ruthenium9 for example have shown certain advantages
in some cases over more established procedures, such
as BuchwaldÀHartwig,10 Ullmann, and Goldberg coupl-
ings.11 Such direct CÀH activaton/amination reactions
require fewer steps and proceed under milder conditions
in comparison to the more classical coupling reactions.12
However, construction of these heterocycles via an intra-
molecular CÀN bond formation strategy remains challen-
ging. In this context, Buchwald reported on a CÀH
activation/intramolecular amination for carbazole synthe-
sis catalyzed by palladium, which unveiled a new ap-
proach to the intramolecular formation of CÀN bonds.13
Since then, Pd-catalyzed intramolecular direct amination
of CÀH bonds has been widely exploited and has now
become well established.7 More recently, metal-free or less
expensive Cu-catalyzed direct CÀN bond formation via
CÀH activation/amination utilizing various oxidants has
become regarded as an effective and practical strategy, for
the construction of such hetereocycles.14
Table 1. Optimization of Reaction Conditionsa
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catalyst
oxidant
additive yield/
b
entry (5 mol %)
(1.5 equiv)
solvent
PhMe
(1.5 equiv)
%
1c Cu(OTf)2 PhI(OAc)2
2c Cu(OTf)2 PhI(OAc)2
3c Cu(OTf)2 PhI(OAc)2
4c Cu(OTf)2 PhI(OAc)2
5c Cu(OTf)2 PhI(OAc)2
6c Cu(OTf)2 PhI(OAc)2
;
38
PhMe
K2CO3
TFA
48
52
PhMe
PhMe
NaOAc 55
DMF
;
;
;
;
;
;
;
;
;
;
30
AcOH
52
€
M. B.; Kerwin, S. M. Bioorg. Med. Chem. 2002, 10, 3997. (m) Knolker,
H.-J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303. (n) Horton, D. A.;
Bourne, G. T.; Smythe, M. L. Chem. Rev. 2002, 103, 893.
7
8
9
Cu(OTf)2 PhI(OAc)2
Cu(OAc)2 PhI(OAc)2
AcOH/Ac2O
AcOH/Ac2O
AcOH/Ac2O
AcOH/Ac2O
AcOH/Ac2O
88
82
(7) (a) Yoo, E. J.; Ma, S.; Mei, T.-S.; Chan, K. S. L.; Yu, J.-Q. J. Am.
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T. Org. Lett. 201113, 2102. (c) Haffemayer, B.; Gulias, M.; Gaunt, M. J.
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M. C. J. Am. Chem. Soc. 2009, 131, 11701. (g) Mei, T.-S.; Wang, X.;
Yu, J.-Q. J. Am. Chem. Soc. 2009, 131, 10806. (h) Wasa, M.; Yu, J.-Q.
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R. H.; Brasche, G.; Zheng, N.; Buchwald, S. L. J. Org. Chem. 2008, 73,
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CuI
PhI(OAc)2
PhI(OAc)2
42
10 CuBr
44
11 Cu(OTf)2 oxone
83
n.d.d
12 Cu(OTf)2 Fe2(NO3)3 9H2O AcOH/Ac2O
3
13 Cu(OTf)2 BQ
AcOH/Ac2O
AcOH/Ac2O
82
14 Cu(OTf)2 K2S2O8
81
a Reaction conditions: 1a (0.3 mmol), oxidant (0.45 mmol), AcOH
(1 mL), Ac2O (1 mL), 80 °C for 2 h. b Isolated yield. c solvent (2 mL),
120 °C for 24 h. d n.d. = not detected.
Herein, we report a copper-catalyzed intramolecular
CÀH bond amination reaction of purine and itsderivatives
related to our previous work.15 By employing PhI(OAc)2
as a simple oxidant, a useful and facile alternative process
for the synthesis of purine-fused polycyclics is provided
that might be useful in medicinal studies.
€
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