A study of the lithiation of 2,6-dibromopyridine with butyllithium, and its application to synthesis of L-739,010

Mono-lithiation of 2,6-dibromopyridine by n-BuLi is complicated by deprotonation of the pyridine ring by the resulting mono-lithium species. This problem can be eliminated by a reverse addition, but this causes formation of the undesired dilithio species. However, rapid lithium-halogen exchange between 2,6-dibromopyridine and 2,6-dilithiopyridine produces 2-brom-6-lithiopyridine cleanly. Thus, using reverse addition, the mono-lithiated pyridine can be generated in 98% yield. Copyright (C) 1996 Elsevier Science Ltd