Highly enantioselective Friedel–Crafts reaction of indoles with N-sulfonyl aldimines catalyzed by heteroarylidene malonate-type bis(oxazoline) copper(II) complexes

The enantioselective Friedel–Crafts addition of indoles to N-sulfonyl aldimines was studied using a heteroarylidene malonate-type bis(oxazoline) as a chiral ligand. High to excellent enantioselectivities (up to >99% ee) were achieved using the complex of copper(II)–L1b with a benzyl group. The effects of ligand structure, solvent, temperature and substrate on the reaction were also investigated.

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(S)-N-[Indol-3-yl-(4-nitrophenyl)methyl]-4-methylbenzenesulfonamideC22H19N3O4SEe = 87%[α]D25=-23.2 (c 0.32, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(4-fluorophenyl)methyl]-4-methylbenzenesulfonamideC22H19FN2O2SEe = 94%[α]D25=-7.6 (c 0.25, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(4-chlorophenyl)methyl]-4-methylbenzenesulfonamideC22H19ClN2O2SEe = 91%[α]D25=-15.1 (c 0.25, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(4-bromophenyl)methyl]-4-methylbenzenesulfonamideC22H19BrN2O2SEe = 93%[α]D25=-15.5 (c 0.40, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(4-cyanphenyl)methyl]-4-methylbenzenesulfonamideC23H19N3O2SEe = 95%[α]D25=-28.5 (c 0.30, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(4-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC23H19F3N2O2SEe = 96%[α]D25=-33.0 (c 0.42, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(3-nitrophenyl)methyl]-4-methylbenzenesulfonamideC22H19N3O4SEe = 89%[α]D25=-7.2 (c 0.28, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(3-cyanphenyl)methyl]-4-methylbenzenesulfonamideC23H19N3O2SEe = 94%[α]D25=-28.2 (c 0.30, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(3-bromophenyl)methyl]-4-methylbenzenesulfonamideC22H19BrN2O2SEe = 90%[α]D25=-18.2 (c 0.25, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(3-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC23H19F3N2O2SEe = 88%[α]D25=-24.0 (c 0.38, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[Indol-3-yl-(2-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC23H19F3N2O2SEe = 96%[α]D25=-72.4 (c 0.30, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-(Indol-3-yl-phenylmethyl)-4-methylbenzenesulfonamideC22H20N2O2SEe = 90%[α]D25=-10.8 (c 0.25, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[5-Methoxy-indol-3-yl-(4-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC24H21F3N2O3SEe = 91%[α]D25=-24.5 (c 0.30, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[5-Methyl-indol-3-yl-(4-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC24H21F3N2O2SEe = 95%[α]D25=-25.0 (c 0.28, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[5-Chloro-indol-3-yl-(4-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC23H18ClF3N2O2SEe = 97%[α]D25=-28.2 (c 0.28, CH3CO2C2H5)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-N-[6-Chloro-indol-3-yl-(4-trifluoromethylphenyl)methyl]-4-methylbenzenesulfonamideC23H18ClF3N2O2SEe = >99%[α]D25=-50.0 (c 0.15, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)