Aqueous olefin metathesis: recent developments and applications

Abstract

Olefin metathesis is one of the most powerful C–C double-bond-forming reactions. Metathesis reactions have had a tremendous impact in organic synthesis, enabling a variety of applications in polymer chemistry, drug discovery and chemical biology. Although challenging, the possibility to perform aqueous metatheses has become an attractive alternative, not only because water is a more sustainable medium, but also to exploit biocompatible conditions. This review focuses on the progress made in aqueous olefin metatheses and their applications in chemical biology.

Acid‐Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water

“…[29,30] However,a lthough the use of olefin metathesis in organic solvents has been ex-tensively demonstrated, applicationsi na queous media have been considerably less explored. [31] 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,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. However,t he direct use of unprotected carbohydrates in aqueousm ediaw ould significantly increase the applicability to biologicals ystemsa nd other situations in whichw ater is desired as solvent.…”

Ring-opening metathesis polymerization-induced self-assembly (ROMPISA)

“…Catalysts for aqueous metathesis have been reviewed extensively elsewhere and will not be discussed here. 34 It should be noted, however, that despite significant progress in the development of water-soluble Ru-based metathesis catalysts, few possess catalytic activity comparable to that of G3 in organic solvent. Water-soluble G3-derivatives have been reported, but these generally require the use of additional additives such as Brønsted or Lewis acids to promote phosphine or pyridine dissociation.…”

“…We believe that this field will greatly expand in the near future as new catalysts developed for aqueous metathesis of small molecules and the identification of new core-forming monomers have provided a roadmap toward overcoming these key challenges. 33,34 To the best of our knowledge, the first study introducing the concept of in situ preparation of block copolymer nano-objects via ROMPISA was reported by Xie and coworkers. 35 In this early report, a solvent-soluble poly(2,3-bis(2-bromoisobutyryloxymethyl)-5-norbornene) (PBNBE) macroinitiator was first synthesized using (PCy 3 ) 2 (Cl) 2 RuQCHPh (G1) as the catalyst.…”

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

“…Alkene and alkyne metathesis [1][2][3][4], constituting highly versatile and powerful catalytic processes for constructing complex organic molecules [5][6][7][8][9][10][11][12], have found broad application in the fields of pharmaceutical synthesis [13][14][15], materials science [16][17][18][19][20], or in advanced techniques and technologies [21][22][23][24][25][26][27][28][29][30]. Thus, numerous multistep total syntheses of organic compounds, including bioactive molecules [31][32][33][34][35] and natural products [36,37], have been performed in a highly chemo-and stereoselective manner through metathesis routes [38][39][40][41][42][43].…”