Synthesis of Alkenylphosphonic Acids Using the Wittig Reaction

Synthesis of Alkenylphosphonic Acids Using the Wittig Reaction 

The Wittig reaction involves the interaction of an aldehyde or ketone with a phosphorus-containing carbanionic species, in which the phosphorus is bonded directly to the carbanionic site. At the time of discovery of the reaction, that specification described the triphenylphosphonium alkylides 343 later developments employed the anions from tert-phosphine oxides, the use of which has been described elsewhere in this series and also from a wide variety of phosphonic and phosphinic esters. This latter application will be considered more fully in Chapter 6. An early application of the reaction to the synthesis of alkenephosphonic acids, and which involved an ylide, employed the stable compound 344, generated from 345 by the action of a strong base. Reactions between 344 and aliphatic or aromatic aldehydes at 100 °C in toluene or dmso gave the diphenyl esters of (alk-1-enyl)phosphonic acids or (2-arylethenyl)phosphonic acids.  

The use of esters of a (substituted-methyl)phosphonic acid to provide the carbanion site next to phosphoryl phosphorus was a natural step forward. The most successful development has been the use of the carbanion 346 derived from esters of methylenebisphospho-nic acid (or its monoalkylated derivatives). The anion 346 reacts with an aldehyde to afford the alkenylphosphonic diester 347 (R = Et, Ph, PhCH—CH, 2-thienyl, 2-pyridinyl, etc,) . Use of the protected 3-pyridinylcarboxaldehyde 348 allowed the preparation of the ester 349, which, after reduction of the C=C bond and hydrolysis, afforded the phosphonic acid 350 Such reactions have also been carried out under phase-transfer condi-tions. Reactions between the lithium salt of the ester 351 and benzaldehyde or but-2-enal give the (alk-1 -enyl)phosphonic esters 352 and 353 in the ratio 1 4 the lithium salts 354 and 355 are formed concomitantly in the ratio 4 1.  

COOEt), whereas the use of the phosphonate (Wadsworth-Emmons) reagent gave large-lythe(Z)-alkenes362 . 

Some steric control in alkenephosphonic acid formation was achieved using the stanny-lated phosphonic diesters 363, generated in situ from the lithiated phosphonic diester and R 3SnCl, and from which the (E)- and (Z)-alkenephosphonic diesters were, respectively, the thermodynamically controlled and the kinetically controlled products, the stereochemistry of the reaction appearing to be governed by Purified trimethylsilyl 

---

E. Synthesis of Alkenylphosphonic Acids Using the Wittig Reaction... 

---