Organocatalytic asymmetric addition of aliphatic thiols to nitro olefins and nitrodienes

The N-3,5-bis(trifluoromethyl)phenyl thiourea derivative of readily available chiral 1-benzyl-3-aminopyrrolidine was an effective organocatalyst for the asymmetric sulfa-Michael reaction. The adducts of aliphatic thiols to nitro olefins and nitrodienes were formed in good yields and with up to 87% ee in the presence of 2.5 mol % of the organocatalyst.

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(S)-Benzyl (2-nitro-1-phenylethyl) sulfideC15H15NO2S77% ee[α]D20=+185.5 (c 1.54, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(4-fluorophenyl)-2-nitroethyl) sulfideC15H14FNO2S69% ee[α]D20=+172.0 (c 0.35, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(4-bromophenyl)-2-nitroethyl) sulfideC15H14BrNO2S70% ee[α]D20=+170.0 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(4-chlorophenyl)-2-nitroethyl) sulfideC15H14ClNO2S75% ee[α]D20=+185.7 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(2,6-dichlorophenyl)-2-nitroethyl) sulfideC15H13Cl2NO2S66% ee[α]D20=+138.0 (c 0.58, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(2,4-dichlorophenyl)-2-nitroethyl) sulfideC15H13Cl2NO2S68% ee[α]D20=+100.6 (c 0.54, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(2-chlorophenyl)-2-nitroethyl) sulfideC15H14ClNO2S67% ee[α]D20=+83.2 (c 0.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(4-nitrophenyl)-2-nitroethyl) sulfideC15H14N2O4S50% ee[α]D20=+134.7 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(4-methoxyphenyl)-2-nitroethyl) sulfideC16H17NO3S69% ee[α]D20=+175.5 (c 0.51, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-Benzyl (1-(naphthalen-2-yl)-2-nitroethyl) sulfideC19H17NO2S70% ee[α]D20=+191.0 (c 0.52, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(R)-2-(1-(Benzylthio)-2-nitroethyl)thiopheneC13H13NO2S268% ee[α]D20=+175.3 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R) (by chemical correlation)

(S)-2-(1-(Benzylthio)-2-nitroethyl)phenolC15H15NO3S26% ee[α]D20=+72.4 (c 0.38, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(4-Chlorobenzyl) (2-nitro-1-phenylethyl) sulfideC15H14ClNO2S60% ee[α]D20=+157.5 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(4-Chlorobenzyl) (1-(2,4-dichlorophenyl)-2-nitroethyl) sulfideC15H12Cl3NO2S68% ee[α]D20=+99.5 (c 0.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(E)-Benzyl(1-nitro-4-phenylbut-3-en-2-yl) sulfideC17H17NO2S67% ee[α]D20=+154.8 (c 0.30, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(E)-(4-Methoxybenzyl)(1-nitro-4-phenylbut-3-en-2-yl) sulfideC18H19NO3S70% ee[α]D20=+166.5 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(E)-(4-(tert-Butyl)benzyl)(1-nitro-4-phenylbut-3-en-2-yl) sulfideC21H25NO2S82% ee[α]D20=+213.6 (c 0.66, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(E)-2-(((1-Nitro-4-phenylbut-3-en-2-yl)thio)methyl)furanC15H15NO3S78% ee[α]D20=+261.0 (c 0.40, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(S)-(E)-(4-Chlorobenzyl)(1-nitro-4-phenylbut-3-en-2-yl) sulfideC17H16ClNO2S58% ee[α]D20=+169.9 (c 0.98, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S) (by chemical correlation)

(R)-1-(1-Benzylpyrrolidin-3-yl)-3-phenylthioureaC18H21N3S[α]D20=-39.3 (c 0.89, CH2Cl2)Source of chirality: (R)-(−)-1-benzyl-3-aminopyrrolidineAbsolute configuration: (R)

(R)-1-(1-Benzylpyrrolidin-3-yl)-3-(2,4-bis(trifluoromethyl)phenyl)thioureaC20H19F6N3S[α]D20=-56.5 (c 0.46, CH2Cl2)Source of chirality: (R)-(−)-1-benzyl-3-aminopyrrolidineAbsolute configuration: (R)

(R)-1-((1-Benzylpyrrolidin-3-yl)methyl)-3-(3,5-bis(trifluoromethyl)phenyl)thioureaC21H21F6N3S[α]D20=+7.8 (c 0.32, CH2Cl2)Source of chirality: (R)-(+)-1-Benzylpyrrolidine-2-methanolAbsolute configuration: (R)