Alkenyl, Alkynyl, Aryl, Heteroaryl and Related Acids

One route to (l-alkynyl)phosphonic esters depends on the base-catalysed destruction of enol phosphates (123) obtained in situ from (2-oxoalkyl)phos-phonates in the case of (123) (R = Et), a mixture of (1-butynyl)- and (2-butynyl)-phosphonic esters was obtained, but in all other quoted cases only the acetylenic compound was obtained. A second route starts with diethyl (trichloromethyl)-phosphonate (a reagent of increasing synthetic importance) followed by sequential reaction in one-pot with BuLi (two equivalents), an aldehyde (RCHO), and a lithiumdialkylamide, and gives the products (Et0)2P(0)CsCR in very high yields.  

Reactions between diethyl hydrogenphosphonate and ArX (X = I or Br) to give diethyl arylphosphonates have been carried out in the presence of a phase transfer catalyst. Bis(trimethylsilyl) phenylphosphonite reacts with alkyl halides to give [(ar)alkylphenyl]phosphinic derivatives, and it also adds to a,P-unsaturated carboxylic esters (as well as to nitriles and amides) to give (2-functionalized-l-alkyl)phosphinic derivatives.  

Relatively few syntheses of (heteroaryl)phosphonic derivatives have been noted during the year. The C-phosphorylated imidazoles (127) (R = alkyl or aryl) were obtained from diethyl (cyanomethyl)phosphonate and (2-hydroxy-5-thiazolyl)-and [3-hydroxy-5-(l,2,4-triazolyl)]-phosphonic diesters were obtained by the lithiation of the corresponding 2- and 3-methoxy systems, followed by phosphorylation with (Et0)2P(0)Cl, and subsequent demethylation of the products with aqueous HCl or HBr.  

The benzoselenophene phosphonic acid (128) has been obtained from phenyl-ethynylphosphonic acid and Se02-HBr and classical reactions were employed in the synthesis of the pyridone acids (129) (R = aryl or heteroaryl, R = H or COOMe).  

Reagents i, R 2CuLi, Et20 ii, NH4CI, H2O iii, H2, 10% Pd (Lindiar), MeOH 

130 and 131, have been prepared by the reaction of trimethylsilyl phosphites with perfluoroalkenes and perfluoroepoxides.  

Reports of examples of arylphosphonates include those of water-soluble phosphinic-polyphosphonic acids, e.g. 132, and the phosphonate 133 which when coupled to alcohols, to give e.g. 134, act as linkers to proteins in experiments intended to generate antibodies to catalyse cationic cyclisation reactions.Novel water-soluble phosphonate-substituted phthalocyanines have been prepared.The phosphonate esters 135 are insoluble in water but can be hydrolysed by hydrochloric acid to give the water-soluble phosphonic acids 136. Aromatic phosphonate-phosphines 137, and their air-stable complexes, have been obtained from the reaction of 4-halogeno-substituted phenylphosphonates with lithium diphenylphosphide.  

New mercaptoaryl- and mercaptoheteroaryl-phosphonates (139) have been prepared by or /io-lithiation of the corresponding O, O-diisopropyl S -aryl/hetero-aryl phosphorothioates 138 followed by sulfur to carbon rearrangement. A simple and efficient synthesis of the 2-substituted 3-diethylphosphono 5-methyl-furans 141 from the ketal phosphonate 140 has been reported. Acylation of a- 

3 Halogenoalkyl and Related Acids. - A wide range of a-fluoroalkyl-phosphonates have been prepared by a variety of methods (fluorinated amino acid analogues are discussed in 3.1.6). 

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Alkenyl, Alkynyl, Aryl, Heteroaryl and Related Acids. - Alkenyl-phosphonates have been prepared by the dehydration of P-hydroxyphosphonates with DCC and CuCh, by dehydrohalogenation of P-bromoalkylphosphonates with triethyl orthoformate, and from alk-l-ynylphosphonates 116 by hydrogenation using Lindlar s catalyst (to give the m-isomer 118) and by stereoselective addition of alkylcuprates to give 117 (Scheme 7). A convenient... 

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