Abstract
Palladium-catalysed cross-coupling reactions have remarkably contributed to the transformation of carbon-carbon and carbon-heteroatom bonds in synthetic chemistry. As the application of these versatile reactions expands in academic and industrial settings, so does the demand for robust and active catalysts. Catalyst systems derived from biaryl phosphines have proven to be successful in this regard, contributing significantly to the tremendous advancements of this field. The main objective of this study was to develop novel biaryl phosphacyclic ligands and explore their catalytic potentials in Pd-catalysed cross-coupling reactions. Furthermore, studies of the ligands’ stereoelectronic properties were aimed to provide critical structure-activity correlations, which could be pivotal in future ligand design and development in this field of research.
The discovery and advancement of biaryl phosphine ligands in Pd-catalysed cross-coupling reactions is summarised in Chapter 1. This chapter highlights not only the synthesis of various biaryl phosphines and their catalytic evaluation at bench-top and industrial scales, but also ligand properties, which are often synonymous with overall catalytic potentials. Following the “state-of-the-art” dialkylbiaryl phosphines as well as industrially relevant P-bridged phosphines, our ligand design approach was based on combining the indispensable benefits of both the easily tuneable biaryl backbone, and the rigid 9-phosphabicyclo[3.3.1]nonane (s-Phob) and 1,3,5,7-tetramethyl-2,4,6-trioxa-8-phosphatricyclo[3.3.1.1]decane (Cg) frameworks. The synthesis and characterisation of the novel biaryl P-bridged phosphacyclic ligands are described in Chapter 2.
Prior to their catalytic evaluation, the investigation of steric and electronic properties of the newly developed biaryl phosphacyclic ligands is discussed in Chapter 3. This chapter, which included a comprehensive assessment of experimental and theoretical methods for ligand parameterisation, revealed the reliability of steric and electronic parameters derived from the corresponding phospho-selenides.
The evaluation of the newly developed biaryl phosphacyclic ligands as well as commercially available dialkylbiaryl phosphines in Pd-catalysed Suzuki-Miyaura (Chapter 4), borylation (Chapter 5), and Heck (Chapter 6) cross-coupling reactions demonstrated the significant role of the ligand’s steric properties in the described
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reactions. Although the ligand’s electronic properties appeared to contribute less to ligand efficiency, the sensitivity of the preferred ligand steric bulk was noticeable in coupling reactions of aryl chlorides. The strongly electron-deficient biphenyl phosphacyclic ligand derived from the Cg moiety (biphenyl-Cg, L3) exhibited optimal steric bulk for efficient Pd-catalysed coupling reactions of aryl chlorides with a variety of coupling partners. On the other hand, the outstanding of the efficiency of the biphenyl phosphacyclic ligand derived from the less hindered s-Phob moiety (biphenyl-s-Phob, L1) in Pd-catalysed coupling reactions of sterically hindered substrates is also noteworthy. The overall conclusions and experimental procedures are described in Chapters 6 and 7, respectively.