Through the Michaelis-Arbuzov Reaction

Early attempts to synthesize phosphonic diesters with P—C(sp) bonding met with little success. Nevertheless, reactions of type 33 have been performed with = Ph or substitut- 

In efforts to prepare the ethynylphosphonic diesters 224 (R = H), reactions have been carried out with 223 (R = Me3Si, X = 1) and with 223 (R = Et3Sn) Thermolysis of the silicon-containing esters afforded the corresponding 224 (R = and the trialkyltin 

The reaction between a trialkyl phosphite and dichloroacetylene proceeds in two stages, the initial product being the dialkyl (2-chloroethynyl)phosphonate, which reacts further to give a tetraalkyl ethynediyl)bisphosphonate (225) .  

The iodonium tosylates 226 have received some attention as alternative substrates in the Michaelis-Arbuzov reaction, with yields in their reactions with trialkyl phosphites of between 35 and 90% for R = Pr, Bu, EtMeCH, cyclopentyl, Ph, or 4-methylphenyl  

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In spite of the apparent simplicity of the procedure, the formation of epoxyalkylphos-phonic acid derivatives through the Michaelis-Arbuzov reaction is very poorly exempli-... 

Preparations of (3-oxoalkyl)phosphonic diesters through the Michaelis-Arbuzov reaction appear to have been limited to the use of trialkyl phosphites in combination with the methiodides, hydrochlorides " " or acetates derived from Mannich bases (reaction 29). 

A very useful modification of the Wittig reaction involves the reaction of phosphonate-stabilized carbanions with aldehydes or ketones, which is known as the Homer-Wadsworth-Emmons (HWE) reaction [7, 151,152], This reaction was originally described by Homer et al. [153, 154] and further defined by Wadsworth and Emmons [155]. Phosphonate-stabilized carbanions are more nucleophilic and more basic than phosphonium ylides. They are prepared by the addition of suitable bases to the corresponding alkylphosphonates, which are readily accessible through the Michaelis-Arbuzov reaction of trialkyl phosphites with alkyl halides (usually a-halo carbonyl compounds) [143]. In contrast to the Wittig reaction, the HWE reaction yields phosphate salt byproducts that are water-soluble and hence are readily separated from the desired alkene products by simple extraction. 

The reaction with phosphite esters is known as the Michaelis-Arbuzov reaction and proceeds through an unstable trialkoxyphopsphonium intermediate. The second stage is another example of the great tendency of alkoxyphosphonium ions to react with nucleophiles to break the O—C bond, resulting in formation of a phosphoryl P—O bond. 

The reaction of trimethyl phosphite with an allenic chloromethyl ketone proceeds with the formation of an oxaphospholene and not through the Michaelis-Arbuzov or Perkow rearrangements. ... 

This reaction, discovered by Alichaelis and Kaehne (222) and explored later by Arbuzov (15), has been widely employed for the synthesis of phosphonate and phosphinate esters and phosphine oxides. The extensive literature on the Michaelis-Arbuzov reaction has been summarized through 1949 in two reviews by Kosolapoff (177,178). 

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... 

Through the Michaelis-Arbuzov and Michaelis-Becker reactions. .. 199... 

A (l-oxoalkyl)phosphonic diester (9 R = R O), generally available through a Michaelis-Arbuzov reaction using the acyl chloride R COCl and the phosphorus(III) ester (R 0)3P, is converted into its / -toluenesulphonylhydrazone (Scheme 2), and the latter is then decomposed by the action of a base, very often simply aqueous KOH or Na2C03. The method was originally applied to esters from acetyl- and benzoyl-phosphonic acids and has since been applied to a wide range of dimethyl (l-oxoalkyl)phosphonates and also to analogous phosphinic esters (10 R = Ph or substituted phenyl)to (l-oxoalk-2-enyl) phosphonic diesters and to (3-oxoalk-l-enyl)phosphonic diesters An exception... 

Esters of (A -formylaminomethyl)phosphonic acid (159), important as precursors to the corresponding esters of (isocyanomethyl)phosphonic acid (160) [themselves useful in further syntheses of (aminoalkyl)phosphonic acids (Section IV.D.l)], have been made through the variation of the Michaelis-Arbuzov reaction which employs quaternary ammonium salts, e.g. 158 . The very few examples of this modification include its combination with the Gabriel reaction in a preparation of (phthalimidomethyl)phosphonic diesters ... 

Polyhydroxy(cyclo)alkyl phosphonic esters in the /nyo-inositol series have been prepared through a simple application of the Michaelis-Arbuzov reaction, and the displacement of methanesulphonyl groups from (137) occurs in reactions with simple trialkyl phosphites to give, for example, (138). Interest continues in carbohydrate-like... 

The reaction with phosphite esters is known as the Michaelis-Arbuzov reaction and proceeds through an unstable trialkoxyphosphonium ion intermediate. The... 

Phosphonylation and formylation reactions can be used successively in multistep procedures. For example, 1,3-/ .v(brornornclhyl)benzene undergoes an initial phosphonylation through Michae-lis-Becker or Michaelis-Arbuzov reactions, followed by oxidation of the benzylic bromide with 2-nitropropane and EtONa (Scheme 5.52) or Fe/HiO to give the corresponding 3-formyl-bcnzy I phosphonate in satisfactory overall yield (30-37%). 

On the basis of such evidence, it now seems to be widely accepted that the intermediates in valence expansion reactions of the Michaelis-Arbuzov type can have either an ionic, or a non-ionic, pentacoordinate structure, or both can be involved, possibly sequentially, or through equilibration, the choice being dependent on the ligands surrounding the central phosphorus atom, i.e. on the nature of the reactants. Thus reaction 1 might well be written as reaction 4. 

Variations in the types of reactants have been noted which are a reminder of those variations described in the previous chapter for the basic Michaelis-Arbuzov reaction. In this case, a a-haloketone reacts with a phosphorous chloride the reaction is envisaged as proceeding through a phosphonium intermediate which, when decomposed through alcoholysis, yields a (2-oxoalkyl)phosphonic derivative (Scheme 50). The usual pattern of... 

In complete contrast to the (l-oxoalkyl)phosphonic acids, for which essentially only one synthesis is available, based on the Michaelis-Arbuzov or Michaelis-Becker reactions, there are several procedures available for the synthesis of those acids with the 0x0 group at C(2) or at a carbon atom site even further from the phosphoryl centre. Historically, esters of (2-oxoalkyl)phosphonic acids were also obtained through application of the Michaelis-Arbuzov and Michaelis-Becker reactions, but it soon became apparent that complications occur, the major one being the concomitant formation, in many instances, of enol phosphates and, in some cases, this reaction became the main one, indeed, sometimes the only one. Several other procedures are now available for the preparation of oxoalkyl acids which place the 0x0 group accurately and with no side reactions of any importance, and these are therefore considered first in the following survey. 

Cl, CH2OH, CH2N3, etc). In these syntheses, the introduction of the CH2P(0)(0R)2 moiety occurred through Michaelis-Arbuzov reactions as, for example, in the conversion of... 

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