Halogenoalkyl and Related Acids

4 Halogenoalkyl and Related Acids. - The synthesis of (2-chloroethyl)phos-phonic acid has been reviewed. Michaelis-Arbuzov and Michaelis-Becker reactions continue to be employed in the synthesis of polyhalogenated-alkyl 

The replacement of OH on carbon adjacent to phosphorus by Br or I using allyl bromide or Mel in the presence of carbonyldiimidazole, has been reported. The electrolysis of diisopropyl (trichloromethyl)phosphonate in DMF containing the alkyl halide RX with a carbon cathode and magnesium anode affords diisopropyl (l,l-dichloroalkyl)phosphonates (132) interestingly, the corresponding diethyl esters may be reduced further. A similar reaction leading to (l-chloro-l-cycloalkyl)phosphonic diesters (133) has already been referred to.  

Syntheses of further halogen-containing and additionally functionalized phosphonic diesters will be referred to in several of the following sections. 

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Halogenoalkyl and Related Acids. Fluorinated phosphonates are often designed as a new class of biological phosphate mimics. They are used as enzyme inhibitors and metabolite probes. Therefore, these compounds have attracted much attention. During the period of this review a number of new methods of synthesis, including the preparation of novel fluorinated phosphonates, have been reported. A complementary triflate displacement approach to (a-mono-fluoroalkyl) phosphonates (219) has been elaborated. Treatment of alkyl triflates or iodides with the potassium salt of (a-fluoro-a-phenylsulfonylmethyl) phosphonate (220) yields (a-fluoro-a-phenylsulfonylalkyl) phosphonates (221), which can be cleanly desulfonated affording (219) (Scheme 58). 

Halogenoalkyl and Related Acids. - A wide range of a-fluoroalkyl-phosphonates have been prepared by a variety of methods (fluorinated amino acid analogues are discussed in 3.1.6). 

Halogenoalkyl and Related Acids. In view of their extensive applications as, for example, phosphate mimics, new routes to a-mono- and -di-fluoroalkylphos-phonates are always welcome and during the period of this review a substantial number have been reported. A variety of functionalised examples of such compounds have been prepared from the readily available difluorophosphonate (188). ° For example, the monofluoro analogue (191) of serine phosphate has been synthesised by the reaction of (188) with organocopper reagents to give (190) followed by reduction and further functionalisation (Scheme 28). The... 

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