Halides arylphosphonic

Dialkyl arylphosphonates and alkenylphosphonates are prepared by the coupling of halides or triflates with the dialkyl phosphonate 783[64l-643]. 

A useful new method of preparing arylphosphonates (123) involves the reaction of trialkyl phosphites with aryl halides in the presence of a nickel catalyst.The suggested mechanism is via the nickel complex (124), and is non-radical. 

A Michaelis-Becker approach using the sodium salt of dialkyl phosphites has been successful for the formation of C-P bonds to aromatic rings.184 Reaction of the dialkyl phosphite in DMF with the appropriate diaryliodonium halide provides the corresponding dialkyl arylphosphonate in good yield (81 to 93%). This approach to the arylphosphonate esters proceeds in superior yield under relatively mild conditions and therefore is one to be accorded serious consideration for the preparation of such materials. 

The earliest developments in transition metal-assisted formation of aromatic C-P linkages were the result of the efforts of Tavs28 that were concerned with the use of Ni(II) halide salts for the reaction of aryl halides with trialkyl phosphites. These reactions involved conditions reminiscent of the Michaelis-Arbuzov reaction (heating at an elevated temperature) and produced arylphosphonate products in reasonable yield (Figure 6.8). 

Similarly, copper salts (cupric and cuprous) facilitate the reaction of aryl halides with trialkyl phosphites in the formation of dialkyl arylphosphonates under conditions like those found in nickel systems.37-39 Again, the copper salts appear to undergo an initial reaction with the phosphites to form a complex that subsequently undergoes reaction with the aryl halide. The requirement for copper is also similar to that for nickel saltstonly a catalytic amount is needed. Further, a preference among halides on the aromatic ring is noted iodide is replaced preferentially to other halides (Figure 6.10).40... 

A new entry for the synthesis of vinyl- and arylphosphonates has been achieved by reaction of vinyl or aryl halides with trialkyl phosphites in the presence of (TMS)3SiH under standard radical conditions [72]. An example of this intermolecular C—P bond formation is given in Reaction (7.62). Interestingly, the reaction works well either under UV irradiation at room temperature or in refluxing toluene. 

Table 4 Yields of Dialkyl Arylphosphonates Formed in the Photostimulated Reaction of Dialkyl Phosphite Ions with Aryl Halides ArX + (ROhPO" - (RO>2P( —Q)Ar ...

The palladium-catalysed cross-coupling of aryl halides or vinyl halides with dialkyl phosphonates (31) to yield dialkyl arylphosphonates and dialkyl vinylphosphonates, respectively, was first reported by Hirao and co-workers 69 the halides used most frequently are bromides and the reaction is stereospecific with haloalkenes. Subsequently, analogous reactions of alkyl alkylphosphinates (32), alkyl arylphosphinates (32), alkyl phosphinates (33), and secondary phosphine oxides (34), replacing [P—H] bonds with [P—C] bonds to yield various phosphinates and tertiary phosphine oxides, have been developed (Figure 7.1). Alkyl phosphinates (33) may be mono- or diarylated as desired by the selection of appropriate conditions. Aiyl and vinyl triflates have also found limited... 

Reactions between diethyl hydrogenphosphonate and ArX (X = I or Br) to give diethyl arylphosphonates have been carried out in the presence of a phase transfer catalyst. Bis(trimethylsilyl) phenylphosphonite reacts with alkyl halides to give [(ar)alkylphenyl]phosphinic derivatives, and it also adds to a,P-unsaturated carboxylic esters (as well as to nitriles and amides) to give (2-functionalized-l-alkyl)phosphinic derivatives. ... 

The low reactivity of aromatic halides in the Arbusov reaction has been partially overcome through the use of palladium catalysts. The reaction of phosphites with diphenyliodonium iodide in the presence of copper salts gives arylphosphonates (1), presumably by initial nucleophilic substitution and an Arbusov reaction. Anionic resins also appear to catalyse the... 

The mode of reaction of alkyl- or arylphosphonic halides with Grignard reagents in ether is most often unpredictable. Bis(p-tolyl)phenyl-phosphine oxide is reported as the major product from phenylphos-phonic dichloride and the required quantity of Grignard reagent (148). Attempted synthesis of diallylphenylphosphine oxide under similar circumstances gave only undistillable black oils and tars (13). Equimolar quantities of reactants furnished diphenylphosphinic acid in good yield plus a small quantity of triphenylphosphine oxide (45). 

All of the ramifications of this process are not yet explored, but it suggests that attempted synthesis of mixed tertiary phosphine oxides via reaction of arylphosphonic dihalides or diarylphosphinic halides with alkyllithium reagents might be complicated by side reactions. 

Slightly unconventional modifications have been applied, occasionally with advantage, to otherwise conventional preparative reactions. Thus, the Michael-Becker reaction between dibromomethane and sodium dialkyl phosphites in solvents containing liquid ammonia is aided by exposure of the reaction mixtures to ultraviolet radiation. Dialkyl arylphosphonates are obtained in very high yield from the reaction between trialkyl phosphites and aromatic hydrocarbons when carried out in the presence of trisodium phosphate in an electrochemical system (see Organophosphorus Chemistry , Vol. 12, p. 105). The bond between phosphorus and aromatic carbon is also formed when aryl halides react with the P(0)H function in the presence of a combination of tetrakis-... 

Dialkyl arylphosphonates are also obtained from sodium dialkyl phosphites and aryl halides in the presence of Cu I in HMPTin a similar reaction, diethyl (l-cycloalkenyl)phosphonates with carbon rings having up to 12 atoms were prepared in 50—70% yields from the 1-cycloalkenyl chloride and the copper(i) adduct from triethyl phosphite. ... 

A P n.m.r study has been made of the PdCl2-catalysed reactions between unactivated aryl halides and trialkyl phosphites which lead to dialkyl arylphosphonates. Several Pd-containing species have been recognised as participating in the general reaction scheme.Other applications Pd(0)-catalysis are to be found later in this Report. 

The stereochemistry of alkylation of chiral phosphorus-stabilised carbanions (138) has been investigated and shown to be highly sensitive to the nature of the nitrogen substituent. Phase-transfer catalysed alkylation of 2-(diethoxyphosphinyl)cyclohexanone (139) gives bothO-(140) and C-(141) alkylated products. The latter predominate when reactive, non-sterically demanding alkyl halides are used. a-Arylphosphonates (142) have been synthesised in good yields by the copper(l) salt-mediated arylation of phosphonate carbanions. Under similar conditions A-(2-iodophenyl)-substituted phosphonates provide benzoxazole-(143) and oxindole-(144) substituted phosphonates. 

For insoluble development in Heck-type reactions is P-C and N-C bond formation, which results from coupling of aryl halides with phosphorous compounds [38] and amines [39]. The first application in aqueous medium was achieved by coupling of a dialkyl phosphite with an aromatic iodide to give an arylphosphonate in 99% yield. In 1996, Stelzer and co-workers presented a P-C cross-coupling reaction between primary and secondary phosphines and functional aryl iodides to water-soluble phosphines [Eq. (9)], which are potentially applicable as ligands in aqueous-phase catalysis [40]. 

Arbuzov and Michaelis-Becker reactions provide facile and versatile procedures for the formation of carbon-phosphorus bonds. These methods, however, are not applicable to the formation of sp hybridized carbon-phosphorus bonds. Only few methods have been reported for the syntheses of arylphosphonates and vinylphospho-nates. Direct reaction of aryl or vinyl halides with trialkyl phosphite in the presence of nickel halide requires severe reaction conditions [21,22], and the stereochemistry of vinylphosphonates has not been clarified. Synthesis of dialkyl arylphosphonates 22 [23, 24] is achieved by the palladium-catalyzed reaction (Scheme 2.12), which is called by Hirao reaction . The stereoselective synthesis of dialkyl vinylphosphonates 23 [24-26] is similarly accomplished by this method (Scheme 2.13). A variety of modified procedures have been developed recently [27-37]. 

A nickel-catalyzed route to the formation of arylphosphonates starting from aryl halides and secondary phosphites has been reported (Scheme 4.243) [336]. While some of the methods described previously added nickel salts such as NiCl to the reaction mixture along with a ligand to solubilize/stabilize the metal center, the authors opted to use a preformed nickel complex. A significant electronic effect was observed in this... 

Arylphosphonic acid esters from phosphites and halides... 

---