Enantioselective Henry reaction catalyzed by copper(II)—Cinchona alkaloid complexes

An enantioselective Henry reaction was efficiently carried out under mild reaction conditions in the presence of catalytic 9-epi and natural Cinchona alkaloids and copper (II) acetate. The best catalytic performance was observed for native quinine (12 mol %) and Cu(OAc)2 (10 mol %). Aromatic and aliphatic aldehydes with nitromethane and its α-substituted derivatives provided the corresponding β-nitroalcohols in good to reasonable yields, high syn-diastereoselectivity, and (S)-enantioselectivity of up to 94% ee.

Figure optionsDownload as PowerPoint slide

(−)-(S)-1-(Anthracene-9-yl)-2-nitroethan-1-olC16H13NO368% Ee[α]D20=-10.5 (c 0.16, CH2Cl2)Source of chirality: chiral ligand in asymmetric reactionAbsolute configuration: (S) (by chemical correlation)

syn-(1S,2S)-1-(Anthracene-9-yl)-2-nitrobutan-olC18H17NO390% Ee[α]D20=5.5 (c 0.18, CH2Cl2)Source of chirality: chiral ligand in asymmetric reactionAbsolute configuration: (1S,2S) (by chemical correlation)

anti-(1S,2R)-1-(Anthracene-9-yl)-2-nitrobutan-olC18H17NO397% Ee[α]D20=16.2 (c 0.11, CH2Cl2)Source of chirality: chiral ligand in asymmetric reactionAbsolute configuration: (1S,2S) (by chemical correlation)