Handbook of Functionalized Organometallics Applications in S

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11 Polyfunctional Metal Carbenes for Organic Synthesis
Metal tuning of tetracoordinated metal carbenes revealed that replacement of tungsten
for molybdenum renders the metal carbene a more selective although less reactive
species. Molybdenum carbene 142b has emerged as a well-defined metathesis catalyst
[69] that dominated the area until Grubbs developed ruthenium-based complexes
highlighted by his first-generation catalyst 143 (Scheme 11.35) [70].
R
Ph
R
O
Mo
R
O N
R
142a : R = CH 3, 142b : R = CF 3
Cl
Cl
PCy 3
Ru
PCy 3
143
Scheme 11.35 Schrock's molybdenum carbene 142b and
Grubbs' first-generation ruthenium carbene 143 as the first
routinely applied olefin metathesis catalysts.
These two types of complexes combine high activity with an impressive tolerance
of polar functional groups and have made olefin metathesis one of the key
reactions in modern organic synthesis. They, and higher-generation Grubbs catalysts,
including a strongly coordinated N-heterocyclic (NHC) coligand and/or a
hemilabile chelating carbene ligand, are widely applied in the synthesis of fine
chemicals and in polymer chemistry and allowed the development of a variety of
metathesis reaction patterns including cross-metathesis (CM) [58d], acyclic diene
metathesis (ADMET) polymerization, ring-closing metathesis (RCM) and ringopening
metathesis polymerization (ROMP) [58]. Moreover, the metathesis concept
has been extended to enynes [71] and alkynes [72].
Compared to Grubbs catalyst 143, the Schrock-type catalysts like commercially
available 142b are more sensitive to moisture and oxygen and less compatible
with functional groups; on the other hand, they are generally more reactive and,
for instance ± in contrast to 143 ± allow for the formation of tri- and tetrasubstituted
double bonds.
The basics and the synthetic potential of olefin metathesis has been recently presented
in a comprehensive handbookand several reviews [58]. Thus, this chapter will
be restricted to demonstrate the scope and flexibility of this type of reaction in the total
synthesis of a complex natural product skeleton such as epothilone. The first total syntheses
of these antitumor-active 16-membered macrolactones were based on a ringclosing
metathesis (RCM) strategy (Scheme 11.36) [73]. Grubbs catalyst 143 has been
used for the construction of the endocyclic 1,2-disubstituted C12±C13 double bond in
epothilone C 148 that, after epoxidation, affords epothilone A 150 [74]. In this
approach, ruthenium carbene 143 is more efficient than Schrockmolybdenum catalyst
142b [75a]. However, the RCM-route to epothilone D 149, the desoxy precursor
of epothilone B 151 bearing a trisubstituted C=C bond, requires the molybdenum
carbene catalyst 142b; attempts to initiate ring-closure with 143 failed [75].
Ph