Functionalization of Pyridines at the C4 Position via Metalation and Capture.

ABSTRACT: The functionalization of pyridines at positions remote to the N-atom remains an outstanding problem in organic synthesis. The inherent challenges associated with overriding the influence of the embedded N-atom within pyridines was overcome using n-butylsodium, which provided an avenue to deprotonate and functionalize the C4-position over traditionally observed addition products that are formed with organolithium bases. In this work, we show that freshly generated 4-sodiopyrdines could undergo transition metal free alkylation reactions directly with a variety of primary alkyl halides bearing diverse functional groups. In addition, after transmetalation to zinc chloride a simple and efficient Negishi cross-coupling protocol was formulated for a variety of aromatic and heteroaromatic halides.

SUBMITTER: Hsu HH 

PROVIDER: S-EPMC11933531 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature