Metal-Catalyzed Asymmetric Synthesis of P-Stereogenic Phosphines

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The Chemical Catalysis Program supports Professor David S. Glueck at Dartmouth College for a project that describes a plan for further development of a recently reported new reaction, platinum-catalyzed asymmetric phosphination. The plan is to understand the process in which a chiral metal catalyst couples a racemic secondary phosphine PHR(R') with a benzyl halide ArCH2X to give an enantioenriched tertiary phosphine PR(R')(CH2Ar) via metal-mediated stereocontrol at phosphorus. The development of such P-stereogenic chiral ligands has been relatively slow because of a lack of general synthetic methods. Asymmetric phosphination is a new and potentially useful approach to this problem. This reaction will be applied to the asymmetric synthesis of novel C2-symmetric bidentate diphosphines (the most common ligand class for industrial applications) and to analogous C3-symmetric tridentate triphosphines, which are virtually unexplored. In both cases, catalyst control may lead to asymmetric amplification and very high enantiomeric excess in the desired product, which may be separated from unwanted diastereomers. Chiral phosphines are particularly useful in asymmetric catalysis, which is commonly employed in the pharmaceutical industry to make single-enantiomer drugs.With the support of the Chemical Catalysis Program in the Chemistry Division at the National Science Foundation, Professor David S. Glueck will develop a better understanding of metal-catalyzed asymmetric phosphination and new chiral phosphines, valuable ligands in asymmetric catalysis that have potential applications in the pharmaceutical industry. Studies of catalyst and substrate control of selectivity and the effect of catalyst symmetry on chiral recognition and reactivity will be broadly useful in homogeneous catalysis. Graduate and undergraduate students will receive training in synthesis and characterization of inorganic, organometallic, and organic compounds, mechanistic studies of their reactions, and in catalysis, and will have an opportunity to present their work to other scientists and to the public. The results will be disseminated broadly in publications and conference presentations. They will be integrated into Dartmouth courses and in presentations to local middle school students. This project will also continue to broaden the participation of underrepresented groups, especially women, in research at the graduate and undergraduate levels.