Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl ketones with o-bromoacetophenones

Article abstract of DOI:10.1016/j.cclet.2015.07.022

The coupling reactions of simple methyl ketones with o-bromoacetophenones and subsquential cyclization reactions were realized to produce a range of 1-naphthols. These cascade reactions were initiated by a rare Cu-catalyzed arylation reaction of methyl ketones with aromatic bromides.

Full text of DOI:10.1016/j.cclet.2015.07.022

G Model
CCLET 3399 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
2
Original article
3
4
Facile synthesis of 1-naphthols through a copper-catalyzed arylation
of methyl ketones with o-bromoacetophenones
a
a,
Q1 Zhen-Bang Lou a,b, Xin-Long Pang a,b, Chao Chen b, , Li-Rong Wen , Ming Li
*
*
5
6
7
8
a College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
b Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University,
Beijing 100084, China
A R T I C L E I N F O
A B S T R A C T
Article history:
The coupling reactions of simple methyl ketones with o-bromoacetophenones and subsquential
cyclization reactions were realized to produce a range of 1-naphthols. These cascade reactions were
initiated by a rare Cu-catalyzed arylation reaction of methyl ketones with aromatic bromides.
ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Received 15 May 2015
Received in revised form 10 July 2015
Accepted 20 July 2015
Available online xxx
Keywords:
Copper
Arylation
Ketones
Naphthol
9
10
1. Introduction
initiated by a rare Cu-catalyzed arylation reaction of methyl 31
ketones with aromatic bromides (Scheme 1)! Since substituted o- 32
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Cu-catalyzed arylation reactions are very practical and efficient
to transfer aromatic halides into more valuable aromatic
compounds [1]. Although a large variety of hetero-atomed (N, O
and S) nucleophiles are generally applied as the partner of aromatic
halides in these reaction [2–4], C-nucleophiles are limited to highly
activated carbonyl compounds such as keto-esters, malonic acid
derivatives, or diketones [5]. Very recently, the first example of Cu-
bromoacetophenones are more economical, readily available but 33
less reactive than corresponding o-iodoacetophenones, it is worth 34
reporting that the Cu-catalyzed arylation reactions of simple 35
methyl ketones with o-bromoacetophenones and subsquential 36
cyclization reactions to 1-naphthols [10].
37
catalyzed
a
-arylation of benzyl phenyl ketones with aromatic
2. Experimental
38
iodides was also realized [6]. The Cu-catalyzed arylation of simple
ketones (such as methyl ketones) is very attractive but remains a
big challenge [7]. On the other hand, only aromatic iodides (other
than bromides and chlorides) gave satisfactory results in most Cu-
catalyzed arylation reactions.
As one part of our ongoing project on synthesizing cyclic
compounds with copper catalysts [8], recently, we reported a
specific example that Cu-catalyzed arylation reaction of simple
methyl ketones with o-iodoacetophenones was realized under
very mild conditions and a tandem cyclization followed to give
useful 1-naphthol derivatives [9]. After great effort, the reaction
was found to be applicable to o-bromoacetophenones, which was
All the reactions were carried out in a pre-dried screwcapped 39
tube with a Teflon-lined septum under N2 atmosphere. Bromo 40
acetophenone derivatives except bromoacetophenone 1a were 41
prepared according to the literatures. All of the solvents were 42
freshly distilled. Column chromatography was performed on silica 43
gel (particle size 10–40
mm, Ocean Chemical Factory of Qingdao, 44
China). 1H NMR and 13C NMR spectra were recorded on a JEOL AL- 45
300 MHz or AL-400 MHz spectrometer at ambient temperature 46
with CDCl3 as the solvent. Chemical shifts (d) were given in ppm, 47
referenced to the residual proton resonance of CDCl3 (7.26), to the 48
carbon resonance of CDCl3 (77.16). Coupling constants (J) were 49
given in Hertz (Hz). The term m, dq, q, t, d, s referred to multiplet, 50
doublet quartet, quartet, triplet, doublet, singlet. Mass spectra 51
were obtained using Bruker Esquire ion trap mass spectrometer in 52
positive mode. The reaction progress was monitored by GC-MS if 53
*
Corresponding authors.
E-mail addresses: chenchao01@mails.tsinghua.edu.cn (C. Chen),
applicable, using n-dodecane as internal standard.
54
liming928@qust.edu.cn (M. Li).
http://dx.doi.org/10.1016/j.cclet.2015.07.022
1001-8417/ß 2015 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Z.-B. Lou, et al., Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl
ketones with o-bromoacetophenones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.07.022

G Model
CCLET 3399 1–5
2
Z.-B. Lou et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
Scheme 1. Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl ketones with o-bromoacetophenones.
55
2.1. General procedure for the preparation of desired compound 3a-l
with Et2O (5 mL ꢀ 3), dried over anhydrous Na2SO4. Evaporation of
the solvent followed by purification on silica gel (petroleum ether/
diethyl ether: 25/1 to 10/1) provided the corresponding product
3a-l as a solid or yellow oil.
64
65
66
67
56
57
58
59
60
61
62
63
A sealed tube was charged with the mixture of CuI (0.1 mmol,
19.0 mg), 1,10-phenanthroline (0.2 mmol, 36.0 mg), NaOtBu
(6 mmol, 0.576 g) and bromo acetophenone derivatives
1
(1.0 mmol). The tube was evacuated and recharged with N2 for
3 times. Before toluene (2.0 mL) was added, the tube was sealed
and the mixture was allowed to stir at 120 8C for 4 h. After
completion, the mixture was cooled to room temperature, then
2 mol/L HCl aq. (1–2 mL) was added and the mixture was extracted
2.2. General procedure for the preparation of desired compound 3m-q
68
A sealed tube was charged with the mixture of CuI (0.1 mmol,
19.0 mg), 1,10-phenanthroline (0.2 mmol, 36.0 mg), NaOtBu
(6 mmol, 0.576 g) and o-bromoacetophenone 1a (1.0 mmol). The
69
70
71
Scheme 2. The best condition for the formation of 3a.
Fig. 1. 1-Naphthols 3 formed by the dimerization of 1.
Please cite this article in press as: Z.-B. Lou, et al., Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl
ketones with o-bromoacetophenones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.07.022

G Model
CCLET 3399 1–5
Z.-B. Lou et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
3
72
73
74
75
76
77
78
79
80
81
tube was evacuated and recharged with N2 for 3 times. After
toluene (2.0 mL) was added, ketone 1m-q (3 equiv., 3 mmol) was
added to the tube slowly. Then the tube was sealed and the mixture
was allowed to stir at 120 8C for 4 hours. After completion, the
mixture was cooled to room temperature, then 2 mol/L HCl aq. (1–
2 mL) was added and the mixture was extracted with Et2O
(5 mL ꢀ 3), dried over anhydrous Na2SO4. Evaporation of the
solvent followed by purification on silica gel (petroleum ether/
diethyl ether: 25/1 to 10/1) provided the corresponding product
3m-q as a solid.
ring-fused 1-naphthols were obtained (3k-3l). The structure of 3l 104
was unequivocally confirmed with X-ray diffraction (Fig. 2).
105
Encouraged by the successful synthesis of 1-naphthols via the 106
homo-dimerization of o-bromoacetophenones 1, we attempted to 107
realize the cross-cyclization of o-bromoacetophenone 1a with 108
other simple ketones. Apparently, this reaction is more challeng- 109
ing since the homo-dimerization of o-bromoacetophenones 110
should be avoided. To our delight, as shown in Table 1, it was 111
found when simple ketones 1m-1q were used much excess to o- 112
bromoacetophenone 1a, only cross-cyclization products were 113
isolated. Interestingly, when asymmetric ketone, 2-butanone 114
1n was employed, only 2-ethyl-1-naphthol 3n was isolated, 115
which indicated CH3 group was more reactive than CH2 group 116
in this reaction. Propiophenone 1q was also fit for this reaction 117
to produce 3,4-disubstituted 1-naphthol 3q, albeit in a lower 118
82
3. Results and discussion
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
The beginning study stemmed from the synthesis 1-naphthols
via dimerization of o-bromoacetophenones 1a. We attempted to
carry out the reaction under the same reaction as used in the case
of o-iodoacetophenones but failed to get any product 2a [9].
Considering the lower reactivity of o-bromoacetophenones, the
reaction temperature was raised to 80 8C with THF as the solvent.
Excitingly, the expected product 2a was formed in 20% yield. It is
worth noting that NaOtBu was found as the best base for this
reaction and the amount of NaOtBu was crucial: 2a was formed in
58% yield with 5 equiv. of NaOtBu, and in 70% yield with 6 equiv. of
Q2 NaOtBu (See Table S1 in Supporting information). When the
reaction was carried out in toluene at 120 8C, 3a was isolated in
84% yield after normal work-up (Scheme 2) (For the details of
optimization, see Supporting information).
yield.
119
We also attempted the reaction of o-iodine acetophenone with 120
1o-1q according to the condition in Table 1. Unfortunately, under 121
this condition, the reaction gave messy products due to the strong 122
reactivity of o-iodine acetophenone.
123
It is worth noting that those synthesized 1-naphthols 3a-3l 124
with one bromo-atom were able to be further modified. For 125
example, compound 3a was reduced to give 3o by the treatment 126
with HCOONH4 solution in the presence of Pd/C (10%) (Scheme 3) 127
[11]. Under a standard Suzuki-coupling condition with phenyl- 128
boronic acid, compound 3a was successfully converted to 3r in 129
75% yield (Scheme 4) [12]. Moreover, the modification of 130
compound 3a was sometimes able to be done in one pot during 131
its formation from 1a (Scheme 5). When 1a was reacted with 132
trifluoroethanol in the standard condition [13], product 3s was 133
Inspired by the above result,
a series of substituted o-
bromoacetophenones 1 were homo-dimerized to give functional-
ized 1-naphthols 3, and the results were listed in Fig. 1. Generally,
o-bromoacetophenones 1 with a range of substitutents such as
methyl, methoxide, fluoro, and bromo groups (1b-1j) could
perform the reactions well to give substituted phenyl-1-naphthols
(3b-3j). Excitedly, when polycyclic substrates (1k-1l) were used,
isolated in 78% yield.
134
Table 1
1-Naphthols 3m-3q formed by the reaction of 1a with methyl ketones.
.
1m-1q
3m-3q
Yield (%)
58
43
64
63
45
Q5
Fig. 2. Crystal structure of 3l (CCDC number: 935169). Hydrogen atoms are omitted
for clarity.
Please cite this article in press as: Z.-B. Lou, et al., Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl
ketones with o-bromoacetophenones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.07.022

G Model
CCLET 3399 1–5
4
Z.-B. Lou et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
Scheme 3. The reductive of 1-naphthol 3a in the presence of Pd/C.
Scheme 4. Suzuki-coupling of 1-naphthol 3a and phenylboronic acid.
Scheme 5. Synthesis of compound 3s in one pot from 1-naphthol 3a.
pling of aryl halides with imidazoles, Tetrahedron Lett. 40 (1999) 2657–2660;
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
135
4. Conclusion
(c) S.E. Creutz, K.J. Lotito, G.C. Fu, J.C. Peters, Photoinduced Ullmann C–N cou-
pling: demonstrating the viability of a radical pathway, Science 338 (2012) 647–
651;
(d) C.C. Malakar, A. Baskakova, J. Conrad, U. Beifuss, Copper-catalyzed synthesis
of quinazolines in water starting from o-bromobenzylbromides and benzami-
dines, Chem. Eur. J. 18 (2012) 8882–8885;
(e) W. Liu, L.Y. Han, R.L. Liu, L.G. Xu, Y.L. Bi, Copper-catalyzed N-arylation of 2-
arylindoles with aryl halides, Chin. Chem. Lett. 25 (2014) 1240–1243;
(f) M. Hamidreza, M.G. Mohammad, Practical copper-catalyzed N-arylation
of amines with 20% aqueous solution of n-Bu4NOH, Chin. Chem. Lett. 23
(2012) 301–304.
136
137
138
139
140
141
142
143
144
In conclusion, we have developed Cu-catalyzed cyclization
reaction for the synthesis of 1-naphthols by the dimerization of o-
bromoacetophenones 1 or cross-cyclization of o-bromoacetophe-
nones 1 with simple ketones 1m-1q. The process was initiated by a
rare Cu-catalyzed arylation of simple methyl ketones with
aromatic bromides. The cascade strategy with simple substrates
and catalyst marks
approaches. Therefore, we believe this method will be very useful
in organic chemistry and medicinal chemistry.
a significant departure from known
[3] (a) Cu-catalyzed arylation reactions with O-nucleophiles, see: F. Ullmann, P.
Sponagel, Ueber die phenylirung von phenolen, Chem. Ber. 38 (1905) 2211–2212;
(b) A. Ouali, J.F. Spindler, A. Jutand, M. Taillefer, Nitrogen ligands in copper-
catalyzed arylation of phenols: structure/activity relationships and applications,
Adv. Synth. Catal. 349 (2007) 1906–1916;
145
Acknowledgment
(c) D. Maiti, S.L. Buchwald, Orthogonal Cu- and Pd-based catalyst systems for the
O- and N-arylation of aminophenols, J. Am. Chem. Soc. 131 (2009) 17423–17429;
(d) Y.P. Zhang, A.H. Shi, Y.S. Yang, C.L. Li, Impregnated copper on magnetite as
catalyst for the O-arylation of phenols with aryl halides, Chin. Chem. Lett. 25
(2014) 141–145.
146 Q3
147
148
This work was supported by National Natural Science Founda-
tion of China (Nos. 21102080, 21372138) and Tsinghua University
Initiative Scientific Research Program (No. 2011Z02150).
[4] (a) Cu-catalyzed arylation reactions with S-nucleophiles, see: N. Barbero, R.
SanMartin, E. Dominguez, An efficient copper-catalytic system for performing
intramolecular O-arylation reactions in aqueous media. New synthesis of
xanthones, Green Chem. 11 (2009) 830–836;
(b) H. Deng, Z. Li, F. Ke, X. Zhou, Cu-catalyzed three-component synthesis of
substituted benzothiazoles in water, Chem. Eur. J. 18 (2012) 4840–4843.
[5] (a) Cu-catalyzed arylation reactions with activated C-nucleophiles, see: W.R.H.
Hurtley, CCXLIV. – replacement of halogen in orthobromo-benzoic acid, J. Chem.
Soc. (1929) 1870–1873;
149
References
150
151
152
153
154
155
156
157
158
159
160
161
162
[1] (a) For reviews on the catalytic Ullmann reaction, see: F. Monniers, M. Taillefer,
Catalytic C–C, C–N, and C–O Ulmann-type coupling reactions, Angew. Chem. Int.
Ed. 48 (2009) 6954–6971;
(b) G. Evano, N. Blanchard, M. Toumi, Copper-mediated coupling reactions and
their applications in natural products and designed biomolecules synthesis,
Chem. Rev. 108 (2008) 3054–3131;
(c) A.W. Thomas, S.V. Ley, Modern synthetic methods for copper-mediated
C(aryl)–O, C(aryl)–N, and C(aryl)–S bond formation, Angew. Chem. Int. Ed. 42
(2003) 5400–5449.
(b) T. Minami, T. Isonaka, Y. Okada, J. Ichikawa, Copper(I) salt-mediated arylation of
phosphinyl-stabilized carbanions and synthetic application to heterocyclic com-
pounds, J. Org. Chem. 58 (2009) 7009–7015;
(c) Y. Fang, C. Li, O-arylation versus C-arylation: copper-catalyzed intramolecular
coupling of aryl bromides with 1,3-dicarbonyls, J. Org. Chem. 71 (2006) 6427–6431.
[6] G. Danoun, A. Tlili, F. Monnier, M. Taillefer, Direct copper-catalyzed a-arylation of
benzyl phenyl ketones with aryl iodides: route towards tamoxifen, Angew. Chem.
Int. Ed. 51 (2012) 12815–12819.
[2] (a) Cu-catalyzed arylation reactions with N-nucleophiles, see: F. Ullmann, Ueber
eine neue bildungsweise von diphenylaminderivaten, Chem. Ber. 36 (1903) 2382–
2384;
(b) A. Kiyomori, J.F. Marcoux, S.L. Buchwald, An efficient copper-catalyzed cou-
Please cite this article in press as: Z.-B. Lou, et al., Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl
ketones with o-bromoacetophenones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.07.022

G Model
CCLET 3399 1–5
Z.-B. Lou et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
5
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
[7] R. Xie, Y. Ling, H. Fu, Copper-catalyzed synthesis of benzocarbazoles via a-C-
arylation of ketones, Chem. Commun. 48 (2012) 12210–12212.
[8] (a) Y. Wang, C. Chen, J. Peng, M. Li, Copper(II)-catalyzed three-component cascade
annulation of diaryliodoniums, nitriles, and alkynes: a regioselective synthesis of
multiply substituted quinolines, Angew. Chem. Int. Ed. 52 (2013) 5323–5327;
(b) X. Su, C. Chen, Y. Wang, et al., One-pot synthesis of quinazoline derivatives via
[2 + 2 + 2] cascade annulation of diaryliodonium salts and two nitriles, Chem.
Commun. 49 (2013) 6752–6754;
(e) A.G. Sergeev, T. Schulz, C. Torborg, et al., Palladium-catalyzed hydroxylation 229
of aryl halides under ambient conditions, Angew. Chem. Int. Ed. 48 (2009) 7595– 230
7599;
231
(f) S. Akai, T. Ikawa, S. Takayanagi, et al., Synthesis of biaryl compounds through 232
three-component assembly: ambidentate effect of the tert-butyldimethylsilyl 233
group for regioselective diels-alder and hiyama coupling reactions, Angew. Chem. 234
Int. Ed. 47 (2008) 7673–7676;
235
(g) X. Huang, J. Xue, A novel multicomponent reaction of arynes, b-keto sulfones, 236
(c) F. Wang, C. Chen, G. Deng, C. Xi, Concise approach to benzisothiazol-3(2H)-one
via copper-catalyzed tandem reaction of o-bromobenzamide and potassium thio-
cyanate in water, J. Org. Chem. 77 (2012) 4148–4151.
and Michael-type acceptors: a direct synthesis of polysubstituted naphthols and 237
naphthalenes, J. Org. Chem. 72 (2007) 3965–3968;
238
(h) H. Tsukamoto, Y. Kondo, Palladium(II)-catalyzed annulation of alkynes with 239
ortho-ester-containing phenylboronic acids, Org. Lett. 9 (2007) 4227–4230;
[9] Z. Lou, S. Zhang, C. Chen, et al., Concise synthesis of 1-naphthols under mild
conditions through a copper-catalyzed arylation of methyl ketones, Adv. Synth.
Catal. 356 (2014) 153–159.
[10] (a) K. Okuma, R. Itoyama, A. Sou, N. Nagahora, K. Shioj, Tandem carbon–carbon
bond insertion and intramolecular aldol reaction of benzyne with aroylacetones:
novel formation of 4,40-disubstituted 1,10-binaphthols, Chem. Commun. 48 (2012)
11145–11147;
240
(i) T. Hamura, T. Suzuki, T. Matsumoto, K. Suzuki, Tandem ring expansion of alkenyl 241
benzocyclobutenol derivatives into substituted naphthols, Angew. Chem. Int. Ed. Q4242
Engl. 118 (2006) 6442–6444;
243
(j) X. Zhang,S. Sarkar,R.C. Larock,Synthesisofnaphthalenesand2-naphtholsbythe 244
electrophilic cyclization of alkynes, J. Org. Chem. 71 (2009) 236–243.
245
[11] R. Abazari, F. Heshmatpour, S. Balalaie, Pt/Pd/Fe trimetallic nanoparticle produced 246
via reverse micelle technique: synthesis, characterization, and its use as an 247
efficient catalyst for reductive hydrodehalogenation of aryl and aliphatic halides 248
(b) D. Mal, A.K. Jana, P. Mitra, K. Ghosh, Benzannulation for the regiodefined
synthesis of 2-alkyl/aryl-1-naphthols: total synthesis of arnottin I, J. Org. Chem.
76 (2011) 3392–3398;
(c) H. Xu, S. Li, H. Liu, H. Fu, Y. Jiang, Simple and efficient copper-catalyzed cascade
synthesis of naphthols containing multifunctional groups under mild conditions,
Chem. Commun. 46 (2010) 7617–7619;
(d) G. Chai, Z. Lu, C. Fu, S. Ma, Studies on the tandem reaction of 4-aryl-2,3-
allenoates with organozinc reagents: a facile route to polysubstituted naphthols,
Chem. Eur. J. 15 (2009) 11083–11086;
under mild conditions, ACS Catal. 3 (2013) 139–149.
[12] N. Miyaura, A. Suzuki, Palladium-catalyzed cross-coupling reactions of organo- 250
boron compounds, Chem. Rev. 95 (1995) 2457–2483.
249
251
[13] D. Vuluga, J. Legros, B. Crousse, D. Bonnet-Delpon, Facile access to fluorinated aryl 252
and vinyl ethers through copper-catalysed reaction of fluoro alcohols, Eur. J. Org. 253
Chem. (2009) 3513–3518.
254
Please cite this article in press as: Z.-B. Lou, et al., Facile synthesis of 1-naphthols through a copper-catalyzed arylation of methyl
ketones with o-bromoacetophenones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.07.022