Oxidation of phosphites

Kinetic studies of the oxidation of phosphites such as triisopropyl phosphite with BTSP 1949 to give phosphates such as triisopropyl phosphate [177] led to the discovery that oxidation of diphosphite nucleotide intermediates such as 2008 with BTSP 1949 at -20 °C in the presence of TMSOTf 20 (instead of iodine in... 

The stoichiometry of this reaction is usually close to unity [6-9]. Thus, cumyl hydroperoxide oxidizes triphenyl phosphite in the stoichiometry A[ROOH]/A[Ph3P] from 1.02 1 to 1.07 1, depending on the proportion between the reactants [6], The reaction proceeds as bimolecular. The oxidation of phosphite by hydroperoxide proceeds mainly as a heterolytic reaction (as follows from conservation of the optical activity of reaction products [5,11]). Oxidation is faster in more polar solvents, as evident from the comparison of k values for benzene and chlorobenzene. Heterolysis can occur via two alternative mechanisms... 

Of these reactions, the reaction of the peroxyl radical with phosphite is the slowest. The rate constant of this reaction ranges from 102 to 103 L mol 1 s 1 which is two to three orders of magnitude lower than the rate constant of similar reactions with phenols and aromatic amines. Namely, this reaction limits chain propagation in the oxidation of phosphites. Therefore, the chain oxidation of trialkyl phosphites involves chain propagation reactions with the participation of both peroxyl and phosphoranylperoxyl radicals ... 

The mild conditions offered by the approach of phosphitylation of the anomeric hemiacetals and subsequent oxidation of phosphites to phosphates suggest a very attractive alternative to the 1-0-lithiation method used in lipid A synthesis considering the complexity of the substrates. Indeed, an application of the phosphoramidite methodology was reported to be effective for the stereoselective instalment of the a-anomeric phosphate... 

Oxidation of phosphites to phosphazenes can also be achieved by reactions with diazo-compounds 38... 

Oxidation of phosphites to phosphates.5 This oxidation can be conducted with t i liloroperbcnzoic acid in 01,0, It is particularly useful in the phosphite tricstcr synthesis of oligonucleotides. Previously, iodine in aqueous solution was used as OHidunl. but use of aqueous solvents requires a drying step at a later stage. 

The oxidation of phosphites by iodine was found to proceed to completion in neutral solution 2 (see Estimation, p. 149). Over a narrow range of concentrations the reaction was found to be uni-molecular with respect to iodine and phosphorous acid.3 It is said to be catalysed by hydrogen ions which are formed as the reaction proceeds.4 A further study of the velocity constants showed that the mechanism was more complicated than had previously been supposed, and that the two tautomeric forms participated in different ways.5 A solution of iodine in potassium iodide contains the ions I- and Iij", and also molecular iodine, I2. The latter reacts directly with the normal form of phosphorous acid and this reaction is repressed by hydrogen ions. Simultaneously, the phosphorous acid changes into another form with which the I8 ion reacts. This second reaction is accelerated by hydrogen ions either directly or, more probably, because they accelerate the tautomeric change. 

In this particular case, we decided to take advantage of the favorable thermodynamic equilibrium constant that drives the oxidation of phosphite to phosphate mediated by a recently described phosphite dehydrogenase (PTDH) [117] to a nearly irreversible process [118]. The exquisite selectivity of PTDH for phosphite also precludes any side reaction that can occur in case, for example, an ADH is used. These characteristics render PTDH as an ideal candidate for use as a coenzyme regenerating enzyme (GRE) in combination with BVMOs or other NAD(P)H-dependent enzymes. 

Derivatives of phosphonic acids, RP==O(0H)2, can be prepared by several different oxidative methods. Primary phosphines RPH2 are oxidized to phosphonic acids by hydrogen peroxide or by sulfur dioxide thus, phenylphosphine gave benzenephosphonic acid (96%) on reaction with sulfur dioxide at room temperature in a sealed tube. Phosphinic acids, RI sO(OH)H, can also be oxidized to the corresponding phosphonic acids with hydrogen peroxide. Ozone oxidized the dioxaphosphorane (54) to the phosphonic ester in 73% yield. Ozone is also capable of stereospecific oxidation of phosphite esters to phosphates. For example, the cyclic phosphite (SS) was oxidized to the phosphate (56) with retention of configuration. Peroxy acids and selenium dioxide are other common oxidants for phosphite esters. 

The oxidation of phosphites to phosphates is very important in the chemistry of nucleoside phosphites, which must be handled under anhydrous conditions. For this purpose, anhydrous hydrogen peroxide bis(trimethylsilyl) peroxide, cumene hydroperoxide, and iV-methylmor ... 

The barrier to inversion about phosphorus in phosphites is large enough for tricovalent phosphites chiral at phosphorus to be configurationally stable, but the conditions for the coupling of phosphoramidites epimerised them at P about 10 times faster than it coupled them, although the oxidation of phosphites to phosphates and thiophosphates proceeded with complete retention of phosphorus stereochemistry. ... 

Product Quantum Yields ((()p) for the Photoinduced Oxidation of Phosphites by Fe20(DPX) (10)... 

Bis(trimethylsilyl)peroxide was reacted with 3-lithiofuran and 3-lithiothiophene to give the 3-trimethylsiloxy derivatives in good yield. These derivatives proved to be good dienes for cycloadditions160 (equation 168). This same silyl peroxide was employed in the oxidation of phosphites to phosphates in high yield161 (equation 169). 

Oxidation of phosphites to phosphates. Phosphites are converted into phosphates by photooxidation in acetone in the presence of Rose Bengal or Methylene Blue yield 65-85%. ... 

After all the hypophosphite wass consumed, hydrogen formation proceeded further, although slower, owing to the further oxidation of phosphite into phosphate [278] ... 

The effect of added chloride was investigated in detail in the oxidation of phosphite to phosphate. Determination of the order in Til ll at a series of chloride concentrations yielded a rate law... 

Hayakawa, Y, Uchiyama, M, and Noyori, R. (1986) Solid-phase synthesis of oligodeoxyribonucleotides using the (trimethylsilyUperoxide oxidation of phosphites Tetrahedron Lett. 27,4195-4196. 

Ogilvie, K. K and Nemer, M J (1981) Nonaqueous oxidation of phosphites to phosphates in nucleotide synthesis. Tetrahedron Lett 22, 2531-2532. 

The oxidation of phosphite with hydroperoxide is mainly heterolytic. This is indicated by the retention of optical activity in alcohol if hydroperoxide is optically active and in phosphate if phosphite is active. The more polar the solvent, the faster... 

E Djouani, E. Richaud, B. Fayolle, J. Verdu. Modelling of thermal oxidation of phosphite stabilized polyethylene. Polymer Degradation and Stability 96(7), 1349-1360, July (2011). 

Other Reactions. Treatment of an active hydroxy compound with 2,2 -dipyridyl disulfide and n-BuyP yields the corresponding thiopyridyl derivative. This methodology has been applied to the preparation of 5-arylthio-5 -deoxyribonucleosides (eq 8). Monophosphate esters [R0P(0)(0H)2] will react similarly to form the activated triphenylphosphonium adduct, which, in the absence of an added external nucleophile, dimerizes yielding a pyrophosphate. A-Methylimidazole has been found to catalyze this transformation. The addition of alcohols or amines, however, traps the phosphoryloxyphosphonium salt as the mixed diphosphate ester or mixed ester/amide, respectively (eq 9). Chlorotrimethylsilane and (pyS)2 have also been reported to facilitate the oxidation of phosphites to phosphates. ... 

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