Little-Ring Metathesis

Ring-closing metathesis has been used to establish a new route to functionalized cyclobutenes, a surprising result given the generally accepted idea that ring strain precludes formation of small cyclic rings using this approach (J. Am. Chem. Soc. 2008, 130, 1562). Ring-closing metathesis is popular for synthesizing medium and large rings from diene or enyne precursors. But strained cyclopropenes and cyclobutenes can easily be reopened by the carbene catalyst. In fact, cyclobutenes are starting materials for ring-opening metathesis polymerization and other metathesis reactions. However, Olivier Debleds and Jean-Marc Campagne of Institut Charles Gerhardt Montpellier, in France, surmised that the orientation of 1,5-enynes previously made in their lab might lead to less reactive cyclobutenes under the appropriate conditions. By using the Hoveyda-Grubbs second-generation ruthenium catalyst, the researchers were able to prepare several cyclobutenes (one example shown). They subsequently used the cyclobutene shown in a Diels-Alder reaction with a cyclic azo derivative to form a tricyclic compound, a reaction that could prove useful in natural products synthesis.