Chemistry for Medicinal Chemistry

Pyridines and diazines are ubiquitous in pharmaceuticals and agrochemicals, yet there are limits in the synthetic methods that can directly transform these structures. We will present three distinct strategies for manipulating these heterocycles into more valuable derivatives. First, we will show that they can be converted into phosphonium salts with a wealth of subsequent reactivity, particularly via phosphorus-ligand coupling reactions. Second, we have devised a strategy for pyridine functionalization using a ring-opening, electrophile-coupling, and ring-closing process that exploits Zincke-type intermediates. Third, we will present the concept of deconstruction-reconstruction as a means to achieve both transformation of azines C-H bonds and skeletal editing of these heterocycles. Our lab has also performed mechanistic and computational studies of the regioselectivity of these processes and their reaction pathways.

Speaker: Andy McNally, Colorado State University