Diaminophosphine oxides as preligands for Ni-catalyzed Suzuki cross-coupling reactions of aryl chlorides with arylboronic acids

Article abstract of DOI:10.1016/j.tetlet.2014.11.020

The first investigation of air- and moisture-stable diaminophosphine oxides as preligands in the Ni-catalyzed Suzuki cross-coupling reactions of aryl chlorides with arylboronic acids has been reported. The results show that under the optimized reaction conditions, the new catalytic system with a Ni(II) σ-aryl complex as precatalyst and a diaminophosphine oxide as preligand tolerates a variety of functional groups and is efficient for both electron-rich and electron-deficient aryl chlorides, though it shows higher efficiency for activated arylboronic acids than deactivated ones. Steric effects were observed for both aryl chlorides and arylboronic acids.

Full text of DOI:10.1016/j.tetlet.2014.11.020

Accepted Manuscript
Diaminophosphine Oxides as Preligands for Ni-Catalyzed Suzuki Cross-Cou-
pling Reactions of Aryl Chlorides with Arylboronic Acids
Feng Hu, Blessy N. Kumpati, Xiangyang Lei
PII:
S0040-4039(14)01902-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.11.020
TETL 45404
Reference:
Tetrahedron Letters
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Accepted Date:
22 October 2014
4 November 2014
5 November 2014
Please cite this article as: Hu, F., Kumpati, B.N., Lei, X., Diaminophosphine Oxides as Preligands for Ni-Catalyzed
Suzuki Cross-Coupling Reactions of Aryl Chlorides with Arylboronic Acids, Tetrahedron Letters (2014), doi: http://
dx.doi.org/10.1016/j.tetlet.2014.11.020
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Diaminophosphine Oxides as Preligands for Ni-Catalyzed Suzuki Cross-Coupling
Reactions of Aryl Chlorides with Arylboronic Acids
Feng Hu, Blessy N. Kumpati, Xiangyang Lei*
Department of Chemistry and Biochemistry, Lamar University, Beaumont, TX, 77710, USA
* Corresponding author. Email: xlei@lamar.edu
Graphic Abstract
Abstract
The first investigation of air- and moisture-stable diaminophosphine oxides as preligands in the
Ni-catalyzed Suzuki cross-coupling reactions of aryl chlorides with arylboronic acids has been reported.
The results show that under the optimized reaction conditions, the new catalytic system with a Ni(II)
σ-aryl complex as precatalyst and a diaminophosphine oxide as preligand tolerates a variety of
functional groups and is efficient for both electron-rich and electron-deficient aryl chlorides, though it
shows higher efficiency for activated arylboronic acids than deactivated ones. Steric effects were
observed for both aryl chlorides and arylboronic acids.
Keywords: Diaminophosphine oxides; Ni(II) σ-aryl complexes; Suzuki cross-coupling reactions; Aryl
chlorides; Arylboronic acids
Transition metal-catalyzed Suzuki cross-coupling reactions are powerful tools in synthetic
chemistry.1-4 Among transition metal catalysts, Ni-based catalytic systems, due to their low cost, low
toxicity, and high reactivity, have played an important role in the construction of C-C bonds, especially
in the formation of biaryl/polyaryl motifs that have been proven to be significant in biological
molecules and chemical materials.5-13 In order to achieve high catalytic efficiency, ligands have been
employed as a key controlling element in transition metal catalysis. Although various ligands have been
1

used in Ni-catalyzed cross-couplings, the electron-rich mono- and bi-dentate phosphine ligands, which
are often prone to oxidation, are predominantly employed.5,6 A notable development of
phosphorus-based ligands was reported by Li in 2001,14,15 showing that air-stable alkyl-substituted
secondary phosphine oxides (SPOs) allow for the transformation of less reactive aryl chlorides in a
variety of cross-coupling reactions. However, with alkyl-substituted SPOs, it is difficult to modify the
electronic property of the respective phosphine oxide without altering its steric property at the same
time. Recently, heteroatom–substituted SPOs, specifically diaminophosphine oxides whose electronic
and steric properties can be finely tuned, have attracted considerate attention as preligands in a variety
of reactions, such as Pd-catalyzed Suzuki cross-coupling reactions,16-18 Pd-19 or Ni-catalyzed17,18,20,21
Kumada cross-coupling reactions, Ir-22 or Pd-catalyzed23,24 asymmetric allylic amination and alkylation,
Ru-catalyzed arylation via C-H bond functionalization,17,25,26 and Ni-catalyzed asymmetric
hydrocarbamoylations of alkenes.27 To our best knowledge, however, diaminophosphine oxides have
not been used as preligands in the Ni-catalyzed Suzuki cross-coupling reactions. As a continuation of
our research interest in Ni-catalyzed cross-coupling reactions,28-30 herein, we report the first
investigation of air- and moisture-stable diaminophosphine oxides as preligands with air-stable and
easy-to-handle Ni(II) σ-aryl complexes as precatalysts in the Suzuki cross-coupling reactions of aryl
chlorides with arylboronic acids.
Precatalysts 1-2 (Fig. 1)30,31 and preligands L1-L3 (Fig. 2)18 were easily prepared according to
literature procedures. In the preliminary study, we examined the cross-coupling reaction of
p-chloroanisole (3a) with phenylboronic acid (4a) to optimize the reaction conditions. As shown in
Table 1, when complex 1 was employed as precatalyst with K2CO3 as base and toluene as solvent at 110
oC, sterically hindered preligand L3, which bears aromatic substituents on nitrogen atoms, showed
higher efficiency than preligands L1 and L2 (entries 1-3). Similarly, preligand L3 was the most
efficient one when complex 2 was used as precatalyst under the same reaction conditions (entries 4-6).
Figure 1. Structures of Ni(II) σ-aryl complexes
Figure 2. Structures of diaminophosphine oxides used
used in this study.
in this study.
2

Table 1
Optimization of reaction conditionsa
Entry
1
Precat.
Preligand
L1
Base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
K3PO4
Cs2CO3
CsF
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
T (oC)
110
110
110
110
110
110
110
110
110
110
110
80
Yield (%)b
37
65
73
32
56
64
96
79
43
26
6
1
1
1
2
2
2
1
2
1
1
1
1
1
1
1
1
1
1
2
L2
3
L3
4
L1
5
L2
6
L3
7
L3
8
L3
9
L3
10
11
12
13
14
15
16
17
18c
L3
Na2CO3
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
L3
4
L3
EtOH
80
9
L3
DMF
110
80
45
58
11
73
56
L3
MeCN
L3
DMSO
1,4-Dioxane
Toluene
110
80
L3
L3
110
L3
a Reaction conditions: 3a (1.0 mmol), 4a (1.2 mmol), precat. (0.05 mmol), preligand (0.10 mmol), base (3.0 mmol),
solvent (3 mL), 18 h.
b GC yields using hexadecane as the internal standard.
c 1 (0.025 mmol), L3 (0.05 mmol), 24 h.
These results are consistent with the reported efficiency sequence of preligands L1-L3 in the
Ni-catalyzed Kumada cross-coupling reactions.20 Between complexes 1 and 2, precatalyst 1 is more
efficient (entries 1 and 4, 2 and 5, 3 and 6), and its higher efficiency was further confirmed when K3PO4
was used as base with L3 as preligand (entries 7 and 8). Base K3PO4 was more efficient than K2CO3,
Cs2CO3, CsF, and Na2CO3 (entries 3, 7, and 9-11). Among toluene, THF, EtOH, DMF, MeCN, DMSO,
and 1,4-dioxane, toluene is the best choice for solvent (entries 7 and 12-17). In addition, the yield
decreased from 96% to 56% when the precatalyst loading was reduced from 5.0 to 2.5 mol% (entry 18).
3

Finally, the optimal reaction conditions were set as entry 7 in Table 1. It is worthy to point out that under
the optimal reaction conditions, the cross-coupling of 3a with 4a catalyzed by NiCl2·6H2O yielded only
trace amount of cross-coupling product 5a.
Next, we examined the cross-coupling reactions of a variety of aryl chlorides with phenylboronic
acid to determine the scope of aryl chlorides. As shown in Table 2, aryl chlorides bearing
Table 2
Scope of aryl chloridesa
Entry
1
ArCl
Product
Yield (%)b
p-MeO-Ph-Cl (3a)
p-Me-Ph-Cl (3b)
o-Me-Ph-Cl (3c)
p-MeO-Ph-Ph (5a)
94
84
76
69
22
88
66
80
91
87
90
72
85
83
0
2
p-Me-Ph-Ph (5b)
3
4c
o-Me-Ph-Ph (5c)
2,5-Dimethoxy-Ph-Cl (3d)
p-HOCH2-Ph-Cl (3e)
Ph-Cl (3f)
2,5-Dimethoxy-Ph-Ph-p-OMe (5d)
p-HOCH2-Ph-Ph (5e)
Ph-Ph (5f)
5
6
7c
1-Cl-naphthalene (3g)
o-MeO2C-Ph-Cl (3h)
o-MeO2C-Ph-Cl (3i)
p-OHC-Ph-Cl (3j)
p-NC-Ph-Cl (3k)
p-PhOC-Ph-Cl (3l)
p-F-Ph-Cl (3m)
1-(p-MeO-Ph)-naphthalene (5g)
o-MeO2C-Ph-Ph (5h)
o-MeO2C-Ph-Ph (5i)
p-OHC-Ph-Ph (5j)
8
9
10
11
12
13c
14c
15
16
17
18d
19e
p-NC-Ph-Ph (5k)
p-PhOC-Ph-Ph (5l)
p-F-Ph-Ph-p-OMe (5m)
3,5-Difluoro-Ph-Ph-p-OMe (5n)
o-O2N-Ph-Ph (5o)
3,5-Difluoro-Ph-Cl (3n)
o-O2N-Ph-Cl (3o)
p-O2N-Ph-Cl (3p)
p-Ph-Ph-Cl (3q)
p-O2N-Ph-Ph (5p)
0
p-Ph-Ph-Ph (5q)
88
70
67
p-Cl-Ph-Cl (3r)
p-Ph-Ph-Ph (5q)
1,3,5-Trichlorobenzene (3s)
1,3,5-Tri(p-MeO-Ph)benzene (5r)
a Reaction conditions: 3 (1.0 mmol), 4a (1.2 mmol), 1 (0.05 mmol), L3 (0.10 mmol), K3PO4 (3.0 mmol), toluene
(3 mL), 110 oC, 18 h.
b Isolated yields.
c p-MeOPhB(OH)2 (1.2 mmol).
d 4a (2.4 mmol), 1 (0.10 mmol), L3 (0.20 mmol), K3PO4 (6.0 mmol), and toluene (4 mL).
e p-MeOPhB(OH)2 (3.6 mmol), 1 (0.15 mmol), L3 (0.30 mmol), K3PO4 (9.0 mmol), and toluene (6 mL).
4

electron-donating groups such as methoxy and methyl groups can efficiently couple with phenylboronic
acid to provide the corresponding biaryl products in good to excellent yields (entries 1–3). The coupling
of aryl chloride 3d with phenylboronic acid resulted in a crude product that is difficult to purify.
Substitution of phenylboronic acid by 4-methoxyphenylbonoric acid in the reaction facilitated the
purification of product by column chromatography and gave a good yield (entry 4). Probably due to the
effect of the active hydroxyl group, the coupling of aryl chloride 3e with phenylboronic acid gave a low
yield (entry 5). Neutral chlorobenzene (3f) and 1-chloronaphthalene (3g) coupled efficiently with
phenylboronic acid and 4-methoxylphenylbonoric acid, respectively (entries 6 and 7). Aryl chlorides
containing electron-withdrawing groups such as methoxycarbonyl, formyl, cyano, and fluoro groups
yielded the corresponding biaryl products in good to excellent yields (entries 8-14), though
nitro-substituted aryl chlorides 3o and 3p did not give any detectable cross-coupling product. This
result is consistent with literature and is probably due to the deactivation of the catalyst by the nitro
group by the formation of a stable (nitroso)nickel(II) species.29 The coupling of 4-chlorobiphenyl (3q)
and 1,4-dichlorobenzene (3r) with phenylboronic acid, respectively, gave p-terphenyl in good yields
(entries 17 and 18). The coupling of 1,3,5-trichlorobenzene (3s) with 4-methoxylphenylbonoric acid
also gave the corresponding polyphenyl in a good yield (entry 19). These results demonstrated that this
catalytic protocol was efficient for the formation of polyaryls. Steric effects were observed as the
ortho-substituted aryl chlorides generally gave lower yields than their para-substituted analogs (entries
1 and 4, 2 and 3, 8 and 9, respectively).
In order to determine the scope of arylboronic acids, the cross-coupling reactions of p-chloroanisole
(3a) with various arylboronic acids (4) were examined. As shown in Table 3, phenylboronic acids
bearing electron-donating groups and naphthylboronic acids successfully coupled with p-chloroanisole
to give the cross-coupling products in good to excellent yields (entries 1–6). The yield sequences of
p-tolylboronic acid > m-tolylboronic acid > o-tolylboronic acid (entries 2-4) and 2-naphthylboronic
acid > 1-naphthylboronic acid (entries 5 and 6) are probably due to steric effects. Except for arylboronic
acid 4h, which gave the corresponding cross-coupling product in a good yield (entry 7), phenylboronic
acids containing electron-withdrawing groups such as methoxycarbonyl, cyano, and formyl groups
gave no cross-coupling product at all (not shown). This is because electron-deficient boronic acids are
generally less reactive than electron-rich ones due to the rate-determining transmetalation step of the
catalytic cycle.32,33 Other possible reasons include the poor solubility of some arylboronic acids in
5

Table 3
Scope of arylboronic acidsa
Entry
ArB(OH)2
Product
Yield (%)b
1
2
3
4
5
6
7
8
9
p-MeO-PhB(OH)2 (4b)
p-Me-PhB(OH)2 (4c)
m-Me-PhB(OH)2 (4d)
o-Me-PhB(OH)2 (4e)
1-B(OH)2-naphthalene (4f)
2-B(OH)2-naphthalene (4g)
p-F-PhB(OH)2 (4h)
p-MeO-Ph-Ph-p-OMe (5s)
p-Me-Ph-Ph-p-OMe (5t)
m-Me-Ph-Ph-p-OMe (5u)
o-Me-Ph-Ph-p-OMe (5v)
1-(p-MeO-Ph)-naphthalene (5g)
2-(p-MeO-Ph)-naphthalene (5w)
p-F-Ph-Ph-p-OMe (5m)
3-(p-MeO-Ph)-furan (5x)
3-(p-MeO-Ph)-pyridine (5y)
93
90
83
75
70
78
78
68
0
3-B(OH)2-furan (4i)
3-B(OH)2-pyridine (4j)
a Reaction conditions: 3a (1.0 mmol), 4 (1.2 mmol), 1 (0.05 mmol), L3 (0.10 mmol), K3PO4 (3.0 mmol), toluene
(3 mL), 110 oC, 18 h.
b Isolated yields.
toluene, the strong coordination ability of functional groups (such as COOMe and CN) to the active
Ni(0) species, and the enhanced protodeboronation of arylboronic acids due to the presence of
electron-withdrawing groups.34 The coupling of heteroarylboronic acid 4i with p-chloroanisole resulted
in a good yield (entry 8), while heteroarylboronic acid 4j did not yield any cross-coupling product
(entry 9).
Similar to the other cross-coupling reactions using Ni(II) σ-aryl complexes as precatalysts,29,35 the
catalytic mechanism is believed to start with the activation of precatalyst 1 to form the active Ni(0)
species, and the observation of a small amount of 1-arylnaphthalene confirmed the precatalyst
activation process. The subsequent main catalytic cycle involves three basic steps: oxidative addition,
transmetalation, and reductive elimination. In solution, diaminophosphine oxides exist in equilibrium
between pentavalent phosphorus tautomer 6 and trivalent phosphinous acid 7 (Fig. 3).36,37 At room
temperature pentavalent tautomer 6 predominates. In the presence of base and Ni catalyst at elevated
temperature, the equilibrium is believed to shift and yield predominantly complex 8. It is proposed that
in complex 8 a phosphinous and a phosphinito ligand is associated by a strong hydrogen bond.
Therefore, the high catalytic activity achieved with diaminophosphine oxides as preligands is probably
6

due to the generation and subsequent deprotonation of the phosphinous acid nickel complex.
Figure 3. Generation and subsequent deprotonation of the phosphinous acid nickel complex (R = aryl or alkyl group).
In summary, with air-stable and easy-to-handle Ni(II) σ-aryl complexes as precatalysts, air- and
moisture-stable diaminophosphine oxides are efficient preligands for the Suzuki cross-coupling
reactions of aryl chlorides with arylboronic acids. The new catalytic system tolerates a variety of
functional groups and works for both electron-rich and electron-deficient aryl chlorides under the
optimal reaction conditions, though it shows higher efficiency for activated arylboronic acids than
deactivated ones. Steric effects were observed for both aryl chlorides and arylboronic acids.
Acknowledgements
We thank the Robert A. Welch Foundation (Grant No. V-1815) for financial support of this research.
Supplementary data
Supplementary data (experimental procedures, spectra data, and NMR spectra) associated with this
article can be found, in the online version, at….
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9