Oligo(ethylene glycol) Length Effect of Water-Soluble Ru-Based Olefin Metathesis Catalysts on Reactivity and Removability

Abstract

A study of reaction kinetics and removal efficiency of a family of ruthenium (Ru)-based olefin metathesis catalysts containing ethylene-glycol-oligomer-tethered N-heterocyclic carbene (NHC) ligands has been carried out, with a focus on variation of ethylene glycol oligomer length. The length of ethylene glycol oligomer was precisely defined by sequential addition of repeating units. Due to the dual solubility of ethylene glycol oligomer, the produced catalyst was highly soluble in both aqueous and organic solvents (dichloromethane). In aqueous solution, the polarity increase with longer ethylene glycol oligomers enhanced the reactivity in homogeneous solution. The length of ethylene glycol oligomer did not significantly affect olefin metathesis rate in organic solution. Yet the removal efficiency of catalyst strongly relies on the length of ethylene glycol oligomer. A longer ethylene glycol oligomer demonstrated better catalyst removal efficiency. The tested catalyst removal method was aqueous extraction from organic solution using its higher water solubility property compared to its lower organic solvent (dichloromethane) solubility property. The results obtained from the aqueous extraction catalyst removal method demonstrated similar and/or better removal rates compared to previously reported host-guest catalyst removal methods.

Olefin Metathesis in Continuous Flow Reactor Employing Polar Ruthenium Catalyst and Soluble Metal Scavenger for Instant Purification of Products of Pharmaceutical Interest

“…The main approaches to reduce the heavy metal content are ,, (1) reduction of catalyst loading; (2) conventional purification methods such as recrystallization, distillation, chromatography, and nanofiltration; − (3) addition of scavengers into postreaction mixtures; − (4) self-scavenging catalysts being complexes with modified ligands containing an additional functional group; , (5) usage of heterogeneous catalysts. − The latter was not utilized in our research because of typical problems which may occur, such as metal leaching, low catalytic efficiency, and clogging, particularly in a flow system. There is minimal information about heterogeneous catalysts being utilized in the industrial setting …”

Semiheterogeneous Purification Protocol for the Removal of Ruthenium Impurities from Olefin Metathesis Reaction Products Using an Isocyanide Scavenger

“…Tailored self-scavenging catalysts contain tags that facilitate the removal of both the catalyst and its byproducts after the reaction is complete. ,− Similar to heterogeneous catalysts, the syntheses of such complexes often requires lengthy and expensive modifications.…”

Acid‐Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water

“…To address this limitation, several strategies to enable olefin metathesis in aqueous media have been proposed,i ncluding the use of biphasic systems, [32] immobilized catalysts, [33,34] nanoreactors and micellar catalysis, [35][36][37][38][39] artificial metallo-enzymes, [40] as well as modificationso ft he catalysts or the reaction conditions to increase the reactivity. [41][42][43][44][45][46][47][48][49][50] Unfortunately,m any of these systems are either incompatiblew ith water-soluble substrates or have av ery narrow substrate scope. [31,51,52] The olefin metathesis reactionhas nevertheless been applied to carbohydrates to somee xtent, [53] generally by using protected structures in organic solvents.…”

“…The majority of biologically interesting structures, such as unprotected peptides and carbohydrates, have therefore been largely incompatible with the reactions. To address this limitation, several strategies to enable olefin metathesis in aqueous media have been proposed, including the use of biphasic systems, immobilized catalysts, nanoreactors and micellar catalysis, artificial metallo‐enzymes, as well as modifications of the catalysts or the reaction conditions to increase the reactivity . Unfortunately, many of these systems are either incompatible with water‐soluble substrates or have a very narrow substrate scope …”