Esters, phosphonic, with

Phosphonothioate Esters of Phenols. Phosphonates with a single P—C bond are highly toxic and persistent iasecticides but have not been used extensively because some compounds produce delayed neuropathy leading to irreversible paralysis ia higher animals, including humans. Such compounds specifically inhibit an enzyme, neurotoxic esterase, that is responsible for the growth and maintenance of long nerve axons (31,32). 

Neutral Extractants. Many neutral organophosphoms extractants are available phosphate esters, phosphonate esters, phosphinate esters, and phosphine oxides. The most popular neutral extractant is tributylphosphate (TBP), which reacts with RE elements according to a solvation mechanism ... 

Cellulosic, polyester, and acrylic fibers lubricated with a surfactant-based oiling composition containing an organic phosphorus ester neutralized with an amine showed less pilling, good antistatic properties, and anticorrosiveness. The phosphorus ester salts were hexyl phosphate trimethylamine salt, dodecamethy-lene caproate phosphonate ethylamine salt, and polyethylene glycol dodecyl ether phosphate dimethylamine salt [262]. 

Allylic phosphonate esters react with imines, in the presence of a palladium catalyst, to give P-lactams. " Alkynyl reagents such as BuC=CO Li react with imines to form P-lactams. 

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... 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

A series of 1-aminoalkanediphosphonic acids has been reported by the treatment of the N-phenylthiourea derivatives of a>-diethoxyphos-phinoylaldehydes with triphenyl phosphite.343 This constitutes an approach toward the analogues of aspartic and glutamic acid in which both carboxylate sites have been replaced by phosphonic acid functions. A similar approach has also been reported to be of use for the preparation of (diphenyl ester) phosphonate analogues of ornithine, lysine, and homolysine.344345... 

Finally, (3-bromoacrylate esters react with trialkyl phosphites to provide the unsaturated phosphonates (Equation 3.24), presumably through an addition-elimination route.392... 

The use of a blend of succinamate and phosphoric acid esters, modified with phosphonic acid, produced good results. These collectors are known as collectors from the PL500 series. 

Amongst the reported syntheses of phosphonic esters, one of cyclohexylphos-phonic esters depends on treatment of cyclohexanthione with trialkyl phosphites followed by desulphurization of the intermediate esters (47) with Raney nickel.41... 

List was the first to explore this possibility, examining the Hantzsch ester mediated reduction of a,P-unsaturated aldehydes [209], Using 20 mol% of the binaphthyl derived phosphonate salt of morpholine (153) in dioxane at 50 °C, a series of P-aryl a,P-unsaturated aldehydes underwent transfer hydrogenation with Hantzsch ester 154 with excellent levels of absolute stereocontrol (96-98% ee) (Scheme 63). The method was also applied to the aliphatic substrates ( )-citral and famesal to give the mono-reduced products in 90% and 92% ee, respectively. Significantly, in line with many of the chiral secondary amine catalysed transformations described above the reactions follow a simple and practical procedure without the need for exclusion of moisture and air. 

Subsequently, List reported that although the method described above was not applicable to the reduction of a,P-unsaturated ketones, use of a chiral amine in conjunction with a chiral anion provided an efficient and effective procedure for the reduction of these challenging substrates [210]. Transfer hydrogenation of a series of cyclic and acyclic a,P-unsaturated ketones with Hantzsch ester 119 could be achieved in the presence of 5 mol% of valine tert-butyl ester phosphonate salt 155 with outstanding levels of enantiomeric control (Scheme 64). A simple mechanistic model explains the sense of asymmetric induction within these transformations aUowing for reliable prediction of the reaction outcome. It should also be noted that matched chirality in the anion and amine is necessary to achieve high levels of asymmetric induction. 

Pudovik and Kuzovleva have studied the reaction of dialkyl phosphonates with ethyl profHolate and have shown diat, in the presence of sodium alkoxide, a bis adduct (470) is formed, whereas with excess of the ester, under similar conditions, a mono adduct (471) is formed (Scheme 74). 

The halogen-fluorine exchange with an HF-amine complex allows the transformation of a gem-dichloro goup into a difluoro group. While this reaction is difficult to initiate in nonactivated positions, it is efficient in the benzylic position and in the a position of functional groups (e.g., esters, phosphonates) (Figure 2.10). ... 

Furo[3,4-f]pyranones are produced by an intramolecular hetero-Diels-Alder reaction of a,/3-unsaturated 7-keto esters, 81. The Horner-Wadsworth-Emmons reaction of phosphonates with a-diketones is used to assemble compounds 81 (Scheme 17) <2004TL4297>. 

Functionalized polymers are of interest in a variety of applications including but not limited to fire retardants, selective sorption resins, chromatography media, controlled release devices and phase transfer catalysts. This research has been conducted in an effort to functionalize a polymer with a variety of different reactive sites for use in membrane applications. These membranes are to be used for the specific separation and removal of metal ions of interest. A porous support was used to obtain membranes of a specified thickness with the desired mechanical stability. The monomer employed in this study was vinylbenzyl chloride, and it was lightly crosslinked with divinylbenzene in a photopolymerization. Specific ligands incorporated into the membrane film include dimethyl phosphonate esters, isopropyl phosphonate esters, phosphonic acid, and triethyl ammonium chloride groups. Most of the functionalization reactions were conducted with the solid membrane and liquid reactants, however, the vinylbenzyl chloride monomer was transformed to vinylbenzyl triethyl ammonium chloride prior to polymerization in some cases. The reaction conditions and analysis tools for uniformly derivatizing the crosslinked vinylbenzyl chloride / divinyl benzene films are presented in detail. 

A less common approach to the synthesis of phosphinates is the reaction of electrophilic phosphonates with carbon nucleophiles such as Grignard reagents or lithium enolates. For example, the phosphinic acid analogue 71 of the amino acid statine was synthesized by displacement of tert-butyl lithioacetate on a 5-phenyl phosphonothioate 70 (Scheme 23)d104l The racemic diastereomers of the 5-phenyl phosphonothioate were obtained in pure form, and the displacement of the phenylsulfanyl moiety was found to be stereospecific, although the stereocenter at phosphorus would later be lost on hydrolysis of the ester. A similar displacement reaction has been described using the p h osp h on och I ori d ate.1711... 

C-Acylations of C,H-acidic compounds have also been realized on insoluble supports. The few examples that have been reported include the C-acylation of support-bound ester enolates with acyl halides [9], Claisen condensations of polystyrene-bound ketones with benzoic acid esters, the C-acylation of nitriles with acyl nitriles or anhydrides, and the C-acylation of phosphonates with acyl halides (Entries 5-9, Table... 

Acylation of liihiated phosphonic ester 36 with methyl ester 35 gives, through a Cony Kwiatkowski reaction,21 the p ketophospho-nic ester 11. 

Hydrogenation of a-acylamino or a-halogeno (3-keto phosphonates with a BINAP-Ru complex gives the corresponding syn alcohols selectively with >98% ee (Scheme 1.58) [243a,251]. The sense of enantio- and diastereoface discrimination is the same as that in the case of ot-substituted [3-keto carboxylic esters (see Table of Scheme 1.57). 

The first example of a catalytic asymmetric Horner-Wadsworth-Emmons reaction was recently reported by Arai et al. [78]. It is based on the use of a chiral quaternary ammonium salt as a phase-transfer catalyst, 78, derived from cinchonine. Catalytic amounts (20 mol%) of organocatalyst 78 were initially used in the Homer-Wadsworth-Emmons reaction of ketone 75a with a variety of phospho-nates as a model reaction. The condensation products of type 77 were obtained in widely varying yields (from 15 to 89%) and the enantioselectivity of the product was low to moderate (< 43%). Although yields were usually low for methyl and ethyl phosphonates the best enantioselectivity was observed for these substrates (43 and 38% ee, respectively). In contrast higher yields were obtained with phosphonates with sterically more demanding ester groups, e.g. tert-butyl, but ee values were much lower. An overview of this reaction and the effect of the ester functionality is given in Scheme 13.40. 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

The regiospecific nucleophilic displacement of 1,2-cyclic sulfamidates 130 with methyl thioglycolate or a-amino esters 130 can be accompanied by lactamization (thermal, base mediated, or cyanide catalyzed) to give thiomorpho-lin-3-ones and piperazin-2-ones 131 (Scheme 19) <20030L811>. If malonate esters, phosphonate-stabilized esters, or aryl-substituted enolates were used as nucleophiles in this reaction, trisubstituted pyrrolidines were obtained in high yield <2004OL4727>. 

Chiral PCPs can be used for heterogeneous asymmetric catalysis.43,52 162 164 167 The chiral porous ZrIV phosphonate with Run-binap fragments (binap = 2,2 -bis(diphenylphosphanyl)-1,1 -binaphthyl) has a permanent porosity, and shows asymmetric catalytic activity in the hydrogenation of (3-keto esters with enantiomeric excess values of up to 95%.162... 

Mulzer (Scheme 8 upper left) obtained the a,/(-unsaturated ester 33 with Z configuration from aldehyde 26a via a Still-Gennari olefination with phosphonate ester 34. Reduction of the ester with DIBAH and application of L-imidazole-PPhj gives allylic iodide 35. This acts as electrophile on the -anion of sulfone 36. After reductive removal of the phenylsulfone, group 28b is obtained [23]. 

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [11L1, Scheme 3.111 j as the butane-2,3-diace-tal 111 2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase.205 Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111 1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase206 and influenza neuraminadase207-208 as well as shikimic add derivatives.209 210... 

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