The development of novel organocatalytic and transition-metal catalysed methodologies for amide bond formation

  • Christopher McPherson

Student thesis: Doctoral Thesis

Abstract

With the formation of amide bonds being one of the most widely performed reactions within organic chemistry, highly efficient and atom economical approaches enabling the transformation are desired. Traditional methodologies, in which a stoichiometric coupling reagent is utilised, although efficient, have several inherent drawbacks hindering their general applicability, including stoichiometric by-product formation, low atom economy and poor cost effectiveness. Therefore, the development of atom economical catalytic approaches to facilitate the facile synthesis of amide bonds would successfully address the aforementioned outstanding issues.Building upon previous research performed within the Jamieson group, one such approach is the trifluoroethanol-catalysed amidation of unactivated ester derivatives. However, in the initial studies, the general applicability of this methodology was limited by the incompatibility of acyclic secondary amines under the reaction manifold, and additionally, stereoerosion when the use of α-stereogenic ester substrates was examined. Further optimisation of the progenitor conditions successfully addressed these limitations, allowing the synthesis of a diverse range of acyclic tertiary amides and chiral secondary amides, with the latter synthesised in good to excellent levels of stereoretention (Scheme 1.1).Additionally, a multicomponent approach enabling the formation of secondary amides fromepoxides, amines and unactivated esters, mediated by the organobase BEMP, has also been developed. The use of a multicomponent process, employing only catalytic quantities of base, limits by-product formation, thereby resulting in a highly atom efficient amide bond forming method (Scheme 1.2). This approach has also been further adapted to enable the synthesis of corresponding oxazolidinone moieties. The use of transition-metal catalysis has also been employed to facilitate amide bond formation. Utilising silanoate-derived imidate salt species, synthesised from the corresponding nitriles as amide surrogates, a Buchwald-Hartwig amidation methodology has been developed, enabling the synthesis of secondary amides (Scheme 1.3). Investigations into the use of these species in other amide bond forming transformations have also been carried out.
Date of Award1 Oct 2017
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorCraig Jamieson (Supervisor) & (Supervisor)

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