The development of new and convenient methodologies for the efficient synthesis of heteroaromatic ring systems remains an area of high interest. Oxidative cyclizations with radical or radical ion intermediates are potentially useful strategies to achieve these types of cyclizations. Based on previous results from our group,1 it was hypothesized that radical ions would be susceptible to intramolecular nucleophilic attack whereas radicals would preferentially react with built-in radical traps. Our research has focused on evaluating different groups in terms of their nucleophilicity or radical trap ability when built into the oxime derivative at a strategic location. The oxime derivatives were subjected to photooxidation or thermal oxidation in different solvents and the product formation was followed by GC/MS and NMR analysis. Oxime ethers with built-in aromatic groups were found to undergo a cyclization reaction yielding phenanthridines. Mechanistic studies are consistent with a pathway that involves the aromatic ring acting as a nucleophile, attacking the nitrogen of the oxime ether radical cation.2 This methodology is possibly useful for the synthesis of heterocyclic structures if it could be expanded to involve aromatic nucleophiles that can contain additional heteroatoms such as nitrogen, oxygen, or sulfur. We have prepared a series of pyridinyl, furanyl, and thiophenyl-substituted benzaldehyde oximes and oximes ether to determine whether it is possible to use these heteroaromatic ring systems as nucleophiles. Preliminary results suggest that under the PET conditions used for our previous studies, cyclization does not occur. We hypothesize that the heteroaromatic rings are activated as a result of the presence of the heteroatom and therefore less reactive similar to aromatic rings with strong electron-donating groups. Alternative strategies to achieve the desired oxidative cyclization reactions involve direct photolysis as well as transition metal-catalyzed processes utilizing oximes, oxime ethers, and oxime esters. The results from these reactions will be presented and discussed. 1. de Lijser, H. J. P.; Tsai, C. K. J. Org. Chem., 2004, 69, 3057. 2. Hofstra, J. L.; Grassbaugh, B. R.; Tran, Q. M.; Armada, N. R.; de Lijser. H. J. P. J. Org. Chem., 2015, 80, 256.

Inducing oxidative cyclization reactions of benzaldehyde oximes with built-in heteroaromatic nucleophiles via photochemical and metal catalysis

251st National Meeting (2016)

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