Brønsted Acid-Catalysed Synthesis and Functionalisations of Heterocycles

Abstract

This thesis is focused on the investigation of new procedures for the Brønsted acid catalysed synthesis and functionalisation of heterocycles using inexpensive, commercially available Brønsted acids.

First, in Chapter 1, the concept and background of Brønsted acid catalysis is detailed. The use of Brønsted acid catalysts for a variety of different reactions and mechanistic aspects are described, with intention to place the work of this thesis in the context of the literature.

Second, in Chapter 2, the synthesis of γ-hydroxy-α,β-unsaturated ketones is explored and optimised. Once developed, the use of γ-hydroxy-α,β-unsaturated ketones in a Brønsted acid-catalysed reaction to form substituted furans is investigated. The optimised procedure uses readily available para-toluenesulfonic acid as the catalyst and the reaction proceeds under mild conditions to furnish substituted furans in good yields. Mechanistic control experiments have identified two possible reaction pathways and the validity of both is discussed.

Third, in Chapter 3, the Brønsted acid-catalysed Friedel-Crafts alkylation of indole in water is explored. Salicylic acid, a readily available, inexpensive Brønsted acid is identified as a suitable catalyst and reaction conditions are optimised. The use of substituted indoles, substituted nitroalkenes, and other heterocycles and Michael acceptors is then investigated. Control reactions probe the possible hydrogen bonding mode of activation with the salicylic acid catalyst.

Finally, in Chapter 4, the use of chiral organic Brønsted acids for the enantioselective Friedel-Crafts alkylation of indole is investigated. Chiral Brønsted acids based on salicylic acid were designed and their syntheses were attempted. Then, their use for catalysing the Friedel-Crafts alkylation was examined in water and dichloromethane. Unfortunately, no enantioselectivity was observed.

Date of Award	27 Mar 2024
Original language	English
Awarding Institution	University of Bath
Supervisor	James Taylor (Supervisor) & Simon Lewis (Supervisor)