Nitrile Anions: Unmasking Fundamental Reactivity

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This renewal project seeks to exploit the potential of C-metallated nitriles in performing previously difficult or impossible transformations. Five specific objectives address several long-standing synthetic challenges: 1) development of the first conformationally controlled asymmetric alkylation of C-metallated nitriles through 1,2- and 1,3-internal asymmetric induction; 2) exploitation of chelation for internal 1,3- and 1,4-asymmetric alkylations of C-metallated nitriles; development of the first general synthesis of chiral Grignard reagents; 4) execution of the first general intra- and intermolecular conjugate addition-alkylation to alkenenitriles; and 5) computational determination of the structure, and 13C NMR shifts, of C- and N-metallated nitriles with Mg, Zn, and Cu counter ions. Portions of the project will be achieved through an international collaboration with Professor Paul Knochel, at Ludwig-Maximilian's University in Munich, Germany.With this award, the Organic and Macromolecular Chemistry Program and the Office of International Science and Engineering are supporting the research of Dr. Fraser F. Fleming of the Department of Chemistry at Duquesne University. Professor Fleming along with his collaborator, Professor Jeffrey D. Madura, and their students will study the structures and reaction chemistry of a class of molecules known as nitrile anions. Development of this family of reactions promises to provide new tools for the controlled synthesis of the complex organic molecules required in the discovery and development of new pharmaceuticals. Students trained during the course of this work will gain skills in computational chemistry and organic synthesis. Graduate student exchange, through collaboration with Dr. Paul Knochel, is anticipated to benefit the a cadre of graduate students at Duquesne University as ideas and techniques learned in the Knochel group are brought back and implemented in the PI's research group.