Catalyst Grubbs-Hoveyda

The most widely used catalysts for RCM are Grubbs ruthenium catalyst 9 and its second generation analogue 10, as well as first and second generation Hoveyda-Grubbs catalysts 11 and 12 (Fig. 6) [38]. The latter have superior stability and reactivity, expanding the applicability of the method considerably. Schrock molybdenum catalyst 13 has also been described for macrocy-clization [38]. 

The ene-yne CM of fatty acid-derived terminal alkenes with several alkyne derivatives was shown by Bruneau et al. [75], These reactions, which led to renewable conjugated dienes, were performed in a one-pot two-step procedure. In the first step, the ethenolysis of methyl oleate was performed in the presence of the first-generation Hoveyda-Grubbs catalyst (2.5 mol%) using dimethyl carbonate as solvent at room temperature. After completion of the ethenolysis (90% conversion), C4 (1 mol%) and the corresponding alkyne (0.5 equivalents with respect to olefins) were added and the reaction was run at 40°C for 2 h (Scheme 9). The desired dienes were thus obtained in high yields close to the maximum theoretical value (50%). Moreover, in order to maximize the formation of functional dienes, the same reaction sequence was applied to the diester obtained by SM of methyl oleate. In this way, the yield of functional dienes was increased up to 90% depending on the... 

Effective CM of allyltrimethylsilane with allyl alcohols has been reported by Cossy et al. [74] and was achieved with the Hoveyda-Grubbs catalyst (Eq. 42). 

A series of CMs of a,/i-unsaturated carbonyl compounds with allylsilanes have been tested in the presence of the Hoveyda-Grubbs catalyst (Eq. 44) [76]. Functionalized allylsilanes have been obtained in moderate-to-good yield and very good stereoselectivity in favour of the E isomer. Examples have proved a high functional group tolerance of the Hoveyda-Grubbs catalyst. 

Generation Grubbs catalyst 2" Generation Grubbs catalyst Hoveyda-Grubbs catalyst... 

The remaining lone pair on carbon (which is not delocalized) can coordinate to Ru, just like the phosphine lone pair, giving a catalyst known as Grubbs IT (the second generation of the Grubbs T we made use of in the metathesis described above). In another widely used catalyst (known as the Hoveyda-Grubbs catalyst ) the second phosphine is also replaced by intramolecular coordination. 

At another GlaxoSmithKline site, in the USA, the development of a drug for osteoporosis and osteoarthritis required a seven-membered heterocycle with two controlled chiral centres. This time the Hoveyda—Grubbs catalyst had to be used but the loading is very low indeed. Notice also that a free OH group does not interfere. 

E. de Brito Sa , J.M.E. de Matos, Ring closing metathesis by Hoveyda-Grubbs catalysts a theoretical approach of some aspects of the initiation mechanism and the influence of solvent. Inorg. Chim. Acta 426, 20-28 (2015)... 

When enyne 298 was treated with second-generation Hoveyda-Grubbs catalyst 299 in the presence of methyl vinyl ketone (300), the first step was a ring[Pg.561]

II) first-generation Grubbs catalyst (III) second-generation Grubbs catalyst and (IV) second-generation Hoveyda-Grubbs catalyst (HG-II) [5]. 

Figure 21.2. Relative activities of variants of the Hoveyda-Grubbs catalyst.

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