易于处理]的电荧光N-F试剂没有反应。在此提案中，我们基于使用Silyl基团暂时激活烯烃向亲电氟化的两种解决方案。第一种方法具有带有悬而未决的亲核氨基化氨基的各种烯丙基硅烷的关键亲电荧光细胞化。该反应会产生用氧化裂解释放出所需的氟吡咯烷。该路线提供了允许对目标的立体化学调制作为Allylsilanes E/Z几何形状的函数的优势。第二个溶液具有烯丙基氟化物的合成碘酰胺，还带有悬而未决的亲核N- tosyl基团。我们建议开发的化学反应将与氟化吡咯烷胺和其他与生物学相关的靶标的合成质疑，这是由于对氨基群的进一步功能操作而产生的。

项目成果

Metal free fluoroamination of allylsilanes: A route to 3-fluoropyrrolidines

烯丙基硅烷的无金属氟胺化：制备 3-氟吡咯烷的途径

• DOI: 10.1016/j.jfluchem.2012.05.013
• 发表时间: 2012
• 期刊: Journal of Fluorine Chemistry
• 影响因子: 1.9
• 作者: Combettes L

Stereoselective Synthesis of Fluorinated Pyrrolidines

氟化吡咯烷的立体选择性合成

• 发表时间: 2010
• 作者: Marie Schuler

Synthesis of 3-fluoropyrrolidines and 4-fluoropyrrolidin-2-ones from allylic fluorides.

• DOI: 10.1002/chem.201201576
• 发表时间: 2012-10
• 期刊: Chemistry
• 作者: L. E. Combettes;M. Schuler;Rakesh Patel;Baltasar Bonillo;B. Odell;A. Thompson;T. Claridge;V. Gouverneur