Abstract
The design of catalysts for transition metal-mediated reactions is an active field in chemistry in the 21st century. It has been well recognised that ligands employed in these processes have a significant impact on the outcome of the reactions. The design and application of ligands in homogeneous catalysis reactions were the overarching aims of this project.
Two areas were explored in this project, on the ligand synthesis side:
1. The use of directed ortho metallation (DoM) technology to synthesise unsymmetrical phosphines.
2. The synthesis of sterically hindered phosphines and their application to transition metal-mediated reactions.
For the first sub-project, a range of N,N-dialkyl-diphenylphosphinic amides was synthesised in near quantitative yields. Deprotonation with s-BuLi and quenching the anion formed in the reaction with a range of electrophiles resulted in the desired ortho-substituted products in good yields. Differentiation of the second aromatic ring was possible, if the isolated mono-substituted products were used in further DoM reactions as starting materials. This methodology provided a range of highly substituted unsymmetrical phosphinic amides. Incorporation of other directing groups can change the selectivity of subsequent DoM reactions providing efficient routes to 2,2’ and 2,6-disubstituted products.
Hydrolysis of the phosphinic amide moiety to the phosphinic acid with aqueous HCl, chlorination (SOCl2) and reaction of the acid chloride with a range of Grignard reagents provided an efficient method for the conversion of the phosphinic amide into a P-chirogenic but racemic phosphine oxide. Known methodology can convert this phosphine oxide into a phosphine that can be applied to transition metal catalysed reactions. This methodology provides an
effective method for the synthesis of highly functionalised unsymmetrical phosphines. The approach facilitated substantial modifications to the ligand, which allows for efficient tailoring thereof for the metal-mediated reaction in which it is to be used.
In the second sub-project, the DoM reaction was again employed but with (diaryl or dialkyl) phosphines as electrophilic quenches, resulting in the isolation of sterically hindered phosphines. Comparison between the ligands was made using the palladium-catalysed Suzuki reactions (catalytic approaches), Vaska type complexes (electronic effects) and phosphine selenium coupling constants (stereo-electronic effects). It was concluded that steric bulk and electronic characteristics affect the activity of catalysts formed from the ligands of this study, in line with the literature. The ligands were successfully applied to the palladium-catalysed Suzuki reaction using strongly deactivated aryl bromides and also some activated aryl chlorides as substrates at low (0.1% Pd) catalyst loadings. Significant improvements in catalytic activity were observed as the project progressed, using a structure-activity study as a guide.
Prof. D.B.G. Williams