Proline-based dipeptides as efficient organocatalysts for asymmetric aldol reactions in brine

Simple N-proline-based dipeptides with two N–H groups in combination with 2,4-dinitrophenol (DNP) catalyze the direct asymmetric aldol reactions of aldehydes with a broad range of ketones to furnish the corresponding aldol products in high yields (up to 99%) and with high enantioselectivities (up to 97%) and diastereoselectivities (up to >99:1, anti/syn) at room temperature and in brine.

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(S)-2-Amino-N-(4-(piperidin-1-yl)pyridin-3-yl)propanamideC13H20N4O[α]D25=+16.5 (c 0.2, CHCl3)Source of chirality: (S)-alanineAbsolute configuration: (S)

(S)-2-Amino-N-(4-(piperidin-1-yl)pyridin-2-yl)propanamideC13H20N4O[α]D25=-15.3 (c 0.2, CHCl3)Source of chirality: (S)-alanineAbsolute configuration: (S)

(S)-N-((S)-1-Oxo-1-((4-(piperidin-1-yl)pyridin-3-yl)amino)propan-2-yl)pyrrolidine-2-carboxamideC18H27N5O2[α]D25=-230.2 (c 0.2, CHCl3)Source of chirality: (S)-alanine and (S)-prolineAbsolute configuration: (S,S)

(S)-N-((S)-1-Oxo-1-((4-(piperidin-1-yl)pyridin-2-yl)amino)propan-2-yl)pyrrolidine-2-carboxamideC18H27N5O2[α]D25=-94.9 (c 0.2, CHCl3)Source of chirality: (S)-alanine and (S)-prolineAbsolute configuration: (S,S)