Biomedical Engineering Reference
In-Depth Information
8-hydroxyquinoline (
) met the better compromise between yield (85%), prac-
ticability, and scale-up (
H
10 kg).
Another example of heterocyclic ring acting as nucleophile for this cross-
coupling transformation was published in 2002 by Srirangam and coworkers on the
preparation of AG3433, a potent inhibitor of matrix metalloprotease [58]. In this case,
the copper-mediated
N
-arylation takes place with an electron-deficient pyrrole
analogue and an arylboronic acid. The reaction occurs at room temperature with
stoichiometric amounts of Cu(OAc)
2
and with a high degree of chimiocompatibility.
Additional relevant examples are the synthesis of nilotinib (AMN107) by Huang
and Shakespeare [59] and the preparation of (
L14
)-psychotrimine by Takayama and
coworkers [60]. Both syntheses took advantage of copper cross-coupling reactions
between aryl halides with a substituted imidazole derivative and an indole ring of a
tryptamine building block, respectively.
3.3.5.4. Enamides Formation Enamides are structural subunits present in
many natural product cores. Surprisingly, it is only in the twenty-first century that
efficient and more practical methods have been introduced for helping chemists to
build complex molecules via enamides construction. Among them, copper-mediated
coupling reactions of amides and vinyl halides have proven their efficacy and attracted
the interest of many groups working in the field of natural product synthesis.
The concept to assemble vinyl iodides with amides was introduced by Porco and
Shen [61] and elegantly illustrated in 2002 with the total synthesis of lobatamide C
(Scheme 3.26) [62].
The coupling of
E
-
O
-methyloxime amide
61
with vinyl iodide
62
under
copper(I) thiophenecarboxylate (CuTC)/1,10-phenanthroline catalysis represents the
key step in the preparation of salicylate antitumor macrolide in which the desired
enamide subunit
was isolated with 45% yield along with 10% of the easily
separable
Z
-oxime stereoisomer.
Another elegant example that illustrates the powerful utility of such coupling
reactions was reported in 2006 byWeinreb and coworkers. The authors have devised a
simple and straightforward way of preparing
63
-haloenamides via copper(I)-catalyzed
inter- and intramolecular coupling of lactams with (
E
)-2-chloro and (
E
)-2-bromo
vinyl iodides (Scheme 3.27) [63]. The method affords the desired products in
moderate to good yields (up to 91%) and provides an appealing option for the
syntheses of chartellines A-C and chartellamides A and B. One year later, the same
b
N
MeO
MeO
NH
2
N
N
N
MeO
O
O
N
61
CuTC,
L6
dba, Cs
2
CO
3
DMA, 65°C
45%
O
O
OH
O
O
O
OEt
O
I
HO
PO
OEt
OP
O
Me
63
62
O
S
Me
CuTC =
O
-
Cu
+
Lobatamide C
SCHEME 3.26
Lobatamide C synthesis by Porco and Shen.
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