Grubbs’s first-generation catalyst

M. Shair and co-workers were the first to apply the enyne metathesis for macrocyclization during the biomimetic synthesis of (-)-longithorone A." The two 16-membered paracyclophane building blocks, one diene and one dienophile component, were prepared using 50 mol% Grubbs s first-generation catalyst under 1 atm ethylene gas pressure. These components, after several additional steps, underwent two facile Diels-Alder cycloaddition reactions to afford the natural product. 

By their very nature, all of the metathesis catalysts should be amenable to removal by complexation with additional ligands added after completion of the metathesis step. An especially simple and straightforward procedure is to use the triol 3 (Figure 13.1) to convert the catalyst into water-soluble derivatives. The one drawback is that this method is somewhat wasteful, as a large excess is required - up to 86 equiv. of triol 3 for the removal of Grubb s first-generation catalyst, and at least 10 mol equiv. for others [15]. An aqueous wash or filtration through silica gel suffices to reduce ruthenium levels to at least below 200 ppm, and often even lower. 

Arisawa et al. reported the synthesis of quinolines 41 from dienes 39 (Scheme 26.11) [18]. RCM of dienes 39 protected by Bn, Ac, or Boc on nitrogen with Grubbs s first-generation catalyst 1 or second-generation catalyst 2 gave dihydroquinoUnes 40... 

Step 2 Grubbs s first generation ring closing metathesis (RCM) catalyst was employed. 

The short total synthesis of (+)-differolide based on a tandem enyne metathesis / [4+2] cycloaddition was accomplished by T.R. Hoye et al." The enyne metathesis was carried out on ally propynoate using Grubbs s first-generation metathesis catalyst. The catalyst was added to the substrate slowly to maintain high substrate and low ruthenium carbene concentrations. The initially formed 2-vinylbutenolide readily dimerized via a Diels-Alder cycloaddition in which the vinyl group participated as the dienophile to afford the natural product. 

Scheme 26.12 shows examples of the synthesis of pyrroles. Dieltiens et al. obtained pyrroles 43 by an RCM/oxidation sequence of diallyamines 42 in which Grubbs s second-generation catalyst 2 and chloranil (44) were used simultaneously [19]. At first, Dieltiens et al. used an RuCls catalyst system for the oxidation [19b]. However, there was a modification to use chloranil (44) because of the slow reaction rate of the RuCb catalyst system. 

ADMET polymerization of dienes containing functional groups has been explored to some extent. It appears that diene ethers such as 36 are tolerant of Schrock s W-alkylidene catalysts when undergoing ADMET polymerization, but Grubbs first-generation catalyst is required to successfully polymerize diene alcohol 37,61 because the OH group is too Lewis basic for catalysis by W- and Mo-alkylidenes.62... 

Figure 5.1 Alkene metathesis catalysts Grubbs-type first generation, second generation, and third generation. (From left side, top row to right side, second row) Grubbs-Blechert-Hoveyda catalyst, Grela s nitro derivative, and Schrock-type catalyst [7-11].

Figure 27 Grubb s first and second generation catalysts.

Hoveyda and coworkers [227] used a domino process to give chromanes 6/3-8 by treatment of 6/3-7 in the presence of ethylene. One of the first-generation Grubbs catalyst 6/3-9 and one of Blechert s [228] early examples allowed the synthesis of bicyclic compounds of different sizes, depending on the length of the tether thus, the reaction of 6/3-10 led to 6/3-11 using 30 mol% of the Schrock Mo complex 6/3-12. 

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