Phosphonyl radicals

The characteristics of a large number of phosphonyl radicals [L2P(0)] have been extensively listed over the last three decades [1]. Phosphonyl radicals are a radicals [7] (Fig. 2) and due to the significant s-character of their SOMO they exhibit phosphorus hyperfine coupling constants ap ranging from 30 mT to 70 mT [1]. 

The reactivity of electrochemically generated phosphonyl radicals has been recently reviewed by Kargin and Budnikova [8] and will not be considered here. The reactivity of phosphonyl radicals is mainly accounted for by the three processes [9] shown in Scheme 2 radical addition (1), atom transfer (2 and 3), and electron transfer (4). 

Scheme 3 Radical chain reaction involving phosphonyl radicals...

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

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. 

Addition of phosphonyl radicals onto alkenes or alkynes has been known since the sixties [14]. Nevertheless, because of the interest in organic synthesis and in the initiation of free radical polymerizations [15], the modes of generation of phosphonyl radicals [16] and their addition rate constants onto alkenes [9,12,17] has continued to be intensively studied over the last decade. Narasaka et al. [18] and Romakhin et al. [19] showed that phosphonyl radicals, generated either in the presence of manganese salts or anodically, add to alkenes with good yields. 

Murphy et al. showed that EPHP [25] and L2P(0)H [26] can also be used in radical C-C bond forming reactions (Scheme 8). Recently, Piettre et al. [27] used the sodium salt of hypophosphorous acid as H-donor and the subsequent phosphonyl radical as phosphonylating agent for the preparation of 3-fura-nosyl-6 -furanosylphosphinate (Scheme 9). 

Scheme 10 Reductive cyclization involving phosphonyl radicals. Reprinted with permission from [28a]. Copyright 2001 Pergamon Press...

Because of their fast addition onto alkenes, phosphonyl radicals have found wide use as initiating radicals in photo-polymerizations. Several groups [31]... 

Fig. 3 Photo-initiators releasing phosphonyl radicals for photo-initiated free radical polymerizations...

Phosphonyl radicals have been used to functionalize the (60)-, (70)- and (76)-fullerenes [35]. Radical phosphonylation (Scheme 12) of alkenes has been developed by Motherwell et al. [36] for the preparation of fluorophosphony-lated analogs of riboses that exhibit high potential biological activity [37]. 

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). 

Scheme 16 1,4-Addition of phosphonyl radical to enones triggered by a SET...

The light-induced addition elimination reaction of diethyl phosphite to both 1,3,3,4,4-penta-fluorocyclobutene and l-chloro-3,3,4,4-tetrafluorocyclobutene afforded a mixture of diethyl 3,3,4,4-letrafluorocyclobutene-l-phosphonate (11) and tetraethyl 3,3,4,4-tetrafluorocyclobutane-1,2-diphosphonate (12). The postulated mechanism of addition involves phosphonyl radical attack at the cyclobutene moiety.17... 

In another series of experiments, addition of phosphonyl radicals to carbohydrate gem-difluoroenol ethers was investigated as a route to new anomeric carbohydrate difluoromethylene phosphonates 261,262 Phosphonyl radicals could be produced from either diethyl phosphite in the presence of di-ferf-butyl peroxide in refluxing octane, or diethyl(phenylselenyl)phosphonate, on treatment with n-Bu3SnH (plus AIBN) added slowly to a benzene solution under reflux. With the first method,... 

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]. 

A different approach must be used for the photochemical hydrophosphination of electron-poor olefins, and this involves a PET reaction. Silyl phosphites (e.g., 30) were used as electron donors, whereas conjugated ketones have the double role of electron acceptors and absorbing species. Thus, the irradiation of a mixture containing 2-cydohexenone and 30 generated an ion pair. The phosphoniumyl radical cations decomposed to give trimethylsilyl cations (which in turn were trapped by the enone radical anion) and phosphonyl radicals. A radical-radical combination afforded the 4-phosphonylated ketones in yields ranging from 78% to 92% (Scheme 3.20) [49]. This reaction was exploited for the preparation of substituted phosphonates, which serve as key intermediates in the synthesis of a class of biologically active compounds. 

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-... 

Free radical promoted, cationic polymerization also occurs upon irradiation of pyridinium salts in the presence of acylphosphine oxides. But phosphonyl radicals formed are not oxidized even by much stronger oxidants such as iodonium ions as was demonstrated by laser flash photolysis studies [51, 52]. The electron donor radical generating process involves either hydrogen abstraction or the addition of phosphorus centered or benzoyl radicals to vinyl ether monomers [53]. Typical reactions for the photoinitiated cationic polymerization of butyl vinyl ether by using acylphosphine oxide-pyridinium salt combination are shown in Scheme 10. 

It is interesting that hydrogen abstraction to form phosphonyl radicals is comparable to that of phenyl-substituted silanes (1.2 x 105 M s )4 On the other hand, Turro and Jockusch showed that phosphinoyl radicals [R2P(0) ] are... 

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. 

Herpin, T.E, Houlton, J.S., Motherwell, W.B., Roberts, B.P., and Weibel, J.-M., Preparation of some new anomeric carbohydrate difluoromethylenephosphonates via phosphonyl radical addition to gem-difluoroenol ethers, J. Chem. Soc., Chem. Commun., 613, 1996. 

Balczewski. P.. Novel 1-phosphonyl radicals derived from I-mono and l.l-diheterosubslilulcd 2-oxoalkylphosphonates as useful phosplioroorganic intermediates in organic synthesis, Tetrahedmn, 53, 2199, 1997. 

Balczewski, R, and Pietrzykowski, W.M., A free radical approach to functionalization of phosphonates utilizing novel 2- and 3-phosphonyl radicals. Tetrahedron, 52, 13681, 1996. 

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