Rational Design and Evaluation of Upgraded Grubbs/Hoveyda Olefin Metathesis Catalysts: Polyfunctional Benzylidene Ethers on the Test Bench

Abstract

The series of upgraded Grubbs/Hoveyda second-generation catalysts (H2IMes)(Cl)2RuC(H)(C6H4OR) (E2 (71% yield), R = CH(Me)(C(O)OMe); M2 (58% yield), R = CH(C(O)OMe)2; Kme2 (88% yield), R = CH2C(O)Me; Ket2 (63% yield), R = CH2C(O)Et); C2 (58% yield), R = C(Me)CN) were prepared by the reaction of the Grubbs second-generation catalyst (H2IMes)(Cl)2Ru(CHPh)(PCy3) (G2) with the appropriate ortho-substituted ether H(Me)CCHC6H4OR in the presence of CuCl as a phosphine scavenger. The X-ray structures of these complexes reveal that the terminal oxygen of the ester, ketone, or malonate group installed as the terminal substituent of the benzylidene ether is coordinated to the metal, giving an octahedral structure. In contrast, the nitrile group of the complex C2 remains uncoordinated. Even more sophisticated complexes, incorporating both a coordinating group R (ester or ketone) as a terminal substituent of the ether and an electron-withdrawing group X (NO2 or C(O)Me) on the aromatic ring, were synthesized: (H2IMes)(Cl)2RuC(H)[(C6H3X)OR] (NE2 (69% yield), R = CH(Me)(C(O)OMe), X = NO2; KE2 (57% yield), R = CH(Me)(C(O)OMe), X = C(O)Me; KK2 (56% yield), R = CH2C(O)Me, X = C(O)Me). All these complexes were used as catalyst precursors in standard metathesis reactions and compared with commercial catalysts such as Grubbs II (G2), Grubbs/Hoveyda II (H2), and Nitro catalyst (N2). The catalysts NE2, KE2, N2, and M2 exhibit excellent performances in the RCM of diallyl malonate or the RCM of diallyltosylamide at 0 °C. The catalysts M2, N2, and Kme2 are also very efficient for the RCM of allyl methallyl malonate to yield a trisubstituted olefin. The same complexes are also active for cross-metathesis, and several low-loading tests are also presented. Finally, a very challenging example of the synthesis of BILN 2061 (hepatitis C virus HCV NS3 protease inhibitor having antiviral effect in infected humans) is presented, where the best performances are recorded with E2 (95% conversion) and N2 (93% conversion). The enhanced activity of the reported complexes is understood in terms of their enhanced stability and their ability to liberate progressively and continuously the active species in solution.

Helicenes as Chirality‐Inducing Groups in Transition‐Metal Catalysis: The First Helically Chiral Olefin Metathesis Catalyst

“…The alternative approach to chiralN HC ligands requires one or two centers of chirality in the backbone. [39] In the presence of the phosphine scavenger CuCl [40,41] the helically chiralRu-alkylidene (M)-6 was obtained. [11,12] In catalysts such as 5a,t he stereoinduction relies on as o-called "gearing"-effect: [13][14][15] the Naryl substituents rotate out of plane to avoid steric interaction with the substituentsi nt he backbone.I nt he process, one of the two enantiotopicc oordinationh emispheres becomes more crowded than the other.…”

“…[29,30] As ap roof-of-concept we investigated the feasibility of asymmetrico lefin metathesis reactions, [14,[31][32][33][34][35] catalyzed by a helicallyc hiral metathesis initiator,w hich was designed according to the general principles outlined above and summarized in Figure 1. [39] In the presence of the phosphine scavenger CuCl [40,41] the helically chiralRu-alkylidene (M)-6 was obtained. [26] To avoid steric overcrowding of the NHC ligand,w hich might result in problems upon ligationa nd low catalytic activity, [11] we aimed at the synthesis of an unsymmetrical NHC with just one N-helicenyl substituent.…”

“…Unsymmetrical NHCs can be used to modulate steric congestion around the metal centera nd influence conformational preferencesa rising from ar otation around the Ru-NHC bond. [39] In the presence of the phosphine scavenger CuCl [40,41] the helically chiralRu-alkylidene (M)-6 was obtained. In this method, oxazolium salts such as 3 are reactedw ith amines, in our case 2-amino [6]helicene (M)-1.…”

An Ion‐Responsive Pincer‐Crown Ether Catalyst System for Rapid and Switchable Olefin Isomerization

“…Control over ligand substitution would provide amethod for optimizing catalysis and tuning reactivity,b ut general methods to tune substrate binding are lacking.I ns mall organometallic catalysts,l igand hemilability provides some control over substrate access. [9][10][11] Substrate access has been most effectively controlled with supramolecular catalyst constructs that use large groups or encapsulation to physically block as ubstrate from reaching the catalyst. [8] The hemilabile donor acts as a" gate" that mediates substrate binding based on the metal-ligand bond strengths of the particular donor and the chelate size.B ut it has proven difficult to tune the degree of gating in hemilabile ligands.…”

Reactivation of a Ruthenium-Based Olefin Metathesis Catalyst

“…2 The most popular ruthenium-based olefin metathesis promoters are the seminal systems discovered by Grubbs and the highly robust catalysts introduced by Hoveyda. 3 Despite tremendous advances in catalyst design in recent years, 4 there remain some limitations to this technology including catalyst decomposition, high catalyst costs, and ruthenium contamination of the organic products. Much understanding regarding catalyst decomposition 5 has been gained and used to develop more stable systems, 6 while the issue of high catalyst costs has motivated studies to substantially decrease catalyst loadings.…”