FLUPYRProject reference: 220034
Funded under :
Synthesis of Fluorinated Pyrrolidines
Total cost:EUR 169 390,93
EU contribution:EUR 169 390,93
Coordinated in:United Kingdom
Topic(s):PEOPLE-2007-2-1.IEF - Marie Curie Action: "Intra-European Fellowships for Career Development"
Call for proposal:FP7-PEOPLE-2007-2-1-IEFSee other projects for this call
Funding scheme:MC-IEF - Intra-European Fellowships (IEF)
"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 fluoropyrrolidines. 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 biologically relevant targets."
OX1 2JD OXFORD
Tel.: +44 1865 289811
Fax: +44 1865 289801