Through the Alkylation or Phosphorylation of Carbanions

Given a sufficiently strong base, the activation produced by the phosphoryl group next to an adjacent C—H bond will allow deprotonation and the generation of a highly reactive carbanion. Butyllithium has been commonly used for this purpose, but a preference has been shown in recent work for Ida. Treatment of the anion from methyl methyl(4-morpholinyl)phosphinate (284) with farnesyl chloride yields 285, which, on acidolysis, affords the phosphonic acid 286, employed in the synthesis of a pyrophosphonate analogue of farnesyl pyrophosphate . Alkylation of the carbanion from the chiral phosphonic diamide 287 (X = Me or higher alkyl) leads to the diastereoisomeric phosphonic 

The stereochemical outcome of the alkylation process also depends on the nature of the base used to generate the carbanion. Use of the substrates 297 (R = NPr 2, = Me or PhCH2) with Ida-thf-R X gave 86-94% of the meso compound 301. On the other hand, the benzylation of 298 (R = NPr 2, R = PhCH2) gave only 302 when lithium tetram-ethylpiperidide was used, but mixtures of299 and 302 in the ratio 18 82 (Ida used) or 80 20 (BuLi used).  

The anions from simple dialkyl alkylphosphonates and Ida in thf have been mono- and di-silylated and stannylated.  

The behaviour of bisphosphoryl compounds such as 310 towards strong bases is reminiscent of that of analogous carbonyl compounds. Initial carbanion formation occurs at the more acidic site, but treatment of the initial anion with a stronger base generates a dianion, which may then be selectively monoalkylated at the more reactive site .  

The well established alkylation of phosphorylated benzyl carbanions has been complemented by the arylation of purely alkyl species. Thus, diethyl (chloromethyl)phosphonate reacts with aryllithium reagents to give the diethyl esters of benzylic phosphonic acids The alternative procedure has been adopted in a synthetic route to isoprenyl (phos-phinylmethyl)phosphonates. Here, a lithiated dialkyl alkylphosphonate is acylated using an ester of the phosphonochloridic acid, R P(0)(0H)C1, where R is an isoprenoid residue. The acylation process has also been carried to with (R0)2P(0)C1 or (Me2N)2P(0)Cl  

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