Phosphonates reaction

Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

The presence of trialkyl phosphite 198 in the above mentioned reduction of the gem-dibromocyclopropanes 150 with dialkyl phosphonate and triethylamine alters the reaction course. Dialkyl cyclopropanephosphonates 199 are produced via reductive phosphonation [104]. Trialkyl phosphite participates in the carbon-phosphorous bond formation. It is supported by the exclusive formation of diisopropyl cyclopropylphosphonate in the phosphonation reaction with diethyl phosphonate and triisopropyl phosphite. (Scheme 74)... 

Preparation of dimethyl (4-methoxybenzyl)phosphonate — Reaction of a benzyl halide with a trialkyl phosphite... 

Preparation of diphenyl l-(benzylcarbamoyl)-4-(phthalimido)-l-phosphonate — Reaction of a phthalimido-protected aminoaldehyde with a triaryl phosphite in the presence of benzyl carbamate... 

Preparation of diethyl l-(4-pyridyl)-l,2-dihydropyridine-2-phosphonate — Reaction of phosphorus trichloride with a pyridylpyridinium chloride... 

Preparation of diethyl pyridine-2-phosphonate — Reaction of an N-methoxy pyridinium salt with a dialkyl phosphite salt... 

Preparation of diethyl 3,3-diethoxypropynyl-l-phosphonate — Reaction of a sodium salt of a dialkyl phosphite with an acetylenic halide492... 

Starting from the readily available a-acetoxyallyl phosphonates, reaction to the y-substituted systems (23) takes place under Pd catalysis. 

Treatment of 1,1 -dibromocyclopropanes with triethyl phosphite in the presence of triethylamine and water at 90 °C gives mixtures of diethyl cis- and fra .t-cyclopropylphosphonates 1 (A and B, reductive phosphonation) (Table 24). The relative amount of the reactants is crucial for the outcome of the reaction. In the absence of water the dibromide is recovered almost quantitatively, and if too much water is used, the dibromides may be reduced to the corresponding monobromocyclopropanes, in particular if an electron-withdrawing group is attached to the ring (see Section 5.2.1.1.1.5.1.). Evidence implies that diethyl phosphonate, which is formed by hydrolysis of triethyl phosphite, plays an important role in the phosphonation reaction. This is supported by the observation that reductive phosphonation also can be carried out at 90 °C using a mixture of triethyl phosphite, diethyl phosphonate and triethylamine (C and 1,1-Dichlorocyclopropanes are unreactive under these conditions. 

Davis and coworkers carried out a Wittig-cyclization sequence with the partially protected 2-deoxyamino sugar 191 using an amino acid based phosphonate. Reaction of 191 with the cesium enolate 192 gave a 53% yield of epimers 193 and 194 (1 1 ratio) in which epimerization of the 2-amino group had taken place. The maimo isomer 194 was then epimerized to the more stable gluco 193 derivative by simple treatment with t-BuOLi in methanol (Scheme 38) [54]. 

Homer-Wadsworth-Emmons reaction/Still-Gennari phosphonate reaction... 

Savignac and coworkers drew a comparison between the transition metal-catalysed and the photostimulated phosphonation reactions and concluded that the latter process produced more uniformly good results, and also showed that the addition of one equivalent Nal to mixtures of aryl bromide and metal dialkyl phosphite greatly accelerated the phosphonation process". ... 

Oxirane rings also suffer rupture when acted upon by phosphorylcarbanions. The products are then dialkyl (3-hydroxyalkyl)phosphonates Reactions between dialkyl (lithiomethyl)phosphonate and a, -unsaturated aldehydes yields dialkyl (2-hydroxyalk-3-en-1 -yl)phosphonates. ... 

Yet another synthesis which employs phosphorus(III)triesters is the reaction which occurs between diethyl trimethylsilyl phosphite and bis(alkylthio)ketals more specifically, such acetals of aromatic aldehydes react in the presence of a Lewis acid (SnCl4 was actually employed) to give diethyl (a-alkylthiobenzyl)phosphonates (reaction 17) ... 

Reactions of Ketones with Methylenephosphoranes.—Intramolecular Wittig reactions have been used to prepare a variety of cyclic compounds including bicyclic alkenes (41) and cyclic imines. In a similar way both Wittig and phosphonate reactions can be used to synthesize many strained bicyclic alkenes (42), but fail with the most strained examples, e.g., (43). Intramolecular Wittig... 

The aim of this chapter is to collect and discuss the use of phosphonates in the synthesis of biologically active or natural products in the last decade. Since in this period, innumerable syntheses of such compounds have been effected with these reagents, we have restricted our discussion to such cases where more extensive use of phosphonates in total syntheses is reported. Therefore, the synthetic approaches to bioactive products, where a single Horner-Wittig or other phosphonate reaction was use are beyond the scope of this review. Moreover, this article is not intended to provide a comprehensive coverage of the field. It highlights some of the recent developments reported in the literatme with the hope to stimulate further research in this area. 

IV. FRACTIONATION OF IMPURE RADIOLABELED PHOSPHONATE REACTION MIXTURES BY ANION EXCHANGE CHROMATOGRAPHY... 

Condensation Polymerization Routes to Polymeric Phosphonates. Reaction of a phosphonyl dichloride with an aliphatic diol produces polyphosphonates which are low melting and hydrophilic. Industrial interest has been concentrated on the polyphosphonates made from aromatic diols or aromatic phosphonyl dichlorides. 

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