Chemistry Reference
In-Depth Information
Me
Me
N
N
Mo
Mo
O
O
O
O
SiMe
3
Fe
Fe
Me
3
Si
Me
3
Si
Me
3
Si
Matched enantiomer
Mismatched enantiomer
Figure 8E.4.
Proposed model for enantioselectivity in the catalytic enantioselective RCM of
ferrocenes.
The stereochemical outcome of the reaction depicted in Equation 8E.1 can be ratio-
nalized through the proposed mechanistic model shown in Figure 8E.4 [31]. After initia-
tion at the terminal olefi n of the substrate, the catalyst may coordinate to the
1,1 - disubstituted olefi n. In the mismatched enantiomer, steric interactions between the
substituent on the cyclopentadienyl moiety and the
tert
-butyl group of the chiral ligand
disfavor formation of the molybdacyclobutane. In the matched enantiomer, a proton
takes the place of the bulky trimethylsilyl group, allowing for facile formation of the
metallacycle. Therefore, it is critical that the terminal olefi n is located on the substituted
cyclopentadienyl ligand only; when both olefi ns are terminal, little or no enantioselectiv-
ity is observed.
8E.2.6. Stereogenic - at - Mo Complexes with Only Monodentate Ligands: Application
to Enantioselective Synthesis of Quebrachamine
The continuing quest for design and development of more effective catalysts (i.e., more
reactive, longer living, more selective) stands as one of the most compelling goals of
research in olefi n metathesis [1b]. As illustrated above, in many examples, enantioselec-
tive olefi n metathesis reactions require high catalyst loadings and/or long reaction times,
regardless of whether Ru-based catalysts or the more active Mo complexes are utilized.
At times, only one catalyst is capable of promoting the desired transformation (e.g., the
enantioselective RCM of enol ethers in Scheme 8E.6).
Recently, in the context of efforts toward total synthesis of
Aspidosperma
alkaloid
quebrachamine (Scheme 8E.8), wherein the penultimate step features a desymmetriza-
tion by RCM [32], the need for a substantially more effective chiral olefi n metathesis
catalyst became abundantly clear. Although the RCM can be catalyzed by the available
achiral Mo or Ru complexes, albeit not with high effi ciency, none of the existing chiral
Mo catalysts (e.g.,
1
-
4
) afford the desired enantiomerically enriched product, even under
forcing conditions (up to 50 mol % catalyst, up to 80°C, up to 48 h). With chiral Ru cata-
lysts, only racemic product could be obtained. Thus, the development of a new more
reactive and selective class of catalysts proved to be imperative for successful completion
of an enantioselective total synthesis of quebrachamine.
