Asymmetric fluorination of 4-substituted pyrazolones catalyzed by quinine

An asymmetric fluorination process of 4-substituted pyrazolones catalyzed by quinine is revealed. The reaction afforded a wide range of 4-fluorinated pyrazol-5-ones with excellent yields (up to 98%) and moderate to good enantioselectivities (up to 81% ee).

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4-Benzyl-4-fluoro-1,3-diphenyl-1H-pyrazol-5(4H)-oneC22H17FN2O51% ee[α]D22 = −51.6 (c 0.28, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(4-fluorobenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC22H16F2N2O40% ee[α]D22 = −45.0 (c 0.55, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-1,3-diphenyl-4-(4-(trifluoromethyl)benzyl)-1H-pyrazol-5(4H)-oneC23H16F4N2O41% ee[α]D22 = −51.1 (c 0.36, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(2-nitrobenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC22H16FN3O342% ee[α]D22 = −37.4 (c 0.56, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(3-methylbenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC23H19FN2O71% ee[α]D26 = −95.2 (c 0.46, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(4-methoxybenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC23H19FN2O267% ee[α]D25 = −65.8 (c 0.55, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(2-methylbenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC23H19FN2O68% ee[α]D25 = −75.4 (c 0.50, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(furan-2-ylmethyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC20H15FN2O257% ee[α]D22 = −69.0 (c 0.45, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-1,3-diphenyl-4-(thiophen-2-ylmethyl)-1H-pyrazol-5(4H)-oneC20H15FN2OS45% ee[α]D22 = −76.0 (c 0.58, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-4-(naphthalen-1-ylmethyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC26H19FN2O81% ee[α]D26 = −89.8 (c 0.55, CH2Cl2)Source of chirality: asymmetric fluorination

4-Allyl-4-fluoro-1,3-diphenyl-1H-pyrazol-5(4H)-oneC18H15FN2O35% ee[α]D26 = −43.5 (c 0.47, CH2Cl2)Source of chirality: asymmetric fluorination

4-Fluoro-1,3-diphenyl-4-(prop-2-ynyl)-1H-pyrazol-5(4H)-oneC18H13FN2O40% ee[α]D21 = −35.7 (c 0.45, CH2Cl2)Source of chirality: asymmetric fluorination

4-Benzyl-3-(4-bromophenyl)-4-methyl-1-phenyl-1H-pyrazol-5(4H)-oneC23H19BrN2O37% ee[α]D26 = −19.4 (c 0.66, CH2Cl2)Source of chirality: asymmetric fluorination

4-Benzyl-4-fluoro-1-phenyl-3-p-tolyl-1H-pyrazol-5(4H)-oneC23H19FN2O51% ee[α]D26 = −43.5 (c 0.53, CH2Cl2)Source of chirality: asymmetric fluorination

4-Benzyl-4-fluoro-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-5(4H)-oneC23H19FN2O253% ee[α]D26 = −28.1 (c 0.46, CH2Cl2)Source of chirality: asymmetric fluorination