Biomedical Engineering Reference
In-Depth Information
PCy
3
N
N
i
-Pr
i
-Pr
Mes
Mes
PCy
3
N
N
Mes
Mes
N
Mo
Me
Me
Cl
Cl
Ru
O
F
3
C
Me
Ph
Cl
Cl
Cl
Cl
Ru
Ru
Cl
Cl
O
Ru
Ph
PCy
3
F
3
C
O
Ph
PCy
3
O
F
3
C
Me
CF
3
1
2
(G-I)
3
(G-II)
4
(HG-I)
5
(HG-II)
Schrock catalyst
First generation
Grubbs catalyst
Second generation
Grubbs catalyst
First generation
Hoveyda-Grubbs catalyst
Second generation
Hoveyda-Grubbs catalyst
FIGURE 5.1
Commonly used metathesis catalysts.
and moisture and the necessity of rigorously controlled inert atmosphere for both its
preparation and handling proved less attractive on a practical setting. Independently,
Grubbs and coworkers developed ruthenium-based first generation catalyst
)
that showed remarkable stability toward air and moisture, with even wider func-
tional group tolerance including alcohols and carboxylic acids, albeit with lower
activity compared to catalyst
G-I
(
2
[5]. The practice of catalyst design has since evolved
into an active and fruitful research field, culminating in the discovery of second
generation Grubbs catalyst,
1
G-II
(
3
) [6], and the first and second generations of the
Hoveyda-Grubbs catalysts,
), respectively (Figure 5.1) [7].
These landmark scientific achievements were ultimately recognized with the 2005
Nobel Prize in Chemistry [8] and cemented olefin metathesis as a versatile and
indispensable tool in chemical synthesis, particularly in the construction of complex
molecular architectures.
To date, metathesis reactions can be broadly classified according to the
participating alkene and alkyne reacting partners (alkene metathesis, alkyne
metathesis, and enyne metathesis), as well as the newly formed carbon-carbon bond
in an intermolecular (cross-metathesis) or intramolecular (ring-closing metathesis)
settings (Schemes 5.1-5.4).
In this chapter, application of the metathesis reaction in the synthesis of
complex bioactive molecules will be described. Several seminal reviews have already
highlighted notable contributions in this field, and this chapter serves to provide a
glance at pioneering examples and the most recent advances. Owing to the vast
volume of work in this domain, the selection of examples is by no means compre-
hensive, but simply serves to highlight the state-of-the-art technology and illustrate
the important principles behind this vibrant and growing area [9].
HG-I
(
4
)and
HG-II
(
5
[M]
[M]
R
1
R
1
R
2
n
n
M
Alkene
cross-
metathesis
Alkene
ring-closing
metathesis
M
M
M
n
R
1
R
2
R
1
n
M
R
2
M
R
1
n
SCHEME 5.1
Catalytic cycles for the alkene cross-metathesis and ring-closing metathesis.
Search WWH ::
Custom Search