Synthesis of enantiomerically pure diethyl (R)- and (S)-2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates

The synthesis and ee determination of diethyl 3-azido-2-hydroxypropylphosphonates from 2,3-epoxypropylphosphonates have been optimised. Enantiomerically enriched diethyl (R)- and (S)-2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates (R)-3a–j and (S)-3a–h as well as (S)-3j were synthesised from diethyl (R)- and (S)-2,3-epoxypropylphosphonates in a reaction sequence including azidolysis followed by 1,3-dipolar cycloaddition with selected alkynes.

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Diethyl (R)-3-azido-2-hydroxypropylphosphonateC7H16N3O4PEe = 96%[α]D20=-4.4 (c 1.45, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-2-hydroxy-3-(4-methoxycarbonyl-1,2,3-triazol-1-yl)propylphosphonateC11H20N3O6PEe = 96%[α]D20=-3.7 (c 5.2, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-3-(4-benzoyloxymethyl-1,2,3-triazol-1-yl)-2-hydroxypropylphosphonateC17H24N3O6PEe = 95%[α]D20=-1.3 (c 2.15, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propylphosphonateC15H22N3O4PEe = 96%[α]D20=+0.7 (c 2.0, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-3-[4-(2-fluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonateC15H21FN3O4PEe = 92%[α]D20=+0.6 (c 1.48, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-3-[4-(3-fluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonateC15H21FN3O4PEe = 96%[α]D20=+0.6 (c 2.06, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-3-[4-(2,4-difluorophenyl)-1,2,3-triazol-1-yl]-2-hydroxypropylphosphonateC15H20F2N3O4PEe = 96%[α]D20=-1.0 (c 3.51, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-2-hydroxy-3-[4-(2-pyridinyl)-1,2,3-triazol-1-yl]propylphosphonateC14H21N4O4PEe = 94%[α]D20=-2.3 (c 1.82, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-2-hydroxy-3-[4-(1-methyl-1H-imidazol-5-yl)-1,2,3-triazol-1-yl]propylphosphonateC13H22N5O4PEe = 92%[α]D20=-2.4 (c 1.82, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-3-(5-amino-4-carbamoyl-1,2,3-triazol-1-yl)-2-hydroxypropylphosphonateC10H20N5O5PEe = 96%[α]D20=-1.0 (c 1.3, CH3OH)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (R)-2-hydroxy-3-(4,5-dimetoxycarbonyl-1,2,3-triazol-1-yl)propylphosphonateC13H22N3O8PEe = 100%[α]D20=-3.7 (c 1.82, CHCl3)Source of chirality: Jacobsen’s catalyst (S,S)-salen Co(III)–OAcAbsolute configuration: (R)

Diethyl (S)-3-azido-2-hydroxypropylphosphonateC7H16N3O4PEe = 96%[α]D20=+4.1 (c 1.63, CHCl3)Source of chirality: Jacobsen’s catalyst (R,R)-salen Co(III)–OAcAbsolute configuration: (S)