Ring-Closing Metathesis
of Co<sub>2</sub>(CO)<sub>6</sub>–Alkyne Complexes for the
Synthesis of 11-Membered
Dienediynes: Overcoming Thermodynamic Barriers
- Publication date
- Publisher
Abstract
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 <i>o</i>-(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 Co<sub>2</sub>(CO)<sub>6</sub>–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