The discovery of chemical methods enabling the construction of carbocycle‐fused uracils which embody a three‐dimensional and functional‐group‐rich architecture is a useful tool in medicinal chemistry oriented synthesis. In this work, an unprecedented amine‐catalyzed [4+2] cross‐cycloaddition is documented; it involves remotely enolizable 6‐methyluracil‐5‐carbaldehydes and β‐aryl enals, and chemoselectively produces two novel bicyclic and tricyclic fused uracil chemotypes in good yields with a maximum level of enantiocontrol. In‐depth mechanistic investigations and control experiments support an intriguing homo‐synergistic organocatalytic approach, where the same amine organocatalyst concomitantly engages both aldehyde partners in a stepwise eliminative [4+2] cycloaddition, whose vinylogous iminium ion intermediate product may diverge—depending upon conditions—to either bicyclic targets by hydrolysis or tricyclic products by a second homo‐synergistic trienamine‐mediated stepwise [4+2] cycloaddition.
Unlocking Access to Enantiopure Fused Uracils by Chemodivergent [4+2] Cross‐Cycloadditions: DFT‐Supported Homo‐Synergistic Organocatalytic Approach / Curti, Claudio; Rassu, Gloria; Lombardo, Marco; Zambrano, Vincenzo; Pinna, Luigi; Battistini, Lucia; Sartori, Andrea; Pelosi, Giorgio; Zanardi, Franca. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 59(2020), pp. 20055-20064. [10.1002/anie.202007509]
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