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 ortho-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.