Visible-light promoted dearomative [2+2] cycloaddition of cinnammyls on (benzo)heterocycles

The ambition to produce complex molecules from simple precursors is a growing demand in various fields such as the pharmaceutical industries. Visible – light promoted dearomative cycloadditions achieve this goal in a green and sustainable way, becoming increasingly popular in this area. These reactions can follow two paths: the arene’s activation or the arenophile’s activation. The first pathway has been extensively explored in literature, with Dhar’s group and Glorius’ group presenting two different methods to dearomatize benzoheterocycles in 2019 and 2020, respectively, leading to a lack of knowledge regarding the second activation route. This project is focused on the dearomative [2+2] cycloaddition on (benzo)heterocycles using a cinnamyl fragment as arenophile, since its double bond can be easily sensitized via EnT. The method demonstrated functional group tolerance with yields up to 99% and good diasterospecificity. The project led to the synthesis of several products, incuding challenging substrates like furans and thiophenes, which were dearomatized under this condition. Notably, the reaction proposed allows to obtain a fused tricyclic structure with complete atom economy under mild conditions, using a low photocatalyst loading and a cheap light source; this approach opens new opportunities in the design of complex molecules for pharmaceutical applications. References [1] Martins S. Oderinde, T. G. Murali Dhar, Et Al. Synthesis of Cyclobutane-Fused Tetracyclic Scaffolds via Visible-Light Photocatalysis for Building Molecular Complexity, J. Am. Chem. Soc 6, 3094-3103 (2020) [2] F. Strieth-Kalthoff, F. Glorius, Et Al. Discovery of Unforeseen Energy Transfer Based Transformations Using a Combined Screening Approah, Chem 5, 2183–2194 (2019)