Organocatalyzed Baylis–Hillman reaction: an enantioselective approach

A convenient protocol has been developed for the synthesis of Baylis–Hillman adducts in the presence of a base and an organocatalyst. We have designed and synthesized organocatalysts based on hydrogen bonding using a pyrrolidine ring as the backbone and applied them to Baylis–Hillman transformations. This method provides products in good to high yields (73–90%) and with excellent enantiomeric excesses (up to 96%) and reasonable reaction times.

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(S)-1-Acetyl-N-tosylpyrrolidine-2-carboxamideC14H18N2O4S[α]D27=-125.7 (c 0.5, ethyl acetate)Source of chirality: l-ProlineAbsolute configuration: (S)

(R)-Methyl 2-[(4-fluorophenyl)(hydroxy)methyl] acrylateC11H11FO3[α]D27=-53.2 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-(hydroxy(4-nitrophenyl) methyl)acrylateC11H11NO5[α]D27=-15.5 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-(hydroxy(3-nitrophenyl)methyl)acrylateC11H11NO5[α]D27=-61.3 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: 2-(R)

(R)-Methyl 2-[(4-cyanophenyl)(hydroxy)methyl]acrylateC12H11NO3[α]D27=-58.4 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-[(4-chlorophenyl)(hydroxy)methyl]acrylateC11H11ClO3[α]D27=-10.2 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-[(2-chlorophenyl)(hydroxy)methyl]acrylateC11H11ClO3[α]D27=+11.7 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-(hydroxy(phenyl)methyl)acrylateC11H12O3[α]D27=-44.6 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-(hydroxy(4-hydroxyphenyl)methyl)acrylateC11H12O4[α]D27=-9.4 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-(hydroxy(4-methoxyphenyl)methyl)acrylateC12H14O4[α]D27=-12.3 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Methyl 2-(hydroxy(p-tolyl)methyl)acrylateC12H14O3[α]D27=+31.2 (c 0.5, ethyl acetate)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-1-Acetyl-N-(methylsulfonyl) pyrrolidine-2-carboxamideC8H14N2O4S[α]D27=-89.5 (c 0.5, ethyl acetate)Source of chirality: L-ProlineAbsolute configuration: (S)

(S)-1-Acetyl-N-(4-nitrophenylsulfonyl) pyrrolidine-2-carboxamideC13H15N3O6S[α]D27=-112.5 (c 0.5, ethyl acetate)Source of chirality: L-ProlineAbsolute configuration: (S)