Palladium-catalyzed Suzuki-Miyaura reaction of aryl chlorides in aqueous media using tetrahydrodiazepinium salts as carbene ligands

Article abstract of DOI:10.1055/s-2005-872673

A highly effective, easy to handle, and environmentally benign process for palladium-mediated Suzuki cross-coupling was developed. The in situ prepared three-component system of Pd(OAc)₂, 1,3-dialkyltetrahydrodiazepinium chlorides (2a-e), and K

Full text of DOI:10.1055/s-2005-872673

2
394
LETTER
Palladium-Catalyzed Suzuki–Miyaura Reaction of Aryl Chlorides in Aqueous
Media Using Tetrahydrodiazepinium Salts as Carbene Ligands
a
a
a
b
b
P
I
alladium
s
-Catalyz
m
e
d
Suzuki–Miyaura
a
R
eaction
o
i
f
A
ryl
l
A
Ö
queous
M
edia zdemir,* Nevin Gürbüz, Yetkin Gök, Engin Çetinkaya, Bekir Çetinkaya
a
Inönü University, Faculty of Science and Arts, Chemistry Department, 44280 Malatya, Turkey
Fax +90(422)3410212; E-mail: iozdemir@inonu.edu.tr
b
Department of Chemistry, Ege University, 35100 Bornova-Izmir, Turkey
Received 13 June 2005
chlorides, but an oxime-carbapalladacycle is employed as
the catalyst. In the course of our search for NHC based
ligands, we already reported the use of in situ formed
Abstract: A highly effective, easy to handle, and environmentally
benign process for palladium-mediated Suzuki cross-coupling was
developed. The in situ prepared three-component system of
1
4
Pd(OAc) , 1,3-dialkyltetrahydrodiazepinium chlorides (2a–e), and imidazolidin-2-ylidenepalladium(II) system which shows
2
K CO catalyzes quantitatively the Suzuki–Miyaura cross-coupling high activities in various coupling reactions of aryl
2
3
15
of deactivated aryl chloride.
bromides and aryl chlorides. In order to obtain an even
Key words: tetrahydrodiazepinium, Suzuki–Miyaura reaction, more stable and active system we have also investigated
benzo-annelated derivatives.16
palladium, C–C coupling, N-heterocyclic carbene
In order to find more efficient palladium catalysts we have
prepared a series of new 1,3-dialkyl-4,5,6,7-tetrahydro-
The palladium-catalyzed cross-coupling of aryl halides
with arylboronic acids to form biaryls has emerged as an
1
,3-diazepinium chloride (2, Scheme 1), containing a
saturated diazepine ring and we report here an in situ
prepared Pd-carbene-based catalytic system for the
1
,2
extremely powerful tool in organic synthesis. Sterically
3
4,5
hindered, electron-rich alkyl phosphines and carbene
17
Suzuki–Miyaura coupling reaction in aqueous media.
ligands have received increasing interest in recent years.
However, the phosphine ligands and the phosphine–palla-
dium complexes are liable to being air- and moisture-sen-
sitive at elevated temperatures, placing significant limits
on their synthetic application. Therefore, in terms of prac-
tical application, the development of more reactive and
stable ligands is of importance for the palladium-cata-
lyzed Suzuki reaction. Recently, nucleophilic N-hetero-
The 1,4-dialkyl-1,4-diaminobutanes were prepared ac-
cording to a known method.18 1,3-Dialkyltetrahydrodi-
azepinium chlorides 2 are conventional NHC precursors.
According to Scheme 1, the salts 2a–e were prepared by
treatment of 1,4-dialkyl-1,4-diaminobutane and ammoni-
um chloride with triethyl orthoformate (Scheme 1).1 It
has been found that in situ formation of the ligand by
deprotonation of the bis(imidazolinium)bromides, leads
to significantly better results than employing the pre-
formed carbene.19
5a
6
cyclic carbenes (NHC’s), with a stronger s-donor
7
electronic property than bulky tertiary phosphines, have
emerged as a new family of ligands. In contrast to metal
complexes of phosphines, the metal–NHC complexes We started our investigation with the coupling of p-chlo-
appeared to be extraordinarily stable towards heat, air, and roacetophenone and phenylboronic acid, in the presence
moisture due to their high metal–carbon bond energies.8 of only 1 mol% Pd(OAc)
and 2 mol% 2. Table 1 summa-
2
The development of new ligands or the application of ex- rizes the results obtained in the presence of 2a–e (Table 1,
isting ligands in this reaction, particularly those involving entries 1–5).
aryl chlorides as substrates, is still of considerable impor-
R2
R2
tance. A major advance achieved by increasing the cata-
lytic activity is the extension of the Suzuki reaction to
unactivated aryl chlorides, as noted by the research groups
R1
R1
R3
R3
R2
R2
3
a,b
9
10
of Buchwald, Fu, and Herrmann as well as several
R1
R1
Cl–
N
NH
1
1
NH Cl
4
other groups. The use of water as a solvent for chemical
reactions clearly has both economical and environmental
advantages because it is inexpensive, abundant, nontoxic,
nonflammable, and readily separable from organic com-
+
CH(OEt)3
R1
N
R1
NH
R2
R2
R3
R3
1
2
R1
pounds. There have been a number of reports of the
palladium-mediated Suzuki reaction, being performed
using water as solvents, for the coupling of aryl boronic
R1
R2
R2
1
3
1
2
acids with aryl iodides or activated bromide and aryl
2
1
3
a
R = H, R , R = CH3
1
2
3
d
e
R , R = H, R = OCH3
2
1
3
1
2
3
b
c
R = H, R , R = OCH3
R , R = H, R = N(CH3)2
SYNLETT 2005, No. 15, pp 2394–2396
1
9
.0
9
.2
0
0
5
1
2
3
R = H, R , R = OCH3
Advanced online publication: 07.09.2005
DOI: 10.1055/s-2005-872673; Art ID: G16305ST
Scheme 1 The synthesis of 1,3-diazepinium salts.
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Palladium-Catalyzed Suzuki–Miyaura Reaction of Aryl Chlorides in Aqueous Media
2395
To survey the reaction parameters for the catalytic Table 1 The Suzuki–Miyaura Coupling Reaction of Aryl Chlorides
with Phenylboronic Acida
Suzuki–Miyaura reaction, we chose to examine Cs CO ,
2
3
K CO , and K PO as bases with DMF–H O (1:1) and di-
2
3
3
4
2
B(OH)2
+
R
Cl
oxane as solvent. We found that the reactions performed
in DMF–H O (1:1) with Cs CO or K CO at 60 °C
2
2
3
2
3
Pd(OAc)2 (1 mmol%)
a–e (2 mmol%)
appeared to be the best. In addition, the reactions were
performed in air without degassing the water and DMF
prior to use.
2
R
DMF/H2O, K2CO3
Under those conditions, p-chloroacetophenone, p-chloro-
toluene, p-chlorobenzaldehyde, p-chloroanisole, and p-
chlorobenzene, react very cleanly with phenylboronic
acid in goods yields (Table 1, entries 3, 8, 13, and 23). The
higher performance of the 1,3-dialkyltetrahydrodiazepin-
ium salts 2 is thought to be due to its better electron-do-
nating ability and greater steric hindrance.
b
Entry
R
LHX
2a
2b
2c
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
COCH3
95
95
98
84
91
82
81
86
74
72
89
87
91
86
89
75
77
74
75
72
78
79
90
73
68
COCH3
COCH3
COCH3
2d
2e
In conclusion, we have demonstrated that in situ generat-
ed tetrahydrodiazepin-2-ylidene palladium complexes are
very effective in Suzuki–Miyaura coupling reactions, sur-
COCH3
CH3
2a
2b
2c
passing the corresponding imidazolidin-2-ylidene palladi-
um complexes.15a The procedure is simple and efficient
CH3
for various aryl chlorides and does not require induction
periods. The advantage of the catalyst is its low loading
capabilities and that it can be used in air. Further work is
underway to optimize the reactivity of these N-hetero-
cyclic carbene precursors for C–C and C–N coupling with
CH3
CH3
2d
2e
1
1
1
1
1
1
CH3
CHO
CHO
CHO
CHO
CHO
OCH3
OCH3
OCH3
2a
2b
2c
Pd(OAc) , and transition metal complexes of Ru, Pd, Rh,
2
and Ir to explore their catalytic activity.
Acknowledgment
2d
2e
This work was financially supported by the Technological and
Scientific Research Council of Turkey TÜBITAK [TÜBITAK
COST D17 and TBAG-2474 (104T085)] and Inönü University
Research Fund (B.A.P.: 2005/42)
16
2a
2b
2c
1
1
1
2
2
7
8
9
0
1
References
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(
(
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a
Reaction conditions: p-R-C H Cl (1.0 mmol), phenylboronic acid
1.5 mmol), K CO (2 mmol), Pd(OAc) (1 mmol%), 2 (2 mmol%),
6
4
(
2 3 2
H O–DMF (1:1, 6 mL).
2
b
Purity of compounds was checked by NMR spectroscopy and yields
are based on aryl chloride. All reactions were performed three times
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6
(
b) Herrmann, W. A.; Weskamp, T.; Böhm, V. P. W. Adv.
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(
5) (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand, G.
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Synlett 2005, No. 15, 2394–2396 © Thieme Stuttgart · New York

2
396
I. Özdemir et al.
LETTER
1
(7) Huang, J.; Schanz, H.-J.; Stevens, E. D.; Nolan, S. P.
Organometallics 1999, 18, 2370.
6.92 (s, 1 H, 2-CH). 13C{ H} NMR (75.47 MHz, DMSO):
d = 25.8, 50.2 (NCH CH CH CH N), 51.3, 56.9 [2,4,6-
2
2
2
2
(
8) Schwarz, J.; Böhm, V. P. W.; Gardiner, M. G.; Grosche, M.;
Herrmann, W. A.; Hieringer, W.; Raudaschl-Sieber, G.
Chem.–Eur. J. 2000, 6, 1773.
(CH O) C H CH ], 57.3 [2,4,6-(CH O) C H CH ], 92.3,
3 3 6 2 2 3 3 6 2 2
103.4, 156.3, 160.9 [2,4,6-(CH O) C H CH ], 163.4 (2-
3
3
6
2
2
CH). Anal. Calcd for C H N O Cl: C, 60.66; H, 7.12; N,
2
5
35
2
6
(
9) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1998, 37,
5.65. Found: C, 60.68; H, 7.10; N, 5.67.
3
387.
10) Herrmann, W. A.; Böhm, V. P. W. J. Organomet. Chem.
999, 576, 23.
1,3-Bis(3,4,5-trimethoxybenzyl)-4,5,6,7-tetrahydro-1,3-
diazepinium chloride (2c). Yield: 1.23 g (87%); mp 151–
152 °C. H NMR (300.13 MHz, DMSO): d = 1.78 (quintet,
(
(
1
1
11) (a) Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
Angew. Chem. Int. Ed. 2003, 42, 3690. (b) Franki, M.;
Maas, G.; Schatz, J. Eur. J. Org. Chem. 2004, 607.
J = 7.2 Hz, 4 H, NCH CH CH CH N), 3.34 (t, J = 7.2 Hz, 4
2
2
2
2
H, NCH CH CH CH N), 3.65 and 3.78 [s, 18 H, 3,4,5-
2
2
2
2
(CH O) C H CH ], 4.64 [s, 4 H, 3,4,5-(CH O) C H CH ],
3
3
6
2
2
3
3
6
2
2
(
(
c) Colacot, T.; Shea, H. A. Org. Lett. 2004, 6, 3731.
d) Vargas, V. C.; Rubio, R. J.; Hollis, T. K.; Salcido, M. E.
6.88 [s, 4 H, 3,4,5-(CH O) C H CH ], 9.11 (s, 1 H, 2-CH).
3 3 6 2 2
1
3
1
C{ H} NMR (75.47 MHz, DMSO): d = 25.0, 48.9
(NCH CH CH CH N), 56.8,60.7[3,4,5-(CH O) C H CH ],
Org. Lett. 2003, 5, 4847.
2
2
2
2
3
3
6
2
2
(
(
12) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media;
Wiley: New York, 1997.
13) (a) Genet, J.-P.; Savignac, M. J. Organomet. Chem. 1999,
60.3 [3,4,5-(CH O) C H CH ], 106.9, 131.4, 138.3, 153.8
3 3 6 2 2
[3,4,5-(CH O) C H CH ], 159.5 (2-CH). Anal. Calcd for
3
3
6
2
2
C H N O Cl: C, 60.66; H, 7.12; N, 5.65. Found: C, 60.67;
25 35 2 6
576, 305. (b) Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org.
H, 7.11; N, 5.64.
Chem. 2002, 67, 2721. (c) Bumagin, V.; Bykov, V. V.
Tetrahedron 1997, 53, 14437. (d)Parisot, S.;Kolodziuk, R.;
Henry, C. G.; Iourtchenko, A.; Sinou, D. Tetrahedron Lett.
1,3-Bis(p-methoxybenzyl)-4,5,6,7-tetrahydro-1,3-
diazepinium chloride (2d). Yield: 1.82 g (79%); mp 298–
299 °C. H NMR (300.13 MHz, DMSO): d = 1.71 (quintet,
1
2002, 43, 7397. (e) LeBlond, C. R.; Andrews, A. T.; Sun,
J = 6.8 Hz, 4 H, NCH CH CH CH N), 3.01 (t, J = 6.8 Hz, 4
2
2
2
2
Y.; Sowa, J. R. Org. Lett. 2001, 3, 1555.
H, NCH CH CH CH N), 3.81 (s, 6 H, p-CH OC H CH ),
2 2 2 2 3 6 4 2
(
(
14) Botella, L.; Najera, C. Angew. Chem. Int. Ed. 2002, 41, 179.
15) (a) Gürbüz, N.; Özdemir, I.; Demir, S.; Çetinkaya, B. J. Mol.
Catal. A: Chem. 2004, 209, 23. (b) Özdemir, I.; Çetinkaya,
B.; Demir, S.; Gürbüz, N. Catal. Lett. 2004, 97, 37.
4.64 (s, 4 H, p-CH OC H CH ), 7.01 and 7.39 (d, J = 8.4 Hz,
3 6 4 2
1
3
1
8 H, p-CH OC H CH ), 8.89 (s, 1 H, 2-CH). C{ H} NMR
3
6
4
2
(75.47 MHz, DMSO): d = 23.1, 46.3 (NCH CH CH CH N),
2
2
2
2
50.7 (p-CH OC H CH ), 55.8 (p-CH OC H CH ), 115.0,
3
6
4
2
3
6
4
2
(c) Özdemir, I.; Demir, S.; Yaşar, S.; Çetinkaya, B. Appl.
123.5, 131.9 (p-CH OC H CH ), 160.2 (2-CH). Anal. Calcd
3 6 4 2
Organomet. Chem. 2005, 19, 55. (d) Gürbüz, N.; Özdemir,
I.; Seçkin, T.; Çetinkaya, B. J. Inorg. Organomet. Polym.
for C H N O Cl: C, 67.27; H, 7.25; N, 7.47. Found: C,
21 27 2 2
67.30; H, 7.23; N, 7.46.
2
004, 14, 149.
1,3-Bis(p-dimethylaminobenzyl)-4,5,6,7-tetrahydro-1,3-
diazepinium chloride (2e). Yield: 3.11 g (92%), mp 247–
248 °C. H NMR (300.13 MHz, DMSO): d = 1.68 (quintet,
(
16) (a) Özdemir, I.; Gök, Y.; Gürbüz, N.; Yaşar, S.; Çetinkaya,
E.; Çetinkaya, B. Polish J. Chem. 2004, 78, 2141.
1
(
b) Özdemir, I.; Gök, Y.; Gürbüz, N.; Çetinkaya, E.;
Çetinkaya, B. Synth. Commun. 2004, 34, 4135.
c) Özdemir, I.; Gök, Y.; Gürbüz, N.; Çetinkaya, E.;
J = 6.8 Hz, 4 H, NCH CH CH CH N), 2.89 [s, 12 H, p-
2
2
2
2
(CH ) NC H CH ], 3.52 (t, J = 6.8 Hz, 4 H,
3
2
6
4
2
(
NCH CH CH CH N), 4.54 [s, 4 H, p-(CH ) NC H CH ],
2 2 2 2 3 2 6 4 2
Çetinkaya, B. Heteroat. Chem. 2004, 15, 419. (d) Özdemir,
I.; Alici, B.; Gürbüz, N.; Çetinkaya, E.; Çetinkaya, B. J. Mol.
Catal. A: Chem. 2004, 217, 37.
6.73 and 7.27 (d, J = 8.4 Hz, 8 H, p-(CH ) NC H CH ), 8.87
3 2 6 4 2
(s, 1 H, 2-CH). C{ H} NMR (75.47 MHz, DMSO):
1
3
1
d = 24.7, 48.5 (NCH CH CH CH N), 40.7 [p-
2
2
2
2
(
17) General procedure for the synthesis of 1,3-dialkyl-
(CH ) NC H CH ], 60.1 [p-(CH ) NC H CH ], 112.9,
3 2 6 4 2 3 2 6 4 2
4,5,6,7-tetrahydro-1,3-diazepinium chloride (2): To a
122.2, 130.1, 151.1 [p-(CH ) NC H CH ], 158.3 (2-CH).
3 2 6 4 2
solution of 1,4-bis(alkylamino)butane (1 mmol) in
Anal. Calcd for C H N Cl: C, 68.89; H, 8.29; N, 13.97.
23 33 4
CH(OEt) (30 mL), NH Cl (1 mmol) was added; the reaction
mixture was heated for 18 h at 100 °C. A white solid was
precipitated. The precipitate was then crystallized from
Found: C, 68.88; H, 8.30; N, 13.97.
General procedure for the Suzuki–Miyaura coupling
reaction
3
4
EtOH–Et O (1:2).
Pd(OAc) (1.0 mmol%), 1,3-dialkyltetrahydrodiazepinium
2
2
1,3-Bis(2,4,6-trimethylbenzyl)-4,5,6,7-tetrahydro-1,3-
chlorides, 2 (2.0 mmol%), aryl chloride (1.0 mmol),
diazepinium chloride (2a). Yield: 2.20 g (73%); mp 217–
phenylboronic acid (1.2 mmol), K CO (2 mmol), H O–
2
3
2
1
218 °C. H NMR (300.13 MHz, DMSO): d = 1.90 (quintet,
DMF (6 mL, 1:1) were added to a small Schlenk tube in air
and the mixture was heated at 60 °C for 0.5 h. At the
conclusion of the reaction, the mixture was cooled, extracted
J = 7.2 Hz, 4 H, NCH CH CH CH N), 2.09 and 2.23 [s, 18
2
2
2
2
H, 2,4,6-(CH ) C H CH ], 3.66 (t, J = 7.2 Hz, 4 H,
3
3
6
2
2
NCH CH CH CH N), 4.58 [s, 4 H, 2,4,6-(CH ) C H CH ],
with Et O, filtered through a pad of silica gel, washed
2
2
2
2
3
3
6
2
2
2
6
.77 [s, 4 H, 2,4,6-(CH ) C H CH ], 7.30 (s, 1 H, 2-CH).
thoroughly, concentrated, and purified by flash
chromatography on silica gel. The purity of the compounds
was checked by GC and yields are based on aryl chloride.
(18) Gök, Y.; Çetinkaya, E. Turk. J. Chem. 2004, 28, 157.
(19) (a) Semeril, D.; Bruneau, C.; Dixneuf, P. H. Adv. Synth.
Catal. 2002, 344, 585. (b) Semeril, D.; Cleran, M. D.;
Bruneau, C.; Dixneuf, P. H. Adv. Synth. Catal. 2001, 343,
184. (c) Castarlenes, R.; Alaoui-Abdallaoui, ; Semeril, D.;
Mernari, B.; Guesmi, S.; Dixneuf, P. H. New J. Chem. 2003,
27, 6. (d) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H.
M.; Yang, C.; Nolan, S. P. J. Organomet. Chem. 2002, 653,
69. (e) Zhang, C.; Trudell, M. L. Tetrahedron Lett. 2000, 41,
595.
3
3
6
2
2
13
1
C{ H} NMR (75.47 MHz, DMSO): d = 19.8, 49.9
NCH CH CH CH N), 21.3, 24.9 [2,4,6-(CH ) C H CH ],
(
2
2
2
2
3 3
6
2
2
54.3 [2,4,6-(CH ) C H CH ], 126.7, 129.9, 138.6, 138.9
3 3 6 2 2
[
2,4,6-(CH ) C H CH ], 154.5 (2-CH). Anal. Calcd for
3 3 6 2 2
C H N Cl: C, 75.25; H, 8.84; N, 7.02. Found: C, 75.23; H,
25
35
2
8.85; N, 7.04.
1,3-Bis(2,4,6-trimethoxybenzyl)-4,5,6,7-tetrahydro-1,3-
diazepinium chloride (2b). Yield: 1.48 g (90%); mp 233–
1
234 °C. H NMR (300.13 MHz, DMSO): d = 1.66 (quintet,
J = 7.2 Hz, 4 H, NCH CH CH CH N), 3.55 and 3.67 [s, 18
H, 2,4,6-(CH O) C H CH ], 3.46 (t, J = 7.2 Hz, 4 H,
NCH CH CH CH N), 4.50 [s, 4 H, 2,4,6-
2
2
2
2
3
3
6
2
2
2
2
2
2
(
CH O) C H CH ], 6.02 [s, 4 H, 2,4,6-(CH O) C H CH ],
3 3 6 2 2 3 3 6 2 2
Synlett 2005, No. 15, 2394–2396 © Thieme Stuttgart · New York