Asymmetric organocatalytic N-nitroso-aldol reaction of oxindoles

An organocatalytic enantioselective N-nitroso-aldol reaction of 2-oxindoles promoted by a cinchona alkaloid catalyst has been developed. The reaction shows exclusively N-selectivity, affording corresponding products with good to excellent yields (up to 100%) and moderate enantioselectivity. The regioselectivity of nitroso-aldol reaction being controlled by different cinchona catalysts was also observed.

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(S)-3-(Hydroxy(phenyl)amino)-3-methylindolin-2-oneC15H14N2O2Ee 67%[α]D20=+43.4 (c 0.5, THF)Absolute configuration: (S)

(S)-3-Allyl-3-(hydroxy(phenyl)amino)indolin-2-oneC17H16N2O2Ee 67%[α]D20=+41.4 (c 5, THF)Absolute configuration: (S)

(S)-3-Cinnamyl-3-(hydroxy(phenyl)amino)indolin-2-oneC23H20N2O2Ee 62%[α]D20=+33.8 (c 0.4, THF)Absolute configuration: (S)

(S)-3-Benzyl-3-(hydroxy(phenyl)amino)indolin-2-oneC21H18N2O2Ee 72%[α]D20=+62.0 (c 0.5, THF)Absolute configuration: (S)

(S)-3-(Hydroxy(phenyl)amino)-3-(4-methoxybenzyl)indolin-2-oneC22H20N2O3Ee 64%[α]D20=+78.4 (c 0.5, THF)Absolute configuration: (S)

(S)-3-(Hydroxy(phenyl)amino)-3-(4-methylbenzyl)indolin-2-oneC22H20N2O2Ee 67%[α]D20=+68.8 (c 0.5, THF)Absolute configuration: (S)

(S)-4-((3-(Hydroxy(phenyl)amino)-2-oxoindolin-3-yl)methyl)benzonitrileC22H17N3O2Ee 59%[α]D20=+88.2 (c 0.5, THF)Absolute configuration: (S)

(S)-3-(3-Chlorobenzyl)-3-(hydroxy(phenyl)amino)indolin-2-oneC21H17ClN2O2Ee 66%[α]D20=+57.6 (c 0.5, THF)Absolute configuration: (S)

(S)-3-(Benzo[d][1,3]dioxol-5-ylmethyl)-3-(hydroxy(phenyl)amino)indolin-2-oneC22H18N2O4Ee 63%[α]D20=+55.0 (c 1.0, THF)Absolute configuration: (S)

(S)-3-Methyl-3-(phenylamino)indolin-2-oneC15H14N2OEe 65%[α]D20=-13.6 (c 1.0, DCM)Absolute configuration: (S)