[NiCl2(dppp)]-catalyzed cross-coupling of aryl halides with dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphine

Article abstract of DOI:10.1002/chem.201103723

We present a general approach to C-P bond formation through the cross-coupling of aryl halides with a dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphane by using [NiCl₂(dppp)] as catalyst (dppp=1,3-bis(diphenylphosphino)propane). This catalyst system displays a broad applicability that is capable of catalyzing the cross-coupling of aryl bromides, particularly a range of unreactive aryl chlorides, with various types of phosphorus substrates, such as a dialkyl phosphite, diphenylphosphine oxide, and diphenylphosphane. Consequently, the synthesis of valuable phosphonates, phosphine oxides, and phosphanes can be achieved with one catalyst system. Moreover, the reaction proceeds not only at a much lower temperature (100-120 °C) relative to the classic Arbuzov reaction (ca. 160-220 °C), but also without the need of external reductants and supporting ligands. In addition, owing to the relatively mild reaction conditions, a range of labile groups, such as ether, ester, ketone, and cyano groups, are tolerated. Finally, a brief mechanistic study revealed that by using [NiCl₂(dppp)] as a catalyst, the Ni^II center could be readily reduced in situ to Ni⁰ by the phosphorus substrates due to the influence of the dppp ligand, thereby facilitating the oxidative addition of aryl halides to a Ni⁰ center. This step is the key to bringing the reaction into the catalytic cycle. Making bonds: C-P bonds were formed by the Ni-catalyzed cross-coupling of aryl halides and phosphorus substrates without the need of external reductants. Aryl bromides and less reactive aryl chlorides underwent smooth coupling with several different phosphorus substrates to afford phosphonates, phosphine oxides, and phosphines (see scheme; dppp=1,3-bis(diphenylphosphino)propane). Due to the mild reaction conditions, a range of labile groups, such as ether, ester, ketone, and cyano groups, are tolerated. Copyright

Full text of DOI:10.1002/chem.201103723

DOI: 10.1002/chem.201103723
[NiCl2ACHTUNGTRENNUNG(dppp)]-Catalyzed Cross-Coupling of Aryl Halides with Dialkyl
Phosphite, Diphenylphosphine Oxide, and Diphenylphosphine**
Yu-Long Zhao,[a, b] Guo-Jie Wu,[b] You Li,[a] Lian-Xun Gao,[a] and Fu-She Han*[a, c]
Abstract: We present a general ap-
thesis of valuable phosphonates, phos-
phine oxides, and phosphanes can be
achieved with one catalyst system.
Moreover, the reaction proceeds not
only at a much lower temperature
(100–1208C) relative to the classic Ar-
buzov reaction (ca. 160–2208C), but
also without the need of external re-
ductants and supporting ligands. In ad-
dition, owing to the relatively mild re-
action conditions, a range of labile
groups, such as ether, ester, ketone,
and cyano groups, are tolerated. Final-
ly, a brief mechanistic study revealed
À
proach to C P bond formation through
the cross-coupling of aryl halides with
a dialkyl phosphite, diphenylphosphine
oxide, and diphenylphosphane by using
[NiCl
N
that by using [NiCl2ACTHNGUTERNNU(G dppp)] as a cata-
bis(diphenylphosphino)propane). This
catalyst system displays a broad applic-
ability that is capable of catalyzing the
cross-coupling of aryl bromides, partic-
ularly a range of unreactive aryl chlor-
ides, with various types of phosphorus
substrates, such as a dialkyl phosphite,
diphenylphosphine oxide, and diphe-
nylphosphane. Consequently, the syn-
lyst, the NiII center could be readily re-
duced in situ to Ni0 by the phosphorus
substrates due to the influence of the
dppp ligand, thereby facilitating the ox-
idative addition of aryl halides to a Ni0
center. This step is the key to bringing
the reaction into the catalytic cycle.
À
Keywords: aryl halides · C P bond
formation · homogeneous catalysis ·
nickel · phosphine oxide · phos-
phites
Introduction
boranes.[10] In addition, a few protocols based on Cu cata-
lysts have also been reported.[11] However, a general catalyst
system that is capable of catalyzing the cross-coupling of
various types of phosphorus substrate is absent. Moreover,
highly reactive aryl iodides or triflates combined with a long
reaction time and/or high temperature was essentially re-
quired in most cases. The coupling of readily available aryl
chlorides has been largely unexplored.
Despite the great advance in transition-metal-catalyzed
Csp2 X (X=C, N, O, S, and so forth) bond formation over
the past decades, relatively limited protocols for C P cou-
À
À
pling are available. This fact belies the importance of phos-
phorus compounds, such as phosphonates, phosphine oxides,
and phosphanes, in materials science,[1] biochemistry,[2] and
catalytic chemistry.[3] Since the pioneering work of Hirao
et al.,[4] the Pd-catalyzed cross-coupling reactions of aryl hal-
ides with various phosphorus compounds have been fre-
quently studied,[5] including H-phosphine oxides,[6] H-phos-
phites,[7] H-phosphanes,[8] silylphosphanes,[9] and phosphane–
À
As another premier method for Csp2 P bond formation,
the Ni-catalyzed reaction of aryl halides with trialkyl phos-
phites (P(OR)3), namely, the Tavs or Arbuzov reaction,[12] is
also promisingly attributed to the use of ligand-free NiX2
(X=Cl and Br) compounds as catalysts and under base-free
conditions.[13] However, this protocol has not been accepted
as a common method owing to the high reaction tempera-
ture, which generally ranges from 160–2208C. Moreover, the
reaction is often limited to trialkyl phosphites and other
phosphorus substrates, such as HP(O)(OR)2, HP(O)R2, and
[a] Dr. Y.-L. Zhao, Y. Li, Prof. Dr. L.-X. Gao, Prof. Dr. F.-S. Han
Changchun Institute of Applied Chemistry
Chinese Academy of Sciences
5625 Renmin Street, Changchun, Jilin 130022 (P.R. China)
Fax : (+86)431-8526-2936
HPR2, have been rarely considered.[14]
A mechanistic
study[12] revealed that the high thermal activation energy re-
quired in this reaction arises mainly from the reduction of
NiII to Ni0 (A1) and the oxidative addition of aryl halides to
A1 to form the NiII species (A2; Scheme 1).
E-mail: fshan@ciac.jl.cn
[b] Dr. Y.-L. Zhao, G.-J. Wu
Department of Chemistry
Northeast Normal University
Changchun, Jilin 130024 (P.R. China)
To overcome these problems, very recently, Zhao and co-
workers[15] disclosed a useful method for the coupling of
ArX (X=I, Br) and diphenylphosphine oxide in aqueous
media at 708C. This method represents a great advance in
[c] Prof. Dr. F.-S. Han
State Key Laboratory of Fine Chemicals
Dalian University of Technology
Dalian 116024 (P.R. China)
À
Ni-catalyzed C P bond formation. However, a combination
of 2.0 equivalents of Zn powder as external reductant and
[**] dppp=1,3-bis(diphenylphosphino)propane.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103723
9622
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Chem. Eur. J. 2012, 18, 9622 – 9627

FULL PAPER
a potential catalyst, thus affording the desired product 3a in
75% yield at a considerably lower temperature of 1008C
(Table 1, entry 5). In addition, a base is also indispensable in
this transformation because it may act to deprotonate the
H-phosphonate diester.[19] K3PO4 was optimal, as seen from
the results (Table 1, entries 5 and 8–14). A brief examination
of solvents suggested that dioxane was a better option
(Table 1, entries 5 versus 15–18).
With the optimized catalyst, base, and solvent, we further
inspected the effect of external ligands, such as bpy, dppf,
PCy3, and 2-(di-tert-butylphosphino)biphenyl on the trans-
formation. Unfortunately, a markedly lowered yield of 3a
was observed in the presence of various external ligands
(Table 1, entries 19–22). These results further demonstrated
À
Scheme 1. Reaction mechanism of a Ni-catalyzed C P bond-formation
reaction between aryl halides and trialkyl phosphites.
20 mol% of 2,2’-bipyridine (bpy) as an external
ligand were required for effective cross-coupling.
On the basis of our well-established experiences
[16]
À
in Ni-catalyzed C C cross-coupling and a careful
Table 1. Optimization of the reaction conditions.[a]
analysis of the Tavs reaction mechanism,[12] we have
become interested in developing an active Ni cata-
À
lyst system for a general and mild C P bond forma-
tion under conditions that are external-reductant
and ligand free. Such a procedure would be more
appealing in terms of the philosophy of efficient
synthesis referred to as atom economic and
Run Catalyst
Catalyst Equivalents Base
Solvent
Yield
[%][b]
loading
AHCTUNGTRENGN[UN mol%]
of 2
ACHTUNGTRNE(NUNG equiv)
green.[17] Herein, we disclose that the [NiCl
2ACTHNUTRGNE(NUG dppp)]
À
complex is a highly active catalyst that allows C P
coupling to proceed smoothly without the need of
external reductants and external supporting ligands
at a significantly lower temperature relative to the
conventional Arbuzov reaction. Most significantly,
the catalyst exhibits a broad applicability not only
to aryl halides but also to various types of phospho-
rus substrate, such as HP(O)(OR)2, HP(O)R2, and
HPR2.
1
2
3
4
5
6
7
8
NiCl2
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
[NiCl
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
10
10
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.0
2.0
2.0
1.5
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
–
K2CO3 (1.5)
Na2CO3 (1.5) dioxane trace
Cs2CO3 (1.5)
NaOAc (1.5)
tBuOK (1.5)
dioxane n.r.[c]
dioxane n.r.
dioxane n.r.
dioxane 43
G
2A
2A(PCy3)2]
2A(dppe)]
2A(dppp)]
2A(AsPh3)2]
2A(dppf)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
2A(dppp)]
R
CHTUNGTRENNUNG
E
CHTUNGTRENNUNG
R
N
dioxane 75
R
N
dioxane n.r.[d]
dioxane trace[d]
dioxane n.r.[e]
dioxane 30
G
CHTUNGTRENNUNG
T
CHTUNGTRENNUNG
9
N
R
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
G
N
U
R
dioxane 11
dioxane trace
E
N
R
N
dioxane
9
R
N
DIPEA (1.5) dioxane trace
Results and Discussion
N
E
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (1.5)
K3PO4 (2.0)
K3PO4 (1.5)
K3PO4 (2.0)
K3PO4 (2.0)
K3PO4 (1.5)
toluene
DMF
THF
20
N
E
n.r
To develop a Ni-based catalyst that is not only uni-
versally applicable but also highly active, we de-
signed a ligand-based strategy. Because numerous
reports have demonstrated that the redox property
of a transition-metal ion is affected profoundly by
the nature of the ligated ligands,[18] we assumed that
the reduction of NiII to Ni0 should also occur easily
if a NiII complex coordinates with an appropriate
ligand, thereby making the oxidative addition of an
aryl halide to a Ni0 center proceed under mild con-
ditions. Consequently, the thermal activation energy
of the whole catalytic cycle would be lowered.
With this assumption in mind, an extensive
survey of the reaction conditions was carried out
(Table 1). Initially, the catalytic efficiency of free
[NiCl2 and various nickel complexes was evaluated
(Table 1, entries 1–7). The results showed that
R
G
trace[f]
N
R
CH3CN trace[f]
dioxane 16[g]
dioxane 57[h]
dioxane 39[i]
dioxane 42[j]
dioxane 76
dioxane 76
dioxane 79
dioxane 91
dioxane 88
N
CHTUNGTRENNUNG
R
CHTUNGTRENNUNG
E
CHTUNGTRENNUNG
N
CHTUNGTRENNUNG
R
CHTUNGTRENNUNG
E
CHTUNGTRENNUNG
G
CHTUNGTRENNUNG
N
CHTUNGTRENNUNG
A
CHTUNGTRENNUNG
[a] Reaction conditions: 1-bromonaphthalene (1a; 1.0 mmol), dimethyl phosphite (2),
[NiCl2A(dppp)], K3PO4, solvent (4 mL), 1008C, 6–12 h. [b] Yield of the isolated product.
CTHUNGTRENNUNG
[c] No reaction (n.r.). [d] The catalyst was pre-prepared in situ by stirring NiCl2 and
AsPh3 or dppf for 3 h in dioxane at 1008C and the other reagents were charged.
[e] No base was used. [f] Stirred at 808C. [g] 2,2’-Bipyridine (5 mol%) was used as an
external ligand. [h] Dppf (5 mol%) was used as an external ligand. [i] PCy3 (10 mol%)
was used as an external ligand. [j] 2-(Di-tert-butylphosphino)biphenyl (10 mol%) was
used as an external ligand. DIPEA=diisopropylethylamine, dppe=1,2-bis(diphenyl-
phosphino)ethane, dppf=1,1’-bis(diphenylphosphino)ferrocene, PCy3 =tricyclohexyl-
among several nickel complexes [NiCl2ACTHNUTRGNEUNG(dppp)] is phosphine.
Chem. Eur. J. 2012, 18, 9622 – 9627
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9623

F.-S. Han et al.
our assumption that ligands play a crucial rule in the cou-
pling. Finally, the loading amount of [NiCl2A(dppp)] and the
amount of K3PO4 and dimethyl phosphite were optimized
(Table 1, entries 23–27). Extensive surveys of various reac-
tion parameters led to the following optimized conditions:
hindered and electronically enriched phenyl substrates sup-
press the reaction. Based on the reaction mechanism,[12]
these factors may decrease the rate of oxidative addition of
aryl halides to the Ni0 center and/or the reductive elimina-
tion.
CTHUNGTRENNUNG
dimethyl phosphite (2.0 equiv), [NiCl
(dppp)] catalyst
Some more results of interest: the reaction is tolerant of
a range of aryl chlorides with structural features that are
similar to aryl bromides, including delocalized naphthyl
(3a,b), less-delocalized phenyl (3e,g), and heteroaromatic
(3l) chlorides, although a somewhat elevated temperature is
required (1208C). These results are of particular interest be-
cause aryl chlorides are widely available and much cheaper
than aryl bromides and iodides. However, a general proce-
dure for the coupling of this class of substrate has been
(10 mol%), and K3PO4 (2.0 equiv) in dioxane at 1008C.
Under these conditions, aryl phosphonate 3a could be ob-
tained in 91% yield (Table 1, entry 26).
Having established the optimized conditions, we exam-
ined the generality of the methodology by varying the struc-
tures of the aryl halides. Unsubstituted naphthyl bromides
reacted smoothly with phosphite 2 to afford the coupled
products 3a and 3b in excellent yields (Table 2). In addition,
À
largely unexplored in transition-metal-catalyzed C
P bond formation owing to the notoriously unreac-
tive nature of these compounds.[20] It is also worth
noting that due to the significantly lowered reaction
temperature, a range of functional groups on the
aryl-ring periphery, such as ether, ester, ketone, and
cyano groups, is tolerated.
Table 2. Cross-coupling of dimethyl phosphite with various aryl halides.[a]
Having examined the scope and limitations of the
methodology for the cross-coupling of aryl halides
with phosphite compounds, we shifted our attention
to the coupling reactions with phosphine oxides as
the phosphorus source. Accordingly, the reaction of
1-bromonaphthalene
1
and diphenylphosphine
oxide (4) was investigated (Table 3). The results
showed that 1 could be coupled far more efficiently
with diphenylphosphine oxide than with dimethyl
phosphite (2). Complete conversion and an excel-
lent yield of 5a were obtained under the otherwise
identical conditions used to couple phosphite 2,
except that the catalyst loading and molar ratio of
phosphine oxide 4 were decreased to 5 mol% and
1.5 equivalents, respectively. Furthermore, these
conditions also exhibit a broad compatibility with
a rich range of aryl bromides and unreactive chlo-
ride derivatives, including delocalized naphthyl sub-
strates (5a–d), less-delocalized phenyl compounds
(5e–i), and heteroarenes (5k–o), except that a deac-
tivated substrate (5j) is less reactive. More to the
point, relative to the outcome with dimethyl phos-
[a] Reaction conditions: aryl halide (0.5 mmol), dimethyl phosphite (2; 1.0 mmol),
[NiCl2ACHTUNGTRENNUNG(dppp)] (10 mol%), K3PO4 (1.0 mmol, 2.0 equiv), dioxane (2 mL), 1008C, 6-
24 h; the yield of the isolated product is given. [b] Reaction was carried out at 1208C.
[c] The yield was determined by 1H NMR spectroscopic analysis due to the contamina-
tion of a small amount of inseparable deacetylated product.
naphthyl analogues modified either by a strong electron-rich
OMe group or an electron-deficient ester group also under-
went smooth coupling to afford 3c and 3d, respectively.
Moreover, a range of the nonfused aromatics (i.e., less elec-
tron-deficient systems) are also viable substrates. For in-
stance, bromobenzene substituted with electron-withdrawing
acetyl and cyano groups at the para- and meta-positions
were coupled with dimethyl phosphite in high yields to give
3e and 3 f. Equally interestingly, heteroaromatic bromides
are also compatible with the reaction conditions, as exempli-
fied by the coupling of 3-bromoquinoline (3j) and N-acetyl
indole (3k). It should be noted that although good coupling
efficiencies were generally observed for an array of aryl bro-
mides, the poor yields for 3h and 3i suggest that sterically
phite (3h, Table 2), the sterically hindered ortho-cyano-sub-
stituted aryl bromide can be coupled smoothly with diphe-
nylphosphine oxide to give 5i in 94% yield. Finally, the re-
action is also tolerant of various functional groups.
Next, we investigated the reaction of aryl halides with sec-
ondary phosphine 6. A wide array of aryl bromides includ-
ing naphthyl (Table 4, entries 1–8), phenyl (Table 4, en-
tries 9–12), heteroaromatic (Table 4, entries 13–16), and
a compound with a sterically encumbered structural motifs
(entry 12, Table 4) underwent smooth coupling with diphe-
nylphosphine 6 (1.2 equiv) in the presence of 5 mol%
[NiCl2ACHTNUTRGNE(NUG dppp)]. Although high-to-excellent overall yields
were observed for various aryl halides, the coupling reaction
formed a mixture of phosphine oxides 5 and phosphines 7.
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À
Ni-Catalyzed C P Bond Formation
FULL PAPER
Table 3. Cross-coupling of various aryl halides with diphenylphosphine oxide.[a]
oxygen involved in the reaction system, although all
the reagents and solvent were degassed prior to
use. Namely, the oxidation of phosphine 6 by the
trace amount of oxygen generates the correspond-
ing secondary phosphine oxide 4, and the product 4
is coupled with aryl halides to produce the triaryl-
phosphine oxide 5.
To demonstrate the utility of this result, the
direct synthesis of triarylphosphine oxide 5b from
phosphine 6 was explored. After examining differ-
ent procedures, phosphine oxide 5b could be ob-
tained in 87% yield as a single product when the
reaction was carried out by a prior oxidation of
phosphine 6 in an oxygen atmosphere at room tem-
perature, followed by recharging of 2-bromonaph-
thalene and [NiCl2ACTHNUGRTENUNG(dppp)] to the reaction vessel in
situ and heating the reaction mixture at 1008C
(Table 4, entry 6). The yield is comparable to the
coupling of 2-bromonaphthalene and H-diphenyl-
phosphine oxide (4; 95% yield; 5b in Table 3).
On the other hand, to suppress the formation of
phosphine oxides, we investigated the coupling of
the H-phosphine–borane complex [(HPPh2)BH3] in-
stead of HPPh2. Unfortunately, the phosphine–
borane complex displayed a markedly lower reac-
tivity, with only small amount of coupled products
of triarylphosphine and triarylphosphine oxide ob-
served under the reaction conditions. Control ex-
periments revealed that by heating at 1008C,
HPPh2BH3 decomposes slowly to Ph2PH, which was
oxidized partially to Ph2P(O)H. Consequently,
[a] Reaction conditions: aryl halide (0.5 mmol), diphenylphosphine oxide (4;
0.75 mmol), [NiCl2ACHTUNGTRENNUNG(dppp)] (5 mol%), K3PO4 (1.0 mmol, 2.0 equiv), dioxane (4 mL),
1008C, 12–24 h; the yield of the isolated product is given. [b] The reaction was carried
out at 1208C.
Despite this drawback, the method still has some interesting
points because both phosphines 7 and phosphine oxides 5
are valuable compounds. Furthermore, they can be trans-
formed with respect to each other by means of oxidation or
reduction reactions. In addition, phosphines and phosphine
oxides can be easily separated by column chromatography.
More importantly, the observation of phosphine oxide 5
has further implications. It may provide an alternative path-
way for the synthesis of phosphine oxides from H-phos-
phines. To this end, we inspected the reasons for the forma-
tion of phosphine oxides 5. Several control experiments
were carried out, the results showed that external addition
of 1 or 2% H2O (v/v) to the reaction mixture of 2-bromo-
naphthalene and 6 resulted in a negligible change in the
ratio of 7b/5b (Table 4, entry 2 versus entries 3 and 4).
These observations ruled out the influence of a trace
amount of water on the reaction. In addition, 5b was not
observed by stirring a solution of triarylphosphine 7b in an
oxygen atmosphere overnight, thus suggesting that 5b was
not formed from the oxidation of 7b. However, when the re-
action was carried out in an oxygen atmosphere diluted with
nitrogen, phosphine oxide 5b was obtained as the major
product, although the total yield was somewhat diminished
(Table 4, entry 5). Thus, a summary of the results on the
control experiments suggested that the formation of phos-
phine oxides 5 is due most possibly to the trace amount of
Ph2PH and Ph2P(O)H were coupled with aryl halides to
form triarylphosphines and triarylphosphine oxides, respec-
tively, in the reaction mixture.
À
Finally, to confirm whether the general and mild C P
cross-coupling is really promoted by the ligand-based strat-
egy (see above), three control experiments were carried out.
When a mixture of 1-bromonaphthalene, K3PO4, and [NiCl2-
AHCTUNGTRENNUNG
CTHUNGTRENNUNG
cles remained insoluble. In contrast, when the aryl halide
was replaced by dimethyl phosphite or diphenylphosphine
oxide, a slight- or deep-yellow homogeneous solution, re-
spectively, was formed rapidly within several minutes. These
observations are in good agreement with the previous exper-
imental description,[12] thus indicating that a Ni0 complex
was formed in the system. The results were further con-
firmed by X-ray photoelectron spectroscopic (XPS) analysis;
namely, the nickel 2p3/2 binding energies for the two nickel
species treated by dimethyl phosphite 2 and diphenylphos-
phine oxide 4 were 852.4 and 853.1 eV, respectively, which
are almost the same as that for Ni0 powder (i.e., 852.8 eV)
and some other Ni0 complexes.[21] In contrast, the nickel 2p3/
2
binding energy for the divalent [NiCl2ACTHNUTRGNEUNG(dppp)] complex was
855.1 eV. Thus, the combination of the control experiments
and XPS analysis clearly demonstrated that by appropriate
design of the ligands the reduction of the metal center from
Chem. Eur. J. 2012, 18, 9622 – 9627
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9625

F.-S. Han et al.
Table 4. Cross-coupling of various aryl halides with diphenylphosphine.[a]
NiII to Ni0 by various phospho-
rus substrates in situ and the
0
À
subsequent Ni -catalyzed C P
bond formation proceeded at
a significantly lower tempera-
ture without the need of exter-
nal reductants and supporting
ligands. Finally, it should be
mentioned that although the
important role of the dppp
ligand in affecting the general
Entry
Product 7
Yield
of 7
Product 5
Yield
of 5
Yield
of 5+7
[%]
[%][b]
[%][b]
1
70
24
94
2
3
4
5
6
58
54
58
8
39
41
39
56
87
97[c]
95[d]
97[e]
64[f]
87[g]
À
and relatively mild C P cou-
pling reaction has been demon-
strated, phosphites, phosphine
oxides, and phosphines may
also serve as coligands to pro-
mote this transformation be-
cause these phosphorus com-
pounds were effective ligands
in the Suzuki–Miyaura cross-
0
7
42
51
93
coupling,[22] C P bond addi-
8
49
25
30
47
72
47
63
47
46
8
96
88
77
93
80
À
tion,[23] and other reactions.[24]
9
Conclusion
By utilizing
strategy, we have achieved
Ni0-catalyzed cross-coupling
a
ligand-based
10
11
12
a
of aryl halides with various
phosphorus substrates under
relatively mild reaction condi-
tions in the absence of external
reductants and supporting li-
gands. As one of its notable
features, this method allows
aryl bromides and, particularly,
less-reactive aryl chlorides to
be coupled efficiently. In addi-
13
51
48
99
tion,
a range of functional
groups, such as ether, ester,
ketone, and cyano groups, are
also tolerated, which is attribut-
ed to the mild conditions.
Moreover, the method exhibits
good compatibility with various
types of phosphorus substrate,
such as a H-phosphite, H-phos-
phine oxide, and H-phosphine.
To the best of our knowledge,
a catalyst system that not only
14
15
68
42
12
48
80
90
16
31
54
85
À
enables C P bond formation
[a] Reaction conditions: aryl halide (0.5 mmol), diphenylphosphine 6 (0.6 mmol), [NiCl2ACTHNUTRGNE(NUG dppp)] (5 mol%),
under mild conditions but also
exhibits such a broad applica-
bility both to aryl halides and
phosphorus sources that has
been rarely disclosed. Finally,
K3PO4 (1.0 mmol, 2.0 equiv), dioxane (2 mL), 1008C, 10–18 h. [b] Yield of the isolated product. [c] Average
yield of three trials in anhydrous dioxane. [d] Average yield of two trials by adding 1% H2O (v/v). [e] Average
yield of three trials by adding 2% H2O (v/v). [f] Average yields of two runs. The reaction was carried out in an
oxygen atmosphere diluted with nitrogen (O2/N2 =1:4 (v/v)). [g] Phosphine 6 was stirred in an oxygen atmos-
phere diluted with nitrogen (O2/N2 =1:2 (v/v)) for 3 h at room temperature. The aryl halide and [NiCl
were then added to the reaction mixture, which was stirred at 1008C.
2ACHTUNGTRNE(NUNG dppp)]
9626
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Chem. Eur. J. 2012, 18, 9622 – 9627

À
Ni-Catalyzed C P Bond Formation
FULL PAPER
14, 7108; c) S. Greenberg, D. W. Stephan, Chem. Soc. Rev. 2008, 37,
1482.
the [NiCl2ACHTUNGTRENNUNG(dppp)] catalyst is cheap, readily available, and
markedly air and moisture stable, thus facilitating operation
on the benchtop. Owing to these advantages, we believe the
method presented herein should find a broad application in
[6] M. Toffano, C. Dobrota, J.-C. Fiaud, Eur. J. Org. Chem. 2006, 650.
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15122, and references therein.
À
C P bond formation.
Experimental Section
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71, 5020.
General methods: All the reactions were carried out under N2. The diox-
ane solvent was dried over molecular sieves (4 ꢁ) or distilled according
to the standard method. Anhydrous NiCl2 and the ligands were pur-
chased from J&K Chemical Ltd and Alfa Aesar, respectively. Unless oth-
1
erwise noted, the H and 13C NMR spectra were recorded at 400 (or 600)
and 100 (or 150) MHz, respectively, in CDCl3 with trimethylsilane (TMS)
as an internal standard. All the chemical shifts were given in ppm. All
coupling constants J are reported in Hertz (Hz).
General procedure for Ni-catalyzed cross-coupling reactions of aryl hal-
ides with phosphorus substrates (with the coupling of aryl halides with di-
[12] T. M. Balthazor, R. C. Grabiak, J. Org. Chem. 1980, 45, 5425, and
references therein.
methyl phosphite as
a representative): An aryl halide (0.5 mmol,
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Lohier, P.-J. Madec, J. S. O. Santos, Eur. J. Inorg. Chem. 2008, 138;
b) T. E. Clark, A. Martin, M. Makha, A. N. Sobolev, D. Su, H. W.
Rohrs, M. L. Gross, C. L. Raston, Cryst. Growth Des. 2010, 10, 3211.
[14] A few examples concerning the Ni-catalyzed coupling of a secondary
phosphine with aryl triflates, especially binaphthyl-based triflates,
have been used for the synthesis of phosphines, see: a) A. C. Max-
well, S. P. Flanagan, R. Goddard, P. J. Guiry, Tetrahedron: Asymme-
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J. Org. Chem. 2010, 5996.
1.0 equiv), [NiCl2A(dppp)] (10 mol%), and anhydrous K3PO4 (1.0 mmol,
CHTUNGTRENNUNG
2.0 equiv) were added to a 25 mL Schlenk tube equipped with a magnetic
bar. The tube was evacuated (3ꢂ10 min) under vacuum and backfilled
with N2. Dimethyl phosphite and dried dioxane (2.0 mL) were injected
through a syringe, and the reaction mixture was stirred at 1008C (1208C
for aryl chlorides) until the aryl halide had disappeared, as monitored by
TLC analysis. The reaction mixture was poured into water (30 mL) and
extracted with CH2Cl2 (3ꢂ20 mL). The combined organic layers were
dried over anhydrous Na2SO4, filtered, and concentrated to dryness. The
crude material was purified by flash chromatography on silica gel with
hexane/acetone (or hexane/ethyl acetate) as the eluent to obtain the de-
sired cross-coupled products. See the Supporting Information for detailed
[15] X. Zhang, H. Liu, X. Hu, G. Tang, J. Zhu, Y. Zhao, Org. Lett. 2011,
13, 3478.
1
experimental procedures, characterization data, and the H and 13C NMR
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[17] a) B. M. Trost, Science 1991, 254, 1471; b) B. M. Trost, Science 1983,
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Am. Chem. Soc. 2008, 130, 2073, and references therein; b) J. Min,
Q. Zhang, W. Sun, Y. Cheng, L. Wang, Dalton Trans. 2011, 40, 686;
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Lee, P.-T. Chou, W.-Y. Hung, H.-C. Chiu, Dalton Trans. 2011, 40,
1132.
spectra of the coupled products.
Acknowledgements
Financial support from the “Hundred Talent Program”, Academy-Locali-
ty Cooperation Program of CAS, and State Key Laboratory of Fine
Chemicals (KF1008) is acknowledged.
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À
[20] The approximate bond-association energies of Ph X are 96, 81, and
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Received: November 26, 2011
Revised: March 21, 2012
Published online: July 2, 2012
À
Chem. Soc. Rev. 2004, 33, 218; b) D. S. Glueck, Chem. Eur. J. 2008,
Chem. Eur. J. 2012, 18, 9622 – 9627
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9627