Catalytic Asymmetric Fluorination of Alkyl 1-indanone-2-carboxylates Ruled by Pybox-Eu(III) Combination

Abstract

A highly enantioselective catalytic method for the synthesis of quaternary α-fluoro derivatives of 3-oxo esters is described. The reaction uses europium (III) triflate and commercially available chiral pybox-type C2-symmetric ligand. Excellent results in terms of yields and enantioselectivities were assured using the electrophilic NFSI reagent under mild reaction conditions.

Asymmetric Preparation of α-Quaternary Fluorinated β-keto Esters. Review

“…In general, comparing substituent's with similar steric hindrance, the presence of electron withdrawing groups in the benzene harmed the ee (23 and 25, Figure 3). Access to both enantiomers of the α-fluorinated oxo ester is guaranteed by the commercial availability of both (R,S) and (S,R) ind-pybox C2-symmetric ligands [53].…”

“…The enantioselectivity of the reaction stems from the efficient blockage of one of the faces. See as an example the catalytic cycle proposed for the asymmetric fluorination using europium (III) triflate and (S,R)-ind-pybox combination [53] (Scheme 2). Kesavan's group reported that ethyl 2-methyl-3-oxobutanoate (32, Figure 5) underwent fluorination in 84% yield and 70% ee (only one example) using the Cu(II)/(S,S)-Nap-(R,R)-Box (2, Figure 2) combination [45].…”

“…The enantioselectivity of the reaction stems from the efficient blockage of one of the faces. See as an example the catalytic cycle proposed for the asymmetric fluorination using europium (III) triflate and (S,R)-ind-pybox combination [53] (Scheme 2).…”

Catalytic Strategies for the Asymmetric Construction of Cyclic Frameworks with a Halogenated Tetrasubstituted Stereocenter

“…In addition to the pybox‐Eu complex, pybox‐La(III) complex was also applied in this reaction. Unfortunately, lower enantioselectivities were generally observed …”

Enantioenriched Quaternary α-Pentafluoroethyl Derivatives of Alkyl 1-Indanone-2-Carboxylates

“…17 As far as we know, there are no examples regarding the enantioselective -pentafluoroethylation of alkyl 1-indanone-2-carboxylates. In the past, our group have previously reported the asymmetric introduction of different electrophiles in β-dicarbonyl systems though lanthanide-pybox catalysis, from α-amination 18 to the most recent fluorination 19 and trifluoromethylation 20 reactions. Herein, we present our recent studies on the construction, for the first time, of enantioenriched pentafluoroethylated quaternary centres on alkyl 1-indanone-2-carboxylates using a combination of La(OTf)3 with pybox type ligands.…”