Amino acid- and imidazolium-tagged chiral pyrrolidinodiphosphine ligands and their applications in catalytic asymmetric hydrogenations in ionic liquid systems

Herein we report the synthesis of amino acid- and imidazolium-tagged chiral pyrrolidinodiphosphine ligands and the catalytic efficiency and reusability of their corresponding Rh-catalysts in the asymmetric hydrogenation of methyl (Z)-2-acetamidocinnamate in different reaction media, including classical organic solvents, ionic liquid (IL) [bmim]BF4 (1-n-butyl-3-methyl-imidazolium tetrafluoroborate) and [bmim]BF4/cosolvent systems. The effects of the ionic tag structures, IL, cosolvents, Rh precursors, and halide impurities on catalytic activity and enantioselectivity were studied in detail. In the hydrogenation reaction, the amino acid- and imidazolium modified ligands gave higher ee values than the classical pyrrolidinodiphosphine, (2S,4S)-N-(tert-butoxycarbonyl)-4-(diphenylphosphino)-2-[(diphenylphosphino) methyl] pyrrolidine (BPPM), both in pure methanol and in the [bmim]BF4/MeOH system. The catalyst recycling experiments demonstrated that introducing the amino acid and imidazolium moieties into the pyrrolidinodiphosphine backbone resulted in much better immobilization and reusability of the Rh-catalysts in [bmim]BF4, and after several cycles there was no significant loss in activity, enantioselectivity, or Rh.

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Boc-l-Asp(OtBu)-PPM (PPM: (2S,4S)-4-(diphenylphosphino)-2-[(diphenyl-phosphino) methyl] pyrrolidine)C42H50N2O5P2[α]D20=-27.0 (c 0.5, CH2Cl2)(S)-tert-butyl 3-(tert-butoxycarbonylamino)-4-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-4-oxobutanoatechiral source: trans-4-Hydroxy-L-proline

Boc-l-Asp(PPM)-OtBuC42H50N2O5P2[α]D20=-10.3 (c 0.5, CH2Cl2)(S)-tert-butyl 2-(tert-butoxycarbonylamino)-4-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-4-oxobutanoatechiral source: trans-4-Hydroxy-L-proline

Boc-d-Asp(PPM)-OtBuC42H50N2O5P2[α]D20=-37.2 (c 0.1, CH2Cl2)(R)-tert-butyl 2-(tert-butoxycarbonylamino)-4-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-4-oxobutanoatechiral source: trans-4-Hydroxy-L-proline

Boc-l-Glu(OtBu)-PPMC43H52N2O5P2[α]D20=-14.2 (c 0.5, CH2Cl2)(S)-tert-butyl 4-(tert-butoxycarbonylamino)-5-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-5-oxopentanoatechiral source: trans-4-Hydroxy-L-proline

Boc-l-Glu(PPM)-OtBuC43H52N2O5P2[α]D20=-8.7 (c 0.5, CH2Cl2)(S)-tert-butyl 2-(tert-butoxycarbonylamino)-5-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-5-oxopentanoatechiral source: trans-4-Hydroxy-L-proline

NH2-l-Asp-PPM·CF3COOHC33H34N2O3P2·CF3COOH[α]D20=-37.5 (c 0.24, EtOH)(S)-3-carboxy-1-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-1-oxopropan-2-aminium trifluoroacetatechiral source: trans-4-Hydroxy-L-proline

NH2-l-Asp(PPM)-OH·CF3COOHC33H34N2O3P2·CF3COOH[α]D20=-7.8 (c 0.25, MeOH)(S)-3-carboxy-1-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-1-oxopropan-3-aminium trifluoroacetatechiral source: trans-4-Hydroxy-L-proline

NH2-d-Asp(PPM)-OH·CF3COOHC33H34N2O3P2·CF3COOH[α]D20=-15.0 (c 0.1, MeOH)(R)-3-carboxy-1-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-1-oxopropan-3-aminium trifluoroacetatechiral source: trans-4-Hydroxy-L-proline

NH2-l-Glu-PPM·CF3COOHC34H36N2O3P2·CF3COOH[α]D20=-12.0 (c 0.25, MeOH)(S)-4-carboxy-1-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-1-oxobutan-2-aminium trifluoroacetatechiral source: trans-4-Hydroxy-L-proline

NH2-l-Glu(PPM)-OH·CF3COOHC34H36N2O3P2·CF3COOH[α]D20=-7.8 (c 0.25, MeOH)(S)-4-carboxy-1-{(2’S,4’S)-4’-(diphenylphosphino)-2’-[(diphenylphosphino)methyl]pyrrolidin-1’-yl}-1-oxobutan-4-aminium trifluoroacetatechiral source: trans-4-Hydroxy-L-proline

[C35H36N3OP2]BF4[α]D20=-34.8 (c 0.25, MeOH)1-{1’- {(2’’S,4’’S)-4’’-(diphenylphosphino)-2’’-[(diphenylphosphino)methyl]pyrrolidin-1’’-yl}-1’-oxoeth-2’-yl}-3-methyl-imidazolium tetrafluoroboratechiral source: trans-4-Hydroxy-L-proline