A New Methodology for Preparing Benzylated Aminopyridines Yields Unprecedented Site-Selective Organocatalysts

While developing site-selective alcohol-modifying catalysts, we found that Lewis acid-promoted benzylation or cyclative dibenzylation of aminopyridines with alcohols effectively overcomes the synthetic challenges typically thwarting access to new aminopyridines, a key family of nucleophilic organocatalysts. Using this innovative approach, we successfully prepared unprecedented (2,5-diarylpyrrolidino)pyridines and new (N-benzyl-N-methylamino)pyridines with expanded ortho-alkoxy tails on the aryls. The new catalysts, with their bulky outer sphere, exhibit remarkable activity and site-selectivity in the phosphorylation of a model diol amphiphile.