The feasibility of ring-closing metathesis (RCM) as a
synthetic entry to 10- and 11-membered dienediynes fused to a
benzothiophene core was explored by experimental and theoretical
investigations. An established sequence of iodocyclization of o-(buta-1,3-
diynyl)thioanisoles followed by Sonogashira coupling to form diethynylbenzothiophenes
was used to synthesize terminal benzothiophene-fused
enediyne diolefins as substrates for RCM. Encountering an unexpected
lack of reactivity of these substrates under standard RCM conditions, we
applied DFT calculations to reveal that the underlying cause was a positive
change in Gibbs free energy. The change in Gibbs free energy was also found
to be positive for RCM of indole- and benzannulated terminal diolefins when
affording smaller than 12-membered rings. We found that modification of the
enediyne−diolefin substrate as the Co2(CO)6−alkyne complex allowed the
target benzothiophene-fused 11-membered dienediyne to be obtained via
RCM; the alkyne complexation strategy therefore provides one valid technique for overcoming challenges to macrocyclization of
this kind.