P-phosphonylation

SGI-mediated polymerization in miniemulsion SGI (Figure 15) is a versatile nitroxide suitable for the polymerization of styrene, acrylates, and even methacrylates (when copolymerized with 10mol.% styrene " or acrylonitrile to impart livingness to the system). SGI is an acyclic P-phosphonylated nitroxide with a more favorable equilibrium constant than TEMPO. For highly reactive monomers such as BA, additional SGI is required to maintain a controlled polymerization. 

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). 

Restricted rotation in a series of ditert-buty1 phosphines (30 R = H, Aik, Ph etc) has been studied using molecular mechanics calculations.10 Rotation about the P-N bond in phosphonyl acetamides has a barrier of dG 16.3 heal mol 1. 66... 

The phosphonyl adduct 300 reacted with a dilute solution of anhydrous hydrogen chloride in ethanol or with sodium ethoxide to afford an essentially quantitative yield of the P-N cleaved product 304 with inversion of configuration. Addition of sodium ethoxide to a solution of 304 in methanol resulted in the formation of enantiomerically pure (+)-(.V)-ethyl methyl phenylphosphonate (305). It also reacted quantitatively with methylmagnesium iodide at room temperature to give the product of P-S bond cleavage 306, which upon acid catalyzed methanolysis afforded enantiomerically pure (+)-(R)- methyl methylphenylphosphinate (307) (Scheme 72) [108],... 

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. 

Phosphonate peptides can be synthesized either by formation of the P—O bond or the O—C bond. The former coupling is typically carried out via reaction of an alcohol (e.g., an a-hydroxy acid) with an activated phosphonyl spedes in a manner similar to phosphonamidate synthesis (Section 10.10.2.1). The latter process employs the phosphonate anion as a nucleophile in a displacement reaction on an ester with a leaving group in the a-position. 

Peroxide Bis-[(2-clhoxycarbonyl-2-methoxycarbonyl-1 -trifluoro-mcthyl-elhenylamiiio)-phenyl-phosphonyl]- E12a, 947 (As P(0-OR)2 = N-R H20 ... 

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... 

A phospho-transfer process is the transfer of a phospho group, [(R0)2P=0] or derivative thereof, between chemical sites. When this process results in the formation of a new [P—O] bond it is called phosphorylation, a ubiquitous biological process, and the product is a phosphate ester, 1 (or derivative thereof) (Scheme 1). Phospho-transfer leading to [P—C] bond formation is termed phosphonylation, the product of which is a phosphonate, 2 (or derivative thereof) (Scheme 1). 

Benschop, H.P., Keijer, J.H. (1966). On the mechanism of ageing of phosphonylated cholinesterases. Biochim. Biophys. Acta 128 586-8. 

De Bisschop, H.C., de Meerleer, W.A.P, Willems, J.L. (1987). Stereoselective phosphonylation of human serum proteins by soman. Biochem. Pharmacol. 36 3587-91. 

Notable were highly enantioselective additions of N-phosphonyl imines with dialkyl zinc or hydroxyketones and a one-pot reaction of alkynylzirconocenes with alkynyl phosphazenes and zinc carbenoids to give single isomer cyclopropylphosphonamides. The importance of enantioselective and dynamic kinetic asymmetric transformations is illustrated in many publications. Other interesting reports cover the use of phosphoramidates for the synthesis of allylic amines as well as the first example of C-P cleavage of a-aminophosphono acids using periodate. 

Thermally induced and UV-light mediated alcoholysis reactions of 2,3-oxaphosphabicyclo [2.2.2] octenes bearing sterically demanding substituents at the P-atom (475) with different alcohols were studied. The observed sensitivity to steric effects suggests that phosphonylation of alcohols follows two parallel pathways which are consistent with EA and Sn(2)P (or AE) mechanisms (Figure 90). ... 

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