Asymmetric transfer hydrogenation using a rhodium(I) IN SITU system containing Chiral Sulphoxide Ligands
Creators: name: Macfarlane, Kenneth Shawn
Publisher: name: University of British Columbia
Year: 2010

description: This thesis describes the results from in situ catalytic rhodium(I) systems with acylated methionine sulphoxide ligands for the transfer hydrogenation of aryl alkyl ketones (eq. 1) and imines (eq. 2) from 2-propanol. All the chiral ligands studied are easily prepared derivatives of the amino acid methionine and include: N-acetyl-(S)-methionine-(R,S)-sulphoxide [(S)-AMSO], N-acetyl-(R)-methionine-(R,S)-sulphoxide [(R)-AMSO], and N-benzoyl-(S)-methionine-(R,S)-sulphoxide [(S)-BMSO]. [equation 1 omitted] [equation 2 omitted] The catalytic results for the transfer hydrogenation of acetophenone by (S)-AMSO with [RhCl(1,5-hexadiene)]₂ as the rhodium(I) precursor are, conversion = 26% and e.e. = 30% of the (R)-(+)-1-phenylethanol. The analogous system with (R)-AMSO as the chiral ligand gave approximately the same chemical and optical yields. However, when the ligand is (R)-AMSO, the (S)-(-)-alcohol is produced in excess, as opposed to the R enantiomer. A system with [RhCl(1,5-cyclooctadiene)]₂ added as the catalyst precursor gave, with either (S)- or (R)-AMSO as the chiral ligand, similar results for the optical yield (31-32%), but gave a somewhat larger chemical yield (34-36%) of 1-phenylethanol. With propiophenone as the substrate, the [RhCl(1,5-hexadiene)]₂/ (S)-AMSO system gave a 21% yield of 1-phenyl-l-propanol with 35% e.e. of the (R)-(+)-alcohol. (S)-BMSO was less successful as a ligand under the catalytic conditions used in these studies, giving both low chemical and optical yields with [RhCl(1,5-hexadiene)]₂ (10% and 13%, respectively). Use of this ligand with [RhCl(1,5-cyclooctadiene)]₂ gave more reasonable chemical yields (29%), but no enantiomeric excess was observed in the product. All the catalytic reactions required the addition of KOH as a cocatalyst for the successful transfer of hydrogen from 2-propanol. The reverse reaction, where 1-phenylethanol acts as the hydrogen donor, and acetone as the hydrogen acceptor (or substrate), was also shown to be catalysed by these rhodium(I)-AMSO in situ systems. The chemical yield of acetophenone produced by transfer of hydrogen from racemic 1-phenylethanol to acetone was 15%. However, no e.e. was observed in the remaining 1-phenylethanol, showing it was not enantioselectively dehydrogenated. This in situ rhodium-(5)-AMSO system also catalysed the transfer hydrogenation of the imine N-benzylideneaniline to N-phenylbenzylamine in 80% yield. However, two prochiral imines N-(1-methylbenzyhdene)benzylamine and N-(1-methoxy-2-propylidene)2,6-dimethyl-aniline were not reduced under similar catalytic conditions; KOH was also added as a cocatalyst in these systems. Several attempts at preparing coordination compounds of the ligands AMSO and BMSO proved unsuccessful. Further preparations of coordination compounds were not pursued in favour of concentrating on the more successful transfer hydrogenation studies involving these chiral ligands. [equation 1 omitted] [equation 2 omitted] The catalytic results for the transfer hydrogenation of acetophenone by (S)-AMSO with [RhCl(1,5-hexadiene)]₂ as the rhodium(I) precursor are, conversion = 26% and e.e. = 30% of the (R)-(+)-1-phenylethanol. The analogous system with (R)-AMSO as the chiral ligand gave approximately the same chemical and optical yields. However, when the ligand is (R)-AMSO, the (S)-(-)-alcohol is produced in excess, as opposed to the R enantiomer. A system with [RhCl(1,5-cyclooctadiene)]₂ added as the catalyst precursor gave, with either (S)- or (R)-AMSO as the chiral ligand, similar results for the optical yield (31-32%), but gave a somewhat larger chemical yield (34-36%) of 1-phenylethanol. With propiophenone as the substrate, the [RhCl(1,5-hexadiene)]₂/ (S)-AMSO system gave a 21% yield of 1-phenyl-l-propanol with 35% e.e. of the (R)-(+)-alcohol. (S)-BMSO was less successful as a ligand under the catalytic conditions used in these studies, giving both low chemical and optical yields with [RhCl(1,5-hexadiene)]₂ (10% and 13%, respectively). Use of this ligand with [RhCl(1,5-cyclooctadiene)]₂ gave more reasonable chemical yields (29%), but no enantiomeric excess was observed in the product. All the catalytic reactions required the addition of KOH as a cocatalyst for the successful transfer of hydrogen from 2-propanol. The reverse reaction, where 1-phenylethanol acts as the hydrogen donor, and acetone as the hydrogen acceptor (or substrate), was also shown to be catalysed by these rhodium(I)-AMSO in situ systems. The chemical yield of acetophenone produced by transfer of hydrogen from racemic 1-phenylethanol to acetone was 15%. However, no e.e. was observed in the remaining 1-phenylethanol, showing it was not enantioselectively dehydrogenated. This in situ rhodium-(5)-AMSO system also catalysed the transfer hydrogenation of the imine N-benzylideneaniline to N-phenylbenzylamine in 80% yield. However, two prochiral imines N-(1-methylbenzyhdene)benzylamine and N-(1-methoxy-2-propylidene)2,6-dimethyl-aniline were not reduced under similar catalytic conditions; KOH was also added as a cocatalyst in these systems. Several attempts at preparing coordination compounds of the ligands AMSO and BMSO proved unsuccessful. Further preparations of coordination compounds were not pursued in favour of concentrating on the more successful transfer hydrogenation studies involving these chiral ligands.