Arbuzov-type process

Trialkyl phosphites undergo reaction with alkynyliodonium tosylates, resulting in dialkyl alkynylphosphonates, 102, via an Arbuzov-type process [78] [Eq. (55)]. 

An important steric hindrance of the carbon in the a-position to the oxygen (or a bicyclic structure) reduces or even inhibits formation of the phosphoryl group by substitution reaction on this carbon. It must be pointed out that phosphoryl formation occurs, generally, in Arbuzov-type reactions, by a substitution process, but can take place also by a -elimination which is favoured by major steric hindrance. 

Several promising processes are applied to the synthesis of 2-cyanoethylphosphonates, including, for example, the thermally induced Michaelis-Arbuzov-type rearrangement of diethyl 2-cyanoal-lylphosphite to diethyl 2-cyanoallylphosphonate (Scheme 6.30).- " -4 ... 

Several possible reactions may give rise to impurities in the preparation of phosphonic or phosphinic acid esters by the Michaelis-Arbuzov reaction, and it is possible that, in some cases, such reactions become preponderant. Triethyl phosphite, for instance, has been successfully used as a dehalogenating agent, in particular, for debrominations. Isomerization of allylic groups may occur through S T-type processes (reaction 5) or be induced thermally (reactions 6 and 7) 25,126... 

Although the Michaelis-Arbuzov reaction has been widely used for the preparation of phosphonates and the path shown in Scheme 10.50 has been generally accepted, it appears that if the alkyl group attached to oxygen is capable of leaving without the help of the nucleophile, some portion of the reaction may proceed by an SNl-type process. 

During the synthesis of a group of potential threonine synthase inhibitors, Zervosen studied the synthesis of allylic phosphonates through an Arbuzov-type reaction between allylic bromides and trialkyIphosphites (Scheme 4.48) [100]. Trimethylphosphite was nsed as a representative phosphorus nucleophile in this chemistry. Similar to many of the Arbuzov-type reactions, the chemistry was operationally simple and proceeded under solvent-free conditions. Although the temperature of this process was lower than several of the systems described previously, there are still many substrates that will not survive heating to 100 °C for 8h. 

In another related process, aryl ethers have been shown to undergo a facile cleavage reaction upon treatment with copper salts in the presence of an amine (Fig. 8-8). The driving force for the reaction is primarily the stabilisation of the phenoxide by co-ordination to the metal. Simple azo complexes have been shown to undergo these reactions under very mild conditions. The process is somewhat reminiscent of the Arbuzov reactions discussed in Chapter 4. The pyridine probably functions as both a ligand and as a base in this reaction. Reactions of this type are the basis of a useful conversion of a methoxy-substi-tuted dye, 8.6, to the corresponding phenol, 8.7, in the presence of copper(n) salts and ammonia. 

The reaction of trialkylphosphines, especially triphenylphosphine, with alkyl halides is particularly useful since the resultant phosphonium salts are easily converted to the phosphonium ylid on treatment with a suitable base (sec. 8.8r kk Ylids are, of course, the reactive species in the well-known Wittig olefination reaction, which will be discussed in section 8.8.A.i. A related Sn2 process involves reaction of a trialkylphosphite with an alkyl halide, the Arbuzov reaction (sometimes called the Michaelis-Arbuzov reaction). Triethylphos-phite (70) reacts with iodomethane to give the phosphonium salt, 71. Heating generates the monoalkyl phos-phonic ester (72). This type of phosphonic ester can be converted to an ylid and used in the well-known Horner-Wadsworth-Emmons oiefination (sec. 8.8.A.iii). 

There are two types of P(V) compounds, i.e., the pentacovalent and the ionic phosphonium salts. The most famUiar outcome of the attack at a pentacovalent phosphorus atom by nucleophiles is substitutive fragmentation. On the other hand, there are numerous ways for a nucleophile to attack R4P compounds direct Sn2 displacement, simple addition, and addition-elimination. Many reactions, especially the biphilic processes, involve formation of R4P compounds followed by a counterion-initiated decomposition. The Arbuzov and Perkov reactions are representative. 

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