Chemistry Reference
In-Depth Information
TABLE 8E.1.
(
Continued
)
Time (h);
Temp ( ° C)
Conv (%);
Yield (%)
Entry
Product
Catalyst; mol %
ee (%)
8
3a
; 2
4; 60
>
98; 98
>
98
Me
Me
Si
9
7b
; 4
2; 40
<
2; nd
nd
O
1 0
8a
; 2
2; 40
93; nd
30
Me
Me
11
7b
; 4
2; 40
68; nd
86
Me
Me
Si
1 2
8a
; 0.8
2; 40
> 98; 77
92
O
1 3
13
; 2.5
2; 40
> 98; 82
5
Me
Me
Me
nd = not determined.
entries 1-4 is afforded by complex
11a
(entry 3), although a longer reaction time and
elevated temperature are required.
The necessity for the use of appropriate substrates (olefi ns bearing specifi c substitu-
tion patterns that afford high enantioselectivities), entailing nontrivial syntheses of the
prochiral trisubstituted olefi ns, remains a signifi cant limitation of Ru-catalyzed enanti-
oselective RCM. A synthesis scheme that incorporates Ru-catalyzed enantioselective
RCM would thus suffer the complication that subsequent elaboration must be accom-
plished through nontrivial chemo- and regioselective modifi cation of product olefi ns. In
contrast, a substrate bearing 1,1-disubstituted prochiral alkenes would afford a product
with a combination of 1,1-disubstituted and endocyclic trisubstituted alkenes, thus
diminishing the residual symmetry of the starting material. (For one approach to solving
the problem of olefi n differentiation after enantioselective RCM, see Section 8E.2.4).
8E.2.1.2. Mechanistic Models
The current mechanistic models for Ru-catalyzed
enantioselective RCM are outlined in Scheme 8E.4. Initiation of the complex proceeds
through dissociation of either the phosphine ligand or chelated etherate moiety [8].
Subsequent coordination of the least-substituted olefi n of the triene to the Ru center
affords
I
(R =Ar for initiation or H for propagation), which upon [2 + 2] cycloaddition,
followed by cycloreversion, furnishes
II
. As all the steps in the catalytic cycle are in
principle reversible, any step that involves the substrate covalently bound to Ru can be
enantiodetermining; release of the RCM product, however, is most likely irreversible,
thus limiting the enantiodetermining step to olefi n coordination (formation of
II
) or
formation or cleavage of the ruthenacyclobutane. Olefi n coordination is likely barrier-
less [9], while the latter two are microscopic reverses of one another for symmetrically
substituted ruthenacyclobutanes. Thus, formation or cleavage of the ruthenacyclobutane
can be enantiodetermining, depending on substrate and stereochemistry of the
intermediates.
The symmetry and polydentate nature of the ligand strongly affect the energetics of
the catalytic cycle. For Ru complexes that bear a monodentate ligand, rotation about
the C
NHC
-Ru bond has been shown to be facile at temperatures as low as − 80 ° C [10] .
