Fluorofunctionalisation of alkenes via electrochemically generated hypervalent iodine reagents

Abstract

The inclusion of Cₛₚ³-F bonds into bioactive compounds has a broad range of benefits. This, along with general synthetic routes, will be discussed in chapter one.

The difluoroalkyl functionality has garnered recent attention due its ability to adopt a gauche conformation in solution. However, current syntheses are limited to the difluorination of electron deficient alkenes. Therefore, the development of a novel electrochemical vicinal difluorination of alkenes will be discussed in chapter two.
This approach utilises electrochemistry to enable access to new substrate classes in a sustainable and scalable manner. Two methods will be presented: an “in-cell” method for the difluorination of electron poor alkenes, and an “ex-cell” method for the difluorination of electron rich alkenes.

Fluorofunctionalisation of unactivated alkenes is an interesting problem because it poses significant diastereo- and regioselective problems. Hence, the chlorofluorination of alkenes has only ever been completed with anti-diastereoselectivity. Thus, the development of a diastereodivergent chlorofluorination of alkenes will be discussed in chapter three. Both syn- and anti-methods had good functional group tolerance. Afterwards mechanistic investigations were conducted to propose the origins of the elegant diastereoselectivity swap and regioselectivity.

The results in this thesis have been communicated:
S. Doobary, A. T. Sedikides, H. P. Caldora, D. L. Poole, A. J. J. Lennox, Angew. Chem. Int. Ed. 2020, 59, 1155-1160
D. Heard, S. Doobary, A. J. J. Lennox, ChemElectroChem, 2021, 8, 2070-2074
S. Doobary, A. D. J. Lacey, H. P. Caldora, D. L. Poole, N. Fey, A. J. J. Lennox, Manuscript in preparation

Date of Award	25 Jan 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Alastair J J Lennox (Supervisor) & David J Fermin (Supervisor)