HYDROGEN TRANSFER REACTIONS IN ORGANIC SYNTHESIS

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In the health-related research, the ever-increasing demand for stereocontrolled preparation of organic molecules for study of structure/reactivity relationships (with the ultimate goal of developing new drugs), for biological probes and sensors, and for other applications fuels basic and applied research in the field of organic synthesis. This grant proposes basic research in developing new strategies and reagents based on free radical reactions for the synthesis of organic molecules. Implementation of these strategies will increase understanding of important new classes of organic reactions, and will provide new options to biomedical scientists for the stereocontrolled preparation of organic molecules. Bimolecular radical reactions are most commonly conducted by using reagents such as tributyltin hydride and tris(trimethylsilyl)silane. A case is made that these reagents are inherently limited because their reactions occur with bimolecular chain transfer steps. The concept of unimolecular chain transfer (UMCT) reactions is introduced, and experimental evidence is provided that certain silicon hydrides will propagate radical chains by a UMCT mechanism. Several bimolecular radical addition reactions have already been successful, and these strongly hint at the advantages of the UMCT method. During the next granting period, a logical series of mechanistic and synthetic experiments will be conducted in parallel. Mechanistic experiments will be directed at understanding the scope and limitations of intramolecular hydrogen transfer reactions of silicon hydrides and at identifying optimal substituents on silicon. "Orthogonal chains" will also be studied. Early synthetic experiments have as a goal the introduction on new classes of UMCT reagents for bimolecular radical addition reactions. Later experiments will focus on control of stereochemistry, and on development of tandem reactions of UMCT reagents. In the long range, it is envisioned that a new strategy to conduct bimolecular radical addition reactions will emerge.