Transesterification phosphonic acid esters

Because of the possibility of racemization during the transesterification reaction (strong basic conditions) alternative methods are reported. These include transesterification in the presence of the KF/18-crown-6 ether 461 or the use of titanium tetraalkoxides. 471 The methods are efficient and represent a route to any required dialkyl ester using diphenyl esters as starting materials. Diphenyl groups can also be removed by hydrogenation in the presence of platinum dioxide (Adams catalyst) to provide the free phosphonic acid moiety directly)46 ... 

Masked ionomeric groups may also be used. They generate ions during melt processing. Examples include phosphonate esters that form phosphonic acid salt in the melt by transesterification with a salt, e.g., zinc stearate. 

Conventional organic synthesis procedures are sometimes employed to prepare the simpler types of those molecules included here. Thus, (v/c-dihydroxyalkyl)phosphonic diesters are obtainable through the hydroxylation of the corresponding unsaturated acid esters using OSO4 and standard techniques. The isolation and purification of a diol may prove to be difficult because of possible intramolecular transesterification, sometimes accompanied by dehydration (reaction 12)" ... 

Transesterification of H-phosphonate diesters is a simple synthetic route for the preparation of a variety of different esters of H-phosphonic acid (Scheme 3.1). 

It was found that the transesterification of dimethyl H-phosphonate with 1,2-propane-diol yields 4-methyl-2-hydro-2-oxo-l,3,2-dioxaphospholane [56]. Obviously, the first stage of the reaction furnished methyl-2-hydroxypropyl H-phosphonate. Subsequent intramolecular transesterification of the methyl-2-hydroxypropyl phosphonate yielded 4-methyl-2-hydro-2-oxo-l,3,2-dioxaphospholane. The specific reactivity of these esters of H-phosphonic acid is determined by the presence of a P-hydroxyl gronp. The role of the P-hydroxyl gronp may be regarded as an intramolecular catalysis. The reactivity enhancement of P-hydroxylethyl esters of H-phosphonic acid probably can be explained through hydrogen bonding, which favors the intramolecular transesterification reaction. 

In the synthesis of 6 -deoxyhomonucleoside-6 -phosphonic acids the phosphonate was masked as the diphenyl ester [42]. On transesterification with sodium benzyloxide in dimethyl sulphoxide the dibenzyl ester was formed, and subsequently hydrogenated to give the desired compound (Fig. 6.19). 

The main problem here is removing the phenyl ester groups from the phosphonic moiety.We have found that convenient routes for deblocking are hydrogenation on Adams catalyst and transesterification methods followed by hydrogen bromide in glacial acetic acid treatment. The best results ewre obtained if transesterification was carried out using potassium fluoride-crown ether-methanol system. 

The transesterification of dialkyl H-phosphonates with hydroxyl-containing compounds is accompanied by side reactions, resulting in the formation of ether compounds and H-phos-phonic acid monoalkyl esters [28,36,37]. The formation of these side products is due to the nucleophilic attack of the oxygen atom of the alcohol on the ot-carbon atom of the alkoxy group, the second electrophilic center in the molecule of dialkyl H-phosphonates. 

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