As society faces a future of dwindling petrochemical supplies at increasing cost, much attention has been focused on methods to degrade biomass into renewable commodity-chemical building blocks. Reported here is a powerful complementary approach that amplifies the complexity of molecular structures present in plant materials. Essential-oil phenylpropenoids are transformed via acrylate cross-metathesis into potent antioxidants that are widely used in perfumery and cosmetics, and in treating disorders associated with oxidative damage.

Phosphine-stabilized metathesis catalysts are among the most popular and widely used catalysts in organic synthesis. The second-generation Grubbs catalyst GII, in particular, dominates synthetic applications of olefin metathesis. This is commonly true even for reactions that are fundamentally incompatible with free PCy3, which is released upon entry of GII into the catalytic cycle. A leading example is cross-metathesis with electron-deficient olefins such as acrylates, for which yields are seriously degraded by a deleterious side reaction involving attack of free PCy3 on the acrylate olefin, and production of an enolate anion that decomposes the active catalyst. Here we describe a simple, powerful means of upgrading the performance of GII and its indenylidene analogue M2 to levels matching or exceeding that of the important, but more costly, phosphine-free Hoveyda catalyst HII. Key to this improvement is carrying out the reaction in the presence of a phenol-functionalized polymer resin. We demonstrate that, at standard catalyst loadings (which correspond to low concentrations of PCy3), the beneficial effect of phenol arises not from protonation of PCy3 itself, but from protonation of the enolate, thereby converting this aggressive base into an innocuous phosphonium salt. The methodology is showcased in the demanding cross-metathesis of the renewable phenylpropanoid trans-anethole with 2-ethylhexyl acrylate (an efficient route to the high-value antioxidant octylmethoxycinnamate, an active ingredient in sunscreen formulations with the tradename Octinoxate), as well as methyl acrylate, a ubiquitous and more sterically accessible coupling partner. Experiments with water-saturated toluene indicate that water cannot be substituted for the resin as a sacrificial proton donor, such treatment resulting in drastically reduced productivity. Control experiments involving macrocyclization indicate that the resin has an additional protective function beyond enolate quenching, potentially due to hydrogen bonding of polar contaminants present as impurities in the reagents or reaction medium.

No abstract

The underexploited biorenewable p-cymene is employed as a solvent for the metathesis of various substrates. p-Cymene is a nontoxic compound that can be obtained in large amounts as a side product of the cellulose and citrus industry. For the cross-metathesis of estragole with methyl acrylate, this solvent prevents the consecutive double-bond isomerization of the product and affords the best yield of all solvents tested. Undesired consecutive isomerization is a major challenge for many substrates in olefin metathesis, including pharmaceutical precursors, and the use of p-cymene as a solvent may be a way to prevent it. This solvent results in a better metathesis performance than toluene for the three substrates tested in this work, matching its performance for two other substrates.

No abstract