Tandem reactions have become a popular method for the synthesis of complex molecules from simple starting materials. Those involving transition metals as catalysts have become especially prevalent because of the low catalyst loadings, the potential for asymmetric induction with chiral ligands, and the ease with which they construct polycyclic carbocycles and heterocycles. The focus of this proposal is the development of an enantioselective three-component transition metal-catalyzed C-H insertion reaction between an aryl imine, a tethered olefin, and an exogenous olefin or alkyne to afford annulated products. To achieve this goal, readily available substrates will be synthesized and exposed to a transition metal and chiral ligand. A survey of temperature, solvent, and concentration will be performed in order to determine the optimal conditions for this process. This three-component reaction will provide access to complex polycyclic carbocycles and heterocycles from inexpensive starting materials. This proposal will no doubt improve upon existing C-H bond functionalization methodology and will provide the pharmaceutical industry with useful, new tools for the synthesis of bioactive targets.
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| Ischay, Michael A; Takase, Michael K; Bergman, Robert G et al. (2013) Unstabilized azomethine ylides for the stereoselective synthesis of substituted piperidines, tropanes, and azabicyclo[3.1.0] systems. J Am Chem Soc 135:2478-81 |
