Stereocontrolled access to α-fluoro-β-ketoesters

The effect of a fluorine atom on the asymmetric Michael reaction between a chiral α-fluoro-β-enaminoester derived from (S)-1-phenylethylamine and various electrophilic alkenes is studied. α-Fluoro-α-substituted ketoesters are obtained in good yields with fairly good enantioselectivity.

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Ethyl (R)-2-acetyl-2-fluoro-5-oxo-hexanoateC10H15FO4Ee = 60%[α]D20=-23 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

Ethyl (R)-2-acetyl-4-benzenesulfonyl-2-fluoro-butanoateC14H17FO5SEe = 77%[α]D20=-33 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

Ethyl (R)-2-acetyl-4-benzyloxycarbonyl-2-fluoro-butanoateC16H19FO5Ee = 75%[α]D20=-30 (c 1.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

Ethyl (R)-2-acetyl-4-cyano-2-fluoro-butanoateC9H12FNO3Ee = 74%[α]D20=-60 (c 1.1, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)