Palladium-catalyzed Suzuki couplings using a novel diaminophosphine oxide as ligand

Article abstract of DOI:10.1016/j.cclet.2012.02.004

A novel diaminophosphine oxide was synthesized and applied as ligand in palladium-catalyzed Suzuki couplings reaction of aryl bromides and chlorides. The coupling reaction proceeded smoothly at mild conditions using 2 mol% Pd ₂(dba)₃ in the presence of ^tBuOK.

Full text of DOI:10.1016/j.cclet.2012.02.004

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 521–524
www.elsevier.com/locate/cclet
Palladium-catalyzed Suzuki couplings using a novel
diaminophosphine oxide as ligand
*
Wen Peng Mai , Hui Hui Wang, Jin Wei Yuan, Liang Ru Yang, Zhi Cheng Li
*
Chemistry and Chemical Engineering School, Henan University of Technology, Zhengzhou 450001, China
Received 28 November 2011
Available online 30 March 2012
Abstract
A novel diaminophosphine oxide was synthesized and applied as ligand in palladium-catalyzed Suzuki couplings reaction of
aryl bromides and chlorides. The coupling reaction proceeded smoothly at mild conditions using 2 mol% Pd2(dba)3 in the presence
t
of BuOK.
# 2012 Wen Peng Mai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Palladium; Suzuki reaction; Coupling; Diaminophosphine oxide
Palladium-catalyzed Suzuki reactions are extremely powerful synthetic tools now [1–3]. It is a clear proof that it won
the Nobel Prize of Chemistry in 2010 due to its widely application in natural products, industrial intermediates,
pharmaceuticals and molecular materials [4–7]. A lot of palladium catalysts efficiently promote Suzuki couplings of aryl
halides and other electrophiles with arylboronic acids. In these catalyst systems, ligands such as phosphorus ligands,
carbene ligands, nitrogen ligands play important role [8–11]. A wide variety of ligands were developed to promote the
efficiency ofthetransformation, but the studyofdiaminophosphineoxideasligandremainsrare[12]. Phosphorusligands,
especially electron-rich phosphine ligands are often air-sensitive and therefore require air-free handling to minimize
ligand oxidation. Phosphine oxides maybe solve the problem because they are more stable and antioxidative in air.
Li first presented an alternative method that use alkyl-substituted secondary phosphine oxide in palladium-
catalyzed Suzuki couplings [13]. Ackermann and Boln [12] have reported a diaminophosphine oxide as new and high
efficient ligand in Suzuki reaction. This type of ligand has potential value in palladium-catalyzed cross-couplings, but
it has received little attention.
1. Results and discussion
Herein we wish to report a new diaminophosphine oxide (L1) (Scheme 1) as novel and efficient ligand for
palladium-catalyzed Suzuki cross-couplings of aryl bromides and chlorides with arylboronic acids. As shown in
Scheme 1, we synthesized new phosphine oxide compounds L1 and L2 in moderate yields using modified procedure.
L3 is known ligand which was reported by Ackermann and Boln [12].
* Corresponding author.
E-mail address: wpmai@yahoo.com.cn (W.P. Mai).
1001-8417/$ – see front matter # 2012 Wen Peng Mai. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2012.02.004

522
W.P. Mai et al. / Chinese Chemical Letters 23 (2012) 521–524
Ph
Ph
Ph
Ph
Ph
NH2
H
N
Ph
Ph
H2N
PCl3
CH2Cl2/H2O
47 %
Ph
N
N
P
Ph
Ph
Ph
Cl
P
N
H
NEt3/dry THF
92 %
O
H
Ph
L1
PCl3
PhPCl2
N
HN
O
NH HN
N
N
CH2Cl2/H2O
65 %
P
H
toluene
52 %
H
O
L3
L2
Scheme 1. Synthesis of L1, L2 and L3.
With L1 and L2 in hand, we first tested their catalytic activity with Pd2(dba)3 for Suzuki reaction using
phenylbromide (1a) and phenylboronic acid (2a) as substrates. The reaction conditions and results were summarized
in Table 1. Treatment with a mixture of 1a and 2a, Pd2(dba)3 and L1 in THF at 80 8C in open air for 6 h, coupling
product 3aa was obtained in 31% yield (Table 1, entry 1). The yield decreased to 20% when using Cs2CO3 as base
(Table 1, entry 2), whereas tBuOK was used as base, the yield of coupling product 3aa was improved to 94% in THF
under 70 8C (Table 1, entry 3). Dioxane and DMF were both effective for this reaction, but not better than THF under
the same conditions (Table 1, entries 4 and 5). In the presence of L2, 77% product yield was obtained under the same
conditions (Table 1, entry 7). Et3N as base was not effective in this catalyst system (Table 1, entry 6). L2 is not better
than L1, though the reaction temperature was improved to 110 8C in toluene (Table 1, entries 8 and 12). At room
temperature, the yield of product 3aa was reduced to 42% comparing with entry 3 (Table 1, entry 11). Only 60% yield
was obtained when L3 was used as ligand (Table 1, entry 9). Notably, the reaction almost could not proceed without L1
ligand (Table 1, entry 13).
Under the optimized reaction conditions, the coupling reactions between a lot of aryl bromides and some
arylboronic acids were carried out and the results were summarized in Scheme 2. As shown in Scheme 2, both
electron-rich and electron-deficient aryl bromides were efficiently coupled with arylboronic acids to give biaryl
Table 1
Palladium-catalyzed Suzuki reaction of phenylbromide with phenylboronic acida.
Pd2(dba)3/L
(HO)2B
+
Br
Base/Solvent/T
1a
2a
3aa
Entry
Base
Solvent
T/8C
Ligand
Yield (%)b
1
2
K2CO3
Cs2CO3
tBuOK
tBuOK
tBuOK
Et3N
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
THF
80
80
L1
L1
L1
L1
L1
L1
L2
L2
L3
L1
L1
L1
-
31
20
94
73
80
Trace
77
83
60
52
42
93
10
THF
3
THF
70
4
Dioxane
DMF
THF
70
5
70
6
80
7
THF
70
8
Toluene
THF
110
70
9
10
11
12
13
Toluene
THF
70
19(rt)
Toluene
THF
110
70
a
Pd2(dba)3 (2.0 mol%), 1a (2.0 mmol), 2a (2.0 mmol) and ligand (4.0 mol%) in 10 mL of the indicated solvent at indicated temperature for 6 h.
Isolated yield.
b

W.P. Mai et al. / Chinese Chemical Letters 23 (2012) 521–524
523
Pd2(dba)3 2 %
+
X
(HO)2B
tBuOK
L1 4 %
THF
R
R
R'
X = Br, Cl
R'
MeO
F
1 (93 %)
3 (84 %)
7 (95 %)
2 (90 %)
6 (90 %)
4 (96 %)
8 (87 %)
MeO
MeO
MeO
MeO
MeO
5 (81 %)
MeO
11 (88 %)
47 % (X = Cl)
12 (94 %)
55 % (X = Cl)
10 (76 %)
9 (91 %)
trace (X = Cl)
Scheme 2. Pd2(dba)3-catalyzed Suzuki cross-coupling of aryl halides with arylboronic acids.
O
P
N
Pd
P
N
.P.
N
Pd
N
N
N
H
OH
OH
Scheme 3. PO-phosphinous acid tautomeric equilibrium.
products (1–12) in excellent yields (76–96%). For arylboronic acids which have ortho substituent groups such as 2-
methoxyphenylboronic acid, 81% and 76% product yields were obtained respectively (Scheme 2, compounds 5 and
10). This indicated that the ortho group in the arylboronic had little effect in the couplings. For compound 4 or 9, the
good yields were obtained when 1-naphthaleneboronic acid was used as substrate. When 4-methylphenylboronic acid
was used as coupling partner, the product yield has slightly decreased (Scheme 2, compound 3 and 8). But compound
12 is exception, 94% product yield was obtained when 4-methylphenylboronic acid coupled with 1-
bromonaphthalene. Trace product was observed when phenylchloride coupled with 2-methoxyphenylboronic acid
which indicated arylchloride was not effective in this catalyst system (Scheme 2, compound 10). But compound 11 and
12 could be obtained in middle yields when using phenylchloride and 1-chloronaphalene as substrates. So
arylchlorides could be activated under this catalyst system if there is not bulky steric group on substrates. The reason
that L1 (compared to Ackermann’s similar ligand) was not very efficient for Suzuki reaction of aryl chlorides was
unclear.
The use of phosphine oxides (POs) as ligands in cross-coupling reaction had few reports [14–16]. In fact, POs are
the precursors of various phosphine ligands due to the tautomeric equilibrium between the POs and the tricoordinate
trivalent phosphinous acid form [17]. Thoug the equilibrium is generally shifted towards the POs form, it could be
displaced in favor of the trivalent P compound by coordination to palladium (Scheme 3). The large bulk of trityl group
on nitrogen could accelerate the reductive elimination. So we thought the electron-rich and bulky intermediate might
play key roles in the Suzuki cross-coupling reactions.
2. Conclusion
In summary, we have developed an efficient Suzuki cross-coupling reaction using novel and air-stable
diaminophosphine oxide as ligand. Many aryl bromides including electron-deficient and electron-rich bromides were
reacted with arylboronic acids smoothly in good yields under mild conditions.

524
W.P. Mai et al. / Chinese Chemical Letters 23 (2012) 521–524
Acknowledgments
We gratefully acknowledge Henan University of Technology for financial support (The Introduction of Talent
Fund) and NSFC (No. 21172055).
References
[1] N. Miyaura, Top. Curr. Chem. 219 (2002) 11.
[2] J. Hassan, M. Sevignon, C. Gozzi, et al. Chem. Rev. 102 (2002) 1359.
[3] N. Miyaura, A. Suzuki, Chem. Rev. 95 (1995) 2457.
[4] K. Pomeisl, A. Holy, R. Pohl, et al. Tetrahedron 65 (2009) 8486.
[5] J.P. Heiskanen, O.E. Hormi, Tetrahedron 65 (2009) 518.
[6] A. Suzuki, J. Organomet. Chem. 576 (1999) 147.
[7] H.Y. Liu, K. Wang, H.Y. Fu, et al. Chin. Chem. Lett. 22 (2011) 738.
[8] J.P. Wolfe, R.A. Singer, B.H. Yang, et al. J. Am. Chem. Soc. 121 (1999) 9550.
[9] N. Kudo, M. Perseghini, G.C. Fu, Angew. Chem. Int. Ed. 45 (2006) 1282.
[10] F.W. Li, S.Q. Bai, T.S. AndyHor, Organometallics 27 (2008) 672.
[11] T. Karthikeyan, S. Sankararaman, Tetrahedron 50 (2009) 5834.
[12] L. Ackermann, R. Boln, Angew. Chem. Int. Ed. 44 (2005) 2444.
[13] G.Y. Li, Angew. Chem. Int. Ed. 40 (2001) 1513.
[14] C. Wolf, R. Lerebours, Org. Lett. 6 (2004) 1147.
[15] W. Yang, Y. Wang, J.R. Corte, Org. Lett. 5 (2003) 3131.
[16] J.W. Han, J.C. Castro, K. Burgess, Tetrahedron Lett. 44 (2003) 9359.
[17] D. Martin, D. Moraleda, T. Achard, Chem. Eur. J. 17 (2011) 12729.