Palladium catalyzed dehydration of primary amides: a step economical synthesis of Vildagliptin

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Jarrod Lee Stanley (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Mitchell Croatt

Abstract: The development of reactions that facilitate a concise path to chemical complexity has long been a focus within the synthetic community. Specifically, the use of readily available starting materials towards efficient routes to chemically relevant molecules is imperative. These designed reactions exhibit utility to applications within synthetic, medicinal, and materials science. Herein, efforts to endow the scientific community with efficacious syntheses is realized with the step economical synthesis of Vildagliptin. A novel Selectfluor-modified palladium catalyst enabled the dehydration of primary amides for a concise route to nitrile moieties. These reactions were studied for their unique reactivities and to elucidate mechanistic insight. Following successful manipulation of more than 20 substrates, the utility of the methodology turned to the total synthesis of Vildagliptin. Vildagliptin is a nitrile bearing anti-diabetic medication that can be formed using a primary amide precursor. Once Vildagliptin was synthesized using the dehydration methodology, a more efficacious route was desired and efforts began towards a one-pot synthesis of the medication. The capability to produce chemically relevant products in a step economical manner will benefit not only the synthetic community, but also the recipients of medications and products resulting from such developments.

Additional Information

Publication
Thesis
Language: English
Date: 2021
Keywords
Chemoselective, Dehydration, Organic, Palladium, Synthesis, Vildagliptin
Subjects
Drugs $x Synthesis
Palladium catalysts
Amides
Nitriles

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