Triarylphosphines as Aryl Donors for Pd(II)-Catalyzed Aromatic Coupling of Oxabenzonorbornadienes

Article abstract of DOI:10.1021/acs.orglett.5b02366

A new approach was developed for Pd(II)-catalyzed aromatic coupling of oxabenzonorbornadienes with triarylphosphines as both ligands and aryl donors. Diverse functional groups including halo- (F-, Cl-, and Br-), CF₃-, and furyl groups are well tolerated. For unsymmetrical triarylphosphines, the migration ability of aryls is consistent with the electronic property of substituents and maintains the order EDG-Ar > H-Ar > EWD-Ar (EDG means electron-donating group, EWG means electron-withdrawing group). A preliminary mechanistic study was also disclosed.

Full text of DOI:10.1021/acs.orglett.5b02366

Letter
pubs.acs.org/OrgLett
Triarylphosphines as Aryl Donors for Pd(II)-Catalyzed Aromatic
Coupling of Oxabenzonorbornadienes
Hui Zhou,†,§ Jixing Li,†,§ Huameng Yang,† Chungu Xia,*,† and Gaoxi Jiang*,†,‡
†State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical
Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, P. R. China
‡Division of Advanced Nanomaterials, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou
215123, P. R. China
§University of Chinese Academy of Sciences, Beijing 100049, P. R. China
S
* Supporting Information
ABSTRACT: A new approach was developed for Pd(II)-catalyzed
aromatic coupling of oxabenzonorbornadienes with triaryl-
phosphines as both ligands and aryl donors. Diverse functional
groups including halo- (F−, Cl−, and Br−), CF3-, and furyl groups
are well tolerated. For unsymmetrical triarylphosphines, the
migration ability of aryls is consistent with the electronic property
of substituents and maintains the order EDG−Ar > H−Ar >
EWD−Ar (EDG means electron-donating group, EWG means
electron-withdrawing group). A preliminary mechanistic study was also disclosed.
ransition-metal catalyzed coupling reactions have emerged
provoked the C−P bond cleavage (Scheme 1, eq 1).7 Since
then, considerable effort has been directed toward the
T
as the most reliable and powerful strategy for carbon−
carbon bond formation.1 Among these great achievements,
coupling reactions, namely Heck, Negishi, and Suzuki reactions,
were highlighted by the Nobel Prize in chemistry in 2010.2
Conventionally, the current coupling aryl partners are usually
limited in halides, organoboron, organosilane, and traditional
organometallic (Li−, Mg−, Sn−, and Zn−) reagents (Figure 1,
Scheme 1. Ar3P as Ar Donor in Pd-Catalysis
challenging topic. Nevertheless, besides several reports in
stoichiometric reactions with transition-metal compounds,8
only a few catalytic processes were achieved, wherein
triarylphosphines normally function as the diarylphosphinating
agents.9 A breakthrough in direct activation of a stable C−P
bond was made by Oshima and co-workers in 2003.10 They
realized a Pd(OAc)2-catalyzed oxidative Heck-type coupling
reaction between olefins and arylphosphonic acids, in which the
use of an overstoichiometric amount of tetrabutylammonium
fluoride (TBAF) was crucial for the fission of a carbon−
phosphorus bond. To the best of our knowledge, the success in
using simple triarylphosphines as aryl donors for a catalytic
cross-coupling reaction is unprecedented. Herein, we report the
first example of a Pd(II)-catalyzed aromatic coupling of
oxabenzonorbornadienes with triarylphosphines in the absence
of any additional activators under neutral reaction conditions
Figure 1. Typical aryl donors for coupling reaction.
left). Despite these important advances, excavation of new
surrogates to strengthen the extensive variations of coupling
reactions is still in strong demand. Tertiary phosphines,
containing three thermodynamically highly stable C−P bonds,
are currently widely utilized in organic synthesis as reagents,3
organocatalysts,4 and supporting ligands in transition-metal
catalysis,5 but further exploitation of tertiary phosphine itself in
the direct activation of the C−P bond remains unexplored yet
of great interest and significance that may be due to its intrinsic
characteristics: (i) possesses high C−P bond energy of around
513 kJ/mol,6 (ii) exhibits strong interaction to metal catalysts,
and (iii) is easily oxidized to Ar3PO (Figure 1, right). The
first report for arylation of olefins with triarylphosphines as aryl
doners was given by Kikukawa and co-workers in 1972, wherein
the use of stoichiometric amounts of Pd(OAc)2 in acetic acid
Received: August 17, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02366
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(Scheme 1, eq 2). Obviously, the process provided a catalytic
method for the activation of a stable C−P bond and opened a
new window for the application of phosphines.
different substitution patterns were employed to react with 1a
under the standard reaction conditions. As demonstrated in
Table 2, several interesting functional groups, including
Initially, we treated oxabenzonorbornadiene 1a11 with
triphenylphosphine (PPh3, 1.2 equiv) 2a in the presence of
10 mol % of Pd(OAc)2 under oxygen (1 atm) in p-xylene at
120 °C for 12 h (Table 1, entry 1). To our delight, about 5% of
a
Table 2. Substrate Scope of Tri(homo)arylphosphines
a
Table 1. Optimizaiton of Reaction Conditions
b
entry
Ar
3
yield (%)
1
4-CH3OC6H4
4-CH3C6H4
4-FC6H4
3ab
3ac
3ad
3ae
3af
84
82
70
64
48
73
80
81
13
30
2
3
b
entry
[Pd] (mol %)
oxidant
solvent
yield (%)
5
4
4-ClC6H4
c
5
4-CF3C6H4
3-CH3OC6H4
3-CH3C6H4
3-ClC6H4
1
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
PdCl2 (10)
O2
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
toluene
dioxane
THF
d
6
3ag
3ah
3ai
2
Ag2CO3
n.d.
d
7
3
K2S2O8
n.d.
d
8
4
TBHP
n.d.
9
2-CH3OC6H4
2-furyl
3aj
5
DDQ
13
10
3ak
6
BQ
40
a
7
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
72
Reaction conditions: 1a (0.2 mmol), PAr3 (1.2 equiv), Pd(OTf)2 (2.0
8
70
mol %), Cu(OAc)2 (1.2 equiv), p-xylene (1.5 mL), 120 °C, 12 h.
b
9
70
Yields of isolated products after column chromatography are given.
10
11
12
13
14
15
16
66
electron-donating and -withdrawing substituents, were well
tolerated, while the steric properties played a dramatic role in
the reactivity. Using 4-position substituted triarylphosphines
2b−f containing the CH3O-, CH3-, F-, Cl-, and even CF3-
group, the transformations afforded 3ab−af in 84−48% yields
smoothly (entries 1−5). Gratifyingly, 2g−i bearing the CH3O-,
CH3-, and Cl-group at the 3-position are well suitable for the
aromatic coupling process and readily furnished the corre-
sponding products 3ag−ai in 73−81% yield (entries 6−8). In
contrast to 2b and 2g, 2j bearing a CH3O group at the 2-
position seems less reactive which may be due to the increased
steric hindrance (entry 9).12 Significantly, the relatively unstable
trifurylphosphine 2k is also compatible with this trans-
formation, and the reaction enabled the formation of 3ak in
30% yield predominantly (entry 10).
CH3CN
DMF
69
63
CH2Cl2
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
p-xylene
65
77
Pd(OTf)2 (10)
Pd(OTf)2 (2.0)
Pd(OTf)2 (2.0)
Pd(OTf)2 (2.0)
Pd(OTf)2 (2.0)
Pd(OTf)2 (2.0)
Pd(OTf)2 (2.0)
80
78
e
17
85(80)
75
e
e
e
e
,
,
,
,
f
18
19
20
21
g
h
i
77
80
82
a
Reaction conditions: 1a (0.2 mmol), PPh3 (1.2 equiv), oxidant (1.0
equiv), [Pd] (10−2.0 mol %), solvent (1.5 mL), 120 °C, 12 h.
b
c
d
Determined by GC-Mass using a standard. O2 (1 atm). n.d. means
e
not detected. Cu(OAc)2 (1.2 equiv); isolated yield is given in
parentheses. PPh3 (1.5 equiv). PPh3 (1.0 equiv). Reaction was
performed at 100 °C. Reaction was performed at 140 °C.
f
g
h
Remarkably, we were pleased to find that different kinds of
tri(hetero)arylphosphines are also quite applicable to the
transformation. As shown in Scheme 2, triarylphosphines 2l
and 2m underwent the reaction to smoothly afford the mixtures
of 3aa/3ah and 3aa/3ad in good yields (eqs 3 and 4). The
i
desired product 2-phenylnaphthalene 3aa was detected by GC-
MS. Encouraged by the rudimentary result, further optimization
to improve the chemical yield was conducted. Examination of
oxidants reveals that Cu(OAc)2 is the best choice and provided
3aa in 72% yield predominantly with the simultaneous
formation of diphenylphosphinic acid after workup (entries
2−7). Changing the solvent gave comparable or worse yields
than p-xylene (entries 8−13). Further screening of Pd(II)-
catalysts revealed that PdCl2 and Pd(OTf)2 significantly
improved the reaction, giving 3aa in 77% and 80% yield,
respectively (entries 14 and 15). Remarkably, even lowering the
loading of Pd(OTf)2 to 2.0 mol % also facilitated the adduct in
78% yield (entry 16). Increasing the amount of Cu(OAc)2 to
1.2 equiv gave the best result, producing 3aa in 80% isolated
yield (entry 17). Control experiments that included changing
the loading of PPh3 (entries 18 and 19) and the reaction
temperature (entries 20 and 21) proved to be less effective.
With the optimized conditions in hand, we next investigated
the substrate scope with respect to both phosphines and
oxabenzonorbornadienes to evaluate the generality of the
reaction. First, a series of tri(homo)arylphosphines with
Scheme 2. Tri(hetero)arylphosphines as Substrates
B
DOI: 10.1021/acs.orglett.5b02366
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Letter
ratios of 3aa/3ah and 3aa/3ad indicate that electron-rich aryl
groups migrated preferentially, which suggests that the
migrating aryl group in the reaction has nucleophilic character.
It is noteworthy that 3aa was monitored exclusively and
isolated in 71% yield with cyclohexyldiphenylphosphine 2n as
the starting material (eq 5).
Scheme 3. Control Experiments
Next the scope of oxabenzonorbornadienes for the new
catalytic system was investigated (Table 3). It is found that
a
Table 3. Substrate Scope of Oxabenzonorbornadienes
cleavage was not observed and the oxide was recovered in
>95% yield, while 3aa was isolated in 15% yield with 20 mol %
of Pd(PPh3)4 as the catalyst, indicating the phenyl transferred
from the PPh3 ligand (eq 7). When 1,4-methanonaphthalene
was used instead of 1a, no reaction occurred (eq 8).
Although the mechanism of this catalytic transformation is
not completely clear yet, on the basis of previous reports7,14
and the above-mentioned observations, a possible mechanism is
proposed in Scheme 4. The reaction of the Pd(II) salt with
Scheme 4. Plausible Mechanism
a
Reaction conditions: 1b−i (0.2 mmol), 2b (1.2 equiv), Pd(OTf)2
(2.0 mol %), Cu(OAc)2 (1.2 equiv), p-xylene (1.5 mL), 120 °C, 12 h.
b
All yields are isolated.
oxabenzonorbornadienes possessing diverse substituents in
different ring positions worked well. The treatment of 1b−h
with 2b under the reaction conditions described above
generated the corresponding products in good yields.
Compounds 3bb and 3cb were obtained in 82% and 59%
yield, respectively, when 1b and 1c were used as the substrates
(entries 1−2). Symmetrically difluoro-substituted compound
1d enabled the formation of 3db in moderate yield readily
(entry 3). Surprisingly, 1e having a dibromo group undertook
the reaction well, providing 3eb in 48% yield predominantly
(entry 4), which indicated that Pd(II) species rather than Pd(0)
might be involved in the catalytic process.12 Along with
oxabenzonorbornadiene substrates with substituted benzenes,
C1-substituted ones (1f and 1g) were also employed and
regioselectively produced 3fb and 3gb in 77% and 62% yields,
respectively (entries 5 and 6). Even using highly sterically
hindered C1, C4-disubstituted compound 1h as the substrate,
the reaction also effectively produced the corresponding
adducts 3hb in 73% yield (entry 7).
PPh3 and oxidant Cu(OAc)2 gave the key active compound Pd-
A reasonably that involved C−P bond cleavage of PPh3 and the
interchange between phenyl group and anion.7 Pd-A reacted
with 1 via oxidative addition to afford intermediate Pd-B,
followed by β-O-elimination15 to form Pd-C, and then
compounds 3-OH16 and Pd-D were liberated after acidolysis.
Dehydration of 3-OH led to the desired product 3. Pd-A was
regenerated by the reaction of Pd-D, PPh3, and Cu(OAc)2 with
the release of PPh2X; the latter was hydrolyzed and oxidized to
the isolated diphenylphosphinic acid.
In summary, we developed the first catalytic approach for
Pd(II)-catalyzed aromatic coupling of oxabenzonorbornadienes
with triarylphosphines under neutral reaction conditions, in
which triarylphosphines function as both ligands and aryl
donors. The catalytic process underwent stable C−P bond
cleavage and tolerated diverse functional groups, which allowed
new potential in the application of phosphines. The preliminary
mechanistic study reveals that the β-O-elimination of oxo-
bridged dienes plays the key role for such a catalytic cycle.
Further investigations to define the details of the mechanism
and the scope of this catalyst system are currently in progress in
our laboratory.
To explore the mechanism of this transformation, several
control reactions were performed (Scheme 3). The C−P bond
cleavage product was not monitored in the absence of the Pd-
catalyst (eq 6). With tris(4-methoxyphenyl)phosphine oxide as
the aryl donor under the identical conditions, the C−P bond
C
DOI: 10.1021/acs.orglett.5b02366
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b02366.
■
S
Complete experimental details and characterization data
for the compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
(12) Wallow, T. I.; Goodson, F. E.; Novak, B. M. Organometallics
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■
(13) Wang, X.; Lu, Y.; Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc. 2010,
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*E-mail: cgxia@lzb.ac.cn.
*E-mail: gxjiang2012@sinano.ac.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Hundred Talent Program of
Chinese Academy of Sciences (CAS) and the Natural Science
Foundation of Jiangsu (Grant No. BK20151235) are gratefully
acknowledged.
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