Phosphonate condensation

V-phenyltrifluoro-methanesulfoni-mide 458, 593 f., 715, 761, 773, phosphonate condensation 276 phosphonate-aldehyde condensation... 

This reaction apparently proceeds by way of the normal phosphonate condensation product, the diazoalkylidene, which then spontaneously loses nitrogen to form the transient alkylidene car-bene. Careful work showed that, after statistical corrections were applied, the reactivity of a C-H bond toward insertion was approximately 0.003 for primary C-H bonds (methyl), 1.0 for secondary C-H bonds (methylene), 7.5 for benzylic (methylene) C-H bonds and 18.6 for tertiary C-H bonds. These relative reactivities are very similar to those previously observed for intramolecular C-H insertion by an alkylidene carbenoid generated from a vinyl bromide27. It was shown subsequently that the alkylidene carbene insertion reaction proceeds with retention of absolute configuration28. Using this approach, (l )-3-dimethyl-3-phenyl-l-cyclopentene and (i )-4-methyl-4-phenyl-2-cyclohexcnonc were prepared in high enantiomeric purity. 

The frequently observed difficulties in the activation of u,p-didehydropeptides, especially in the case of AAla, can be avoided by peptide construction using the corresponding (1-sub-stituted amino acids and subsequent p-elimination in the peptide)158-161 A further possibility is the phosphonate condensation, where the corresponding, modified phosphorylglycine esters can react with aldehydes to yield u,p-didehydropeptidesII5l l62 IM (Scheme 26). 

The ( )-double bond at C-6 of a racemic JH1 is formed by condensation of ethyl ketone 178 with phosphorane 194 in the New Brunswick synthesis. In this synthesis about 40 % (Z)- and 60 % ( )-isomer were formed which were separated by preparative gas chromatography. Compound 182 was converted into ( )-JHl by use of the phosphonate method 148,149) (Scheme 36). Applying two Wittig reactions and a phosphonate condensation the same authors could prepare racemic JH2 171148,149) (Scheme 36). 

Stromberg has reported a detailed kinetic study of the pivaloyl chloride-promoted nucleoside TZ-phosphonate condensation step with a suitably protected nucleoside in the presence of differently substituted pyridines. He also investigated the stability of /Z-phosphonate nucleosidic dimers under various organic and aqueous basic conditions. Strong bases such as DBU and fluoride ions cleaved the dinucleoside ZZ-phosphonates rapidly, as also did a combination of protic solvent and a base. ... 

This reaction apparently proceeds by way of the normal phosphonate condensation product, the diazo-alkylidene, which then spontaneously loses nitrogen to form the transient alkylidene carbene. 

Various practical syntheses have been developed for the central carotenoid unit 8 [11]. One method developed at BASF (Scheme 2) starts with the addition of bromine to butadiene (14) in the gas phase, yielding a mixture of the dibromobutene isomers 75 and 16 which react with triethyl phosphite to produce f )-butene-l,4-diphosphonate (17) in virtually quantitative yield. After phosphonate condensation with methylglyoxal dimethylacetal (18) and hydrolysis of the intermediate Cio-bisacetal, crystalline 8 is obtained as an ( /Z)-mixture [12]. 

In a similar manner, the condensation of diethyl (bromo-oxoalkyl)phosphonates (8) with thioformamide gave the corresponding thiazole (9) (Scheme 5). 

The dimer of phosphonic acid, diphosphonic acid [36465-90-4] (pyrophosphoms acid), H4P2O3, is formed by the reaction of phosphoms trichloride and phosphonic acid in the ratio of 1 5. It is also formed by the thermal decomposition of phosphonic acid. Unlike the chemistry of phosphoric acid, thermal dehydration does not lead to polymers beyond the dimer extended dehydration leads to a disproportionation to condensed forms of phosphoric acid, such as [2466-09-3] and phosphine. 

The Darzens condensation reaction has been used with a wide variety of enolate equivalents that have been covered elsewhere. A recent application of this important reaction was appljed toward the asymmetric synthesis of aziridine phosphonates by Davis and coworkers.In this application, a THF solution of sulfinimine 34 (0.37 mmol, >98% ee) and iodophosphonate 35 (0.74 mmol) was treated with LiHMDS (0.74 mmol) at -78 °C to give aziridine 36 in 75% yield. Treatment of 36 with MeMgBr removed the sulfinyl group to provide aziridine 37 in 72% yield. 

A multitude of 2,3,5-trisubstituted furans are available via the Paal-Knorr condensation. As with the synthesis of disubstituted furans, the scope of this version of the reaction is broad and includes incorporation of aryl, alkyl, ester, and phosphonate substituents. 

The synthesis starts by elaboration of a small unit that will provide the bridgehead nitrogen, the carboxyl group, and a phos-phonate unit that will close the six-membered ring by intramolecular ylide condensation. Thus, the amino group of phosphonate,... 

Condensation with the ylide from diethyl (carboxyethyl)-phosphonate gives the corresponding ester largely as the E isomer. The epoxide is then opened with acetate (117) and... 

The strategy for the construction of 13 from aldehyde 16 with two units of phosphonate 15 is summarized in Scheme 12. As expected, aldehyde 16 condenses smoothly with the anion derived from 15 to give, as the major product, the corresponding E,E,E-tri-ene ester. Reduction of the latter substance to the corresponding primary alcohol with Dibal-H, followed by oxidation with MnC>2, then furnishes aldehyde 60 in 86 % overall yield. Reiteration of this tactic and a simple deprotection step completes the synthesis of the desired intermediate 13 in good overall yield and with excellent stereoselectivity. 

Intramolecular phosphonate-ketone condensation (Homer-Wadsworth-Emmons)... 

Photosensitive functions are in many cases also heat sensitive, so the preparation of photosensitive polyimides needs smooth conditions for the condensations and imidization reactions. Some chemical reactants, which can be used for polyamide preparation, have been patented for the synthesis of polyimides and polyimide precursors. For example, chemical imidization takes place at room temperature by using phosphonic derivative of a thiabenzothiazoline.102 A mixture of N -hydroxybenzotriazole and dicyclohexylcarbodiimide allows the room temperature condensation of diacid di(photosensitive) ester with a diamine.103 Dimethyl-2-chloro-imidazolinium chloride (Fig. 5.25) has been patented for the cyclization of a maleamic acid in toluene at 90°C.104 The chemistry of imidazolide has been recently investigated for the synthesis of polyimide precursor.105 As shown in Fig. 5.26, a secondary amine reacts with a dianhydride giving meta- and para-diamide diacid. The carbonyldiimidazole... 

An alternative procedure for effecting the condensation of phosphonoacetates is to carry out the reaction in the presence of lithium chloride and an amine such as diiso-propylethylamine. The lithium chelate of the substituted phosphonate is sufficiently acidic to be deprotonated by the amine.262... 

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