Catalytic asymmetric nitroaldol (Henry) reactions with copper(II)/cyclopropane-based bisoxazoline complexes

A series of cyclopropane-based bisoxazolines were synthesized from (R)- and (S)-amino alcohols, and applied to copper-catalyzed enantioselective nitroaldol reactions between nitromethane and various aldehydes. The reactions generated β-hydroxy nitroalkanes in high yields (97%) and with good enantioselectivities (up to 87% ee). The effects of the oxazoline stereocenters constructed in the Henry reactions were also studied.

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(1R,2S)-1,2-Bis[4(S)-isopropyloxazolin-2-yl]-3,3-dimethylcyclopropaneC17H28N2O2[α]D20=-131.3 (c 1.6, CHCl3)Source of chirality: (S)-valinol

(1R,2S)-1,2-Bis [4(S)-tert-butyloxazolin-2-yl]-3,3-dimethylcyclopropaneC19H32N2O2[α]D20=-135.8 (c 2.1, CHCl3)Source of chirality: (S)-tert-leucinol

(1R,2S)-1,2-Bis[4(S)-benzyloxazolin-2-yl]-3,3-dimethylcyclopropaneC25H28N2O2[α]D20=-56.5 (c 0.78, CHCl3)Source of chirality: (S)-phenylalaninol

(1R,2S)-1,2-Bis[4(R)-phenyloxazolin-2-yl]-3,3-dimethylcyclopropaneC23H24N2O2[α]D25=+160.2 (c 1.5, CHCl3)Source of chirality: (R)-phenylglycinol

(1R,2S)-1,2-Bis[4(S)-phenyloxazolin-2-yl]-3,3-dimethylcyclopropaneC23H24N2O2[α]D20=-152.3 (c 2.0, CHCl3)Source of chirality: (S)-phenylglycinolAbsolute configuration: (1R,2S)

(1R,2S)-1,2-Bis[4(R)-phenyloxazolin-2-yl]-3,3-dimethylcyclopropaneC17H28N2O2[α]D25=+126.5 (c 2.4, CHCl3)Source of chirality: (R)-phenylglycinolAbsolute configuration: (1R,2S)