Cobalt-Catalyzed [6 + 2] Cycloaddition of Alkynes with 1,3,5,7-Cyclooctatetraene as a Key Element in the Direct Construction of Substituted Bicyclo[4.3.1]decanes

A new,
effective catalytic system based on Co­(acac)2 has been
developed for [6 + 2] cycloaddition of terminal alkynes
to 1,3,5,7-cyclooctatetraene to give substituted bicyclo[4.2.2]­deca-2,4,7,9-tetraenes
in high yields (68–85%). The electrophilic activation of double
bonds in the bicyclic products with m-CPBA is an efficient method
for the synthesis of substituted bicyclo[4.3.1]­deca-2,4,8-triene-7,10-diols,
which form the key structural moieties of numerous natural biologically
active compounds. The structures of the obtained compounds were reliably
proven by modern spectral methods and X-ray diffraction. The mechanism
of the discovered rearrangement was studied both using deuterium-labeled
bicyclo[4.2.2]­deca-2,4,7,9-tetraenes and utilizing quantum chemical
calculations. The obtained substituted bicyclo[4.3.1]­deca-2,4,8-triene-7,10-diols
and their keto derivatives showed high antitumor activity in vitro
against Hek293, Jurkat, K562, and A549 tumor cell lines.