Modular synthesis of benzo[b]phosphole derivatives via BuLi-mediated cyclization of (o-alkynylphenyl)phosphine

Article abstract of DOI:10.1021/ol800684x

(Chemical Equation Presented) Treatment of an (o-alkynylphenyl)phosphine with a stoichiometric amount of BuLi effects a cyclization reaction to produce a 3-lithiobenzo[b]phosphole, which affords a variety of 3-substituted benzophospholes upon reaction with electrophiles. An example is given for the synthesis of a bis-benzo[b]phosphole, which can be further converted to the corresponding benzo[b]phosphole oxide possessing high electron affinity.

Full text of DOI:10.1021/ol800684x

ORGANIC
LETTERS
2008
Vol. 10, No. 11
2263-2265
Modular Synthesis of
Benzo[b]phosphole Derivatives via
BuLi-Mediated Cyclization of
(o-Alkynylphenyl)phosphine
Hayato Tsuji,*,† Kosuke Sato,† Laurean Ilies,† Yoshimitsu Itoh,† Yoshiharu Sato,‡
and Eiichi Nakamura*,†,‡
Department of Chemistry, School of Science, The UniVersity of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan, and Nakamura Functional Carbon Cluster
Project, ERATO, Japan Science and Technology Agency, Department of Chemistry,
School of Science, The UniVersity of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan
tsuji@chem.s.u-tokyo.ac.jp; nakamura@chem.s.u-tokyo.ac.jp
Received March 25, 2008
ABSTRACT
Treatment of an (o-alkynylphenyl)phosphine with a stoichiometric amount of BuLi effects a cyclization reaction to produce a 3-lithiobenzo[b]-
phosphole, which affords a variety of 3-substituted benzophospholes upon reaction with electrophiles. An example is given for the synthesis
of a bis-benzo[b]phosphole, which can be further converted to the corresponding benzo[b]phosphole oxide possessing high electron affinity.
Benzo[b]phospholes are heavy-atom congeners of indoles,1 and
their applications as physiologically and electronically active
materials are of interest. Functionalized benzophospholes2–4 are
less synthetically accessible than phospholes and dibenzo-
phospholes and hence have been studied much less fre-
quently.5 We have been exploring for some time a modular
approach to the synthesis of new π-electron systems and have
demonstrated the synthesis of a variety of functionalized
benzo[b]furans and indoles,6 benzo[1,2-b:4,5-b′]difurans,7
and benzo[b]siloles.8 Herein, we report the modular synthesis
(4) For a synthesis of 3-halobenzo[b]phosphole oxides, see: Ichihashi,
Y.; Fukazawa, A.; Yamaguchi, S. 88th Annual Meeting of Chemical Society
of Japan, Tokyo, Japan, March 26-30, 2008, 3H4-48.
(5) For recent reviews, see: (a) Hobbs, M. G.; Baumgartner, T. Eur.
J. Inorg. Chem. 2007, 3611–3628. (b) Baumgartner, T.; Re´au, R. Chem.
ReV. 2006, 106, 4681–4217. (c) Mathey, F. Angew. Chem., Int. Ed. 2003,
42, 1578–1604.
† The University of Tokyo.
‡ Nakamura Functional Carbon Cluster Project, ERATO.
(1) Katritzky, A. R. ComprehensiVe Heterocyclic Chemistry; Pergamon:
Oxford, 1984; Vol. 4, Part 3, pp 658-712.
(2) For a review, see: Aitken, R. A. Science of Synthesis; Thomas, J.,
Ed.; Thieme: Stuttgart, 2000; Vol. 10, pp 789-808
.
(6) (a) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Angew. Chem.,
Int. Ed. 2006, 45, 944–947. (b) Nakamura, M.; Ilies, L.; Otsubo, S.;
Nakamura, E. Org. Lett. 2006, 8, 2803–2805.
(3) For examples of 3-functionalized benzophospholes, see: (a) Rausch,
M. D.; Klemann, L. P. J. Am. Chem. Soc. 1967, 89, 5732–5733. (b) Winter,
W. Tetrahedron Lett. 1975, 45, 3913–3914. (c) Balthazor, T. M. J. Org.
Chem. 1980, 45, 2519–2522. (d) Ma¨rkl, G.; Jin, G. Y.; Berr, K. P.
Tetrahedron Lett. 1993, 34, 3103–3106. (e) Cordaro, J. G.; Stein, D.;
(7) Tsuji, H.; Mitsui, C.; Ilies, L.; Sato, Y.; Nakamura, E. J. Am. Chem.
Soc. 2007, 129, 11902–11903.
(8) Ilies, L.; Tsuji, H.; Sato, Y.; Nakamura, E. J. Am. Chem. Soc. 2008,
130, 4240–4241.
Gru¨tzmacher, H. J. Am. Chem. Soc. 2006, 128, 14962–14971
.
10.1021/ol800684x CCC: $40.75
Published on Web 05/06/2008
2008 American Chemical Society

of 2,3-disubstituted benzo[b]phospholes by the use of a new
synthetic module, 3-lithiobenzo[b]phosphole 2 (M ) Li, eq
1), which can be quantitatively generated by base-promoted
cyclization of (o-alkynylphenyl)phosphine 1. We also report
the electrochemical properties of a 2,3-diaryl-substituted
benzo[b]phosphole oxide (Scheme 2), and suggest its po-
tential utility as an n-type organic semiconductor.
reaction of 2 with 1,2-diiodoethane gave 3-iodobenzo[b]phosphole
5 in 90% yield (entry 2, Table 2). This iodide will serve as an
Umpolung counterpart8 of the lithium compound 2. The bulky
Mes* group effectively protected the phosphorus atom against air
oxidation and electrophilic attacks.
Scheme 1. Synthesis of 2,3-Disubstituted Benzo[b]phospholes
via the 3-Lithiobenzo[b]phosphole Module 2a
Screening of the reaction conditions of the base-promoted
cyclization of (o-alkynylphenyl)phosphine 1 was performed for the
reaction shown in eq 1 (Mes* ) 2,4,6-tri-tert-butylphenyl). The
yield of the desired 3 and the degree of C3-deuteration were
determined by 1H NMR, the results being summarized in Table 1.
We first examined zinc reagents in analogy to the cyclization of
the oxygen and nitrogen analogues6 and found that the reaction of
1 with diethylzinc was very slow. The reaction in THF was
unacceptably slow (entry 1, Table 1), and the reaction in toluene
at higher temperature afforded 3 in 96% yield with deuterium
incorporation as low as 50% (entry 2, Table 1). When BuLi was
used as a base, however, the reaction proceeded smoothly at -40
°C in THF and produced benzophosphole 3 in 92% yield with
96% deuterium incorporation, indicating the intermediacy of the
3-metallobenzophosphole 2 (M ) Li) (entry 3, Table 1). In toluene,
the cyclization required 40 °C and produced 3 in 81% yield with
very poor deuterium incorporation (entry 4, Table 1). The low
deuterium incorporation is probably caused by in situ protonation
of 2 by the starting material 1.
aConditions: (method a) electrophile (1.2 equiv), -78 °C to rt, 3-12
h; (method b) (1) ZnCl2 (1.0 equiv), (2) electrophile (1.2 equiv),
Pd2(dba)3•CHCl3 (5 mol %), PPh3 (20 mol %), rt, 2-24 h. Details for each
reaction are shown in the Supporting Information.
Palladium catalysis expands the scope of the synthetic meth-
odology. Thus, one-pot, three-step, two-component coupling of 1
and an electrophile was achieved through the intermediacy of 2
and the corresponding 3-zinciobenzo[b]phosphole module under
the Negishi cross-coupling conditions using Pd2(dba)3·CHCl3 and
PPh3 (method b in Scheme 1). The results are summarized in entries
3-6, Table 2. Iodobenzene and p-cyanophenyl iodide reacted
smoothly in a few hours and gave 2,3-diaryl-substituted products
6 and 8 in 83% and 83% yield, respectively (entries 3 and 5, Table
2). However, p-anisyl iodide reacted slowly and afforded the
product 7 in lower yield (24 h, 67% yield, entry 4, Table 2). A
three-component coupling using a bifunctional electrophile, p-
diiodobenzene, gave 1,4-bis(3-benzo[b]phospholyl)benzene 9 in
77% yield (based on p-diiodobenzene; entry 6, Table 2). 1H, 13C,
and 31P NMR spectra of 9 showed a single set of resonance signals,
suggesting rapid interconversion among isomers.
The structure of 1,4-bis(3-benzo[b]phospholyl)benzene 9 was
unambiguously determined by single-crystal X-ray structural
analysis (Figure 1). The crystal used for the measurement
contained only one diastereomer. The molecule has an inversion
center and the phosphorus center is pyramidal. The two
benzophosphole planes are twisted against the phenylene bridge
with a dihedral angle of 64.4(2)°, and the 2-phenyl groups are
twisted against the phosphole rings with dihedral angles of
33.1(2)°.
Table 1. Screening of the Reaction Conditions for
Base-Promoted Intramolecular Cyclization in Eq 1
conditions
D
yielda incorpb
time
(h)
entry
base
solvent T (°C)
(%)
(%)
1
2
3
4
Et2Znc THF
Et2Znc toluene
n-BuLid THF
n-BuLid toluene
reflux
reflux
-40
7
8
6
9
96
92
81
0
50
96
23
40
12
a Yield of compound 3 monitored by 1H NMR using CH2Br2 as an
internal standard. b Percent deuterium incorporation at the 3-position of
compound 3 determined by 1H NMR. c A toluene solution of Et2Zn (1.1
M) was added to the solution of 1 at room temperature and the reaction
mixture was heated at the indicated temperature. d A hexane solution of
BuLi (1.61 M) was added at -78 °C, and the reaction mixture was kept at
the indicated temperature.
The Mes* group can be removed and replaced by a phenyl
group, as shown for 1,4-bis(3-benzo[b]phospholyl)benzene 9.
Reductive cleavage of the P-C (ipso carbon of the Mes* group)
bond was achieved by treatment with an excess of lithium metal,
and acidic aqueous quenching afforded the P-H derivative 10,
which was used for the subsequent reaction without further
purification. Thus, copper-mediated P-arylation9 of 10 followed
The synthesis of a variety of 3-substituted benzophospholes was
achieved by reactions of the 3-lithiobenzophosphole 2 with
electrophiles (Scheme 1). Direct reactions of 2 with electrophiles
(method a, Scheme 1) were first examined, two examples being
shown in Table 2. The reaction with benzaldehyde afforded a
secondary alcohol 4 in 68% isolated yield (entry 1, Table 2). The
(9) Gelman, D.; Jiang, L.; Buchwald, S. L. Org. Lett. 2003, 5, 2315–
2318.
2264
Org. Lett., Vol. 10, No. 11, 2008

Table 2. Synthesis of 2,3-Difunctional Benzo[b]phospholes
Scheme 2
.
Transformation of the Mes* Group on the
Phosphorus Center
According to the Protocol Shown in Scheme 1a
phole oxide) 11.10 Showing the longest absorption maximum
wavelength of 340 nm and an absorption edge wavelength of 415
nm, the UV absorption spectrum in CH2Cl2 indicated that 11 is
transparent in the visible to IR region. Photoexcitation at 300 nm
in CH2Cl2 caused blue emission (λemmax ) 468 nm) with a quantum
yield of 0.02. The cyclic voltammogram in THF showed a
reversible first reduction potential at -2.09 V. The potential is
shifted toward the positive side by ca. 0.5 V as compared with a
structurally equivalent bis(benzosilole) (the PhPdO moiety in 11
replaced by a Me2Si moiety).8 Thus, 11 has an electron-accepting
property similar to other known phosphorus-containing π-electron
systems.11 The electron drift mobility of compound 11 measured
by the time-of-flight technique using a vacuum-deposited film at
room temperature was found to be 5 × 10-6 cm2/Vs at an electric
field of 2.5 × 105 V/cm. This level of mobility does not warrant
immediate applications to organic electronics, but suggests that
certain structural modifications can lead to a fruitful outcome.
In conclusion, we have developed a BuLi-mediated cycliza-
tion of an (o-alkynylphenyl)phosphine 1 to 3-lithiobenzo[b]-
phosphole 2, which can then produce a variety of new
benzo[b]phosphole derivatives, including the bis-benzophosp-
hole 9. The cyclic voltammetry and charge mobility measure-
ments of the phosphine oxide 11 indicate electron-accepting
and -transporting abilities of benzophosphole oxide derivatives,
hence suggesting the utility of the present synthesis for
applications in organic electronics.
a Reaction conditions are summarized in Scheme 1, except for entry 6
(see Supporting Information). b Isolated yield based on 1 except for entry
6. c 0.36 equiv of p-diiodobenzene to 1 was used. d Isolated yield based on
p-diiodobenzene.
by oxidation with hydrogen peroxide afforded the P-phenylben-
1
zo[b]phosphole oxide 11 in 16% overall yield from 9. H, 13C,
Figure 1. ORTEP drawing of 1,4-bis(3-benzo[b]phospholyl)ben-
zene 9 (50% probability for thermal ellipsoids). Hydrogen atoms
Acknowledgment. This research was supported by KAK-
ENHI provided by MEXT/JSPS (to E.N., Grant No.
18105004) and the Global COE Program for Chemistry
Innovation.
are omitted for clarity.
and 31P NMR spectra of 11 indicated the presence of two
diastereomers. This example of the transformation of the Mes*
group together with the flexibility of the functionalization of the
3-positions as shown above demonstrates the utility of 3-lithio-
benzo[b]phosphole 2 as a viable module for the synthesis of
functionalized benzo[b]phospholes.
Supporting Information Available: Experimental details
and CIF file of compound 9. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL800684X
(10) Details on the measurements are given in the Supporting Informa-
tion.
The utility of the benzophosphole products as organic electronic
materials was examined briefly. We first examined the photo-
physical and electrochemical properties of the bis(benzo[b]phos-
(11) For example: Fukazawa, A.; Hara, M.; Okamoto, T.; Son, E.-C.;
Xu, C.; Tamao, K.; Yamaguchi, S. Org. Lett. 2008, 10, 913–916.
Org. Lett., Vol. 10, No. 11, 2008
2265