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The synthesis of r-fluoroglutamic acid, HOOCCIIFCHyCH(.\'I-I2)COOI-I, was achieved by two independent methods, both of which involved the Michael reaction: (1) methyl a-fluoroacrylate and diethyl acetamido~nalonate gave the transesterilied intermediate, which on hydrolysis produced r-lluoroglutamic acid (3lC% yield); (2) ethyl a-acetamidoacrylate and diethyl fluoromalonate reacted under mild conditions to give, after hydrolysis, the required amino acid in 56% overall yield. Of the two procedures, the second is preferable, since it is based on Inore readily available starting ~naterials and gives a higher yield.

a-Monofluoroalkanoic acids are important intermediates in the synthesis of biologically active fluorine compounds. General methods of preparation have been examined, based on the three following reagents: (a) hydrogen fluoride + N-bromoacetamide; (b) diethyl monofluoromalonate; and (c) perchloryl fluoride. The first of these is the recommended procedure for simple unsubstituted a-fluoro acids; however, the fluoromalonate route is less vigorous, and is therefore the method of choice for those a-fluoro acids that contain labile functional groups.

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The addition of "BrF", using N-bromoamides in anhydrous hydrogen fluoride, to a number of aliphatic alkenes has been studied. As expected, the bromine atom in the resultant vicinal fluorobromides exhibited relatively low reactivity in nucleophilic and hydrogenolytic reactions.The bromine monofluoride addition reaction, first described by Bowers (2, 3, 4), has been employed mainly in the synthesis of fluorinated steroids. Its application to aliphatic alkenes was undertaken here partly to extend the scope of the reaction and partly to obtain the resultant vicinal fluorobromides as intermediates in other syntheses; of particular interest was their potential use in the synthesis of a-monofluoroalltanoic acids (5). While this work was in progress, parallel studies using perchloryl fluoride were continuing, with a-monofluoroalltanoic acids again as the main goal (5). The two methods are complementary, in that they permit the introduction of the fluorine atom a t centers of l o~v electron density (bromoniuin ion) and high electron density (carbanion) respectively. Prior to this work, the only cornillon aliphatic vicinal fluorohalides were those derived from ethane. Of these, 1-bromo-2-fluoroethane had been reported by Schrader (6) to be formed by the direct addition of "BrF" (using a mixture of bromine and fluorine) to ethylene; the present work may thus be considered as a refinement of this original procedure.+ RCH=CH? + CH3CONII?Br 1-Alkenes of inediuin chain length on treatment with a molar quantity of N-bromoacetainide and excess anhydrous hydrogen fluoride in ether gave the expected products in good yield (70-go%), with sillall amounts of isomeric 2-bromo-1-fluoroalkanes. The structures of the major products were shown to be the 1-bromo-2-fluoroalltanes by nuclear magnetic resonance (n.m.r.) spectroscopy and by their conversion in high yield to the corresponding a-n~onofluoroalkanoic acids (5). The ininor products were isolated in only a few instances (for example, in the addition to ally1 bromide); they proved to be the anti-Markovnikov isomers. The minor product was usually not removed from the mixture, because it was destroyed or removed in many of the subsequent reactions. Yields are shown in Table I. lT1zis paper was presenled i n purl al llze Secolzd Inlernalional Syrnposiz~?n on Fluorine