Phosphonylation additive

Electrophilic reaction can account for the additions of morpholine or phosphonyl (Scheme 14), or... 

An alternative approach is to have the chiral auxiliary on the enolate. Sweeney has reported the addition of bromoacyl sultam 102 to phosphonyl imines 103, which afforded the cis- or trans-aziridines with high levels of diastereoselectivity depending on the imine substituent (Scheme 1.30) [55]. 

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). 

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. 

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

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

Romakhin et al. [49] showed that anodically generated phosphoniumyl radicals can add onto alkenes to yield phosphonylated alkenes through an anodic oxi-dation/addition/anodic oxidation/elimination/nucleophilic attack sequence (Scheme 17). 

Reaction of perthiophosphonic anhydrides (64) with amines leads first to (105) and then, by further attack, to (106). With ammonia itself the second addition proceeds at the same phosphorus atom as the initial attack, giving (107) and (108). The anhydride (64) is also reported to react with 1,3-dioIs to give cyclic phosphonyl disulphides (109). Thermal decomposition of phenylphosphinic anhydride (110) may lead to the formation of PhP since in the presence of benzil the formation of the phosphorane (111) was observed. ... 

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],... 

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>. 

The authors have also observed that reverse addition of a carboxylic acid to a mixture of PPAA, hydroxylamine and TEA gave a lower hydroxamate yield (16% with oleic acid) compared to the direct addition, suggesting a certain competition between carboxylate and hydroxylamine for phosphonylation. 

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... 

Discussion Catalyst 52 is prepared from Boc-(L)-ter -leucine in five steps, with a 75% overall yield [41]. Details of imine and phosphite preparation are also provided by Jacobsen and co-workers [81]. The hydrophosphonylation reactions as reported by Jacobsen can be carried out without any special precautions, in unpurified commercial diethyl ether (Et20) and under an ambient atmosphere. A reduction in temperature was shown to have a beneficial effect on product enantiopurities, but with a decrease in reaction rates. Unbranched aliphatic aldehydes were incompatible with the reaction conditions as reported, due to their rapid decomposition prior to phosphonylation. Although phosphite ester groups that are more electron-withdrawing than o-nitrobenzyl significantly increase the overall reaction rates, products are obtained with diminished optical purities, possibly due to a retro-addition pathway. 

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). 

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... 

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. 

Addition of diethyl phosphite to aldimines bearing less bulky substituents (e.g., CH3 or Et)39 proceeds with very low stereoselectivity and leads to the various diastereomeric products in comparable amounts. For this reason a new phosphonylating agent was introduced, trisftri-methylsilyl) phosphite40. However, the stereoselectivity with this reagent is not much improved, although yields increased by ca. 20 %. 

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. 

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