The broad objective of the proposed research is the development of new mechanisms for alkene functionalizations. These reactions are important for the synthesis of nitrogen containing compounds, including heterocycles, which have shown considerable activity in a number of different Pharmaceuticals and other biologically active molecules. Easy accessibility to these types of organic compounds is valuable to the synthesis and screening of pharmaceutical targets.
The specific aims of the application focus on the use of redox-active ligands to affect catalyst oxidizing ability in selective alkene oxidations. The use of palladium catalysts containing oxidized redox-active ligands will be developed and applied to Pd-catalyzed aerobic oxidations. By increasing the electrophilicity of the catalyst, improvements to reaction rates, product yields and catalyst lifetimes are proposed. In addition, a novel reaction mechanism for alkene 1,2-difunctionalizations using redox-active ligands will be developed. Alkene difunctionalization reactions are limited;however, if a general method of difunctionalization were available, it would provide access to a wide variety of heterocycles including aziridines, piperizines and imidazolines. The limitation of current methodology is the need to oxidize the Pd catalyst from Pd(ll) to Pd(lll) or (IV) to induce reductive displacement from a Pd-alkyl intermediate. Rather than oxidizing the metal center, oxidation of a redox-active ligand is proposed to contain enough oxidizing potential to promote reductive displacement of difunctionalized product. To achieve these goals, palladium complexes bound to redox-active ligands will be prepared and studied by electrochemistry to gain an understanding of their oxidation and reduction properties. Stoichiometric reactions will be carried out to develop a fundamental understanding of the behavior of palladium complexes containing redox-active ligands. Finally, these results will be used to develop catalytic processes for alkene functionalizations.
The synthesis of small, biologically active molecules is important in the development of new Pharmaceuticals. Accessing some of these of compounds is not always straightforward. The proposed plan of research focuses on developing new ways of synthesizing these biologically important molecules.
| Campbell, Alison N; Stahl, Shannon S (2012) Overcoming the ""oxidant problem"": strategies to use O2 as the oxidant in organometallic C-H oxidation reactions catalyzed by Pd (and Cu). Acc Chem Res 45:851-63 |
| Campbell, Alison N; Meyer, Eric B; Stahl, Shannon S (2011) Regiocontrolled aerobic oxidative coupling of indoles and benzene using Pd catalysts with 4,5-diazafluorene ligands. Chem Commun (Camb) 47:10257-9 |
| Campbell, Alison N; White, Paul B; Guzei, Ilia A et al. (2010) Allylic C-H acetoxylation with a 4,5-diazafluorenone-ligated palladium catalyst: a ligand-based strategy to achieve aerobic catalytic turnover. J Am Chem Soc 132:15116-9 |
