Ring-Closing Metathesis Synthesis of Medium and Large Rings: Challenges and Implications for Sustainable Synthesis

Synthesis of medium-sized and macrocyclic rings by ring closing metathesis (RCM) reactions of dienes involves challenges not found in synthesis of the more common five- and six-membered rings. This review discusses factors that determine the probability and efficiency of cyclization, and experimental methods that have been used to increase selectivity for RCM products, with specific reference to the concentrations at which RCM can be achieved. These issues have important implications for the environmental and economic sustainability of large-scale synthetic processes utilizing RCM for assembly of rings larger than six members.