Isoquinoline-based diimine ligands for Cu(II)-catalyzed enantioselective nitroaldol (Henry) reactions

A series of isoquinoline-based chiral diimine ligands are conveniently prepared via Bischler–Napieralski cyclization. The C2-symmetric diimine ligand 1a is effective in Cu(II)-catalyzed enantioselective Henry reactions between nitromethane and various aldehydes (11 examples), showing 50–89% yield and 75–93% ee.

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(S)-2-(Cyclohexylmethyl)-1-toluenesulfonylaziridineC16H23NO2S[α]D24=-6.4 (c 0.22, CHCl3)Initial source of chirality: (S)-2-amino-3-cyclohexylpropan-1-olAbsolute configuration: (S)

(S)-1-Cyclohexyl-3-phenylpropan-2-amineC15H23N[α]D23=+9.7 (c 0.27, CHCl3)Initial source of chirality: (S)-2-amino-3-cyclohexylpropan-1-olAbsolute configuration: (S)

N,N′-Bis((S)-1-cyclohexyl-3-phenylpropan-2-yl)oxalamideC32H44N2O2[α]D23=-21.9 (c 0.29, CHCl3)Initial source of chirality: (S)-2-amino-3-cyclohexylpropan-1-olAbsolute configuration: (S,S)

(3S,3′S)-3,3′-Bis(cyclohexylmethyl)-3,3′,4,4′-tetrahydro-1,1′-biisoquinolineC32H40N2[α]D23=-12.9 (c 0.37, CHCl3)Initial source of chirality: (S)-2-amino-3-cyclohexylpropan-1-olAbsolute configuration: (3S, 3′S)

(R)-3,3-Dimethyl-1-phenylbutan-2-amineC12H19N[α]D22=+48.6 (c 0.88, CHCl3)Initial source of chirality: (S)-2-amino-3,3-dimethylbutan-1-olAbsolute configuration: (R)

N, N′- Bis((R)-3,3-dimethyl-1-phenylbutan-2-yl)oxalamideC26H36N2O2[α]D22=36.3 (c 0.54, CHCl3)Initial source of chirality: (S)-2-amino-3,3-dimethylbutan-1-olAbsolute configuration: (R,R)

(3R,3′R)-3,3′-Di-tert-butyl-3,3′,4,4′-tetrahydro-1,1′-biisoquinolineC26H32N2[α]D22=+204.8 (c 0.62, CHCl3)Initial source of chirality: (S)-2-amino-3,3-dimethylbutan-1-olAbsolute configuration: (3R, 3′R)

Dichloro[(3S,3′S)-3,3′-diisobutyl-3,3′,4,4′-tetrahydro-1,1′-biisoquinoline]-palladium(II)C26H32Cl2N2Pd[α]D23=-702.5 (c 0.43, CHCl3)Initial source of chirality: (S)-2-amino-4-methylpentan-1-olAbsolute configuration: (3R,3′R)

(S)-1-(3-Fluorophenyl)-2-nitroethanolC8H26FN2O391% ee[α]D23=+26.8 (c 0.26, CH2Cl2)Initial source of chirality: asymmetric nitroaldol reactionAbsolute configuration: (S)