Date of Award

Summer 2018

Document type

Thesis

Degree Name

PhD (Doctor of Philosophy)

First Supervisor

Professor Mauro F. A. Adamo

Funder/Sponsor

Irish Research Council

Keywords

Phase Transfer Catalysis, Amide Synthesis, Chiral Triazolium Salts

Abstract

The purpose of this work is the discovery and development of new catalytic methodologies towards the synthesis of amides and cyclic compounds, with the aid of phase transfer reagents. In particular, it is focused on triazocyclic compounds, which are conveniently obtained by the reaction of organic azides with enolates, or by copper-catalysed azide-alkyne cycloaddition. Triazocyclic compounds display a wide scope of reactivity, which is still partially unexplored. Finally, we pursue the discovery of innovative applications of 1,2,3-triazoles and 1,2,3-triazolium salts in the field of organocatalysis.

Chapter 1 A novel two-step sequence for the preparation of amides starting from azides and enolisable aldehydes. The reaction proceeded via the formation of triazoline intermediates that were converted into amides via Lewis acid catalysis. Preliminary studies on the preparation of triazolines under chiral phase transfer catalysis are also presented, demonstrating that enantioenriched amides could be prepared from achiral aldehydes in moderate to low enantioselectivity.

Chapter 2 The reactivity of ester enolates with organic azides was studied. The condensation of 2- alkylacetoacetic esters with aromatic azides under organic base catalysis provided 5-hydroxy- 4-alkyl-1,2,3-triazoles, which showed strong Brønsted acidity. Three anilide-hydroxytriazoles analogue to SAHA were synthesised in order to test their activity as histone deacetylase inhibitors. In a preliminary study, different organocatalysts bearing the 5-hydroxytriazole motif were designed, and several steps towards their synthesis were made.

Chapter 3 A novel stereoselective synthesis of 3,4-dihydropyran-2-ones under phase transfer catalysis is described. The reaction of cinnamic thioesters and acetylacetone was promoted by Cinchona-derived quaternary ammonium salts. 3,4-Dihydropyran-2-ones were obtained in good yields and enantioselectivity when the reaction was carried out in the presence of catalytic amounts of N-benzylquininium bromide and phenol.

Chapter 4 Novel and chiral binaphthalene-derived-1,2,3-triazolium salts were synthesised following a simple 3-step procedure, starting from commercially available (S)-2,2’-diamino-1,1’- binaphthalene. Chiral triazolium salts were used as phase transfer catalysts for different organic reaction. The 1,2,3-triazolium-catalysed Michael addition of nitromethane to 5- stytylisoxazoles provided the desired nitroadduct in 90% yield and 56% enantiomeric excess.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

File Size

24.7 MB

Comments

A thesis submitted for the degree of Doctor of Philosophy from the Royal College of Surgeons in Ireland in 2018.

Available for download on Saturday, May 30, 2020

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