4-Thiazolidinone, fluorination

A series of a-sulphenyl lactams, thiacyclohexanones, thiolanones, and thiazolidinones have been fluorinated to produce the corresponding diastereo-mers, some of which have been shown to possess biological activity [35, 36, 40-42]. 

Tominaga and coworkers [82,83] reported a thiirane synthesis starting from 2-mercapto-l,3-thiazole derivative 180 bearing a trimethylsilyl group (Scheme 56). Treatment of 180 with CsF in acetonitrile and then with an aldehyde provided adducts 182 that fragmented via the spiro-isomer 183. Interestingly, the use of TASF as the fluorine anion source provided alcohols 185. The latter products were slowly transformed into the respective thiiranes 184 and thiazolidinone on storage (Table 9). 

In the case of 4-thiazolidinone 1, the Et3N 3HF/MeCN system proved rather effective and convenient for anodic fluorination, which is a highly regioselective reaction giving monofluorinated derivative 2. These are the first examples of effective anodic fluorination of sulfur-containing heterocyclic compounds (92JOC3755, 90JOC6074). Subsequent oxidation with peradds affects the sulfur atom to form 3 (Scheme 3). 

Fuchigami T, Narizuka S, Konno A (1992) Electrolytic partial fluorination of organic compounds. 4. Regioselective anodic monofluorinatiora of 4-thiazolidinones and its application to the synthesis of monofluoro 3-lactams. J Org Chem 57 3755-3757... 

In 2009, the same authors disclosed that the enantioselectivity of these reactions could be dramatically improved to 99% ee by the help of a catalytic amount of hexafluoroisopropanol (HEIP). As shown in Scheme 6.7, the flu-orinations of A/-(arylacetyl)thiazolidinones with NFSI induced by a catalyst generated in situ from Ni(Cl04)2-6H20 and (/ ,/Z)-DBFOX in the presence of molecular sieves, 2,6-lutidine, and 30 mol% of HFIP afforded the corresponding fluorinated chiral thiazolidinones in excellent yields (87-98%) and with... 

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