The proposed research addresses the direct asymmetric synthesis of amines. Rather than relying on indirect routes such as carbonyl addition or oxidative alkene functionalization to form chiral alpha-branched amines, stereocontrolled free radical addition reactions will be used, creating a new stereocenter and a new carbon-carbon bond in a single operation from achiral precursors. Within this context are addressed three specific aims - internal diastereocontrol by preexisting stereochemistry using temporary tethers in radical cyclization, external stereocontrol in intermolecular radical addition using nitrogen-linked removable and reusable chiral auxiliaries, and catalyst stereocontrol with Lewis acids bearing chiral ligands.
Nitrogen-containing groups ("amines") with precisely defined three-dimensional structure (stereochemistry) are found in many biologically active molecules and designed pharmaceuticals. Experimental methods for the direct synthesis of such compounds with the necessary stereochemical control are uncommon. With the support of the Organic Synthesis Program, Professor Gregory K. Friestad, of the Department of Chemistry at the University of Vermont and State Agricultural College, is studying new methods for the synthesis of amines. Professor Friestad explores the introduction of stereochemistry in reactions of free radicals (molecular groupings containing an unpaired electron) through a variety of approaches, including the temporary linking of reactants. These studies are leading to an enhanced understanding of the reaction chemistry of free radicals and to new and efficient methods for the synthesis of biologically active amines.
