Totally diastereoselective addition of aryl Grignard reagents to the nitrone-based chiral glycine equivalent MiPNO

The reaction of the chiral nitrone MiPNO (2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-one) with Grignard reagents is totally diastereoselective. Using simple and functionalized arylmagnesium reagents, enantiopure hydroxylamines were obtained in fair to good yields, which in turn could be easily transformed into new chiral ketonitrones. The preparation of enantiopure l-phenylglycine derivatives is also described.

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(2R,5R)-5-Biphenyl-4-yl-1-hydroxy-2-isopropyl-2,3-dimethyl-imidazolidin-4-oneC20H24N2O2>98% ee[α]D25=-123.9 (c 0.96, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-2-isopropyl-2,3-dimethyl-5-pentafluorophenyl-imidazolidin-4-oneC14H15F5N2O2>98% ee[α]D25=+14.8 (c 0.94, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-5-(4-methoxycarbonylphenyl)-2-isopropyl-2,3-dimethylimidazolidin-4-oneC16H22N2O4>98% ee[α]D25=-82.9 (c 1.00, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-2-isopropyl-5-(4-methoxy-phenyl)-2,3-dimethyl-imidazolidin-4-oneC15H22N2O3>98% ee[α]D25=-104.1 (c 1.04, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-2-isopropyl-2,3-dimethyl-5-p-tolyl-imidazolidin-4-oneC15H22N2O2>98% ee[α]D25=-115.0 (c 1.00, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-2-isopropyl-2,3-dimethyl-5-phenyl-imidazolidin-4-oneC14H20N2O2>98% ee[α]D25=-108.2 (c 0.98, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2S,5S)-1-Hydroxy-2-isopropyl-5-(2-methoxy-phenyl)-2,3-dimethyl-imidazolidin-4-oneC15H22N2O3>98% ee[α]D25=+61.7 (c 1.04, acetone)Source of chirality: (S)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2S,5S)

(2R,5R)-5-(4-Dimethylamino-phenyl)-1-hydroxy-2-isopropyl-2,3-dimethyl-imidazolidin-4-oneC16H25N3O2>98% ee[α]D25=-111.3 (c 1.10, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-2-isopropyl-2,3-dimethyl-5-thiophen-2-yl-imidazolidin-4-oneC12H18N2O2S>98% ee[α]D25=-64.9 (c 1.24, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-5-(4-Bromo-phenyl)-1-hydroxy-2-isopropyl-2,3-dimethyl-imidazolidin-4-oneC14H19BrN2O2>98% ee[α]D25=-106.9 (c 1.38, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)

(2R,5R)-1-Hydroxy-5-(4-iodo-phenyl)-2-isopropyl-2,3-dimethyl-imidazolidin-4-oneC14H19IN2O2>98% ee[α]D25=-104.8 (c 1.14, acetone)Source of chirality: (R)-2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-oneAbsolute configuration: (2R,5R)