Development of electrophilic amination reactions for the synthesis of nitrogen heterocycles

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

A range of C-N bond forming reactions using hydroxylamine-derived N-O donors have been developed. Initial studies focused on the development of a dearomatising amination reaction of phenols and naphthols. Whilst attempts at developing C-N bond forming dearomatisation reactions of N-acyloxysulfonamides and N-acyloxycarbamates were largely unsuccessful, further studies identified an effective transition metal-free protocol for dearomatising aminations of N-tosyloxycarbamates. Under acidic conditions, in situ Boc-deprotection of N-tosyloxycarbamate derivatives occurs to generate an electrophilic nitrogen source that can trigger dearomatisation via nucleophilic attack of a pendant arene. Through the dearomative cyclisation of phenol- and naphthol-substituted N-tosyloxycarbamates, spirocyclic pyrrolidines were obtained in good to excellent yield. Mechanistic experiments suggest the reaction proceeds via an SEAr-like mechanism. Annulative derivatisations of the dearomatised products provides access to complex natural product-like scaffolds. Preliminary studies demonstrated the feasibility of an asymmetric variant of the dearomatising amination reaction.
Additionally, a metal-free aziridination of alkenes using the previously developed N-O donors was demonstrated. The stereospecific aziridination of di-, tri- and tetrasubstituted alkenes was achieved to form azabicyclo[3.1.0]hexane and azabicyclo[4.1.0]heptane motifs. Computational studies validate a concerted mechanism akin to an aza-Prilezhaev-type pathway.

Date of Award29 Sep 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorTim Gallagher (Supervisor), Paul G Pringle (Supervisor) & John Bower (Supervisor)

Cite this

Development of electrophilic amination reactions for the synthesis of nitrogen heterocycles
Farndon, J. J. (Author). 29 Sep 2020

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)