Simple synthetic protocol for the preparation of enantiomeric 3-oxabicyclo[3.3.0]oct-6-en-2-ones

Diastereomeric amides produced via the decomposition of easily available (±)-7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one by treatment with (+)- or (−)-α-methylbenzylamines were transformed into bicyclic lactam-aminals, which can easily be separated using the column chromatography on SiO2. The latter products lead to enantiomeric 3-oxabicyclo[3.3.0]oct-6-en-2-ones after the removal of the chiral auxiliary.

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(1S,2R)-(Dichloromethyl)-N-[(1R)-1-phenylethyl]cyclopent-3-ene-1-carboxamideC15H17Cl2NO[α]D20=+69 (c 0.5, CH3OH)Source of chirality: (+)-[(1R)-1-phenylethyl]amineAbsolute configuration: (1S,2R,1R)

(3aS,6aR)-3R-Hydroxy-2-[(1R)-phenylethyl]-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-1(2H)-oneC15H17NO2[α]D20=+142.4 (c 0.65, CH3OH)Source of chirality: (+)-[(1R)-1-phenylethyl]amineAbsolute configuration: (3aS,6aR,3R,1R)

(3aR,6aS)-3S-Hydroxy-2-[(1R)-phenylethyl]-3,3a,6,6a-tetrahydrocyclopenta[c]pyrrol-1(2H)-oneC15H17NO2[α]D20=+37.8 (c 0.8, CH3OH)Source of chirality: (+)-[(1R)-1-phenylethyl]amineAbsolute configuration: (3aR,6aS,3S,1R)

(1R,2S)-2-(Hydroxymethyl)-N-[(1R)-1-phenylethyl]cyclopent-3-ene-1-carboxamideC15H19NO2Ee >95%[α]D20=+168.5 (c 0.425, CH3OH)Source of chirality: (+)-[(1R)-1-phenylethyl]amineAbsolute configuration: (1R,2S,1R)

(1S,2R)-2-(Hydroxymethyl)-N-[(1R)-1-phenylethyl]cyclopent-3-ene-1-carboxamideC15H19NO2Ee >95%[α]D20=-1.8 (c 1.05, CH3OH)Source of chirality: (+)-[(1R)-1-phenylethyl]amineAbsolute configuration: (1S,2R,1R)

(−)-(1R,5S)-3-Oxabicyclo[3.3.0]oct-6-en-2-oneC7H8O2[α]D20=-68.0(c 0.93, CHCl3)Source of chirality: (+)-[(1R)-1-phenylethyl]amineAbsolute configuration: (1R,5S)