Photochemical reactions in the absence of external (photo)catalyst represent a sustainable approach to the synthesis of complex molecular structures, which would be otherwise difficult to access using classical synthetic methods.
Within this doctoral work, we developed photoinduced transformations of pyrazolo[1,2-a]pyrazolones, important biomimetics that absorb visible light. The method enables the selective synthesis of 1,2-diazepnes and 5,5,4-tricyclic products simply by changing the irradiation wavelength. The high stereoselectivity of the transformations was rationalized using spectroscopic methods and quantum-mechanical calculations. The reaction can also be performed on a larger scale, both in a flow system and through a one-pot approach starting from azomethine imines. Based on experimental and computational results, a reaction mechanism was proposed in which the diazepine products are formed via triplet biradical intermediates, while the subsequent 4π-electrocyclization most likely proceeds synchronously through singlet excited states. The developed transformations thus provide a stereoselective and atom-economical approach to 3D-rich molecular structures.
The methodology was further extended to pyrazolo[1,2-a]pyridazinones. A one-pot protocol was developed that prevents the rapid rearrangement of the starting tetrahidropyridazinones. Owing to their absorption of the visible light, pyrazolo[1,2-a]pyridazinones can be readily converted into structurally diverse tricyclic, aldehyde, and oxidized products in the absence of external (photo)catalysts. The oxidized products can also be further photoisomerized to form Z-isomers.
Given the importance of heterobicyclic systems, we also explored their implementation in photoresponsive systems. Pyrido[1,2-a]pyrimidines and their analogues proved to be suitable scaffolds for the design of novel photoswitches. In these systems, optical properties and Z-isomer stability can be tuned by varying the molecular structure. The synthesized compounds absorb across a broad region of the visible spectrum and exhibit high fatigue resistance. Two of them also showed partial inhibition of the growth of Staphylococcus aureus upon irradiation, indicating the possibility of photoinduced activation and light-controlled biological activity. These results demonstrate that such heterobicyclic scaffolds represent promising platforms for the development of new photoswitches, while a better understanding of the relationship between molecular structure and photophysical properties may facilitate their rational design.
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