Synthesis and Photophysical Properties of λ5-Phosphinines as a Tunable Fluorophore

Article abstract of DOI:10.1021/jacs.7b13018

A practical synthesis of a variety of λ⁵-phosphinines, which show distinct fluorescence both in solution and solid state, is described. Both C4-selective electrophilic substitutions and the following conversions realized an easy preparation of a wide range of derivatives having several substituents for electronic modification, which provides the potential for fine-tuning of the photophysical properties.

Full text of DOI:10.1021/jacs.7b13018

Communication
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5
Synthesis and Photophysical Properties of λ ‑Phosphinines as a
Tunable Fluorophore
†
†
†
†
‡
‡
Naoki Hashimoto, Rika Umano, Yusuke Ochi, Kiyoka Shimahara, Jun Nakamura, Shigeki Mori,
Hidetoshi Ohta,† Yutaka Watanabe, and Minoru Hayashi*
†
,†
†Department of Materials Science and Biotechnology, Graduate School of Science and Engineering, Ehime University, 3 Bunkyo-cho,
Matsuyama 790-8577, Japan
‡
Division of Material Science, Advanced Research Support Center (ADRES), Ehime University, 2-5 Bunko-cho, Matsuyama
790-8577, Japan
*
S Supporting Information
5
Scheme 1. λ -Phosphinine Formed by the Reaction of
Phosphonium Salt 2 and Aldimines 3
ABSTRACT: A practical synthesis of a variety of λ5-
phosphinines, which show distinct fluorescence both in
solution and solid state, is described. Both C4-selective
electrophilic substitutions and the following conversions
realized an easy preparation of a wide range of derivatives
having several substituents for electronic modification,
which provides the potential for fine-tuning of the
photophysical properties.
luorophores attract great interest as functional materials
F
because of wide and general purposes in a variety of fields
1
including fluorescence probes. A variety of aromatic and
heterocyclic fluorophores have been created and modified for
tuning their properties as desired. Recently, fluorophores
including a phosphorus atom come into the spotlight because
Herein, we report a novel and versatile synthesis of
5
fluorescent λ -phosphinines based on our fortuitous discovery.
2
−4
Their photophysical properties tuned by the electronic
perturbation with several substituents introduced by the
transformations developed here are also described.
of their excellent properties.
Contrary to emerging
2
innovations about 5-membered phospholes, 6-membered
phosphacycles are relatively less investigated as a fluorophore
though the series of those compounds are known from 1960s
as phosphinines, a heavy analogue of pyridine. Among those
phosphacycles, λ -phosphinines having a phosphorus-ylide in
3
,4
5
We have identified the real substrates necessary for λ -
5
−7
phosphinine formation; one is bis(cyanomethyl)-phosphonium
11
5
salt 2, and the other is an aldimine. 3,4-Disubstituted 2,6-
5
dicyano-λ -phosphinine 1 (R = nPr) was formed almost
the cycle are unique molecules because they are structurally and
3
quantitatively when phosphonium salt 2 reacted with an excess
of aldimine 3 (Scheme 1).
Although a mechanism of this cyclization is not clear, we
electronically quite different from pyridine-like λ -phosphi-
4
,6
5
nines. Mar
̈
kl’s early extensive works established access to λ -
5
phosphinines via pyrylium salts. Recently, Kostyuk and
Matveeva reported several synthetic routes toward λ -
31
5
observed two ylidic intermediates by P NMR monitoring of
11
the reaction; they may be attributed to alkenyl ylide 4A
initially formed via double addition of the ylide to aldimines
and dihydrophosphinine 4B formed by the following electro-
phosphinines, via sigmatropic rearrangement of phosphonium
ylides and cycloaddition of phosphonium-iodonium ylides with
8
5
alkynes. In addition, λ -phosphinines have potential as a
fluorophore; Dimroth and Muller reported photophysical
8b−d
cyclization similar to the reaction reported by Kostyuk et al.
Further dehydrogenative aromatization of 4B gave λ -
phosphinine 1. Unfortunately, λ -phosphinine 1 (R = nPr),
having two substituents at the C3 and C4 positions, showed a
̈
7
5
5
4,9
features of λ -phosphinines including fluorescence. However,
limitations due to elaborating synthetic scheme prevented fine-
tuning of their properties; an easy, effective and versatile
5
5
low quantum yield (Φ : 0.02) despite its brilliant visible
synthetic method of λ -phosphinine derivatives will open up
F
fluorescence. We anticipated that the use of 1,3-dialdimine
instead of two moles of an imine can avoid the incorporation of
any substituent at the C3,C4,C5-positions, and can also bypass
the oxidation step. Indeed, the reaction of phosphonium salt 2
with 1,3-dialdimine 5 in the presence of DBU gave 2,6-dicyano-
their application.
We have serendipitously found a formation of a trace amount
of an unexpected compound with a distinct fluorescence,
5
during our study about a synthesis of new 3-oxo-λ -phosp-
1
0
hole. After the initial discovery of this fluorescent compound,
we made considerable efforts to track its formation, and finally
5
found a new synthetic route toward λ -phosphinine 1 (Scheme
Received: December 9, 2017
1
1
1).
©
XXXX American Chemical Society
A
DOI: 10.1021/jacs.7b13018
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
5
1
,1-diphenyl-λ -phosphinine 6a as a sole product in fairly good
1
2
yield (Scheme 2).
5
Scheme 2. Synthesis of the Parent λ -Phosphinine 6a
Figure 2. Frontier molecular orbitals of 6a calculated at the B3LYP/6-
3
1+G(d, p) level; left: HOMO, right: LUMO.
for incorporation of several substituents at the C4 position for
tuning the properties. Indeed, the reaction of 6a under the
Vilsmeier−Haack conditions gave 4-formyl derivative 6b in
good yield (Scheme 3a). 4-Bromophosphinine 6c was obtained
The result was seriously affected by the solvent used and
amount of the base. Several optimizations of the reaction
conditions revealed that use of 2 equiv of DBU in DMSO gave
the best results. Two cyano groups are necessary for the
effective formation of ylides during the cyclization. Noteworthy
is that the multistep transformation proceeded successfully at rt
with concurrent formation of two C−C bonds and cleavage of
two C−N bonds. It is no doubt that DBU plays essential roles
as a base (for deprotonation to form nucleophilic ylides) and an
5
Scheme 3. Several Conversions of 6a to 4-Substituted λ -
a
Phosphinines
+
acid (DBU-H formed by deprotonation will protonate the
amine to be eliminated). A plausible mechanism of the reaction
11
is shown in Scheme S5.
The structure of 6a was unequivocally determined by an X-
13
ray crystallographic analysis (Figure 1). The asymmetric unit
a
(
a) POCl (1.2 equiv), DMF, 60 °C, 3 h (84%); (b) Py·HBr (1.0
3
3
equiv), CH Cl , rt, 1 h (88%); (c) Ph PCHPh (1.1 equiv), THF, rt,
1
3
2
2
3
Figure 1. Crystal structure of 6a. (Left: topview, right: sideview)
Only one of three structures in asymmetric unit is shown. Hydrogen
atoms are omitted for clarity. Thermal ellipsoids are drawn at the 50%
probability level. Selected bond lengths [Å] and angles [°]: P(2)−
C(6) 1.747(8), P(2)−C(10) 1.750(9), C(6)−P(2)−C(10) 102.3(4),
C(31)−P(2)−C(37) 105.9(4).
1
2 h (56%); (d) Phenylacetylene (1.2 equiv), 5 mol % PdCl (dppf),
2
1
0 mol % CuI, DBU (1.5 equiv), DMF, 80 °C, 12 h (69%); (e)
PhB(OH) (1.7 equiv), 4 mol % PdCl (PPh ) , 2 M Na CO aq. (8
2
2
3
2
2
3
equiv), toluene−H O−EtOH, reflux, 24 h (76%).
2
by electrophilic bromination with pyridinium bromide
perbromide (Scheme 3b). Smooth progress of these electro-
philic substitutions indicates that sufficient nucleophilicity at
the C4 is preserved despite two electron-withdrawing cyano
groups at the C2- and C6-positions. Further conversions of
these two fundamental compounds, 6b and 6c, allow us to
prepare 4-alkenyl, 4-alkynyl and 4-aryl derivatives. 4-Formyl-
phosphinine 6b could be converted into 4-alkenylphosphinine
derivatives by the Wittig olefination. The reaction of
benzylidenephosphorane with 6b at rt for 12 h gave the
of 6a contains three independent molecules with similar
metrical data. The 6-membered ring is distorted around the
14
phosphorus but is almost flat. The phosphorus atom is
approximately proper tetrahedral orientation; therefore two
phenyl groups are extended over the phosphinine plane.
Essentially equal two P−C bond lengths (P2−C6:1.747 Å and
P2−C10 1.750 Å) show no existence of bond alternation inside
the phosphinine ring. These characteristics are nearly identical
5
to the previously reported λ -phosphinines except small
8a,b,e
15
differences of P−C bond lengths.
desired 4-β-styrylphosphinine 6d in 56% yield (Scheme 3c).
DFT calculation of 6a at B3LYP/6-31+G(d,p) level showed
that both HOMO and LUMO are delocalized over the
phosphinine ring and cyano groups. It is noteworthy that the
HOMO shows a significant orbital contribution at the C4
position, whereas no contribution of the C4 to the LUMO is
estimated, as illustrated in Figure 2. Thus, an electronic
modulation at the C4 position will mostly modulate the
HOMO level, but it will affect essentially little to the LUMO.
This is favorable to tune the photophysical properties of the λ -
phosphinines by substitution at the C4 position.
The C4 should be the most nucleophilic because of an ylidic
nature of PC bond and resonance structure of the
phosphinine ring; electrophilic substitution would be effective
4-Bromo derivative 6c was subjected to the Sonogashira and
the Suzuki−Miyaura cross-coupling reactions to give the 4-
alkynyl and the 4-aryl derivatives, respectively (Scheme 3d,e).
The reaction of 6c with phenylacetylene in the presence of Pd
and Cu catalysts and DBU in DMF gave 4-(2-phenylethynyl)-
phosphinine 6e in 69% yield. DPPF was the best ligand in this
coupling reaction. The reaction of 6c with phenylboronic acid
in the presence of Pd catalyst and aqueous base successfully
afforded 4-phenylphosphinine 6f in 76% yield. The success of
these fundamental conversions indicated that fine electronic
tunings at the C4-position would be available based on these
schemes by using more electronically modified substrates in
these well-established reactions.
5
B
DOI: 10.1021/jacs.7b13018
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
5
As described, the most important feature of these series of λ5-
phosphinines is the presence of two cyano groups at C2- and
C6-positions. DFT calculations revealed that two cyano groups
The photophysical properties of the λ -phosphinines 6a−6f
5
were examined (Figure 3, Table 1). All prepared λ -
11
electronically impact to both HOMO and LUMO. For
example, HOMO of 6a (−5.82 eV) lies about 1 eV higher than
5
that of λ -phosphinine 7 without cyano groups (Figure S4), and
LUMO of 6a (−2.23 eV) lies about 1 eV lower than that of 7.
The LUMO levels of 6a−6f are substantially the same (ΔE <
0
.2 eV) whereas the HOMO levels are varied at a range of 0.94
eV, as anticipated (vide supra). Small HOMO−LUMO gaps of
6
a−6f resulted in absorption and emission of visible light of
which wavelength is mainly affected by its HOMO. The low-
lying LUMO characterized this core as an electron-accepting
part. On the other hand, two cyano groups did not affect
aromaticity of the phosphinine; this type of phosphinine
naturally shows low aromaticity (NICS(0) of 7 is −2.53,
NICS(0) of 6a is −2.46). However, two cyano groups play a
crucial role to stabilize the ylidic structure of the phosphinine; 7
5
Figure 3. (a) Ambient and fluorescence images of λ -phosphinines
(
6b, 6a, 6c, 6f, 6e, 6d: left to right); (upper) in CHCl irradiated at
52 nm; (middle) solid under ambient light; (bottom) solid irradiated
at 352 nm. (b) Normalized emission spectra of 6a−6f.
3
3
5
5
Table 1. Photophysical Data for λ -Phosphinines
was reported as highly reactive and air-sensitive molecule, but
the phosphinines reported here are thermally and chemically
quite stable and remain intact for a long time even in the air in
the solid state.
λabs,max/nm
λem,max/nm
F
λem,max/nm
,
bd
a
,
c
a
,
d
Compd
(log ε)
(Φ /%)
(Φ /%)
F
16,17
6
6
6
6
6
6
a
b
c
d
e
f
458 (4.22)
434 (4.09)
482 (4.22)
506 (4.05)
489 (4.17)
480 (4.14)
491 (92)
463 (72)
519 (52)
581 (13)
538 (61)
525 (75)
561 (14)
514 (42)
554 (5)
In conclusion, we have synthesized a series of novel
5
fluorescent 2,6-dicyano-λ -phosphinines via newly developed
one-pot, multistep ring formation. Regioselective functionaliza-
616 (5)
5
tion and further conversions enabled preparation of λ -
572 (11)
557 (17)
phosphinines with several substituents at the C4-position,
which were suitable for tuning their photophysical properties.
More detailed study for this new fluorophore is now under
investigation.
a
b
c
In CHCl . In solid state. Only the longest absorption maxima is
3
d
shown. Emission maxima upon excitation at the absorption maximum
wavelength.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b13018.
■
phosphinines 6a−6f showed distinct fluorescence. Substituent
at the C4-position significantly influenced both the absorption
and the emission, both in solution and solid phase. The images
of fluorescence both in solution and in the solid state, and the
normalized emission spectra of 6a−6f are shown in Figure 3.
The parent phosphinine 6a shows absorption maxima at 458
*
S
Structural analysis, mechanistic investigations and full
experimental and computational details (PDF)
NMR data (ZIP)
X-ray crystallographic data for 6a (CIF)
X-ray crystallographic data for 6d (CIF)
4
nm with ε of 10 level. Emission maxima of 6a appeared at 491
nm with excellent quantum yield (Φ = 0.92) in CHCl
F
3
5
solution. Noteworthy is that most of the symmetrical λ -
phosphinines showed distinct fluorescence with high quantum
yields. As anticipated by the DFT calculations (vide supra), an
electron-withdrawing substituent caused hypsochromic shifts
both in absorption and emission (formyl, 6b; 24 nm/28 nm).
AUTHOR INFORMATION
Corresponding Author
*mhayashi@ehime-u.ac.jp
ORCID
Hidetoshi Ohta: 0000-0002-8767-5689
Minoru Hayashi: 0000-0001-9672-1758
■
4
-Bromo derivative 6c showed bathochromic shifts (24 nm/28
nm), due to efficient electron-donation over the electro-
negativity of the bromine atom. 4-Alkenyl, 4-alkynyl and 4-aryl
derivatives 6d−6f also showed bathochromic shifts, at emission
Notes
maxima range from 525 to 581 nm. Except for 6d, symmetrical
5
The authors declare no competing financial interest.
2
0
,6-dicyano-λ -phosphinines showed high quantum yields (Φ :
F
.92−0.52). Two cyano groups appeared to be essential for
5
ACKNOWLEDGMENTS
high quantum yields; quantum yields of similar λ -phosphinines
■
with two heteroaryls instead of cyano groups are reported as
This work was supported by JSPS KAKENHI Grant Number
JP15K05430 (Grant-in-Aid for Scientific Research(C)) and
partially supported by JSPS KAKENHI Grant Number
JP15H00754 (Grant-in-Aid for Scientific Research on In-
novative Areas “New Polymeric Materials Based on Element-
Blocks (No. 2401)”. We also thank Division of Applied Protein
Research (APR), the Advanced Research Support Center
(ADRES), Ehime University for the measurements of NMR
spectra. M.H. received funding from JSPS (JP15K05430 and
JP15H00754).
9
0
.05−0.20 (Table S2), where the symmetrical derivative also
4b
showed better quantum yield. A relatively weak fluorescence
of 4-alkenyl derivative (Φ : 0.13) is attributed to nonemissive
F
transition by its stilbene-like structure. Those compounds are
also emissive in the solid state, probably because the tetrahedral
orientation of the phosphorus should effectively avoid strong
π−π interaction, which will cause quenching of the emission in
the solid state. Solid state fluorescence showed substantial red
shifts with relatively high quantum yields.
C
DOI: 10.1021/jacs.7b13018
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
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11) See Supporting Information for details.
(
12) Although 1,3-dialdimine 5 exists as a conjugate imine-enamine
form, it was depicted as a dialdimine form for an analogy to Scheme 1.
(
13) Results of crystallographic analyses were submitted as CIF file.
(
14) Deviations of each atom location from the mean plane of
phosphinine ring are less than 0.023 Å.
15) The structure of 6d was confirmed by an X-ray crystallographic
analysis; see: Supporting Information.
16) Decomposition was observed when a chloroform solution of 6a
(
(
and 6c left in the air with exposure to the light. No decomposition was
observed with shade.
(
17) 2,4,6-Triaryl derivatives are also reported as air and moisture
4b
stable solid.
D
DOI: 10.1021/jacs.7b13018
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX