Novel bisimidazolium pincers as low loading ligands for in situ palladium-catalyzed Suzuki-Miyaura reaction in the ambient atmosphere

Article abstract of DOI:10.1039/c2cc36375e

A series of novel triazinonide-bridged bisimidazolium pincers were easily synthesized by quaternization of functionalized N-phenylimidazoles with highly reactive cyanuric chloride under mild conditions. The pincer 3c was proven to be a very efficient ligand for in situ Pd-catalyzed Suzuki-Miyaura reaction with ppm-level catalyst loading.

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Novel Bisimidazolium Pincers as Low Loading Ligands for in situ
Palladium-Catalyzed Suzuki-Miyaura Reaction in Ambient Atmosphere
Chao Gao, Hongjun Zhou, Siping Wei, Yinsong Zhao, Jingsong You and Ge Gao*
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
5
DOI: 10.1039/b000000x
phenylimidazole 2a in dry acetonitrile under reflux. To our
A series of novel triazinonide-bridged bisimidazolium pincers
were easily synthesized by quaternization of functionalized N-
phenylimidazoles with highly reactive cyanuric chloride
under mild conditions. The pincer 3c was proven to be a very
45 delight, precipitate formed quickly and the pure compound was
1
easily obtained by column chromatography on silica gel. The H
NMR of the product in DMSO-d6 showed a set of three singlets
of the hydrogens on the imidazolium ring, and a set of a typical
mono-substituted phenyl ring signals. The singlet at 10.97 ppm
50 was attributed to the hydrogen on C-2 of the imidazolium,
indicating the successful quaterization of N-phenylimidazolium.
However, the 13C NMR surprisingly showed two signals at 165.4
and 159.9 ppm of the triazine ring, suggesting two different
carbons (see ESI).
10 efficient ligand for in situ Pd-catalyzed Suzuki-Miyaura
reaction with ppm-level catalyst loading.
N-heterocyclic carbenes (NHCs) are considered as better σ-
donors and weaker π-acceptors compared with phosphine
ligands.1 Among them, pyridine-bridged bisimidazolium salts, the
15 precursors of CNC pincers, have attracted much attention because
the tridentate rigidity gives metal complexes high stability against
air, moisture and heat.2 Researches in this field have led to novel
organometallic
complexes,3
transition
metal-catalyzed
reactions,4,2c,5 soft materials6 and luminescent materials.7 To date,
20 most reported bisimidazolium pincers are type I bearing alkyl
wingtip (R
= alkyl group), which are obtained by the
quaternization of N-alkylimidazole with 2,6-dibromopyridine8a,b
or 2,6-bis(benzimidazolyl)pyridine with alkyl halides.8c Type II
pincers bearing aryl wingtip (Ar = aryl group) are very limited.
25 Only N-mesitylimidazole and N-2,6-diisopropylphenylimidazole
were reported to be directly quaternized with 2,6-dihalopyridine
at high temperature for searval days.9 However, type II pincers
are of particular interest because the steric and electronic
properties of the pincers can be subtly tuned by substitutions on
30 the aryl ring. The high reaction temperature obstructs the
introduction of functional groups and the long reaction time
makes this method less efficient. Therefore, a mild and efficient
methodology to synthesize type II pincers is very demanding.
55
Scheme 1 Proposed synthetic route for 3a.
To determine the structure of the product, the product was
firstly converted to hexafluorophosphate (PF6 ) salt and the single
-
crystal was grown in MeOH/CH2Cl2 (Figure 1). The X-ray
60 diffraction analysis revealed that 3a had crystallographically-
imposed mirror symmetry and the triazine ring was substituted by
two imidazoliums and an oxygen atom. The length of the C-O
bond (O1-C1) is 1.242(19) Å, which is more likely a C=O double
bond (1.230 Å for ureas but 1.362 Å for phenols).13 There is only
65 one PF6 counter anion, suggesting delocalization of another anion
within the triazine ring to balance one positively charged
imidazolium. So the actual structure of the product is determined
35
Cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) 1 is a highly
reactive and commonly used reagent, in which three carbons are
very electronically deficient and can be easily substituted by
nucleophiles such as oxygen and nitrogen, etc.10 Cyanuric
chloride even reacted with N-methylmorpholine to afford
-
to be a triazinonide-bridged bisimidazolium salt 3a (PF6 salt), a
type II pincer analogue.14 The triazinonide is slightly bent as the
70 dihedral angels of N1′-C1-N1-C2 and N1′-C2′-N2-C2 are -
4.09(18)˚ and -3.12(2)˚, respectively. The triazinonide,
imidazolium and phenyl rings are not coplanar. The imidazolium
40 trimorpholium salt11 and pyridine to form tripyridinium salts.12
We envisaged that N-arylimidazole may also react with cyanuric
chloride to form triimidazolium salts (Scheme 1). We then tried
the reaction of cyanuric chloride with
3 equivalents N-
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coupling reaction, the in situ catalysis is rare.17 We chose the
coupling between phenylboronic acid with 4-bromo-N,N-
dimethylaniline, a relatively less reactive substrate as the model
reaction. After screening various conditions (Table S2), the
45 optimized conditions were set to be 0.005 mol% ligand and
palladium acetate, 2 equivalents potassium phosphate in a mixed
solvent of methanol/water (v/v, 1:1) at 100 ˚C for 7 hours. In
comparison with different ligands, it clearly showed that steric
hindered ligand (3b) and electron-rich ligands (3c, 3d and 3e)
50 exhibited better reactivities than electron-deficient ligand 3f
(Table S2, entries 9-13). Ligand 3c, bearing electron-donating 4-
N,N-dimethylaminophenyl wingtips, stood out as the best ligand
and gave a 94% isolated yield of the target coupling product.
ring twists out of the triazinonide ring -168.27(11)˚ (N1-C2-N3-
C3) and the phenyl ring twists out of the imidazolium ring
154.16(12)˚ (C3-N4-C6-C7). In addition, the HRMS showed a
main peak at 382.1412, which was ascribed to the cationic part of
3a with the molecular formula of C21H16N7O+ (382.1411).
5
Fig. 1 ORTEP drawing of 3a (PF6-) (Ellipsoids are at 50% probability
level; PF6- and solvent molecule are omitted for clarity). Symmetry
operation: x, 1/2-y, z.
10
With the defined structure of the product 3a in hand, the
reaction was proposed to take place through the substitution of
the first two chlorines of cyanuric chloride by N-phenylimidazole
followed by the hydrolysis of the third chlorine by water during
workup12a,15 (Scheme 1). The mild conditions make this reaction
15 a practical method to prepare novel type II imidazolium pincers.
Various N-aryl imidazoles with bulky, electron donating,
electron-withdrawing groups were then successfully reacted with
cyanuric chloride to afford a range of type II pincers (3a-f) in
good yields (Scheme 2). Pincers 3a-f were all stable in air and at
20 elevated temperature.
55 Scheme 3 Synthesis of type I imidazolium pincer 3g and hydrolysis of
3g. Inset: ORTEP drawing of hydrolysate 4 (Ellipsoids are at 50%
probability level and solvent molecule is omitted for clarity).
For comparison, the pyridine-bridged analogue of pincer 3b,
3b′, was synthesized in 70% yield by quaternization of
60 mesitylimidazole with 2,6-dibromopyridine at 150 ˚C for 3 days,
following the literature procedure.9a However, the pyridine-
bridged analogue of pincer 3c could not be obtained. Using
pincer 3b′ for the model reaction resulted in only 56% yield of
the coupling product, which was much lower than the yield
65 obtained by using pincer 3b (Table S2, entry 14 vs 9). This
suggested a positive effect of the triazinonide bridge in this type
II pincers over pyridine bridge. In order to illustrate the Pd
species involved in the catalysis, the ligand 3a was directed
t
reacted with Pd(OAc)2 in the presence of BuONa and afforded
1
70 the Pd complex in 46% yield. H NMR, 13C NMR, HRMS and
Scheme 2 Synthesis of type II imidazolium pincers 3a-f.
elemental analysis supported the classical 1:1 pincer-Pd
complex4a as Pd(L3a)Cl (See ESI)
However, N-alkyl imidazoles are much more reactive than N-
aromatic imidazoles and type I imidazolium pincers could not be
25 obtained by this procedure. Reaction of n-butylimidazole 2g and
1 in a 2:1 ratio resulted in a hydrolyzed zwitterionic product 4
after workup, which was characterized by X-ray analysis. Two
water molecules and 2g attacked triazine ring to form two
carbonyl groups and an imidazolium substituent with the anion
30 delocalizing on N2-C3-N3 to balance the positively charged
imidazolium. Type I pincer 3g was finally obtained in 52% yield
by the reaction in dry acetonitrile at 0 ˚C within 20 minutes
followed by fast filtration and washes with cold acetonitrile. It
needs to point out that pincer 3g is unstable in ambient
35 atmosphere and must be stored under nitrogen in refrigerator,
otherwise hydrolysis to 4 occurs rapidly (Scheme 3).16
By applying ligand 3c, various bromobenzenes and
phenylboronic acids were coupled under the optimized conditions,
75 and the results were summarized in Table 1. Bromobenzene
reacted with phenylboronic acid to afford biphenyl in 98% yield
(entry 1). Couplings with various arylboronic acids contained
both electron donating group and electron withdrawing group
gave nice yields, but the results with the later were little lower
80 (entries 2-5). The reactions of less reactive bromobenzenes with
electron donating group all gave high yields over 94%, except the
slightly decreased yield with ortho-methoxy substitution,
probably due to steric hindrance effect (entries 6-9). The cross
couplings between both substituted phenylboronic acids and
85 bromobenzenes all exhibited satisfactory results (entries 10-13).
Most of the coupling reactions showed turnover numbers (TON)
over 18000, indicating this is an efficient catalytic Suzuki-
Miyaura reaction.
The catalytic activities of the bisimidazolium pincers 3a-f were
then evaluated by in situ coordination with palladium to catalyze
the Suzuki-Miyaura coupling reaction. Although there have been
40 a lot of reports about the CNC-Pd catalyzed Suzuki-Miyaura
Table 1 Suzuki couplings between aryl halides and arylboronic acidsa
2
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30 † Electronic Supplementary Information (ESI) available: Detailed
experimental procedures, analytical data and the crystallographic data of
3a (PF6-) and 4. CCDC 898254, 898255. See DOI: 10.1039/b000000x/
Pd(OAc)2 (0.005 mol%)
Ligand 3c (0.005 mol%)
Ar2
Ar1 Br
+
B(OH)2
Ar1 Ar2
K3PO4, MeOH/H2O
100 C, 7 h
1
For reviews, see: (a) W. A. Herrmann, Angew. Chem. Int. Ed., 2002,
41, 1290; (b) E. A. B. Kantchev, C. J. O’Brien and M. G. Organ,
Angew. Chem. Int. Ed., 2007, 46, 2768; (c) G. C. Fortman and S. P.
Nolan, Chem. Soc. Rev., 2011, 40, 5151.
Entry
Ar1Br
Ar2B(OH)2
Yieldb (%)
TON
35
40
45
50
55
60
65
70
75
80
85
90
Br
Br
Br
B(OH)2
1
2
3
98
94
96
19600
18800
19200
2
(a) J. A. Loch, M. Albrecht, E. Peris, J. Mata, J. W. Faller and R. H.
Crabtree, Orgnometallics, 2002, 21, 700; (b) K. Inamoto, J. Kuroda,
K. Hiroya, Y. Noda, M. Watanabe and T. Sakamoto, Orgnometallics,
2006, 25, 3095; (c) K. Inamoto, J. Kuroda, E. Kwon, K. Hiroya and T.
Doi, J. Organomet. Chem., 2009, 694, 389.
For selected examples, see: (a) A. A. D. Tulloch, A. A. Danopoulos,
G. J. Tizzard, S. J. Coles, M. B. Hursthouse, R. S. Hay-Motherwell
and W. B. Motherwell, Chem. Comm., 2001, 1270; (b) A.
Danopoulos, D. Pugh and J. Wright, Angew. Chem. Int. Ed., 2008,
47, 9765; (c) A. Mrutu, D. A. Dickie, K. I. Goldberg and R. A. Kemp,
Inorg. Chem., 2011, 50, 2729; (d) D. H. Brown and B. W. Skelton,
Dalton Trans., 2011, 40, 8849.
For reviews, see: (a) E. Peris and R. H Crabtree, Coord. Chem. Rev.,
2004, 248, 2239; (b) I. Moreno, R. S. Martin, B. Inés, F. Churruca,
and E. Domínguez, Inorg. Chim. Acta., 2010, 363, 1903; (c) N.
Selander and K. J. Szabό, Chem. Rev., 2011, 111, 2048.
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Padilla, F. Rominger and M. Limbach, Orgnometallics, 2011, 30,
1885; (b) Z. Wang, X. Feng, W. Fang and T. Tu, Synlett, 2011, 7,
951; (c) G. Urgoitia, R. SanMartin, M. T. Herrero and E. Domínguez,
Green Chem., 2011, 13, 2161; (d) R. SanMartin, B. Inés, M. J. Moure,
M. T. Herrero and E. Domínguez, Helv. Chim. Acta, 2012, 95, 955;
(e) R. P. Yu, J. M. Darmon, J. M. Hoyt, G. W. Margulieux, Z. R.
Turner and P. J. Chirik, ACS Catal., 2012, 2, 1760.
(a) T. Tu, W. Assenmacher, H. Peterlik, R. Weisbarth, M. Nieger and
K. H. Dötz, Angew. Chem. Int. Ed., 2007, 46, 6368; (b) T. Tu, W.
Assenmacher, H. Peterlik, G. Schnakenburg and K. H. Dötz, Angew.
Chem. Int. Ed., 2008, 47, 7127; (c) T. Tu, X, Bao, W. Assenmacher,
H. Peterlik, J. Daniels and K. H. Dötz, Chem. Eur. J., 2009, 15, 1853.
(a) C. S. Lee, S. Sabiah, J. C. Wang, W. S. Hwang and I. J. B. Lin,
Orgnometallics, 2010, 29, 286; (b) C. S. Lee, R. R. Zhuang, S.
Sabiah, J. C. Wang, W. S. Hwang and I. J. B. Lin, Orgnometallics,
2011, 30, 3897.
(a) J. C. C. Chen and I. J. B. Lin, J. Chem. Soc., Dalton Trans., 2000,
839; (b) J. A. Loch, M. Albrecht, E. Peris, J. Mata, J. W. Faller and
R. H. Crabtree, Organometallics, 2002, 21, 700; (c) T. Tu, J.
Malineni and K. H. Dötz, Adv. Synth. Catal., 2008, 350, 1791
(a) A. A. Danopoulos, A. A. D. Tulloch, S. Winston, G. Eastham and
M. B. Hursthouse, Dalton Trans., 2003, 1009; (b) D. Pugh, A. Boyle
and A. A. Danopoulos, Dalton Trans., 2008, 1087.
MeO
B(OH)2
Ph2N
F3
B(OH)2
3
C
Br
Br
4
5
6
7
89
91
89
97
17800
18200
17800
19400
B(OH)2
F
B(OH)2
B(OH)2
OMe
Br
4
5
MeO
B(OH)2
Br
MeO
N
Br
B(OH)2
B(OH)2
8
9
98
94
94
19600
18800
18800
Br
N
N
Br
Br
MeO
B(OH)2
10
F
F
11
12
92
18400
6
F
B(OH)2
NC
O
Br
96
98
19200
19600
F
B(OH)2
B(OH)2
MeO
13
Br
7
8
9
a
Conditions: arylbromides (1.0 mmol), arylboronic acid (1.1 mmol),
Pd(OAc)2 (0.005 mol%), ligand 3c (0.005 mol%), K3PO4 (2.0 mmol),
H2O/MeOH (v/v 1:1, 1 mL) at 100 ˚C for 7 h. b Isolated yield.
5
In summary, we disclose here a facile and mild method to
synthesize bisimidazolium pincers of type II analogue by using
highly reactive cyanuric chloride to quaternize arylimidazoles.
This method provides access to various functionalized
bisimidzolium pincers, which could not be obtained by traditional
10 synthesis. The in situ Pd-catalyzed Suzuki-Miyaura reaction
using these pincers showed that pincer 3c, which bears 4-N,N-
dimethylaminophenyl wingtips is a highly efficient ligand with
Pd-3c loading as low as 0.005 mol%. The high efficiency of the
ligand was demonstrated to take advantage of the unusual
15 triazinonide bridge over the traditional pyridine bridge and the
electron-donating 4-N,N-dimethylaminophenyl wingtips which
could not be obtained before. The strategy presented here
provides an easy way to prepare functional NHC pincer
precursors.
10 For a review, see: (a) G. Blotny, Tetrahedron, 2006, 62, 9507; (b)
H.-S. Moon, E. M. Jacobson, S. M. Khersonsky, M. R. Luzung, D. P.
Walsh, W. Xiong, J. W. Lee, P. B. Parikh, J. C. Lam, T.-W. Kang, G.
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124, 11608.
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Heterocycles, 1990, 31, 2055; (b) F. Cherioux and P. Audebert,
Chem. Mater., 1998, 10, 1984; (c) S. Brasselet, F. Cherioux, P.
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13 F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen
and R. Taylor, J. Chem. Soc., Perkin Trans. 2 1987, S1.
20
We thank the financial support from the NSFC (Nos 20902063,
21172159 and 21021001) and the SRF for ROCS, SEM (No
20111568-8-2). We also thank the Centre of Testing & Analysis,
Sichuan University for NMR measurements and X-ray analyses.
14 (a) F. Gómez-de la Torre, A. de la Hoz, F. A. Jalón, B. R. Manzano,
A. Otero, A. M. Rodríguez, M. C. Rodríguez-Pérez, A. Echevarría
and J. Elguero, Inorg. Chem., 1998, 37, 6606; (b) R. M. Claramunt, P.
Cornago, M. Cano, J. V. Heras, M. L. Gallego, E. Pinilla and M. R.
Torres, Eur. J. Inorg. Chem., 2003, 2693; (c) J. Manzur, C. Acuña, A.
Vega and A. M. García, Inorg. Chim. Acta, 2011, 374, 637.
Notes and references
95 15 M. A. Bigdeli, G. H. Mahdavinia, S. Jafari and H. Hazarkhani, Catal.
Comm., 2007, 8, 2229.
16 (a) A. Poethig and T. Strassner, Orgnometallics, 2011, 30, 6674; (b)
A. Poethig and T. Strassner, Organometallics, 2012, 31, 3431.
17 T. Tu, J. Malineni, X. Bao and K. H. Dötz, Adv. Synth. Catal., 2009,
25 Key Laboratory of Green Chemistry and Technology of Ministry of
Education, College of Chemistry, and State Key Laboratory of
Biotherapy, West China Medical School, Sichuan University, 29
Wangjiang Road, Chengdu 610064, PR China. Fax: (+86) 28-85412203;
E-mail: gg2b@scu.edu.cn
100
351, 1029.
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