Synthetic methods of nitrile oxides and their synthetic applications

Abstract

I. Synthetic Methods of Nitrile Oxides and Their Synthetic Applications; Nitrile oxides could be conveniently prepared from aldoximes utilizing 1-chlorobenzotriazole in dichloromethane. The reaction and work-up procedures are simple and the isolated yields high. The reaction of hydroximoyl chlorides with molecular sieves, irrespective of their pore sizes, proceeded very slowly and cleanly to the corresponding nitrile oxides, which subsequently reacted with dipolarophiles to give isoxazolines in good to excellent yields. Some nitrile oxides were generated from hydroximoyl chlorides by alkali metal fluoride in the presence of methyl acrylates to give isoxazoline derivatives in good yields. Thirteen 4-acylisoxazole-5-carboxylate derivatives were prepared in moderate to high yields via the cycloaddition reaction of nitrile oxides with β-acylpyruvates. β-Acylpyruvates, unlikely ordinary β-diketones, showed high dipolarophilic reactivity toward nitrile oxides in the absence of base. Reactivity of nitrile oxides toward the 5,6-double bond of uracil and cytosine nucleosides was studied. 1,3-Diolar cycloaddition reaction product, dihydroisoxazolopyrimidine derivative, was obtained as the first product. In cytosine nucleosides these dihydroisoxazolopyrimidine derivatives were stable to isolate, whereas, for uracil nucleosides, we could isolate the ring-opened 5-aroylpyrimidine nucleoside oxime derivatives. The reactivith of dihydrofuranose moiety in the unsaturated nucleoside derivatives such as 2``,3``-didehydro-2``,3``-dideoxythymidine(d4T) toward less stable nitrile oxides were so low that we could not obtained the desired products. With stable nitrile oxides, however, we could obtain the 1,3-dipolar cycloaddition reaction products in good yields. Hydrogen bonding effect in nitrile oxides plays an important role in the regio-and stereochemistry. We have observed that the hydrogen bonding effect could control the regiochemistry in the reaction of nitrile oxides w...