Asymmetric fluorination of β-keto esters catalyzed by chiral rare earth perfluorinated organophosphates

Novel chiral rare earth metal complexes bearing perfluorinated binaphthyl phosphate ligand RE[(R)-F8BNP]3 (RE = rare earth; F8BNP = 5,5′,6,6′,7,7′,8,8′-octafluoro-1,1′-binaphthyl-2,2′-diyl phosphate) have been synthesized and used as a catalyst for the asymmetric electrophilic fluorination reaction of β-keto esters. The use of Sc[(R)-F8BNP]3 catalyst in combination with 1-fluoropyridinium triflate (NFPY–OTf) as a fluorinating agent was found to give the desired α-fluoro-β-keto esters in high chemical yields and enantiomeric excesses (up to 88% ee) under mild conditions.

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(R)-5,5′,6,6′,7,7′,8,8′-Octafluoro-1,1′-binaphthyl-2,2′-diyl hydrogen phosphateC20H5F8O4PEe >99%[α]D23=-363.6 (c 1.0, DMSO)Source of chirality: (R)-5,5′,6,6′,7,7′,8,8′-octafluoro-2,2′-dihydroxy-1,1′-binaphthylAbsolute configuration: R

Scandium(III) (R)-5,5′,6,6′,7,7′,8,8′-octafluoro-1,1′-binaphthyl-2,2′-diyl phosphateC60H12F24O12P3Sc·3H2OEe >99%[α]D21=-156.4 (c 0.50, DMSO)Source of chirality: (R)-5,5′,6,6′,7,7′,8,8′-octafluoro-2,2′-dihydroxy-1,1′-binaphthylAbsolute configuration: R

tert-Butyl 1-fluoro-2-oxocyclopentanecarboxylateC10H15FO3Ee = 84%[α]D23=-72.7 (c 1.08, CHCl3)Source of chirality: asymmetric synthesis

Methyl 1-fluoro-2-oxocyclopentanecarboxylateC7H9FO3Ee = 87%[α]D22=-97.5 (c 0.46, CHCl3)Source of chirality: asymmetric synthesis

Ethyl 1-fluoro-2-oxocyclopentanecarboxylateC8H11FO3Ee = 76%[α]D21=-72.8 (c 1.10, CHCl3)Source of chirality: asymmetric synthesis

Isopropyl 1-fluoro-2-oxocyclopentanecarboxylateC9H13FO3Ee = 75%[α]D21=-68.4 (c 0.94, CHCl3)Source of chirality: asymmetric synthesis

Benzyl 1-fluoro-2-oxocyclopentanecarboxylateC13H13FO3Ee = 47%[α]D22=-38.6 (c 1.73, CHCl3)Source of chirality: asymmetric synthesis

Methyl 1-fluoro-2-oxocyclohexanecarboxylateC8H11FO3Ee = 81%[α]D22=-87.7 (c 0.95, CHCl3)Source of chirality: asymmetric synthesis

Methyl 2-fluoro-2-methyl-3-oxo-3-phenylpropionateC11H11FO3Ee = 75%[α]D21=+75.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesis

tert-Butyl 2-fluoro-2-methyl-3-oxo-3-phenylpropionateC14H17FO3Ee = 78%[α]D21=+52.1 (c 0.26, CHCl3)Source of chirality: asymmetric synthesis