alkylidene [Mo]-I (Schrock’s catalyst)10 and the ruthenium
benzylidene catalysts [Ru]-I (Grubbs first-generation cata-
lyst),11 [Ru]-II (Grubbs second-generation catalyst),12 and
[Ru]-III (Hoveyda-Grubbs catalyst)13 (Figure 2), has ex-
panded the variety of functional groups amenable to CM and
thus made olefin metathesis practical and useful in organic
synthesis. As a consequence, olefin CM has been widely used
in the synthesis of various drugs and other complex natural
products.14
Table 1. Influence of the Catalyst on the Reaction Selectivitya
NMR ratiob (%)
entry
catalyst
4
6a
7
1
2
3
4
5
6
[Ru]-I (10 mol %)
[Ru]-II (10 mol %)
[Ru]-II (5.0 mol %)
[Ru]-II (2.5 mol %)
[Ru]-II (1.0 mol %)
[Ru]-III (10 mol %)
100
10
9
31
46
100
0
42
55
50
44
0
0
48
36
19
10
0
a
All reactions were carried out on a 0.5 mmol scale using 1.5 equiv of
olefin in refluxing CD2Cl2. Ratio determined by 1H NMR of the crude
b
reaction mixture.
Figure 2. Commercially available ruthenium metathesis complexes.
material was observed when using 10 mol % of either [Ru]-
I or [Ru]-III (Table 1, entries 1 and 6). On the other hand,
the use of [Ru]-II, under otherwise identical conditions, led
to a quasi 1:1 mixture of the desired coupled product 6a
and the undesired isomerized byproduct 7, along with the
unreacted starting material 4 (6a/7/4 ) 42:48:10, Table 1,
entry 2). Olefin isomerization with ruthenium catalysts is a
well-known process which has been reported by several
groups.16 Unfortunately, this undesired side reaction is
detrimental for the efficiency of the CM. Therefore, we
decided to focus our attention on developing conditions that
would eliminate, if not minimize, the formation of 7.
First, lowering the catalyst loading from 10 to 1 mol %
decreased the amount of byproduct 7 formed. However, the
level of conversion also dropped from 90% to 54% (Table
1, entries 3-5).
It is well documented that, if a chelation of the evolving
carbene occurs with a functional group present in the starting
material such as the lactone, the catalyst can be complexed
in the form of an unreactive intermediate which will prevent
the CM from taking place. Thus, to further decrease the
amount of 7 formed, the influence of various additives, which
would compete with the ruthenium carbene for the coordina-
tion, was studied.17
All the reactions were performed using 1.5 equiv of
4-methylpentene, 2.5 mol % of [Ru]-II catalyst, and 5.0 mol
% of the selected additive in refluxing CD2Cl2. The results
are reported in Table 2.
Interestingly, whereas complete conversion of the starting
material was observed in almost all cases, the product
distribution varied from one additive to another. Although
the use of chlorodicyclohexylphosphine (Cy2PCl) favored
the formation of the undesired isomerized byproduct 7
(6a/7/4 ) 16:84:0, Table 2, entry 2), chlorodiphenylphos-
Whereas metathesis reactions on substrates bearing various
types of functionalities are fully documented in the literature,
to our knowledge, only one example of a CM reaction
involving an exocyclic enone has been reported so far.15 This
example concerns the CM reaction between R-methylene-
â-lactones and various terminal olefins. Herein, we wish to
report our endeavor focused on the development of a highly
efficient CM between R-methylene-γ-butyrolactone and a
large variety of olefinic partners by using additives which
tend to limit the formation of the undesired isomerized
byproduct.
To select the most suitable catalyst along with the best
reaction conditions, preliminary experiments were carried out
using a slight excess of 4-methylpentene (1.5 equiv) as the
olefinic partner. Due to the volatility of both the starting
material and the isomerized byproduct, the reactions were
performed in refluxing CD2Cl2 and directly analyzed by 1H
NMR (Table 1). Interestingly, no conversion of the starting
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