Michaelis-Arbuzov rearrangements

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... 

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. 

Also known as the Michaelis-Arbuzov rearrangement. For reviews, see Petrov Dogadina lonin Garibina Leonov Russ. Chem. Rev. 1983,52. 1030-1035 Bhaltacharya Thyagarajan Chem. Rev. 1981, 81.415-430. For related reviews, see Shokol Kozhushko Russ. Chem. Rev. 1985, 53, 98-104 Brill Landon Chem. Rev. 1984,84, 577-585. 

The reaction of functionalized iminium salts 4 derived from aziridines with trimethylphosphite gives aminophosphonates 11 by a Michaelis-Arbuzov rearrangement. This reaction is general(6 ). 

The Michaelis-Arbuzov reaction is also known as the Michaelis-Arbuzov-Kaehne reaction or the Michaelis-Arbuzov rearrangement and is sometimes named after Arbuzov only. For reviews of the reaction see Refs 6, 12,17, and 18. 

Apart from their properties as ligands, other aspects of the reactivity of phosphinite esters have been of interest. It has been shown that phosphinite esters (77) undergo the Michaelis-Arbuzov rearrangement to give the phosphine oxides (78) between room temperature and 80°C in the presence of trimethylsilyl halides, the reaction not needing the presence of any alkyl halide. The rearrangement proceeds even more efficiently at room temperature in the... 

Renard, P.-Y., Vayron, P., Leclerc, E., Valleix, A., Mioskowski, C. Lewis acid catalyzed room-temperature Michaelis-Arbuzov rearrangement. Angew. Chem., Int. Ed. Engl. 2003, 42, 2389-2392. 

Aksnes, G., Aksnes, D. Mechanism of the Michaelis-Arbuzov rearrangement in aceto- nitrile. Acta Chem. Scand. 1963,17, 2121-2122. 

The reaction is presumed to occur by initial formation of HjfMenO) PO], which then undergoes direct P-alkylation by nucleophilic attack of phosphorus on carbon with displacement of halide. An alternative alkylation mechanism involving nucleophilic attack of oxygen on carbon, followed by a Michaelis-Arbuzov rearrangement i) of a dialkyl phenylphosphonite (C6H5(MenO)POR) intermediate with the alkyl halide was effectively eliminated by the observation that reaction of methyl phenylphosphinate with a tenfold excess of methyl-c/3 iodide gave the product distribution shown in Eq. (2). 

P-Macroheterocycles, formation of metallo complexes from 86MI16. Michaelis-Arbuzov rearrangement of phosphorus heterocycles ... 

Diethyl iodomethylphosphonate was obtained for the first time in 1936 by A. E. Arbuzov and Kushkova by the reaction of diiodomethane with triethyl phosphite in 60% yield (Scheme 3.1). Similar results were obtained in later studies (30-59%),even after experimental modifications aimed at limiting the formation of the major byproduct, tetraethyl methylenediphosphonate. Under the optimized conditions, dimethyl iodomethylphosphonate is obtained in 27% yield. This low yield can be explained by a second side reaction, the Michaelis-Arbuzov rearrangement between trimethyl phosphite and the methyl iodide coproduct, which gives dimethyl methylphosphonate. ... 

Analogously, ethyl 4-fluoro-3-methylcrotonate is brominated with NBS in the presence of AIBN and then reacted with triethyl phosphite to produce good yields (72-78%) of a-fluorophosphonate, a key intermediate in the synthesis of fluorinated vitamin A esters (Scheme 3.3)7 Following a similar procedure (radical bromination and Michaelis-Arbuzov rearrangement), ( )-l-fluoro-3-(l-trityl-l,2,4-triazol-3-yl)-2-propenylphosphonate, a good inhibitor of imidazoleglycerol phosphate dehydratase, has been prepared in 25% overall yield. ... 

Alkylation of dialkyl cyanomethylphosphonates gives somewhat higher yields of oc-substituted cyanomethylphosphonates than those obtained by Michaelis-Arbuzov rearrangement from trialkyl phosphites and substituted haloacetonitriles. 

Substituted haloacetates (R and R 7 = H) are exceptions to the rule that branched-chain halides are unreactive in the Michaelis-Arbuzov reaction. A large variety of easily available a-chloro or bromo esters "- react with trialkyi phosphites at 160-190°C to produce a-substituted phosphonoacetic esters in fair to excellent yields (31-96% , Scheme 8.7, Table 8.2). Because secondary a-haloacetates are stable compounds that may be either easily prepared on laboratory scale or may be obtained commercially, the Michaelis-Arbuzov rearrangement appears as a reaction of special importance. 

Another attractive route to co-amino-(o-(hydroxycarbonyl)alkylphosphonic adds involves the use of the classical Michaelis-Arbuzov and Michaelis-Becker reactions. For example, the suitably protected 2-amino-(o-bromoalkanoates are readily converted into 3-amino-3-carboxypropylphosphonates (Scheme 8,82) ° or substituted 6-amiuo-6-c trboxyhcxylphosphonatcs by the Michaelis-Arbuzov rearrangement with trialkyl phosphites. However, it appears that, when enantiomerically pure bromide is used, the Michaelis-Arbuzov reaction is responsible for some racemization. It has been found that the extent of racemization is greater when the reaction is run at 150°C using triethyl phosphite than with trimethyl phosphite at 110°C for only the required amount of time. ... 

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