Grubbs’ catalysts advantages

The most straightforward application of the Grubbs reaction is to effect homologation of a terminal vinyl group. One concern with the use of the second generation Grubbs catalyst 3 is the cost, about 100/mmol. In conjunction with a total synthesis of the macrolide RK-397, Frank McDonald of Emory reported (J. Am. Chem. Soc. 126 2495, 2004) that the conversion of 1 to 2 required 10 mol % of 3, but that it proceeded efficiently with just 2 mol % of the Hoveyda Ru catalyst 4 (J. Am. Chem. Soc. 122 8168,2002). The alkene so prepared was cleanly trans. An advantage of 4 is that it avoids the use of the expensive PCy,. 

The two-directional tandem metathesis of 1 to 2 proceeded smoothly using 20 mol % of the second generation Grubbs catalyst (now commercially available only from Aldrich and from Materia) under an atmosphere of ethylene. The conversion of 2 to 3 took advantage of the differing reactivity of the two ketones. Addition of hydride to 2 from the less hindered face of the less hindered ketone delivered 4. 

A great advantage of Grubbs catalysts is that they are tolerant of a large range of functional groups, thus... 

Fully intramolecular [2 + 2 + 2] cyclization of triynes affords tricyclic products with complete chemo- and regioselectivity. Despite this advantage, this method is underdeveloped, which is probably due to the diminished accessibility of the triyne substrates. Peters and Blechert reported the first ruthenium-catalyzed fully intramolecular cyclotrimerization using the metathesis cascade strategy with Grubbs catalyst [23]. Later, Yamamoto et al. demonstrated that complex 6 efficiently catalyzes the cyclization of various triynes [14]. Examples of 1,6,11-triyne cyclization are summarized in Table 3.11. As an example, diether 58 (X = = O, R = H) underwent [2 + 2 + 2]... 

Although the Grubbs ruthenium benzylidene 17 has a significant advantage over the Schrock catalyst 3 in terms of its ease of use, the molybdenum alkylidene is still far superior for the cross-metathesis of certain substrates. Acrylonitrile is one example [28] and allyl stannanes were recently reported to be another. In the presence of the ruthenium catalyst, allyl stannanes were found to be unreactive. They were successfully cross-metathesised with a variety of alkenes, however, using the molybdenum catalyst [39] (for example Eq. 20). 

For the cross-metathesis of functionalised alkenes the ill-defined classical catalyst systems currently offer very few advantages (cost and heterogeneous catalysis) over the more functional group tolerant Schrock and Grubbs alkylidene... 

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