Phosphonic diamides synthesis

Given a sufficiently strong base, the activation produced by the phosphoryl group next to an adjacent C—H bond will allow deprotonation and the generation of a highly reactive carbanion. Butyllithium has been commonly used for this purpose, but a preference has been shown in recent work for Ida. Treatment of the anion from methyl methyl(4-morpholinyl)phosphinate (284) with farnesyl chloride yields 285, which, on acidolysis, affords the phosphonic acid 286, employed in the synthesis of a pyrophosphonate analogue of farnesyl pyrophosphate ". Alkylation of the carbanion from the chiral phosphonic diamide 287 (X = Me or higher alkyl) leads to the diastereoisomeric phosphonic... 

Much attention has been devoted to the conversion of aldehydes into the trimethylsilyl ethers of (a-hydroxyalkyl)-phosphonic acids 210 or analogous -phosphinic acids, or of the corresponding (a-hydroxyalkyl)phosphonic diamides 211 by the use of dialkyl trimethylsilyl phosphite or Me3SiOP(NEt2)2 (or other phosphorodiamidite) It is a reaction which occurs very readily, even at room temperature, and the ready methanolytic or hydrolytic removal of the silyl protecting group makes the procedure an attractive alternative to the direct synthesis of the (a-hydroxyalkyl)phosphonic acids from dialkyl hydrogenphosphonates and carbonyl compounds. Silyl-protected hydroxy-phosphonic and -phosphinic acid derivatives are useful for further synthetic development. ... 

New developments in the synthesis of a-hydroxy phosphonic acids and their derivatives have concentrated on their asymmetric formation. The chiral phosphonic diamides (629) (in which R = isopropyl, 2,2-dimethylpropyl, or benzyl or a derivative thereof) in either racemic or optically active forms were converted into their anions and allowed to react with aldehydes to give the products (630) the diastereoisomeric composition of the latter could be ascertained by the use of P NMR spectroscopy, and after acidic hydrolysis and subsequent methylation (diazomethane) it was possible to isolate optically active forms of the dimethyl esters of (l-hydroxyalkyl)phos-phonic acids, the (/ ,R)-diamide giving rise to the (5)-acids as their esters. The best results were achieved when R = Bu CFl2, and enantiomeric excesses were generally above 85% . 

Phosphonic mono- and di-amides have been widely examined as substrates in the WEH reaction with the considerable success in the use of their carbanions in the non-stereose-lective synthesis of (j5-hydroxyalkyl)phosphonic diamides the result of decreased elec-trophilicity of the phosphorus atom. The fission of such diamides occurs when they are heated in a high-boiling solvent the separated threo and erythro stereoisomers from, for example, benzylic phosphonic diamides undergo decomposition into ( )- and (Z)-alkenes, respectively, although the exact mechanism is unclear The successful release of alkene from the thiophosphinic amide 175 is possible after methylation to 176 the yields of unsymmetrical disubstituted alkenes are 50 99%, and even for tri- and tetra-substituted alkenes yields of 53-93% are achievable . 

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... 

The classical reaction between a (haloalkyl)phosphonic diester and NaN3, best carried out in a polar solvent, e.g dmf has been developed into an asymmetric synthesis. The reaction between (chloromethyl)phosphonic dichloride and the chiral auxiliary (5)-(phenylaminomethyl)pyrrolidine (314) is followed by separation of the product 1,3,2-diazaphosph(V)olidines 315 (R = H X = Cl) and 316 (R = H X = Cl), obtained in yields of 36 and 45%. Alkylation (BuLi, RX) of the cyclic diamides and reaction between the products and NaN3, to give 315 and 316 (R = alkyl X = N3), is then followed by acidoly-... 

Jansa P, Baszczynski O, Dracinsky M, Votruba I, Zidek Z, Bahador G, Stepan G, Cihlar T, Mackman R, Holy A et al (2011) A novel and efficient one-pot synthesis of symmetrical diamide (bis-amidate) prodrags of acyclic nucleoside phosphonates and evaluation of their biological activities. Eur J Med Chem 46 3748-3754... 

Blazis VJ, Koeller KJ, Spilling CD (1995) Reactions of chiral phosphorus acid diamides the asymmetric synthesis of chiral alpha-hydroxy phosphonamides, phosphonates, and phosphonic acids. J Org Chem 60 931-940... 

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