Parts–per–million of ruthenium catalyze the selective chain–walking reaction of terminal alkenes

The chain–walking of terminal alkenes (also called migration or isomerization reaction) is currently carried out in industry with unselective and relatively costly processes, to give mixtures of alkenes with significant amounts of oligomerized, branched and reduced by–products. Here, it is shown that part–per–million amounts of a variety of commercially available and in–house made ruthenium compounds, supported or not, transform into an extremely active catalyst for the regioselective migration of terminal alkenes to internal positions, with yields and selectivity up to >99% and without any solvent, ligand, additive or protecting atmosphere required, but only heating at temperatures >150 °C. The resulting internal alkene can be prepared in kilogram quantities, ready to be used in nine different organic reactions without any further treatment.


S5
added and stirring was continued for 5 min. Acetonitrile (6 mL) was added and stirring was continued for further 5 min. Following the general procedure described above for the isomerization reaction, a mixture of neat 2 (356 mg, 2 mmol) and Ru(methylallyl)2(COD) (3.0 g, 0.0005 mol%) was heated in a 2 ml vial equipped with a magnetic stir bar at 200 °C. After cooling the mixture was added to round-bottomed flask with the reaction mixture and the resulting slurry was stirred for 1 h. The mixture was poured onto 15 mL sat. NaHCO3 and 20 mL sat. Na2S2O3 solution. Phases were separated and the aqueous layer was extracted with ethyl acetate. The combined organic phases were dried over MgSO4, filtered and concentrated under vacuum. The crude product was purified by chromatography on a silica gel (30% AcOEt in hexane) to give 297 mg (70%) of 32 as a yellow oil 46 .
Oxidation. Following the general procedure described above for the isomerization reaction, a mixture of neat 2 (89 mg, 0.5 mmol) and Ru(methylallyl)2(COD) (0.8 g, Epoxidation. Following the general procedure described above for the isomerization reaction, a mixture of neat 2 (89 mg, 0.5 mmol) and Ru(methylallyl)2(COD) (0.8 g,  Supplementary Figure 11. Influence in the isomerization reaction of the addition of HCl gas (acid), DBU (base), product 2 and substrate 1 during reaction, for the isomerization of methyl eugenol 1 to methyl isoeugenol 2 catalyzed by 50 ppm of Ru(methyallyl)2(COD) at 150 ºC. Error bars represent a 5% uncertaintity. For orange, green and yellow line, the reaction was carried out with the catalyst and acid or base. For red, gray, blue line, reaction was carried out with acid or base but without catalyst. S14 Supplementary Figure 12. FT-IR spectra for the isomerization of methyl eugenol 1 (black line) to methyl isoeugenol 2 catalyzed by 300 ppm of Ru3(CO)12 (red line) at 150 ºC and different reaction times. The inset shows the diagnostic area, where the complete disappearance of the CO peaks from the beginning of the reaction is observed, although somewhat blurred by starting material alkene traces.
Comments: The determination of the active Ru species for the isomerization reaction was difficult due to the tiny amounts of metal employed, which is below the detection limit of many techniques, however, some measurements with high sensibility towards the metal, either soluble or supported, were informative. For instance, the isomerization of 1 to 2 catalyzed by Ru3(CO)12 was followed by Fourier-transformed infrared spectroscopy (FTIR, Fig. S12) and the peak associated to CO seemingly disappears from the beginning of the reaction, despite impurities of alkene 1 partially hide the peak. Besides, it was found that the Ru catalyst (10 ppm) co-distils with alkene product 24 at kg scale, which supports the formation of an alkene-Ru complex after total exchange of the CO ligands. complex. Ru II Ru III Ru II Ru III * * * * S17 signals can be attributed to the apparently irreversible Ru II to Ru III oxidation, presumably involving some MeCN-coordinated form. The CV of the Ru3(CO)12 complex presents an ill-defined anodic wave at ca. -0.2 V preceding a prominent anodic current ca. 0.5 V. As a result, in the subsequent negative-going potential scan, a cathodic peak appears at -0.6 V. This signal, quite similar to the third cathodic wave recorded for the Ru III complex, can be assigned to the reduction of the Ru II (MeCN)n species previously generated in the anodic scan. In all cases, however, after reaction with isoeugenol, the voltammograms collapse to a quite similar profile consisting of a unique, well-defined anodic wave at -0.30 V in the initial anodic scan. These signals are a blueprint of Ru II species, as observed for Ru(methylallyl)2(COD) and their common appearance suggests the formation of a common Ru II per-alkene complex 45 regardless the initial Ru source, either by oxidation of Ru 0 or reduction of Ru III under the heating reaction conditions. S18 2050 2100 2150 2200

Supplementary
Wavenumber (cm -1 ) Comments: The similar catalytic results observed above for soluble and supported Ru suggests that the Ru-supported solid catalyst can also be employed to unveil the true Ru catalytic species. Figure S15 shows the HF1 region (2050-2200 cm -1 ) of the lowtemperature CO-probe FTIR spectrum of RuCl3 impregnated on silica (Ru-SiO2), carried out after performing the Ru-catalyzed isomerization of 1-pentene in the IR chamber, in order to avoid any contact with the atmosphere. Ru-SiO2 was selected for this study because it is known that Ru is present on surface in a variety of oxidation states, from Ru III to Ru 0 , and the HF1 region contains diagnostic signals for all these oxidation states 46 .

Ru III
The results show that the Ru n+ sites at 2134 cm -1 do not admit CO after the isomerization reaction, without exposition to the atmosphere, since the alkenes are strongly attached to this site. In contrast, other Ru n+ sites (2090 and 2057 cm -1 ) re-admit CO just after reaction, which indicates that the alkenes are barely coordinated. If the sample is then exposed to the atmosphere and washed, as in a regular batch procedure, the Ru n+ sites at 2134 cm -1 re-appear and even increase its relative number to the other metal sites. Despite the exact interpretation of a Ru-CO FT-IR spectrum is not conclusive with different COcoordinated species co-existing, one can say in a first approximation that the Ru n+ sites at 2134 cm -1 are labile during the catalysis, and since these sites have been previously assigned to species compatible with Ru II , while the inactive Ru sites at 2090 and 2057 cm -1 have been assigned to Ru 0 and Ru I-III , respectively 47 , Ru II seems the active Ru oxidation state.