Divergent synthesis of 2,5-diarylphospholes based on cross-coupling reactions: Substituent effects on the optical and redox properties of benzenephospholebenzene φ-systems

Article abstract of DOI:10.1246/cl.2011.919

Divergent synthesis of 2,5-diarylphosphole derivatives was achieved by using two kinds of Pd-catalyzed cross-coupling reactions. In addition, para- and P-substituent effects on the optical and redox properties of the benzenephospholebenzene φ-systems were

Full text of DOI:10.1246/cl.2011.919

doi:10.1246/cl.2011.919
Published on the web September 5, 2011
919
Divergent Synthesis of 2,5-Diarylphospholes Based on Cross-coupling Reactions:
Substituent Effects on the Optical and Redox Properties
of Benzene-Phosphole-Benzene ³-Systems
Yoshihiro Matano,*1 Yusuke Kon,1 Arihiro Saito,1 Yoshifumi Kimura,2 Toshihiro Murafuji,3 and Hiroshi Imahori1,4,5
1Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8510
2Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
3Department of Chemistry, Graduate School of Medicine, Yamaguchi University, Yamaguchi 753-8512
4Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Nishikyo-ku, Kyoto 615-8510
5Fukui Institute for Fundamental Chemistry, Kyoto University, Sakyo-ku, Kyoto 606-8103
(Received March 10, 2011; CL-110206; E-mail: matano@scl.kyoto-u.ac.jp)
Divergent synthesis of 2,5-diarylphosphole derivatives was
achieved by using two kinds of Pd-catalyzed cross-coupling
reactions. In addition, para- and P-substituent effects on the
optical and redox properties of the benzene-phosphole-benzene
³-systems were disclosed experimentally.
Bu3Sn
SnBu3
I
I
Br
Br
P
P
P
Ph O
2b
Ph O
Ph O
2a
1
In recent years, ³-conjugated phospholes have gained
increasing attention as promising materials for applications in
optoelectronics due to the characteristic properties of phosphole,
such as high emitting ability, high electron-accepting ability, and
versatile reactivity at phosphorus.1 In particular, phospholes
bearing aryl groups at the ¡ (2,5-) positions have been frequently
studied because polarizable and chemically tunable ³-networks
can be constructed by linking a phosphorus-bridged diene with
arene functions. In this regard, several methods have been
established for the synthesis of 2,5-diarylphospholes.2 However,
the number of aryl groups introduced to the ¡ positions is
still limited, and thereby the development of phosphole-based
³-conjugated materials awaits a general method for the divergent
synthesis of 2,5-diarylphospholes starting from readily accessible,
common synthons.
Chart 1.
Stille
[Pd2(dba)3] (5 mol%)
(2-furyl)3P (20 mol%)
CuI (200 mol%)
1 +
I
X
or
P
O
3a–f
NMP
X
X
Ph
2a, 2b +
Bu3Sn
NMe2
3a (X = NO2; 86%) 3d (X = Cl; 67%)
3b (X = CN; 70%) 3e (X = H; 60%)
3c (X = CHO; 79%) 3f (X = NMe2; 23–25%)
Negishi
[Pd(PPh3)4] (20 mol%)
3g (X = OMe; 24%)
2a +
BrZn
OMe
THF
Cross-coupling reactions,3 which are among the most reliable
methods to connect two different ³-systems, have not been fully
addressed in the synthesis of 2,5-diarylphospholes. This is partly
due to the lack of information about the phosphole synthons that
are applicable to cross-coupling conditions.4-6 Recently, we
succeeded in preparing the first example of ¡,¡¤-linked poly-
phosphole by using a Pd-CuI-promoted Stille-type coupling7
Scheme 1. Synthesis of 2,5-diarylphosphole P-oxides 3.
amount of 2,2¤-biphosphole (a homo-coupling product derived
from 1),10 the target phosphole 3a could be easily separated
from this side product by column chromatography.11 Therefore,
we applied this Stille-type coupling to the synthesis of other
between 2,5-bis(tributylstannyl)phosphole
1 and 2,5-diiodo-
phosphole 2a (Chart 1).8,9 We envisioned that 1 as well as
2,5-dihalophospholes 2a and 2b would also be converted to a
variety of 2,5-diarylphospholes by the cross-coupling method-
ology. Herein, we report the first divergent synthesis of
2,5-diarylphospholes bearing para-substituted phenyl, heteroaryl,
or ¢-styryl groups starting from 1 or 2a, 2b based on the Stille and
Negishi reactions. In addition, we have investigated para- and
P-substituent effects on their optical and redox properties.
Scheme 1 depicts the synthesis of 2,5-diarylphosphole
P-oxides 3. The starting materials 1 and 2a were prepared
according to a reported procedure.8 The 2,5-dibromophosphole 2b
was newly prepared by bromolysis of 1 with NBS. Treatment of 1
with p-iodonitrobenzene in the presence of [Pd2(dba)3] (5 mol %),
tris(2-furyl)phosphine (20 mol %), and CuI (200 mol %) in
N-methylpyrrolidone (NMP) at room temperature afforded
2,5-bis(p-nitrophenyl)phosphole P-oxide 3a in 86% yield. Al-
though we could not completely suppress the formation of a small
2,5-diarylphospholes. When 1 was treated with p-cyano-,
p-formyl-, or p-chloroiodobenzene under the same Pd-CuI con-
ditions, the corresponding 2,5-diarylphosphole P-oxides 3b-3d
were obtained in 67-79% yields. The conversion from
1/iodobenzene to 3e12 was found to proceed smoothly at 80 °C.
The Stille-type coupling also took place between 2a, 2b and
tributyl(p-dimethylaminophenyl)stannane at 80 °C, affording 3f
in 23-25% yields. We further conducted Negishi coupling
between 2a and p-methoxyphenylzinc bromide in the presence
of [Pd(PPh3)4]. In this reaction, the desired coupling product 3g
was isolated as the major product. Although the yield was not
satisfactory in some cases, we have established a new, convenient
method for the synthesis of a series of 2,5-diarylphosphole
P-oxides. The successful isolation of 3a-3c represents an
advantage of the Pd-catalysis protocol, which allows delivery of
reactive functions such as nitro, cyano, and formyl groups from the
iodoarene substrates to the phosphole products.
Chem. Lett. 2011, 40, 919-921
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

920
3
2
1
0
Absorption
Fluorescence
Pd–CuI
NMP
1 +
S
S
I
3a
3e
3f
S
P
O
5 (71%)
Ph
norm
I
Pd–CuI
NMP
1 +
I
P
O
Ph
6 (52%)
300
400
500
/ nm
600
700
Figure 1. UV-vis absorption (solid line) and fluorescence (dashed
line) spectra of 3a, 3e, and 3f in CH2Cl2.
Pd–CuI
Br
1 +
Ph
NMP
Ph
Ph
P
Table 1. Optical and electrochemical data for 3-8 in CH2Cl2
Ph
O
7 (54%)
-ab/nm (log ¾) -em/nma (ΦF ) ¸f/nsa
E
red/Vc
b
3-8 (X)
3a (NO2)
3b (CN)
3c (CHO)
3d (Cl)
412 (4.41)
394 (4.23)
407 (4.39)
392 (4.23)
387 (4.15)
507 (0.30)
496 (0.25)
504 (0.36)
500 (0.28)
491 (0.14)
588 (0.01)
525 (0.05)
527 (0.66)
452 (0.46)
534 (0.04)
N.f.e (®)
2.24 ¹1.37, ¹1.63
2.29 ¹1.69, ¹1.93
2.09 ¹1.61, ¹1.73
1.97 ¹2.01
1.39 ¹2.02
0.12 ¹2.05
0.52 ¹2.24
2.50 ¹1.37, ¹2.15
2.41 ¹2.73
S
N
Pd
NMP
S
S
2b +
Bu3Sn
P
N
N
O
Ph
8 (31%)
3e (H)d
3f (NMe2) 466 (4.33)
3g (OMe)
4a (NO2)
4e (H)
411 (4.26)
423 (4.37)
369 (4.26)
432 (4.24)
481 (4.60)
442 (4.43)
424 (4.19)
Scheme 2. Synthesis of 5-8. Pd-CuI: [Pd2(dba)3] (5 mol %),
(2-furyl)3P (20 mol %), CuI (200 mol %). Pd: [Pd(PPh3)4] (20 mol %).
5
6
7
8
a
0.48 ¹2.09
®
¹1.56, ¹1.79
HSiCl3
556 (0.17)
519 (0.25)
3.23 ¹1.84
1.95 ¹1.69, ¹2.08
3a, 3e
ð1Þ
P
toluene
X
X
Ph
-ex = 400 (for 3a-3e), 440 (for 3f, 3g, 4a, 5, 7, and 8), and
4a (X = NO2; 82%), 4e (X = H; 71%)
b
c
380 nm (for 4e). Absolute fluorescence quantum yields. De-
When heated with excess trichlorosilane (HSiCl3) in toluene
at reflux, 3a and 3e were reduced at the phosphorus center to give
·3-P derivatives 4a and 4e, respectively (eq 1). In addition to the
para-substituted phenyl groups, 2-thienyl, 2-azulenyl, ¢-(E)-
styryl, and 2-thiazolyl groups were introduced to the ¡-positions
of the phosphole ring by the Stille-type coupling between 1 and the
corresponding organyl halides or a Stille coupling between 2b and
2-(tributylstannyl)thiazole, yielding 2,5-diorganylphospholes 5-8
in 31-71% yields (Scheme 2). Phosphole derivatives 3-8 were
characterized by standard spectroscopic techniques. The 31P NMR
spectra of 3a-3g showed singlet peaks at ¤P 53.6-55.1, indicating
that the para-substituent effects on the 31P chemical shifts are not
significant. By contrast, the reductive deoxygenation from ·4-P=O
(3a and 3e) to ·3-P (4a and 4e) induced upfield shift of the 31P
peak by ca. 20 ppm. The other phosphole P-oxides 5-8 displayed
their 31P resonances in the range of ¤P 50.8-53.8 ppm.
termined by DPV (0.1 M n-Bu4N+ PF6 ; Ag/Ag+); Reduction
¹
potentials (Ered) vs. Fc/Fc+. dData from ref. 12. ΦF was
e
remeasured. N.f.: Non-fluorescent.
¹1
¹1
(¦¯ab = ¹3460 cm and ¦¯em = ¹3150 cm vs. 4e) are much
larger than those of the ·4-P=O/NO2 derivative 3a (¦¯ab
=
¹1570 cm¹1 and ¦¯em = ¹640 cm¹1 vs. 3e). This implies that the
substituent effect of NO2 groups on the HOMO-LUMO gap is
enhanced by the P-deoxygenation. To get an additional insight into
these spectral features, we carried out DFT calculations (B3LYP/
6-31G*) of P-H models 3e-M, 3f-M, 4a-M, and 4e-M (Figure S2,
Tables S1-S4 in SI16). In the optimized structure of 3f-M, the
HOMO is spread over the NMe2 groups, whereas the LUMO is
localized at the phosphole subunit. In 4a-M, the LUMO is spread
over the NO2 groups, whereas the HOMO does not have electron
density on them. The NMe2-substitution destabilizes the HOMO
more largely than the LUMO (3f-M vs. 3e-M). By contrast, the
NO2-substitution stabilizes the LUMO more greatly than the
HOMO (4a-M vs. 4e-M). As a consequence, the HOMO-LUMO
gaps become narrow for both para-substituted derivatives
(¦EH-L = 3.08 for 3f-M; 2.97 eV for 4a-M) relative to the
unsubstituted references (¦EH-L = 3.32 for 3e-M; 3.71 eV for
4e-M), which correlates well with the experimentally observed
results. More importantly, the DFT calculations suggested that the
HOMO-LUMO transitions in 3f and 4a possess intramolecular
charge-transfer (CT) character.
In order to reveal the optical properties of 3-8, UV-vis
absorption and fluorescence spectra were measured in CH2Cl2
(Figure 1, Figure S1 in the Supporting Information; SI,16 and
Table 1). The absorption and fluorescence maxima (-ab and -em
)
of the para-substituted diphenylphosphole derivatives 3a-3d, 3f,
3g and 4a are red-shifted relative to those of the unsubstituted
references 3e and 4e. The -ab and -em values also depend on the ¡-
substituents (5-8 vs. 3e). Among 3a-3g, the red shifts of -ab and
-
induced by the electron-donating substituents are larger than
em
those induced by the electron-withdrawing groups, and the largest
red shifts were observed for the ·4-P=O/NMe2 derivative 3f
¹1
¹1
(¦¯ab = ¹4380 cm and ¦¯em = ¹3360 cm vs. 3e). It is also
noteworthy that the red shifts of the ·3-P/NO2 derivative 4a
To know the combined effects of the para- and P-substituents
on the polarizability of 2,5-diarylphospholes, we measured
Chem. Lett. 2011, 40, 919-921
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

921
solvatochromism of absorption and fluorescence spectra of 3e, 3f,
4a, and 4e using eight solvents with different polarity (Table S5 in
SI16). With increasing the solvent polarity from cyclohexane
(³* = 0) to DMF (³* = 0.88), -ab/-em of 3f and 4a shifted to
longer wavelength by 670/1810 and 1090/3230 cm¹1, respective-
ly, showing a good linear correlation with ³*.13 On the other hand,
-ab/-em of 3e and 4e were insensitive to the solvent polarity and
almost constant. These results suggest that the combination of
·4-P=O/NMe2 (pull/push) or ·3-P/NO2 (push/pull) is effective
for enhancing the polarizability of the benzene-phosphole-
benzene ³-systems. The larger solvent effect on -em than on -ab
in the cases of 3f and 4a is indicative of the larger structural
change in the excited state due to the CT character.
Except for 3f and 6, the present phosphole derivatives are
moderately fluorescent with fluorescent quantum yields (Φf) of
0.04-0.66. To evaluate the substituent effects on the photophysical
processes from excited singlet (S1) states, fluorescence lifetimes
(¸f) were measured in CH2Cl2 at 22 °C. The fluorescence decays
were well-fitted by the single-exponential component. As listed in
Table 1, ¸f of 3a-3g varied from 0.12 to 2.29 ns depending on the
para-substituents. With Φf and ¸f values in hand, we calculated
rate constants for radiative decay (kr) and nonradiative decay
(internal conversion and intersystem crossing, knr) from the S1
states (Table S6 in SI16). In comparison with kr and knr of 3e
(1.4 © 108 and 6.2 © 108 s¹1, respectively), the para-substituent
effects on kr are small (kr = 0.8-1.7 © 108 s¹1), while those on knr
are relatively large (knr = 3.1-83 © 108 s¹1). It is likely that the
substituent effects on Φf depend on the change in knr rather than the
change in kr. In particular, knr of 3f and 3g are 3-14 times as large
as knr of 3e, which suggests that the rotation at the NMe2 and OMe
groups in 3f and 3g accelerates the vibronic relaxation from their
S1 states in solution.14
This paper is in celebration of the 2010 Nobel Prize awarded
to Professors Richard F. Heck, Akira Suzuki, and Ei-ichi Negishi.
References and Notes
1
For example, see: a) F. Mathey, Angew. Chem., Int. Ed. 2003, 42,
1578. b) M. Hissler, P. W. Dyer, R. Réau, Coord. Chem. Rev. 2003,
244, 1. c) L. D. Quin, Curr. Org. Chem. 2006, 10, 43. d) T.
Baumgartner, R. Réau, Chem. Rev. 2006, 106, 4681; Correction: T.
Baumgartner, R. Réau, Chem. Rev. 2007, 107, 303. e) M. Hissler, C.
Lescop, R. Réau, Pure Appl. Chem. 2007, 79, 201. f) M. G. Hobbs,
T. Baumgartner, Eur. J. Inorg. Chem. 2007, 3611. g) R. Réau, P. W.
Dyer, in Comprehensive Heterocyclic Chemistry III, ed. by A. R.
Katritzky, C. A. Ramsden, E. F. V. Scriven, R. J. K. Taylor, Elsevier,
Oxford, 2008, Vol. 3, Chap. 3.15, pp. 1029-1048. doi:10.1016/
B978-008044992-0.00315-1. h) Y. Matano, H. Imahori, Org.
Biomol. Chem. 2009, 7, 1258. i) A. Fukazawa, S. Yamaguchi,
Chem.®Asian J. 2009, 4, 1386.
2
3
For synthetic methods until the ’90s, see: F. Mathey, in Science of
Synthesis, ed. by E. J. Thomas, Georg Thieme Verlag, Stuttgart,
2000, Vol. 9, Chap. 9.14, pp. 553-600. See also recent papers cited
in refs. 1d, 1g, and 1h.
For example, see: a) Metal-Catalyzed Cross-Coupling Reactions, ed.
by A. de Meijere, F. Diederich, Wiley-VCH, Weinheim, 2004. b)
J. K. Stille, Angew. Chem., Int. Ed. Engl. 1986, 25, 508. c)
Handbook of Organopalladium Chemistry for Organic Synthesis,
ed. by E. Negishi, Wiley-Interscience, New York, 2002, Vol. 1,
Part III. d) E. Negishi, Q. Hu, Z. Huang, M. Qian, G. Wang,
Aldrichimica Acta 2005, 38, 71.
4
For transition-metal-catalyzed cross- and homo-coupling of ¡-
halophospholes, see: a) E. Deschamps, L. Ricard, F. Mathey, Angew.
Chem., Int. Ed. Engl. 1994, 33, 1158. b) S. Holand, F. Gandolfo, L.
Ricard, F. Mathey, Bull. Soc. Chim. Fr. 1996, 133, 33. c) T.-A.
Niemi, P. L. Coe, S. J. Till, J. Chem. Soc., Perkin Trans. 1 2000,
1519.
5
6
For Sonogashira reactions of ¡-ethynylphospholes, see: Y. Matano,
M. Nakashima, H. Imahori, Angew. Chem., Int. Ed. 2009, 48, 4002.
Pd-catalyzed cross-coupling reactions have been applied to the
synthesis of ¢-arylated benzo[b]phosphole derivatives. a) H. Tsuji,
K. Sato, L. Ilies, Y. Itoh, Y. Sato, E. Nakamura, Org. Lett. 2008, 10,
2263. b) A. Fukazawa, Y. Ichihashi, Y. Kosaka, S. Yamaguchi,
Chem. ®Asian J. 2009, 4, 1729.
The redox behavior of 3-8 was studied by cyclic voltammetry
and differential pulse voltammetry (DPV). In most cases, electro-
chemical oxidations occurred irreversibly, whereas reductions
occurred reversibly or quasi-reversibly. As summarized in Table 1,
the introduction of the electron-withdrawing and electron-donating
groups at para-positions causes anodic (for 3a-3d) and cathodic
(for 3f and 3g) shifts of the reduction potentials (Ered) over the
range from ¦Ered = +0.39 to ¹0.22 V (vs. 3e).15 As expected, the
nitro groups made the most significant impact on the electron-
accepting ability of the ³-systems. The P-oxidation state (4a and
4e) and the other ¡-substituents (5-8) also exhibited their own
electronic effects on the redox properties.
7
V. Devreux, J. Wiesner, H. Jomaa, J. Rozenski, J. V. der Eycken,
S. V. Calenbergh, J. Org. Chem. 2007, 72, 3783.
8
9
A. Saito, Y. Matano, H. Imahori, Org. Lett. 2010, 12, 2675.
We recently succeeded in preparing three kinds of phosphole-
heterole-phosphole ³-systems (heterole: pyrrole, furan, and thio-
phene) by using the Stille-type reactions of 2-tributylstannyl-5-
phenylphosphole and 2-iodo-5-phenylphosphole. Y. Matano, A.
Saito, M. Fujita, H. Imahori, Heteroat. Chem., in press.
doi:10.1002/hc.20708
In summary, we have established convenient methods for the
divergent synthesis of 2,5-diarylphosphole derivatives based on
cross-coupling reactions starting from the common phosphole
synthons. The electronic effects of the para-substituents attached
to the terminal ¡-phenyl groups on the optical and redox properties
of the benzene-phosphole-benzene ³-systems were evaluated for
the first time. Notably, the chemical functionalization at the
phosphorus center from ·4-P=O to ·3-P has proven to change the
electron-donating/-accepting abilities as well as the polarizability
of the whole ³-systems. The present results provide valuable
information about the synthesis and fundamental properties of
phosphole-containing hybrid ³-conjugates.
10 In the absence of CuI, the formation of biphosphole was suppressed,
but the conversion rate from 1 to 3 was slowed down significantly.
11 Pd-catalyzed homo-coupling of arylstannanes was reported. For
example, see: a) L. S. Liebeskind, S. W. Riesinger, J. Org. Chem.
1993, 58, 408. b) V. Farina, B. Krishnan, D. R. Marshall, G. P. Roth,
J. Org. Chem. 1993, 58, 5434. c) L. S. Liebeskind, M. S. Yu, R. H.
Yu, J. Wang, K. S. Hagen, J. Am. Chem. Soc. 1993, 115, 9048.
12 A. Saito, T. Miyajima, M. Nakashima, T. Fukushima, H. Kaji, Y.
Matano, H. Imahori, Chem.®Eur. J. 2009, 15, 10000.
13 Kamlet-Taft plots (M. J. Kamlet, J. L. M. Abboud, M. H. Abraham,
R. W. Taft, J. Org. Chem. 1983, 48, 2877) between ¯em and modified
³* parameters showed linear solvation energy relationship with
large slopes (absolute values: 2.3 © 103 cm¹1 for 3f; 4.1 © 103 cm
¹1
for 4a). See Figure S3 in SI.16
14 Although we cannot exclude the contribution of intersystem
crossing, no phosphorescence of 3g was observed even at ¹196 °C.
15 In 3a and 4a, electrochemical reductions of the nitro groups took
place at Ered = ca. ¹1.4 V.
16 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
We thank Dr. Hirohiko Watanabe (Hamamatsu Photonics K.K.)
for some photophysical measurements. This work was partially
supported by Grants-in-Aid (Nos. 21108511 and 22350016) from
the Ministry of Education, Culture, Sports, Science and Technology
(MEXT), Japan and Asahi glass foundation.
Chem. Lett. 2011, 40, 919-921
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/