Amir Hoveyda’s group recently demonstrated that H-bonding can significantly increase the rate and levels of stereochemical control in Ru-catalyzed olefin metathesis reactions. They developed facile diastereoselective ring opening/cross-metathesis reactions (DROCM) using achiral Ru catalysts. Ring opening and cross metathesis of cyclopropenes and cyclobutenes with enantiomerically enriched allylic alcohols afforded the desired products, and the stereochemical information of the allylic alcohol was efficiently transferred to the newly formed stereocenter.
The best diastereoselectivities were achieved with the 2nd Generation Grubbs systems using chiral allylic alcohols as substrates. In contrast to the free allylic alcohols, methyl ethers react much slower and with lower and the opposite sense of selectivity, which suggests that a rate-accelerating intramolecular hydrogen bond may be operative.
The selectivity of the reactions can be explained by the formation of H-bond between the alcohol and the chloride ligand. The hydrogen bond increases the electronic density difference between the carbene and the coordinating olefin, facilitating metallacyclobutane formation.
Unfortunately, the hydrogen bonding ensures only the excellent diastereoselectivity, but cannot exert strong control over the E/Z selectivity. Reactions with cyclobutenes proceed with much lower E/Z selectivity compared to the cyclopropenes. Design of catalysts that promote high diastereoselectivity and furnish high E/Z selectivity is in progress in the Hoveyda group.