Paving the Way to Novel Phosphorus-Based Architectures: A Noncatalyzed Protocol to Access Six-Membered Heterocycles

Article abstract of DOI:10.1002/anie.201507960

Phosphorus-based heterocycles provide access to materials with properties that are inaccessible from all-carbon architectures. The unique hybridization of phosphorus gives rise to electron-accepting capacities, a large variety of coordination reactions, a

Full text of DOI:10.1002/anie.201507960

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Angewandte
Communications
International Edition: DOI: 10.1002/anie.201507960
German Edition: DOI: 10.1002/ange.201507960
Phosphorus Heterocycles
Paving the Way to Novel Phosphorus-Based Architectures:
A Noncatalyzed Protocol to Access Six-Membered Heterocycles
Carlos Romero-Nieto,* Alicia López-Andarias, Carolina Egler-Lucas, Florian Gebert,
Jens-Peter Neus, and Oliver Pilgram
Abstract: Phosphorus-based heterocycles provide access to
materials with properties that are inaccessible from all-carbon
architectures. The unique hybridization of phosphorus gives
rise to electron-accepting capacities, a large variety of coordi-
nation reactions, and the possibility of controlling the elec-
tronic properties through phosphorus postfunctionalization.
Herein, we describe a new noncatalyzed synthetic protocol to
prepare fused six-membered phosphorus heterocycles. In
particular, we report the synthesis of novel phosphaphenalenes.
These fused systems exhibit the benefits of both five- and six-
membered phosphorus heterocycles and enable a series of
versatile postfunctionalization reactions. This work thus opens
up new horizons in the field of conjugated materials.
tional architectures, that is, materials with temperature-
dependent luminescence, electrochromism, liquid crystallin-
[
3]
ity, supramolecular self-assembly, and gel properties. Unrav-
eling the full potential of phosphorus heterocycles requires,
however, the development of novel systems. In this context,
improved synthetic protocols to access five- and six-mem-
bered phosphorus heterocycles have recently emerged. They
[
4]
are largely based on radical and metal-catalyzed reactions
[
5]
[6]
[7]
[8]
with Cu, Al, Ag, and Pd.
In view of synergistically merging the intriguing proper-
ties of five- and six-membered phosphorus heterocycles, we
envisaged the development of novel phosphaphenalene
derivatives (Figure 1). Particularly, we targeted phosphorus-
based architectures exhibiting: 1) high electron delocaliza-
5
4
T
(
he unique properties of phosphorus heterocycles are
a continuous source of scientific breakthroughs. Phosphinines
Figure 1), six-membered phosphorus heterocycles, offer new
perspectives in coordination chemistry and catalytic trans-
tion, 2) a reversibly accessible l s phosphorus center,
3) stability in air, and 4) versatile postfunctionalization reac-
tions.
To prepare the phosphaphenalenes, we investigated con-
ditions suitable for the construction of the phosphorus ring
from phenylphosphane-substituted naphthalene derivatives.
Our first attempts to isolate the corresponding naphthyl-
chlorophenylphosphane from A (Scheme 1) were, however,
unsuccessful. Further investigations revealed a new noncata-
lyzed protocol to access six-membered phosphorus hetero-
cycles. We observed the formation of the phosphorus ring to
occur simply when the lithiated naphthalene A was treated
with an equimolecular amount of dichlorophenylphosphane
at 08C. To obtain air-stable heterocycles, we subsequently
exposed the reaction mixture to H O , according to estab-
[1]
formations; they exhibit high electron delocalization over
the whole ring and special s-donating and p-accepting
properties. In turn, the five-membered analogues, phospholes
(
Figure 1), are at the center of materials science. The
3
3
particular nonhybridization of the l s phosphorus atom
and its capacity to reversibly reach the l s state have led to
materials with outstanding optoelectronic properties. Thus,
some of us recently developed phosphole-based multifunc-
5
4
[2]
2
2
[
9]
lished procedures.
Motivated by this finding and in order to explore the
synthetic scope of this new synthetic protocol, we expanded
our studies to a set of substrates A containing different
aromatic substituents (Scheme 1). Thus, our methodology was
found to be compatible with a variety of both substituted and
unsubstituted thiophenes; 1a,b and 2a,b are accessible using
our standard conditions. Compound 3, on the other hand, can
only be obtained by increasing the reaction temperature to
Figure 1. Molecular structures of phosphinines (left), phospholes
5
08C in a modified protocol. Other electron-rich heterocycles
(right), and designed phosphaphenalene (bottom).
such as furan and pyrrole, as well as benzothiophene lead to
the fused phosphaphenalenes 4, 5, and 6, respectively. To
further validate the versatility of the reaction, we also tested
aromatic hydrocarbons and obtained the phenyl- and naph-
thalene-substituted phenalenes 7 and 8. Accessing the pyri-
dine derivative 9 demonstrated, moreover, the compatibility
of our synthetic protocol with electron-deficient heterocycles.
To get further insight into the extension of the cyclization,
we targeted the preparation of five- and seven-membered
phosphorus rings (Scheme 2). Reaction of 10 under our
[
*] Dr. C. Romero-Nieto, A. López-Andarias, Dr. C. Egler-Lucas,
F. Gebert, J. P. Neus, O. Pilgram
Organisch-Chemisches Institut
Ruprecht-Karls-Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
E-mail: carlos.romero.nieto@oci.uni-heidelberg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201507960.
1
5872
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Scheme 3. Proposed mechanism.
according to a classical electrophilic aromatic substitution
mechanism. Major difficulties in isolating the chlorophos-
phane intermediate prevented us from direct experiments to
elucidate the reaction mechanism in greater detail. To
circumvent this bottleneck, we turned to low-temperature
31
1
P{ H} NMR measurements (Figure 2). The results are
consistent with our hypothesis. In situ monitoring of the
reaction to obtain 5 at À808C allowed us to detect the
formation of the chlorophosphane intermediate with a singlet
[11]
at d =+ 86.2 ppm. Surprisingly, several experiments indi-
cated the formation of the cyclized product already at low
temperature; that is, appearance of a singlet at d =
À46.4 ppm. When we increased the temperature stepwise,
the signal at d =+ 86.2 ppm progressively faded away giving
rise to the fully cyclized product between À30 and À208C.
Finally, treatment with H O afforded a singlet at d =+ 8.6
2
2
Scheme 1. Noncatalyzed reaction to access fused phosphaphenalene
derivatives 1–9.
ppm, which is characteristic of the oxidized phosphaphena-
lenes 5 (see the Supporting Information). To sum up, we were
able to detect the progressive formation of the cyclized
phosphorus ring from its chlorophenylphosphane precursor,
without the mediation of any catalyst. All fused phosphaphe-
nalenes were characterized by standard analytical techniques
[12] 31
1
(see the Supporting Information).
P{ H} NMR spectra of
1–9 are characterized by a singlet whose chemical shift varies
from d = 6.0 to 10.1 ppm.
Scheme 2. Attempts to access five- and seven-membered phosphorus
heterocycles.
standard and modified conditions led exclusively to the
formation of 12. In turn, when we exposed 13 to our synthetic
conditions, we were also unable to detect the formation of
derivative 14. The latter results are in consonance with the
reaction enthalpies obtained from DFT calculations (see the
Supporting Information). Whereas the formation of six-
membered heterocycles appears exothermic, the annulations
of five- and seven-membered rings correlate with endother-
mic processes. Thus, our methodology is found to be highly
selective for the synthesis of six-membered phosphorus
heterocycles.
A plausible mechanism for the cyclization reaction is
shown in Scheme 3. Phosphorus atoms can act as either
[2f, 10]
nucleophiles or electrophiles.
We therefore propose
3
1
1
a nucleophilic attack of the Ar peripheral ring on the
phosphorus center followed by the elimination of HCl,
Figure 2. In situ P{ H} NMR spectra of the synthesis of 5 at
increasing temperatures from À808C to 258C.
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Scheme 4. Postfunctionalization reactions of 3: a) HSiCl , 1008C;
3
Figure 3. X-ray structures of a) 3, top view, b) 3, front view, c) 5, and
d) 9. Thermal ellipsoids at the 50% probability level; hydrogen atoms
omitted for clarity. Selected bond lengths [Š] for 3: C1–C2 1.441(8),
C2–C3 1.465(9), C3–C4 1.439(9), C4–C5 1.434(8), C1–C6 1.364 (8),
C2–C7 1.385(8); for 5: C1–C2 1.392(5), C2–C3 1.459(5), C3–C4
b) H O , 08C; c) Au(tht)Cl; d) P(NMe ) ; e) NBS/AcOH; f) NIS/
2
2
2 3
AcOH; g) 2-(tributylstannyl)thiophene, Pd(PPh ) , 1208C. NBS=N-
3
4
bromosuccinimide, NIS=N-iodosuccinimide, tht=tetrahydrothio-
phene.
1
.446(5), C4–C5 1.440(5), C1–C6 1.419(6), C6–C7 1.346(6); for 9: C1–
C2 1.399(5), C2–C3 1.485(5), C3–C4 1.442 (5), C4–C5 1.425 (5), C1–
C6 1.398 (5), C2–C7 1.400(5), C7–C8 1.371(6).
on both the phosphorus atom and the main framework
5
4
(
Scheme 4). Whereas l s phosphorus centers provide air and
3
3
moisture stability, l s centers have attracted particular
The most interesting structural features were available
from X-ray diffraction analyses. Figure 3 shows the molecular
attention as they enable a wide array of reversible reactions
[9b,c,13,14]
with Lewis acids and transition metals.
Thus, we
[
13]
structures of 3, 5, and 9 in the solid state.
All three
focused on establishing suitable conditions to reversibly
5
4
3 3
structures are essentially planar (Figure 3b and Figures S2
and S3 in the Supporting Information); 5 exhibits a slight twist
of 12.28 due to the repulsion between the methyl group of the
pyrrole and the naphthalene moiety (Figure S2). Particularly
in 3, the six-membered phosphorus heterocycle does not
exhibit any bond alternation; the bond lengths are in the
range of 1.43–1.46 Š. A similar scenario is known for
convert the l s center into its l s relative. As a result, we
found that treatment of 3 with HSiCl at 1008C quantitatively
3
5
4
3 3
reduces its l s phosphorus atom into the l s center of 15
(Scheme 4). The latter compound was found to be very
versatile. Treatment of 15 with Au(tht)Cl leads to the gold
derivative 16; this complexation is quantitatively reversed by
the reaction with P(NMe ) . In turn, the oxidation of 15 with
2
3
[
1a]
phosphinines. Compounds 5 and 9 exhibit shorter C1-C2
distances (Figure 3). The fused heterocycles, pyrrole and
pyridine, appear nevertheless distorted; that is, they feature
irregular bond length distribution. The latter is consistent
with a high degree of p-conjugation. DFT calculations
provide further information on the electronic distribution
H O2 at 08C regenerates the pentavalent state of the
2
phosphorus atom. Moreover, compound 3 can be regioselec-
tively halogenated at the a positions of the sulfur atom by
treatment with N-bromosuccinimide, providing derivative 17.
Asymmetric functionalization is particularly appealing for
materials development. In this context, 3 can be monohalo-
genated to obtain 18 by simple treatment with N-iodosucci-
nimide. Finally, 17 can also be converted by selective Stille
cross-coupling into the monosubstituted 18. This derivative
presents great potential as a building block for obtaining
further extended systems.
(
see the Supporting Information). The frontier orbitals of 3, 5,
and 8 are fully delocalized over the entire fused systems, with
a large contribution of the phosphorus center in both HOMO
and LUMO. Finally, the X-ray crystallographic data reveal
different angles between the exocyclic phenyl ring and the
main framework. The latter angles strongly differ as a function
of the fused aromatic ring: from 114.98 for 3 to 123.38 and
To conclude, we have discovered a new non-catalyzed
synthetic protocol to access fused six-membered phosphorus
heterocycles. The versatility of this reaction enables preparing
fused phosphaphenalenes with a wide variety of heterocycles
as well as with aromatic hydrocarbons. The new phospha-
phenalene derivatives synergistically converge properties
from the five- and six-membered phosphorus heterocycles;
1
24.58 for 5 and 9, respectively. This phenomenon was already
observed in extended phosphole derivatives; it is attributed to
[14]
different electronic densities at the phosphorus center.
The evaluation of the postfunctionalization reactions is
commonly employed to ascertain the potential of phosphorus
[15]
5
4
heterocycles as promising building blocks.
To prove the
that is, a) high electron delocalization, b) reversible l s
versatility of our phosphaphenalene derivatives, we repre-
sentatively targeted the postfunctionalization reactions of 3
center and c) versatile postfunctionalization reactions. Alto-
gether, both this new synthetic protocol and the phospha-
1
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Angew. Chem. Int. Ed. 2015, 54, 15872 –15875

Angewandte
Chemie
phenalene structures introduce new opportunities to develop
superior phosphorus-based architectures. Detailed spectro-
scopic investigations to further corroborate the potential of
the new phosphaphenalenes as building blocks for functional
materials are currently underway.
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[
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13] Crystal data for 3: (C H OPS): M = 332.33, T= 200(2) K,
2
0
13
r
monoclinic, space group C2/c, a = 29.618(4), b = 14.9711(18), c =
Keywords: cyclization · phosphaphenalene ·
phosphorus heterocycles · postfunctionalization
3
À3
1
6.587(2) Š, V= 6372.9(13) Š , Z = 16, 1calcd = 1.38 gcm , m =
À1
0
.30 mm , l = 0.71073 Š, qmax = 22.7, 16395 measured reflec-
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How to cite: Angew. Chem. Int. Ed. 2015, 54, 15872–15875
Angew. Chem. 2015, 127, 16098–16102
2
F = 1.04, R = 0.068, wR = 0.136 (I > 2s(I)), largest difference
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2
À3
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(
C H NO P): M = 347.33, T= 200(2) K, monoclinic, space
2
1
18
2
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Published online: November 9, 2015
guchi, C. Wang, A. Fukazawa, M. Taki, Y. Sato, T. Sasaki, M.
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