6H-Dibenzo[d,f-[1,3]diazepin-6-ylidene,5,7-dihydro-5,7-diphenylphosphanyl]: A new ligand for palladium-catalyzed Mizoroki-Heck coupling

Article abstract of DOI:10.1016/j.catcom.2014.07.031

A novel and conveniently prepared diphosphine ligand 6H-Dibenzo[d,f-[1,3] diazepin-6-ylidene,5,7-dihydro-5,7-diphenylphosphanyl] (DADPP) combined with [Pd(C₃H₅)Cl]₂ affords an efficient catalytic system for Mizoroki-Heck cross-coupling of aryl halides with alkenes. The system could give the yield of 95% for 4-chloronitrobenzene with 0.05 mol.% [Pd(C ₃H₅)Cl]₂. For the bromide-substituted substrates, the highest turnover number (TON) is up to 96,000,000.

Full text of DOI:10.1016/j.catcom.2014.07.031

Catalysis Communications 57 (2014) 14–18
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
6H-Dibenzo[d,f-[1,3]diazepin-6-ylidene,5,7-dihydro-5,
7-diphenylphosphanyl]: A new ligand for
palladium-catalyzed Mizoroki–Heck coupling
⁎
Zhi-jie Jiang, Wei Wang, Rong Zhou, Lei Zhang, Hai-yan Fu, Xue-li Zheng, Hua Chen, Rui-xiang Li
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu, Sichuan 610064, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 June 2014
Received in revised form 15 July 2014
Accepted 21 July 2014
Available online 28 July 2014
A novel and conveniently prepared diphosphine ligand 6H-Dibenzo[d,f-[1,3]diazepin-6-ylidene,5,7-dihydro-5,7-
diphenylphosphanyl] (DADPP) combined with [Pd(C3H5)Cl]2 affords an efficient catalytic system for Mizoroki–
Heck cross-coupling of aryl halides with alkenes. The system could give the yield of 95% for 4-chloronitrobenzene
with 0.05 mol.% [Pd(C3H5)Cl]2. For the bromide-substituted substrates, the highest turnover number (TON) is up
to 96,000,000.
© 2014 Published by Elsevier B.V.
Keywords:
Mizoroki–Heck coupling
Palladium
Phosphine
Aryl halide
1. Introduction
containing two nitrogen atoms, 6H-Dibenzo[d,f-[1,3]diazepin-6-yli-
dene,5,7-dihydro-5,7-diphenyl-phosphanyl] (DADPP) (Scheme 1).
Palladium-catalyzed Mizoroki–Heck coupling is one of the most im-
portant tools for constructing C-C bonds in organic synthesis [1–5].
Pd(0) is usually considered as the active species in this transformations.
However, the bare Pd(0) is very unstable and easy to aggregate, which
leads to the deactivation of Pd(0) species. In order to effectively solve
this problem, a high catalyst loading has to be required in the catalysis
process [6]. Furthermore, the addition of phosphine ligand is also found
to be a useful and reliable method [1,7]. In the past decades, a few
multidentate phosphines were used to mediate Heck reaction with an ex-
tremely low catalyst loading [8–16]. However, these phosphine ligands
did not exhibit good performance toward the chloride-substituted sub-
strates. Moreover, the tedious synthetic routes of multidentate phos-
phines limit their wide applications. Some diphosphines containing
nitrogen atom, which are easily prepared, have also shown good activities
in Heck reaction with excellent regioselectivities by chelating to the pal-
ladium species. Among them, N, N-bis(diphenylphosphinomethyl)-
amine (L) (Scheme 1), seemed to facilitate the coupling of chlorobenzene
with alkenes [17]. It has been revealed that the electronic effect of nitro-
gen atom played a key role [18–20]. Although great progress has been
made, to date, extending the lifetime of the Pd(0) active species still re-
mains a challenge. Herein, we developed a simple palladium-catalyzed
system for Mizoroki–Heck coupling with a new diphosphine ligand
2. Experimental
2.1. Synthesis of DADPP
A 100-mL three-necked flask equipped with a magnetic bar was
charged with [Ph2P(CH2OH)2]+Cl− (1.7 g, 4 mmol), 20 mL ethanol, 10
mL triethylamine and 20 mL toluene. 2,2′-Diaminobiphenyl (368 mg,
2 mmol) was dissolved in toluene and added dropwise into the mix-
ture, and then refluxed for 30 h (Scheme 2). At the end of the reaction,
removed the solvent and the residue was washed with 2 × 10 mL
ethanol and 2 × 10 mL H2O, then the desired product was obtained
⁎
Corresponding author. Tel./fax: +86 28 85412904.
E-mail address: liruixiang@scu.edu.cn (R. Li).
Scheme 1. Structure of ligands DADPP and L.
http://dx.doi.org/10.1016/j.catcom.2014.07.031
1566-7367/© 2014 Published by Elsevier B.V.

Z. Jiang et al. / Catalysis Communications 57 (2014) 14–18
15
Scheme 2. Synthesis of DADPP.
as a white solid (720 mg, 62% yield). 1H NMR (400 MHz, CDCl3): δ 7.44–
6.96 (m, 28H), 4.70 (s, 2H), 3.71 (t, J = 6.2 Hz, 4H) ppm. 13C NMR
(101 MHz, CDCl3): δ 148.27, 137.77, 133.05, 128.32, 123.64, 120.52,
81.85, 77.48 and 53.95 ppm. 31P NMR (162 MHz, CDCl3):
δ −26.23 ppm. HRMS (ESI) m/z: calc for [C39H34N2P2 Na]+: 615.2089;
found: 615.2090.
presence of Na2CO3 (Table 1, entry 3). Furthermore, after screening var-
ious solvents (Table 1, entries 3, 6–9), DMA was found to be an optimum
solvent in this reaction system.
Subsequently, we devoted much effort to screen palladium species.
It was found that other palladium precursors such as PdCl2, Pd(dba)2
and Pd(COD)Cl2 also could give the relatively satisfying results except
Pd(OAc)2 (Table 2, entries 1, 3–5 and 7). However, when the molar
ratio of substrate to catalyst (S/C) was increased to 5,000, the obvious
difference of the catalytic results was shown with the different palladi-
um precursors (Table 2, entries 2, 6 and 8). Among them, [Pd(C3H5)Cl]2
gave the best result in 87% yield with a TON of 4,350 (Table 2, entries 1).
Thus, [Pd(C3H5)Cl]2 was chosen as the catalyst precursor in the following
experiments. Compared with other well-known simple ligands, such as
dppe, dppb, P-Phos and Bisbi, the bidentate phosphine ligand L, DADPP
was favourable for accelerating the reaction (Table 2, entries 10–14). A
low yield of 6% was obtained in the absence of ligand DADPP (Table 2,
entry 9). Based on these optimization studies (Tables 1 and 2), further re-
actions were performed at 130 °C under nitrogen using [Pd(C3H5)Cl]2/
DADPP, Na2CO3 in DMA.
2.2. General procedure for the Heck coupling
Na2CO3 (212 mg, 2 mmol), 4-chloronitrobenzene (1 mmol) and
styrene (1.5 mmol) were added successively into a dried Schlenk
tube under nitrogen. Then the DMA (0.1 mL) solution of DADPP
(0.002 mmol) and [Pd(C3H5)Cl]2 (0.0005 mmol), which was reacted at
100 °C for 10 min prior to use, was added into the mixture. The reaction
was performed at 130 °C. At the end of reaction, the mixture solution was
extracted with ethyl acetate (3 × 5 mL). Combined organic phase was
washed with brine (3 × 5 mL) and dried over MgSO4. The dried solution
was filtered and purified with silica gel chromatography (petroleum
ether 60–90 °C) to give a corresponding product.
With the optimal reaction conditions in hand, we explored the
scope of the halide substrates for Heck coupling. As expected, for
low-cost and less-active aryl chlorides, this catalytic system gave
low yields in the presence of 0.1 mol.% Pd. However, when the
Pd loading was increased to 0.2 mol.%, 2-chloronitrobenzene, 4-
chlorobenzonitrile and 2-chlorobenzonitrile could afford the correspond-
ing coupling products 2–4 in moderate yields of 71%, 52% and 48%, re-
spectively (Table 3, entries 2–4). However, for 4-chlorobenzaldehyde,
only a moderate yield of 60% was achieved even if increasing Pd loading
to 1 mol.% (Table 3, entry 5). The low reactivity was usually attributed
to the reluctance of the aryl-chloride bond to oxidative addition to
Pd(0) [1]. Under the optimized reaction conditions, good to excellent
3. Results and discussion
To evaluate the catalytic reactivity of [Pd(C3H5)Cl]2/DADPP system,
the coupling of 4-chloronitrobenzene with styrene was used as a
model reaction to explore the optimum conditions. According to the
well-established mechanism [21–23], bases are crucial for the regener-
ation of the Pd active species. The effect of NaOAc, NaHCO3, Na2CO3,
K3PO4 and NaOH on the reaction was investigated in DMA (Table 1).
Desired product was almost not observed when NaOAc or NaHCO3
was used as the base (Table 1, entries 1–2). K3PO4 obviously promoted
the reaction, but a low conversion of 36% was obtained (Table 1, entry
4). Gratifyingly, the highest conversion of 100% was obtained in the
Table 2
Effect of palladium precursors and ligands on the Heck coupling reactiona.
Table 1
Effect of bases and solvents on Heck reaction of 4-chloronitrobenzene with styrenea
Entry
Pd
Ligand
DADPP
S/C
Yield (%)
1
[Pd(C3H5)Cl]2
1,000
5,000
1,000
1,000
1,000
5,000
1,000
5,000
1,000
1,000
1,000
1,000
1,000
1,000
94b
87
78
24
93
53
82
21
6c
85
77
71
80
6
2
3
4
5
6
7
8
9
10
11
12
13
14
PdCl2
Pd(OAc)2
Pd(dba)2
DADPP
DADPP
DADPP
Entry
Base
Solvent
S/C
Yield (%)
Pd(COD)Cl2
DADPP
1
2
3
4
5
6
7
8
9
NaOAc
NaHCO3
Na2CO3
K3PO4
DMA
DMA
DMA
DMA
DMA
n-butanol
NMP
1,000
1,000
1,000
1,000
1,000
1,000
1,000
1,000
1,000
–
–
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
none
P-Phos
Bisbi
dppe
dppb
L
100
36
20
–
36c
NaOH
b
Na2CO3
Na2CO3
Na2CO3
Na2CO3
b
EtOH
DMF
–
45
aReaction condition: 4-chloronitrobenzene 1 mmol, styrene 1.5 mmol, Na2CO3 2.0 mmol,
DMA 3 mL, catalyst [Pd(C3H5)Cl]2/DADPP = 1/4, 130 °C, 20 h, GC yield, 2,2′,6,6′-
Tetramethoxy-4,4′-bis(diphenylphosphino)-3,3′-bipyridine (P-Phos), 2,2′-bis(diphenyl-
phosphinomethyl)-1,1′-biphenyl (Bisbi) and 1,4-bis(diphenylphosphino)-butane (dppb).
b2 h.
aReaction condition: 4-chloronitrobenzene 1 mmol, styrene 1.5 mmol, catalyst [Pd(C3H5)
Cl]2/DADPP = 1/4, [Pd] 0.1 mol.%, base 2.0 mmol, solvent 3 mL, 130 °C, 20 h and GC
yield.
b70 °C.
c110 °C.
cNo ligand.

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Z. Jiang et al. / Catalysis Communications 57 (2014) 14–18
Table 3
Heck coupling of aryl halides with styrene catalyzed by [Pd(C3H5)Cl]2/DADPPa
Entry
1
ArX
S/C
T (h)
2
Product
Yield (%)
94
1,000
1
2
500
24
2
71
3
4
5
500
500
100
24
24
24
3
4
5
52
48
60
6
7
8
10,000
100,000
24
48
6
7
3
95
81b
10,000
24
83
10,000
24
72
96
120
24
80 b
91 b
60 b
63 b
21
1,000,000
10,000,000
10,000,000
1,000
9
4
10
11
100,000
10,000
48
24
8
9
95
90
12
13
1,000
24
10
5
69
10,000
100,000
24
48
89
95b
14
15
10,000
24
11
12
88
10,000
24
85
16
17
10,000
10,000
24
24
13
14
78
61
18
19
10,000
10,000
24
48
15
16
91
96c
20
21
500
24
24
17
18
74
78
1,000
22
23
500
500
24
24
19
82
–
10b
24
500
24
20
78

Z. Jiang et al. / Catalysis Communications 57 (2014) 14–18
17
Table 3 (continued)
Entry
ArX
S/C
T (h)
24
Product
Yield (%)
25
5,000
21
95
26
27
2,000
2,000
24
24
22
23
87
91
aReaction condition: catalyst [Pd(C3H5)Cl]2/DADPP = 1/4, aryl bromides 1 mmol, styrene 1.5 mmol, Na2CO3 2 mmol, DMA 3 mL, 130 °C, under nitrogen and isolated yields.
bGC yield.
cStyrene 3.0 mmol.
yields of coupled products were obtained for a wide range of aryl bro-
mides with styrene (Table 3). As expected, aryl halides with electron-
withdrawing substituents in para positions reacted smoothly, and aryl
halides with electron-donating substituents were less reactive. For exam-
ple, even with 0.00001 mol.% palladium, 4-bromobenzonitrile could give
a yield of 60% after 96 h (Table 3, entry 8), which is much higher than the
best value reported in the literature (35,500) [24–27]. The electron-poor
4-bromobenzaldehyde was almost completely converted into the desired
product at a palladium loading of 0.001 mol.% for 48 h (Table 3, entry 13).
The results demonstrated that the catalyst did not deactivate during the
long period and showed a good stability. It is noteworthy that the cou-
pling took place on both sites of 1,4-dibromobenzene with styrene
(Table 3, entry 19). Using 2-bromobenzonitrile and 2-bromoanisole as
the substrates, low conversions (21% and 10%) were observed due to ste-
ric hindrance (Table 3, entries 9 and 23). For electronic factor or poison of
heteroatom to Pd active species, Heck coupling of heteroaryl halides gen-
erally proceeds slowly and requires high catalyst loadings [28]. However,
in our system, 2-bromothiophene and 3-bromofuran still gave the TONs
of 1,740 and 1,820, respectively (Table 3, entries 26–27). In addition,
a higher TON of 4,750 was obtained for 3-bromopyridine (Table 3,
entry 25).
4-bromobenzotrifluoride and 4-bromoacetophenone underwent the
Heck coupling with n-butyl acrylate to afford the desired products in
85% and 84%, respectively (Table 4, entries 3 and 4). The maximum
TON of 96,000,000 was achieved for 4-bromobenzaldehyde (Table 4,
entry 5), which can take an advantage over the TON value achieved by
Tedicyp in 72 h for the same substrate (210,000) [20].
4. Conclusions
In summary, we have developed a highly efficient Pd-catalyzed
Mizoroki–Heck coupling reaction of aryl halides using a new diphosphine
DADPP as ligand, which was easily synthesized from readily available ma-
terials. The protocol features wide substrate scope and high functionality
tolerance. A variety of aryl halides, even some heteroaryl halides, can
smoothly react with olefins to afford the corresponding products. Impor-
tantly, current catalytic system has a predominant activity for electron
deficient alkenes as long as the amount of [Pd(C3H5)Cl]2 is in the low
range of 0.005–0.0000 005 mol.%.
Acknowledgments
Inspiringly, the coupling of aryl bromides bearing electron-with-
drawing groups with activated terminal olefin n-butyl acrylate could
be performed at the very low catalyst loadings (Table 4). For example,
This project was supported by the National Natural Science Founda-
tion of China (grant no. 21202104).
Table 4
Heck coupling of aryl bromides with n-butyl acrylate catalyzed by [Pd(C3H5)Cl]2/DADPPa
Entry
1
ArX
S/C
T (h)
Product
Yield (%)
100,000
1,000,000
24
44
120
44
72
120
44
72
120
44
72
120
44
72
120
44
72
24
96
43b
25b
89
100,000,000
1,000,000
10,000,000
100,000,000
1,000,000
10,000,000
100,000,000
1,000,000
10,000,000
100,000,000
1,000,000
10,000,000
100,000,000
1,000,000
10,000,000
100,000,000
2
3
4
5
6
25
26
27
28
29
90b
82b
96
83b
85b
98
87b
84b
98
93b
96b
98
97b
78b
120
aReaction condition: catalyst [Pd(C3H5)Cl]2/DADPP = 1/4, butyl acrylate 1 mmol, styrene 1.5 mmol, Na2CO3 2 mmol, DMA 3 mL, 130 °C, under nitrogen and isolated yields.
bGC yield.

18
Z. Jiang et al. / Catalysis Communications 57 (2014) 14–18
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