Four-Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides.

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.

Site-Selective Switching Strategies to Functionalize Polyazines.

Many drug fragments and therapeutic compounds contain multiple pyridines and diazines. Developing site-selective reactions where specific C-H bonds can be transformed in polyazine structures would enable rapid access to valuable derivatives. We present a study that addresses this challenge by selectively installing a phosphonium ion as a versatile functional handle.

Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts.

Methods that directly functionalize pyridines are in high demand due to their presence in pharmaceuticals, agrochemicals, and materials. A reaction that selectively transforms the 4-position C-H bonds in pyridines into C-PPh groups that are subsequently converted into heteroaryl ethers is presented. The two step sequence is effective on complex pyridines, pharmaceutical molecules, and other classes of heterocycles.