Highly diastereo- and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water

A new set of 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamide has been designed and proved to be effective in catalyzing the direct aldol reactions of cyclic ketones with a series of aromatic aldehydes. Furthermore, to the best of our knowledge, there are no reports on the aldol reaction generating the products in very good yields (>99%) and with excellent diastereoselectivities up to >99:1 and enantioselectivities up to >99% by using lower catalyst loadings (only 3 mol %), without using any additives in a large amount of water under mild conditions.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(2S,4R)-4-(tert-Butyldimethylsilyloxy)-N-tosylpyrrolidine-2-carboxamideC18H30N2O4SSi[α]D20=-6.2 (c 0.005, CHCl3)Source of chirality: (2S,4R)-4-hydroxyprolineAbsolute configuration: (2S,4R)

(2S,4R)-4-(tert-Butyldimethylsilyloxy)-N-(4-nitrophenylsulfonyl)pyrrolidine-2-carboxamideC17H27N3O6SSi[α]D20=-12.4 (c 0.005, CHCl3)Source of chirality: (2S,4R)-4-hydroxyprolineAbsolute configuration: (2S,4R)

(2S,4R)-4-(tert-Butyldimethylsilyloxy)-N-(o-tolylsulfonyl)pyrrolidine-2-carboxamideC18H30N2O4SSi[α]D20=-2.5 (c 0.005, CHCl3)Source of chirality: (2S,4R)-4-hydroxyprolineAbsolute configuration: (2S,4R)

(2S,4R)-4-(tert-Butyldimethylsilyloxy)-N-(phenylsulfonyl)pyrrolidine-2-carboxamideC17H28N2O4SSi[α]D20=-8.6 (c 0.005, CHCl3)Source of chirality: (2S,4R)-4-hydroxyprolineAbsolute configuration: (2S,4R)