ИСТИНА

The bridged azabicyclic structural fragment is the core element in a large number of natural products and bioactive compounds. 1,3-Dipolar cycloaddition reaction is an effective way for modifying an unsaturated bond. Thus, cycloaddition of nitrile oxides generated in situ leads to the formation of an isoxazoline ring which is a hidden equivalent of some functional groups that can be used at the corresponding synthesis stage. We have studied the direction of 1,3-dipolar addition reaction of the aromatic nitrile oxides to the derivatives of 2-azabicyclo[2.2.1]heptanes, 7-azabicyclo[2.2.1]heptanes and 2-oxa-3-azabicyclo[2.2.1]heptanes. For this purpose the synthesis of bicyclic alkenes was carried out according to the described methods [2]. The synthesis of the derivatives containing an electron-withdrawing substituent included two stages: the interaction of cyclopentadiene with imine formed in situ led to the formation of unsubstituted product which was acylated at the second stage. The 2-oxa-3-azabicyclo[2.2.1]heptane was synthesized from N-tert-butoxycarbonylhydroxylamine and cyclopentadiene. Then, the phenyl nitrile oxide, the p-methoxyphenyl nitrile oxide and the p-nitrophenyl nitrile oxide were chosen as 1,3-dipoles, which were generated in situ by the reaction of substituted chlorobenzaldoximes with triethylamine. As a result of the reaction of the aromatic nitrile oxides with bicyclic derivatives, a mixture of regioisomers was obtained exclusively with the exo arrangement of the isoxazoline ring. The exo arrangement of the isoxazoline ring was proved by 1H NMR spectroscopy. The endo-arrangement of protons is evidenced by the value of their spin-spin coupling constant of 8 Hz.