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Title: Optically active methylene-diphos ligands via a P/Si exchange reaction
Author: Hazeland, E. Louise
ISNI:       0000 0004 6059 3792
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2016
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The synthesis of optically-active diphos ligands is normally multi-step and/or requires an optical resolution step. This thesis reports a mild, one-step route to optically active, C1-backbone diphos ligands via a P/Si exchange reaction between a chlorophosphite and a (phosphinomethyl)silane. The route is remarkably efficient, where the only by-product of the reaction is CISiMe3 which is volatile and readily removed from the reaction mixture. The route is shown to be modular,and has been used to make R2P(CH2)P(OR')2, R2P(CH2)PR'2, R2P(CHR" )P(OR')2 and R2P(NH)P(OR)2 type ligands, where P(OR)2 and PR'2 are optically active phosphacycles. Rh(I) complexes of the C1-backbone diphos ligands were applied to the asymmetric hydrogenation of three benchmark substrates DMI, MAA and MAC with up to 99% ee obtained; the catalyst loading was reduced to 0.2 mol% for one example. Furthermore, analysis of the quadrant blocking diagrams for the complexes confirmed that the absolute configurations of the products of asymmetric hydrogenation conform to the quadrant rule. The potential of this synthetic route for high throughput experimentation methods was demonstrated through a one-pot procedure to generate the Rh(I) complex in situ. The 97% ee obtained compared favourably with the 98% ee obtained with the isolated complex. A mechanistic investigation was carried out in order to understand the scope and limitations of the P/Si exchange route. The order of reaction with respect to both P reagents was found to be (pseudo) zero order. An initial rate dependence was found on the initial concentration of the chlorophosphite, suggesting an impurity was catalysing the reaction; this was identified as HCI (H+); the reaction was completely inhibited by addition of NEt3. The mechanism has been proposed to proceed via a secondary phosphine ylide intermediate R2P(H)CHSiMe3. Evidence for this intermediate was provided by: (i) the observation of exchange of the optically active phosphacycle during a cross-over experiment; (ii) a Peterson-like reaction upon addition of an aldehyde to a phosphinosilane; (iii) deuterium incorporation into the CH2 backbone of the diphos product upon addition of DCI to the reaction of the chlorophosphite with the (phosphinomethyl)silane. Kinetic simulations of the proposed model gave excellent fits with a wide range of experimental data, including varying concentrations of both of the reagents and addition of HCI. The P/Si exchange route was extended to the synthesis of optically active, unsymmetrical diphos ligands with a NH-backbone. The free ligands were found to form almost exclusively as the P-P=N tautomer in solution, and then tautomerised to the PNP isomer upon heating or coordination to Pd(II) or Rh(I). Furthermore, the proton of the PNP was found to reside on the P of the PiPr2 group in solution, evident from a large J PH value in both the 1 Hand 31 P NMR spectra. A Rh(I) complex of one P rp ligand was applied to the asymmetric hydrogenation of DMI, MAA and MAC, but the PNP complex gave only 57-80% ee. To probe electronic effects in asymmetric hydrogenation, two isosteric C1-backbone ligands were prepared, one with a binol group and one where the 0 atoms are replaced by CH2 groups. The asymmetric hydrogenation results from their Rh(I) complexes compared. The Rh(I) complex of the ligand with two strongly σ-donating P-.atoms gave lower enantioselectivities than the phosphine-phosphonite derivative. The crystal structures of the [PtCh(L)] (L = (binol)PCH2PtBu2 or (R2HC)PCH2PtBu2) complexes showed differences in the P-Pt bond lengths which may point to the source of the difference in the selectivity of the ligands in catalysts. Finally, ligands of the type R2P(CHR" )P(OR')2 ligands have been synthesised via the P/Si exchange reaction. The presence of a chiral centre on the backbone lead to two diastereomers of the ligand. The Rh(I) complexes of these ligands were screened for the asymmetric hydrogenation of MAA and MAC and in most cases were observed to give slightly higher enantioselectivities than the CH2 analogues.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available