1,3-Dipolar cycloaddition in the synthesis of trifluoromethyl-substituted isoxazolidinyl derivatives of nucleobases

Abstract

Two series of nonhydroxyl isoxazolidinyl nucleoside analogues containing a trifluoromethyl group have been conveniently prepared in moderate or good yields by direct 1,3-dipolar cycloaddition. Isoxazolidines 5-7 derived from fluorinated N-vinyl nucleobases and N-alkyl-methylenenitrones were obtained with complete regiocontrol and stereocontrol and the reactions proceeded with full transfer of the dipolarophile geometry to the cycloadduct. The cycloaddition reactions of N-alkyl-trifluoromethylnitrones with N-vinyl nucleobases led with very high diastereoselectivity to cis and trans stereoisomers of isoxazolidines 13-17. Interestingly, the diastereoselectivity was strongly determined by the steric factor and definitely was dependent on the character of N-alkyl substituent in the nitrone.