Michael P. Doyle

Michael P. Doyle:  Dirodium Carboxamidates in Catalysis and Materials

The major focus of our research program is the development of highly selective and efficient catalytic processes for the synthesis of biologically relevant compounds. Investigations are built upon unique, highly efficient and selective, catalytic uses of dirhodium carboxamidates. The fixed stereodefined geometry of these catalysts provides access to highly enantioenriched products in metal carbene reactions of diazoacetates and, together with their low oxidation potentials, also provides capabilities for highly selective Lewis acid catalyzed reactions and efficient chemical oxidations with high turnover numbers and high selectivities. (See: "Perspective on Dirhodium Carboxamidates as Catalysts," J. Org. Chem. 2006, 71, 9253-9260 and "Catalytic Carbene Insertion into C-H Bonds," Chem. Rev., 2010, 110, 704-724.). We are developing diazo chemistry for catalytic stereoselective transformations to further enhance applicability of catalytic metal carbene chemistry in organic synthesis. New catalytic syntheses of multi-functional β-keto-α-diazoesters with subsequent catalytic transformations provide highly efficient access to more complex carbon frameworks than previously possible through reactions with diazocarbonyl compounds (see "Highly Enantioselective Catalytic Synthesis of Functionalized Chiral Diazoacetoacetates," X. Xu, W.-H. Hu, and M. P. Doyle, Angew. Chem. Int. Ed. 2011, DOI: 10.1002/anie.201102405).

Lewis acidic chiral dirhodium(II,III) carboxamidate catalysts are being used to broaden the range of asymmetric Lewis acid catalyzed carbon-carbon bond forming transformations. Reactivity and selectivity enhancement through chiral Rh25+ catalysts expands their utilization to Lewis acid catalyzed reactions for which chiral Rh24+ catalysts are ineffective. (See: "Solvent Enhancement of Reaction Selectivity: A Unique Property of Cationic Chiral Dirhodium Carboxamidates," X. Wang, C. Weigl, and M. P. Doyle, J. Am. Chem. Soc. 2011, 133, 9572-9579).

Catalytic oxidative methodologies to prepare compounds that are of biological significance are being developed. Newly discovered tert-butyl hydroperoxide oxidations catalyzed by dirhodium caprolactamate, based in large part on its low oxidation potential and solubility in water and organic solvents, offer a unique opportunity to develop a spectrum of oxidative transformations, compatible with water as a solvent, that are not easily achieved by other methods (especially allylic and benzylic oxidations). Applications encompass reactions with steroids, phenolic compounds, unsaturated fatty acid derivatives, terpenes, amines, and other biologically relevant substrates. (See: "Dirhodium-Catalyzed Phenol and Aniline Oxidations with T-HYDRO. Substrate Scope and Mechanism of Oxidation," M. O. Ratnikov, L. E. Farkas, E. C. McLaughlin, G. Chiou, H. Choi, S. H. El-Khalafy, and M. P. Doyle, J. Org. Chem. 2011, 73, 2585-2593).

PhRh(cap)₄RhPh

Our discovery of bis(phenyl)dirhodium(III) compounds has opened an entirely new area in dirhodium chemistry. Their structural rigidity, stability, and design flexibility are ideal for the generation of new materials. Opportunities now exist for the creation of novel organometallic structures and for examination of their electronic, physical and spectroscopic properties. (See: "Conformational Isomers of Extraordinary Stability: Carboxamidate-Bridged Dimetalloorganic Compounds," M. P. Doyle, J.-H. Xie, L. Zhou, Y. Sun, Y. Liu, and H. Sun, Chem. Commun., 2009, 3005-3007.)