Sterically Tuned N-Heterocyclic Carbene Ligands for the Efficient Formation of Hindered Products in Ru-Catalyzed Olefin Metathesis

Formation of tetrasubstituted C-C double bonds via olefin metathesis is considered very challenging for classical Ru-based complexes. In the hope to improve this condition, three ruthenium olefin metathesis catalysts bearing sterically reduced N-heterocyclic carbene (NHC) ligands with xylyl "arms" were synthesized, characterized using both computational and experimental techniques, and tested in a number of challenging reactions. The catalysts are predicted to initiate much faster than the analogue with mesityl N-substituents. We also foreboded the rotation of xylyl side groups at ambient temperature and the existence of all four atropoisomers in the solution, which was in agreement with experimental data. These catalysts exhibited high activity at relatively low temperatures (45-60 °C) and at reduced catalyst loadings in various reactions of sterically hindered alkenes, including complex polyfunctional substrates of pharmaceutical interest, such as yangonin precursors, chrysantemic acid derivatives, analogues of cannabinoid agonists, α-terpineol, and finally a thermally unstable peroxide.