Copper-Catalyzed Formation of 2-Aminobenzophenones
COMMUNICATION
was obtained in 55% (yield obtained from NMR spectrosco-
py); whereas if 5 mol% of BHT was used, only a trace of 2a
was detected. These results support that the catalytic reac-
tion goes through a radical mechanism.
Acknowledgements
We thank the National Science Council of Republic of China (NSC-101–
2628-M-007–004) for support of this research.
The significance of this copper-catalyzed intramolecular
À
C N bond-formation reaction is demonstrated by its appli-
Keywords: acridones · aminobenzophenone · bipyridine ·
copper · oxidation · total synthesis
cation to the total synthesis of an acridone natural product
arborinine. The synthetic Scheme by using this methodology
as the key step is shown in Scheme 2. Thus, treatment of
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Scheme 2. Total synthesis of arborinine. a) CuI (1.0 mol%), 2,2’-bipyri-
dine (1.0 mol%) and DMAc, 1608C, 12 h, 96%; b) conc. HCl
(20.0 equiv), MeOH, heat at reflux, 12 h, 84%.
aminobenzophenone 1x in the presence of CuI and bpy in
DMAc at 1608C for 12 h provided 2x in 96% yield. After a
successful acid-catalyzed selective demethylation reaction of
2x, we obtained arborinine in 84% yield. The overall yield
of arborinine from 5 was 43%, which is much higher than
those reported earlier.[18] It is interesting to note that arbori-
nine has been shown to exhibit several biological effects.[19]
Interestingly, the present catalytic reaction also proceeded
smoothly on a 10.0 mmol scale of substrate 1a under the
standard reaction conditions. Product 2a was readily isolat-
ed in 85% yield.
In conclusion, we have successfully developed a CuI/bpy-
À
catalyzed synthesis of acridone derivatives through C H
À
functionalization and C N bond formation of 2-aminoben-
zophenone in one pot. The protocol generally requires very
low catalyst loading (1.0 mol%) and is successfully applied
to the total synthesis of arborinine with excellent yield. Fur-
thermore, the present catalytic reaction involves an unusual
pseudo-1,2-migration of the substituent on the arene ring
leading to the formation of two regioisomers.
Experimental Section
General procedure for the copper-catalyzed synthesis of acridone: A
sealed tube containing CuI (1.0 mol%) and 2,2’-bipyridine (1.0 mol%),
was evacuated and purged with oxygen gas three times. Then, DMAc
(1.0–5.0 mL), 2-aminobenzophenone 1a (0.50 mmol), were sequentially
added to the system through a syringe under an oxygen atmosphere and
the reaction mixture was allowed to stir at 1408C for 12 h. When the re-
action was completed, the mixture was cooled and diluted with CH2Cl2
(10 mL). The mixture was filtered through a Celite and silica gel pads
and was washed with CH2Cl2/MeOH (50 mL). The combined filtrate was
concentrated and the residue was purified by a silica gel column by using
hexane/EtOAc as eluent to give pure 2a in 97%.
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Chem. Eur. J. 2013, 19, 460 – 464
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