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Synthesis of Fluorinated Pyrrolidines

Objective

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.

Field of science

  • /humanities/languages and literature/literature - general
  • /natural sciences/mathematics/pure mathematics/geometry

Call for proposal

FP7-PEOPLE-2007-2-1-IEF
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Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
Wellington Square University Offices
OX1 2JD Oxford
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 169 390,93
Administrative Contact
Linda Polik (Ms.)