Biomedical Engineering Reference
In-Depth Information
trans
-oxirane carboxamides and (
Z
)-1-aryl-2-bromoethenes catalyzed by CuI/
L15
to afford enamides in high yields and selectivities (49-91%;
Z
/
E
up to 95:5) [70].
The method was fruitfully used to prepare some
Clausena
alkaloids as exemplified
by (
-clausenamide. In the same year, Ma and coworkers personalized the same
copper/ligand system for surpassing the major challenge on elaborating the 15-
membered cyclopeptide alkaloids abyssenine B and mucronine E: the formation of
their enamide subunit [71]. Palmerolide A, a polyketide bearing a carbamate and a
vinyl amide functionality with intriguing biological properties (e.g., antitumor,
ATPase inhibitor), was also a target in which a copper cross-coupling reaction was
used on the last step, allowing the successful installation of the enamide moi-
ety [72]. The same method was also adopted by Dias and coworkers in the last step
of their total synthesis of crocacin D, an antifungal and cytotoxic natural
antibiotic [73].
þ
)-
x
3.3.5.5. Intramolecular/Cyclization Since 2001, copper-mediated cross-
coupling reactions were successfully applied to both the construction of small-
and medium-sized nitrogen heterocycles and the preparation of macrocyclic
lactams or enamides and thus found applications in many natural product
syntheses.
One appealing example dealing with the preparation of imidazoindolone
scaffolds was reported in 2006 by Lautens and coworkers [74]. Hence, by using
gem
-dibromovinyl moieties
as starting material, the authors reported a CuI-
catalyzed tandem intramolecular amidation as the key step for the preparation of the
imidazoindolone core
77
of fumiquinazoline I and asperlicin. The reaction takes place
at 120
C in toluene in the presence of ligand
76
andK
2
CO
3
as the base. The optimized
reaction conditions afforded the desired substituted imidazoindoles in good yields (up
to 84%) with moderate to good preservation of the pendant amino acid arm
stereochemistry (up to 93% ee) (Scheme 3.29).
In the total synthesis of SB-214857 (Scheme 3.30; see also Scheme 3.23) by
Ma and Xia in 2001, an alternative pathway for the construction of the seven-
membered heterocyclic core was proposed via an intramolecular cross-coupling
reaction of aryl iodide-
L7
b
-amino ester starting material
78
[75]. Completion of
the synthesis required six additional steps from
79
. In the total synthesis of
(
)-psychotrimine by Takayama and coworkers (Scheme 3.30; see also
Scheme 3.25), a copper-mediated intramolecular amination was used to build the
tricyclic motif
[76]. In this transformation, ligand-free conditions, stoichio-
metric amounts of copper, and the nature of the base were found crucial for a good
outcome of the reaction.
One of the most impressive and elegant examples of copper-mediated
intramolecular C-N bond formation in the total synthesis of (
81
)-yatakemycin, an
antitumor and antibiotic natural product, was published in 2006 by Fukuyama and
coworkers [77]. The subgram-scale synthesis of yatakemycin is characterized by the
construction of all five aryl-nitrogen bonds by means of CuI aryl amination
reactions using the same catalytic system as shown in Scheme 3.31.
þ
Search WWH ::
Custom Search