Figure 5 (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
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Two recent, excellent examples of olefin metathesis from the Stoltz group demonstrate the usefulness of Catalyst 6 (see Figure
5) for natural-product synthesis. Catalyst 6 was successfully used for a key RCM step in the synthesis of elatol, a natural
product from chamigrene, which has broad antimicrobial activity (21). In another recent example, the Stoltz group reported
the synthesis of (–)–Cyanthiwigin F where Catalyst 6 completed both a RCM and CM step in the same reaction flask (22).
The metathesis catalysts shown in Figures 4 and 5 are typical 5-coordinate ruthenium olefin-metathesis catalysts. The first
step in the metathesis reaction involving these catalysts is the dissociation of the donor ligand trans to the phosphine or the N -heterocyclic carbene ligand , generating the catalytically active 4-coordinate, 14-electron species. This 14-electron species binds an olefin, forms a
metallocyclobutane ring, and productively undergoes a cycloreversion to yield the new olefinic product. Efficient dissociation
of the donor ligand and olefin binding are key for fast initiation of these catalysts.
Piers' catalysts are another new addition to the ruthenium olefin-metathesis catalyst family. Piers' catalysts adopt a pseudo-tetrahedral
geometry and possess an open coordination site trans to the phosphine (see Catalyst 1, Figure 1) or the N -heterocyclic carbene ligand (see Catalyst 2, Figure 1) (6, 7). This open coordination site eliminates the need for any ligand
dissociation prior to olefin coordination. As such, olefin binding and activation is anticipated to be more facile with Piers'
catalysts.
Catalysts 1 and 2 are highly active for the metathesis of terminal olefins. For example, Catalyst 2a reacts with ethylene
at –50 °C (8). Kinetic studies on the initiation of metathesis with o –isopropoxystyrene as a test substrate indicated that the initiation rate of Catalyst 2a (see Figure 1) at –10 °C is similar
to the initiation rate of the Grubbs catalyst (see Catalysts 3 and 4, Figure 4) at 35 °C (6). Piers' catalysts offer the additional
advantage of running metathesis reactions at lower temperatures when the substrates may be temperature sensitive or to suppress
double-bond migration.
Use of Piers' olefin-metathesis catalysts
The Piers' group is developing these novel catalysts and, along with Materia, is exploring their use for a range of industrial
applications, including ethenolysis, RCM, CM, self-metathesis, and ring-opening metathesis polymerization (ROMP). In general,
Catalysts 1 and 2 (see Figure 1) are more active than the Grubbs catalysts (see Catalysts 3 and 4, Figure 4) for the metathesis
of terminal olefins. In addition, Piers' catalysts are very active at low temperatures, and thus, are of interest to those
applications where low temperatures are desired. Not too surprising, Catalysts 1 and 2 are somewhat slower for metathesis
reactions involving only internal olefins such as the CM of internal olefins, which is likely due to the steric bulk of the
cationic PCy3 alkylidene moiety (23).
Reaction 1
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The high efficiency of Piers' catalysts for metathesis involving ethylene and other terminal olefins is particularly valuable
for the industrially significant ethenolysis and RCM reactions described below.
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