N-Heterocyclic Carbene Catalysed Umpolung Reaction of Pyridiniums

Abstract

The pyridine ring is an important heterocyclic structure prevalent within biologically active compounds which can be functionalised through activation as the more reactive pyridinium ring. N-Heterocyclic carbenes (NHCs) are a class of reactive species which have received significant attention as organocatalysts since their isolation in 1991. Presented herein is a novel reaction for the functionalisation of pyridiniums using a catalytic NHC. Using an NHC, pyridinium C-H bonds at the 4-position were subject to a polarity inversion to access aryl anion equivalents for an intramolecular reaction towards Michael acceptors, eventually yielding indenopyridines. This procedure represents the first example of arene Umpolung catalysed by NHCs proceeding through a deoxy-Breslow intermediate and mechanistic studies were performed to find supporting evidence. Building on these results, identification of a suitable activating group allowed the extension of this procedure to encompass pyridine functionalisation through the more active pyridinium. Finally, intermolecular reactivity was explored and direct NHC addition to amino-pyridiniums was observed.

Date of Award	1 Aug 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Nicholas Turner (Supervisor) & Michael Greaney (Supervisor)