Research in the M. P. Watson Group is centered on the discovery of new catalytic, stereoselective methods for organic synthesis by utilizing the power of both transition metal and Brønsted acid catalysts. 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 insights into questions of fundamental reactivity and catalyst design.
Selective Activation of Relatively Strong Bonds
One project within our group is focused on the selective activation of relatively 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 Transformations via a-Metalloamines and a-Metalloethers
Motivated by the prevalence of biologically active amines and ethers, we are investigating novel routes to prepare these compounds via a-metalloamine and a-metalloether intermediates. Our efforts are focused on the development of general conditions for the catalytic preparation of these intermediates and on their elaboration 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 cyclization of N-benzoyl aminals to valuable isoindolinones, structures that are found in a variety of biologically active molecules (DOI: 10.1021/ol201248c). Our mechanistic experiments are consistent with the metalloamide intermediate proposed above. We are now exploring similar approaches for the preparation of other nitrogen-containing molecules.
Brønsted Acid-Catalyzed Reactions of Unactivated Olefins
Another project is directed toward the design of new chiral Brønsted acid catalysts for additions across unactivated olefins. We are working to synthesize chiral Brønsted acid catalysts that are more acidic than currently available chiral Brønsted acids and are capable of participating in secondary stabilizing interactions with the substrate. These Brønsted acids have the potential to catalyze highly enantioselective additions of H–X (X = C, O, N, etc.) across olefins, allowing rapid access to a variety of biologically active molecules.
