Isoxazoles, phosphorylated

Chloro- and 5-bromo-isoxazoles have been prepared by reaction of 5-isoxazolones with the appropriate phosphoryl halide (77JMC934). 3-Phenyl-5-trifluoromethylisoxazole has been synthesized by reaction of benzonitrile iV-oxide with 3,3,3-trifluoropropyne (77JMC934). 

Quite independently of Cornforth s efforts, a similar approach was designed and executed by Stevens and coworkers (75JA5940, 76T1599). The isoxazoles were synthesized by one of the three routes outlined in Scheme 25, in which primary nitro compounds are transformed into nitrile oxides by dehydration with either phosphoryl chloride or phenyl isocyanate, or else the same oxides were formed by dehydrogenation with LTA (syn product) or NBS (syn and anti). Reaction of the unstable nitrile oxides in situ with an appropriately substituted alkyne then afforded the isoxazole (294). 

Sharp JW, Ross CM, Koehnle TJ, Gietzen DW. 2004. Phosphorylation of Ca /calmodulin dependent protein kinase type II and the a-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor in response to a threonine-devoid diet. Neuroscience 126 1053-1062. 

Aristova, N.V., Gorin, B.L, Kovalenko, S.V., Pavlov, V.A., and Moskva, V.V., Phosphorylated isoxazoles, Khim. Geterotsikl. Soedin., 1287,1990 Chem. Heterocycl. Compd. (Engl. Transl.), 1076,1990. Kouno, R., Okauchi, T., Nakamura, M., Ichikawa, J., and Minami, T., Synthesis and synthetic utilisation of a-functionahzed vinylphosphonates bearing P-oxy or P-thio substiments, J. Org. Chem., 63,6239,1998. Nifant ev, E.E., Patlina, S.L, and Matrosov, E.L, Synthesis of phosphorylated pyrazolones, Khim. Geterotsikl. Soedin., 513, 1977 Chem. Heterocycl. Compd. (Engl. Transl.), 414, 1977. 

The cycloaddition of an arylnitrile oxide to methyl ethynylmethylphosphinate in an inert solvent at 5 °C produces a (5) -phosphinoylated-isoxazole 513 in high yield " and phosphorylated 1,2,4-oxadiazoles 514 are obtainable in a similar addition to (R0)2P(Z)CN (Z = O or Phosphorylated nitrile oxides, e.g. 515, are generally prepared by the Et3N-dehydrobromination of the product from the bromination of the oxime of a j5-(dialkoxyphosphinoyl)acetaldehyde, and then used in situ in reactions with alkenes to give isoxazolines and with alkynes to give isoxazoles . The chlorination and subsequent dehydrochlorination of diethyl (nitromethyl)phosphonate yield the nitrile oxides 516 (R = EtO Pr O or morpholinyf and these, with unsaturated centres, yield isomerically phosphorylated isoxazolines and isoxazoles. 

K.D. Shin, M.Y. Lee, D.S. Shin, S. Lee, K.H. Son, S. Koh, Y.K. Paik, B.M. Kwon, D.C. Han, Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation, J. Biol. Chem. 280 (2005) 41439-41448. 

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