Optimization of Ring‐Closing Metathesis: Inert Gas Sparging and Microwave Irradiation

Abstract

A systematic study of a ring-closing metathesis towards a tetrasubstituted double bond as part of a seven-membered ring in a 5.7.5-tricyclic guaianolide system is described. By combining two techniques, namely sparging an inert gas through the solution together with dielectric heating via microwave irradiation a high-yielding ring-closing metathesis reaction in this particularly challenging case was achieved. The results obtained compare favorably with conventional heating conditions or with microwave irradiation in a closed system. The key aspects seem to be that rapid microwave irradiation diminishes catalyst decay by allowing the required high reaction temperature to be reached quickly and homogeneously and thereby providing enough energy for a successful metathesis reaction, while inert gas sparging is purging off evolving ethylene to shift the equilibrium to the product.

Cleavage of a chiral auxiliary using RCM on an especially sterically crowded alkene: Syntheses of chiral carbo- and heterocycles

“…Thomas and co-workers have shown that the presence of a gem-dimethyl group at the allylic position of a terminal double bond shuts down a metathetic macrocyclization (not shown) [10]. A difficult RCM was successfully achieved from 13 by microwave irradiation as well as N 2 sparging to remove ethylene (Scheme 2, bottom) [11]. Generally, the second generation Grubbs (9) or Nolan catalysts (21,cf.…”

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

“…Because RCM is typically carried out at elevated temperatures in a vessel open to an atmosphere of N 2 or Ar, the low solubility of ethylene in organic solvents [58] normally results in its rapid, irreversible loss from solution. Volatilization can be accelerated further by deliberately sparging reaction solutions: Reiser and coworkers have noted that this has a beneficial effect on yields [59]. The entropic gain adds greatly to the driving force for both oligomerization and RCM: because regeneration of the starting α,ω-diene is impossible once the ethylene has escaped, the metathesis equilibria simplify to the pathways shown in Figure 5.…”

Microwave‐Assisted Olefin Metathesis

“…[23] By combining two techniques, namely, sparging an inert gas through the solution together with dielectric heating by µW irradiation, a high-yielding RCM was achieved in this sterically demanding case. The key aspects seem to be that rapid µW irradiation allows the catalyst a longer lifetime, while sparging with the inert gas purges the evolving ethylene to shift the equilibrium to the product.…”