From allylic alcohols to chiral tertiary homoallylic alcohol: palladium-catalyzed asymmetric allylation of isatins

A palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as an allyl donor was developed by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols 3-allyl-3-hydroxy-2-oxindoles were prepared directly from allylic alcohols in one step with excellent yields and moderate enantioselectivities. This represents the first catalytic asymmetric allylation of ketones with allylic alcohol as the allylating agent.

Figure optionsDownload as PowerPoint slide

N-Methyl-N-phenyl-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC24H22NO2PEe = 100%[α]D25=-25.5 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

N-Ethyl-N-phenyl-[(R)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC25H24NO2PEe = 100%[α]D25=+89.8 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (R)

N,N-Diphenyl-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC29H24NO2PEe = 100%[α]D25=-171 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

N-Phenyl-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC23H20NO2PEe = 100%[α]D17=-103 (c 0.5, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

N-Methyl-N-(4-methoxyphenyl)-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC25H24NO3PEe = 100%[α]D25=-20.4 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

N-Methyl-N-(4-chlorophenyl)-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC24H21NO2PClEe = 100%[α]D25=+8.9 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

N-Methyl-N-(2,6-dimethylphenyl)-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC26H26NO2PEe = 100%[α]D25=-105 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

(Indolin-1-yl)-[(S)-1,1′-spirobiindane-7,7′-diyl]-phosphoramiditeC25H22NO2PEe = 100%[α]D25=-144 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (S)

N-Methyl-N-phenyl-[(R)-1,1′-spirobiindane-6,6′-dimethyl-7,7′-diyl]-phosphoramiditeC26H26NO2PEe = 100%[α]D25=+219 (c 1.0, CH2Cl2)Source of chirality: resolutionAbsolute configuration: (R)

(+)-3-Allyl-3-hydroxy-1-methylindolin-2-oneC12H13NO2Ee = 71%[α]D29=+21.4 (c 1.05, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-1,3-Diallyl-3-hydroxyindolin-2-oneC14H15NO2Ee = 63%[α]D29=+18.9 (c 0.98, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-3-hydroxy-1-neopentylindolin-2-oneC16H21NO2Ee = 62%[α]D29=+37.3 (c 1.35, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-1-benzyl-3-hydroxyindolin-2-oneC18H17NO2Ee = 56%[α]D29=+5.2 (c 1.55, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-3-hydroxy-1-phenylindolin-2-oneC17H15NO2Ee = 62%[α]D29=+23.3 (c 1.25, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-3-hydroxy-1-tosylindolin-2-oneC18H17NO4SEe = 47%[α]D29=+5.2 (c 1.33, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-5-chloro-3-hydroxy-1-methylindolin-2-oneC12H12NO2ClEe = 46%[α]D29=+2.7 (c 0.98, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-3-hydroxy-5-methoxy-1-methylindolin-2-oneC13H15NO3Ee = 53%[α]D29=+8.0 (c 1.33, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-3-hydroxy-1,5-dimethylindolin-2-oneC13H15NO2Ee = 54%[α]D29=+7.0 (c 1.33, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-7-chloro-3-hydroxy-1-methylindolin-2-oneC12H12NO2ClEe = 52%[α]D29=+11.3 (c 1.40, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Allyl-3-hydroxy-1,7-dimethylindolin-2-oneC13H15NO2Ee = 64%[α]D29=+15.8 (c 1.33, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Hydroxy-1-methyl-3-(2-methylallyl)indolin-2-oneC13H15NO2Ee = 48%[α]D29=+15.1 (c 1.18, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Hydroxy-1-methyl-3-(2-phenylallyl)indolin-2-oneC18H17NO2Ee = 57%[α]D29=+6.0 (c 1.55, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Hydroxy-3-(2-(4-methoxyphenyl)allyl)-1-methylindolin-2-oneC19H19NO3Ee = 50%[α]D29=+1.1 (c 1.70, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-Hydroxy-1-methyl-3-(2-(4-(trifluoromethyl)phenyl)allyl)indolin-2-oneC19H16F3NO2Ee = 60%[α]D29=+3.0 (c 1.90, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

(+)-3-(2-Benzylallyl)-3-hydroxy-1-methylindolin-2-oneC19H19NO2Ee = 48%[α]D29=+9.7 (c 1.80, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: unknown