(Diethoxyphosphoryl)acetonitrile Oxide

[113847-95-3]  · C6H12NO4P  · (Diethoxyphosphoryl)acetonitrile Oxide  · (MW 193.14)

(nitrile oxide bearing an additional functionality)

Preparative Method: the reagent is a highly reactive intermediate and cannot be isolated. It is generated in situ from (diethoxyphosphoryl)acetaldehyde oxime1 by bromination with N-Bromosuccinimide and elimination with Triethylamine,2 and used in synthesis by trapping with a coexisting dipolarophilic reagent.

Handling, Storage, and Precautions: Use in a well ventilated fume hood.

3-Acylisoxazoline Synthesis.

(Diethoxyphosphoryl)acetonitrile oxide, like other nitrile oxides, undergoes exclusive regioselective cycloadditions to monosubstituted alkenes to give 5-substituted 3-(phosphorylmethyl)isoxazolines which can be regioselectively lithiated with Lithium Diisopropylamide at the side chain and then alkylated in good yields (eq 1).2,3 The alkylated products can be further lithiated with n-Butyllithium. Air oxidation of the lithiated intermediates gives 3-acylisoxazolines in good yields. Horner-Emmons alkenations of the lithiated 3-phosphorylmethylisoxazolines and alkylated derivatives offer a convenient synthetic route to 3-[(E)-1-alkenyl)]isoxazolines.3

Furanone Synthesis.

Cycloaddition reactions of (diethoxyphosphoryl)acetonitrile oxide with unprotected propargylic alcohols proceed smoothly to give 5-(1-hydroxyalkyl)isoxazoles. The adduct to 1-methyl-3-butyn-2-ol is then lithiated with butyllithium at the side chain (-78 °C, THF), alkylated with Iodomethane (-78 °C, 94%), and finally reduced with Raney Nickel to cause a cleavage of the nitrogen-oxygen bond (W-2, ethanol, AcOH, rt) to give 5-(phosphorylmethyl)-3(2H)-furanones (eq 2).4 These compounds are useful for the synthesis of 5-[1-(E)-alkenyl]-3(2H)-furanone derivatives through a Horner-Emmons alkenation procedure. One application has been shown by the effective synthesis of geiparvarin (eq 2).4

Furan Synthesis.

Cycloadditions of (diethoxyphosphoryl)acetonitrile oxide to THP-protected allylic alcohols followed by alkylation of the phosphorus-stabilized anion produces 5-(1-hydroxyalkyl)isoxazolines. These can be reductively cleaved and aromatized (sodium acetate in AcOH) to give 2-(1-phosphoryl)alkylfurans (eq 3) whose Horner-Emmons alkenations lead to 2-[1-(E)-alkenyl)furan derivatives.5

Synthetic applications to 2-hydroxy-4-oxo-5-alkenoates,6 5-[(E)-1-alkenyl]-3-hydroxy-4,5-dihydro-2(3H)-furanones,6 (Z)-5-alkylidene-2(5H)-furanones,6 and (E)-4-oxo-5-alkenoates7 have also been reported.


1. Razumov, A. I.; Moskva, V. V. ZOB 1964, 34, 2589 (CA 1964, 70, 140 707a).
2. Tsuge, O.; Kanemasa, S.; Suga, H.; Nakagawa, N. BCJ 1987, 60, 2463.
3. Tsuge, O.; Kanemasa, S.; Suga, H. CL 1986, 60, 183.
4. Tsuge, O.; Kanemasa, S.; Suga, H. CL 1987, 323.
5. Tsuge, O.; Kanemasa, S.; Suga, H. BCJ 1988, 61, 2133.
6. Kanemasa, S.; Nakagawa, N.; Suga, H.; Tsuge, O. BCJ 1989, 62, 171.
7. Kanemasa, S.; Nakagawa, N.; Suga, H.; Tsuge, O. BCJ 1989, 62, 180.

Shuji Kanemasa

Kyushu University, Kasuga, Japan



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