Palladium-catalyzed direct synthesis of phosphole derivatives from triarylphosphines through cleavage of carbon-hydrogen and carbon-phosphorus bonds

Article abstract of DOI:10.1002/anie.201307115

(Phosp)hole in one: A palladium-catalyzed synthesis for directly assembling phosphole skeletons from triarylphosphines through C-H and C-P bond cleavage was developed. This approach overcomes several of the limitations of the so far reported methods. Phospholes bearing a range of functionalities (including Br, F, CO₂Me, Ac, and CN) and an array of fused rings (naphthalenes, anthracenes, furans, and pyrroles) can be easily synthesized. Copyright

Full text of DOI:10.1002/anie.201307115

Angewandte
Chemie
DOI: 10.1002/anie.201307115
Heterocycle Synthesis
Hot Paper
Palladium-Catalyzed Direct Synthesis of Phosphole Derivatives from
Triarylphosphines through Cleavage of Carbon–Hydrogen and
Carbon–Phosphorus Bonds**
Katsuaki Baba, Mamoru Tobisu,* and Naoto Chatani*
Phospholes have recently received much attention as promis-
ing organic materials because of their characteristic optical
and electronic properties, which are derived from the
phosphorus-bridged 1,3-dienic p system.[1] The method most
frequently used for the synthesis of phospholes involves the
À
nucleophilic substitution of a P X bond with a stoichiometric
amount of an organometallic species such as organolithium or
organomagnesium reagents.[2] The issue of functional group
compatibility associated with this classical method has been
addressed to some extent by using transition metal catalysis.
Catalytic [2+2+2] cycloaddition of dialkynylphosphines with
polyynes has been used for the synthesis of helicene
analogues of phospholes.[3] More versatile synthesis is enabled
À
by catalytic C P bond formation reactions. The intramolec-
ular cross-coupling of aryl halides or their equivalents with
hydrophosphines has been successfully used in the synthesis
of a phosphole skeleton (Scheme 1a).[1h] However, this
À
Scheme 1. Catalytic synthesis of phospholes through C P bond forma-
tion.
method still needs considerable improvement in terms of
the degree of functionalization of the starting material and
the instability of a hydrophosphine group. In this context,
Takai and Kuninobu et al. made notable progress by devel-
oping a palladium-catalyzed synthesis of dibenzophosphole
oxides by dehydrogenative cyclization of hydrophosphine
oxides (Scheme 1b).[4] In view of the widespread availability
and stability of triarylphosphines, a more synthetically
valuable approach would involve intramolecular cross-cou-
pling between triarylphosphine and an arene through simul-
taneous cleavage of C P and C H bonds (Scheme 1c).
Herein, we report the realization of a catalytic reaction of
this type.
À
À
We expected that the reaction of biphenylphosphine 1a
with a suitable transition metal complex would afford metal-
[*] K. Baba, Prof. Dr. N. Chatani
Department of Applied Chemistry, Faculty of Engineering
Osaka University
lacycle
2 through a common cyclometalation process
(Scheme 2).[5] If one of the phenyl groups on the phosphorus
Suita, Osaka 565-0871 (Japan)
E-mail: chatani@chem.eng.osaka-u.ac.jp
Dr. M. Tobisu
Center for Atomic and Molecular Technologies
Graduate School of Engineering, Osaka University
Suita, Osaka 565-0871 (Japan)
E-mail: tobisu@chem.eng.osaka-u.ac.jp
Scheme 2. Working hypothesis.
[**] This work was supported by a Grant-in-Aid for Scientific Research on
Innovative Areas “Molecular Activation Directed toward Straight-
forward Synthesis” and “Organic Synthesis Based on Reaction
Integration” from MEXT (Japan) and ACT-C FS from JST (Japan).
K.B. expresses his special thanks for JSPS Research Fellowship for
Young Scientists. We thank Professors Tetsuya Sato and Masahiro
Miura (Osaka University) for their assistance in obtaining solid-
state photoluminescence spectra, Dr. Nobuko Kanehisa (Osaka
University), Prof. Masato Ohashi (Osaka University), and Prof.
Tetsuaki Fujihara (Kyoto University) for X-ray crystallographic
analysis of 29, and the Instrumental Analysis Center, Faculty of
Engineering, Osaka University for MS and HRMS.
center in 2 is eliminated, the desired phosphole 3a would be
À
formed. Although such metal-mediated C P bond cleavage
of a simple triarylphosphine is apparently a challenge,[6–9]
À
À
reports by us and Xi and co-workers on C Si and C Ge
bond cleavage in the catalytic syntheses of siloles[10] and
germoles[11] via intermediates analogous to 2 encouraged us to
pursue the development of this new mode of phosphole
synthesis.
Not surprisingly, a simple extension of the methods for Si
and Ge did not work with phosphorus-based substrate 1a
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201307115.
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because of the difference in fundamental properties between
groups 14 (Si and Ge) and 15 (P). After several experiments,
the expected reaction was found to occur by mixing 1a with
a catalytic quantity of Pd(OAc)2 at 1608C (Scheme 3).[12]
Scheme 3. Palladium-catalyzed synthesis of phosphole.
Since the generated phosphole 3a is susceptible to oxidation
upon workup, the product was isolated as oxide 4a by
treatment with aqueous H2O2. Alternatively, complexation
with BH3 afforded 3a·BH3 as a stable and crystalline solid.
Notably, this synthesis can be conducted on the gram scale
without any modification (1.5 g of 4a were synthesized
successfully). A biphenyl bearing a PMePh group, as in 1b,
underwent palladium-catalyzed cyclization to deliver P-alkyl
phosphole oxide 4b through exclusive cleavage of the P–Ar
bond rather than the P–Me bond.[13]
This operationally trivial method was successfully applied
to the synthesis of a diverse array of phospholes (Scheme 4).
The high functional group tolerance allows access to a range
of electronically different phospholes bearing ether (6 and
16), amine (7 and 15), ketone (8), ester (9), nitrile (10), and
fluoride (11) groups. The compatibility of chlorides and
bromides (as in 12 and 13), which can serve as handles for
further structural modification of the phosphole skeleton, is
Scheme 4. Reaction scope. Reaction conditions: biarylphosphine
(0.30 mmol), Pd(OAc)2 (0.015 mmol), and toluene (1.0 mL) in
a sealed tube at 1608C, for 12 h. Yields of isolated products are
shown. [a] The reaction was set up in a glovebox because of the
sensitivity of the starting phosphine to oxygen.
À
particularly useful (see Scheme 8). C P bond formation can
occur smoothly with substrates bearing an ortho substituent to
deliver 1-substituted dibenzophospholes, as in 14 and 15.
Substrates bearing a meta substituent underwent regioselec-
tive cyclization at the less hindered site to form 17 as the
major product. Unlike the substrates required for the
reported methods for the synthesis of phospholes
(Scheme 1a,b), the starting biarylphosphines used in this
study are readily accessible. Some of them are commercially
available ligands (for example, 15 is derived from a ligand
known as PhDavePhos[14]). Others can be rapidly prepared
from the commercially available (2-bromophenyl)diphenyl-
phosphine (26) through a cross-coupling reaction, and the
subsequent phosphole formation can be performed without
isolation of the biarylphosphine intermediate 27 (Scheme 5).
The modularity of this synthesis enables various p systems,
including naphthalenes (20–22), phenanthrenes (19), furans
(23), pyrroles (24), and pyridines (25), to be incorporated into
the phosphole framework.
Scheme 5. Synthesis of phosphole 28 from 26. dba=dibenzylidene-
acetone.
A possible mechanism is depicted in Scheme 6. The
cyclopalladated complex B.[15] Subsequent reductive elimina-
tion from B leads to the formation of phosphonium C along
reaction is initiated by the reaction of PdII with 1a to form the
2
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1008C led to the formation of phosphole 4a (Scheme 7b).
This mechanistic scenario is also consistent with the observa-
tion of cyclization of 1c, in which the more electron-deficient
aryl group on the phosphorus was eliminated preferentially
over the phenyl group (Scheme 7c).[20] Third, by examining
the reaction of 1d (Scheme 7d), the fate of the cleaved aryl
group was determined to be the corresponding arene, as is
proposed in Scheme 6 .
The functionalized phospholes obtained in the present
study are amenable to further elaboration. For example, the
Suzuki–Miyaura reaction of bromophosphole 13 followed by
catalytic C–H amination[21] enables rapid assembly of the
extended p-conjugated molecule 34 (Scheme 8).
Scheme 6. A possible mechanism.
with Pd0.[6a–c,16] The phosphonium C immediately undergoes
oxidative addition to Pd0, which is in close proximity, to
provide phosphole 3a and {PhPd(OAc)} (D) through cleav-
[8a,b,17]
À
age of a C P bond.
Finally, D is protonated by AcOH,
which is released in the initial cyclometalation step, to
regenerate Pd(OAc)2 (A).[18]
Several experimental results that support our proposed
mechanism were obtained (Scheme 7). First, cyclopalladated
complex B could indeed be synthesized by the reaction of 1a
with Pd(OAc)2 (1 equiv) at 508C. X-ray crystallographic
analysis revealed that the complex was formed as a dimer (29,
Scheme 7a). Heating a solution of 29 in toluene at 1008C
afforded phosphole 4a, thus suggesting that the metallacycle
29 is a plausible intermediate for the catalytic cycle.[19]
Second, the potential intermediacy of phosphonium salt C
Scheme 8. Synthetic elaboration of 13. Bn=benzyl.
In summary, a palladium-catalyzed method for the syn-
thesis of phospholes from triarylphosphines has been devel-
oped. Synthetic advantages over reported methods include
1) operational simplicity, 2) direct use of simple starting
materials, 3) excellent functional group compatibility, and
4) high modularity of the aromatic component to be incorpo-
rated. These features enable rapid access to a structurally
diverse array of phosphorus-based p systems, the physical
properties of which are of significant interest.[22] The appli-
cation of this method to the synthesis of elaborated phosphole
derivatives and other heterocyclic compounds is being
actively investigated by us.
À
in the C P bond cleavage process was confirmed. The
reaction of independently synthesized 30 with [Pd(PPh3)4] at
Received: August 13, 2013
Published online: && &&, &&&&
Keywords: carbon-hydrogen bond cleavage ·
.
carbon-phosphorus bond cleavage · homogeneous catalysis ·
palladium · phosphole
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À
[13] As mentioned later, C P bond cleavage is likely to occur
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À
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À
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À
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4
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Angew. Chem. Int. Ed. 2013, 52, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Heterocycle Synthesis
(Phosp)hole in one: A palladium-cata-
lyzed synthesis for directly assembling
phosphole skeletons from triarylphos-
K. Baba, M. Tobisu,*
N. Chatani*
À
À
&&&& — &&&&
phines through C H and C P bond
cleavage was developed. This approach
overcomes several of the limitations of
the so far reported methods. Phospholes
bearing a range of functionalities
(including Br, F, CO2Me, Ac, and CN) and
an array of fused rings (naphthalenes,
anthracenes, furans, and pyrroles) can be
easily synthesized.
Palladium-Catalyzed Direct Synthesis of
Phosphole Derivatives from
Triarylphosphines through Cleavage of
Carbon–Hydrogen and Carbon–
Phosphorus Bonds
Angew. Chem. Int. Ed. 2013, 52, 1 – 5
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5
These are not the final page numbers!