The design, synthesis, stability, and catalytic activity of nitro-substituted Hoveyda-Grubbs metathesis catalysts are described. The highly active and stable meta- and para-substituted complexes are attractive from a practical point of view. These catalysts operate in very mild conditions and can be successfully applied in various types of metathesis [ring-closing metathesis, cross-metathesis (CM), and enyne metathesis]. Although the presence of a NO(2) group leads to catalysts that are dramatically more active than both the second-generation Grubbs's catalyst and the phosphine-free Hoveyda's carbene, enhancement of reactivity is somewhat lower than that observed for a sterically activated Hoveyda-Grubbs catalyst. Attempts to combine two modes of activation, steric and electronic, result in severely decreasing a catalyst's stability. The present findings illustrate that different Ru catalysts turned out to be optimal for different applications. Whereas phosphine-free carbenes are catalysts of choice for CM of various electron-deficient substrates, they exhibit lower reactivity in the formation of tetrasubstituted double bonds. This demonstrates that no single catalyst outperforms all others in all possible applications.

The development of accessible metathesis catalysts that combine high activity with excellent tolerance to a variety of functional groups has been key to the widespread application of olefin metathesis in organic synthesis. In spite of the general superb application profile of the ruthenium carbene 1 a, its limited thermal stability and the low activity towards substituted double bonds are major drawbacks. [1] Specifically, the preparation of substituted olefins with electron-withdrawing functionality (such as a,b-unsaturated carbonyl compounds, nitriles, sulfones, etc.) through cross metathesis (CM) with terminal alkenes remains a difficult task. The newly introduced highly active ruthenium alkylidene complexes with sterically demanding N-heterocyclic carbene (NHC) [3] ligands have dramatically alleviated this limitation. [2] Compounds of type 1 b and 1 c were found to be efficient catalysts in the reactions of previously metathesisinactive substrates, including a,b-unsaturated olefins (Scheme 1). [2,4] Hoveyda and co-workers have recently established 2 as a remarkably robust complex, which promotes olefin metathesis by a ™release±return∫ mechanism. [5] Despite the fact that phosphane-free catalyst 2 was found to be more sluggish than 1 b, [6] it has a superior general reactivity toward electrondeficient olefins. [7] The fact that the ruthenium carbene 2 is air-stable and can be easily purified by standard silica-gel chromatography and recycled after the reaction is a particularly appealing facet of this chemistry. [5,8] Blechert and Wakamatsu have shown recently that the replacement of the isopropoxystyrene ™ligand∫ in 2 by binolor biphenyl-based styrene results in a large improvement in the activity of the catalyst, as complexes 4 and 5 are much more reactive than both 2 and the ™second-generation∫ Grubbs catalyst 1 b. [9] During our project aimed at the preparation of the immobilized metathesis catalyst, we prepared the bromo analogue 3 of Hoveyda©s catalyst 2. [10] Although the reactivity patterns of complexes 2 and 3 were in general similar, the latter system was visibly less reactive in some model reactions. [4b] This result once again shows that even a small variation in the isopropoxystyrene ™ligand∫ can result in a change in the activity of the catalyst. Impressed by results published recently by Blechert and Wakamatsu, [9] we decided to investigate the electronic effects in the isopropoxystyrene ™ligand∫ sphere of complex 2 which are not fully understood. [11] At first, we decided to test whether a decrease in the electron density of the styrene part of 2 would result in increased catalyst reactivity.As illustrated in Scheme 2, we used commercially available 6 as a starting material for preparation of the corresponding ruthenium carbene 9. The green microcrystalline complex 9 was easily obtained in good yield (83 %) by the reaction of 1 b (1 equiv) and CuCl (1 equiv) with styrene 8 (1 equiv), followed by routine flash chromatography. Having secured an efficient method for the preparation of complex...

The data reported in this paper demonstrate that great care must be taken when choosing an appropriate catalyst for a given metathesis reaction. First-generation catalysts were found to be useful in the metathesis of sterically unhindered substrates. Second-generation catalysts (under optimised conditions) showed good to excellent activities toward sterically hindered and electron-withdrawing group (EWG)-substituted alkenes that do not react using the first-generation complexes. A strong temperature effect was noted on all of the reactions tested. Interestingly, attempts to force a reaction by increasing the catalyst loading were much less effective. Therefore, when possible, it is suggested that metathesis transformations should be carried out with a second-generation catalyst at 70 degrees C in toluene. However, different second-generation catalysts proved to be optimal for different applications and no single catalyst outperformed all others in all cases. Nevertheless, some empirical rules can be deduced from the model experiments, providing preliminary hints for the selection of the optimal catalysts.