Low Catalyst Loading in Ring-Closing Metathesis Reactions

An efficient procedure is described for ring-closing metathesis reactions. A conversion of 95?% for diethyl diallylmalonate in dilute solution could be achieved within a few minutes, reaching TOF=4173 min-1, with very low loading of commercially available Ru catalysts that contained unsaturated NHC ligands. In general, only 50 to 250 ppm of the catalyst is required to achieve near-quantitative conversion into a broad variety of 516-membered heterocyclic compounds. The practicality of this procedure was illustrated in the synthesis of 58-membered N-tert-butoxycarbonyl (N-Boc)- and N-para-toluenesulfonyl (N-Ts)-protected cyclic amines and 916-membered lactones. The synthesis of macrocyclic proline-based lactams required slightly higher catalyst loadings. Along with monocyclic products, oligomeric byproducts, mostly cyclodimers, were isolated and characterized.