New class of bifunctional thioureas from l-proline: highly enantioselective Michael addition of 1,3-dicarbonyls to nitroolefins

A new class of bifunctional tertiary amine thiourea was synthesized from l-proline. The reported thiourea is amenable to steric and electronic modifications at the stereogenic center bearing a thiourea moiety. Excellent enantioselectivity was obtained in the Michael addition of 2,4-pentanedione to various nitro olefins using the new organocatalyst. The construction of contiguous stereocenters via the Michael reaction of substituted 1,3-dicarbonyls to nitro olefins was also carried out with very good yield, enantioselectivity, and diastereoselectivity.

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(S)-2-((S)-Azido(phenyl)methyl)-1-tritylpyrrolidineC30H28N4[α]D25=-99.3 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

(S)-2-((S)-Azido(phenyl)methyl)pyrrolidineC11H14N4[α]D25=-184.6 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

(S)-2-((S)-Azido (phenyl)methyl)-1-ethylpyrrolidineC13H18N4[α]D25=-165.3 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

(S)-2-((S)-Azido(phenyl)methyl)-1-benzylpyrrolidineC18H20N4[α]D25=-105.0 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

(S)-2-((S)-Azido(phenyl)methyl)-1-methylpyrrolidineC12H16N4[α]D25=-119.0 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-((S)-1-ethylpyrrolidin-2-yl)(phenyl)methyl)thioureaC22H23F6N3S[α]D25=-82.2 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

1-((S)-((S)-1-Benzylpyrrolidin-2-yl)(phenyl)methyl)-3-(3,5-bis(trifluoromethyl)phenyl)thioureaC27H25F6N3S[α]D25=-127.2 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

1-(3,5-Bis(trifluoromethyl)phenyl)-3-((S)-((S)-1-methylpyrrolidin-2-yl)(phenyl)methyl)thioureaC21H21F6N3S[α]D25=-43.5 (c 1.0, CHCl3)Source of chirality: (S)-ProlineAbsolute Configuration: (S,S)

(R)-3-(2-Nitro-1-phenylethyl)pentane-2,4-dioneC13H15NO4ee = 96%[α]D25=-196.2 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(2-Chlorophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14ClNO4ee = 98%[α]D25=-152.4 (c 0.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(3-Chlorophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14ClNO4ee = 99%[α]D25=-46.7 (c 0.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(4-Chlorophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14ClNO4ee = 98%[α]D25=-19.2 (c 0.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(2-Bromophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14BrNO4ee = 99%[α]D25=-209.3 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(3-Bromophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14BrNO4ee = 96%[α]D25=-132.6 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(4-Bromophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14BrNO4ee = 97%[α]D25=-137.1 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(4-Fluorophenyl)-2-nitroethyl)pentane-2,4-dioneC13H14FNO4ee = 97%[α]D25=-12.9 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(2-Methoxyphenyl)-2-nitroethyl)pentane-2,4-dioneC14H17NO5ee = 94%[α]D25=-186.1 (c 0.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(4-Methoxyphenyl)-2-nitroethyl)pentane-2,4-dioneC14H17NO5ee = 94%[α]D25=-119.7 (c 2.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(2-Nitro-1-(p-tolyl)ethyl)pentane-2,4-dioneC14H17NO4ee = 96%[α]D25=-78.2 (c 2.8, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(S)-3-(2-Nitro-1-(thiophen-2-yl)ethyl)pentane-2,4-dioneC11H13NO4See = 94%[α]D25=-80.6 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (S)

(R)-3-(2-Nitro-1-(2-nitrophenyl)ethyl)pentane-2,4-dioneC13H14N2O6ee = 98%[α]D25=-130.6 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(4-Hydroxy-3-methoxyphenyl)-2-nitroethyl) pentane-2,4-dioneC14H17NO6ee = 95%[α]D25=-38.1 (c 0.25, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(3-Bromo-4-methoxyphenyl)-2-nitroethyl) pentane-2,4-dioneC14H16BrNO5ee = 95%[α]D25=-118.1 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-3-(1-(Benzo[d][1,3]dioxol-5-yl)-2-nitroethyl)pentane-2,4-dioneC14H15NO6ee = 95%[α]D25=-102.0 (c 0.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R)

(R)-Ethyl 1-((S)-2-nitro-1-phenylethyl)-2-oxocyclopentanecarboxylateC16H19NO5ee = 99%[α]D25=-58.8 (c 0.5, CHCl3)Source of chirality: Asymmetric synthesisAbsolute Configuration: (R,S)