Hoveyda-Grubbs

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]. 

Fig. 3 Olefin metathesis catalysts Schrock tungsten (Cl) and molybdenum (C2) alkylidene complexes, Grubbs first- (C3) and second-generation (C4) catalysts, Hoveyda-Grubbs second-generation catalyst (C5), and Grubbs third-generation catalyst (C6)...

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... 

CM reactions with terpenoids containing two double bonds such as citronellene are hampered by low yields because of RCM competition among other side reactions. Mauduit et al. performed the CM of several terpenoids with n-butyl acrylate and crotonaldehyde using Hoveyda-Grubbs type catalysts containing an aminocarbonyl function [89]. Yields below 43% were obtained in all cases with 1 mol% catalyst. In contrast to these results, the hydrated masked form of citronellene, i.e., dihydromyrcenol, gave 71% yield of the CM product. It was thus proposed that in order to avoid selectivity problems in the CM of terpenoids containing two double bonds, masked derivatives can be used followed by a simple elimination step to recover the olefin functionality. 

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... 

In our new antithetic plan (Scheme 21), Weinreb s oxazolidinone 77 would remain a key synthetic objective. However, the Hoveyda-Grubbs reaction would now be applied to the diene 88. The new route would also block 0(4) of the vinyl aldehyde precursor with a TES ether to prevent hemiacetal formation from occurring. The crucial Vasella... 

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