Phosphonate esters, preparation

Comins, D.L., Jacobine, A.E. Marshall, J.A., and Turnbull, M.M., Phosphonate ester preparation from active methylene compounds and phosphorochloridate esters, Synthesix, 309, 1978. 

MixedPhosphona.te Esters. Unsaturated, mixed phosphonate esters have been prepared from monoesters of 1,4-cyclohexanedimethanol and unsaturated dicarboxyhc acids. Eor example, maleic anhydride reacts with this diol to form the maleate, which is treated with benzenephosphonic acid to yield an unsaturated product. These esters have been used as flame-retardant additives for thermoplastic and thermosetting resias (97). 

The synthesis and surface-active properties of higher hydroxyalkanediphos-phonates are discussed in Ref. 67. Phosphorus-containing betaines as hydrolytically stable surfactants, free from alkali salt impurities, were prepared by a reaction of amidoamines and equimolar amounts of phosphonate esters with 1.5-2 eq of formaldehyde at 60-140°C in a polar solvent [72]. 

Various cyclic phosphonate esters 36 and 37 have been described previously as products from the HHT reaction of 25 with the appropriate cyclic phosphite. A complementary method has also been developed from the V-protected phosphonyl chloride 84, which was readily prepared from the corresponding phosphonic acid 83. Subsequent reaction of 84 with the appropriate diol produced the cyclic phosphonate esters 85 (63). Higher homologs of 85 have also been prepared from the analogous propane or butane diols. 

An Arbuzov reaction between gem-dibromocyclopropanes yields phosphonate esters (55) accompanied by debrominated compounds successful reaction requires the presence of traces of water (and is thus not the normal Arbuzov reaction) which, by studies with D2O, has been shown to supply the a-proton of (56), Normal Arbuzov reactions, using ethyl diphenyl phosphite, have been used to prepare a phosphonate isostere of B-D-arabinose-1,5-diphosphate. ... 

Mixed phosphonate esters can be prepared from alkylphosphonate monoesters, although here the activation is beheved to occur at the alcohol.65... 

Russian workers83 84 have synthesized a series of phosphorus-containing crowns utilizing O—P—O bonds in the macrocycle, i.e. cyclic phosphonate esters (7). One of these is claimed to have been prepared in 40% yield (equation 29). 

Addition of phosphates to chiral sulfinimines derived from aromatic aldehydes has been used to prepare a-amino phosphonate esters asymmetrically.35 The sulfinimines employed, p- Me Ph S (= O) N=C H A r. have sufficiently bulky substituents to prevent inversion, as shown by 1H-NMR over a wide range of temperatures. 

This reaction sees extensive application in the preparation of phosphonate esters for use in the Homer-Emmons Reaction. 

P-Mannich bases arc prepared from phosphonic esters possessing hydroxy groups. -" Representative compounds of this type are 420 (Fig. 160), which give cross-linked polyurethanes of structure 421, by reaction with diisocyanates. 

Phosphonate esters can be prepared either by the Arbuzov reaction (rearrangement) or by the alkylation of esters with DMMP (dimethyl methylphosphonate) (Scheme 4.28). Variation of the reaction conditions and reagents allows one to synthesize E- and Z-aUcenes with a high degree of stereoselectivity, as shown in Scheme 4.29. For example, 6-heptenal (4.33) on reaction with 4.34 in the presence of NaH gives -nonadienoate (4.35) on the other hand, in the presence of a base n-BuLi, Z-nonadienoate (4.36) is the major product. 

Derivatives of phosphonic acids, RP==O(0H)2, can be prepared by several different oxidative methods. Primary phosphines RPH2 are oxidized to phosphonic acids by hydrogen peroxide or by sulfur dioxide thus, phenylphosphine gave benzenephosphonic acid (96%) on reaction with sulfur dioxide at room temperature in a sealed tube. Phosphinic acids, RI sO(OH)H, can also be oxidized to the corresponding phosphonic acids with hydrogen peroxide. Ozone oxidized the dioxaphosphorane (54) to the phosphonic ester in 73% yield. Ozone is also capable of stereospecific oxidation of phosphite esters to phosphates. For example, the cyclic phosphite (SS) was oxidized to the phosphate (56) with retention of configuration. Peroxy acids and selenium dioxide are other common oxidants for phosphite esters. 

The application of the Michael addition of phosphonate esters in the synthesis of coronafacic acid was reported by Shibasaki and coworkers and is outlined in Sch. 61 [89]. The Michael adduct ent-427 was prepared in 94 % ee in the same fashion as its enantiomer 427 (Sch. 59) by employing a catalyst prepared from (5)-BINOL. 

It has already been reported that antibodies prepared against the transition state of a reaction show considerable catalytic activity [113]. For example, antibodies prepared against a phosphonic ester (as a transition state analogue for alkaline ester hydrolysis) enhanced the rate of ester hydrolysis by 10 -10" fold. Recently, similar systems based on imprinted polymers which display high catalytic activity have been successfully prepared. Initial attempts were performed by several groups [114-117] with imprinted polymers based on non-stoichiometric, non-covalent interactions, which, however, gave results far below those obtained with antibodies. Rate enhancements up to 6.7-fold were reached in one case. 

Phosphonates have also been prepared from alcohols and (Ar0)2P(=0)Cl, NEts and a TiCl4 catalyst. ° The reaction of (R0)2P(=0)H and aryl iodides with a Cul catalyst leads to aryl phosphonates. " Polymer-bound phosphonate esters have been used for olefination. Dienes are produced when allylic phosphonate esters react with aldehydes. 

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