Highly Efficient Olefin-Metathesis Catalysts - Pharmaceutical Technology

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Highly Efficient Olefin-Metathesis Catalysts
The authors describe the Piers' catalysts and detail latest progress in olefin-metathesis catalyst technology.


Pharmaceutical Technology


Ethenolysis


Reaction 2
Ethenolysis involves the CM of ethylene and an internal olefin to generate terminal olefins. The ethenolysis of soybean oil to produce 9-decenoic acid is of significant interest to the chemical industry as an antimicrobial agent and as a monomer for polymer-industry applications (24–26). More recently, reports on the synthesis of additional biologically active molecules involving CM reactions of ethylene with internal olefins have been published as well (27). Given the high reactivity of Piers' catalysts with ethylene, we were interested in exploring their use for the ethenolysis of seed oils. This use is important as natural seed oils represent a renewable source of olefinic raw materials that can provide atom-efficient and environmentally friendly products. The affordability of these olefinic sources, coupled with their worldwide availability and inherent functionality, has already contributed to their use in several areas (24). Olefin metathesis offers new and exciting opportunities for the conversion of these unsaturated seed oils into commodity chemicals that can have wide-ranging applications.


Reaction 3
Ethenolysis can be complicated by secondary metathesis reactions (secondary processes generate undesired internal olefins) and by the self-metathesis of internal olefins. For an ethenolysis of methyl oleate model reaction, see Reaction 1, along with a competing self-metathesis process, see Reaction 2.


Reaction 4
Piers' Catalyst 1b (see Figure 1) demonstrated very good selectivity for the desired ethenolysis products, while Piers' Catalyst 2b (see Figure 1) led to the formation of significant amounts of self-metathesis products, and thus, low ethenolysis selectivity.


Figure 6 (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
The same trend was observed for Grubbs Catalysts 3 and 4 (see Figure 4) (28). The catalytic performance of Piers' Catalyst 1b and Grubbs Catalyst 3 for the ethenolysis of methyl oleate were compared at 20 C and 40 C, using toluene as the solvent and 0.02 mol% catalyst under 150 psi ethylene (see Figure 6). Data points were taken at 2 h (29). As shown in Figure 6, Catalysts 1b and 3 showed similar efficiency at 40 C. At 20 C, however, Catalyst 1b is much more active than Catalyst 3.

Ring-closing metathesis


Figure 7 (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
RCM is one of the most used metathesis reactions for the synthesis of biologically active molecules. Studies in the Piers' group and at Materia have shown the advantage of Piers' catalysts. The high efficiency of Piers' Catalyst 2a (see Figure 1) for RCM at low temperature (0 C) was initially reported by Piers and coworkers (6, 7). Using RCM of diethyl diallymalonate as a model reaction (see Reaction 3), they have shown that Catalyst 2a (see Figure 1) outperformed Catalyst 1a (see Figure 1) as well as the other olefin-metathesis catalysts.


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