Thiazolidine-based organocatalysts for a highly enantioselective direct aldol reaction

A set of enantiopure thiazolidine-based organocatalysts have been synthesized from l-cysteine, in a straightforward manner allowing numerous structural variations. In particular, organocatalyst 3a exhibits the highest catalytic performance working in an aqueous medium. It catalyzed the direct catalytic asymmetric intermolecular aldol reaction between unmodified ketones and an aldehyde with excellent stereocontrol and furnished the corresponding aldol products in up to 99% ee. Compound 3a also showed excellent asymmetric catalytic activity in the asymmetric Michael reaction (up to 99% ee).

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(R)-N-((S)-1-Hydroxy-1,1,3-triphenylpropan-2-yl)thiazolidine-4-carboxamideC25H26N2O2S[α]D20=-44 (c 1, CH2Cl2)Source of chirality: l-cysteine (R) and l-phenylalanine (S)Absolute configuration: (R,S)

(R)-N-((S)-1-Hydroxy-3-phenylpropan-2-yl)thiazolidine-4-carboxamideC13H18N2O2S[α]D20=-20 (c 1, CH2Cl2)Source of chirality: l-cysteine (R) and l-phenylalanine (S)Absolute configuration: (R,S)

(R)-N-((S)-1-Hydroxy-3-methyl-1,1-diphenylbutan-2- yl)thiazolidine-4-carboxamideC21H26N2O2S[α]D20=-73 (c 0.25, CH2Cl2)Source of chirality: l-cysteine (R) and l-valine (S)Absolute configuration: (R,S)

(R)-N-((R)-1-Hydroxy-3-(methylthio)-1,1-diphenylpropan-2-yl)thiazolidine-4-carboxamideC20H24N2O2S2[α]D20=-67 (c 1, CH2Cl2)Source of chirality: l-cysteine (R) and (S)-methyl-l-cysteine (R)Absolute configuration: (R,R)