Synthetic manipulation of azaheterocycles and their applications towards new bond transformations

Searching for new synthetic methods to create useful organic building blocks and synthetic intermediates from nitrogen-containing heterocycles, such as imidazolines (cyclic aminals) and pyridines, remains a prime focus in the synthetic organic community. Nitrogen heterocycles (azaheterocycles) are privileged molecular building blocks used in the construction of many active pharmaceutical ingredients, organic dyes, and natural products. In fact, they are found in ~88% of small molecule drugs approved by the US FDA since 2015. The main objective of the research described herein was to develop new synthetic tactics involving azaheterocycle ring systems as reaction intermediates leading to making new chemical bonds. In one investigation, imidazolidine and benzimidazoline ring systems which feature cyclic aminal structural motifs were successfully employed as hydride sources in transition metal-catalyzed reductive cross-coupling reactions. In related investigations, general and efficient synthetic methods for elaboration of pyridine ring systems through generation of reactive alkylidene dihydropyridine intermediates (anhydrobases) were revealed. This work resulted in development of new avenues for construction of structurally more complex heterocyclic ring systems through formation of new carbon-carbon and carbon-sulfur bonds.