From phosphonates

The reaction has been extended to include carbanions generated from phosphonates. This is often referred to as the Horner-Wittig or Homer-Emmons reaction. The Horner-Emmons reaction has a number of advantages over the conventional Wittig reaction. It occurs with a wider variety of aldehydes and ketones under relatively mild conditions as a result of the higher nucleophilicity of the phosphonate carbanions. The separation of the olefinic product is easier due to the aqueous solubility of the phosphate by-product, and the phosphonates are readily available from the Arbusov reaction. Furthermore, although the reaction itself is not stereospecific, the majority favor the formation of the trans olefin and many produce the trans isomer as the sole product. 

Most common is the preparation of alkyl phosphonic acid esters (phospho-nates) 4 (Z,Z = OR) from phosphorous acid esters (phosphites) 1 (Z,Z = OR). The preparation of phosphinic acid esters (Z = R, Z = OR) from phosphonous acid esters, as well as phosphine oxides (Z,Z = R) from phosphinous acid esters is also possible. 

Therefore in many countries the use of surfactants derived from phosphonic acid are limited by law, especially for surfactants of mass products like household detergents that will flow into wastewater effluents. The difficulty in formulating detergents without inorganic polyphosphates is discussed in Ref. 206. 

Ylids are usually prepared from triphenylphosphine, but other triarylpho-sphines, trialkylphosphines, and triphenylarsine " have also been used. The Wittig reaction has also been carried out with other types of ylids, the most important being prepared from phosphonates " ... 

An intramolecular cycloaddition also occurred with 3-ylidenepiperazine-2,5-diones such as 124 or 125, obtained by Wittig-Horner-Emmons reaction from phosphonate 121 and aldehydes 122 or 123, respectively. The products of the Diels-Alder reaction are the bridged bicyclo[2.2.2]diazaoctane rings 126 and 127 that have been found in biologically active secondary metabolite such as VM55599 and brevianamide A. The different type of structures employed in this case requires a chemoselective reaction in order to produce the expected products as single diastereoisomers after 20 days (Scheme 18) <2001JOC3984>. 

Phosphonothioic dichlorides, general preparation from phosphonic di-... 

Syntheses of pyrans 105 from phosphonic unsaturated nitrile 106 require continuous reflux (00PS(165)17) (Scheme 35). 

Reaction of the anion from phosphonate (5-1) with ethyl meta-triflurophenoxy-methylacetate results in acylation of the phosphonate by the displacement of ethoxide and the formation of (5-3). Condensation of the yhde from this intermediate with the biphenyl ester at position 11 of Corey lactone (5-4) leads to the enone (5-5) with the usual formation of a tmns olefin expected for this reaction. The very... 

Scheme 17 Formation of Phosphonamidates from Phosphonic Acid Monoester 4-65-67-72-731...

In the 1960s organic phosphates (phosphonates) were introduced, such as ATMP and HEDP, which proved to be superior to phosphates in many ways, including their thermal stability and sequestering power. Although the corrosion inhibition of carbon steel, derived solely from phosphonates, remains a weak feature, this can be enhanced by syneigizing with other inhibitors, such as zinc. Like the polyacrylates, phosphonate chemistry has endured and remains a second basic DCA constituent of almost all modern formulations. 

This variation of the Wittig reaction uses ylides prepared from phosphonates.12 The Horner-Wadsworth-Emmons method has several advantages over the use of phosphoranes. These ylides are more reactive than the corresponding phosphoranes, especially when substituted with an electron withdrawing group. In addition the phosphorus product is a phosphate ester and soluble in water - unlike the Ph3PO product of the Wittig reaction - which makes it easy to separate from the olefin product. Phosphonates are also cheaper than phosphonium salts and can easily be prepared by the Arbuzov reaction from phosphanes and halides. 

Phosphonic acid esters are derived from phosphonic acid (often erroneously called phosphorous acid), which is shown with some of its esters in Figure 18.3 Only two of the H atoms of phosphonic acid are ionizable, and hydrocarbon groups may be substituted for these atoms to give phosphonic acid esters. It is also possible to have esters in which a hydrocarbon moiety is substituted for the H atom that is bonded directly to the phosphorus atom. An example of such a compound is dimethylmethylphosphonate, shown in Figure 18.3. This type of compound has the same elemental formula as triesters of the hypothetical acid P(OH)3, phosphorous acid. Examples of triesters of phosphorous acid, such as trimethylphosphite, are shown in Figure 18.3. 

Radical-based dephosphorylation via a phosphonyl radical constitutes one formulation for the mechanism of C-P bond cleavage during microbial degradation of organophospho-nates.80 Frost has demonstrated that anhydrides 117 derived from phosphonic acid and thiohydroxamic acid react in a chain sequence with thiols, Bu3SnH and CC14 to give dephosphoryl-... 

At this point it should be noted, that olefination involving reaction of PO-stabilized carbanions like those from phosphonates, phosphinates, phosphine oxides, phos-phonamides or thiophosphonates (Horner reaction 47), Horner-Wadsworth-Emmons reaction48 ) with carbonyl compounds almost exclusively yields ( )-olefins. This olefination is essentially restricted to PO-activated compounds carrying stabilizing groups on the carbanionic C-atom. However, these compounds are more reactive than the corresponding resonance-stabilized ylides. Therefore, this olefination method... 

The reagent control of the diastereoselectivity originating from phosphonate A (which you know from the olefination of Figure 9.17). 

It is possible to use ancillary ligands in addition to phosphonic acids in building up nanosized cluster compounds of late transition metal ions. Thus, the reaction of CuCl2 with tert-butylphosphonic acid in the presence of 3,5-dimethylpyrazole affords a dodecanuclear copper phosphonate with an interesting cage structure,3 Similarly, large vanadium phosphonate clusters with up to 18 vanadium atoms have been assembled from phosphonic acids.35... 

While all the above molecular phosphates were prepared starting from phosphonic acids and phosphate esters, there are a few examples of molecular phosphates synthesized from phosphoric acid in aqueous medium. Although under hydrothermal conditions the reactions of phosphoric acid with metal ions generally result in extended open framework structures, it has been possible to isolate molecular zero-dimensional metal phosphates.4142... 

Primary phosphines are unpleasant and toxic reagents. They can be prepared from phosphonous halides, RPCI2, using LiAlILt. As is the case for secondary phosphines, easy access to pure phosphonous halides are required to make this route efficient. It has been found that compound 28 can be reduced to primary phosphine 29 using a mixture of UAIH4 and Me3SiCl (Scheme 13).31 This procedure appears useful, as phosphinates of type RP(0)(0Et)2 are often robust compounds that can be prepared in a number of ways. (e.g. Michaelis-Arbusov reaction, palladium-catalysed coupling of diethyl phosphite with aryl bromides, etc.)... 

Unlike the carbanions derived from phosphonate esters, the carbanions of dimethyl methylphosphonate18 and, in some instances phosphine oxides (Homer-Wittig reaction), do not react directly with aldehydes and ketones to give the corresponding alkene.2,3 Rather, the reaction yields an intermediate P-hydroxy derivative that can be isolated and purified to high diastereoisomeric purity. Subsequent reaction then gives the desired alkene with control of stereochemistry (see Schemes 3, 5 and Protocols 7, 8). 

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. 

Cychc dioxodiphosphazanes, [R(0)PNR ]2, are obtained from phosphonic acid dichlorides and primary amines,... 

Synthesis of fused D-A systems such as 665 involved /-butyldiphenylsilyl protection of 4,7-dihydroxy-l,3-benzo-dithiole-2-thione 661, then the Horner-Wittig reaction of the resulting 662 with the carbanion derived from phosphonate 663 and finally deprotection of the TTF 664 to the required 665, obtained as green crystals (Scheme 94) <2003AG2871, 2004JOC2164>. 

Unsyimnetrical ketones result from the alkylation of the carbanion generated in situ from phosphonate (61) with LDA, as shown in equation (30). ... 

Separation of the olefin product from the water-soluble phosphate ester by-product formed from phosphonates circumvents the problem often encountered in removing PhgP = O. 

An alternative, economical procedure for generating (Z)-unsaturated esters from phosphonates and aldehydes avoiding the use of the expensive 18-crown-6 is the olefmation with ethyl diarylphosphonoacetates in the presence of NaH or Triton B (benzyltrimethylammonium hydroxide). Condensations of (diarylphosphono)acetates with base-labile or functionalized aldehydes are best carried out in the presence of Nal and DBU in THF solvent. ... 

The stereoselective synthesis of the anti-ulcer 3,4-dihydroisocoumarin AI-77B was accomplished by E.J. Thomas and co-workers. The key transformation was the stereoselective dihydmxylation of 4-(Z)-alkenylazetidinones that were prepared from 4-formylazetidinone via the Still modified HWE olefination. The benzyl b/s(trifluoroethyl) phospho-noacetate was prepared from phosphonic dichloride and 2,2,2-trifluoroethanol and was alkylated using benzyl... 

Biological chemistry and its needs increasingly dominate the phosphorus(v) acids area and the majority of novel results relate to compounds derived from phosphonic and phosphinic, rather than phosphoric acids. Numbers of studies of compounds related to inositol and to carbohydrates continue to appear, although few contain truly novel results. Phosphorus-containing analogues of amino acids... 

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