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.

氟化结构单元在生命科学中变得越来越重要，因此代表了一类高价值的化合物。在这种情况下，氟化的含氮杂环是制药和农业化学工业的关键目标。考虑到这些化合物的可及性差，我们建议探索新的合成方法来获得氟化吡咯烷。在大量的文献中，亲电诱导的环化反应，一个非常有吸引力的途径来获得含氟氮杂环是亲电氟环化的烯烃带有一个挂接的亲核氨基。然而，这种途径目前是不可能的，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。在这个建议中，我们提出了两个解决方案，这个问题的基础上使用的甲硅烷基暂时激活烯烃亲电性。第一种方法的特点是一个关键的亲电氟环化的各种烯丙基硅烷轴承挂起亲核甲苯磺酰化氨基。该反应生成甲硅烷基化氟吡咯烷，其在氧化裂解时释放所需的氟化吡咯烷。该途径的优点是允许调节靶的立体化学作为烯丙基硅烷的E/Z几何形状的函数。第二个解决方案的特点是顺式选择性碘胺化烯丙基氟也轴承挂亲核N-甲苯磺酰基基团。我们建议开发的化学将受到挑战的合成氟化吡咯烷和其他生物相关的目标，从进一步的功能操作的氨基。

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

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

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