Synthesis of chiral hydroxylated cyclopentanones and cyclopentanes

A method for the synthesis of enantiomeric 1,3-dihydroxy and 2,3-dihydroxy cyclopentanones, starting from a commercially available 3-methyl-cyclopentane-1,2-dione 1, is described. Dione 1 was subjected to asymmetric 3-hydroxylation to afford 3-methyl-3-hydroxy-1,2-dione 2. The carbonyl groups in 2 were selectively differentiated by converting them either in dimethylacetal 5 or acetonide 6. Stereoselective reduction of those acetals by using NaBH4 afforded chiral methyl 1,2-dihydroxy cyclopentanone 9 and 1,3-dihydroxy cyclopentanone 10, respectively. The diols obtained were further converted to the corresponding diastereomeric triols 11–13 by hydride reduction.

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(2R,3S)-2,3-Dihydroxy-3-methyl-cyclopentanoneC6H10O3[α]D25 = +115 (c 0.34, acetone)de ∼100% (NMR)Source of chirality: asymmetric synthesis

(2S,5R)-2,5-Dihydroxy-2-methyl-cyclopentanoneC6H10O3[α]D22 = +243 (c 0.80, MeOH)de ∼100% (NMR)Source of chirality: asymmetric synthesis

(2S)-2-Hydroxy-5,5-dimethoxy-3-methyl-cyclopentanoneC8H14O4[α]D25 = −38 (c 2.47, CHCl3)Source of chirality: asymmetric synthesis

(3aS,6aS)-3a-Hydroxy-2,2,6a-trimethyl-tetrahydro-cyclopenta[1,3]dioxol-4-oneC9H14O4[α]D24 = +125 (c 1.75, CHCl3)Source of chirality: asymmetric synthesis

(3aR,4R,6aS)-2,2,6a-Trimethyl-tetrahydro-cyclopenta[1,3]dioxole-3a,4-diolC9H15O4[α]D25 = −96 (c 3.55, CHCl3)de ∼100% (NMR)Source of chirality: asymmetric synthesis