Metal-Catalyzed Asymmetric Synthesis of P-C and P-P Bonds

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The Chemical Catalysis Program supports Professor David S. Glueck at Dartmouth College for research on new methods to prepare chiral phosphorus (P)-stereogenic phosphines via metal-catalyzed asymmetric synthesis of P-carbon (C) and P-P bonds. Chiral phosphines are useful in asymmetric catalysis, which is commonly employed in the pharmaceutical industry to make single-enantiomer drugs. However, the development of P-stereogenic chiral ligands has been relatively slow because of a lack of general synthetic methods. This project further develops the metal-catalyzed stereocontrolled formation of P-C bonds, a new and potentially useful approach to this problem, and investigates analogous processes to make P-P bonds, which are virtually unexplored. In both cases, secondary phosphine substrates containing two stereocenters separated by a linker (*P~P* or *P~C*) have been designed so that interactions between these atoms and the catalyst result in selectivity higher than that enforced by the catalyst alone (positive cooperativity). The resulting P-stereogenic phosphiranes and diphosphines are potentially useful building blocks for other P-stereogenic phosphines, while the unique stereoelectronic properties of phosphirane ligands are also under investigation. Related studies take advantage of new substrates derived from cheap naturally occurring chiral compounds, enabling stereocontrol using achiral catalysts, and investigating an unusual method for screening racemic catalysts to prepare C2-symmetric bis(phosphines) and rare C3-symmetric triphosphines. This project develops a better understanding of metal-catalyzed formation of phosphorus-carbon and phosphorus-phosphorus bonds and new chiral phosphines, valuable ligands in asymmetric catalysis with potential applications in the pharmaceutical industry. Studies of positive cooperativity are broadly useful in homogeneous catalysis. Graduate and undergraduate students receive training in the synthesis and characterization of inorganic, organometallic, and organic compounds, mechanistic studies of their reactions, and in catalysis. The students have opportunities to present their work to other scientists and to the public. The results are disseminated broadly in publications and conference presentations, and they are integrated into Dartmouth courses and outreach presentations. This project continues to broaden the participation of underrepresented groups, especially women and Native Americans, in research at the graduate and undergraduate levels.