Abstract
Formation of tetrasubstituted C–C double bonds via olefin metathesis is considered very challenging for classical Ru-based complexes. In the hope to improve this condition, three ruthenium olefin metathesis catalysts bearing sterically reduced N-heterocyclic carbene (NHC) ligands with xylyl “arms” were synthesized, characterized using both computational and experimental techniques, and tested in a number of challenging reactions. The catalysts are predicted to initiate much faster than the analogue with mesityl N-substituents. We also foreboded the rotation of xylyl side groups at ambient temperature and the existence of all four atropoisomers in the solution, which was in agreement with experimental data. These catalysts exhibited high activity at relatively low temperatures (45–60 °C) and at reduced catalyst loadings in various reactions of sterically hindered alkenes, including complex polyfunctional substrates of pharmaceutical interest, such as yangonin precursors, chrysantemic acid derivatives, analogues of cannabinoid agonists, α-terpineol, and finally a thermally unstable peroxide.
Highlights
Well-defined ruthenium olefin metathesis catalysts are widely utilized in modern organic chemistry due to their universality and good stability toward air and moisture.[1−4] Despite the fact that the most popular ruthenium catalysts Ru1−Ru4 (Figure 1a) enabled the synthesis of a variety of products with differently substituted double bonds, the effective and economically viable synthesis of crowded alkenes still remains a challenge.[5,6]
This key observation led to the development of other catalysts bearing sterically reduced N-heterocyclic carbene (NHC) ligands (Figure 1b).[5,6,11−13] in many cases, the improved activity in the formation of substituted C−C double bonds was at the expense of the catalyst’s thermal stability
We report on the synthesis and characterization of indenylidene-type Ru-complexes stabilized by new NHC ligands bearing N-xylene NHC side groups, as well as their characterization supported by computational methods (DFT B3LYP-D3 for geometry optimization, M06-D3 for Gibbs free energy evaluation, and SAPT2+3 for very accurate interaction energy, see the Supporting Information) and catalytic activity evaluation in a set of challenging metathesis reactions, including complex polyfunctional substrates
Summary
Well-defined ruthenium olefin metathesis catalysts are widely utilized in modern organic chemistry due to their universality and good stability toward air and moisture.[1−4] Despite the fact that the most popular ruthenium catalysts Ru1−Ru4 (Figure 1a) enabled the synthesis of a variety of products with differently substituted double bonds, the effective and economically viable synthesis of crowded alkenes still remains a challenge.[5,6] Compared to Schrock’s highly active molybdenum alkylidenes (e.g., Mo1),[7] the formation of sterically hindered C−C double bonds was always the Achilles’ heel of ruthenium metathesis catalysts. RCM of substrates 1, 9, and 11 catalyzed by Ru8 prepared by Cazin et al led to good results but required higher temperatures (120 °C) and longer reaction times (8 h) according to the published report.[15] In the case of tosylamine derivative 13, a precursor of seven-membered ring product 14, catalyst Ru11 gave complete conversion and a high isolated yield of 94%, a loading of 1 mol % was necessary (the catalyst was added in four separated portions of 0.25 mol % each) (Table 4, entry 4).
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