The broad aim of the following research proposal involves the improvement of Cu-catalyzed C-N and C- O bond-forming reactions. Copper mediated nucleophilic substitution of aryl halides are frequently used in the pharmaceutical industry, especially by medicinal chemists, to form aromatic amines and aryl ethers, for the synthesis of potential drug targets. First, intermediates in the catalytic cycle will be isolated, characterized and further studied to gain insight into the mechanism of the reaction. These intermediates will be used to study interesting selectivities that have been observed with Cu-based catalyst systems. Second, new anionic and neutral ligands will be designed and applied in Cu-catalyzed C-heteroatom cross-couplings with the goal of creating systems that display better catalyst activity and stability, and which can operate under mild conditions. Third, new Cu-catalyzed C-heteroatom bond-forming reactions will be developed, and known reactions will be refined for use in organic synthesis. These include the Cu-catalyzed reactions of aryl iodides and bromides with nucleophiles to provide protected and unprotected phenols, silyl enol ethers, diaryl amines and triaryl amines. ? ? Relevance Aromatic-nitrogen and aromatic oxygen compounds are commonly found in photographic materials and in pharmaceutical targets with potential therapeutic applications. These structural motifs are commonly synthesized by copper-catalyzed carbon-nitrogen and carbon-oxygen bond forming reaction. The proposed research seeks to improve known and develop new copper-catalyzed bond-forming reactions for use by medicinal chemists in the pharmaceutical industry, as well as synthetic organic chemists in general. ? ? ?
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| Altman, Ryan A; Hyde, Alan M; Huang, Xiaohua et al. (2008) Orthogonal Pd- and Cu-based catalyst systems for C- and N-arylation of oxindoles. J Am Chem Soc 130:9613-20 |
| Altman, Ryan A; Anderson, Kevin W; Buchwald, Stephen L (2008) Pyrrole-2-carboxylic acid as a ligand for the Cu-catalyzed reactions of primary anilines with aryl halides. J Org Chem 73:5167-9 |
| Altman, Ryan A; Shafir, Alexandr; Choi, Alice et al. (2008) An improved Cu-based catalyst system for the reactions of alcohols with aryl halides. J Org Chem 73:284-6 |
