[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.
(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
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
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.
Kyushu University, Kasuga, Japan