Novel 3-C-aminomethyl-hexofuranose-derived thioureas and their testing in asymmetric catalysis

Both 1,2:5,6-di-O-isopropylidene- and 1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranose-derived ketones provided the corresponding branched 3-C-nitromethyl-congeners in the Henry reaction with nitromethane anion. Reduction of the nitro moiety followed by derivatization with iso(thio)cyanates gave 3-C-aminomethyl-hexofuranose-derived (thio)ureas. The relative configuration of the products in each series was unambiguously established by X-ray analysis. The title products were shown to act as organocatalysts in Friedel–Crafts alkylations of indoles with β-nitrostyrenes and in Michael additions of nitromethane to trans-chalcones.

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(3R)-3-C-Nitromethyl-1,2:5,6-di-O-cyclohexylidene-α-d-allofuranoseC19H29NO8[α]D23 = +48 (c 0.20, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (1R,2R,3R,4R,5R)

3-Deoxy-3-C-nitromethylene-1,2:5,6-di-O-cyclohexylidene-α-d-ribo-hexofuranose (Z:E = 25:1)C19H27NO7[α]D23 = +138 (c 0.48, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (3Z,1R,2R,4S,5R)

(3S)-3-C-Nitromethyl-1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranoseC19H29NO8[α]D25 = +28 (c 0.77, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (1R,2R,3S,4R,5R)

(3R)-3-C-Aminomethyl-1,2:5,6-di-O-cyclohexylidene-α-d-allofuranoseC19H31NO6[α]D25 = +24 (c 0.38, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3R,4R,5R)

(3R)-3-C-(N-Phenyloxycarbonyl)aminomethyl-1,2:5,6-di-O-cyclohexylidene-α-d-allofuranoseC26H35NO8[α]D23 = +48 (c 0.65, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3R,4R,5R)

(3R)-1,2:5,6-Di-O-cyclohexylidene-spiro(3-deoxy-α-d-allofuranose-3,5′-oxazolidin)-2′-oneC20H29NO7[α]D23 = +63 (c 0.37, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3R,4R,5R)

(3S)-(1,2:5,6-Di-O-cyclohexylidene-α-d-glucofuranos-3-C-yl)methylammonium tosylateC26H39NO9S[α]D23 = +1.7 (c 0.40, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3S,4R,5R)

(3S)-3-C-(N-Phenyloxycarbonyl)aminomethyl-1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranoseC26H35NO8[α]D23 = +73 (c 0.17, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3S,4R,5R)

(3S)-1,2:5,6-Di-O-cyclohexylidene-spiro(3-deoxy-α-d-glucofuranose-3,5′-oxazolidin)-2′-oneC20H29NO7[α]D23 = +22 (c 0.52, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3S,4R,5R)

(3R)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-ureidomethyl]-1,2:5,6-di-O-isopropylidene-α-d-allofuranose hemihydrateC22H26F6N2O7·0.5H2O[α]D25 = +26 (c 1.20, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (1R,2R,3R,4R,5R)

(3R)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-thioureidomethyl]-1,2:5,6-di-O-isopropylidene-α-d-allofuranoseC22H26F6N2O6S[α]D25 = +8.0 (c 1.00, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (1R,2R,3R,4R,5R)

(3R)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-thioureidomethyl]-1,2-O-isopropylidene-α-d-allofuranoseC19H22F6N2O6S[α]D20 = +54 (c 0.74, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3R,4R,5R)

(3S)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-ureidomethyl]-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose hydrateC22H26F6N2O7·H2O[α]D25 = +31 (c 0.50, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (1R,2R,3S,4R,5R)

(3S)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-thioureidomethyl]-1,2:5,6-di-O-isopropylidene-α-d-glucofuranoseC22H26F6N2O6S[α]D25 = −13 (c 1.00, CHCl3)Source of chirality: the precursor (d-glucose)Absolute configuration: (1R,2R,3S,4R,5R)

(3S)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-thioureidomethyl]-1,2-O-isopropylidene-α-d-glucofuranoseC19H22F6N2O6S[α]D23 = +18 (c 0.35, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3S,4R,5R)

(3R)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-thioureidomethyl]-1,2:5,6-di-O-cyclohexylidene-α-d-allofuranoseC28H34F6N2O6S[α]D23 = +6.4 (c 0.43, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3R,4R,5R)

(3S)-3-C-[(3,5-Bis(trifluoromethyl)phenyl-thioureidomethyl]-1,2:5,6-di-O-cyclohexylidene-α-d-glucofuranoseC28H34F6N2O6S[α]D20 = +4.0 (c 0.55, CHCl3)Source of chirality: the precursorAbsolute configuration: (1R,2R,3S,4R,5R)