Enantioselective Michael reaction of nitroalkanes onto nitroalkenes catalyzed by cinchona alkaloid derivatives

An effective asymmetric synthesis of optically active 1,3-dinitro compounds via the direct Michael addition of nitroalkanes onto nitroalkenes has been described. In the presence of readily modified cinchona alkaloid derivatives, nitroethane reacted well with a variety of aromatic and heterocyclic aromatic nitroalkenes to afford products with good diastereoselectivities (dr up to 72/28) and enantioselectivities (ee up to 94%). The catalyst loading can be decreased to 2 mol % without compromising the asymmetric induction or the reaction rate.

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(2R,3R)-1,3-Dinitro-2-phenylbutaneC10H12N2O4Ee = 81%[α]D20=+4.9 (c 0.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(4-bromophenyl)butaneC10H11BrN2O4Ee = 81%[α]D20=+8.5 (c 1.13, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(2-chlorophenyl)butaneC10H11ClN2O4Ee = 80%[α]D20=+12.0 (c 1.12, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(3-chlorophenyl)butaneC10H11ClN2O4Ee = 77%[α]D20=+8.0 (c 0.20, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(4-chlorophenyl)butaneC10H11ClN2O4Ee = 82%[α]D20=+10.2 (c 1.02, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(2-fluorophenyl)butaneC10H11FN2O4Ee = 74%[α]D20=+20.2 (c 1.05, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(3-fluorophenyl)butaneC10H11FN2O4Ee = 83%[α]D20=+20.0 (c 1.05, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(4-fluorophenyl)butaneC10H11FN2O4Ee = 80%[α]D20=+7.3 (c 0.87, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(4-methylphenyl)butaneC11H14N2O4Ee = 82%[α]D20=+11.9 (c 1.27, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(4-methoxyphenyl)butaneC11H14N2O5Ee = 84%[α]D20=+16.8 (c 0.67, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(2-furyl)butaneC8H10N2O5Ee = 80%[α]D20=+17.1 (c 0.87, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(2R,3R)-1,3-Dinitro-2-(2-thienyl)butaneC8H10N2O4SEe = 94%[α]D20=+20.2 (c 1.05, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,3R)

(3R,4R)-2-Methyl-4-nitro-3-(nitromethyl)pentaneC7H14N2O4Ee = 79%[α]D20=-2.1 (c 0.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

((3R,4R,E)-(4-Nitro-3-(nitromethyl)pent-1-enyl)benzeneC12H14N2O4Ee = 65%[α]D20=+31.3 (c 0.4, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(S)-(6-Hydroxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl acetateC21H24N2O3[α]D20=+110.1 (c 0.4, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: (2S,4S,5R,9S)

(S)-(6-Hydroxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl propionateC22H26N2O3[α]D20=+99.0 (c 0.4, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: (2S,4S,5R,9S)

(S)-(6-Hydroxyquinolin-4-yl)((2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl isobutyrateC23H28N2O3[α]D20=+89.5 (c 0.4, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: (2S,4S,5R,9S)