Claisen condensation, fluorination

Fluorinated esters have synthetic utility m Claisen condensations [24, 25] (equation 21) and Dieckmann cyclizfitions [26]. 

Higher homologs having a nonterminal fluorine atom were synthesized305 by Claisen condensation of ethyl fluoroacetate with methyl 2,3-O-isopropylidene-DL-glycerate, giving a mixture of the isomeric 2-deoxy-2-fluoro-4,5-0-isopropylidene-DL-3-pentulosonates (540). On... 

Fluorinated esters have synthetic utility in Claisen condensations, c.g. formation of 26, - and Dieekmann cyclizations. ... 

Several routes to this class of compounds have been reported, such as (a) crossed Claisen condensation reactions (50-53) (b) acylation of the anion derived from ethyl fluoroacetate (54) or self-condensation of the anion derived from ethyl bromofluoroacetate (55) (c) electrophilic fluorination of the anion of p-ketoesters (56,57) (d) acylation-hydrolysis of fluoroolefins (58) and (e) acylation of fluorine-containing ketene silyl acetals (Easdon, J.C., University of Iowa, unpublished data). The limitations associated with these methods and the success achieved in the alkylation-hydrolysis of a-fluoro phosphorus ylides prompted us to examine acylation-hydrolysis of these a-fluoro ylides as a general route to 2-fluoro-3-oxoesters. 

In many cases synthesis of the fluorinated 1,3-CCC-bielectrophile precursors is the most difficult part of the syuthetic sequeuce and using classical methods is usually accomplished by the use of highly toxic fluoroacetic add derivatives in Claisen condensation with ethyl formiate [81], ethyl chloroformate [95,96], diethy-loxalate [82, 97], acetyl, benzoyl chlorides [82] or Vilsmeier-type formylation [98, 99] (Scheme 13). The product of Vilsmeier-type formylation is 3-dimethylamino-2-fluoroacrolein 54 which reacts with triethyloxonium tetrafluoroborate and dimeth-ylamine to give the vinamidinium salt 55 [91], which also can be used as 1,3-bielectrophile (see Scheme 19). Also Reformatsky-type synthesis of ethyl a-fluoroacetoacetate 52 starting from ethyl chlorofluoroacetate 56 was described in 20 % yield [82]. 

---