Enantioselective Henry reaction catalyzed by a copper(II) glucoBOX complex

A highly enantioselective Henry reaction has been developed using a chiral copper(II)–glucoBOX complex. The catalytic system works well with a wide range of aromatic, aliphatic and heteroaromatic aldehydes to afford the corresponding nitroalkanols with high enantioselectivity (up to 99%) in excellent yields (up to 95%). The catalyst shows good enantioselectivity with 10 mol % of loading at easily attainable temperature (10 °C) even in the absence of an inert atmosphere.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(R)-1-(4-Bromophenyl)-2-nitroethanolC8H8BrNO3Ee = 89% from HPLC[α]D = −68.6 (c 1.5, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Nitro-1-phenylethanolC8H9NO3Ee = 94% from HPLC[α]D = −42.6 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Chlorophenyl)-2-nitroethanolC8H8ClNO3Ee = 94% from HPLC[α]D = −38.1 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Fluorophenyl)-2-nitroethanolC8H8FNO3Ee = 90% from HPLC[α]D = −42.9 (c 0.99, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Nitro-1-(4-nitrophenyl)ethanolC8H8N2O5Ee = 83% from HPLC[α]D = −33.6 (c 1.1, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Nitro-1-p-tolylethanolC9H11NO3Ee = 91% from HPLC[α]D = −44.3 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-Methoxyphenyl)-2-nitroethanolC9H11NO4Ee = 90% from HPLC[α]D = −31.9 (c 0.9, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2-Bromophenyl)-2-nitroethanolC8H8BrNO3Ee = 89% from HPLC[α]D = −35.2 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Nitro-1-(2-nitrophenyl)ethanolC8H8N2O5Ee = 91% from HPLC[α]D = −222.3 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2-Methoxyphenyl)-2-nitroethanolC8H11NO4Ee = 90%[α]D = −44.0 (c 1.1, CH2Cl2, 90% ee)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2-Chloro-4-fluorophenyl)-2-nitroethanolC8H7ClFNO3Ee = 90% from HPLC[α]D = −82.3 (c 1.46, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(2,4-Dichlorophenyl)-2-nitroethanolC8H7Cl2NO3Ee = 89% from HPLC[α]D = −51.1 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(3,4-Dimethoxyphenyl)-2-nitroethanolC10H13NO5Ee = 89% from HPLC[α]D = −24.6 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesis.Absolute configuration: (R)

(R)-1-(2,5-Dimethoxyphenyl)-2-nitroethanolC10H13NO5Ee = 99% from HPLC[α]D = −36.6 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-2-Nitro-1-(3,4,5-trimethoxyphenyl)ethanolC11H15NO6Ee = 90% from HPLC[α]D = −23.6 (c 1.1, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-(4-(R)-1-(Naphthalen-1-yl)-2-nitroethanolC12H11NO3Ee = 90% from HPLC[α]D = −24.6 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R,R)

(R)-1-(Naphthalen-2-yl)-2-nitroethanolC12H11NO3Ee = 90% from HPLC[α]D = −14.6 (c 1.0, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

R)-1-Nitropentan-2-ol.C5H11NO3Ee = 77% from HPLC[α]D = −15.2 (c 2.1, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-Nitroheptan-2-ol.C7H15NO3Ee = 84% from HPLC[α]D = −8.5 (c 2.5, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-1-Nitrodecan-2-olC10H21NO3Ee = 82% from HPLC[α]D = −4.5 (c 2.5, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-4-Methyl-1-nitropentan-2-olC6H13NO3Ee = 82% from HPLC[α]D = +2.3 (c 2.5, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(S)-1-(Furan-2-yl)-2-nitroethanolC7H7NO4Ee = 90% from HPLC[α]D = −35.2 (c 0.25, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-2-Nitro-1-(thiophen-2-yl)ethanol.C7H7NO3SEe = 92% from HPLC[α]D = + 20.6 (c 0.25, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(R,E)-1-Nitro-4-phenylbut-3-en-2-ol.C10H11NO3Ee = 85% from HPLC[α]D = −34.2 (c 1, CH2Cl2)Source of chirality: Asymmetric synthesisAbsolute configuration: (R,E)

1-(3,4-Dichlorophenyl)-2-nitropropan-1-ol.C9H9Cl2NO3Ee = 86% (anti-isomer) ; ee = 71% (syn-isomer)[α]D = −21.8 (c 0.98, CHCl3)Source of chirality: Asymmetric synthesis

1-(4-Chlorophenyl)-2-nitropropan-1-olC9H8ClNO3Ee = 80% (anti-isomer) ; Ee = 62% (syn-isomer)[α]D = −11.2 (c 0.6, CHCl3)Source of chirality: Asymmetric synthesis

2-Nitro-1-(2-nitrophenyl)propan-1-ol.C9H10N2O5Ee = 68% (anti-isomer): Ee = 73 %(syn-isomer)[α]D = +106 (c 1.56, CHCl3)Source of chirality: Asymmetric synthesis