The use of 1,2-O-isopropylidene-α-d-xylofuranose as a chiral auxiliary in asymmetric cyclopropanation reactions

The stereoselective synthesis of cyclopropylmethylidene acetals derived from 1,2-O-isopropylidene-d-xylofuranose, as a chiral auxiliary, is described. The Simmons–Smith cyclopropanation reaction of the corresponding alkenylidene derivatives with CH2I2/ZnEt2, in different reaction conditions, took place with high stereoselectivity. The diastereomeric excess in each case depended on the solvent and the temperature used in the reaction. The absolute configuration of the new stereogenic centres formed was determined by acid hydrolysis of the cyclopropane moiety of the chiral auxiliary, which was also recovered.

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1,2-O-Isopropylidene-3,5-O-[(S,E)-3-(2-nitrophenyl)-2-propenylidene]-α-d-xylofuranoseC17H19NO7Ee = 100%[α]D25=-12.5 (c 0.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

1,2-O-Isopropylidene-3,5-O-[(S,E)-3-(2-methoxyphenyl)-2-propenylidene]-α-d-xylofuranoseC18H22O6Ee = 100%[α]D25=+5.4 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

1,2-O-Isopropylidene-3,5-O-[(S,E)-3-(4-methoxyphenyl)-2-propenylidene]-α-d-xylofuranoseC18H22O6Ee = 100%[α]D25=+13.0 (c 1.0, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

3,5-O-[(S,E)-3-(4-Dimethylaminophenyl)-2-propenylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC19H25NO5Ee = 100%[α]D25=+19.3 (c 1.0, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

3,5-O-[(S,E)-2-Butenylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC12H18O5Ee = 100%[α]D25=-6.2 (c 1.1, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

3,5-O-[(S,E)-2-Decenylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC18H30O5Ee = 100%[α]D25=-3.6 (c 1.3, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

3,5-O-[(S)-3,3-Diphenyl-2-propenylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC23H24O5Ee = 100%[α]D25=-53.7 (c 1.0, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S)-, α-d-xylofuranose

3,5-O-[(S,E)-2-Hexyl-3-phenyl-2-propenylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC23H32O5Ee = 100%[α]D25=+15.0 (c 1.0, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S,E)-, α-d-xylofuranose

3,5-O-[(S,Z)-2-Hexyl-3-phenyl-2-propenylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC23H32O5Ee = 100%[α]D25=-52.9 (c 1.2, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S,Z)-, α-d-xylofuranose

3,5-O-[(S)-(1-Cyclohexenyl)methylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC15H22O5Ee = 100%[α]D25=-2.8 (c 1.0, CH2Cl2)Source of chirality: chiral poolAbsolute configuration: 3,5-O-(S)-, α-d-xylofuranose

1,2-O-Isopropylidene-3,5-O-[(1S,2R,3R)-(2-phenylcyclopropyl)methylidene]-α-d-xylofuranoseC18H22O5De = 82%[α]D25=-61.7 (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,3R)-2-[(2-nitrophenyl)cyclopropyl]methylidene}-α-d-xylofuranoseC18H21NO7De = 78%[α]D25=-42.8 (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,3R)-2-[(2-methoxyphenyl)cyclopropyl]methylidene}-α-d-xylofuranoseC19H24O6De = 77%[α]D25=-60.6 (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,3R)-2-[(4-methoxyphenyl)cyclopropyl]methylidene}-α-d-xylofuranoseC19H24O6De = 46%[α]D25=-36.9 (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,3R)-(2-methylcyclopropyl)methylidene]-α-d-xylofuranoseC13H20O5De = 65%[α]D25=-21.2 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3R)-, α-d-xylofuranose

3,5-O-[(1S,2R,3R)-(2-Heptylcyclopropyl)methylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC19H32O5De = 100%[α]D25=-26.7 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3R)-, α-d-xylofuranose

3,5-O-[(1S,2R)-(2,2-Diphenylcyclopropyl)methylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC24H26O5De = 100%[α]D25=+77.0 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R)-, α-d-xylofuranose

1,2-O-Isopropylidene-3,5-O-[(1S,2R,3S)-(1-methyl-2-phenylcyclopropyl)methylidene]-α-d-xylofuranoseC19H24O5De = 76%[α]D25=-17.8 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3S)-, α-d-xylofuranose

3,5-O-[(1S,2R,3S)-(1-Hexyl-2-phenylcyclopropyl)methylidene]-1,2-O-isopropylidene-α-d-xylofuranoseC24H34O5De = 66%[α]D25=-16.9 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3S)-, α-d-xylofuranose

1,2-O-Isopropylidene-3,5-O-[(1S,2R,3R)-(1,2-methylidenecyclohexyl)methylidene]-α-d-xylofuranoseC16H24O5De = 67%[α]D25=-10.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: 3,5-O-(1S,2R,3R)-, α-d-xylofuranose

(1R,2R)-trans-1-Heptyl-2-hydroxymethylcyclopropaneC11H22OEe = 100%[α]D25=-17.6 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2R)-trans-