Copper-catalyzed amination of potassium aryl trifluoroborates using aqueous ammonia

Article abstract of DOI:10.1016/j.tetlet.2012.06.011

The conversion of potassium aryl trifluoroborates containing different functionalities into the corresponding aryl amines using a catalytic amount of CuSO₄·5H₂O is described. The methodology uses water as a solvent under aerobic conditions to give the products in good yields.

Full text of DOI:10.1016/j.tetlet.2012.06.011

Tetrahedron Letters 53 (2012) 4240–4242
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Copper-catalyzed amination of potassium aryl trifluoroborates using
aqueous ammonia
⇑
André P. Liesen, Arisson T. Silva, jokderléa C. Sousa, Paulo H. Menezes, Roberta A. Oliveira
Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE 50740-540, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
The conversion of potassium aryl trifluoroborates containing different functionalities into the corre-
sponding aryl amines using a catalytic amount of CuSO4Á5H2O is described. The methodology uses water
as a solvent under aerobic conditions to give the products in good yields.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 3 May 2012
Revised 30 May 2012
Accepted 4 June 2012
Available online 12 June 2012
Keywords:
Potassium organotrifluoroborates
Aromatic amines
Aqueous ammonia
Aryl amines are important building blocks in pharmaceutical,
agrochemical, and polymer industries.1 The most common ap-
proach to prepare this class of compounds generally relays on
the use of transition-metal catalysts to promote the coupling reac-
tion of aryl halides with ammonia or ammonia derivatives.2
Several others methods based on the metal-catalyzed reduction
of nitro aryl3 or aryl azides4 by hydrogenation, electrochemical,5
and hydride transfer conditions6 were also described. For econom-
ical and practical reasons, the use of ammonia is the most conve-
nient and efficient approach. However, the synthesis of aniline
derivatives using ammonia has several drawbacks such as the
ligand displacement from the catalyst by ammonia to form catalyt-
ically unreactive species,7 harsh reaction conditions, and the
formation of undesirable diaryl and triaryl amines by-products.8
Although the aryl halides are still the main substrates to
perform the reaction, boronic acids are also particularly attractive
synthetic intermediates9 due to their unique properties as mild or-
ganic Lewis acids and lower reactivity. However, the tricoordinate
nature of these compounds makes them moisture sensitive, limit-
ing its application in multistep sequences. In addition, boronic
acids possess some limitations such as the difficulty to purify
and some uncertainty about stoichiometry, due to the formation
of boroximes.10
many possibilities of functional group interconversion reactions
involving these compounds including the syntheses of aldehydes,13
ketones,14 alcohols,15 alkynes,16 and alkenes,17 all containing the
organotrifluoroborate moiety, which can be later used in Suzuki–
Miyaura type couplings.
The complete characterization of these salts, including hetero-
nuclei NMR analysis, has proven to be possible since better NMR
pulse sequences were developed, allowing the acquisition of new
data related to 19F–11B coupling constants.18 In addition, exact
mass measurements were obtained for a variety of potassium
organotrifluoroborates using a sector ESI mass spectrometer.19
It is also important to emphasize the recent interest on biolog-
ical activities and toxicological data related to these salts. It is al-
ready described that organotrifluoroborates may act as serine
protease inhibitors,20 growth inhibitors on human tumor cell
lines,21 and some of them appear to have antinociceptive activity.22
Herein, we wish to describe an environmentally benign reaction
for the synthesis of aryl amines based on the reaction of potassium
aryl trifluoroborates and aqueous ammonia under aerobic condi-
tions catalyzed by copper (II).
The potassium organotrifluoroborates 2a–j used in this study
were prepared from the corresponding boronic acids 1a–j using
Organotrifluoroborates have proven to be a good option to
replace boronic acids and boronate esters in transmetallation reac-
tions, providing many advantages over the latter reagents.11 They
are very useful reagents for C–C bond formation12 and there are
KHF2
FG Ar B(OH)2
FG Ar BF3K
MeOH, H2O
0oC
80-94%
2a-j
1a-j
⇑
Corresponding author. Tel.: +55 81 2126 7473; fax: +55 81 2126 8442.
E-mail address: roberta.aoliveira@ufpe.br (R.A. Oliveira).
Scheme 1.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.011

A. P. Liesen et al. / Tetrahedron Letters 53 (2012) 4240–4242
4241
KHF2 in MeOH:H2O in good yields23 and their structures were con-
Table 2
firmed by 1H, 13C, 11B, and 19F NMR analysis (Scheme 1).
Our initial studies focused on the development of an optimum
set of reaction under green chemistry conditions. For this purpose,
potassium 3-nitro-phenyltrifluoroborate (2e) (0.25 mmol) was
treated with different catalysts at 25 °C for 24 h and aqueous
ammonia (4 mL of a 28–30% solution) was used as amino group
source with sodium hydroxide (3 equiv) as base. The obtained
product 3e was characterized by 1H and 13C NMR. The results are
described in Table 1.
Aryl amines (3) prepared from the copper-catalytic amination of ArBF3K (2)
NH4OH (aq.)
FG Ar NH2
FG Ar BF3K
CuSO4. 5 H2O (10 mol%)
NaOH, 25oC, 24h
Entry FG-Ar-BF3K
FG-Ar-NH2
Yielda (%)
As shown in Table 1, the use of copper (II) salts gave the corre-
sponding product in moderate to good yields (Table 1, entries 2–7).
The best results were obtained when CuSO4Á5H2O was used in con-
centrations of 10 and 20 mol %, 3e being obtained in high yields in
both cases. When Cu(OAc)2 was used as a catalyst lower yields
were observed (Table 1, entries 5–7).
1
2
3
2a
2b
2c
3a
3b
3c
75
80
85
BF3K
NH2
Br
BF3K
BF3K
Br
NH2
NH2
F
F
When the reaction was performed with Pd(OAc)2 no product
was observed in the applied concentrations, probably due to the
formation of catalytically unreactive species with ammonia. All
reactions were monitored by 1H NMR until the disappearance of
the starting material which was accomplished after 24 h.
In this way, the suitable catalyst for the proposed reaction was
CuSO4. 5H2O in a concentration of 10 mol %. By extending the reac-
tion conditions to other potassium aryl trifluoroborates, various
functionalized aryl amines were obtained in moderate to good
yields (Table 2) and the formation of the products was confirmed
by the analysis of the 1H and 13C NMR spectra.
NC
BF3K
NH2
NC
4
2d
3d
88
O2N
O
BF3K
NH2
O2N
O
5
6
7
2e
2f
3e
3f
90
92
50
BF3K
NH2
BF3K
NH2
2g
3g
O
O
Inspection of Table 2 shows that the method is tolerant to a
wide range of functional groups, being more efficient when elec-
tron-withdrawing and neutral groups were present in the starting
potassium aryl trifluoroborate. Thus, substrates with the ring con-
taining halogens and cyano, nitro, acetyl, and formyl groups gave
the corresponding functionalized aryl amines in good to moderate
yields (Table 2, entries 1–6).
BF3K
NH2
8
2h
3h
83
40
9
2i
2j
3i
3j
BF3K
NH2
The applications of naphthylamines in the dyestuff industry24
and in heterocyclic chemistry as building blocks25 are well known
and the development of efficient synthetic methods to prepare this
class of compounds is of great interest. In this context, compound
3h was prepared in good yield and high purity using the reaction
conditions (Table 2, entry 8).
b
10
—
BF3K
MeO
NH2
MeO
a
Isolated yield.
b
The corresponding product was not observed.
When a sterically hindered di-ortho-substituted aryl trifluorobo-
rate 2i was used, thecorrespondingaryl aminewas obtained in mod-
erate yield proving, in this case, that the reaction is not only sensitive
to the electronic, but also to steric effects (Table 2, entry 9).
When the electron-donating potassium aryl trifluoroborate
2j was used, the corresponding product 3j was not observed
(Table 2, entry 10).
Recently, the kinetics of hydrolysis of RBF3K to the correspond-
ing boronic acids in the presence and absence of base, buffers, and
glass were studied in detail by Lloyd-Jones and co-workers in the
context of their application in Suzuki–Miyaura coupling.26 They
observed that electron-rich aryl trifluoroborates undergo fast or
very fast hydrolysis, while electron-poor aryl trifluoroborates are
hydrolyzed very slowly.
In our case, this observation together with the fact that elec-
Table 1
tron-rich aryl boronic acids can undergo
a protodeboration
Amination of potassium aryl trifluoroborates using aqueous ammonia: influence of
catalyst
reaction via a SE2 mechanism, the proton transfer being the rate–
determining step followed by the rapid ionic cleavage of C–B
bond,27 that could explain the results observed in Table 2, where
better yields were observed when electron-withdrawing groups
were present in the aromatic ring.
In summary, we have demonstrated that the potassium aryl tri-
fluoroborates are useful substrates for the synthesis of the corre-
sponding aryl amines in good yields under mild conditions. The
green methodology is simple,28 uses water as solvent, low catalyst
loading, and is synthetically useful while it could be applied for the
synthesis of more complex aromatic amines.
O2N
NH2
O2N
BF3K
NH4OH, NaOH
catalyst, 25oC, 24h
2e
3e
Entry
Catalyst (mol %)
3e (%)
1
2
3
4
5
6
7
8
9
10
—
0
CuSO4Á5H2O (5)
CuSO4Á5H2O (10)
CuSO4Á5H2O (20)
Cu(OAc)2 (5)
Cu(OAc)2 (10)
Cu(OAc)2 (20)
Pd(OAc)2 (5)
Pd(OAc)2 (10)
Pd(OAc)2 (20)
50
90
90
50
60
65
0
Acknowledgments
0
0
The authors gratefully acknowledge FACEPE (APQ-1402-1.06/
10), CNPq (484778/2011-0), CAPES, and INCT-INAMI for financial

4242
A. P. Liesen et al. / Tetrahedron Letters 53 (2012) 4240–4242
10. Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40, 275–286.
11. (a) Molander, G. A.; Figueroa, R. Aldrichim. Acta 2005, 38, 49–56; (b) Stefani, H.
A.; Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623–3658; (c) Darses, S.; Genet,
J.-P. Chem. Rev. 2008, 108, 288; (e) Oliveira, R. A. Synlett 2009, 505–506.
12. Santos-Filho, E. F.; Sousa, J. C.; Bezerra, N. M. M.; Menezes, P. H.; Oliveira, R. A.
Tetrahedron Lett. 2011, 52, 5288–5291.
support. P.H.M and A.P.L. are thankful to CNPq for their
fellowships.
Supplementary data
13. Molander, G. A.; Petrillo, D. E. J. Am. Chem. Soc. 2006, 128, 9634–9635.
14. Molander, G. A.; Cooper, D. J. J. Org. Chem. 2007, 72, 3558–3560.
15. Molander, G. A.; Figueroa, R. Org. Lett. 2006, 8, 75–78.
16. Katona, B. W.; Machrouhi, F.; Molander, G. A. J. Org. Chem. 2002, 67, 8416–
8423.
17. (a) Molander, G. A.; Oliveira, R. A. Tetrahedron Lett. 2008, 49, 1266–1268; (b)
Molander, G. A.; Figueroa, R. J. Org. Chem. 2006, 71, 6135–6140; (c) Molander,
G. A.; Ham, J.; Canturk, B. Org. Lett. 2007, 9, 821–824.
Supplementary data (experimental procedures and spectro-
scopic characterization data, as well as 1H, 13C, 19F and 11B NMR
spectra for all synthesized compounds) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/
j.tetlet.2012.06.011. These data include MOL files and InChiKeys
of the most important compounds described in this article.
18. Oliveira, R. A.; Silva, R. O.; Molander, G. A.; Menezes, P. H. Magn. Res. Chem.
2009, 47, 873–878.
19. Petrillo, D. E.; Kohli, R. K.; Molander, G. A. J. Am. Soc. Mass Spectrom. 2007, 18,
404–405.
References and notes
20. Smoum, R.; Rubinstein, A.; Srebnik, M. Org. Biomol. Chem. 2005, 3, 941–944.
21. Queiroz, M.-J. R. P.; Calhelha, R. C.; Vale-Silva, L. A.; Pinto, E.; Lima, R. T.;
Vasconcelos, M. H. Eur. J. Med. Chem. 2010, 45, 5628–5634.
22. Oliveira, R. A.; Savegnago, L.; Jesse, C. R.; Menezes, P. H.; Molander, G. A.;
Nogueira, C. W. Basic Clin. Pharmacol. Toxicol. 2009, 104, 448–454.
23. Vedejs, E.; Fields, S. C.; Hayashi, R.; Hithccock, S. R.; Powell, D. R.; Schrimpf, M.
R. J. Am. Chem. Soc. 1999, 121, 2460–2470.
24. Guinot, S. G. R.; Hepworth, J. D.; Wainwright, M. Dyes and Pigments 1998, 36,
387–393.
25. Yépez, A. F.; Palma, A.; Stashenko, E.; Bahsasb, A.; Amaro-Luis, J. M. Tetrahedron
Lett. 2006, 47, 5825–5828.
26. Lennox, A. J. J.; Lloyd-Jones, G. C. J. Am. Chem. Soc. 2012, 134, 7431–7441.
27. (a) Kuivila, H. G.; Nahabedian, K. V. J. Am. Chem. Soc. 1961, 83, 2159–2163; (b)
Kuivila, H. G.; Nahabedian, K. V. J. Am. Chem. Soc. 1961, 83, 2164–2166; (c)
Nahabedian, K. V.; Kuivila, H. G. J. Am. Chem. Soc. 1961, 83, 2167–2174; (d)
Klingensmith, L. M.; Bio, M. M.; Moniz, G. A. Tetrahedron Lett. 2007, 48, 8242–
8245.
1. (a) Schlummer, B.; Scholz, U. Adv. Synth. Catal. 2004, 346, 1599–1626; (b) Meng,
F.; Zhu, X.; Li, Y.; Xie, J.; Wang, B.; Yao, J.; Wan, Y. Eur. J. Org. Chem. 2010, 6149–
6152.
2. Aubin, Y.; Fischmeister, C.; Thomas, C. M.; Renaud, J. L. Chem. Soc. Rev. 2010, 39,
4130–4145.
3. (a) Pehlivan, L.; Métay, E.; Laval, S.; Dayoub, W.; Demonchaux, P.; Mignani, G.;
Lemaire, M. Tetrahedron Lett. 2010, 51, 1939–1941; (b) Lee, H.-Y.; An, M. Bull.
Korean Chem. Soc. 2004, 25, 1717–1719; (c) Khan, F. A.; Sudheer, C. Tetrahedron
Lett. 2009, 50, 3394–3396; (d) Zhou, Y.; Li, J.; Liu, H.; Zhao, L.; Jiang, H.
Tetrahedron Lett. 2006, 47, 8511–8514; (e) Gamble, A. B.; Garner, J.; Gordon, C.
P.; O’Conner, S. M. J.; Keller, P. A. Synth. Commun. 2007, 37, 2777–2786.
4. Norcliffe, J. L.; Conway, L. P.; Hodgson, D. R. W. Tetrahedron Lett. 2011, 52,
2730–2732.
5. Kokkinidis, G.; Papoutsis, A.; Papanastasiou, G. J. Electroanal. Chem. 1993, 359,
253–271.
6. (a) Ben Taleb, A.; Jenner, G. J. Mol. Catal. 1994, 91, L149–L153; (b) Sharma, U.;
Kumar, P.; Kumar, N.; Kumar, V.; Singh, B. Adv. Synth. Catal. 2010, 352, 1834–
1840; (c) Watanabe, Y.; Ohta, T.; Tsuji, Y.; Hiyoshi, T.; Tsuji, Y. Bull. Chem. Soc.
Jpn. 1984, 57, 2440–2444; For the asymmetric version of the reaction see: (d)
Gladiali, S.; Alberico, E. Chem. Soc. Rev. 2006, 35, 226–236.
7. (a) Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996, 15, 2755–2763;
(b) Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996, 15, 3534–3542;
(c) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030–3039.
8. Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 10028–10029.
9. (a) Cazorla, C.; Métay, E.; Lemaire, M. Tetrahedron 2011, 67, 8615–8621; (b)
Yang, H.; Li, Y.; Jiang, M.; Wang, J.; Fu, H. Chem. Eur. J. 2011, 17, 5652–5660; (c)
Jiang, Z.; Wu, Z.; Wang, L.; Wu, D.; Zhou, X. Can. J. Chem. 2010, 88, 964–968; (d)
Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. Angew. Chem., Int. Ed. 2009, 48, 1114–1116; (e)
Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 4397–4400; (f) Matteson, D. S.; Kim,
G. Y. Org. Lett. 2002, 4, 2153–2155.
28. Representative procedure for the synthesis of 3a: In a flask, at room temperature
and under aerobic conditions, containing
a
mixture of potassium
aryltrifluoroborate 2a (1 mmol, 184 mg), CuSO4Á5H2O (10 mol %, 25 mg) and
NaOH (3 mmol, 120 mg) was added NH4OH (4.0 mL of a 28–30% solution). The
contents were stirred for 24 h. After this period, the reaction was extracted
with dichloromethane (3 Â 10 mL). The combined organic layers were washed
with 1 M HCl (30 mL) and to the aqueous layer was added solid NaHCO3 (until
pH ꢀ9). The resulting mixture was again extracted with dichloromethane
(3 Â 10 mL) and the combined organic layers were dried over anhydrous
MgSO4 and filtered. The solvent was removed in vacuo to yield 69 mg of 3a
(75%) sufficiently pure for characterization. 1H NMR (300 MHz; CDCl3) d 7.34 (t,
J = 7.7 Hz, 2H), 6.95 (t, J = 7.7 Hz, 1H), 6.79 (d, J = 8.5 Hz, 2H), 3.66 (s, 2H); 13C
NMR (75 MHz, CDCl3) d 146.2, 129.0, 118.0, 114.8.