Chemistry Reference
In-Depth Information
OH
Ar =
Ph
4-(Me)Ph
4-(Hal)Ph
4-(MeO)Ph
2-Nap
Ru(Por*)
187
CH
2
Cl
2
, r.t.
Ar
Me
Ar
Me
2
3
3
28-72% yield
62-76% ee
2
Scheme 4.60.
Asymmetric C -H hydroxylation with
187
.
C. echinulata
4 days
47% yield
2+
Me
Me
H
H
H
OH
O
O
O
O
10
10
N
N
NCMe
NCMe
O
Fe
O
N
H
H
N
O
O
Me
Me
236
2 SbF
6
cat.
236
AcOH, H
2
O
2
O
O
235
(+)-Artemisinin
(+)-
237
54% yield
(2X recycled)
Scheme 4.61.
Selective hydroxylation of complex molecule
235
.
tive hydroxylation at C10 in the complex natural product (+)-artemisinin (
235
) was
achieved in 54% yield. The system behaves in a predictable manner and hydroxylates the
most electron-rich and sterically least hindered 3° C-H bond in the molecule exclusively
[18]. In comparison, the hydroxylation occurs at the same position with cultures of
Cun-
ninghamella echinulata
. Other examples were also reported with a high degree of predict-
ability [18]. Although this example is achiral, it represents a signifi cant breakthrough in
this area since it addresses a paradoxical challenge—to simultaneously achieve high reac-
tivity of the metal complex and predictable selectivity in complex molecule functionaliza-
tion [18]. Furthermore, this highlights the synthetic value of such transformations,
particularly when considering that the reaction represents a late stage, selective function-
alization of a complex molecule [18,19]. The method has the potential to increase complex
target synthesis effi ciency greatly, particularly if asymmetric variants can be developed.
4.4.2. Asymmetric C -H Bond Functionalization via Directed C- H Metallation
C -H functionalization via insertion of a reactive metal complex is one of the two emerg-
ing approaches for the development of practical methods for catalytic C- H activation
[23]. Although this area has been extensively developed for many achiral systems with
a wide array of metal catalysts [1,5,13,15,17,19-22,281], transformations with high asym-
metric induction have only recently been reported [13].
The activation of terminal alkyne C-H bonds under mild conditions has been
reported using copper complexes as effective catalysts [282]. Various chiral ligands have
been employed in this chemistry. Asymmetric alkyne C-H activation has been used for
enantioselective syntheses of propargylic amines [282]. An interesting transformation
