Efficient parallel resolution of pentafluorophenyl active esters using quasi-enantiomeric combinations of oxazolidin-2-ones

The parallel resolution of racemic pentafluorophenyl 2-aryl/phenylpropanoates and butanoates using an equimolar combination of quasi-enantiomeric Evans oxazolidin-2-ones is discussed. The levels of diastereoselectivity were excellent (>90% de) leading to separable quasi-enantiomeric oxazolidin-2-ones in good yield. This methodology was used to resolve a series of structurally related 2-aryl/phenylpropanoic and butanoic acids.

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(2S,4R)-4-Phenyl-3-(2-phenylpropanoyl)oxazolidin-2-oneC18H17NO3De >98%; ee >98%[α]D20=+88.5 (c 4.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2S,4R)-4-Phenyl-3-(2-phenylbutanoyl)oxazolidin-2-oneC19H19NO3De >98%; ee >98%[α]D20=+77.4 (c 4.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2S,4R)-4-Phenyl-3-(2-phenyl-3-methylbutanoyl)oxazolidin-2-oneC20H21NO3De >98%; ee >98%[α]D20=+78.4 (c 0.5, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2S,4R)-4-Phenyl-3-[2-(4-methylphenyl)propanoyl]oxazolidin-2-oneC19H19NO3De >98%; ee >98%[α]D20=+121.6 (c 0.6, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2S,4R)-4-Phenyl-3-[2-(4-isobutylphenyl)propanoyl]oxazolidin-2-oneC22H25NO3De >98%; ee >98%[α]D20=+118.7 (c 6.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2S,4R)-4-Phenyl-3-[2-(4-chlorophenyl)propanoyl]oxazolidin-2-oneC18H16ClNO3De >98%; ee >98%[α]D20=+144.4 (c 1.6, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2S,4R)-4-Phenyl-3-[2-(6-methoxynaphthalene-2-yl)-oxazolidin-2-oneC23H21NO4De >98%; ee >98%[α]D20=+166.2 (c 1.5, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,R)

(2R,4S)-4-Isopropyl-3-(2-phenylpropanoyl)oxazolidin-2-oneC15H19NO3De >98%; ee >98%[α]D20=-19.8 (c 3.3, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-4-Isopropyl-3-(2-phenylbutanoyl)oxazolidin-2-oneC16H21NO3De >98%; ee >98%[α]D20=-24.6 (c 5.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-4-Isopropyl-3-[2-(4-methylphenyl)propanoyl]oxazolidin-2-oneC16H21NO3De >98%; ee >98%[α]D20=-26.7 (c 1.8, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-4-Isopropyl-3-[2-(4-isobutylphenyl)propanoyl]oxazolidin-2-oneC19H27NO3De >98%; ee >98%[α]D20=-33.0 (c 1.2, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-4-Isopropyl-3-[2-(4-chlorophenyl)propanoyl]oxazolidin-2-oneC15H18ClNO3De >98%; ee >98%[α]D20=-32.4 (c 1.9, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-4-Isopropyl-3-[2-(6-methoxynaphthalene-2-yl)]-oxazolidin-2-oneC20H23NO4De >98%; ee >98%[α]D20=-59.6 (c 3.3, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2S,4S)-Ethyl 2-oxa-3-(2-phenylpropanoyl)oxazolidin-4-carboxylateC15H17NO5De >98%; ee >98%[α]D20=+24.8 (c 5.3, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-Ethyl 2-oxa-3-(2-phenylbutanoyl)oxazolidin-4-carboxylateC16H19NO5De >98%; ee >98%[α]D20=+30.0 (c 8.2, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-Ethyl 2-oxa-3-(2-phenyl-3-methylbutanoyl)oxazolidin-4-carboxylateC17H21NO5De >98%; ee >98%[α]D20=-8.4 (c 0.9, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-Ethyl 2-oxa-3-[2-(4-methylphenyl)propanoyl]oxazolidin-4-carboxylateC16H19NO5De >98%; ee >98%[α]D20=+34.6 (c 0.6, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-Ethyl 2-oxa-3-[2-(4-isobutylphenyl)propanoyl]oxazolidin-4-carboxylateC19H25NO5De >98%; ee >98%[α]D20=+29.8 (c 0.95, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-Ethyl 2-oxa-3-[2-(4-chlorophenyl)propanoyl]oxazolidin-4-carboxylateC15H16ClNO5De >98%; ee >98%[α]D20=+40.0 (c 1.8, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-Ethyl 2-oxa-3-[2-(6-methoxynaphthalene-2-yl)]oxazolidin-2-oneC20H21NO6De >98%; ee >98%[α]D20=+55.7 (c 3.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2R,4R)-4-Phenyl-3-[2-(4-phenyl)propanoyl]oxazolidin-2-oneC18H17NO3De >98%; ee >98%[α]D20=-165.2 (c 2.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,R)

(2R,4R)-4-Phenyl-3-[2-(4-phenyl)butanoyl]oxazolidin-2-oneC19H19NO3De >98%; ee >98%[α]D20=-160.0 (c 0.74, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,R)

(2R,4R)-4-Phenyl-3-[2-(4-methylphenyl)propanoyl]oxazolidin-2-oneC19H19NO3De >98%; ee >98%[α]D20=-179.1 (c 3.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,R)

(2R,4R)-4-Phenyl-3-[2-(4-isobutylphenyl)propanoyl]oxazolidin-2-oneC22H25NO3De >98%; ee >98%[α]D20=-145.7 (c 3.0, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,R)

(2R,4R)-4-Phenyl-3-[2-(4-chlorophenyl)propanoyl]oxazolidin-2-oneC18H16ClNO3De >98%; ee >98%[α]D20=-156.3 (c 1.2, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,R)

(2R,4R)-4-Phenyl-3-[2-(6-methoxynaphthalene-2-yl)oxazolidin-2-oneC23H21NO4De >98%; ee >98%[α]D20=-164.2 (c 1.3, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,R)

(2S,4S)-4-Isopropyl-3-(2-phenylpropanoyl)oxazolidin-2-oneC15H19NO3De >98%; ee >98%[α]D20=+128.9 (c 3.5, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-4-Isopropyl-3-(2-phenylbutanoyl)oxazolidin-2-oneC16H21NO3De >98%; ee >98%[α]D20=+117.6 (c 0.66, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-4-Isopropyl-3-[2-(4-methylphenyl)propanoyl]oxazolidin-2-oneC16H21NO3De >98%; ee >98%[α]D20=+115.5 (c 0.7, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-4-Isopropyl-3-[2-(4-isobutylphenyl)propanoyl]oxazolidin-2-oneC19H27NO3De >98%; ee >98%[α]D20=+117.3 (c 1.3, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-4-Isopropyl-3-[2-(4-chlorophenyl)propanoyl]oxazolidin-2-oneC15H18ClNO3De >98%; ee >98%[α]D20=+101.5 (c 5.8, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2S,4S)-4-Isopropyl-3-[2-(6-methoxynaphthalene-2-yl)]oxazolidin-2-oneC20H23NO4De >98%; ee >98%[α]D20=+194.3 (c 1.6, CHCl3)Source of chirality: chiral poolAbsolute configuration: (S,S)

(2R,4S)-Ethyl 2-oxa-3-(2-phenylpropanoyl)oxazolidin-4-carboxylateC15H17NO5De >98%; ee >98%[α]D20=-130.5 (c 2.1, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-Ethyl 2-oxa-3-(2-phenylbutanoyl)oxazolidin-4-carboxylateC16H19NO5De >98%; ee >98%[α]D20=-131.1 (c 3.3, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-Ethyl 2-oxa-3-(2-phenyl-3-methylbutanoyl)oxazolidin-4-carboxylateC17H21NO5De >98%; ee >98%[α]D20=+19.6 (c 0.2, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-Ethyl 2-oxa-3-[2-(4-methylphenyl)propanoyl]oxazolidin-4-carboxylateC16H19NO5De >98%; ee >98%[α]D20=-125.6 (c 2.5, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-Ethyl 2-oxa-3-[2-(4-isobutylphenyl)propanoyl]oxazolidin-4-carboxylateC19H25NO5De >98%; ee >98%[α]D20=-125.4 (c 1.20, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-Ethyl 2-oxa-3-[2-(4-chlorophenyl)propanoyl]oxazolidin-4-carboxylateC15H16ClNO5De >98%; ee >98%[α]D20=-130.5 (c 1.2, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(2R,4S)-Ethyl 2-oxa-3-[2-(6-methoxynaphthalene-2-yl)]oxazolidin-2-oneC20H21NO6De >98%; ee >98%[α]D20=-140.3 (c 0.9, CHCl3)Source of chirality: chiral poolAbsolute configuration: (R,S)

(S)-2-Phenylpropanoic acidC9H10O2Ee >98%[α]D20=+69.5 (c 8.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Phenylbutanoic acidC10H12O2Ee >98%[α]D20=+65.5 (c 4.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Phenyl-3-methylbutanoic acidC11H14O2Ee = 82%[α]D20=+48.4 (c 2.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(4-Methylphenyl)-2-methylpropanoic acidC9H10O2Ee >98%[α]D20=+64.8 (c 4.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(4-Isobutylphenyl)-2-methylpropanoic acidC13H18O2Ee >98%[α]D20=+58.2 (c 3.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(4-Chlorophenyl)-2-methylpropanoic acidC9H9ClO2Ee >98%[α]D20=+48.5 (c 4.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(6-Methoxynaphth-2-yl)-2-methylpropanoic acidC14H14O3Ee >98%[α]D20=+93.1 (c 4.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)