Synthesis and application of polar phosphine ligands.

The successful application of Tppts, and its derivatives, in biphasic transition metal-catalysed reactions opened up a new field of chemistry requiring a rational design of water-soluble ligands. The main objective of the research described in this dissertation was the preparation and the application of new water-soluble phosphine ligands. The ligands were prepared by the use of carbon nucleophiles and chlorophenylphosphine derivatives. The carbon nucleophiles included malonate derivates, which were subsequently reduced to the di-alcohols and were transformed into water-soluble phosphines by the reaction with 1,4-butanesultone. Secondary and tertiary malonate nucleophiles were used and the steric demands of compounds containing more than one malonate group were investigated. Various attempts to obtain water-soluble compounds from dimalonate phosphine oxides failed. TBDMS-protected aryl halides were also used as nucleophiles. One (or two) of these silyl ethers was reacted with chlorophenylphosphine derivatives and after deprotection with TBAF the compounds were made water-soluble by a reaction with 1,4-butanesultone. The hydrogenation of arylphosphine oxides to form cyclohexylphosphine oxide derivatives was also investigated. However, these cyclohexylphosphines were more easily obtained by the reaction between the previously mentioned carbon nucleophiles and chlorocyclohexylphosphine derivatives, which were freshly prepared. A series of cyclohexyl-containing water-soluble phosphines was prepared in this way. The oxygen sensitive nature of phosphines lead to two different approaches in the reaction route: the phosphines were either borane protected followed by a subsequent deprotection step, or the phosphines were allowed to oxidise and were reduced back to the free phosphine at a later stage. The efficiency of both approaches in the reaction routes was examined. The deprotection of phosphine-boranes was performed using various “new” deprotecting reagents and the borane-species and free phosphines were separated using water/organic extractions. The various extraction coefficients of the amine-borane complexes were determined. The newly prepared ligands were used in a variety of palladium-catalysed reactions as well as in the hydroformylation of 1-octene employing rhodium. The reactions were performed in both neat organic solvents as well as mixtures between water and DMF or toluene and the results were compared to the use of Tpp and Tppts. It was found that many of the new ligands afforded superior yields compared to those of Tpp and Tppts. In the last part of the study, various diphenylphosphinic amides were used as DoM-groups. Sec- and tert-BuLi were used together with a variety of electrophiles to facilitate ortho-substitution on either one or two rings on the amides. This was seen as a start of a new approach towards functionalised phosphine ligands.Prof. D.B.G. William