Journal of the American Chemical Society
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corresponding primary 2-aminonaphthalene 2a when water was
used as a co-solvent in the reaction. In both cases, use of Cs2CO3
REFERENCES
1
as an additive improved the isolated yield of 2a.
2
Encouraged by the results above, the amination reaction was
subsequently conducted on a gram scale, demonstrating its practi-
cality (Scheme 2). When substrates 1a and 1r were primary ami-
nated either in the presence or absence of Cs2CO3, the corre-
sponding anilines were obtained in similar chemical yields.
3
4
5
6
7
8
9
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Scheme 2. Primary Amination of Arylboronic Acids on a
Gram-Scale Using Aminating Agent DPH (8).
10
11
12
13
14
15
16
17
18
19
20
21
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28
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In summary, the first metal-free amination of aromatic bo-
ronic acids leading to primary arylamines, a reaction that has
eluded synthetic chemists for decades, was demonstrated. The
transformation is operationally simple, proceeds under mild con-
ditions and, affords structurally diverse primary aniline products
in good chemical yield. It is especially noteworthy that a variety
of halogenated primary anilines, that often cannot be prepared via
the transition metal-catalyzed amination of the corresponding
arylboronic acids and aryl halides, are also readily produced using
this method while obviating the formation of undesired N-
polyarylated products. In addition, the reaction can be readily
scaled up to gram-scale, thereby offering a practical route for the
production of structurally diverse primary arylamines. The explo-
ration of related transformations and several powerful aminating
agents is currently under way in our laboratories.
ASSOCIATED CONTENT
Supporting Information
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Complete experimental procedures and characterization data in-
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(17) Aminating agent 8 is commericially available from Corvinus
Chemicals, LLC in multi-gram quantities with >99% purity
(corvinuschemicals@gmail.com).
(18) (a) All calculations were performed in Gaussian 09 with the M06-
2X/6-31G(d,p) functional and basis set in conjunction with the SMD
solvent model for toluene. All structures were confirmed as minima or
saddle points through normal mode analysis and free energies are reported
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1
cluding H and 13C NMR spectra, further computational details
and full reference 18b. This material is available free of charge via
AUTHOR INFORMATION
Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
L.K. gratefully acknowledges the generous financial support
of the UT Southwestern Endowed Scholars in Biomedical Re-
search Program (W.W. Caruth, Jr, Endowed Scholarship in Bio-
medical Research), the Robert A. Welch Foundation (Grant I-
1764), the ACS Petroleum Research Fund (Doctoral New Investi-
gator Grant 51707-DNI1) and the American Cancer Society &
Simmons Cancer Center Institutional Research Grant (New Inves-
tigator Award in Cancer Research, ACS-IRG 02-196). J.R.F.
thanks the NIH (GM31278) and the Robert A. Welch Foundation
(GL-625910) for financial support. D.H.E. thanks BYU and the
Fulton Supercomputing Lab for support of this work.
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