The majority of work done in this project was laboratory work, with synthesis, isolation, and characterization of novel compounds as the most common tasks. Additional aspects included electrochemical and photochemical measurements and theoretical quantum chemistry calculations.
Early in the project, we identified alkoxy indanones as a class of compounds that displayed the physical and chemical properties we were seeking. Upon photochemical activation, they were generating reactive hydrogen-abstracting reactive species; they were non-hygroscopic solids and based on the literature review, we assume that they were non -toxic solids. The reactivity of the alkoxyiodanone was explored and a manuscript is currently in preparation. The hydrogen-abstracting capacity was critical in our attempts to generate the key azahomoallyl radicals. Furthermore, the oxidative quenching of the photocatalyst was also essential because the process that we envisioned required oxidation as the radical terminating step. Despite extensive optimization, we were not able to identify suitable conditions, that would allow us to attach the hypervalent iodine moiety to the aziridines, which were our substrates.
Given that this was relatively early in the project, we explore other compounds, which were depicted in the proposal. However, none of the literature-reported compounds displayed the desired chemical properties. After extensive screening, we identified aziridinylmethyl iodides as the ideal synthetic precursors. The majority of these products could be prepared by modification of reported procedures.
Furthermore, they provided access to a variety of substitution patterns that could modulate the electrophilicity of the target azahomoallyl radicals.
Consequently, we synthesized a library of compounds substituted with groups that could influence the electrophilicity (CN, Br, CH3, OMe, alkyl and polycyclic aromatics). Next, in line with the proposed research, we calculated the electronic parameters of all accessible azahomoallyl radicals and explored their reactivity in the proposed [3+2] cycloaddition. However, we did not observe any structure-reactivity relationship between the electrophilicity of the azahomoallyl radical and its potential to either abstract a hydrogen or to add to an olefin. Most likely, the initial formation of the C-N bond is not rate-limiting, as we initially assumed. Thus, we could not develop the map of the reactivity and we were forced to pivot. We decided to explore the mechanism of the proposed [3+2] cycloaddition of azahomoallyl radicals and olefins in terms of scope, photochemistry and electrochemistry. We discovered that the reaction works well with electron-rich and somewhat strained olefins and can provide polycyclic pyrrolidines with three contiguous stereogenic centers which are relevant compounds in the pharmaceutical research. This discovery was disseminated in the form of a poster at the Gordon research conference on Organic Reactions and Processes at Stonehill College, Easton, United States.
Through electrochemical and photochemical experiments, we established that the reported [3+2] operates via an energy transfer mechanism. The mechanistic research has been published in the European Journal of Organic Chemistry, with open access. Furthermore, the study has been selected for an oral presentation on meeting on the 4th International Symposium on Green Chemistry, which was supposed to be held in Rennes, France, but due to Coronavirus restriction, this meeting was postponed to autumn 2020.
