Radicals phosphonation

Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

The synthesis of biologically active 6-phenanthridinephosphonates (351) have been realised via a radical phosphonation of 2-isocyanobiaiyls... 

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-alkylated alkyl iodides 931. Q.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779-781]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl aicohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783]. 

The acyl phosphonates, acyl phosphine oxides and related compounds (e.g. 81. 82) absorb strongly in the near UV (350-400 nm) and generally decompose by rescission in a manner analogous to the benzoin derivatives.381"285 Quantum yields vary from 0.3 to 1.0 depending on structure. The phosphinyl radicals are highly reactive towards unsaturated substrates and appear to have a high specificity for addition v.v abstraction (see 3.4.3.2). 

Reaction of Unsaturated Compounds with Dialkyl Phosphites The diesters of phosphorous acid are somewhat resistant to oxidation and used as intermediates for the reaction with olefins forming phosphonic acids. The reaction takes place in the presence of free radical initiators, such as di-/-bu-tyl peroxide [104,105]. 

Several cyditol derivatives of varying ring size, for example, (69)/(70), have been prepared based on an enzymatic aldolization as the initial step. Substrates carrying suitably installed C,H-acidic functional groups such as nitro, ester, phosphonate (or halogen) functionalities made use of facile intramolecular nucleophilic (or radical) cyclization reactions ensuing, or subsequent to, the enzyme-catalyzed aldol addition (Figure 10.27) [134—137]. 

The synthesis of a-substituted phosphonates 89, via the electrophilic addition of phosphorylated C-radicals 88 (generated by reaction of BujSnH to the readily accessible a-phosphoryl sulfides (or selenides)) and electrophilic addition to electron rich alkenes, has been described [57] (Scheme 26). A large excess of alkene is necessary to minimize the competitive formation of the undesired compound 90 resulting from direct reduction of the initial radical 88. The ratio 89/90 has been measured for each example. The synthesis of the a-mono- or a,a-di-substituted (R or phosphonates 89 shows that the free radical approach... 

The (a-sulfanylalkyl)phosphonates and their difluorinated derivatives are also, by easy radical cleavage of the C-S bond, useful precursors of phospho-nomethyl or phosphonodifluoromethyl radicals, which can be added to double bonds and so, introduced in a variety of structures. Besides, the use of phospho-nodithioformates as radical trapping agents and their use as RAFT reagent for controlled polymerization open a new interesting field of appHcation for these dithioesters. 

R2P(0)H) and phosphonates (R02P(0)H) as hydrogen atom donors and the corresponding phosphonyl radicals as chain carriers (Scheme 3). 

Fluorinated phosphonates exhibit interesting properties as enzyme inhibitors, chelating agents or as fuel cell electrolytes [29] however, only few methods of preparation for these compounds are available. Burton et al. [30] developed several methods to prepare fluorinated phosphates which involve phosphonyl, and likely phosphoranyl radicals as chain carriers (Scheme 11). 

Scheme 11 Preparation of fluorinated phosphonates involving phosphonyl and phospho-ranyl radicals as chain carriers...

Phosphonate ester (10) is made from chloride (12) available by direct chlorination with photochemical generation of radicals. 

The peroxide-catalysed addition of dimethyl phosphonate to norborna-diene gives nortricyclenes as well as norbornenes. Usually, radicals react with this diene to give only nortricyclene derivatives. The ease of hydrogen abstraction from the parent phosphonate undoubtedly favours trapping of radical (8). 

PVPA was prepared by the free-radical homopolymerization of vinyl-phosphonyl dichloride using azobisisobutyronitrile as initiator in a chlorinated solvent. The poly(vinylphosphonyl chloride) formed was then hydrolysed to PVPA (Ellis, 1989). No values are available for the apparent pA s of PVPA, but unpolymerized dibasic phosphonic acids have and values similar to those of orthophosphoric acid, i.e. 2 and 8 (Van Wazer, 1958). They are thus stronger acids than acrylic acid, which as a pK of 4-25, and it is to be expected that PVPA will be a stronger and more reactive acid than poly(acrylic acid). 

Reactions and Properties of Phosphonic and Phosphinic Acids and their Derivatives.-A free radical mechanism has been proposed to account for the cleavage of the phosphorus-carbon bond in the alkylphosphonic acids (155) by E coli to give a mixture of alkane (methane only, from methylphosphonic acid) and terminal alkene. 

The heats of ionisation and neutralisation of amino and hydroxylic bis and tris phosphonic acids have been investigated.253 Calorimetry in combination with u.v. and n.m.r. spectroscopy uas used to study the adducts of fluoroalkyl carboxylic acids with diethyl phosphonate.254 The heats of formation of the t-butoxytriphenylphosphoranyl radical uas consistent with the phosphonium structure (92).255 There has been a thermal analysis of the adducts of phosphonic and phosphoric acids with... 

Malacria and coworkers reported a vinylation sequence of epoxides by employing vinyl phosphine oxides as a radical trap. The overall sequence relies on the facile elimination of phosphinoyl radicals. With vinyl phosphonates the THF derivatives were obtained (Scheme 22). The reaction works equally well under stoichiometric or catalytic conditions [102,103],... 

In the second instance, two approaches seem to be worthy of special note. The synthetic utility of elemental phosphorus based on it acting as a radical trap appears to be quite valuable, but additional effort is required to determine the variability of the source of the organic free radicals. (Is there some other, more efficacious, source of organic free radicals that works better with this system than acylated iV-hydroxy-2-pyridones ) The other approach that appears ripe for development is the hydrolysis/elimination with "phosphorates" derived from the oxidative addition of white phosphorus to alkenes. We look forward to the continued development of such facile approaches toward the preparation of fundamental phosphonic acids. 

Nitrone reactions with lithiated dialkyl phosphite results in the formation of a-(hydroxyamino)phosphonate, which, depending on the character of the R substituent at a-C lead to a-phosphorylated nitrones (429) or fS-phosphorylated nitroxyl radicals (430) after successive oxidations (Scheme 2.200) (686—689). 

The reason for such a behaviour of arsenic acid is that arsenic is a member of the group 5A elements in the periodic table. Phosphorus and antimony are also group 5 elements and are known to be chemically similar to arsenic. On this basis [8,9], the antimonic acids were found to be poor cassiterite collectors. The alkyl phosphonic acids were not selective collectors. The ethylphenylene phosphonic acid was found to produce similar or better results compared to /7-tolyl arsonic acid. The structural formula for phosphonic acid (Figure 21.5) is similar to that of /7-tolyl arsonic acid but arsenic was replaced with phosphoms. The styrene phosphonic acid radicals are C6H5-CH-CH and p-ethylphenylene CH3-CH2-C6H4. 

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

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