Synthesis of 2,5‐diisoxazolyltetrahydrofurans

Abstract

The synthesis of 2,5‐bis(3‐bromo‐5‐isoxazolyl)tetrahydrofuran (2) and 2,5‐bis(3‐methoxy‐5‐isoxazolyl)tetrahydrofuran (3) have been accomplished in three and four steps respectively. Cis‐ and trans‐isomers have been separated and fully characterized. Differently from synthetic schemes so far utilized for the preparation of the 2,5‐diheteroaryltetrahydrofuran analogs, our approach involves the direct synthesis of a key intermediate containing both isoxazole rings and diol function for the final cyclization. Starting from succinic aldehyde, the new 1,7‐octadiyne‐3,6‐diol (4) was prepared and was submitted to a double cycloaddition with bromonitrile oxide to yield the key intermediate 1,4‐bis(3‐bromo‐5‐isoxazolyl)‐1,4‐butanediol. The methoxy analogs 3 were obtained by methanolysis of the bromo derivatives 2.