The facile synthesis of 2-bromoindoles via Cs2CO 3-promoted intramolecular cyclization of 2-(gem-dibromovinyl)anilines under transition-metal-free conditions

Article abstract of DOI:10.1039/c2ra22172a

2-Bromoindoles were readily prepared through a facile Cs₂CO ₃-promoted intramolecular cyclization of 2-(gem-bromovinyl)-N- methylsulfonylanilines in excellent yields under transition-metal-free conditions. This methodology could be extended to the synthesis of corresponding 2-chloroindoles. The reaction mechanism suggested that cyclization occurs through a key intermediate, phenylethynyl bromide, followed by cyclization in one-pot. The Royal Society of Chemistry.

Full text of DOI:10.1039/c2ra22172a

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
The facile synthesis of 2-bromoindoles via Cs2CO3-
promoted intramolecular cyclization of 2-(gem-
dibromovinyl)anilines under transition-metal-free
conditions3
Cite this: RSC Advances, 2013, 3, 73
Received 15th September 2012,
Accepted 29th October 2012
DOI: 10.1039/c2ra22172a
Pinhua Li,a Yong Ji,b Wei Chen,a Xiuli Zhangb and Lei Wang*ac
www.rsc.org/advances
2-Bromoindoles were readily prepared through a facile Cs2CO3-
promoted intramolecular cyclization of 2-(gem-bromovinyl)-
N-methylsulfonylanilines in excellent yields under transition-
metal-free conditions. This methodology could be extended to
the synthesis of corresponding 2-chloroindoles. The reaction
mechanism suggested that cyclization occurs through a key
intermediate, phenylethynyl bromide, followed by cyclization in
one-pot.
then bromination was reported, extension of its derivatives was
less well investigated owing to the limitations of regioselectivity
and functional group tolerance.5
Gem-Dihaloolefins, as an important kind of synthetic inter-
mediate due to their high reactivity and easy availability, have
attracted considerable attention in recent years.6 Most impor-
tantly, the preparation of various substituted indoles from 2-(gem-
dibromovinyl)anilines and 2-(gem-dibromovinyl)(N-substituted)
anilines via transition-metal-catalyzed tandem cross-coupling
strategies, such as C–N/C–C,7 C–N/C–N,8 C–N/C–P,7a C–N/C–H,9
C–N/carbonylation,10 and C–N/carbonylation/C–C reactions11 have
been developed. Recently, an elegant method for the synthesis of
2-bromoindoles was developed by Lautens et al. via Pd/PtBu3-
catalyzed intramolecular reactions of 2-(gem-dibromovinyl)ani-
lines.12
In continuing our efforts on the organic reactions of gem-
dihaloolefins under metal-free conditions,13 herein we describe an
efficient Cs2CO3-promoted intramolecular cyclization of 2-(gem-
dibromovinyl)-N-methylsulfonylanilines14 for the facile synthesis
of 2-bromoindoles and 2-bromo-N-methylsulfonylindoles by con-
trolling the amount of Cs2CO3 under transition-metal-free,
fluoride-free, mild and environmentally friendly reaction condi-
tions in excellent yields. In addition, this methodology can also be
extended to the synthesis of 2-chloroindole derivatives (Scheme 1).
Introduction
The indole nucleus is an important structural motif frequently
found in natural products, materials, and therapeutic agents, such
as antibiotic, anticancer and anti HIV activity.1 Indole derivatives
are also used as the starting materials for the synthesis of a large
number of alkaloids. Many halogenated indoles are also found in
nature, and several brominated indole natural products have been
isolated.2 They are also present in biologically active compounds,
for example, I (Convolutindole A, isolated from the marine
bryozoan Amathia convolute, a very potent nematocide),2e and II, III
and IV (isolated from the marine blue-green alga Riuularia firma)
(Fig. 1).2f,g
Because of the electron-rich character of indoles, the synthesis
of brominated indoles is a challenging project. The most
straightforward method is electrophilic bromination, and 3-bro-
moindoles are obtained, along with oxidation side-products.3
While unprotected 2-bromoindoles are useful for numerous
applications,4 their syntheses are rare and difficult. Although the
synthesis of 2-bromoindole based on lithiation of the free indole,
aDepartment of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P. R.
China. E-mail: leiwang@chnu.edu.cn; Fax: +86-561-309-0518;
Tel: +86-561-380-2069
bDepartment of Chemistry, Anhui Agricultural University, Hefei, Anhui 230062, P. R.
China
cState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
Electronic supplementary information (ESI) available: Detailed procedures,
3
analytical data, and 1H, 13C NMR and HRMS spectra of all intermediates and
products or other electronic format. See DOI: 10.1039/c2ra22172a
Fig. 1 Representative biologically active 2-bromoindoles.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 73–78 | 73

View Article Online
Communication
RSC Advances
Table 1 Cs2CO3-promoted intramolecular cyclization of 2-(gem-dibromovinyl)
anilines (1a–7a)a
Results and discussion
In our initial attempt to prepare 2-bromoindole (8a) from 2-(gem-
dibromovinyl)aniline (1a) in the presence of Cs2CO3 (1 equiv.) in
EtOH at 80 uC, however, no 8a was obtained (Table 1, entry 1).
When N-substituted derivatives 2a–5a were used as substrates,
there was also no desired 8a detected (Table 1, entries 2–5). To our
delight, a 91% yield of 8a was obtained when 2-(gem-dibromovi-
nyl)-N-methylsulfonylaniline (6a) was used (Table 1, entry 6). 2-
(gem-Dibromovinyl)-N-(p-tolylsulfonyl)aniline (7a) was inferior and
gave 8a in 70% yield (Table 1, entry 7). This result indicated that
the cyclization depends on the nitrogen substituents of substrates.
When the amine is activated by a strong electron-withdrawing
substituent such as sulfonyl, the tandem reaction can proceed
efficiently in one-pot. The sulfonyl group acts as a traceless dual-
activating group to accomplish indole cyclization, and after indole
formation, the sulfonyl group is deprotected via N–S bond
cleavage.
Entry
Substrate, R
Yield (%)b
1
2
3
4
5
6
7
1a, H
0
0
0
0
0
91
70
2a, CH2C6H5
3a, CO2C(CH3)3
4a, COCH3
5a, COCF3
6a, SO2CH3
7a, SO2C6H4(p-CH3)
a
Reaction conditions: 2-(gem-dibromovinyl)aniline (1a–7a, 0.50
mmol), Cs2CO3 (0.50 mmol), EtOH (2.0 mL) at 80 uC for 8 h.
b
Isolated yields.
To further optimize the reaction conditions for the synthesis of
2-bromoindole (8a) through a base-mediated intramolecular
reaction of 2-(gem-dibromovinyl)-N-methylsulfonylaniline (6a), a
variety of bases were examined. As can be seen from Table 2,
Cs2CO3 exhibited the highest reactivity in EtOH among the bases
tested. t-BuOK, K2CO3, K3PO4, BuOLi, Na2CO3, KF and CsF were
less effective (Table 2, entries 1–8). DBU, DIPEA, Et3N, DABCO and
pyridine were ineffective (Table 2, entries 9–13). The solvent also
played an important role in the reaction. EtOH was found to be
the best medium for the reaction when Cs2CO3 was used as a
promoter. Other solvents, DMSO, DMF, THF, MeCN, toluene and
dioxane were less effective, and 18–85% yields of 8a were obtained
(Table 2, entries 14–19). However, the reaction did not occur in
H2O (Table 2, entry 20). When the reaction was performed in the
presence of Cs2CO3 in EtOH at a temperature less than 50 uC, no
reaction was observed. The temperature of 80 uC was found to be
optimal (Table 2, entries 21–23). With respect to the amount of
Cs2CO3 used in the reaction, 1.0 equiv. Cs2CO3 was found to be
the best choice (Table 2, entry 24).
containing substituents on the benzene rings were examined. The
results indicated that a number of functional groups, including
both electron-withdrawing and electron-donating ones were
tolerated, and the corresponding 2-bromoindoles were obtained
in good to excellent yields (Table 3, 8a–r). The reaction proceeded
Table 2 Screening of bases and solvents for the intramolecular cyclization of 2-
(gem-dibromovinyl)-N-methylsulfonylaniline (6a)a
Entry
Base
Solvent/T (uC)
Yield (%)b
1
2
3
4
5
6
7
8
Cs2CO3
t-BuOK
K2CO3
K3PO4
t-BuOLi
Na2CO3
KF
CsF
DBU
DIPEA
Et3N
DABCO
Pyridine
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
EtOH/80
DMSO/80
DMF/80
THF/70
MeCN/80
Toluene/80
Dioxane/80
H2O/80
EtOH/50
EtOH/60
EtOH/70
EtOH/80
91
80
51
35
24
18
15
13
NR
NR
NR
NR
NR
85
73
67
62
22
Having optimized the reaction conditions, the generality of this
transformation was investigated and the results are listed in
Table 3. A variety of 2-(gem-dibromovinyl)-N-methylsulfonylanilines
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
18
NR
NR
12
53
92c
a
Reaction conditions: 2-(gem-dibromovinyl)-N-methylsulfonylaniline
(6a, 0.50 mmol), base (0.50 mmol), solvent (2.0 mL) at the
b
c
temperature indicated in Table 2 for 8 h. Isolated yields. Cs2CO3
(1.0 mmol) was used.
Scheme 1 Preparation of 2-bromo(chloro)indoles.
74 | RSC Adv., 2013, 3, 73–78
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Communication
very well with halogen substituents F, Cl, Br and I on the para-, or
meta-positions of anilines (6b–j) and afforded high yields of
indoles 8b–j, which are potential synthetic intermediates in
organic synthesis and could provide further transformation via
transition-metal-catalyzed cross-coupling reactions. The product
yields of substrates derived from para-haloanilines were superior
to those from meta-haloanilines (Table 3, 8b–e vs. 8f–j). 2-(gem-
Dibromovinyl)-N-methylsulfonylanilines with an electron-donating
functionality, such as CH3, p-CH3OC6H4, C6H5CH2O, CH3SO2O
and OCH2O, on the anilines also underwent the tandem
cyclization smoothly to generate the corresponding products 8k–
p in 86–91% yields. It should be noted that the reaction could
tolerate an ortho-substituted group (8o). Substrates, 6q and 6r,
with electron-withdrawing substituents CH3OCO and CH3CO also
gave the corresponding products 8q and 8r in 86 and 88% yields,
respectively. A more remarkable observation was that the reaction
also proceeded with 2-(gem-dichlorovinyl)-N-methylsulfonylaniline
(6s) to afford 2-chloroindole (8s) in good yield.
Although a facile synthesis of 2-bromo-N-methylsulfonylindoles via
CuI-catalyzed intramolecular cross-coupling of gem-dibromoole-
fins was described,15 it is desirable to develop an efficient and
practical method for their preparation under transition-metal-free
conditions, which can overcome the drawbacks of its expensive,
poisonous, and air-sensitive properties.16 During the investigation
of the reaction of 6a under Cs2CO3/C2H5OH conditions, we were
delighted to find that in the reaction of 6a in the presence of
Cs2CO3 (0.50 equiv.) in EtOH at 80 uC, 2-bromo-
N-methylsulfonylindole (9a) was isolated in 94% yield and no
further deprotection product 6a was found. Then, a number of 2-
(gem-dibromovinyl)-N-methylsulfonylanilines were examined to
explore the generality of the reaction under Cs2CO3 (0.50 equiv.)
in EtOH conditions. Satisfactorily, as shown in Table 4, substrates
with both electron-withdrawing and electron-donating groups on
the aromatic rings underwent the intramolecular tandem cycliza-
tion very cleanly to generate the corresponding 2-bromo-
N-methylsulfonylindoles (9a–r) in excellent yields by controlling
Cs2CO3 with 0.50 equiv. It is obvious that the yields of 9a–r are
superior to the corresponding 8a–r, which are the further
transformation products of 9a–r via a deprecation process.
Compared with the reaction of 6a–r to 8a–r, the similar steric
and electronic effects of the substitutions on the anilines were also
Sulfonamide is one of the most stable nitrogen protective
groups. Generally, most sulfonamides are stable to alkaline
hydrolysis, as well as to catalytic reduction. This property
prompted us to prepare 2-bromo-N-methylsulfonylindoles from
the corresponding 2-(gem-dibromovinyl)-N-methylsulfonylanilines.
Table 3 Synthesis of 2-bromoindoles and 2-chloroindole through Cs2CO3-promoted intramolecular cyclization of 6a
a
b
c
Reaction conditions: 6 (0.50 mmol), Cs2CO3 (0.50 mmol), EtOH (2.0 mL), at 80 uC for 8 h. Isolated yields. DMF (2.0 mL), 110 uC for 8 h.
Ms = CH3SO2, Bn = C6H5CH2.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 73–78 | 75

View Article Online
Communication
RSC Advances
Table 4 Synthesis of 9 through Cs2CO3-promoted intramolecular cyclization of 6a
a
b
c
Reaction conditions: 6 (0.50 mmol), Cs2CO3 (0.25 mmol), EtOH (2.0 mL), at 80 uC for 8 h. Isolated yields. DMF (2.0 mL), 110 uC for 8 h.
Ms = CH3SO2, Bn = C6H5CH2.
found in the reaction of 6a–r to 9a–r. It is noteworthy that 6s also
could undergo the tandem reaction to generate the corresponding
2-chloro-N-methylsulfonyindole (9s) with good yield in DMF at 110
uC.
When the reaction scale was increased up to 10 mmol using
Cs2CO3 and EtOH, 88% and 93% isolated yields of 8a and 9a were
isolated from the starting material 6a, respectively, by increasing
the reaction time to ensure completion (Scheme 2).
2-Arylindoles exhibit good biological activities, such as
antiestrogen, h5-HT2A antagonism, anti-inflammatory properties,
and cytotoxicity.17 Palladium-catalyzed cross-coupling of 2-haloin-
doles with arylmetal species is a powerful method for preparing
them,18 however, this application has been limited owing to the
inaccessibility of 2-haloindoles.19 With the prepared 2-bromoin-
doles in our hands, converting them into the corresponding
2-arylindoles was investigated via palladium-catalyzed cross-
coupling with boronic acids (Scheme 3). The results indicated
that the corresponding products were obtained in excellent yields
under Suzuki reaction conditions in the absence of ligand
(Scheme 3). In the analogous studies, an essential ligand such
as dppf, S-Phos, or PtBu3 is needed.7a,b,e In addition, 10d or 11d
was obtained in a high yield while the reaction of 8d with
4-MeOC6H4B(OH)2 or PhB(OH)2 under controlled coupling condi-
tions (Scheme 3, eqn (2) and (3)). This also implies that the
reactivity of the 2-position C–Br bond of 2,5-dibromoindole (8d) is
superior to its 5-position one towards palladium-catalyzed-
coupling reactions.12
To investigate the reaction mechanism, obtained 9a was
further converted into 2-bromoindole (8a) in the presence of
Cs2CO3 (0.5 equiv.), providing 95% yield (Scheme 4, eqn (1)).
Meanwhile, 2-(gem-dibromovinyl)-N-(tert-butoxycarbonyl)aniline
(3a) only afforded the corresponding phenylethynyl bromide
intermediate A under Cs2CO3 (1.0 equiv.) conditions (Scheme 4,
eqn (2)). When the reaction of 2-(19-methyl-29,29-dichlorovinyl)-
Scheme 2 10 mmol scale reactions of 6a.
76 | RSC Adv., 2013, 3, 73–78
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Communication
Conclusion
In conclusion, we have developed a novel, efficient, economical,
and facile Cs2CO3-promoted intramolecular cyclization of 2-(gem-
dibromovinyl)-N-methylsulfonylanilines for the synthesis of 2-bro-
moindoles and 2-bromo-N-methylsulfonylindoles, respectively,
under transition-metal-free conditions by controlling the amount
of Cs2CO3 used in EtOH reaction media.21 Notably, this
methodology can also be readily extended to the synthesis of
2-chloroindoles. The reaction mechanism investigation indicated
that the tandem cyclization proceeds through a key intermediate
phenylethynyl bromide, followed by the cyclization processes. The
sulfonyl group acts as a traceless dual-activating group to undergo
indole cyclization and easy deprotection in the presence of
Cs2CO3. In addition, the further transformation of 2-bromoindoles
via palladium-catalyzed Suzuki cross-coupling could be carried out
in the absence of ligand. A detailed mechanistic study and further
investigation on transition-metal-free reactions are currently
underway in our laboratory.
Scheme 3 Suzuki coupling of 8a and 8d with boronic acids.
N-methylsulfonylanilines (6t) was performed in Cs2CO3/DMF, no
product was detected and 6t was recovered in 98% yield
(Scheme 4, eqn (3)). In addition, further isotope experiments
indicated that when the reaction of deuterium-labeled 6a-D was
performed under the present reaction conditions, 95% of the
D-enriched element was lost in the product (Scheme 4, eqn (4)).
These results suggested that the intramolecular tandem cycliza-
tion of 6a is through an intermediate phenylethynyl bromide,20
although it can not be obtained because of the fast reaction of B to
9a. The reaction pathway for the generation of 2-bromoindole (8a)
was also shown in Scheme 4. Initially, an elimination of HBr from
6a to intermediate B proceeded smoothly in the presence of
Cs2CO3, followed by an intramolecular nucleophilic addition of
the nitrogen to the carbon–carbon triple bond of B, affording
2-bromo-N-methylsulfonylindole (9a) with the assistance of the
carbonate anion. The as-obtained 9a then underwent a cleavage of
the sulfonamide linkage to afford deprotection product 2-bro-
moindole (8a) under Cs2CO3 conditions.
Acknowledgements
This work was financially supported by the National Science
Foundation of China (Nos. 21172092, 20972057).
References
1 For selected reviews, see: (a) G. R. Humphrey and J. T. Kuethe,
Chem. Rev., 2006, 106, 2875; (b) S. Cacchi and G. Fabrizi, Chem.
Rev., 2005, 105, 2873; (c) M. Somei and F. Yamada, Nat. Prod.
Rep., 2005, 22, 73; (d) M. Somei and F. Yamada, Nat. Prod. Rep.,
¨
2004, 21, 278; (e) G. Collin and H. Hoke, ‘‘Indole’’ In Ullmann’s
Encyclopedia of Industrial Chemistry, 2002, Wiley-VCH,
Weinheim; (f) Comprehensive Heterocyclic Chemistry II, ed. A.
R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon Press,
New York, 1996, vol. 2, p 259. For selected examples, see; (g)
L. Berrade, B. Aisa, M. Ramirez, S. Galiano, S. Guccione, L.
R. Moltzau, F. O. Levy, F. Nicoletti, G. Battaglia, G. Molinaro,
I. Aldana, A. Monge and S. Perez-Silandes, J. Med. Chem., 2011,
54, 3086; (h) K. Krajewski, Y. Zhang, D. Parrish, J. Deschamps,
P. P. Rollera and V. K. Pathak, Bioorg. Med. Chem. Lett., 2006,
16, 3034; (i) N. K. Garg, D. D. Caspi and B. M. Stoltz, J. Am.
Chem. Soc., 2005, 127, 5970; (j) J. F. Payack, E. Vazquez, L. Matty,
M. H. Kress and J. McNamara, J. Org. Chem., 2005, 70, 175.
2 For selected reviews, see: (a) C. K. Narkowicz, A. J. Blackman,
E. Lacey, J. H. Gill and K. Heiland, J. Nat. Prod., 2002, 65, 938;
(b) G. W. Gribble, J. Chem. Soc. Perkin Trans. 1, 2000, 1045; (c) G.
W. Gribble, J. Nat. Prod., 1992, 55, 1353; (d) Indoles, ed. R. J.
Sundberg, Academic Press, San Diego, 1996. For selected
examples, see; (e) C. C. Hughes, A. Prieto-Davo, P. R. Jensen and
W. Fenical, Org. Lett., 2008, 10, 629; (f) G. Bringmann, S. Tasler,
H. Endress, J. Kraus, K. Messer, M. Wohlfarth and W. Lobin, J.
Am. Chem. Soc., 2001, 123, 2703; (g) R. S. Norton and R. J. Wells,
J. Am. Chem. Soc., 1982, 104, 3628.
3 (a) J. C. Powers, in The Chemistry of Heterocyclic Compounds, ed.
Houlihan, W. J., J. Wiley and Sons, New York, 1972, vol. 25, part
2, p. 128; (b) W. C. Frank, Y. C. Kim and R. F. Heck, J. Org.
Chem., 1978, 43, 2947.
4 (a) M. G. Bursavicha, N. Brooijmans, L. Feldberg, I. Hollander,
S. Kim, S. Lombardi, K. Park, R. Mallon and A. M.Gilbert,
Scheme 4 Possible reaction pathway and related experiments.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 73–78 | 77

View Article Online
Communication
RSC Advances
Bioorg. Med. Chem. Lett., 2010, 20, 2586; (b) M. S. Techenor, J.
D. Trzupek, D. B. Kastrinsky, F. Shiga, I. Hwang and D.
L. Boger, J. Am. Chem. Soc., 2006, 128, 15683; (c) J. M. Herbert,
Tetrahedron Lett., 2004, 45, 817; (d) K. Dinnell, G. G. Chicchi, M.
J. Dhar, J. M. Elliott, G. J. Hollingworth, M. M. Kurtz, M.
P. Ridgill, W. Rycroft, K.-L. Tsao, A. R. Williams and C.
J. Swaina, Bioorg. Med. Chem. Lett., 2001, 11, 1237; (e) Y. Liu and
G. W. Gribble, Tetrahedron Lett., 2000, 41, 8717.
5 (a) J. Bergman and L. Venemalm, J. Org. Chem., 1992, 57, 2495.
6 For recent reviews, see: (a) G. Chelucci, Chem. Rev., 2012, 112,
1344; (b) S. Cacchi, G. Fabrizi and A. Goggiamani, Org. Biomol.
Chem., 2011, 9, 641; (c) F. Legrand, K. Jouvin and G. Evano, Isr.
J. Chem., 2010, 50, 588; (d) J.-R. Wang and K. Manabe, Synthesis,
2009, 1405.
L. Wang and M. Wang, Org. Lett., 2011, 13, 5016; (d) X. Zhang
and L. Wang, Green Chem., 2012, 14, 2141.
14 (a) H.-C. Zhang, H. Ye, A. F. Moretto, K. K. Brumfield and B.
E. Maryanoff, Org. Lett., 2000, 2, 89; (b) H.-C. Zhang, H. Ye, K.
B. White and B. E. Maryanoff, Tetrahedron Lett., 2001, 42, 4751.
15 (a) B. Jiang, K. Tao, W. Shen and J. Zhang, Tetrahedron Lett.,
2010, 51, 6342.
16 (a) C.-L. Sun, H. Li, D.-G. Yu, M. Yu, X. Zhou, X.-Y. Lu,
K. Huang, S.-F. Zheng, B.-J. Li and Z.-J. Shi, Nat. Chem., 2010, 2,
1044; (b) E. Shirakawa, K. Itoh, T. Higashino and T. Hayashi, J.
Am. Chem. Soc., 2010, 132, 15537; (c) W. Liu, H. Cao, H. Zhang,
H. Zhang, K. H. Chung, C. He, H. Wang, F. Y. Kwong and
A. Lei, J. Am. Chem. Soc., 2010, 132, 16737; (d) J. Zhao, Y. Zhao
and H. Fu, Angew. Chem., Int. Ed., 2011, 50, 3769.
7 (a) S. Thielges, E. Meddah, P. Bisseret and J. Eustache,
Tetrahedron Lett., 2004, 45, 907; (b) Y.-Q. Fang and
M. Lautens, J. Org. Chem., 2008, 73, 538; (c) Y.-Q. Fang and
M. Lautens, Org. Lett., 2005, 7, 3549; (d) A. Fayol, Y.-Q. Fang and
M. Lautens, Org. Lett., 2006, 8, 4203; (e) M. Nagamochi, Y.-
Q. Fang and M. Lautens, Org. Lett., 2007, 9, 2955; (f) Y.-Q. Fang,
J. Yuen and M. Lautens, J. Org. Chem., 2007, 72, 5152; (g) Y.-
Q. Fang, R. Karisch and M. Lautens, J. Org. Chem., 2007, 72,
1341.
8 (a) J. Yuen, Y.-Q. Fang and M. Lautens, Org. Lett., 2006, 8, 653.
9 (a) C. S. Bryan and M. Lautens, Org. Lett., 2008, 10, 4633; (b) Z.-
J. Wang, J.-G. Yang, F. Yang and W. Bao, Org. Lett., 2010, 12,
3034; (c) Z.-J. Wang, F. Yang, X. Lv and W. Bao, J. Org. Chem.,
2011, 76, 967; (d) X.-R. Qin, X.-F. Cong, D.-B. Zhao, J.-S. You and
J.-B. Lan, Chem. Commun., 2011, 47, 5611; (e) W. Chen,
M. Wang, P. Li and L. Wang, Tetrahedron, 2011, 67, 5913.
10 (a) T. O. Vieira, L. A. Meaney, Y.-L. Shi and H. Alper, Org. Lett.,
2008, 10, 4899.
17 (a) E. von Angerer, N. Knebel, M. Kager and B. Ganss, J. Med.
Chem., 1990, 33, 2635; (b) C. Biberger and E. von Angerer, J.
Steroid Biochem. Mol. Biol., 1998, 64, 277; (c) M. Medarde, A.
C. Ramos, E. Caballero, R. P.-L. De Clairac, J. L. Lopez, D.
G. Gravalos and A. S. Feliciano, Bioorg. Med. Chem. Lett., 1999, 9,
2303; (d) G. I. Stevenson, A. L. Smith, S. Lewis, S. G. Michie, J.
G. Neduvelil, S. Patel, R. Marwood, S. Patel and J. L. Castro,
Bioorg. Med. Chem. Lett., 2000, 10, 2697.
18 (a) L. Chu, M. H. Fisher, M. T. Goulet and M. J. Wyvratt,
Tetrahedron Lett., 1997, 38, 3871; (b) C. A. Merlic and D.
M. McInnes, Tetrahedron Lett., 1997, 38, 7661; (c) A. L. Smith, G.
I. Stevenson, S. Lewis, S. Patel and J. L. Castro, Bioorg. Med.
Chem. Lett., 2000, 10, 2693.
19 (a) R. L. Hudkins, J. L. Diebold and F. D. Marsh, J. Org. Chem.,
1995, 60, 6218; (b) M. Amat, S. Hadida, G. Pshenichnyi and
J. Bosch, J. Org. Chem., 1997, 62, 3158; (c) C. N. Johnson,
G. Stemp, N. Anand, S. C. Stephen and T. Gallagher, Synlett,
1998, 1025.
11 (a) M. Arthuis, R. Pontikis and J.-C. Florent, Org. Lett., 2009, 11,
4608.
12 (a) S. G. Newman and M. Lautens, J. Am. Chem. Soc., 2010, 132,
11416; (b) S. G. Newman, V. Aureggi, C. S. Bryan and
M. Lautens, Chem. Commun., 2009, 5236.
13 (a) W. Chen, Y. Zhang, L. Zhang, M. Wang and L. Wang, Chem.
Commun., 2011, 47, 10476; (b) T. He, H. Li, P. Li and L. Wang,
Chem. Commun., 2011, 47, 8946; (c) T. He, L. Yu, L. Zhang,
20 (a) H. Xu, S. Gu, W. Chen, D. Li and J. Dou, J. Org. Chem., 2011,
76, 2448; (b) J. Liu, W. Chen, Y. Ji and L. Wang, Adv. Synth.
Catal., 2012, 354, 1585; (c) M. Okutani and Y. Mori, J. Org.
Chem., 2009, 74, 442.
21 Cs2CO3 (99.995%) was purchased from Aldrich and contains
Cu (0.30 ppm) and Pd (0.01 ppm); other elements including: Ni,
Co, Fe, Ru, and Rh were not detected (ICP-MS determination
data).
78 | RSC Adv., 2013, 3, 73–78
This journal is ß The Royal Society of Chemistry 2013