Visible Light Induced Remote Functionalizations via Nitrogen Radicals

Abstract

Methods for remote functionalizations are desirable to expand the transformations available in the organic chemists toolbox. Radical methods for remote functionalization are useful as oddelectron species are able to undergo transposition processes to access distal positions within molecules. Nitrogen containing molecules are widespread as bioactive molecules, therefore using nitrogen-centred radicals is desirable as we can access relevant compounds. In this thesis, the development and application of photoinduced protocols to generate iminyl, amidyl and protected aminyl radicals is shown and the variety of cascade remote functionalization protocols that these have enabled. At the outset of my PhD work, within the group a class of electron rich oximes had been developed which could undergo oxidative single electron transfer (SET) with an appropriate excited photocatalyst. In this work, I utilised these easy-to-make nitrogen radical precursors in a photoinduced ring-opening functionalization cascade to generate remotely functionalized nitriles. This breadth of methodology was further shown by the combination with Nickel catalysis which allowed us to engage alkyl bromides, aryl bromides and alkynes to introduce new C-C bonds. By changing the structure of the electron rich oxime to linear ketone derivatives, analogous iminyl radicals could be generated and undergo a 1,5-HAT mechanism to generate remote carbon radicals. These could be functionalized with N-chlorosuccinimide or Selectfluor to generate halogenated ketone derivatives. Finally, by extending this 1,5-HAT/functionalization methodology utilising electrophilic amidyl and protected aminyl radicals, we could introduce halogens, heteroatoms and form new C-C bonds. Furthermore, this strategy could be extended to the selective functionalization of amino acid residues and a dipeptide.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	David Procter (Supervisor) & Daniele Leonori (Supervisor)