A-phosphonyl

The reactivity shown in Scheme 3 results from the low bond dissociation energy (BDE) of the P-H bond [11] k=l.2 10 M s for the H-transfer from R02P(0)H to a primary C-centered radical) and the fast halogen-atom transfer from a C-halogen bond to a phosphonyl radical [9,12] (fc=4 10 M s for f-Bu-Br and k=83 10 M s for Cl3C-Br). Piettre et al. [13] pointed out that these chain reactions were even more efficient when dialkylthiophosphites and the corresponding dialkylphosphinothioyl radicals were involved. 

The p-scission of a phosphoniumyl radical yields a cation and a phosphonyl radical, while its reaction with a nucleophile generates a phosphoranyl radical which can undergo SET reactions and a- or p-fragmentations (Scheme 14). 

The synthesis in Scheme 13.64 was carried out by E. Carreira and co-workers at ETH in Zurich, Switzerland. A key step in the synthesis in Scheme 13.64 is a stereoselective cycloaddition using a phosphonyl-substituted nitrile oxide, which was used to form the C(16)-C(17) bond and install the C(15) oxygen. 

The rate of appearance of p-nitrophenolate ion from p-nitrophenyl methylphosphonate (7), an anionic substrate, is moderately accelerated in the presence of cycloheptaamylose (Brass and Bender, 1972). The kinetics and pH dependence of the reaction are consistent with nucleophilic displacement of p-nitrophenolate ion by an alkoxide ion derived from a cycloheptaamylose hydroxyl group to form, presumably, a phosphonylated cycloheptaamylose. At 60.9° and pH 10, the cycloheptaamylose-induced rate acceleration is approximately five. Interestingly, the rate of hydrolysis of m-nitrophenyl methylphosphonate is not affected by cycloheptaamylose. Hence, in contrast to carboxylate esters, the specificity of cycloheptaamylose toward these phosphonate esters is reversed. As noted by Brass and Bender (1972), the low reactivity of the meta-isomer may, in this case, be determined by a disadvantageous location of the center of negative charge of this substrate near the potentially anionic cycloheptaamylose secondary hydroxyl groups. 

More recently, 2-thioxo-4-thiazolidinones 415 were reported to undergo facile thiophilic addition of a-phosphonyl carbanions and subsequent lactamization to generate bicyclic thiazolo [2,3-A thiazole-3,5-diones 416 (Equation 189) <2004PS1307>. 

Figure 14. A phosphonylated-PPO reverse osmosis membrane before (A) and after (B) testing for 5 months under a pressure of 13.6 atm...

III. Monosaccharides Having a Phosphonyl Group in the Furanose Ring. 176... 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

As may be seen from Table n, the stereochemistry found for the products resulting from the addition of a phosphonyl radical to a difluoroenol ether double... 

Free radical cyclization of 1,6-diene (120) using diethyl phosphite or diphenylpho-sphine oxide initiated by peroxide, produces an organophosphorus compound (121) via the addition of a phosphonyl radical to an olefinic group (eq. 4.42a). Radical addition of PH3 to limonene (122) results in the formation of 4,8-dimethyl-2-phosphabicyclo[3.3.1]-nonane (123) (eq. 4.42b) [121, 122]. 

Ishii and coworkers developed a Mn(OAc)2-catalyzed hydrophosphonation of alkenes 40 (Fig. 47) [271]. The active Mn(III) catalyst is generated by reaction of Mn(OAc)2 with oxygen. Hydrogen abstraction from diethyl phosphite 169 forms a phosphonyl radical, which adds to 40. The resulting alkyl radical is reduced by 169 to continue the chain reaction. Alkylphosphonates 170 were isolated in 51-84% yield. With (3-pinene a cyclobutylcarbinyl radical ring opening was observed in 32% yield, while 1,5-cyclooctadiene underwent a tandem radical addition/ transannular 5-exo cyclization (cf. Fig. 38). 

Radical-based dephosphorylation via a phosphonyl radical constitutes one formulation for the mechanism of C-P bond cleavage during microbial degradation of organophospho-nates.80 Frost has demonstrated that anhydrides 117 derived from phosphonic acid and thiohydroxamic acid react in a chain sequence with thiols, Bu3SnH and CC14 to give dephosphoryl-... 

Binding of sarin and soman to a tyrosine residue present in blood has been observed by Black et al. (51) When sarin or soman was incubated with human plasma, phosphonylated tyrosine was observed by LC/MS after Pronase digestion, in addition to phosphonylated serine. The precise site of this residue has not yet been confirmed but it is associated with the albumin fraction. A phosphonylated tryptic peptide [/-PrO(CH3)P(0)]-Tyr-Thr-Lys, consistent with albumin, has been identified but this sequence is also present in other proteins. Before the advent of modem mass spectrometry, diisopropyl fluorophosphate was reported to bind... 

Several groups have demonstrated that desilylation of dialkyl l-(trimethylsilyl)methylphosphonates initiated by means of fluoride ion (CsF, KF, or TBAF) is an effective process for the transfer of carbanions to electrophilic centers. Some examples involving the fluoride-induced formation of a-phosphonylated carbanions from dialkyl l-(trimethylsilyl)methylphosphonates containing a fragile C-Si bond have been described. Cleavage of the carbon-silicon bond under these conditions offers the advantages of neutral conditions and contributes to obtain better yields from sensitive substrates than those obtained under basic conditions. This procedure, which appears operationally simpler and cleaner than traditional protocols, has been applied to the preparation of alkenes " and 1-alkenylphosphonates" by Homer-Wadsworth-Emmons and Peterson reactions, respectively. 

More recently, another example involving the intermediacy of phosphonylated sul fines has been reported. Treatment of diethyl 3-methyl-l,2-butadienylphosphonate with LDA at low temperature followed by reaction with MejSiCl leads to the desired diethyl l-(trimethylsilyl)-3-methyl-l,2-butadienylphosphonate. The addition of alkyllithiums to the a,P-doublc bond of this very unstable compound gives the a-phosphonylated carbanions, which are allowed to react with an excess of SO2. The resulting sulfines are stirred overnight, and only low yields of diethyl 2-thienylphospho-nates (12-25%) are obtained, contaminated with protonated anion (Scheme 2.23). The separation of these two compounds proved to be problematic. The major disadvantage of the method is the incomplete reaction of the anion with S02. ... 

Wnuk, S.F., Bergolla, L.A., and Garcia, P.L, Jr., Studies toward the synthesis of a-fluorinated phosphonates via tin-mediated cleavage of a-fluoro-a-(pyrimidin-2-ylsulfonyl)alkylphosphonates. Intramolecular cyclization of the a-phosphonyl radicals, J. Org. Chem., 67, 3065, 2002. 

In the presence of DBU and MejSiCl in CH2CI2, the addition of diethyl phosphite to the readily available nitroalkenes gives transient a-phosphonyl nitronates, which are smoothly converted into P-ketophosphonates on treatment with MCPBA. The procedure is useful to prepare a variety of diethyl l-aryl-2-oxoaIkyIphosphonates (Scheme 7.53). ... 

Phosphonylated. V-bciizyI enamine, formed from benzylamine and diethyl 2-oxopropylphosphonate, undergoes aza-annulation with acryloyl chloride in refluxing THF to provide a phosphonylated unsaturated lactam in 72% yield. - Subsequent hydrogenation generates a 78 22 ratio of diastereomeric products in 67% yield (Scheme 7.114). These compounds represent an interesting class of rotationally constrained P-aminophosphonic acid analogues. 

Kim, D.Y, and Kim, J.Y, A new synthesis of a-fluoromalonates from a-fluoro-a-phosphonyl mal-onates using P-C bond cleavage, Synth. Commun., 28, 2483, 1998. 

The lithium salt of diethyl 2-propenylphosphonate behaves as an ambident nucleophile in reactions with a variety of electrophilic reagents. In reaction with methyl methacrylate, the intermediate formed in the lirsl step (conjugate addition at the y-carbon of the phosphonate) has a carbanionic center developed at C-5. The second step involves intermolecular conjugate addition to a second molecule of methyl methacrylate, yielding an intermediate capable of the final 1,6-cyclization to produce a phosphonylated polyfunctionalized derivative of cyclohexane in good overall yield (60%, Scheme 8.63). ... 

Further studies have been reported on a-phosphonyl carbenes. Under irradiation, (94) (from the corresponding diazo-compound) is in equilibrium... 

However, even erythrocyte AChE measurements cannot be expected to be a perfect surrogate for the nervous tissue enzyme this is because pharmacokinetic factors may result in differential access of the inhibitor to the red cell and to neural structures. A further consideration is that, where nerve agents react with the enzyme to produce a phosphonylated structure that does not spontaneously reactivate, red cells of mammals lack the protein synthetic capability to synthesize new AChE. By contrast, in nervous tissue, after inhibition by OPs whose enzyme-inhibitor complex with AChE does not readily reactivate, activity may reappear relatively quickly. Thus, Wehner et al (1985) observed approximately 30% recovery after 24 h in di-isopropylfluorophosphate (DFP)-treated mouse CNS reaggregates, which was clearly due to synthesis de novo of AChE. Another consideration in the interpretation of butyrylcholinesterase activity measurements is that the normal range is relatively wide, rendering interpretation in individual patients difficult unless the results of previous estimations in the patient are available (Swami-nathan and Widdop, 2001). 

The higher reactivity of enol silyl ethers can he exploited in their reaction with imines. For addition to A-phosphonyl imines two types (SEGPHOS and DuPHOS) of ligands... 

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