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

Abstract

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.

A Theoretical Investigation into the Luminescent Properties of d8‐Transition‐Metal Complexes with Tetradentate Schiff Base Ligands

“…Likewise, the concentration and temperature also play crucial roles in RCM reactions 60–63. Notably, for most cases in which dienes were constructed on amino acid, peptide, and peptidomimetic structures, the RCM reaction was performed with a high catalyst loading and at very low concentrations 64,65. On the basis of our previous studies of metathesis reactions under low concentration conditions, we investigated the cyclization of β‐dipeptides I – IV in the presence of GII (5 mol‐%) in toluene at 80 °C for 20 h with a substrate concentration of 0.004 M .…”

“…The outcome might be the result of purely steric effects or other effects such as template strain or H‐bonding interactions. There are several examples in which the formation of macrocycles by selective double cross‐metathesis (or cross‐metathesis followed by RCM, as detected in some cases) is preferred over RCM 65–81…”

Editorial of Special Issue Ruthenium Complex: The Expanding Chemistry of the Ruthenium Complexes

“…With introduction of the new generations of highly active and chemoselective Ru metathesis catalysts endowed with high tolerance towards many functionalities and good stability in the presence of air, moisture and various solvents, including water-containing systems [231,232,233,234,235,236,237,238,239], the diversification of metathesis reactions experienced a strong impetus [240,241,242,243,244,245]. Among metathesis reactions, cross-metathesis (CM) [246,247,248,249] and ring-closing metathesis (RCM) [250,251,252,253,254] have become the most encountered strategies for the synthesis of linear and branched, or carbocyclic and heterocyclic compounds. Ru-catalyzed enyne metathesis (EYRCM) provided an elegant and productive way to obtain small, medium and large cyclic molecules [255].…”

Volume intensified dilution of a ring‐closing metathesis in ethyl acetate by means of a membrane‐assisted process in solvent recycle

“…Though there is a plethora 6 of methods to synthesize macrocycles, ring-closing metathesis (RCM) has become a popular method [7][8][9][10][11] due in part to the high chemoselectivity and functional group tolerance of the catalysts that have been developed over recent decades. 12,13 Furthermore, the inherent reversibility of olefin metathesis reactions can have important implications on the outcome of the equilibrium between RCM and cross-metathesis (CM); the latter leading to acyclic products.…”