Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating Macrocyclization at Ambient Temperatures

Ring-closing
metathesis (RCM) offers versatile catalytic routes
to macrocycles, with applications ranging from perfumery to production
of antiviral drugs. Unwanted oligomerization, however, is a long-standing
challenge. Oligomers can be converted into the cyclic targets by catalysts
that are sufficiently reactive to promote backbiting (e.g., Ru complexes
of N-heterocyclic carbenes; NHCs), but catalyst decomposition
limits yields and selectivity. Incorporation of a hemilabile o-dianiline (ODA) chelate into new catalysts of the form
RuCl2(NHC)­(ODA)­(=CHPh) accelerates macrocyclization, particularly
for dienes bearing polar sites capable of H-bonding: it may also inhibit
catalyst decomposition during metathesis. Significant improvements
relative to prior Ru-NHC catalysts result, with fast macrocyclization
of conformationally flexible dienes at room temperature.