Combining proline and ‘click chemistry’: a class of versatile organocatalysts for the highly diastereo- and enantioselective Michael addition in water

Based on ‘click chemistry’ conditions, a class of novel, facile, versatile pyrrolidine-based triazole derivatives were prepared, and proved to be efficient catalysts for the highly diastereoselective and enantioselective Michael addition of ketones to nitroalkenes. The Cu(I)-catalyzed 1,3-dipolar ‘click’ azide–alkyne cycloaddition provides modular and tunable features for the pyrrolidine-based triazole organocatalysts, and the resulting triazole moiety can serve as a phase tag to complete the reaction in water with an excellent yield and high enantiomeric excess.

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4-Phenyl-1-(((S)-pyrrolidin-2-yl)methyl)-1H-1,2,3-triazoleC13H16N4Ee = 100%[α]D20=+18 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

4-Pentyl-1-(((S)-pyrrolidin-2-yl)methyl)-1H-1,2,3-triazoleC12H22N4Ee = 100%[α]D20=-13 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

1-(((S)-Pyrrolidin-2-yl)methyl)-1H-1,2,3-triazole-4-carboxylic acid methyl esterC9H14N4O2Ee = 100%[α]D20=+12 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

4-Cyclohexenyl-1-(((S)-pyrrolidin-2-yl)methyl)-1H-1,2,3-triazoleC13H22N4Ee = 100%[α]D20=-4 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

4-(Prop-1-en-2-yl)-1-(((S)-pyrrolidin-2-yl)methyl)-1H-1,2,3-triazoleC10H16N4Ee = 100%[α]D20=+12 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)