Phosphinate monoesters

Optically active phosphine monoester 69 was prepared as a stable transition state analogue of the hydrolysis of 70, and used as a template (Scheme 13.17) [52], When heated in the presence of amidine 72, methyl methacrylate, ethylene glycol dimethacrylate and AIBN, polymerization took place and offered the polymer 73, in which the template 69 is attached to the binding sites by a combination of hydrogen bonds and electrostatic interactions. After washing in the presence of MeOH and aqueous NaOH, the template was removed from the cavity, thus leading to a catalytically active MIP. 

Similarly, monobasic forms of other trivalent phosphorus species have been used successfully in such conjugate addition processes, including monoesters of phosphonous acids375 425 426 and secondary phosphine oxides.427-429 The notable exception to the last of these species is the addition of the anion from diphenyl phosphine oxide to unsaturated aldehydes, which appears always to proceed by addition to the carbonyl carbon.427... 

Phosphonamidates are usually prepared by coupling an activated phosphonate monoester with the amine of interest. Since most phosphonate amino add analogues are prepared as their diesters, this procedure first requires selective cleavage to the monoester. Activation from the phosphonic acid oxidation level typically involves preparation of the phosphono-chloridate, but it can also be accomplished by chlorination of an H-phosphinic acid analogue. 

Phosphinate monoalkyl esters are also readily converted into the parent phosphinic acids using TMSBr. 66,104 However, attempted deprotection of a phosphonamidate monoester using this reagent was reported to result in cleavage of the P—N bond. 107 ... 

Scheme 31 Synthesis of Phosphonate Monoesters by Esterification and Oxidation of H-Phosphinic Acids 63-1231...

Acylpalladium complexes are readily prepared through oxidative addition of Pd° complexes to acid chlorides. PdL4 compounds, where L is a tertiary phosphine, react with acid chlorides at room temperature to give trani-L2Pd(COR)Cl complexes. Since carbon monoxide does not insert into palladium acyl bonds, Pd(C0C02R) complexes are made from oxidative addition of oxalyl chloride monoesters. 

A related reaction that yields the same types of products as does the Michaelis-Arbuzov reaction begins with either a phosphinous acid or a monoester of a phosphonous acid. (The corresponding reaction may also be performed with a diester of phosphorous acid.) By treatment with an appropriate base, the conjugate base of the phosphorus-containing acid is generated that serves as the nucleophihc reagent for direct formation of the phosphonate or phosphine oxide product (or phosphonate product from a phosphorous acid diester). This procedure is commonly referred to as the Michaehs Becker reaction. ... 

A new one-pot method has been developed by Kraszewski for the synthesis of aryl nucleoside phosphate (3a-p) and phosphorothioate (4a-p) diesters. This method, based on H-phosphonate chemistry, employed diphenyl phosphoroch-loridate and a series of phenols. Depending on the substituents present on the phenols, oxidation conditions were optimized to avoid competing hydrolysis. A versatile procedure that permits easy access to H-phosphonoselenoate monoesters (5) has been developed by Stawinski. These monoesters, obtained by selenisation of a phosphinate using triphenylphosphine selenide in combination with trimethylsilyl chloride, reacted with a suitable nucleoside in pyridine/acetonitrile in the presence of diphenyl phosphorochloridate to yield... 

Concerning the oxygen-containing bidentate ligands [R E02+ ] and MC, discrete dimeric, tetrameric and hexameric ring assemblies have been reported for organotin carboxylate, phosphinate, phosphonate monoester, phosphate diester, " sulfonate, and tungstate derivatives. 

Addition of hypophosphorous acid, PH(OH)2 to Schiff bases, yielding (l-aminoalkyl)phosphorous acids, can also be effected by mixing the three reactants.129 Further, Schiff bases have also been added to dialkyl thiophos-phites,130 phosphonous monoesters,130 secondary phosphine oxides,117 and metal derivatives of secondary phosphines 131 these phosphides, however, give well-defined products only after hydrolytic working up to phosphine oxides. 

The phosphonates (50) are photochemically reactive and lead to products dependent upon the nature of the substituents. Irradiation of the phosphonate (50a) yields the product (51a) as a result of a photoreaction analogous to a Norrish Type I process. An analogous product (51b) is also encountered in the photolysis of phosphonate (50b). In this instance however other products (52b) and (53b) are produced as a result of Norrish Type II reactivity and fission of the resultant biradical. Norrish Type II fission dominates the photoreactions of (50c) and (50d) yielding the monoester (52c, d) and the olefin (53c, d). Fission of the C—bond to afford the radical (54) and products derived from it is the result of irradiation of the phosphine (55). ... 

Further esterification of monobenzyl benzylphosphonate may be carried through the Mitsunobu procedure, the best yields being achieved using the potassium salt of the substrate. Monoesters of iV-protected (1-aminoalkyl)phosphonic acids are further esterified by alcohols in the presence of BOP-type reagents [(l-aminoalkyl)alkylj- and [(l-aminoalkyl)aryl]-phosphinic acids, again as their potassium salts, have been converted into esters by reactive alkyl halides in the presence of 18-crown-6 ether (see also reference The... 

The aim of this section is to present a short summary of the processes used for the resolution of some simple phosphonic and phosphinic acid derivatives, and to indicate how the enantiomeric purity of such preparations, and of other optically active sulphur-containing organophosphorus esters, may be assessed. In most of the work to be described the phosphonic monoesters and phosphinic acids contining sulphur or selenium were prepared from the corresponding acid chloride this and other preparative routes are indicated in Scheme 11. 

Purine-9-ylalkyl derivatives (15) containing both the phosphonic and phosphinic substituent inhibit purine nucleoside phosphorylase. Compound 15 [R = NH2, R = OH, R r4 = h, = N, X = H, X = CH2)3] had K, = 0.0026 pmol (ref. 39). The phosphonate monoesters 16 (R = Me, R = o-, m- or P-NO2) inhibit the class A j5-lactamase, probably by phosphorylation of the active site of this enzyme" . When R = Ph they also inhibit class C j5-lactamase of Enterobacter cloacae P99 and may led to new antibiotics. They should be useful as active titrants of the enzyme ... 

Without additional reagents Phosphorous and phosphinic acid monoesters... 

Azeotropic water entrainment. A mixture of phosphorous acid, -decanol, and toluene refluxed under argon with removal of the resulting water -> mono- -decyl phosphite. Y 82%. F. e., also phosphinic acid monoesters, s. E. E. Nifant ev, V. R. KiPdisheva, and I. S. Nasonovskii, Zh. Prikl. Khim. 42, 2590 (1969) C. A. 72, 100835. 

The formation of mixed anhydrides 2 is critical for overall yield of the conversion of H-phosphonate monoesters 1 into H-phosphonothioate 4. The transformation of an H-phos-phonate into an H-phosphonothioate function in the ribo series proved to be a stereoselective process. In contradistinction to (his transformation, synthesis of the ribonucleoside 3 -H-phosphonothioate via phosphinate intermediates [202] hardly showed any stereoselectivity. 

Trimethylsilyl)ethanol has been used as a protecting group in phosphate monoester synthesis and involves the use of 2-(lrimethylsilyl)ethyl dichlorophosphite (eq 14). Bis[2-(trimethylsilyl)ethyl] (V,(V-diisopropylphosphoramidite has been prepared from dichloro(diisopropylamino)phosphine and 2-(trimethylsilyl) ethanol and used as a phosphitylating agent in the synthesis of phosphotyrosine containing peptides (eq 15). ... 

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