New synthetic approach to mevalonate and mevaldate fluoroanalogues

6,6,6-Tri- and 6,6-difluoromevalonate were synthesized by new method starting from the corresponding β-alkoxyvinyl polyfluoromethyl ketones. Enantiomers of fluoromevalonates were obtained by column chromatography separation of diastereomeric (S)-(−)-1-phenylethylamides of fluoromevalonates with the following hydrolysis. Racemic 6,6,6-tri- and 6,6-difluoromevaldates were also prepared.

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(3S)-3,5-Dihydroxy-N-[(1S)-1-phenylethyl]-3-(trifluoromethyl)pentanamideC14H18F3NO3Ee >98% (by NMR)[α]D25=-39.4(c1.3,CHCl3)Source of chirality: chiral resolutionAbsolute configuration: (3S)

(3R)-3,5-Dihydroxy-N-[(1S)-1-phenylethyl]-3-(trifluoromethyl)pentanamideC14H18F3NO3Ee >98% (by NMR)[α]D25=-54.0(c0.6,CHCl3)Source of chirality: chiral resolutionAbsolute configuration: (3R)

(3S)-3-(Difluoromethyl)-3,5-dihydroxy-N-((1S)-1-phenylethyl)pentanamideC14H19F2NO3Ee >98% (by NMR)[α]D25=-33.2(c0.7,CHCl3)Source of chirality: chiral resolutionAbsolute configuration: (3S)

(3R)-3-(Difluoromethyl)-3,5-dihydroxy-N-((1S)-1-phenylethyl)pentanamideC14H19F2NO3Ee >98% (by NMR)[α]D25=-45.5(c0.7,CHCl3)Source of chirality: chiral resolutionAbsolute configuration: (3R)

(4R)-4-Hydroxy-4-(trifluoromethyl)tetrahydro-2H-pyran-2-oneC6H7F3O3Ee = 100%[α]D25=-17.0(c0.8,CHCl3)Source of chirality: corresponding phenylethylamideAbsolute configuration: (4R)

(4R)-4-Tetrahydro-4-(difluoromethyl)-4-hydroxy-2H-pyran-2-oneC6H8F2O3Ee = 100%[α]D25=-10.5(c0.7,CHCl3)Source of chirality: corresponding phenylethylamideAbsolute configuration: (4R)