Phosphine-Based Z-Selective Ruthenium Olefin Metathesis Catalysts

Abstract

Whereas a number of highly Z-selective ruthenium-based olefin metathesis catalysts bearing N-heterocyclic carbene ligands have been reported in recent years, Zselectivity has so far been difficult to achieve for phosphinebased catalysts. Guided by predictive density functional theory (DFT) calculations, we have developed phosphine-based ruthenium olefin metathesis catalysts giving 70−95% of the Zisomer product in homocoupling of terminal alkenes such as allylbenzene, 1-octene, allyl acetate, and 2-allyloxyethanol. Starting from a moderately selective catalyst, [P(Cy) 3 ](-S-2,4,6-Ph-C 6 H 2 )ClRu(CH-o-O i PrC 6 H 4 ) (4, Cy = cyclohexyl, i Pr = isopropyl), obtained by substituting a chloride of the Hoveyda−Grubbs first-generation catalyst with 2,4,6-triphenylbenzenethiolate, we moved on to replace Cl and PCy 3 by chelating, anionic phosphine ligands. Such ligands increase selectivity by limiting rotation around the P−Ru bond and by specifically directing the steric bulk of the phosphine substituents toward the selectivity-inducing thiolate ligand. In particular, DFT calculations predicted that o-(dialkylphosphino)phenolate ligands should improve selectivity and activity compared to 4. The most promising of these compounds (8b), based on the o-(ditert-butylphosphino)phenolate ligand, directs the two P-bonded tert-butyl substituents toward the 2,4,6-triphenylbenzenethiolate and has little steric hindrance trans to the thiolate. This compound metathesizes terminal olefins such as allylbenzene and 1-octene with Z-selectivities above 80% and allylacetate above 90%. Although these phosphine-based ruthenium monothiolate catalysts in general achieve somewhat lower activities and Z-selectivities than their second-generation counterparts, they also offer examples giving less substrate and product isomerization and thus higher yields. ■ INTRODUCTIONOlefin metathesis is an important carbon−carbon coupling method of the organic chemist's toolbox. It is, for instance, used extensively in the synthesis of natural products 1−3 and polymers 4,5 and in oleochemistry 6 and has found applications even in peptide and protein modifications. 7−10 Metathesis of terminal olefins to give disubstituted olefins typically results in mixtures of the Z-and E-isomers, with the thermodynamically more stable E-isomer usually being the major product. Separating these isomers is costly and often challenging, which may hamper the assessment of their activity and the application of olefin metathesis in medicinal chemistry. 11−13 In recent years, several catalysts with enhanced Z-selectivity have been reported. The first highly Z-selective catalysts, based on molybdenum and tungsten, were developed by Schrock and Hoveyda. 14−16 More recently, ruthenium-based counterparts, containing an N-heterocyclic carbene (NHC) chelated to the metal center via a Ru−C bond, were discovered by Grubbs and co-workers. 17−19 Highly Z-selective ruthenium-based catalysts were also developed by Hoveyda and co-workers, by replacing the chloride ligands of the Hoveyda−Gru...

Acid‐Assisted Direct Olefin Metathesis of Unprotected Carbohydrates in Water

“…[10][11][12][13][14][15][16][17][18][19][20] Ever since the introductiono ft he olefin metathesis reaction, much efforth as been invested in improving the catalysts. This has resulted in the appearance of commercially available and bench-stable catalysts, [21][22][23][24][25] Z-selective catalysts, [26][27][28] and highly active catalysts for ethenolysis. [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.…”

Recent Developments in Z‐Selective Olefin Metathesis Reactions by Molybdenum, Tungsten, Ruthenium, and Vanadium Catalysts

“…Thus, homocoupling of 1‐octene, allyl acetate and 4‐phenyl‐1‐butene produced 77–95% Z ‐products 73 and 24–47% yield after 8 h at 20 °C (Scheme 34). [97] …”

Recent Advancements in Stereoselective Olefin Metathesis Using Ruthenium Catalysts

“…Additional studies were aimed at understanding the effect of changing the identity of the donor ligand (NHC in 22 and 24). Phosphine supported, or first-generation, analogues of 22 ( Figure 7) were prepared, characterized crystallographically, and studied computationally but generally demonstrated lower activities and Z-selectivities [66]. …”