Alkylphosphonates, electrophilic

Several innovations have significantly extended the scope and synthetic utility of the classical Darzens reaction. For example, a useful supplement has been described to convert diethyl alkylphosphonates into diethyl 1-substituted 1,2-epoxyalky Iphosphonates by a one-pot process. Thus, metallation of diethyl alkylphosphonates with n-BuLi (2 eq) at low temperature in THF followed by electrophilic chlorination using benzenesulfonyl chloride yields diethyl 1-lithio-l-chloroalky 1-phosphonates, which can be converted in moderate to good overall yields (30-80%) into diethyl 1-substituted 1,2-epoxyalky Iphosphonates by reaction with carbonyl compounds (Scheme 4.2). ... 

Chemical transformations of a-hydroxyphosphonates Phosphonate-phosphate rearrangement. Dialkyl alkylphosphonates are, in general, more reactive than the corresponding phosphate esters because the carbon has no unpaired electrons to contribute to allow a pn-dm contribution to the P-C bond. This makes the phosphorus atom of phosphonates more electrophilic than the phosphorus atom of the corresponding phosphate ester. The P-C bond is usually stable to hydrolitic procedures. However, a-hydroxyalkylphosphonates, in the presence of alkali, rearrange to give phosphate with cleavage of the P-C bond [220]. 

Of course, many more potential pathways for the chemical degradation of phosphonates need to be explored. The C-P bond in alkylphosphonates, for example, is weakened by electron-withdrawing substituents. Alpha-carbonyl phosphonates such as the antiviral pharmaceutical phosphonoformate are especially susceptible towards hydrolysis (60). Metal ion-catalyzed conversion of phosphonates into phosphonamides has been observed nucleophilic attack of amine groups at the electrophilic phosphorus atom is believed responsible (61). 

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