Direct amination of pyrimidin-2-yl tosylates with aqueous ammonia under metal-free and mild conditions

Article abstract of DOI:10.1016/j.cclet.2015.01.034

Abstract A metal-free synthesis of pyrimidine functionalized primary amines via direct amination of pyrimidin-2-yl tosylate with aqueous ammonia has been developed under mild conditions. The desired products pyrimidin-2-amines can be generated in excellen

Full text of DOI:10.1016/j.cclet.2015.01.034

G Model
CCLET 3222 1–5
Chinese Chemical Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
1
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Original article
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Direct amination of pyrimidin-2-yl tosylates with aqueous ammonia
under metal-free and mild conditions
* *
Q1 Hai-Peng Gong, Yue Zhang, Yu-Xia Da, Zhang Zhang, Zheng-Jun Quan , Xi-Cun Wang
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Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, Gansu Key Laboratory of Polymer Materials, College of Chemistry and
Chemical Engineering, Northwest Normal University, Lanzhou 730070, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A metal-free synthesis of pyrimidine functionalized primary amines via direct amination of pyrimidin-2-
yl tosylate with aqueous ammonia has been developed under mild conditions. The desired products
pyrimidin-2-amines can be generated in excellent yields in PEG-400, without any catalysts or other
additives.
Received 3 December 2014
Received in revised form 15 January 2015
Accepted 21 January 2015
Available online xxx
ß 2015 Zheng-Jun Quan and Xi-Cun Wang. Published by Elsevier B.V. on behalf of Chinese Chemical
Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.
Keywords:
Ammonia
2-Aminopyrimidines
Pyrimidin-2-yl tosylate
PEG-400
8
9
1. Introduction
utilization as important precursors in the synthesis of pyrimidine 32
bases [12]. In continuation of our ongoing interest in the synthesis 33
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Q2
Primary (hetero)aryl amines are widely used in the synthesis of
natural products, pharmaceuticals, agrochemicals as well as
polymers and materials [1]. The common methods for preparation
of primary amines include coupling of aryl halides with ammonia
[2], reductive amination of carbonyl compounds [3], and hydro-
amination of alkenes [4–6]. Recently, ammonia, as one of the most
attractive sources of nitrogen, has attracted a lot of attentions due
to its great abundance and extremely low cost [7,8]. Very recently,
a few methodological advancements for coupling aryl halides with
aqueous ammonia to deliver aryl primary amines under mild
conditions have been developed [9,10].
Aryl sulfonates that are easily prepared, usually crystalline, and
lower toxicity, are with potential values to investigate as better
materials to synthesize primary amines. Despite great progress
toward the preparation of primary amines has been made, selective
synthesis of primary amines from ammonia still encounters
challenges, i.e. requirement of transition-metal, overreactions of
primary amines with ammonia. Hence, further efforts were needed
to developing a metal-free, mild method for the selective synthesis
of primary amines directly from aqueous ammonia.
of 3,4-dihydropyrimidinone derivatives [13], we are recently 34
interesting in the synthesis of 2-aminopyrimidines. 35
2-Aminopyrimidines show interesting biological activities such 36
as inhibitors of rhoassociated protein kinease [14,15], glycogen 37
synthase kinease 3 (GSK3) [16], and of N-type calcium channels 38
[17]. Notably, the 2-amino-4-arylpyrimidine heterocycle is also 39
found in important drugs such as the hypocholesterolemic agent 40
rosuvastatin [18,19] and the potent anticancer drug Gleevec [20]. 41
Usually, 2-aminopyrimidine subunits are constructed by 42
condensation reactions of enones with corresponding guanidine 43
or nitrogen-containing building blocks [21]. In 2007, Kappe et al. 44
[22] have described a three-step procedure to convert Biginelli 45
DHPMs to 2-methylsulfonyl-pyrimidines, which subsequently 46
converted to 2-aminopyrimidine by the substitution of the reactive 47
sulfonyl group with ammonium acetate as substitute for NH3 48
(Scheme 1, Method A).
49
Herein we developed a metal-free approach for the synthesis 50
of 2-aminopyrimidines directly from pyrimidin-2-yl tosylates 51
with aqueous ammonia under mild conditions in PEG medium 52
(Scheme 1, Method B).
53
3,4-Dihydropyrimidinones and their derivatives have conse-
quently been extensively used as a drug-like scaffold [11] and
2. Experimental
54
Commercially available reagents were used without further 55
purification unless otherwise stated. Melting points were mea- 56
sured on a XT-4 apparatus and are uncorrected. NMR spectra were 57
*
Corresponding authors.
E-mail addresses: quanzhengjun@htmail.com (Z.-J. Quan),
wangxicun@nwnu.edu.cn (X.-C. Wang).
http://dx.doi.org/10.1016/j.cclet.2015.01.034
1001-8417/ß 2015 Zheng-Jun Quan and Xi-Cun Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of
Medical Sciences. All rights reserved.
Please cite this article in press as: H.-P. Gong, et al., Direct amination of pyrimidin-2-yl tosylates with aqueous ammonia under metal-
free and mild conditions, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.01.034

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H.-P. Gong et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
Scheme 1. Synthesis of the 2-aminopyrimidines starting from 3,4-dihydropyrimidinones.
58
59
60
61
62
63
64
recorded at 400 MHz (1H) and 100 MHz (13C), respectively, on a
Varian Mercury plus-400 instrument using CDCl3 as solvent
and TMS as internal standard. High-resolution mass spectra
(HRMS) were obtained on a Bruker Daltonics APEX II 47e mass
spectrometer. Column chromatography was generally performed
on silica gel (200–300 mesh) and TLC inspections were on silica gel
GF254 plates.
2H, J = 6.8 Hz), 2.45 (s, 3H), 2.37 (s, 3H), 0.99 (t, 3H, J = 7.2 Hz); 13
NMR (100 MHz, CDCl3): 168.62, 167.23, 166.30, 161.96, 139.60,
135.66, 128.91, 127.70, 116.12, 61.09, 22.62, 21.27, 13.55; HRMS:
calcd. for C15H18N3O2 [M+H]+: 272.1394; found 272.1400.
Ethyl 2-amino-4-(4-methoxyphenyl)-6-methylpyrimidine-5-
carboxylate (2f): White solid, mp 128–130 8C. 1H NMR
C
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
d
(400 MHz, CDCl3):
d 7.49 (d, 2H, J = 8.0 Hz), 6.91 (d, 2H,
J = 8.0 Hz), 5.95 (d, 2H, J = 29.2 Hz), 4.10 (q, 2H, J = 7.2 Hz), 3.81
(s, 3H), 2.42 (s, 3H), 1.03 (t, 3H, J = 7.0 Hz); 13C NMR (100 MHz,
65
66
2.1. General procedure for the synthesis of 2-amino pyrimidines (2a–
2n)
CDCl3):
115.85, 113.65, 61.07, 55.24, 22.53, 13.66; HRMS: calcd. for
15H18N3O3 [M+H]+: 288.1343; found 288.1348.
Ethyl 2-amino-4-methyl-6-(4-nitrophenyl)pyrimidine-5-
carboxylate (2g): White solid, mp 128–129 8C. 1H NMR
(400 MHz, CDCl3): 8.42 (s, 1H), 8.27 (d, 1H, J = 8.0 Hz), 7.84 (d,
d 168.79, 167.07, 165.56, 161.98, 160.82, 130.88, 129.41,
67
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69
70
71
72
73
74
75
76
77
78
79
80
81
82
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84
85
86
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88
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90
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94
95
96
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98
99
100
101
102
103
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105
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The pyrimidin-2-yl tosylate (1, 1.0 mmol), PEG-400 (2 mL) and
ammonia water (10 mmol) were added into a test tube. The tube
was then sealed with a balloon, and the mixture was stirred at r.t.
for 24 h. Then the mixture was poured into water to precipitate the
product. Crude product was obtained by means of vacuum
filtration, and was further purified by column chromatography
on silica gel with petroleum ether/ethyl acetate (3:1) and (1:1) to
give the corresponding products 2a–i and 2j–n, respectively.
Ethyl 2-amino-4-methyl-6-phenylpyrimidine-5-carboxylate
(2a): White solid, mp 132–133 8C [22]. 1H NMR (400 MHz, CDCl3):
C
d
1H, J = 7.6 Hz), 7.58 (t, 1H, J = 8.0 Hz), 5.75 (s, 2H), 4.11 (q, 2H,
J = 7.2 Hz), 2.49 (s, 3H), 1.03 (t, 3H, J = 7.2 Hz). 13C NMR (100 MHz,
CDCl3):
d 168.45, 167.65, 163.86, 161.94, 140.25, 129.23, 124.11,
123.16, 116.07, 61.43, 22.98, 13.64; HRMS: calcd. for C14H15N4O4
[M+H]+: 303.1088; found 303.1093.
Ethyl
carboxylate (2h): White solid, mp 131–132 8C. 1H NMR
(400 MHz, CDCl3): 8.43 (s, 1H), 8.28 (d, 1H, J = 8.0 Hz), 7.85 (d,
2-amino-4-methyl-6-(3-nitrophenyl)pyrimidine-5-
d
7.52–7.50 (m, 2H), 7.41 (d, 3H, J = 5.2 Hz), 5.82 (s, 2H), 4.05 (q, 2H,
J = 7.2 Hz), 2.48 (s, 3H), 0.94 (t, 3H, J = 7.6 Hz); 13C NMR (100 MHz,
CDCl3): 168.31, 167.48, 166.47, 161.98, 138.60, 129.35, 128.15,
127.63, 115.95, 61.00, 22.58, 13.40.
d
d
1H, J = 7.6 Hz), 7.59 (t, 1H, J = 8.0 Hz), 5.73 (s, 2H), 4.12 (q, 2H,
J = 6.8 Hz), 2.50 (s, 3H), 1.04 (t, 3H, J = 7.0 Hz); 13C NMR (100 MHz,
CDCl3): d 168.45, 167.64, 163.85, 161.92, 148.06, 140.25, 133.86,
129.23, 124.11, 123.16, 116.05, 61.42, 22.98, 13.64; HRMS: calcd.
for C14H15N4O4 [M+H]+: 303.1088; found 303.1095.
Methyl 2-amino-4-(4-fluorophenyl)-6-isopropylpyrimidine-5-
carboxylate (2i): White solid, mp 146–148 8C. 1H NMR (400 MHz,
Ethyl
2-amino-4-(4-fluorophenyl)-6-methylpyrimidine-5-
carboxylate (2b): White solid, mp 167–168 8C. 1H NMR
(400 MHz, CDCl3):
5.82 (d, 2H, J = 10.0 Hz), 4.07 (q, 2H, J = 7.2 Hz), 2.48–2.40 (m, 3H),
1.00 (t, 3H, J = 7.1 Hz); 13C NMR (100 MHz, CDCl3):
168.30,
d 7.53–7.49 (m, 2H), 7.08 (t, 2H, J = 8.6 Hz),
d
167.60, 164.98 (d, J = 38.0 Hz), 162.31, 161.92, 134.70, 129.84 (d,
J = 8.0 Hz), 116.14, 115.27 (d, J = 22.0 Hz), 61.16, 22.65, 13.58;
HRMS: calcd. for C14H15FN3O2 [M+H]+: 276.1143; found 276.1147.
Ethyl 2-amino-4-(4-chlorophenyl)-6-methylpyrimidine-5-car-
boxylate (2c): White solid, mp 164–166 8C. 1H NMR (400 MHz,
CDCl3):
J = 12.4 Hz), 3.62 (s, 3H), 3.13 (s, 1H), 1.25 (t, 6H, J = 3.2 Hz); 13C
NMR (100 MHz, CDCl3): 175.27, 169.32, 164.78, 164.46, 162.42,
d 7.55 (s, 2H), 7.11 (t, 2H, J = 6.6 Hz), 5.56 (d, 2H,
d
134.65, 129.78 (d, J = 8.0 Hz), 115.51, 115.29, 52.14, 32.82, 21.50;
HRMS: calcd. for C15H17FN3O2 [M+H]+: 290.1299; found 290.1302.
6-Methyl-N2-phenylpyrimidine-2,4-diamine (2j): White solid,
CDCl3):
4.08 (q, 2H, J = 7.2 Hz), 2.46 (s, 3H), 1.01 (t, 3H, J = 7.2 Hz); 13C NMR
(100 MHz, CDCl3): 168.11, 167.71, 165.07, 161.83, 137.00,
d 7.46 (d, 2H, J = 8.4 Hz), 7.38 (d, 2H, J = 8.4 Hz), 5.74 (s, 2H),
mp 122–124 8C. 1H NMR (400 MHz, CDCl3):
d
7.67 (s, 1H), 7.52 (d,
2H, J = 7.6 Hz), 7.20 (t, 2H, J = 7.2 Hz), 6.90 (t, 1H, J = 7.4 Hz), 5.70 (s,
1H), 4.77 (s, 2H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3):
165.97,
d
135.66, 129.16, 128.41, 116.09, 61.17, 22.67, 13.53; HRMS: calcd.
for C14H15ClN3O2 [M+H]+: 293.0847; found 293.0851.
d
163.81, 159.45, 139.89, 128.64, 121.97, 119.32, 95.48, 23.25;
HRMS: calcd. for C11H13N4 [M+H]+: 201.1135; found 201.1139.
6-Methyl-N2-o-tolylpyrimidine-2,4-diamine (2k): White solid,
mp 188–190 8C. 1H NMR (400 MHz, CDCl3):
d 7.95 (d, 1H,
J = 8.0 Hz), 7.11 (q, 2H, J = 8.0 Hz), 6.90 (t, 1H, J = 7.2 Hz), 6.60 (s,
1H), 5.71 (s, 1H), 4.60 (s, 2H), 2.21 (s, 3H), 2.17 (s, 3H); 13C NMR
Ethyl
carboxylate (2d): White solid, mp 138–139 8C. 1H NMR
(400 MHz, CDCl3): 7.51 (d, 2H, J = 8.4 Hz), 7.36 (d, 2H,
J = 8.4 Hz), 5.88 (s, 2H), 4.08–4.03 (m, 2H), 2.43 (s, 3H), 0.98 (t,
3H, J = 7.0 Hz); 13C NMR (100 MHz, CDCl3):
168.09, 167.78,
2-amino-4-(4-bromophenyl)-6-methylpyrimidine-5-
d
d
165.19, 161.92, 137.49, 131.39, 129.42, 123.95, 116.11, 61.22,
22.70, 13.56; HRMS: calcd. for C14H15BrN3O2 [M+H]+: 336.0342;
found 336.0345.
(100 MHz, CDCl3): d 166.73, 163.89, 160.33, 137.96, 130.28,
128.36, 126.34, 122.95, 121.83, 95.47, 23.76, 18.10; HRMS: calcd.
for C12H15N4 [M+H]+: 215.1291; found 215.1295.
Ethyl
(2e): White solid, mp 151–153 8C 1H NMR (400 MHz, CDCl3):
7.41 (d, 2H, J = 7.6 Hz), 7.20 (d, 2H, J = 7.6 Hz), 5.87 (s, 2H), 4.08 (q,
2-amino-4-methyl-6-p-tolylpyrimidine-5-carboxylate
6-Methyl-N2-m-tolylpyrimidine-2,4-diamine (2l): Yellow oil.
d
1H NMR (400 MHz, CDCl3):
d
7.38–7.26 (m, 3H), 7.09 (t, 1H,
J = 7.6 Hz), 6.72 (d, 1H, J = 7.2 Hz), 5.70 (s, 1H), 4.75 (s, 2H), 2.24 (s,
Please cite this article in press as: H.-P. Gong, et al., Direct amination of pyrimidin-2-yl tosylates with aqueous ammonia under metal-
free and mild conditions, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.01.034

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H.-P. Gong et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
3
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165
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3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
166.26, 163.84,
solvents, the reaction gave a good yield of 2a and the hydrolyzation 193
of 1a was completely inhibited (entries 6 and 7). Further testing 194
implied that PEG-400 was the best one among the PEG-200, PEG- 195
400, PEG-600 and PEG-800 to give 2a in 86% yield (entries 7–10). 196
Higher temperature slightly enhanced the yield at a shorter time 197
(entries 11 and 12). Therefore, our focus was concentrated on the 198
solvents and reaction conditions. Notably, base can greatly 199
accelerate the translation of 1a into the byproduct 3a (82%), with 200
the yields of 2a tremendously declined (entry 13). Download the 201
amount of aqueous ammonia to 5 equiv. caused lower transfor- 202
mation (entry 14). Thus, the optimal conditions for this reaction 203
were established: using PEG-400 as the reaction medium to 204
159.72, 139.83, 138.43, 128.52, 122.86, 119.97, 116.57, 95.45,
23.48, 21.51; HRMS: calcd. for C12H15N4 [M+H]+: 215.1291; found
215.1297.
6-Methyl-N2-p-tolylpyrimidine-2,4-diamine (2m): Yellow oil.
1H NMR (400 MHz, CDCl3):
d
7.69 (d, 1H, J = 7.2 Hz), 7.35 (d, 2H,
J = 7.2 Hz), 6.98 (d, 2H, J = 7.6 Hz), 5.66 (s, 1H), 4.74 (s, 2H), 2.20 (s,
3H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3):
166.38, 163.85,
d
159.93, 137.30, 131.53, 129.17, 119.79, 95.34, 23.54, 20.69; HRMS:
calcd. for C12H15N4 [M+H]+: 215.1291; found 215.1294.
N2-(4-Chlorophenyl)-6-methylpyrimidine-2,4-diamine (2n):
White solid, mp 136–138 8C. 1H NMR (400 MHz, CDCl3):
d
7.72
(d, 1H, J = 8.0 Hz), 7.45 (d, 2H, J = 8.4 Hz), 7.12 (d, 2H, J = 8.4 Hz),
5.72 (s, 1H), 4.76 (s, 2H), 2.15 (s, 3H); 13C NMR (100 MHz, CDCl3):
perform the reaction at r.t. for 24 h.
205
d
Under the optimized conditions, the amination of pyrimidin-2- 206
yl tosylates (1a–i) with aqueous ammonia was tested in the 207
reaction scope (Scheme 2). In general, good yields of the desired Q3208
products were obtained. The reaction tolerated a variety of 209
pyrimidin-2-yl tosylates containing the electron-withdrawing 210
group as well as the electron-donating group on the phenyl ring 211
to deliver the products (2a–i) with good yields. Compared with the 212
previous reports, this non-catalytic approach was proven to be a 213
powerful tool for the amines preparation in mild conditions with 214
165.48, 163.74, 158.89, 138.43, 128.45, 126.60, 120.41, 95.62,
22.86; HRMS: calcd. for C11H12ClN4 [M+H]+: 235.0745; found
235.0758.
4-Nitroaniline: 1H NMR (CDCl3, 400 MHz):
d 3.64 (s, 2H), 6.59–
6.61 (m, 2H), 7.09–7.10 (m, 2H); 13C NMR (CDCl3, 100 MHz):
116.15, 123.02, 129.03, 144.88.
d
178
3. Results and discussion
the lower-priced ammonia water as ammonia source [22].
215
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187
188
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190
191
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The work was initiated with the optimization of the reaction
conditions of the direct amination of pyrimidin-2-yl tosylate 1a
with aqueous ammonia, utilizing 20 equiv. of sodium dodecyl-
benzenesulfonate (SDBS) as phase-transfer catalyst (PTC) and
dioxane as solvent at 100 8C for 12 h (Table 1). As our prediction,
the reaction afforded the amination product 2-aminopyrimidine
2a in a yield of 69% (entry 1), however, hydrolyzed product
pyrimidin-2-ol 3a of 1a was also isolated in 41% yield. Lowering the
temperature to 50 8C resulted in a higher yield of 2a (entry 2).
When the SDBS was changed to hexadecyl trimethyl ammonium
bromide (HTAB), cetylpyridinium chloride (CPC) and bromohex-
adecyl pyridine (CPB), the yield of 2a increased (84–89%) and trace
of 3a was detected (entries 3–6). In order to find a cheaper PTC, PEG
was tested. To our delight, only using PEG-200 without any other
Given the operational simplicity and broad generality of this 216
direct amination protocol, we explored to demonstrate the utility 217
of this strategy for the similar amine 2-aminopyrimidines using 218
pyrimidin-4-yl tosylates (1j–n) as substrates. The desired products 219
(2j–n) were also obtained in moderate yields under this simple 220
reaction conditions. However, lower yields were observed, which 221
due to the hydrolyzation of the starting materials.
222
To further demonstrate the versatility of the above described 223
amination protocol, aryl- and pyridinyl tosylates were tested with 224
aqueous ammonia. Unfortunately, only the aryl tosylate with 225
strong electron-withdrawing substituent (NO2) underwent the 226
amination to afford 4-nitroaniline in 50% yield. However, phenyl 227
tosylate and pyridine-2-yl tosylate did not undergo amination 228
with aqueous ammonia.
229
Table 1
Optimization of conditions of pyrimidin-2-yl tosylate with NH3ÁH2O.a
Entry
NH3ÁH2O
Solvent (PTC)
Temp
Yield
(%)b
(equiv.)
(8C)
2a
3a
1c
2
10
10
10
10
10
10
10
10
10
10
10
10
10
5
Dioxane/SDBS
Dioxane/SDBS
Dioxane/CTAB
Dioxane/CPC
Dioxane/CPB
Dioxane/PEG-200
PEG-200
50
45
69
89
84
87
78
77
86
74
58
85
88
10
68
41
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
21
3
Trace
Trace
Trace
Trace
Trace
Trace
Trace
Trace
Trace
Trace
82
4
5
6
7
8
PEG-400
9
PEG-600
10
11c
12c
13d
14
PEG-800
PEG-400
PEG-400
100
r.t.
r.t.
PEG-400
PEG-400
Trace
a
Reaction conditions: pyrimidin-2-yl 4-methylbenzenesulfonates (1a) (1.0 mmol), commercial 28% aqueous NH3 (10 mmol), solvent (2 mL).
b
c
Isolated yield.
The reaction time is 12 h.
K3PO4 (0.1 mmol) was added.
d
Please cite this article in press as: H.-P. Gong, et al., Direct amination of pyrimidin-2-yl tosylates with aqueous ammonia under metal-
free and mild conditions, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.01.034

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H.-P. Gong et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
Scheme 2. Scope of the amination of pyrimidin-4-yl tosylates with NH3ÁH2O.
(c) S. Ogo, K. Uehara, T. Abura, S. Fukuzumi, pH-dependent chemoselective
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306
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4. Conclusions
synthesis of a-amino acids. Reductive amination of a-keto acids with ammonia
catalyzed by acid-stable iridium hydride complexes in water, J. Am. Chem. Soc.
126 (2004) 3020–3021.
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236
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In conclusion, we introduced a novel approach for amination of
pyrimidinyl-2-tosylates with aqueous ammonia. The desired
products 2-aminepyrimidines can be generated in high yields in
mild conditions, without any catalysts or other additives.
Meanwhile, the similar pyrimidin-4-yl tosylates and aryl tosylates
substituted by electron-withdrawing substituents such as -NO2
afforded the desired product under the simple reaction conditions.
[4] (a) S. Hong, T.J. Marks, Organolanthanide-catalyzed hydroamination, Acc. Chem.
Res. 37 (2004) 673–686;
(b) V. Lavallo, G.D. Frey, B. Donnadieu, M. Soleilhavoup, G. Bertrand, Homoge-
neous catalytic hydroamination of alkynes and allenes with ammonia, Angew.
Chem. Int. Ed. 47 (2008) 5224–5228;
(c) J. Seayad, A. Tillack, C.G. Hartung, M. Beller, Base-catalyzed hydroamination of
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free and mild conditions, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.01.034