Lithiated Nitriles: Solution Structures and Reaction Stereochemistry

Virginia Polytechnic Institute And State University, Blacksburg VA

Investigators

Abstract

Professor Carlier and his students will first study the structures of lithiated nitriles in solution. They will use a variety of NMR spectroscopic techniques in these studies. Computational studies will be used to compliment and direct experimental work and have led the PI to propose the study of these lithiation reactions in noncoordinating hydrocarbon solvents. Carbon metallated nitriles discovered in these studies will then be used in an enantioselective deprotonation/alkylation reaction sequence which will be applied to enantioselective syntheses of alpha, alpha-disubstituted-alpha-amino acids. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Paul R. Carlier of the Department of Chemistry at Virginia Polytechnic Institute and State University. Professor Carlier and his students will study the structures and reaction chemistry of a class of molecules known as lithiated nitriles. The structures will be predicted using computational chemistry and modelling techniques then studied spectroscopically using nuclear magnetic resonance spectroscopy. Nitriles which can be lithiated on the carbon next to the nitrile functional group will then be used in enantioselective carbon-carbon bond forming reactions called alkylation reactions. These alkylation reactions produce molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer). Development of this family of reactions is one of the most important problems facing the pharmaceutical industry today. Students trained during the course of this work will gain skills in computational chemistry, nuclear magnetic resonance spectroscopy, and organic synthesis. These skills are needed by the pharmaceutical and speciality chemicals industries.