Mechanistic studies of iminoxyl radicals and radical cations – intramolecular cyclization reactions with alkene derivatives
Authors:Wan Shin Kim, Michael Ko
Mentor:Peter de Lijser, Professor of Organic Chemistry, California State University Fullerton
The synthesis of heterocycles is a popular field of study often associated with drug molecule and natural product synthesis. In such applications, many studies have explored the possibility of using oximes and oxime ethers as a building block for heterocycle synthesis, but not so many studies have explored the radical or radical cation cyclization aspect of oximes and oxime ethers. Previous studies have revealed that ortho-alkynyloxime derivatives can undergo efficient electrophilic cyclization, yielding isoquinoline or isoquinoline N-oxide derivatives. However, not much attention has been focused on the oxime radical cation or iminoxyl radical cyclization processes of ortho-alkynyloxime derivatives. In order to study this possibility as well as the regioselectivity of these cyclization processes, we prepared a series of o-alkynyl and o-alkenylbenzaldehyde and acetophenone oximes. The oximes were subjected to photooxidation or thermal oxidation in different solvents and the product formation was followed by GC/MS and NMR. In the case of the o-alkynylacetophenone oximes, NMR analysis of the reaction mixtures shows clear evidence for the formation of cyclized products. Interestingly, o-phenylbenzaldehyde and o-phenylacetophenone oximes do not show such reactivity. Instead, their oxime ethers were found to be reactive, suggesting that the aromatic ring acts as a nucleophile attacking the nitrogen of the oxime ether moiety. Further work is focusing on o-alkenyl oximes, which may react as radical traps or nucleophiles. So far, our studies are limited to 2-styrylbenzaldehyde oxime, which was shown to absorb light in the absence of a sensitizer (even at 420 nm). Most likely this is due to the fact that the compound is highly conjugated. We are currently in the process of preparing less conjugated derivatives to further study these interesting reactions. The results from the o-alkynyl and o-alkenyl compounds will be presented and discussed.