Journal of the American Chemical Society
REFERENCES
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ylmetals (e.g., Table 1, entries 5 & 18) are amenable to catalytic
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primary amination. Presumably, in all of the other cases, the arꢀ
ylmetals undergo rapid and nonꢀproductive quenching by the NHꢀ
oxaziridine reagent before the arylcuprates can form via
transmetallation.
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Aryl
HN
A
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(
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HN
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(
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(
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Aryl
Cu
Cu
O
8
3
6
5
35
workup
(
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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7
8
9
0
1
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4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(I)
reductive
B
Aryl Cu
+
elimination
Science 2015, 349, 1326. (b) Jiao, J.; Murakami, K.; Itami, K. ACS Catal.
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Aryl
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oxidative
addition
H
N
(III)
37
HN
O
Aryl Cu
(5) For reviews on electrophilic amination, see: (a) Daskapan, T.
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Starkov, P.; Jamison, T. F.; Marek, I. Chem. - Eur. J. 2015, 21, 5278. (d)
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10.1002/chem.201601607.
O
Aryl
NHR
5
38
40
R
oxidative
addition
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elimination
(
I)
HN
(III)
NHR
OBz
+
Aryl Cu
C
Aryl Cu
(6) Berman, A. M.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126, 5680.
OBz
25
(7) Tezuka, N.; Shimojo, K.; Hirano, K.; Komagawa, S.; Yoshida, K.;
39
Wang, C.; Miyamoto, K.; Saito, T.; Takita, R.; Uchiyama, M. J. Am.
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Figure 2. Proposed mechanistic pathways.
(8) Gao, H.; Zhou, Z.; Kwon, D.ꢀH.; Coombs, J.; Jones, S.; Behnke, N.
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(
9) (a) Wunderlich, S. H.; Knochel, P. Angew. Chem., Int. Ed. 2007, 46,
In summary, we have developed a novel method for the direct
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the presence of Cu(I)ꢀsalts. This transformation offers a practical
solution for a longꢀstanding synthetic problem of aminating hetꢀ
eroarylmetals directly and efficiently. In addition, the method
does not rely on the presence of directing groups and requires
only equimolar amounts of the aminating reagent. We anticipate
that this general and operationally simple amination approach will
find wide utility in the synthesis of structurally complex moleꢀ
cules such as active pharmaceutical ingredients and natural prodꢀ
ucts.
7
685. (b) Wunderlich, S.; Knochel, P. Chem. Commun. 2008, 6387. (c)
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1
(
ASSOCIATED CONTENT
Supporting Information
(
12) Please see the Supporting Information for detailed DFT calculations
Complete experimental procedures and characterization data inꢀ
in Reference #8.
1
13
cluding H and C NMR spectra. This material is available free
of charge via the Internet at http://pubs.acs.org.
(13) Berman, A. M.; Johnson, J. S. J. Org. Chem. 2006, 71, 219.
AUTHOR INFORMATION
Corresponding Authors
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
L.K. gratefully acknowledges the generous financial support of
Rice University, National Institutes of Health (R01 GMꢀ114609ꢀ
0
1
1), National Science Foundation (CAREER:SusChEM CHEꢀ
455335), the Robert A. Welch Foundation (Grant Cꢀ1764), ACSꢀ
PRF (Grant 51707ꢀDNI1), Amgen (2014 Young Investigators’
Award for LK) and Biotage (2015 Young Principal Investigator
Award) that are greatly appreciated. We thank Professor Daniel
H. Ess (BYU) for helpful discussions.
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