ACS Catalysis
Page 4 of 6
product was observed even at higher temperature. While,
collectively, these experiments suggest that the attack of a
highly electrophilic aminating species onto the aromatic
ring is likely, the exact nature of this reactive intermedi-
ate remains to be determined through detailed mechanis-
tic studies.
(4) Smith, M. B.; March J. In March's Advanced Organic Chem-
th
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
istry: Reactions, Mechanisms and Structure, 6 ed.; John
Wiley & Sons, Inc.: Hoboken, 2007; p. 1815−1818.
(5) (a) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994,
1
16, 7901−7902. (b) Paul, F.; Patt, J.; Hartwig, J. F. J. Am.
Chem. Soc. 1994, 116, 5969−5970. (c) Torborg, C.; Beller, M.
Adv. Synth. Catal. 2009, 351, 3027−3043. (d) Corcoran, E. B.;
Pirnot, M. T.; Lin, S.; Dreher, S. D.; DiRocco, D. A.; Davies,
I. W.; Buchwald, S. L.; MacMillan, D. W. C. Science 2016,
Scheme 5. Kinetic Isotope Effect.
3
53, 279−283.
(6) (a) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M.
P. Tetrahedron Lett. 1998, 39, 2933−2936. (b) Lam, P. Y. S.;
Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan,
D. M. T.; Combs, A. Tetrahedron Lett. 1998, 39, 2941−2944.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
7) (a) Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128,
10028−10029. (b) Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. Angew.
Chem. Int. Ed. 2009, 48, 1114−1116. (c) Xia, N.; Taillefer, M.
Angew. Chem. Int. Ed. 2009, 48, 337−339. (d) Mlynarski, S.
N.; Karns, A. S.; Morken, J. P. J. Am. Chem. Soc. 2012, 134,
16449−16451. (e) Zhu, C.; Li, G.; Ess, D. H.; Falck, J. R.;
Kürti, L. J. Am. Chem. Soc. 2012, 134, 18253−18256. (f)
Borzenko, A.; Rotta-Loria, N. L.; MacQueen, P. M.; Lavoie,
C. M.; McDonald, R.; Stradiotto, M. Angew. Chem. Int. Ed.
In conclusion, we have reported a rare example of di-
rect catalytic synthesis of primary anilines through C–H
amination. Our protocol relies on the use of an exceed-
ingly cheap and simple catalyst (FeSO ) and a new hy-
4
droxylamine-derived reagent under mild reaction condi-
tions. This transformation tolerates a broad scope of sub-
strates and functionalities, as demonstrated in the late-
stage functionalization of several drug derivatives. We
believe that this practical approach to C–H amination will
be of immediate utility to medicinal chemists and further
lays the groundwork for the development of sustainable
amination reactions.
2
015, 54, 3773−3777.
8) (a) Kovacic, P.; Bennett, R. P. J. Am. Chem. Soc. 1961, 83,
21−224. (b) Minisci, F. Synthesis 1973, 1, 1−24. (c) Day, J. C.;
(
2
Katsaros, M. G.; Kocher, W. D.; Scott, A. E.; Skell, P. S. J.
Am. Chem. Soc. 1978, 100, 1950−1951. (d) Lu, F.-L.; Naguib,
Y. M. A.; Kitadani, M.; Chow, Y. L. Can. J. Chem. 1979, 57,
1967−1976. (e) Citterio, A.; Gentile, A.; Minisci, F.; Navar-
rini, V.; Serravalle, M.; Ventura, S. J. Org. Chem. 1984, 49,
4
479−4482.
ASSOCIATED CONTENT
(
9) Erdik, E.; Saczewski, J. Hydroxylamine-O-sulfonic Acid. In
Encyclopedia of Reagents for Organic Synthesis; Fuchs, P.
L.; Bode, J. W.; Charette, A. B.; Rovis, T., Eds.; John Wiley &
Sons, Inc: Hoboken, 2013.
Supporting Information
The supporting Information is available free of charge via the
General information, materials, instrumentation, proce-
dures and characterization data.
(
10) (a) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110,
1147−1169. (b) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q.
Acc. Chem. Res. 2012, 45, 788−802. (c) Tran, L. D.; Roane,
J.; Daugulis, O. Angew. Chem. Int. Ed. 2013, 52, 6043−6046.
AUTHOR INFORMATION
Corresponding Author
(d) De Sarkar, S.; Liu, W.; Kozhushkov, S. I.; Ackermann, L.
Adv. Synth. Catal. 2014, 356, 1461−1479. (e) Matsubara, T.;
Asako, S.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2014,
*Email: morandi@kofo.mpg.de
1
36, 646−649. (f) Shin, K.; Kim, H.; Chang, S. Acc. Chem.
Notes
Res. 2015, 48, 1040−1052. (g) Gensch, T.; Hopkinson, M. N.;
Glorius, F.; Wencel-Delord, J. Chem. Soc. Rev. 2016, 45,
2900−2936. (h) Raghuvanshi, K.; Zell, D.; Rauch, K.;
Ackermann, L. ACS Catal. 2016, 6, 3172−3175. (i) Tezuka,
N.; Shimojo, K.; Hirano, K.; Komagawa, S.; Yoshida, K.;
Wang, C.; Miyamoto, K.; Saito, T.; Takita, R.; Uchiyama, M.
J. Am. Chem. Soc. 2016, 138, 9166−9171.
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Generous funding from the Max-Planck-Society, the Max-
Planck-Institut für Kohlenforschung and the Fonds der
chemischen Industrien is acknowledged. We kindly thank
Prof. B. List for sharing analytical equipment, and our tech-
nical departments for assistance.
(
11) (a) Díaz-Requejo, M. M.; Belderraín, T. R.; Nicasio, M. C.;
Trofimenko, S.; Pérez, P. J. J. Am. Chem. Soc. 2003, 125,
12078−12079. (b) Li, Z.; Capretto, D. A.; Rahaman, R. O.;
He, C. J. Am. Chem. Soc. 2007, 129, 12058−12059. (c) Kantak,
A. A.; Potavathri, S.; Barham, R. A.; Romano, K. M.;
DeBoef, B. J. Am. Chem. Soc. 2011, 133, 19960−19965. (d)
Kim, H. J.; Kim, J.; Cho, S. H.; Chang, S. J. Am. Chem. Soc.
2011, 133, 16382−16385. (e) Samanta, R.; Bauer, J. O.;
Strohmann, C.; Antonchick, A. P. Org. Lett. 2012, 14,
5518−5521. (f) Shrestha, R.; Mukherjee, P.; Tan, Y.; Litman,
Z. C.; Hartwig, J. F. J. Am. Chem. Soc. 2013, 135, 8480−8483.
(g) Allen, L. J.; Cabrera, P. J.; Lee, M.; Sanford, M. S. J. Am.
Chem. Soc. 2014, 136, 5607−5610. (h) Kim, H.; Kim, T.; Lee,
D. G.; Roh, S. W.; Lee, C. Chem. Commun. 2014, 50,
9273−9276. (i) Greulich, T. W.; Daniliuc, C. G.; Studer, A.
Org. Lett. 2015, 17, 254−257.
REFERENCES
(1) (a) Fischer, C.; Koenig, B. Beilstein J. Org. Chem. 2011, 7,
59−74. (b) Okano, K.; Tokuyama, H.; Fukuyama, T. Chem.
Commun. 2014, 50, 13650−13663.
(
2) Kahl, T.; Schröder, K.-W.; Lawrence, F. R.; Marshall, W. J.;
Höke, H.; Jäckh, R. Aniline. In Ullmann's Encyclopedia of
Industrial Chemistry; Wiley-VCH Verlag GmbH & Co.
KGaA: Weinheim, 2011; Vol. 3, p. 465−478.
(
3) (a) D'Aprano, G.; Leclerc, M.; Zotti, G.; Schiavon, G. Chem.
Mater. 1995, 7, 33−42. (b) Shirota, Y.; Kageyama, H. Chem.
Rev. 2007, 107, 953−1010.
ACS Paragon Plus Environment