Chemistry Reference
In-Depth Information
1. MeOH, CO,
Pd(OAc)
2
, dppp
2. LiAlH
4
3. PCC
4. Ph
3
P=CH
2
OTf
OTf
Grubbs II
8.314
8
5
8
6
Scheme 8.86
8.3.4 Cross-Metathesis
The intermolecular metathesis between two alkenes is known as cross-metathesis.
102
With the Grubbs 1
st
generation catalyst, there were few useful applications. This changed with the introduction of the Grubbs 2
nd
generation catalyst. An obvious problem with cross-metathesis is in ensuring selectivity as the alkenes may
not only undergo metathesis with each other (“self-metathesis”), but also with themselves (Scheme 8.87). For
a cross-metathesis between two terminal alkenes, three products are possible, as well as the ethene by-product.
In general, one alkene should be used in excess. This should be an alkene that has a strong tendency to undergo
cross-metathesis, but a weaker tendency for self-metathesis. Electron-poor alkenes, such as methyl acrylate,
appear to fit into this category.
One approach to predicting the selectivity of cross-metathesis is to categorize alkenes according to their
reactivity, including their reactivity towards self-metathesis.
103
As the different catalysts have different
reactivities, this has to be done catalyst by catalyst. The categorization of some alkenes for the widely
used Grubbs second-generation catalyst is shown below (Table 8.2). Most simple alkenes undergo fast self-
metathesis and are type I. Electron-poor alkenes undergo slow self-metathesis and are type II. This category
also includes some sluggish alkenes of other types. Type III alkenes are more bulky versions of type I and
type II alkenes, and type IV alkenes are either very bulky or very electron poor.
Cross-metathesis of two type I or two type II alkenes will result in a statistical mixture, as the rates of the
desired cross-metathesis and the two self-metathesis reactions will all be similar. To obtain a synthetically
useful result, one partner must be used in large excess. A more productive and efficient cross-metathesis
reaction can be achieved using a type I alkene with either a type II or a type III alkene (Scheme 8.88). The
type II alkene will undergo self-metathesis slowly (or not at all); the type I alkene may undergo self-metathesis,
but its self-metathesis product
8.317
may re-enter and undergo productive metathesis itself. A modest excess
of one of the two alkenes is usually used.
Another efficient combination is to combine a type II alkene with a type III alkene (Scheme 8.89). An
example would be the metathesis of a 1,1-disubstituted alkene
8.319
with an acrylate ester
8.320
.This
process can be made more efficient if the acrylate (R
=
H) is changed to a crotonate (R
=
Me), making its
self-metathesis even slower.
Grubbs II
R
1
R
1
R
2
R
1
R
2
R
2
R
1
R
2
Scheme 8.87
