Development of a Novel Organophosphorus-Based Synthetic Methodology and a Quantitative Lewis Basicity Scale

This thesis is split into three parts based on three separate research projects. Part I: In this project, a novel methodology was developed for the formation of ethers from aromatic aldehydes and alcohols. This method was shown to be generally applicable for the synthesis of thirty-four ethers in isolated yields from 63% ‒ 92%. The methodology described in this thesis is a two-step, one-pot process. Step one involves the formation of (α-alkoxyalkyl)phosphonium triflates using aldehyde, phosphine, acid and alcohol. Step two involves the hydrolysis of (α-alkoxyalkyl)phosphonium triflates using NaOH. This methodology is comparable to a reductive etherification reaction but as there is no formal reductant used to access the benzyl ether products, this method serves as a new route to benzyl ethers containing reduction-sensitive functional groups. This methodology was also shown to be highly chemoselective for the aldehyde functional group. It was possible to achieve ether formation in the presence of esters, ketones, carboxylic acids and amides. Part II: Part II of this thesis relates to research conducted on the expansion of a scale for quantifying the Lewis basicity of weak Lewis bases. Originally, Prof. Herbert Mayr and co-workers developed a Lewis basicity scale over 13 orders of magnitude in MeCN. In this work, an extended Lewis basicity scale was developed, using a novel NMR spectroscopic method to enable the Lewis basicity of weakly Lewis basic compounds to be quantified. In this project, the Lewis basicity scale was expanded downwards by 4.5 orders of magnitudes. The Lewis basicity values for 21 Lewis bases was determined using an NMR spectroscopic method that competed two Lewis bases (of comparable Lewis basicity) against a reference Lewis acid. The competition equilibrium constants were established using the relative integrations of all species present in solution as a proxy for the concentrations of the compounds in solution. It was possible to determine the Lewis basicity values which can be converted into an absolute scale by linking to the published absolute equilibrium constants. Part III: Part III of this thesis relates to research conducted on the development of a novel oxidant-expedited synthesis of H-phosphonates from alkyl and aryl phosphites using mild, gaseous oxidants. This methodology was also shown to be amenable to the use of other oxidants. A radical based mechanism is also proposed for these reactions. This mechanism is likely to be common to all of the reactions studied, regardless of the oxidant involved. In total, nine substrates were synthesised using oxygen as the oxidant in 31P NMR spectral yields of 82% to ≥ 98% and six were synthesised using air as the oxidant in 31P NMR spectral yields of 58% to ≥98%.