One-pot synthesis of unsymmetrical 2,3-diarylindoles by site-selective suzuki-miyaura reactions of N -methyl-2,3-dibromoindole

Article abstract of DOI:10.1055/s-0029-1219201

The Suzuki-Miyaura reaction of N-methyl-2,3-dibromoindole with two equivalents of boronic acids gave symmetrical 2,3-diarylindoles. The reaction with one equivalent of arylboronic acid resulted in site-selective formation of 2-aryl-3-bromoindoles. The one

Full text of DOI:10.1055/s-0029-1219201

LETTER
411
One-Pot Synthesis of Unsymmetrical 2,3-Diarylindoles by Site-Selective
Suzuki–Miyaura Reactions of N-Methyl-2,3-dibromoindole
Synthesis of
U
nsymme
u
trical 2,3-D
i
h
a
rylindoles ammad Farooq Ibad,a Munawar Hussain,a Obaid-Ur-Rahman Abid,a Asad Ali,a Ihsan Ullah,a Dhafer Saber
Zinad,a Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
b
Received 16 November 2009
ed the synthesis of symmetrical N-phenylsulfonyl-2,3-di-
arylindoles by twofold Suzuki–Miyaura reactions of 2,3-
dihalo-N-(phenylsulfonyl)indoles.12 The main part of this
study was carried out with N-phenylsulfonyl-2,3-diiodo-
Abstract: The Suzuki–Miyaura reaction of N-methyl-2,3-dibro-
moindole with two equivalents of boronic acids gave symmetrical
2,3-diarylindoles. The reaction with one equivalent of arylboronic
acid resulted in site-selective formation of 2-aryl-3-bromoindoles.
The one-pot reaction of 2,3-dibromoindole with two different aryl- indole, but its 2,3-dibromo-, 2-iodo-3-bromo-, and 2-bro-
boronic acids afforded unsymmetrical 2,3-diarylindoles containing
two different aryl groups.
mo-3-iodoindole derivatives were also employed. The
reactions were carried out using Pd(OAc)2/P(o-Tol)3 and
Key words: catalysis, palladium, Suzuki–Miyaura reaction, site-
selectivity, indole
K2CO3 in acetone–H2O (2:1) or DMF (70 °C). It is impor-
tant to note that the authors report that all attempts to de-
velop site-selective reactions and to prepare
monocoupling products or unsymmetrical 2,3-diarylin-
2,3-Diarylindoles are of considerable pharmacological doles, containing two different aryl groups, were unsuc-
relevance, due to their anti-inflammatory, anti-arthritic, cessful. In fact, site-selective palladium(0)-catalyzed
and antipyretic properties.1 For example, 2,3-bis(4-meth- cross-coupling reactions of 2,3-dihaloindoles have, to the
oxyphenyl)indole (‘indoxole’) has been shown to possess best of our knowledge, not yet been reported.
a stronger anti-inflammatory activity than common drugs,
We have earlier observed7 that Suzuki–Miyaura reactions
of N-sulfonyl- and N-acyl-2,3,4,5-tetrabromopyrrole and
such as aspirin and indomethacin.2 Based on these find-
ings, novel COX-2 inhibitors for the treatment of arthritic
of unprotected 2,3,4,5-tetrabromopyrrole gave unsatisfac-
pain have recently been developed.3 Classic syntheses of
tory results (with regard to yield and site-selectivity). In
contrast, the reactions of N-methyl-2,3,4,5-tetrabromopy-
rrole proceeded in good yields and with excellent site-se-
2,3-diarylindoles include the diaza-Cope rearrangement
of arylhydrazones (Fischer) and the reaction of anilines
with a-halo ketones (Napieralski).1,4 Modern methods to
lectivity. Therefore, we decided to study the use of N-
assemble the indole system include the Fürstner variant of
methyl-2,3-dibromoindole as a substrate in Suzuki–
the McMurry reaction and Pd-catalyzed cross-coupling
Miyaura reactions. Gratifyingly, we have found that the
reactions indeed proceed in high yields and with excellent
reactions.4
An alternative approach to substituted indoles relies on site-selectivity. The results of our efforts are reported
the functionalization of the indole core structure. In recent herein.
years, a number of site-selective palladium(0)-catalyzed
cross-coupling reactions of polyhalogenated heterocycles
have been developed. The site-selectivity of these reac-
N-Methyl-2,3-dibromoindole (1) was prepared as previ-
ously reported.11 The Suzuki–Miyaura reaction of 1 with
various arylboronic acids (2.3 equiv) afforded the sym-
tions is generally influenced by electronic and steric pa-
metrical 2,3-diarylindoles 3a–e (Scheme 1, Table 1).13,14
rameters.5 Recently, we have reported the synthesis of
All products were isolated in high yields (79–91%). This
aryl-substituted thiophenes,6 pyrroles,7 and selenophenes8
includes derivatives prepared from both electron-rich and
by site-selective Suzuki reactions of tetrabromo-
electron-poor arylboronic acids. In contrast, reactions of
thiophene, tetrabromo-N-methylpyrrole, and tetrabromo-
N-phenylsulfonyl-2,3-diiodoindole with electron-poor
selenophene, respectively. A number of Suzuki–Miyaura
arylboronic acids were reported to proceed in only moder-
reactions of monohalogenated indoles have been report-
ate yields (44–55%).12
ed.9 Ohta et al. reported site-selective Suzuki–Miyaura re-
actions of N-TBDS-3,6-dibromoindole.10 The first attack
Br
Ar
ArB(OH)2
occurred at carbon atom C-6. Recently, we have reported
Heck reactions of N-methyl-2,3-dibromoindole which
proceed without site-selectivity.11 Gribble and Liu report-
2a–e
Br
Ar
i
N
N
Me
Me
1
3a–e
Scheme 1 Synthesis of 3a–e. Reagents and conditions: (i) 1 (1.0
equiv), 2a–e (2.3 equiv), K3PO4 (3.0 equiv), Pd(PPh3)4 (3 mol%), 1,4-
dioxane, 110 °C, 6 h.
SYNLETT 2010, No. 3, pp 0411–0414
Advanced online publication: 15.01.2010
DOI: 10.1055/s-0029-1219201; Art ID: G38909ST
1
2.
0
2.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

412
M. F. Ibad et al.
LETTER
Table 1 Synthesis of Symmetrical N-Methyl-2,3-diarylindoles 3a–e
ond step of the one-pot synthesis of 5a–e were carried out
at 110 °C. Potassium phosphate was employed as the
base. The structures are established by 2D NMR experi-
ments and X-ray structural analyses.
2, 3
a
Ar
Yield of 3 (%)a
Ph
91
90
86
79
83
b
4-MeC6H4
4-EtC6H4
4-t-BuC6H4
4-ClC6H4
1) Ar1B(OH)2
Ar2
Br
2) Ar2B(OH)2
i
c
Ar1
Br
d
N
N
Me
5a–e
Me
1
e
Scheme 3 Synthesis of 5a–e. Reagents and conditions: (i) 1) 1 (1.0
equiv), 2k (1.1 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (4 mol%), 1,4-
dioxane, 70 °C, 6 h; 2) 2a,e,f,j,l (1.2 equiv), K3PO4 (1.5 equiv), 110
°C, 8 h.
a Yields of isolated products.
The reaction of 1 with arylboronic acids 2f–j (1.1 equiv)
resulted in site-selective formation of the (rather unstable)
Table 3 Synthesis of Unsymmetrical 2,3-Diarylindoles 5a–e
N-methyl-2-aryl-3-bromoindoles
4a–e
(Scheme 2,
Table 2).13,15 Excellent yields were again obtained for
products derived from both electron-rich and electron-
poor arylboronic acids.
2
5
a
b
c
Ar1
Ar2
Yield of 5 (%)a
k,a
k,f
k,e
k,l
k,j
2,5-(MeO)2C6H3
2,5-(MeO)2C6H3
2,5-(MeO)2C6H3
2,5-(MeO)2C6H3
2,5-(MeO)2C6H3
Ph
69
67
59
71
63
3,5-Me2C6H3
4-ClC6H4
4-FC6H4
4-F3CC6H4
Br
Br
ArB(OH)2
2f–j
Br
Ar
i
N
N
d
e
Me
Me
4a–e
1
Scheme 2 Synthesis of 4a–e. Reagents and conditions: (i) 1 (1.0
equiv), 2f–j (1.1 equiv), K3PO4 (1.5 equiv), Pd(PPh3)4 (3 mol%), 1,4-
dioxane, 70 °C, 6 h.
a Yields of isolated products.
The oxidative addition of palladium usually occurs first at
the most electron-deficient carbon atom.5 The site-selec-
tive formation of 4a–e and 5a–e can be explained by the
fact that carbon atom C-2 is more electron-deficient than
C-3 (Scheme 4). The nitrogen protective group seems to
play an important role. Gribble and Liu reported12 that the
reaction of N-phenylsulfonyl-protected 2,3-diiodo-, 2,3-
dibromo-, 2-iodo-3-bromo-, and 2-bromo-3-iodoindole
with one equivalent of (4-methylphenyl)boronic acid re-
sulted in the formation of mixtures of the 2,3-diarylin-
doles and of the starting material instead of the
Table 2 Synthesis of 2-Aryl-3-bromoindoles 4a–e
2
f
4
a
b
c
Ar
Yield of 4 (%)a
3,5-Me2C6H3
2-MeOC6H4
2-EtOC6H4
3,4-(MeO)2C6H3
4-F3CC6H4
86
71
73
79
84
g
h
i
d
e
j
a Yields of isolated products.
less electron-deficient
2
Our next target was to prepare unsymmetrical 2,3-di-
arylindoles containing two different aryl groups. Due to
the unstable nature of the monocoupling products 4, we
developed a one-pot protocol. The Suzuki–Miyaura reac-
tion of N-methyl-2,3-dibromoindole with two different
arylboronic acids afforded the unsymmetrical 2,3-di-
arylindoles 5a–e in good yields (Scheme 3, Table 3).16,17
Br
strong electronic
difference
high site-selectivity
Br
N
Me
1
more electron-deficient
electron-deficient
In all reactions, the best yields were obtained when
Pd(PPh3)4 was used as the catalyst (3–4 mol%). The use
of Pd(OAc)2 in the presence of XPhos18 or SPhos18 gave
similar results in terms of yield. However, the employ-
ment of Pd(PPh3)4 is significantly cheaper. For the mono-
coupling (synthesis of 4a–e and the first step of the one-
pot synthesis of 5a–e) it proved to be important to carry
out the reaction at 70 °C in order to achieve a good site-
selectivity. In contrast, the synthesis of 3a–e and the sec-
1
Br
low electronic
difference
low site-selectivity
Br
N
1
PhO2S
electron-deficient
Scheme 4 Possible explanation for the site-selectivity of the Suzuki–
Miyaura reactions of 1
Synlett 2010, No. 3, 411–414 © Thieme Stuttgart · New York

LETTER
Synthesis of Unsymmetrical 2,3-Diarylindoles
413
(9) (a) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis
1984, 936. (b) Yang, Y.; Martin, A. R. Synth. Commun.
1992, 22, 1757. (c) Carrera, G. M. J. r.; Sheppard, G. S.
monocoupling product. This might be explained by the
strong electron-withdrawing effect of the sulfonyl group
which results in an increased reactivity of both carbon C-
2 and C-3 of the indole moiety and a less pronounced dif-
ference between their electronic character. In case of N-
methyl-2,3-dibromoindole (1) the electronic character of
C-2 and C-3 appears to be sufficiently different because
site-selective transformations are observed.
Synlett 1994, 93. (d) Tidwell, J. H.; Peat, A. J.; Buchwald,
S. L. J. Org. Chem. 1994, 59, 7164. (e) Banwell, M. G.;
Bissett, B. D.; Busato, S.; Cowden, C. J.; Hockless, D. C. R.;
Holman, J. W.; Read, R. W.; Wu, A. W. J. Chem. Soc.,
Chem. Commun. 1995, 2551. (f) Merlic, C. A.; McInnes,
D. M.; You, Y. Tetrahedron Lett. 1997, 38, 6787.
(g) Merlic, C. A.; McInnes, D. M. Tetrahedron Lett. 1997,
38, 7661. (h) Moody, C. J.; Doyle, K. J.; Elliott, M. C.;
Mowlem, T. J. J. Chem. Soc., Perkin Trans. 1 1997, 2413.
(i) Chu, L.; Fisher, M. H.; Goulet, M. T.; Wyvratt, M. J.
Tetrahedron Lett. 1997, 38, 3871. (j) Carbonnelle, A.-C.;
González-Zamora, E. G.; Beugelmans, R.; Roussi, G.
Tetrahedron Lett. 1998, 39, 4467. (k) For reactions of
triflates, see: Chi, S. M.; Choi, J.-K.; Yum, E. K.; Chi, D. Y.
Tetrahedron Lett. 2000, 41, 919. (l) Joseph, B.; Malapel, B.;
Mérour, J.-Y. Synth. Commun. 1996, 26, 3289.
In conclusion, we have reported the synthesis of symmet-
rical and unsymmetrical 2,3-diarylindoles by Suzuki–
Miyaura reactions of N-methyl-2,3-dibromoindole. The
nitrogen protective groups play an important role for the
site-selectivity.
Acknowledgment
Financial support by State of Pakistan (HEC scholarships for M.H.
and I.U.), by the DAAD (scholarships for M.F.I., A.A. and O.-U.-
R.A.), and by the State of Mecklenburg-Vorpommern (scholarship
for M.H.) is gratefully acknowledged.
(m) Malapel-Andrieu, B.; Mérour, J.-Y. Tetrahedron 1998,
54, 11079.
(10) Kawasaki, I.; Yamashita, M.; Ohta, S. Chem. Pharm. Bull.
1996, 44, 1831.
(11) Hussain, M.; Dang, T. T.; Langer, P. Synlett 2009, 1822.
(12) (a) Liu, Y.; Gribble, G. W. Tetrahedron Lett. 2000, 41,
8717. (b) For metal–halide exchange, see: Liu, Y.; Gribble,
G. W. Tetrahedron Lett. 2002, 43, 7135.
(13) General Procedure for the Synthesis of 3a–e and 4a–e
The reaction was carried out in a pressure tube. A 1,4-
dioxane solution (4 mL) of 1, K3PO4, Pd(PPh3)4, and
arylboronic acid 2 was stirred at 110 °C or 70 °C for 6 h or 8
h. After cooling to 20 °C, a sat. aq solution of NH4Cl was
added. The organic and the aqueous layer were separated,
and the latter was extracted with CH2Cl2. The combined
organic layers were dried (Na2SO4), filtered, and the filtrate
was concentrated in vacuo. The residue was purified by flash
chromatography (silica gel, heptanes).
(14) 2,3-Bis(4-ethylphenyl)-1-methyl-1H-indole (3c)
Starting with 1 (289 mg, 1.0 mmol), 2c (262 mg, 2.3 mmol),
K3PO4 (446 mg, 2.1 mmol), Pd(PPh3)4 (3 mol%), and 1,4-
dioxane (4 mL), 3c was isolated as a yellowish oil (291 mg,
86%). 1H NMR (300 MHz, CDCl3): d = 1.01 (t, J = 7.5 Hz,
3 H, CH3), 1.05 (t, J = 7.5 Hz, 3 H, CH3), 2.40 (q, J = 7.5 Hz,
2 H, CH2), 2.48 (q, J = 7.5 Hz, 2 H, CH2), 3.42 (s, 3 H,
NCH3), 6.90–6.96 (m, 3 H, ArH), 7.02–7.10 (m, 7 H, ArH),
7.25 (d, J = 8.2 Hz, 1 H, ArH), 7.51 (d, J = 7.8 Hz, 1 H,
ArH). 13C NMR (75.47 MHz, CDCl3): d = 15.8 (CH3), 16.0
(CH3), 29.1 (CH2), 29.2 (CH2), 31.2 (CH3), 110.7 (CH),
115.4 (C), 120.0 (CH), 121.0 (CH), 123.0 (CH), 128.1 (C),
128.5 (2 CH), 128.7 (2CH), 130.3 (C), 130.6 (2 CH), 132.0
(2 CH), 133.7 (C), 138.3 (C), 138.4 (C), 142.0 (C), 144.9
(C). IR (ATR): n = 3047 (w), 3022 (w), 2961 (s), 2928 (w),
1797 (w), 1765 (w), 1726 (w), 1519 (m), 1463 (s), 1362 (m),
1325 (m), 1257 (m), 1131 (w), 1115 (w), 1089 (m), 1060
(w), 1017 (m), 967 (w), 923 (w), 869 (m), 836 (s), 801 (w),
740 (s), 652 (w), 629 (m), 545 (m) cm–1. MS (EI, 70 eV):
m/z (%) = 340 (28) [M + 1]+, 339 (100) [M+], 324 (34), 309
(5), 294 (5), 281 (5), 278 (4), 146 (5). HRMS (EI): m/z calcd
for C25H25N [M+]: 339.19815; found: 339.197901.
(15) 3-Bromo-2-(3,4-dimethoxyphenyl)-1-methyl-1H-indole
(4d)
References and Notes
(1) (a) Szmuszkovicz, J.; Glenn, E. M.; Heinzelman, R. V.;
Hester, J. B. Jr.; Youngdale, G. A. J. Med. Chem. 1966, 9,
527. (b) El-Diwani, H.; Nakkady, S. S.; Hishmat, O. H.; El-
Shabrawy, O. A.; Mahmoud, S. S. Pharmazie 1992, 47, 178.
(c) El-Diwani, H. I.; Shmeiss, N. A. M. M.; Saleh, N. M. Pol.
J. Chem. 1995, 69, 470. (d) Shmeiss, N. A. M. M.; Ismail,
M. M. F.; El-Diwani, H. I.; Hassan, A. B.; Nada, S. A.
Modell., Meas. Control C 1997, 55, 11. (e) Jones, R. L.;
Qian, Y.-M.; Wise, H.; Wong, H. N. C.; Lam, W.-L.; Chan,
H.-W.; Yim, A. P. C.; Ho, J. K. S. J. Cardiovasc.
Pharmacol. 1997, 29, 525. (f) Hishmat, O. H.; Ebeid, M. Y.;
Nakkady, S. S.; Fathy, M. M.; Mahmoud, S. S. Boll. Chim.
Farm. 1999, 138, 259.
(2) (a) Glenn, E. M.; Bowman, B. J.; Kooyers, W.; Koslowske,
T.; Myers, M. L. J. Pharmacol. Exp. Ther. 1967, 155, 157.
(b) Kaiser, D. G.; Glenn, E. M.; Johnson, R. H.; Johnston,
R. L. J. Pharmacol. Exp. Ther. 1967, 155, 174.
(c) Whitehouse, M. W. J. Pharm. Pharmacol. 1967, 19,
590. (d) Collier, H. O. J.; James, G. W. L.; Piper, P. J. Br. J.
Pharmacol. 1968, 34, 76. (e) Brune, K.; Graf, P.; Glatt, M.
Agents Actions 1976, 6, 159. (f) Podos, S. M.; Becker, B.
Invest. Ophthalmol. 1976, 15, 841. (g) Spinelli, H. M.;
Krohn, D. L. Arch. Ophthalmol. 1980, 98, 1106. (h) Klug,
R. D.; Krohn, D. L.; Breitfeller, J. M.; Dieterich, D.
Ophthalmic Res. 1981, 13, 122.
(3) For a recent study, see: McAdam, B. F.; Catella-Lawson, F.;
Mardini, I. A.; Kapoor, S.; Lawson, J. A.; FitzGerald, G. A.
Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 272.
(4) For a recent review of indole syntheses, see: Gribble, G. W.
J. Chem. Soc., Perkin Trans. 1 2000, 1045.
(5) Review: Schröter, S.; Stock, C.; Bach, T. Tetrahedron 2005,
61, 2245.
(6) Dang, T. T.; Dang, T. T.; Rasool, N.; Villinger, A.; Langer,
P. Adv. Synth. Catal. 2009, 351, 1595.
(7) Dang, T. T.; Dang, T. T.; Ahmad, R.; Reinke, H.; Langer, P.
Tetrahedron Lett. 2008, 49, 1698.
Starting with 1 (289 mg, 1.0 mmol), 2i (200 mg, 1.1 mmol),
K3PO4 (318 mg, 1.5 mmol), Pd(PPh3)4 (3 mol%), and 1,4-
dioxane (4 mL), 4d was isolated as a yellowish solid (272
mg, 79%), mp 146–148 °C. 1H NMR (300 MHz, CDCl3):
d = 3.59 (s, 3 H, NCH3), 3.84 (s, 3 H, OCH3), 3.87 (s, 3 H,
OCH3), 6.93–6.95 (m, 2 H, ArH), 7.11–7.27 (m, 4 H, ArH),
(8) Dang, T. T.; Villinger, A.; Langer, P. Adv. Synth. Catal.
2008, 350, 2109.
Synlett 2010, No. 3, 411–414 © Thieme Stuttgart · New York

414
M. F. Ibad et al.
LETTER
layers were dried (Na2SO4), filtered, and the filtrate was
concentrated in vacuo. The residue was purified by flash
chromatography (silica gel, heptanes).
7.50–7.53 (m, 1 H, ArH). 13C NMR (62.89 MHz, CDCl3):
d = 30.6 (CH3), 54.9 (OCH3), 55.0 (OCH3), 88.9 (C), 108.6
(CH), 109.9 (CH), 112.8 (CH), 118.2 (CH), 119.5 (CH),
121.7 (CH), 121.8 (C), 122.4 (CH), 126.1 (C), 135.7 (C),
137.0 (C), 147.8 (C), 148.4 (C). IR (ATR): n = 3052 (w),
2960 (w), 2924 (w), 1607 (w), 1584 (w), 1502 (m), 1462
(m), 1445 (m), 1404 (w), 1379 (w), 1339 (w), 1317 (w),
1257 (s), 1239 (s), 1168 (m), 1136 (s), 1022 (s), 945 (m), 911
(w), 858 (m), 812 (m), 777 (w), 750 (s), 654 (m), 575 (w),
547 (w) cm–1. MS (EI, 70 eV): m/z (%) = 348 (18) [M + 1,
81Br]+, 347 (100) [M+, 81Br], 346 (19) [M + 1, 79Br]+, 345
(98) [M+, 79Br], 331 (3), 302 (5), 302 (5), 300(4), 267 (3),
251 (5), 223 (24), 180 (10), 152 (7), 102 (5), 89 (2).
HRMS (EI, 70 eV): m/z calcd for C17H16O2NBr [M+, 81Br]:
347.03385; found: 347.033958; m/z calcd for C17H16O2NBr
[M+, 79Br]: 345.03589; found: 345.035679.
(17) 2-(2,5-Dimethoxyphenyl)-1-methyl-3-phenyl-1H-indole
(5a)
Starting with 1 (215 mg, 0.75 mmol), 2k (150 mg, 0.82
mmol), 2a (110 mg, 0.9 mmol), K3PO4 (488 mg, 2.3 mmol),
Pd(PPh3)4 (4 mol%), and 1,4-dioxane (4 mL), 5a was
isolated as a yellowish oil (177 mg, 69%). 1H NMR (250
MHz, CDCl3): d = 3.40 (s, 3 H, NCH3), 3.44 (s, 3 H, OCH3),
3.52 (s, 3 H, OCH3), 6.54 (d, J = 3.1 Hz, 1 H, ArH), 6.77–
6.82 (m, 1 H, ArH), 6.87–6.98 (m, 3 H, ArH), 7.04–7.18 (m,
5 H, ArH), 7.28 (d, J = 8.3 Hz, 1 H, ArH), 7.56 (d, J = 7.8
Hz, 1 H, ArH). 13C NMR (62.9 MHz, CDCl3): d = 30.7
(NCH3), 55.9 (OCH3), 56.3 (OCH3), 110.5 (CH), 113.3
(CH), 115.7 (C), 115.8 (CH), 119.5 (CH), 119.8 (CH), 120.6
(CH), 122.5 (C), 122.6 (CH), 126.2 (CH), 127.7 (C), 129.0
(2 CH), 130.1 (2 CH), 135.7 (C), 136.7 (C), 138.1 (C), 153.7
(C), 154.4 (C). IR (ATR): n = 3051 (w), 2936 (w), 2832 (w),
1736 (w), 1712 (w), 1602 (w), 1549 (w), 1502 (m), 1485
(m), 1463 (m), 1366 (m), 1273 (m), 1225 (m), 1210 (m),
1039 (m), 1020 (m), 941 (w), 918 (w), 876 (w), 805 (w), 772
(m), 735 (s), 700 (s), 616 (w), 570 (w), 531 (w) cm–1. MS
(EI, 70 eV): m/z (%) = 344 (26) [M + 1]+, 343 (100) [M+],
342 (15), 328 (6), 311 (4), 297 (7), 268 (5), 230 (5), 171 (4),
121 (5). HRMS (EI, 70 eV): m/z calcd for C23H21O2N [M+]:
343.15668; found: 343.156144.
(16) General procedure for the synthesis of 5a-e
The reaction was carried out in a pressure tube. To a dioxane
suspension (4 mL) of 1 (215 mg, 0.75 mmol), Pd(PPh3)4 (3
mol%), and Ar1B(OH)2 (0.82 mmol) was added K3PO4 (238
mg, 1.1 mmol), and the solution was degassed by bubbling
argon through the solution for 10 min. The mixture was
heated at 70 °C under argon atmosphere for 6 h. The mixture
was cooled to 20 °C. To the solution was added Ar2B(OH)2
(0.90 mmol) and K3PO4 (238 mg, 1.1 mmol), and the
solution was degassed again. The reaction mixture was
heated under argon atmosphere for 8 h at 110 °C. After
cooling to 20 °C, the solution was diluted with H2O and
extracted with CH2Cl2 (3 × 25 mL). The combined organic
(18) Billingsley, K.; Buchwald, S. L. J. Am. Chem. Soc. 2007,
129, 3358; and references cited therein.
Synlett 2010, No. 3, 411–414 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.