Dephosphonylation

The hydrolysis of a monoalkyl phosphate may also be classed as a dephosphonylation reaction, that is, one involving removal of the O-phosphono [(HO)gP(O)-] group.259... 

Ketophosphonic acids (98) were found to undergo facile dephosphonylation under fairly mild conditions (Scheme 27). The rate of dephosphonylation was dependent on the electronic nature of the substituent at the carbon atom a to phosphorus, with electron-withdrawing groups accelerating the process. 31P NMR studies supported a mechanism at low pH that either (Scheme 28) involved water attack in a bimolecular process (path a) or transient formation of metaphosphate (path b), a process analogous to the decarboxylation of /3-keto acids.98... 

In contrast to the ready reductive cleavage of a-sulfonyl ketones, reductive dephosphonylation of P-ketophosphonates is surprisingly difficult. All attempts to produce methyl cyclohexyl ketone from di-Zez7-butyl 2-cyclohexyl-2-oxoethylphosphonate by various reducing agents failed... 

One versatile strategy for the synthetic approach to a,a -disubstituted asymmetric ketones has been elaborated (Scheme 7.122). For example, metallation of diethyl alkylphosphonates and acylation of the copper reagents with acyl halides followed by two consecutive alkylations, at the a-carbon and then at the y-carbon, dephosphonylation, and hydrolysis produces highly substituted ketones in 43-73% yields. ... 

In work aimed at elucidating the mode of pyridoxal mediated dephosphonylation of a-aminophosphonic acids, it was found that simple aminophosphonates reacted with pyridoxal to form Schiff bases, which complexed copper(II) ions, but did not react further. In contrast, o-hydroxyphenylphosphaglycine did react with pyridoxal at 40 °C with the formation of pyridoxamine, along with o-hydroxybenzoylphosphonic acid on the one hand (equation 45), and salicylaldehyde and H3PO4 (not shown) on the other. Apparently, the presence of the -hydroxy group is necessary for the success of the reaction, presumably by complexing the copper ion in the fashion indicated. The formation of 6>-hydroxybenzoylphosphonic acid illustrates the capability of a-aminophosphonic acids to participate in transamination (similarly to amino acids), while salicylaldehyde is the result of dephosphonylation (analogous to decarboxylation). 

Copper(ii) and pyridoxal (10) catalyse the dephosphonylation of 2-amino-3-phosphonopropionic acid (11) in the pH range 5—9. Chelation of the Schiff base formed between (10) and (11) to copper(ii) is followed by transammination and... 

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