Chemistry Reference
In-Depth Information
Ph
Ph
Ph
Ph
i-Pr
i-Pr
i-Pr
i-Pr
N
N
N
N
O
O
L
L
H
Me
Ru
Stereogenic axis
Ru
Me
H
O
L
L
H
Me
Me
O
Me
Me
Major
Minor
H
Disfavored
Favored
Figure 8E.1.
Stereogenicity transfer from the stereogenic axis of the Ru-carbene to the stereogenic
center of the enantioselective RCM product.
Thus,
II
(when R
1
≠ R
2
) can exist as a thermodynamic mixture of rotamers (
II
III
) if
the aforementioned ligand rotation is suffi ciently faster than the rate of ruthenacyclobu-
tane formation, which may ultimately result in diminished enantioselectivity. Further-
more, C
NHC
-Ru rotation may be coupled to the catalytic cycle as has been illustrated for
phosphine-Ru complexes [11]. The above considerations do not apply to reactions pro-
moted by
C
2
- symmetric ligands (R
1
= R
2
), where various rotamers are degenerate. More-
over, such factors are irrelevant in the case of complexes that carry a bidentate ligand,
as in such instances interconversion between diastereomeric Ru-carbenes (net stereo-
mutation at the metal center) is possible through productive (as shown) or degenerate
olefi n metathesis (
IV
V
). Alternative pathways, such as polytopal rearrangements,
remain to be investigated.
In contrast to Ru complexes
11
-
12
, carbenes
7
-
10
and
13
do not bear a stereogenic
metal center. One stereochemical feature that the above catalysts share is that the reac-
tive metal - olefi n complexes (
I
and
II
in Scheme 8E.4) possess a stereogenic axis (Ru= C
bond). Control of this axis in the transition state for metallacyclobutane formation is
critical for achieving high enantioselectivity (see Fig. 8E.1). Whereas monodentate
ligands control the stereogenic axis through steric interaction with R
1
or R
2
, relaying
stereogenicity of the NHC backbone, the bidentate ligands in
11
-
12
rely on the differ-
ence in C
carbene
- Ru - X angles (X = halide or O) [12] .
8E.2.2. Temporary Tether Approach in Catalytic RCM: Net
Mo - Catalyzed Enantioselective Cross - Metathesis (CM)
To facilitate “ diffi cult” transformations, tethering strategies have been employed in
organic synthesis [13]. In 1992, application of such an approach to catalytic olefi n metath-
esis was reported [14]. Subsequent to the initial disclosure, a number of research teams
have been able to extend this concept, including applications in complex molecule
synthesis [15] .
A B-based tethering strategy in promoting highly enantioselective catalytic RCM
was fi rst disclosed in 2004. As illustrated in Scheme 8E.5, Mo-catalyzed enantioselective
RCM of mixed allylboronates, which, after oxidation, affords chiral 1,4-diols,
constitutes a net
Z
-selective CM [16]. Several points of this study are noteworthy:
(1) The requisite substrate can be generated
in situ
through ligand exchange of an
alcohol with an allyl boronic ester, allowing the process to be carried out in a single
vessel. (2) Products from kinetic resolution and desymmetrization are obtained with high
