This thesis described investigations into the synthesis and reactions of chiral monophosphines, in five chapters. Chapter 1 introduces asymmetric catalysis, Chapter 2 and 3 describe the synthesis of enantiomerically pure monophosphine via an oxide and borane route respectively. Chapter 4 describes the organometallic reactions of these monophosphines and Chapter 5 contains experimental details of the reactions. <strong>Chapter 1</strong> describes the importance of chirality and significant asymmetric processes. The literature methods of producing homochiral monophosphines are detailed. <strong>Chapter 2</strong> describes the synthesis of enantiomerically enriched monophosphine oxides. Diastereomerically pure (2R, 4S, 5R)-2-chloro-5-phenyl-3,4-dimethyl-1,3,2-oxazaphospholidine was prepared from PCl<sub>3</sub> and (-)-ephedrine. This compound was reacted with 2-adamantyl magnesium bromide to afford (2R, 4S, 5R) and (2S, 4S, 5R)-3,4-dimethyl-2-2-adamantyl-5-phenyl-1,3,2-oxazaphospholidin-2-oxide after oxidation with <sup>t</sup>BuOOH. An X-ray crystal structure was obtained of the R<sub>P</sub> diastereoisomer and a detailed NMR study carried out on the S<sub>P</sub> diastereoisomer. The R<sub>P</sub> diastereoisomer was reacted with 2-methoxyphenylmagnesium bromide to give R<sub>P</sub>-N-methyl-N-(1S,2S)-(1-methyl-2-hydroxy-2-phenyl)-ethyl-P-(2-methoxyphenyl)-P-(2-adamantyl)phosphinamide in 68% yield and 95% d.e. The ephedrinyl residue was replaced by O-methyl under acid catalysis with inversion of configuration and with >85% e.e. Displacement of the methoxy group using phenyl lithium occurred with inversion of configuration to give the corresponding phosphine oxide in 65% e.e., which could be reduced under forcing conditions using polymethylhydrosiloxane in the presence of Ti(O<sup>i</sup>Pr)<sub>4</sub>. <strong>Chapter 3</strong> describes the synthesis of enantiomerically enriched monophosphines via phosphine borane complexes. Diastereomerically pure (2R, 4S, 5R)-2,5-diphenyl-3,4-dimethyl-1,3,2-oxazaphospholidine borane was prepared directly from PhPCl<sub>2</sub> and (-)-ephedrine, followed by oxidation with BH<sub>3</sub>.Me<sub>2</sub>S. This compound reacted regiospecifically with ortho-anisyl lithium to afford the product formed by P-O cleavage with >96% d.e. and with retention of configuration at phosphorus. The ephedrinyl residue was replaced by O-methyl under acid conditions with inversion of configuration and with >98% e.e. Ferrocenyl, 1-adamantyl and tert-butyl lithium reagents displaced the methoxy group with inversion of configuration and with >92% e.e., as determined by <sup>1</sup>H NMR methods. The phosphine borane complexes were then reduced quantitatively with Et<sub>2</sub>NH with retention of configuration and with >98% e.e. <strong>Chapter 4</strong> describes the synthesis of indium and rhodium complexes of (S)-t-butyl-(2-methoxyphenyl)-phenyl phosphine and (S)-ferrocenyl-(2-methoxyphenyl)-phenyl phosphine. The iridium complexes are shown to reduce a range of prochiral olefins, including Z-methyl-2-acetylamino-3-phenylpropenoate (MAC) in up to 19% e.e. The di-(R,R)-(ferrocenyl-(2-methoxyphenyl)-phenyl phosphine) rhodium complex is more selective, reducing MAC in 54% e.e., while the rhodium complex of (S)-t-butyl-(2-methoxyphenyl)-phenyl phosphine reduces MAC in 24% e.e.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:318786 |
| Date | January 1995 |
| Creators | Laing, John Christopher Pettigrew |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:c24d74bf-d5f9-4997-9c14-5aa419dfe8ba |
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