Nucleophilic Attack at Phosphorus

Reactions.—(/) Nucleophilic Attack at Phosphorus. A reinvestigation of the reaction between phosphorus trichloride and t-butylbenzene in the presence of aluminium chloride has shown that the product after hydrolysis is the substituted phosphinic acid (11), and not the expected phosphonic acid (12). Bis(A-alkylamino)phosphines have been reported to attack chlorodiphenyl phosphine with nitrogen, in the presence of a base, to give bis-(A-alkyl-A-diphenylphosphinoamino)phenylphosphines (13). In (13), the terminal phosphorus atoms are more reactive than the central one towards sulphur and towards alkyl halides. 

Two papers have appeared on the reactions of halogenophosphines with tervalent phosphorus compounds. In a detailed study of the reactions at 20 °C of a range of tertiary phosphines with phosphorus trichloride, dichlorophenylphosphine, and chlorodiphenylphosphine, it has been shown that, in general, 1 1 adducts are formed, provided that the tertiary phosphine is a good nucleophile. With diphenylchlorophosphine, for example, an adduct (18) is formed with dimethylphenylphosphine, but not with diphenylmethylphosphine, although the relative importance of steric and electronic factors remains to be established. The related reactions of phosphorus trichloride and of dichlorophenylphosphine are much more complex, and the initial crystalline products are not amenable to analysis. The reactions at 280 °C of a similar system have been shown to lead to halogen exchange, e.g. the conversion of (19) to (20). 

Dichloroethylphosphine has been shown to react with methyl vinyl ketone to form 2-ethyl-5-methyl-A -l,2-oxaphospholen-2-oxide (25), which has been converted to (26) by chlorination in the presence of base. The same phosphine adds to methyl acrylate in the presence of acetic acid to give the phosphine oxide (27). Further examples have appeared of the reactions of the phenylhydrazones of methyl ketones with phosphorus trichloride to produce the heterocycles (28). 

Shvetsov-Shilovskii, N. P. Ignatova, and N. N. Mel nikov, Zhur. obshchei Khim., 1970, 40, 1501. 

---

In the pH range 2—3.5 the phosphonate (78) hydrolyses with loss of ROH at approximately 10 times the rate of comparable esters lacking the vicinal oxime function or in which this function is methylated on oxygen. An intramolecular general-acid catalysis mechanism was proposed, but it was not possible to exclude entirely an intramolecular nucleophilic attack at phosphorus. Intramolecular attack by the vicinal dimethylamino-group takes place preferentially at carbon rather than phosphorus in the phos-phonofluoridate (79). ... 

The mechanism of phosphate ester hydrolysis by hydroxide is shown in Figure 1 for a phosphodiester substrate. A SN2 mechanism with a trigonal-bipyramidal transition state is generally accepted for the uncatalyzed cleavage of phosphodiesters and phosphotriesters by nucleophilic attack at phosphorus. In uncatalyzed phosphate monoester hydrolysis, a SN1 mechanism with formation of a (POj) intermediate competes with the SN2 mechanism. For alkyl phosphates, nucleophilic attack at the carbon atom is also relevant. In contrast, all enzymatic cleavage reactions of mono-, di-, and triesters seem to follow an SN2... 

Methyl[l,2,3]diazaphospholo[l,5- ]pyridine 41 undergoes electrophilic attack at N-2 (Scheme 12). Dimethyl sulfate in the absence of nucleophile led to the salt 42, whereas upon treatment with water, protonation of the same atom was followed by nucleophilic attack at phosphorus and consecutive ring opening to produce 43 <1995S173>. 

Methyl P-bromomethyl-A-r-butylphosphonamidate (360) has been found to rearrange upon treatment with methoxide to give dimethyl f-butylaminomethylphosphonate (362) and dimethyl iV-r-butyl-iV-methylphosphoramidate (363). The authors have proposed that the products are derived from an azaphosphiridine oxide intermediate (361) by nucleophilic attack at phosphorus and cleavage of the P-N or P-C bond, respectively. ... 

Soon after total isomerization of I the decomposition of its isomer II also is completed. The conversion of II into the final mixture of ionic substances consists of two basic steps dealkylation by Me2S to form the S-methyl-O-phenylphosphorothiolate anion III (eq. 3), and nucleophilic attack at phosphorus by the anion III to give a S-methyl diphosphate which is 0-dealkylated to IV by the leaving group MeS (eq. 1). 

The first reagent has a choice it can do either the Wittig or the Peterson reaction it prefers the Peterson reaction. This merely tells us that nucleophilic attack at silicon is faster than nucleophilic attack at phosphorus. The carbanion part of the ylid is next to silicon but it could be nowhere else. 

Other related examples of nucleophilic attack at phosphorus for which some kinetic information is available are reactions of the N-substituted phosphoro-amidates and phosphoradiamidates " and of the methyl phosphoroazidate... 

Routes to functionalised phosphinine systems, e.g., (202), and the phenolic systems (203) and (204), have been developed, the latter behaving as a genuine heterocyclic phenol. Whereas the 2-chlorophosphinine (205) is unreactive towards nucleophilic reagents, nucleophilic attack at phosphorus occurs in the related reactions of the P-W(C0)g complex of (205). The synthesis of the partially delocalised IX , 3X -diphosphabenzene system (206), and the 1X ,3X , 5X -triphosphabenzene system (207), has also been reported. Interest has also continued in the chemistry of azaphosphinine systems, although many of these involve phosphorus in the... 

Laali and coworkers132 investigated the reaction of the gaseous 2-f-butyl-3-phenyl-phosphirenylium ion (a 2jr-Huckel phosphirenylium ion) with aniline and other nucleophiles and dienes via MS" experiments. In ion/molecule reactions, the ion reacts readily with aniline to form an azonium ion via nucleophilic attack at phosphorus by the amino group, as suggested by calculations and MS3 experiments. 

A number of examples of reactions of chlorophosphines with ethylene oxide have been published. Thus the phosphines (34)—(36) are each converted into P chloroethoxy-derivatives, presumably by nucleophilic attack at phosphorus by the epoxide oxygen. 

This problem was solved by Still and Gennari with strongly electron-withdrawing groups (CF3CH20-) on the phosphorus atom. Nucleophilic attack at phosphorus is speeded up and the reaction becomes Z-selective. Conditions have been chosen to get the best Z-selectivity and we can contrast the two results with the same aldehyde.21... 

With a few notable exceptions the di- and triesters of phosphates are generally hydrolyzed quite slowly. These exceptions include the five-mem-bered ring phosphate esters described previously and phosphate esters, which have available to them an intramolecular pathway, that is, phosphate esters that have a pendant nucleophilic functional group in a suitable position to attack the phosphorus atom. Alcohol (12), amine (101), or carboxylic functional groups (1) able to form four- five-, or six-membered rings by nucleophilic attack at phosphorus react relatively rapidly. For example, the hydrolysis of phenylsalicylphosphate (Scheme 5), is accelerated 10 -10 -fold over the analogous intermolecular path (92). 

The major product in the reaction of the allyl anion with trimethylphosphite involves nucleophilic attack at phosphorus with subsequent elimination of methanol (equation 64) A similar series of addition/elimination reactions between several carbanions and trimethylphosphine have been observed in a flowing afterglow reactor (equation 65). In contrast, various carbanions react with trimethylphosphate via S 2 displacement at carbon (equation 66) ... 

The chemistry of pyridylphosphines has been reviewed. Further studies have appeared of the reactions of phosphines bearing 2-pyridyl or 2-benzothiazolyl substituents with butyl-lithium, which result in the formation of biaryl coupling products via an initial nucleophilic attack at phosphorus. A study of the de-diazoniation of arenediazonium salts using triphenylphosphine (and trialkylphosphites) indicates that the reactions proceed via a radical-chain mechanism, initiated by single electron transfer from the phosphine to the diazonium salt, to give... 

---