Mary P. Watson, Professor
University of Delaware
209 Lammot DuPont Lab
Newark, DE 19716
(b. 1977) A.B., 2000 Harvard University; Ph.D., 2006 University of California, Irvine; NIH Postdoctoral Fellow, 2006 - 2009, Harvard University
Catalysis enables new synthetic transformations and greater efficiency and selectivity in known reactions. Intrigued by the ability of both organo- and transition metal catalysts to exert such strong control over reactivity, we are focused on harnessing their power in new transformations. This research will lead to the development of new methods for the synthesis of biologically active molecules and other important materials. These methods will allow greater efficiency and novel bond constructions in the synthesis of stereochemically complex molecules, with applications that extend to natural products synthesis, drug discovery and process chemistry. The development of these methods will also provide a platform for mechanistic investigations, which will provide a deeper understanding of how these catalysts interact with substrates and enable the design of future catalysts.
Selective Activation of Strong Bonds
One project within our group is focused on selective activation of strong bonds by transition metal catalysts. Extremely powerful methods, such as the Heck, Suzuki and Buchwald-Hartwig reactions, have been enabled by the observation that transition metal catalysts selectively activate weak carbon–halide and carbon–oxygen bonds. The development of catalysts for the selective activation of relatively strong C–X bonds and incorporation of both the C- and X-fragments into the products would allow an efficient bond disconnection approach for the formation of highly substituted olefin or alkane products from simple starting materials. The application of homochiral metal catalysts for enantioselective variants of these transformations is also being investigated.
Catalytic Transforormations via α-Metalloamines and α-Metalloethers
Motivated by the prevalence of biologically active amines and ethers, we are investigating novel routes to prepare these compounds via α-metalloamine and α-metalloether intermediates. Our efforts are focused on the development of general conditions for the catalytic preparation of these intermediates and on the elaboration of these intermediates to a variety of important molecules. Our ultimate goal is to use chiral catalysts to enable enantioselective synthesis of chiral amines and ethers.
Within this area, we have recently discovered a novel nickel-catalyzed transformation of readily available N-benzoyl aminals to valuable isoindolinones, structures that are found in Lunesta® and other bioactive molecules. Our mechanistic experiments are consistent with our proposed α-metalloamide intermediate. We are now exploring similar approaches for the preparation of pyrrolidines, benzylic and allylic amines, 1,3-aminoalcohols and a variety of other nitrogen-containing molecules.
- D. M. Shacklady-McAtee, S. Dasgupta and M. P. Watson "Nickel(0)-Catalyzed Cyclization of N-Benzoylaminals for Isoindolinone Synthesis," Org. Lett., (2011) 13, ASAP. DOI: 10.1021/ol201248c.
- M. P. Watson and E. N. Jacobsen "Asymmetric Intramolecular Arylcyanatio of Unactivated Olefins via C–CN Bond Activation," J. Am. Chem. Soc., (2008) 130, 12594 – 12595.
- M. P. Watson, L. E. Overman and R. G. Bergman "Kinetic and Computational Analysis of the Palladium(II)-Catalyzed Asymmetric Allylic Trichloroacetimidate Rearrangement: Development of a Model for Eanntioselectivity," J. Am. Chem. Soc., (2007) 129, 5031 – 5044.
- S. F. Kirsch, L. E. Overman and M. P. Watson "Monomeric Cobalt Oxazoline Palladacycles (COP). Useful Catalysts for Catalytic Asymmetric Rearrangement of Allylic Trichloroacetimidates," J. Org. Chem., (2004) 69, 8101 – 8104.
- L. E. Overman, C. E. Owen, M. M. Pavan and C. J. Richards "Catalytic Asymmetric Rearrangement of Allylic N-Aryl Trifluoroacetimidates. A Useful Method for Transforming Prochiral Allylic Alcohols to Chiral Allylic Amines," Org. Lett., (2003) 5, 1809 – 1812.
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