Generating Molecular Diversity via Addition of Nucleophiles to Electron-Deficient [3]Dendralenes: An Exploratory Study

Electron-deficient dendralenes, bearing enone substructures and possessing an unfavorable disposition of like charges at the neighboring carbons, undergo nucleophilic 1,4-addition (Michael) or 1,6-addition (anti-Michael). Diverse products are obtained, including those of simple addition as well as cyclic and <i>ortho</i>-fused systems arising via multistep sequences, depending on the structure of the substrate and the nature of the nucleophile. Attack of a hydride at an enone fragment triggers the formation of multisubstituted pyranones and furans; furan formation was also initiated by thiolates. A notable exception is the derivative with a five-membered cyclic enone, which prefers simple additions followed by the reshuffling of the double bonds for both H^- and RS^- nucleophiles. By contrast, the latter enone is the only one that can react with stabilized C-nucleophiles, yielding bicyclic compounds. Domino cyclizations can also be induced by the enolization of the enone with DBU, giving mostly polysubstituted furans. However, the dendralene with a five-membered cyclic enone and its analogue with a six-membered ring behave differently: The former gives a mixture, while the latter prefers the formation of an isocoumarin derivative, which is driven by aromatization. DFT calculations have shown that the additions of thiolates are mostly governed by the thermodynamic stability of possible products arising from complex equilibrium processes.