Intramolecular, Pd/Cu-Co-catalyzed P-C Bond Cleavage and Addition onto an Alkyne: A Route to Benzophospholes

Article abstract of DOI:10.1021/acs.orglett.5b02926

Under Pd(II)/CuI cocatalysis, o-diarylphosphinophenylalkynes cyclize in boiling toluene via C-P bond cleavage and arylphosphination of the C≡C bond. This protocol provides an unprecedented atom- and step-efficient access to optoelectronically and biologic

Full text of DOI:10.1021/acs.orglett.5b02926

Letter
pubs.acs.org/OrgLett
Intramolecular, Pd/Cu-Co-catalyzed P−C Bond Cleavage and
Addition onto an Alkyne: A Route to Benzophospholes
†
†
†
†
,†
,†,‡
Yang Zhou, Zhenjie Gan, Bo Su, Jun Li, Zheng Duan,* and Franc o̧ is Mathey*
†College of Chemistry and Molecular Engineering, International Phosphorus Laboratory, International Joint Research Laboratory for
Functional Organophosphorus Materials of Henan Province, Zhengzhou University, Zhengzhou 450001, P.R. China
‡
Nanyang Technological University, Division of Chemistry & Biological Chemistry, 21 Nanyang Link, Singapore 637371
*
S Supporting Information
ABSTRACT: Under Pd(II)/CuI cocatalysis, o-diarylphosphinophenylalkynes
cyclize in boiling toluene via C−P bond cleavage and arylphosphination of the
CC bond. This protocol provides an unprecedented atom- and step-efficient
access to optoelectronically and biologically interesting benzophospholes.
ertiary phosphines have been broadly used as preferred
ligands for transition-metal-centered catalysts due to their
In connection with our efforts to develop new methods for
T
selective activation of P−C bonds of triarylphosphines, herein we
report the first highly atom-efficient and step-economic Pd- and
Cu-co-catalyzed arylphosphination of the CC triple bond to
give 2,3-disubstituted benzophospholes from 2-(arylethynyl)-
phenylphosphines (Scheme 1) via activation of the stable P−Ar
bond.
robust C−P bonds and the unique opportunity to modify the
steric and electronic properties of the ligand. Meanwhile, the C−
P bond activation of tertiary phosphines by transition metals is a
fundamental reaction and an important research topic in both
modern experimental and theoretical chemistry. Many years ago,
it was discovered that transition metals can insert into the C−P
1
bonds of tertiary phosphines. Most of the examples concern the
Scheme 1. Co-catalyzed Synthesis of Benzophospholes
stoichiometric reactions between transition metals and phos-
1a−f
phines to give stable phosphido complexes.
There are only
limited examples of catalytic activation of C−P bonds of tertiary
phosphines where the phosphine was used as a carbon source or
a phosphorus source. For example, as a carbon source, several
groups reported the application of triaryl phosphines as aryl
2
donors in reactions with alkenes or as coupling partners in
3
palladium-catalyzed aryl−aryl couplings. Tetraphenylphospho-
We began our studies with 1a, which was synthesized via the
previously described simple protocol. We observed that when
9
nium salts were used as arylating reagents in Pd-catalyzed
reactions with olefins, organoboron compounds, and terminal
alkynes. However, only one of the substituents on phosphorus
the reaction was carried at 120 °C in toluene with 10 mol % of
4
Pd(OAc) as a catalyst no reaction was observed (Table 1, entry
2
can be utilized in the aforementioned reactions. As a phosphorus
source, a facile phosphination of substituted aryl bromides or aryl
triflates with triarylphosphines as phosphinating agents was
1
). As we added 10 mol % of CuI as co-catalyst, surprisingly, the
reaction proceeded smoothly to give 2a. Subsequent in situ
oxidation with H O gave stable benzophosphole oxide 3a, which
was isolated in 41% yield (entry 2). The structure of 3a was
2
2
5
developed by Chan’s group. Tobisu and Chatani reported a
6
1
13
31
direct synthesis of phospholes and dibenzo-fused six-membered
analyzed by H, C, and P NMR and mass spectrometry and
13a,c,e
7
phosphacycles through a Pd-catalyzed C−P bond cleavage of
compared with the reported one.
with CuI catalyst only (entry 3). Among the other palladium
catalysts, Pd(PPh Cl was found to co-catalyze this reaction
and gave the desired 3a (entry 4). Pd(PPh and PdCl did not
No reaction was observed
triarylphosphines. That said, the cleaved aryl part was left as the
byproduct. The only highly atom-efficient reaction was
developed by Wu et al. through a Ni(0)-catalyzed arylphosphi-
nation of a highly strained three-membered ring system with
)
3
2
2
)
3
4
2
catalyze this reaction (entries 5 and 6). CuBr showed a
comparable activity to CuI, but the reaction time was longer
8
triarylphosphines via C−C and C−P bond cleavage.
(
entry 7). The presence of the lone pair on phosphorus had a
Very recently, we developed a simple method to synthesize
benzophospholes from 2-(arylethynyl)phenylphosphines via
lithium-mediated selective P−C bond cleavage and cyclo9-
addition, but an excess amount of lithium was used.
profound impact on the efficiency of the reaction, and both
oxidation (entry 8) and coordination (entry 9) inhibited the
formation of 2.
1
0
Benzophospholes are frequently used in organic electronics,
1
1
12
bioimaging probes, and catalysts. Several efficient methods
Received: October 8, 2015
13
have been developed for the preparation of these compounds.
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02926
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Letter
a
Table 1. Optimization of the Reaction Conditions
b
entry
1
Pd (10 mol %)
Cu (10 mol %)
yield (%)
1
2
3
4
5
6
7
8
9
1a
Pd(OAc)2
Pd(OAc)2
NR
41
1a
CuI
CuI
CuI
CuI
CuI
CuBr
CuI
CuI
1a
NR
40
1a
Pd(PPh ) Cl
2
3
2
1a
Pd(PPh3)4
PdCl2
trace
trace
1a
c
1a
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
37
1aO
1aB
NR
NR
Figure 1. X-ray crystal structure of 4. The level set for thermal ellipsoids
of all atoms is 30%. Main bond lengths (Å) and angles (deg): P1−C6
1.808(4), C6−C11 1.403(5), C11−C12 1.490(5), C12−C13 1.347(5),
C13−P1 1.825(4), P1−W1 2.5173(11); P1−C27 1.834(3), C6−P1−
C13 90.96(18).
a
Reaction conditions: 1 (1 mmol), 120 °C, toluene (5 mL), for 2 h.
Isolated yield of 3. For 4 h.
b
c
To the best of our knowledge, this is the first catalytic addition
a
Table 2. Variation on the Substituents
of a P−Ph bond across a CC triple bond. In order to confirm
this kind of reaction, we checked this catalytic system (using 10
mol % of Pd(OAc) and 10 mol % of CuI as co-catalyst, at 120
2
°
C, in toluene) with 2-(arylethynyl)phenylphosphine 1b. The
corresponding W(CO) complex 4 was synthesized (Scheme 2),
5
Scheme 2. Synthesis of W(CO) Complex 4
5
and X-ray structural data of 4 were acquired (Figure 1),
confirming the unexpected catalytic addition of P−C bond to a
CC triple bond. It is clearly shown that there is one phenyl
group at the 3-position of the final benzophosphole, which is
definitely coming from the diphenylphosphino group. However,
a
Reaction conditions: 1 (1 mmol), Pd(OAc) (0.1 mmol), CuI (0.1
2
b
c
mmol), toluene (5 mL), at 120 °C for 2 h. Isolated yield. For 4 h.
d
Pd(PPh ) Cl was used instead of Pd(OAc)
3
2
2
2
under same reaction conditions, no reaction between PPh and
3
diphenylacetylene was observed.
(
68%, entry 8) substitutents. No reaction was observed with 1-
Next, we investigated the scope and limitations of this
bimetallic catalyst system with various 2-(arylethynyl)-
phenylphosphines (Table 2). From the results, we can see that
the efficiency of the cyclization reaction is highly dependent on
the electronic nature of the substrates. When 1a, 1b, and 1c were
used, the yields were moderate (entries 1−3, 3a (41%), 3b
naphthyl-substituted 1i (entry 9), which may be due to the steric
hindrance of the naphthalene ring.
Furthermore, the cycloaddition with diisopropyl- (1k) or
diethylamino-substituted phosphine (1l) took place smoothly to
give benzophosphole oxide 5a and 5b after workup, respectively
(
Scheme 3). We propose that the proton on the 3-position in 5a
(52%), 3c (43%)). Low yields were obtained with electron-
donating methoxy-substituted 3e (32%, entry 4), as only 7% of 3f
was achieved with amino substituted 1f, and the yield of 3f could
be improved to 29% by replacing Pd(OAc) with Pd(PPh ) Cl
2
Scheme 3. Case of Alkyl and Amino Substituents
2
3 2
(entry 6). Compound 3f can be used as a fluorescent probe for
the environmental polarity in biological systems. It was
previously synthesized by a stepwise formation of the phospha-
cycle and introduction of the phenyl group at 3-position, with
11
workup stages after each transformation. Good yields were
obtained with electron-withdrawing F (72%, entry 7) and CF3
B
DOI: 10.1021/acs.orglett.5b02926
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Letter
comes from the β-H elimination of an isopropyl-Pd intermediate.
To the best of our knowledge, 1k is the first example of Pd-
Notes
The authors declare no competing financial interest.
3
catalyzed P−Csp bond cleavage.
2
We propose the following reaction mechanism (Scheme 4):
ACKNOWLEDGMENTS
■
(1) both the lone pair on the phosphine and the alkynyl group are
This work was supported by the National Natural Science
Foundation (No. 21272218), Specialized Research Fund for the
Doctoral Program of Higher Education (No. 20134101110004),
Henan Science and Technology Department (No.
Scheme 4. Proposed Mechanism
1
44300510011), Zhengzhou Science and Technology Depart-
ment (No. 131PYSGZ204) and Zhengzhou University of China.
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ASSOCIATED CONTENT
Supporting Information
■
(
5
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b02926.
1
X-ray data for 4 (CIF)
Experimental section; NMR data for 2−5 (PDF)
2
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AUTHOR INFORMATION
Corresponding Authors
■
1
0, 2689. (i) Tsuji, H.; Sato, K.; Ilies, L.; Itoh, Y.; Sato, Y.; Nakamura, E.
Org. Lett. 2008, 10, 2263.
*
E-mail: duanzheng@zzu.edu.cn.
E-mail: fmathey@ntu.edu.sg.
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*
C
DOI: 10.1021/acs.orglett.5b02926
Org. Lett. XXXX, XXX, XXX−XXX