Organocatalytic asymmetric hydroarylation of o-hydroxyl styrenes via remote activation of phenylhydrazones

The first catalytic asymmetric styrene hydroarylation reaction has been established via the enantioselective Friedel–Crafts alkylations of phenylhydrazones with o-hydroxyl styrenes under the catalysis of a chiral phosphoric acid as an organocatalyst, leading to the construction of a chiral 1,1-diarylethane scaffold with high enantioselectivity (up to 89% ee). The investigation on the activation mode suggested that the two reactants, o-hydroxyl styrenes and phenylhydrazones, were simultaneously activated by the catalyst via multiple hydrogen-bonds. The remote activation of the hydrazone functionality by a dual hydrogen-bonding interaction with the catalyst contributed greatly to the hydroarylation reaction of the o-hydroxyl styrenes.

Figure optionsDownload as PowerPoint slide

(R,E)-2-(1-{4-[N′-(4-Nitro-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC21H19N3O3[α]D20 = −28.4 (c 0.16, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-2-(1-{4-[N′-(3-Nitro-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC21H19N3O3[α]D20 = −46.3 (c 0.1, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-4-({4-[1-(2-Hydroxy-5-methyl-phenyl)-ethyl]-phenyl}-hydrazonomethyl)-benzonitrileC22H19N3O[α]D20 = −15.6 (c 0.25, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-3-({4-[1-(2-Hydroxy-phenyl)-ethyl]-phenyl}-hydrazonomethyl)-benzonitrileC22H19N3O[α]D20 = +12.5 (c 0.24, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-2-(1-{4-[N′-(4-Trifluoromethyl-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC22H19F3N2O[α]D20 = −47.8 (c 0.1, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-2-(1-{4-[N′-(3-Trifluoromethyl-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC22H19F3N2O[α]D20 = −19.0 (c 0.12, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-4-({4-[1-(2-Hydroxy-phenyl)-ethyl]-phenyl}-hydrazonomethyl)-benzoic acid methyl esterC23H22N2O3[α]D20 = +94.3 (c 0.1, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-2-Fluoro-5-({4-[1-(2-hydroxy-phenyl)-ethyl]-phenyl}-hydrazonomethyl)-benzonitrileC22H18FN3O[α]D20 = −23.3 (c 0.1, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-4-Methyl-2-(1-{4-[N′-(4-nitro-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC22H21N3O3[α]D20 = +9.6 (c 0.1, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-4-Methoxy-2-(1-{4-[N′-(4-nitro-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC22H21N3O4[α]D20 = +11.3 (c 0.2, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)

(R,E)-4-tert-Butyl-2-(1-{4-[N′-(4-nitro-benzylidene)-hydrazino]-phenyl}-ethyl)-phenolC25H27N3O3[α]D20 = +28.4 (c 0.42, CHCl3)Source of chirality: the catalystAbsolute configuration: (R)