Highly enantioselective tandem double Michael reactions catalyzed by Ni(acac)2/(+)-MINBOL complex

An in situ prepared complex of chiral ligand (+)-MINBOL 1 and Ni(acac)2 (12.5 mol % and 0.5 mol % respectively) can efficiently catalyze enantioselective tandem double Michael reactions. In this reaction, aryl or alkyl nitroalkenes were employed as electrophiles. The corresponding tandem adducts were obtained in good yields and with high enantioselectivities (up to 97% ee).

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(2S,3S)-2-((R)-2-Nitro-1-phenylethyl)-1,3-diphenylpentan-1-oneC25H25NO3ee = 95%[α]D22.4 = −26.9 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-2-Nitro-1-p-tolylethyl)-1,3-diphenylpentan-1-oneC26H27NO3ee = 95%[α]D22.6 = −27.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(4-Bromophenyl)-2-nitroethyl)-1,3-diphenylpentan-1-oneC25H24BrNO3ee = 96%[α]D22.8 = −30.2 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(4-Methoxyphenyl)-2-nitroethyl)-1,3-diphenylpentan-1-oneC26H27NO4ee = 97%[α]D22.8 = −23.7 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(4-Chlorophenyl)-2-nitroethyl)-1,3-diphenylpentan-1-oneC25H24ClNO3ee = 97%[α]D22.8 = −29.9 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-2-Nitro-1-(3-(trifluoromethyl)phenyl)ethyl)-1,3-diphenylpentan-1-oneC26H24F3NO3ee = 96%[α]D22.9 = −17.9 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(3-Chlorophenyl)-2-nitroethyl)-1,3-diphenylpentan-1-oneC25H24ClNO3ee = 94%[α]D22.9 = −24.3 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(3-Bromophenyl)-2-nitroethyl)-1,3-diphenylpentan-1-oneC25H24BrNO3ee = 96%[α]D22.9 = −21.4 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(3-Methoxyphenyl)-2-nitroethyl)-1,3-diphenylpentan-1-oneC26H27NO4ee = 97%[α]D22.8 = −38.8 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-4-Methyl-3-(nitromethyl)-1-phenyl-2-((S)-1-phenylpropyl)pentan-1-oneC22H27NO3ee = 97%[α]D25.8 = −138.7 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,S)

(2S,3S)-3-(Nitromethyl)-1-phenyl-2-((S)-1-phenylpropyl)hexan-1-oneC22H27NO3ee = 97%[α]D26.1 = −85.4 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,S)

(2S,3S)-3-(4-Methoxyphenyl)-2-((R)-2-nitro-1-phenylethyl)-1-phenylpentan-1-oneC26H27NO4ee = 96%[α]D22.9 = −57.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-2-Nitro-1-phenylethyl)-1-phenyl-3-p-tolylpentan-1-oneC26H27NO3ee = 96%[α]D22.9 = −46.8 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-3-(4-Chlorophenyl)-2-((R)-2-nitro-1-phenylethyl)-1-phenylpentan-1-oneC25H24ClNO3ee = 93%[α]D23.0 = −49.2 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-3-(3-Chlorophenyl)-2-((R)-2-nitro-1-phenylethyl)-1-phenylpentan-1-oneC25H24ClNO3ee = 93%[α]D22.8 = −28.6 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-1-(4-Chlorophenyl)-2-((R)-2-nitro-1-phenylethyl)-3-phenylpentan-1-oneC25H24ClNO3ee = 95%[α]D22.8 = −29.8 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)

(2S,3S)-2-((R)-1-(4-Bromophenyl)-2-nitroethyl)-3-(4-methoxyphenyl)-1-phenylpentan-1-oneC26H26BrNO4ee = 91%[α]D22.9 = −57.8 (c 1.0, CH2Cl2)Source of chirality: asymmetric tandem double Michael reactionsAbsolute configuration: (S,S,R)