Chlorodifluoromethyl ketones

The carbon-fluonne bond is normally resistant to cleavage by zinc metal so that the carbon-chlonne bond in chlorodifluoromethyl ketones is selecnvely reduced The... 

Table 5. Aldol Synthesis from Chlorodifluoromethyl Ketones [9]...

Chlorodifluoromethyl Ketone Metal Carbonyl Compound Yield of Aldol (%)... 

The chlorodifluoromethylated ketone 130 proved to be a valuable substrate for promoting SrnI subtitution reaction with sodium phenylthiolate and to generate a new a-(phenylthio)-a,a-difluoroacetophenone derivative 131 (Equation 57) <2001TL3459>. Upon treatment with nitronate anions under classical SrnI reaction conditions or MW irradiation, 6-chloromethyl-5-nitro-imidazo[2,l- ]thiazole 132 yielded 5-nitroimidazothiazoles bearing a trisubstituted ethylenic double bond at the 6-position (Equation 58) <2001SC1257>. 

Aldol condensation of chlorodifluoromethyl ketones with ketones can be effected in moderate yield by use of diethylaluminum chloride (1.1 equiv.) and zinc activated with silver (I) acetate. 

Grignard addition to chlorodifluoroacetic acid constitutes the classic method for the synthesis of chlorodifluoromethyl ketones. A recent example [181] was... 

Chlorodifluoromethylketones underwent aldol reactions (Eq. 124) via zinc enolates, to afford good yields of a,a-difluoro-/ -hydroxy ketones, in a study by the Kyoto group [327]. Copper(I) or silver salt catalysis was essential and boron-trifluoride additive appeared to exert a key role in the conversion to the enolate. Earlier [328], chlorodifluoromethyl ketones had been converted to the di-fluoroenoxy silanes by the action of zinc in the presence of chlorotrimethyl silane. A difluoroenoxy silane was used by McCarthy and co-workers [329] to synthesise a kynureninase inhibitor (Eq. 125) Lewis acid-mediated reaction with a chloroglycinate installed the key carbon-carbon bond. 

An interesting reaction is the addition of phosphonates to chlorodifluoromethyl ketones depending on the reaction temperature, either phosphates, e.g. 6, or phosphonates, e.g. 7, are produced. 8... 

Ishihara, T., Yamanaka, T., Ando, T. New low-valent titanium catalyzed reaction of chlorodifluoromethyl ketones leading to a,a-difluorinated P-hydroxy ketones. Chem. Lett. 1984,1165-1168. 

C(a-Difluoroketones. Enolates of a,a-difluoroketones are generated from chlorodifluoromethyl ketones on treatment with the reagent 1. These enolates react with aldehydes readily. 

Table 12. Synthesis of Diethyl (Chlorodi(luoromethyl)alkylphospho-natcs 7 From Chlorodifluoromethyl Ketones 4 and Diethyl Phospho-nate (5)78...

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