The research work covered in this thesis is focused on the preparation of P-chiral bis-phosphine oxides, and an examination of the effectiveness of these reagents as ligands in various asymmetric catalysed reactions. Racemic tert-butyl-phenylphosphine oxide was converted into (R_p)- and (S_p)- tert-butylphenylphosphinothioic acids 5 and 7. These were then converted into the corresponding resolved secondary phosphine oxides 2 and 3 by desulfurization. The phosphinothioic acids, and the secondary phosphine oxides, were then used in the preparation of the bis-phosphine oxides....[ Read more ]

The research work covered in this thesis is focused on the preparation of P-chiral bis-phosphine oxides, and an examination of the effectiveness of these reagents as ligands in various asymmetric catalysed reactions. Racemic tert-butyl-phenylphosphine oxide was converted into (R_p)- and (S_p)- tert-butylphenylphosphinothioic acids 5 and 7. These were then converted into the corresponding resolved secondary phosphine oxides 2 and 3 by desulfurization. The phosphinothioic acids, and the secondary phosphine oxides, were then used in the preparation of the bis-phosphine oxides.

tert-Buty(phenylhydroxymethyl)phenylphosphine oxide 36 was prepared from the secondary phosphine oxide and paraformaldehyde, and converted into the corresponding phosphinate 203 by treatment with tert-butylphenylphosphinobromidate 36. However, attempts to rearrange this product into the (hydroxymethylene)-bisphosphine oxide 212 in the presence of a strong base were unsuccessful. Further, it was found that lithiated secondary phosphine oxide 2 reacted with benzoyl chloride to give not the (hydroxyphenyl)methylene bis-phosphine oxide 72 as was previously reported, but rather the phosphinate 209. Attempts to rearrange this into the (hydroxyphenyl)methylene bis-phosphine oxide 72 were not successful. Similarly, an attempt to prepare the methylene bis-phosphine oxide 215 by reaction of lithiated secondary phosphine oxide 2 with either the bromidate 36 or imidazolide 198 were not successful.

A series of other bis-phosphine oxides, such as 2,6-bis[(tert-butylphenylphosphinyl)methyl]pyridine 41 and 42, and ethane-1,2-diyl[bis(tert-butylphenylphosphinyl)diamidate] 202 were prepared. Aryl phosphinates such as the BINOL-derived compound 203 were also prepared and rearranged in the presence of strong base into o-hydroxyaryl phosphine oxides, such as the binaphthyl bis phosphine oxides 109 and 110.

The compounds prepared above were used as ligands in the asymmetric catalytic addition of the thiols 2-naphthalenethiol and 2-mercaptoisoborneol to 2-cyclohexenone, 2-cyclopentenone, benzalacetophenone and crotonaldehyde. For the addition reactions ethylenediamine was also used, except in the cases of the pyridyl bis-phosphine oxide ligands 41 and 42, which are already basic. Whilst it was found that the ligands were necessary for the reaction, the enantiomer excesses of the products were generally less than 30%. Similarly, ligand acceleration was observed in the Sharpless AD reaction, but in the case of dihydroxylation of styrene or (E)-stilbene, enantiomer excesses were less than 9%. Finally, the phosphine oxides were evaluated in the presence of scandium triflate or titanium tetraisopropoxide in the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene or trans-1,3-methyl-butadiene in dichloromethane. However, enantiomer excesses was very low, usually less than 20%. Acceleration by the ligands were observed in all cases.

It was concluded that for better results, the tert-butyl and phenyl groups attached to the P-chiral centre have to be replaced by the stereochemically more disparate groups such as methyl and 1-naphthyl. Once methods are developed to synthesize the corresponding ligands, these will be examined.