Synthesis of Phosphorus Imidazo (x,y-a) Pyridine Ligands

Kaitlyn Elise Roberts, University of South Alabama

Abstract

The metal-catalyzed cross-coupling reactions in synthetic organic chemistry have sky-rocketed exponentially since the monumental discoveries from the laboratories Professors Akira Suzuki, Richard Heck, and Ei-ichi Negishi, recipients of the 201 Nobel Prize in chemistry. Cross-coupling reactions are regularly employed in the syntheses of various carbon-carbon and carbon-heteroatom bonds such as C-N, C-P, C-O, and C-S and in the preparation of carbocyclic and heterocyclic single ring or fused ring systems. In the palladium-catalyzed cross-coupling reactions, there are several key mechanistic steps during this process where the final reductive elimination is the rate-determining step and "ligands" can facilitate this key reductive elimination step in a catalytic function. Successful "ligands" can include the electron-donating bulky phosphine containing compounds. Imidazo[x,y-a] pyridine structures are called "privileged structures" in medical chemistry and our group is interested in utilizing "privileged structures" from the medical chemistry literature as viable "ligands" in future cross-coupling reactions. The overall successful syntheses of various phosphorous imidazo[x,y-a] pyridine ligands follows a general synthetic route of halogenation of the core imidazo[x,y-a] pyridine scaffold with subsequent palladium-catalyzed cross-coupling reactions of the halogenated intermediate with dialkyl- and diphenylphosphines. The core imidazo[x,y-a] pyridine intermediates could gbe synthesized from precursors such as imidazo [1,5-a] pyridine, imidazo[1,2-a] pyridine, 2-aminopyridines, and arylacetylenes.