Abstract
Nitrogen-containing heterocycles can have several applications in the pharmaceutical industry since they contain a wide spectrum of biological activities. Imidazolidinones have shown activity against leukemia, lung cancer, and metabolic disorders. These cyclic urea frameworks can be obtained through transition-metal-catalyzed intermolecular cycloaddition using an aziridine moiety as the starting material. These reactions often provide effective one-step procedures that result in heterocyclic derivatives that are challenging to access through conventional approaches. We have previously described the photoreaction of butyl pyridinium salt with the corresponding bicyclic aziridine in continuous flow. Additionally, we reported that the palladium-catalyzed ring opening of bicyclic aziridines with active methylenes exhibited a new SN2’ selectivity. In this study, the reaction between bicyclic aziridines and several isocyanates, in the presence of Pd(0)-catalyst is presented. The reactions proceed through ring opening of the aziridine moiety, with the formation of the π-allylpalladium complex, followed by cyclization via nucleophilic addition of nitrogen to the isocyanate, affording regioselectively imidazolidinones.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/ECMC2022-13424/s1.
Author Contributions
Conceptualization, supervision, F.S. and C.A.M.A.; investigation, M.C.M., and F.S.; data curation, formal analysis and writing, M.C.M., F.S. and C.A.M.A. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Fundação para a Ciência e Tecnologia for financial support (UIDB/04138/2020, UIDP/04138/2020 and 2022.08559.PTDC). The NMR spectrometers are part of the National NMR Network (PTNMR) are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The project leading to this application has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 951996. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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