Thesis-2014-Ross.pdf (6.44 MB)
Novel routes to and reactions of cyclopropanes
thesisposted on 2014-11-21, 09:57 authored by Adam Ross
An array of different cyclopropanes have been synthesised, including the structurally simple 1-phenylcyclopropanol. These were synthesised in yields upwards of 60%, using the well published Kulinkovich reaction. From 1-phenylcyclopropanol, variations of the cyclopropane core structure were synthesised, creating species ideal for palladium cross coupling reactions, such as 1-phenylcyclopropyl methanesulfonate and 1-phenylcyclopropyl 4-methylbenzenesulfonate. These were formed in 50 and 60% yield respectively. Once obtained these cyclopropanes were used to perform Suzuki cross coupling reactions towards the formation of 1,1- diphenyl cyclopropane. Unfortunately, despite various attempts, the palladium cross coupling reactions were unsuccessful. The work did facilitate the discovery of a novel methodology for the synthesis of tetra substituted alkenes. Using similar methodology as that developed for the formation of 1- phenylcyclopropanol, a McMurry reaction was able to be performed on a number of different ketones. This reaction formed a wide array of different tetra-substituted alkenes with yields ranging from 20-99%, depending on the nature of the starting material. The method, involving the use of 9 equivalents of Grignard reagent and stoichiometric amounts of titanium isopropoxide, is a unique way of making low valent titanium in situ, as well as being homogeneous. Methodology for the formation of vinyl cyclopropanes containing an amide moiety has been developed, allowing a variety of different amines to be coupled to two different cyclopropanes. Once these species were synthesised, a palladium catalysed cyclisation, Heck reaction, carbonylation cascade was developed. This allowed the core cyclic structure of the stemona alkaloids to be obtained in a single reaction vessel with good yields of up to 52% depending on the amine used. The cascade was then applied to a fully substituted cyclic natural product core. However, the cascade reaction was unsuccessful. Efforts to alter the structure of the starting material, to remove the potentially hindering bromine, provided no improvement. It was established that the tetrakis(triphenylphosphine) palladium (0) catalyst used was too encumbered for insertion in to the sterically hindered starting material, which is likely to be causing the failure of the reaction.
Publisher© Adam Ross
Publisher statementThis work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/
NotesA Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.