Synthesis of Trisubstituted Pyridines <i>via</i> Chemoselective Suzuki–Miyaura Coupling of 3,5‐ and 4,6‐Dibromo‐2‐tosyloxypyridines

Abstract

Abstract Chemoselective Suzuki–Miyaura reactions on 3,5‐ and 4,6‐dibromo‐2‐tosyloxypyridines have been studied for the preparation of trisubstituted pyridines. The optimized conditions allow for a facile access to 3,5‐ and 4,6‐diaryl‐2‐tosyloxypyridines in yields of 8 to 99%. Further functionalization such as palladium‐catalyzed amination and copper‐free Sonogashira reaction of the tosylate group in the diarylpyridine derivatives obtained was accomplished for the synthesis of novel and biologically relevant trisubstituted pyridines. The formal synthesis of ficuseptine, a bioactive alkaloid, has also been achieved via the palladium‐catalyzed cross‐coupling reaction of 3,5‐dibromo‐2‐tosyloxypyridine in 5 steps from 3,5‐dibromo‐2‐hydroxypyridine with 50% overall yield. magnified image