Design of ruthenium-pseudohalide catalysts for olefin metathesis

Ruthenium-catalyzed olefin metathesis is an exceptionally powerful method for the catalytic formation of new C=C bonds, recognized last year with the Nobel Prize. While the Grubbs-class catalysts RuCl2LL'(CHPh) have led to many advances, they offer limited selectivity and lifetimes. As these shortcomings are associated with the chloride ligands, we sought to incorporate "pseudohalide" ligands. Catalysts RuXX'(CHPh)(IMes)(py) were prepared by use of sterically undemanding ancillary ligands and electron-deficient aryloxides. Their modular structure permits control over selectivity via matching of catalyst and substrate reactivity. While their initiation efficiency lies between that of the second- and third-generation Grubbs catalysts, high efficiency is found in RCM of alpha,o-dienes to form trisubstituted olefins, vinyl alcohols, alpha,beta-unsaturated acrylates, macrolactones, ethers, tertiary amines, thioethers, and silanes. Their performance relative to the most active Grubbs systems is sometimes better, sometimes less so, with the optimum catalyst being a matter of trial and error (though the sustained activity of the aryloxide catalysts means that they often perform better in reactions that require long lifetimes). They are outstanding in enyne metathesis (enabling quantitative formation of tetrasubstituted olefins, a first in Ru-catalyzed metathesis) and in RCM synthesis of macrocycles. Examination of the much longer reaction time of the Grubbs systems led to the unexpected finding that oligomerization of alpha,o-dienes is kinetically dominant, and that RCM products are liberated in a concentration-dependent backbiting reaction. This is extremely important, as oligomers are generally regarded as a dead end in metathesis. This finding completely revises our understanding of the context and protocols for construction of conformationally flexible, medium and large rings by RCM