Phosphonate anions

The anions of malonaldehyde [106, 107] and of organophosphonates [108, 109, 110] are fluorinated in good yields to provide interesting fluorinated intermediates The At-fluoro compound B in Table 3a is also effective in the fluonnation of phosphonate anions [109] (equations 60 and 61). 

NH4OH, MeOH. These conditions result in cleavage of only one ethyl group of a diethyl phosphonate. Selective monodeprotection of a number of alkyl-protected phosphates is fairly general for cases where cleavage occurs by the release of phosphate or phosphonate anions. 

The diketones (178 n = 0, 2, 4, 6, or 7) reacted normally with the phosphonate anion (179) to give unsaturated keto-esters. " However,... 

Olefination Reactions Involving Phosphonate Anions. An important complement to the Wittig reaction involves the reaction of phosphonate carbanions with carbonyl compounds 253 The alkylphosphonic acid esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are generated by treating alkylphosphonate esters with a base such as sodium hydride, n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.254... 

Scheme 2.18 gives some representative olefination reactions of phosphonate anions. Entry 1 represents a typical preparative procedure. Entry 2 involves formation of a 2,4-dienoate ester using an a, 3-unsaturated aldehyde. Diethyl benzylphosphonate can be used in the Wadsworth-Emmons reaction, as illustrated by Entry 3. Entries 4 to 6 show other anion-stabilizing groups. Intramolecular reactions can be used to prepare cycloalkenes.264... 

Among the olefination reactions, those of phosphonium ylides, phosphonate anions, silylmethyl anions, and sulfone anions are discussed. This chapter also includes a section on conjugate addition of carbon nucleophiles to a, (J-unsaturated carbonyl compounds. The reactions in this chapter are among the most important and general of the carbon-carbon bond-forming reactions. 

The DIBAL reduction of esters to aldehydes in the presence of phosphonate anions appears to solve problems of overreduction to alcohol and provides a good general method of 2-carbon homologation... 

Miscellaneous Reactions Reactions of Phosphonate Anions Selected Applications in Synthesis... 

A variety of optically active 4,4-disubstituted allenecarboxylates 245 were provided by HWE reaction of intermediate disubstituted ketene acetates 244 with homochiral HWE reagents 246 developed by Tanaka and co-workers (Scheme 4.63) [99]. a,a-Di-substituted phenyl or 2,6-di-tert-butyl-4-methylphenyl (BHT) acetates 243 were used for the formation of 245 [100]. Addition of ZnCl2 to a solution of the lithiated phos-phonate may cause binding of the rigidly chelated phosphonate anion by Zn2+, where the axially chiral binaphthyl group dictates the orientation of the approach to the electrophile from the less hindered si phase of the reagent. Similarly, the aryl phosphorus methylphosphonium salt 248 was converted to a titanium ylide, which was condensed with aromatic aldehydes to provide allenes 249 with poor ee (Scheme 4.64) [101]. 

Letcher and Van Wazer<1966,2,3 1967,11 have proposed to deal with s and p contributions, and especially their 7r-terms, as being by far the most important in relation to sizeable parameters, e.g. substituent electronegativities and bond angles, of phosphorus. As the latter are known in but a few compounds the use of derived formulae can only be qualitative as for phosphonate anions/1967,71 Of course, the consideration of only s and p orbitals is better when dealing with di- or tri- valent... 

Wadsworth-Emmons reaction of the phosphonate anion of a benzothiazine (compound 239, synthesis shown in Equation (23) has been reported <2004BML1477>. Compound 35 was formylated in a Vilsmeier reaction (Equation 20) <1972CPB1325>. 

Phosphonate peptides can be synthesized either by formation of the P—O bond or the O—C bond. The former coupling is typically carried out via reaction of an alcohol (e.g., an a-hydroxy acid) with an activated phosphonyl spedes in a manner similar to phosphonamidate synthesis (Section 10.10.2.1). The latter process employs the phosphonate anion as a nucleophile in a displacement reaction on an ester with a leaving group in the a-position. 

In the Horner-Emmons reaction (Scheme 3), the sulfonylphosphonate carbanion 5 is formed in the presence of NaH and then reacts with an aldehyde to produce the intermediate 6 that undergoes in situ elimination to yield the vinyl sulfones and phosphonate anion. The sulfonyl group can stabilize the anion in the sulfonylphosphonate 5. The vinyl sulfones that are produced by this method using aldehydes as starting materials are exclusively the E (trans) isomers. The E-isomers of the vinyl sulfones are shown in the NMR spectra based on the coupling constants of the vinylic protons. Although strongly basic conditions are used in the Horner-Emmons reaction and a-amino aldehydes are easily racemized, the amino acid vinyl sulfones prepared by this method still show substantial optical activity. However, the enantiomeric purity of these compounds has not been determined. 5 ... 

Lithium chloride makes it possible to increase the acidity of phosphonate 39 considerably, so that deprotonation and a subsequent llomtr- Mu s orth-Emmons reaction22 (sec Chapters 5 and 8) is possible even with the rather mild base DBU Roush and Ma samunc2 attribute this result to the formation of light ion pair 44) between the lithium cation and the phosphonate anion Macrolacto-ni/ation alone occurs with a yield of 89< . 

These in situ oxidations, followed by condensation with a phosphorous reagent, are normally not possible on ketones, because of their lack of reactivity with stabilized phosphoranes and phosphonate anions. Nevertheless, one-pot condensation with ketones can occur in very favourable... 

A spontaneous cyclization occurs by effect of the Hiinig s base, added during the decomposition of the activated alcohols. This is a rare case in which a ketone condenses in situ with a stabilized phosphonate anion after a Swern oxidation. The condensation is facilitated by the formation of a six-membered ring, and by the relatively high reactivity of a ketone, possessing two activating oxygens at the a-position. 

A 24-analog hydroxystilbene library 34 was constructed from the Horner-Emmons olefination of four resin-bound hydroxybenzaldehyde BBs 33 and six different benzyl phosphonate anions [32], Screening for activity in a cell-based estrogenic assay identified several analogs such as 35 with IC50 values in the 5-15 pM range. 

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