Four‐Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides
Patrick J. Fricke, Ryan D. Dolewski, Andrew McNally
Abstract
Abstract Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4‐alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination‐rearomatization sequence. Pyridine N ‐activation is key to this strategy, and N ‐triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late‐stage functionalization, including methylation of pyridine‐containing drugs. This approach represents an alternative to metal‐catalyzed sp 2 ‐ sp 3 cross‐coupling reactions and Minisci‐type processes.