Y-fluorocrotonate

In Chapter vm (p. 149) we discuss our suggestion that fS oxidation of w-fluorocarboxylic acids takes place in the animal body. Nevertheless, there is some indication that y-fluoro-butyrate (but not y-fluorocrotonate), even if it does undergo oxidation, also acts per se. For example, progressive cardiac failure without ventricular fibrillation is noted in Rhesus monkeys poisoned with fluorobutyrate. Rabbits poisoned with fluorobutyrate do indeed show ventricular fibrillations and weak convulsions, but in addition appear to manifest a para-... 

The synthesis of (XVIII), (XIX), (XX) and (XXI) from methyl fluorocrotonate was accomplished according to the annexed scheme. Methyl y-fluorocrotonate had previously been prepared, and was reported by Kharasch and his co-workers to be a highly toxic compound. It possesses the carbon structure of methyl y-fluorobutyrate, and the double bond in the opposition would undoubtedly facilitate oxidation. The American workers prepared methyl y-fluorocrotonate by an ingenious five-stage process from epifluorohydrin. For the above syntheses we... 

The Diels-Alder additions of methyl y-fluorocrotonate to 2 3-dimethylbuta-l 3-diene and cycZopentadiene were effected by heating the reactants in sealed tubes at 110-120° for about 3 hr. The reduction of the unsaturated products, (XVIII) and (XX), was carried out at room temperature with palladium as catalyst. In both cases the theoretical quantity of hydrogen was absorbed, although the hydrogenation of the dimethyl derivative was much slower than that of the ewdomethylene compound. 

Although our results support the / -oxidation theory, one point must not be overlooked, namely, that fluoroacetic acid is not the actual toxic agent and has to be converted into fluoro-citrate before exerting its activity (see p. 142). It should also be noted that American workers1 showed that both methyl y-fluorobutyrate and methyl -fluorocrotonate,... 

In heavily fluorinated carbonyl compouds, a trifluoromethyl group also polarizes the double bond, but in the opposite way. In ethyl Y,y,y-tri-fluorocrotonate, polarization by the carbonyl function still predominates, and the nucleophile is bound to the beta carbon [II6. ... 

---