Stereoselective cyclopropanation of unsaturated acetals, using carbohydrates with d-gluco, l-rhamno and d-xylo configurations as chiral auxiliaries

The stereoselective synthesis of (2-phenylcyclopropyl)methylidene acetals of sugar derivatives from methyl d-glucopyranoside, dodecyl N-acetyl-2-amino-2-deoxy-d-glucopyranoside, 1,2-O-isopropylidene-d-glucofuranose, methyl l-rhamnopyranoside and 1,2-O-isopropylidene-d-xylofuranose, as a chiral auxiliary, is described. The cyclopropanation reaction of the corresponding alkenylidene derivatives with CH2I2/ZnEt2 took place with different stereoselectivity, depending on the configuration on the acetal carbon, the size of the acetal ring, the sugar configuration, the protecting group of the hydroxyl groups of the sugar and the substitution of the unsaturated system. The stereochemistry of the new stereogenic centres was then determined by acid hydrolysis of the cyclopropane moiety of the chiral auxiliary, which was also recovered.

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Methyl 4-O-benzyl-2,3-O-[(S,E)-3-phenyl-2-propenylidene]-α-l-rhamnopyranosideC23H26O5Ee = 100%[α]D25=-63.2 (c 1.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 2,3-O-(S,E)-, α-l-rhamno

Methyl 4-O-benzyl-2,3-O-[(R,E)-3-phenyl-2-propenylidene]-α-l-rhamnopyranosideC23H26O5Ee = 100%[α]D25=-36.0 (c 0.7, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 2,3-O-(R,E)-, α-l-rhamno

Methyl 4-O-benzyl-2,3-O-[(S,E)-2-methyl-3-phenyl-2-propenylidene]-α-l-rhamnopyranosideC24H28O5Ee = 100%[α]D25=-43.8 (c 1.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 2,3-O-(S,E)-, α-l-rhamno

Methyl 4-O-benzyl-2,3-O-[(R,E)-2-methyl-3-phenyl-2-propenylidene]-α-l-rhamnopyranosideC24H28O5Ee = 100%[α]D25=-6.0 (c 0.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 2,3-O-(R,E)-, α-l-rhamno

3-O-Benzyl-5,6-O-[(S,E)-3-phenyl-2-propenylidene]-1,2-O-isopropylidene-α-d-glucofuranoseC25H28O6Ee = 100%[α]D25=-4.7 (c 0.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 5,6-O-(S,E)-, α-d-glucofuranose

3-O-Benzyl-5,6-O-[(S,E)-2-methyl-3-phenyl-2-propenylidene]-1,2-O-isopropylidene-α-d-glucofuranoseC26H30O6Ee = 100%[α]D25=-10.7 (c 0.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 5,6-O-(S,E)-, α-d-glucofuranose

Methyl 2,3-di-O-benzyl-4,6-O-[(R,E)-3-phenyl-2-propenylidene]-α-d-glucopyranosideC30H32O6Ee = 100%[α]D25=+6.8 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(R,E)-, α-d-glucopyranose

Methyl 2,3-di-O-benzyl-4,6-O-[(R,E)-2-methyl-3-phenyl-2-propenylidene]-α-d-glucopyranosideC31H34O6Ee = 100%[α]D25=+29.2 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(R,E)-, α-d-glucopyranose

Methyl 4-O-benzyl-2,3-O-[(1S,2R,3R)-(2-phenylcyclopropyl)methylidene]-α-l-rhamnopyranosideC24H28O5De = 26%[α]D25=-17.8 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 2,3-O-(1S,2R,3R)-, α-l-rhamno

Methyl 4-O-benzyl-2,3-O-[(1R,2S,3S)-(2-phenylcyclopropyl)methylidene]-α-l-rhamnopyranosideC24H28O5De = 57%[α]D25=-15.3 (c 1.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 2,3-O-(1R,2S,3S)-, α-l-rhamno

1,2-O-Isopropylidene-5,6-O-[(1S,2R,3R)-(2-phenylcyclopropyl)methylidene]-α-d-glucofuranoseC19H24O6De = 49%[α]D25=-6.3 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 5,6-O-(1S,2R,3R)-, α-d-glucofuranose

3-O-Benzyl-1,2-O-isopropylidene-5,6-O-[(1S,2S,3S)-(2-phenylcyclopropyl)methylidene]-α-d-glucofuranoseC26H30O6De = 4.8%[α]D25=+12.9 (c 1.2, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 5,6-O-(1S,2S,3S)-, α-d-glucofuranose

Methyl 4,6-O-[(1R,2R,3R)-(2-phenylcyclopropyl)methylidene]-α-d-glucopyranosideC17H22O6De = 20%[α]D25=+82.8 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(1R,2R,3R)-, α-d-glucopyranose

Methyl 4,6-O-[(1R,2R,3S)-(1-methyl-2-phenylcyclopropyl)methylidene]-α-d-glucopyranosideC18H24O6De = 4.8%[α]D25=+94.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(1R,2R,3S)-, α-d-glucopyranose

Methyl 2,3-di-O-benzyl-4,6-O-[(1R,2R,3R)-(2- phenylcyclopropyl)methylidene]-α-d-glucopyranosideC31H34O6De = 33%[α]D25=+79.9 (c 0.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(1R,2R,3R)-, α-d-glucopyranose

Methyl 2,3-dibenzyl-4,6-O-[(1R,2R,3S)-(1-methyl-2-phenylcyclopropyl)methylidene]-α-d-glucopyranosideC32H36O6De = 4.8%[α]D25=+31.4 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(1R,2R,3S)-, α-d-glucopyranose

1-Dodecyl 2-acetamido-3-O-benzyl-2-deoxy-4,6-O-[(1R,2R,3R)-(2-phenylcyclopropyl)methylidene]-β-d-glucopyranosideC37H53NO6De = 46%[α]D25=+4.0 (c 4.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 4,6-O-(1R,2R,3R)-, α-d-glucopyranose

1,2-O-Isopropylidene-3,5-O-[(1S,2R,3R)-(2-phenylcyclopropyl)methylidene]-α-d-xylofuranoseC18H22O5De = 80%[α]D25=-60.4 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3R)-, α-d-xylofuranose

1,2-O-Isopropylidene-3,5-O-[(1S,2R,3S)-(1-methyl-2-phenylcyclopropyl)methylidene]-α-d-xylofuranoseC19H24O5De = 50%[α]D25=-12.9 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3S)-, α-d-xylofuranose