Arbuzov-Michaelis

An alkyl group can also migrate from oxygen to nitrogen or phosphorus [I, 72] (Michaelis-Arbuzov rearrangement) With this methodology, tetrafluoro-pyndine phosphonates and phosphmates can be obtained [75, 74], Chlorine fluoride... 

The Arbuzov reaction,also called the Michaelis-Arbuzov reaction, allows for the synthesis of pentavalent alkyl phosphoric acid esters 4 from trivalent phosphoric acid esters 1 (Z,Z = R,OR) by treatment with alkyl halides 2. 

R. G. Harvey and E. R. De Sombre, The Michaelis-Arbuzov and related reactions, in Topics in Phosphorus Chemistry, Vol. 1 (M. Grayson and E. J. Griffith, eds.), Wiley-Interscience, New York, 1964. 

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. 

Preparation of tris(trimethylsilyl) phosphite — Preparation of a silyl ester of a trivalent phosphorus acid for Michaelis-Arbuzov reaction... 

The use of an electron-rich trivalent phosphorus center for addition to or substitution at an electrophilic site is a long-established approach to the formation of carbon-phosphorus bonds. The classical studies of the Michaelis-Arbuzov, Michaelis-Becker, Abramov, Pudovik, and related reactions and their mechanisms and synthetic utilities have been thoroughly reviewed. In this chapter, we present only a brief introduction to these reactions and provide several examples of their more facile uses from the older literature. More attention is given to relatively recent developments regarding such reactions that are seen as improvements in their general utility. 

The well-known Michaelis-Arbuzov reaction is historically the fundamental approach to generating C-P bonds using a neutral trivalent... 

Figure 3.3 Adamanyl esters in the Michaelis-Arbuzov reaction. 

A wide variety of reagents have been found to undergo the Michaelis-Arbuzov reaction in a facile manner. Established approaches toward the generation of new C-P bonds using this variety of reagents are briefly summarized in the following ... 

In the instances of phosphorous and phosphonous acid systems, the generation of a new C-P bond via the classical Michaelis-Arbuzov reactions as noted above leads to products that are esters themselves. Isolation of the free acid product requires cleavage of the ester linkage in a separate reaction step, generally after isolation and purification of the initial product. The advent of silyl phosphorus reagents for the Michaelis-Arbuzov reaction allowed free acid products to be isolated simply by water workup of the reaction system. Further, since the byproduct was a silyl-halide, the general concern that the by-product halide would participate in an extraneous Michaelis-Arbuzov reaction was obviated. 

Additional advances have been made in the use of leaving groups other than halide for the nonphosphorus component of the Michaelis-Arbuzov reaction. The sensitive species 3,5-d i-t-b u ty I -4-hydroxybenzyl acetate has been noted to undergo efficient reaction (75-85% isolated yields) with a series of trialkyl phosphites upon heating at relatively low temperature (95°C) without the use of excess phosphite or additional catalyst.138 Chromatographic analysis of the reaction mixture indicates virtually quantitative conversion in the process. 

A useful approach for the preparation of chiral (3-aminophospho-nic acids from the naturally occurring a-amino acids has been reported.139 The overall scheme (Equation 3.4) involves formation of the phthalimide-acid halide from the starting a-amino acid followed by a Michaelis-Arbuzov reaction with triethyl phosphite to give the acylphosphonate. Complete reduction of the carbonyl group in three steps followed by hydrolysis of the ester and amide linkages provides the target material in very high yield without racemization (>99% ee). 

An intriguing reaction has been reported that does not exactly fit into the category of Michaelis-Arbuzov reaction but does involve nucleophilic attack of a neutral trivalent phosphorus for generation of a new C-P bond. Phenyl- and methyldichlorophosphine have been reported to attack the strained cyclopropane ring system of 1,3-dehy-droadamantane, overall adding P-Cl across the most strained bond of the ring system (Equation 3.5).140... 

Virtually simultaneously with the development of the Michae-lis-Arbuzov reaction, another closely related approach toward C-P bond formation was introduced. This involved the reaction of the salts of trivalent phosphorus-centered oxyacids with the same haloal-kanes as used in the Michaelis-Arbuzov reaction. First reported by Michaelis and Becker,142 this approach is commonly known as the "Becker reaction" or the "Michaelis-Becker reaction." Fundamental aspects of this reaction system have been reviewed previously.1 2 143... 

In contrast to the Michaelis-Arbuzov reaction, triaryl phosphites prove to be quite useful for addition to a,(3-unsaturated carbonyl compounds in this type of reaction. A wide variety of unsaturated compounds have been utilized successfully as substrates for such additions, including condensation products of the simple carbonyl compounds with urea,229 thiourea,230-233 N-substituted thioureas,232 234 235 ethyl carbamate,236 2-imidazolidinone,237 2-imidazoli-dinethione,237 and benzyl carbamate.238-240... 

Van den Berg, G.R., Platenberg, D.H.J.M., and Benschop, H.P., Stereochemistry of a Michaelis-Arbuzov alkylation of optically active ethyl trimethylsilyl phenylphosphonite with retention of configuration, Chem. Commun., 606, 1971. 

Hudson, H.R., Rees, R.G., and Weekes, J.E., Methyltrineopentyloxyphospho-nium iodide a crystalline Michaelis-Arbuzov intermediate and its mode of decomposition, Chem. Commun., 1297, 1971. 

Henrick, K., Hudson, H.R., and Kow, A., Michaelis-Arbuzov intermediates x-ray crystal structures of the methyl bromide adducts of neopentyl diphe-nylphosphinite and dineopentyl phenylphosphonite, Chem. Commun., 226, 1980. 

Taira, K. and Gorenstein, D.C., Experimental tests of the stereoelectronic effect at phosphorus Michaelis-Arbuzov reactivity of phosphite esters, Tetrahedron, 40, 3215, 1984. 

Stamm, H. and Gerster, G., Reactions with aziridines. XXI. The (Michaelis-) Arbuzov reaction with N-acyl aziridines and other amidoethylations at phosphorus, Tetrahedron Lett., 1623, 1980. 

Kiddle, J.J. and Gurley, A.F., Microwave irradiation in organophosphorus chemistry 1 The Michaelis-Arbuzov rearrangement, Phosph., Sulf, Silic. Relat. Elem., 160, 195, 2000. 

Trialkyl phosphites undergo reaction with molecular halogen via a mechanism reminiscent of the Michaelis-Arbuzov reaction to form the dialkyl phosphorochloridate in good yield (Equation 4.4).7 With cyclic esters, the halogen performing the displacement reaction at carbon remains attached within the molecule. 

Classical Michaelis-Arbuzov or Michaelis-Becker approaches toward formation of C-P bonds involving aromatic carbon sites are (understandably) not generally feasible. Nucleophilic substitution reactions on aromatic carbon proceed only under particular circumstances relating to the nature of attendant additional substituents, and then often with mechanisms quite different from those observed in... 

For example, in the instance of 9-chloroacridine, the attachment of the halogen (leaving group) at a suitably electrophilic carbon site allows the occurrence of a replacement reaction, presumably occurring via an addition-elimination procedure for phosphorus attachment, followed by the common nucleophilic displacement (ester cleavage) of the Michaelis-Arbuzov process (Figure 6.1).4... 

Nucleophilic attack by a trialkyl phosphite on a significantly electron-deficient aromatic ring involving addition-elimination of a nitro group (as nitrite anion), which completes the final step of the normal Michaelis-Arbuzov reaction (Figure... 

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). 

The use of transition metals for the facilitation of substitution reactions on vinylic carbon has proven to be quite successful. For example, vinylic chlorides in the presence of nickel(II) chloride react with trialkyl phosphites to substitute phosphorus for the halide (Figure 6.17j.71-72 While reminiscent of a direct Michaelis-Arbuzov reaction, including final dealkylation by a chloride ion, the reaction actually involves an addition-elimination process. It appears that chloride provides a more facile reaction than bromide, a characteristic noted in several reaction systems. 

Dittrich, R. and Hagele, G., Michaelis-Arbuzov perhalogentation reaction of olefins. III. The trifluorovinyl halide, CF2CFX, Phosph. Sulf, 10, 127, 1981. 

King, R.B. and Diefenbach, S.P., Transition-metal cyanocarbon derivatives. 5. Reactions of (l-chloro-2,2-dicyanovinyl)manganese derivatives with trialkyl phosphites. A novel variant of the Michaelis-Arbuzov reaction leading to [2,2-dicyanovinylphosphonato]metal complexes, Inorg. Chem., 18, 63, 1979. 

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