A Rigidified Macrocyclic Grubbs Complex: A Rare Example of <i>In</i>- and <i>Out</i>-Isomers that Show a Dramatic Difference in Catalytic Reactivity

The design of a rigidified macrocyclic N-heterocyclic carbene (NHC) ligand led to the formation and structural characterization of in- and out-Ru carbene complexes. In this study, the introduction of a conformational lock was used to rigidify heteroaryl–aryl bonds and thereby enforce a more perpendicular dihedral angle. A forcing metalation step was needed to form the isomeric Ru carbene complexes (Grubbs complexes). The major isomer had the Ru carbene fragment located outside the macrocyclic ring, whereas the minor isomer had the Ru carbene inside the macrocyclic ring. The two new Ru carbene complexes are the first examples of in- and out-isomers of a Grubbs-type complex. The solid-state structures of each isomeric ruthenium carbene complex were determined by X-ray diffraction (XRD) studies. The two Ru complexes showed significantly different catalytic reactivities in the ring-closing metathesis (RCM) of the benchmark substrate, diethyl diallylmalonate. We performed computational studies to determine rotational barriers; scalable energetic barriers were found in the unmetalated NHC ligand, favoring the in-isomer by 2.4 kcal/mol. These calculations, coupled with the attempted interconversion of isomers, support a mechanism featuring rotational isomerization of the NHC nucleophile in a pre-equilibrium step before metalation.