Selective Synthesis of (Z)-Diazadiphosphafulvalene from 2,2′-bis-Azaphosphindole

Article abstract of DOI:10.1021/acs.orglett.7b03971

The unprecedented 2,2′-bis(azaphosphindole) has been synthesized via a new route. Reaction with NaH afforded a dianion derivative 5, which is easily transformed to alkylated bis(azaphosphindole) or (Z)-P,P,N,N-cisoid diazadiphosphafulvalene. The reaction features good regioselectivity and high steroselectivity. Relatively strong fluorescence is observed with diazadiphosphafulvalenes. The X-ray crystal structure analysis showed that dianion ligand 5 is bonded to two Na atoms in a bridging cis-fashion, which allows the synthesis of diazadiphosphafulvalene in a highly stereoselective approach.

Full text of DOI:10.1021/acs.orglett.7b03971

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Selective Synthesis of (Z)‑Diazadiphosphafulvalene from 2,2′-bis-
Azaphosphindole
Haiyang Huang,† Huiying Luo,‡ Guanyu Tao,† Weihua Cai,‡ Jing Cao,*,‡ Zheng Duan,*,†
and Franco̧
is Mathey*,†
†College of Chemistry and Molecular Engineering, International Phosphorus Laboratory, International Joint Research Laboratory for
Functional Organophosphorus Materials of Henan Province, Zhengzhou University, Zhengzhou 450001, People’s Republic of China
‡Department of Anatomy, College of Basic Medicine Zhengzhou University Zhengzhou 450001, People’s Republic of China
S
* Supporting Information
ABSTRACT: The unprecedented 2,2′-bis(azaphosphindole)
has been synthesized via a new route. Reaction with NaH
afforded a dianion derivative 5, which is easily transformed to
alkylated bis(azaphosphindole) or (Z)-P,P,N,N-cisoid diazadi-
phosphafulvalene. The reaction features good regioselectivity
and high steroselectivity. Relatively strong fluorescence is
observed with diazadiphosphafulvalenes. The X-ray crystal structure analysis showed that dianion ligand 5 is bonded to two Na
atoms in a bridging cis-fashion, which allows the synthesis of diazadiphosphafulvalene in a highly stereoselective approach.
ince the discovery of the first tetrathiafulvalene (TTF),1
The classical one-pot condensation method for the synthesis
of azaphosphindoles10 did not provide the desired species. A
modified stepwise route was developed to synthesize this
unknown compound 3 (Scheme 2). Reaction of 2-bromoani-
2
Smany new heterofulvalenes
have been discovered and
developed for electronic, magnetic, and optical applications.3−6
Thanks to continuous and extensive studies, the synthetic
innovations provide not only symmetric I but also dissym-
metric II heterofulvalenes. Unfortunately, the selective syn-
thesis of heterofulvalenes Z-III and E-IV still remains
challenging. Here, we report a selective synthesis of
diazadiphosphafulvalene (Z-III, A = NR, B = PR) (see Scheme
1) from 2,2′-bis-azaphosphindole.
Scheme 2. Synthesis of 2,2′-bis-Azaphosphindole
Scheme 1. Heterofulvalenes
line with oxalyl chloride, followed by a Pd-catalyzed
phosphonylation with triethyl phosphite, gave 2, and
subsequent reduction with LiAlH4 provided 3 in good yield.
This new 2,2′-bis-azaphosphindole is quite stable in the solid
state, and it could be stored without precaution in air and
moisture for several days. Compound 3 was characterized by
1H, 13C, and 31P NMR spectroscopies and by X-ray crystal
analysis. The 31P NMR resonance frequency for 3 (75.1 ppm)
is in the same range as those of 1,3-azaphosphindoles.10,11 The
structure of 3 (depicted in Figure 4 on page s9 in the
Supporting Information (SI)) shows that the two azaphos-
phindolyl rings adopt a coplanar trans conformation (torsion
angle ∠P1−C1−C1′−N2′ = 0.78°). The PC bond length is
1.731 Å, which is within the range of PC bonds in
1,4-Diazadienes and 2,2′-bipyridines are among the most
useful ligands of transition-metal chemistry,7 because of their
ability to stabilize a wide range of oxidation states for a single
element. The phosphorus analogues are not so well-known, as a
result of the ready cyclization of 1,4-diphosphadienes into 1,2-
dihydro-1,2-diphosphetes. In practice, only 2,2′-biphosphi-
nines8 and 3,4-bis(phosphinidene)cyclobutenes9 have been
studied to a certain extent. At the beginning, we wished to
develop a new class of 1,4-diphosphadienes based on the 1,3-
azaphosphindole monomeric unit.
Received: December 21, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b03971
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Letter
azaphospholes.10−12 The length of the C1−C1′ bond that links
the two five-membered rings is 1.445 Å, which is quite close to
the bridge bond length of 2,2′-biphosphinine.8 This coplanarity
and shortening of the C1−C1′ bond indicate a conjugative
interaction between the two azaphosphindole rings.
azaphospholide was trapped with various electrophiles. The
direct reaction with sulfur gave bis-azaphosphindole sulfide 6a.
The reaction between 5 and PhPCl2 proceeded selectively at
nitrogen to give 6b.14 The structure of 6b was confirmed by X-
ray analysis (see Figure 7 on page s16 in the SI). The crystal
structure of 6b exhibits a relative planarity. The dihedral angle
between the two terminal benzo planes is 7.61°.
Interesting observations were made when investigating the
reactions between 5 and alkyl halides. The reactions with 2
equiv of methyl iodide or benzyl bromide selectively provided
P-alkylated products. This selectivity was established by NMR
spectroscopic analysis of their stable oxidized derivatives 6c and
6d, respectively. Note that the two cis/trans isomers of 6c and
6d can be separated by simple silica gel chromatography. The
structure of trans-6d was definitively confirmed by X-ray
diffraction (XRD) analysis (see Figure 8 on page s18 in the SI).
The structure of trans-6d shows that the two azaphosphindole
rings adopt a coplanar trans conformation (torsion angle ∠P2−
C8−C7−N1 = 2.04°).
To understand the reactivity of 3, we first investigated its
nucleophilicity via the reaction with DMAD (dimethyl
acetylenedicarboxylate). The reaction was monitored by 31P
NMR spectroscopy. We observed the disappearance of
compound 3 and a new phosphorus species 4 appeared as an
AB system at 4.1 and 6.6 ppm (Jp‑p = 138.8 Hz). Some
unidentified deposits also formed. The structure of 4 was
resolved by X-ray crystal analysis (see Figure 5 on page s10 in
the SI). To our surprise, two protons were removed and four
molecules of DMAD were incorporated into the final product.
The mechanism of the formation of 4 is unclear yet. We
propose that the reaction is initiated by the nucleophilic attack
of the phosphorus center onto DMAD, followed by domino
additions between DMAD units. However, we cannot explain
the dehydrogenation at the moment (see Scheme 3). Further
experiments, with regard to reaction optimization, mechanism,
and synthesis utility, are in progress.
When the amount of alkyl halide was doubled (4 equiv), a
new tetramethylated product 6e was obtained as a mixture of
cis/trans-isomers after oxidation. It is striking to find that the
(Z)-P,P,N,N-fulvalene compound was obtained exclusively. The
single-crystal XRD analysis (Figure 1) shows that the length of
Scheme 3. Reaction of 3 with
Dimethylacetylenedicarboxylate
Then, we investigated the deprotonation reaction of 3.13 The
reaction of 3 with NaH in THF proceeded smoothly to afford
cleanly the sodium salt 5 (Scheme 4). The 31P NMR spectrum
of 5 showed one upfield singlet at δ = 61 ppm, which is quite
close to those observed in the imidazolium 1,3-benzazaphos-
pholide ion pairs (∼64 ppm), suggesting an increased
localization of electron density at the P atom in 5. Then, the
Figure 1. X-ray crystal structure analysis of compound trans-6e that
was obtained from the mixture of cis and trans isomers. Main bond
lengths: C8−C9, 1.347(3) Å; P1−C1, 1.797(3) Å; P1−C8, 1.831(2)
Å; N1−C6, 1.403(3) Å; and N1−C8, 1.400(3) Å. Main bond angles:
∠C1−P1−C8, 90.35(11)°; ∠C6−N1−C8, 114.1(2)°; and ∠C9−N2−
C11, 112.52(19)°.
the C8−C9 bond that links the two five-membered rings is
reduced to 1.347 Å, which falls into the normal range of CC
double bonds. To the best of knowledge, this is the first
example of diazadiphosphafulvalene.
Scheme 4. Reaction of Dianion 5 with Various Electrophiles
Compound 6e is a mixture of two diastereomers that result
from the different relative orientations of the PO bonds.
However, this problem could be overcome by using
dibromides; when 1,3-dibromopropane, 1,4-dibromobutane,
and o-xylylene dibromide were used, and 6f, 6g, and 6h were
obtained as cis-isomer exclusively, as shown clearly from the
crystal structures of 6g (see Figure 10 on page s23 in the SI)
and 6h (see Figure 2).
In order to gain deeper insights into the origin of observed
stereoselectivity, we prepared N,N,N′,N′-tetramethylethylene-
diamine (TMEDA) complex of 5. Fortunately, crystal of [5-
TMEDA] was obtained through recrystallization from THF at
room temperature. The single-crystal X-ray structure of [5-
TMEDA] (Figure 3) clearly shows that (1) the two P atoms,
being coordinated with one Na+ each, are located on the same
side of the ring skeleton; (2) each Na atom adopts a bridged
coordination, and two Na atoms in a bisazaphospholide unit
form a double-bridged disodium structure and give a polymeric
B
DOI: 10.1021/acs.orglett.7b03971
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Organic Letters
Letter
examined the utility of 6h (ε524 nm = 7223.8 L mol−1 cm−1)
in live-cell imaging. Figure 4 clearly shows the penetration of 6h
Figure 4. Fluorescence microscopic images of living PC12 cells. Cells
stained without 6h (left) and with 6h (4 μM, right). Scale bar = 50
μm.
Figure 2. X-ray crystal structure analysis of compound 6h. Main bond
lengths: C13−C27, 1.341(3) Å; P1−C13, 1.826(2) Å; P1−C7,
1.786(3) Å; C27−N1, 1.408(3) Å; and C20−N1, 1.394(3) Å. Main
bond angles: ∠N2−C13−P1, 110.52(16)°; ∠C7−P1−C13,
90.43(11)°.
across the membrane and lighting up of the cytoplasm of rat
pheochromocytoma cells (PC12). Finally, we determined the
cytotoxicity of 6h using a CCK8 assay and found that, at a
concentration of 4 μM, the cells were completely viable (see
Figures 1 and 2 on pages s8 and s9 in the SI).
In summary, a straightforward access to a range of new
diazadiphosphafulvalenes as their P-oxides or P-sulfide has been
described. By themselves or as their reduced P(III) derivatives,
they open numerous possibilities in coordination chemistry that
we are currently exploring. Their most specific feature is the
coexistence inside a single conjugated backbone of donor
nitrogen and strongly acceptor phosphoryl sites, suggesting
interesting dipolar properties. Additional research is currently
underway in our group.
Figure 3. X-ray crystal structure analysis of compound 5. H atoms and
TMEDA are omitted for clarity. Main bond lengths: P1−Na1,
3.056(2) Å; N1−Na1, 2.547(4) Å; C1−Na1, 2.973(4) Å; P1−C1,
1.739(4) Å; P1−C3, 1.758(5) Å; N1−C1, 1.344(5) Å; N1−C2,
1.374(5) Å; and C1−C1′, 1.460(8) Å. Main bond angles: C1−P1−
Na1, 119.68(14)°; C1−P1−C3, 88.19(19)°; N1−C1−P1, 117.0(3)°;
and N1−C1−C1′, 119.4(2)°.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b03971.
structure of [5-TMEDA]n; (3) each Na atom is coordinated by
two bisazaphospholide moieties in two different ways, through
η1-coordination by one P atom and η2-coordination by a N
C−CN moiety of the second bisazaphospholide unit. This
η2-coordination of Na with NC−CN moiety is crucial to
the selective formation of (Z)-P,P,N,N-diazadiphosphafulva-
lene.
Measurements were performed in CH2Cl2. λmax represents
the wavelength of maximum UV absorption, λF,max represents
the wavelength of fluorescence maximum absorption, and φ is
the fluorescence quantum yield.
Table 1 shows the UV-vis absorption and fluorescence
spectra of 6f−6h in CH2Cl2. 6g (4817 cm−1) and 6h (4788
cm−1) have larger Stokes shifts than that of 6f (1527 cm−1). All
these bridged diazadiphosphafulvalenes exhibit intense emis-
sions with high fluorescence quantum yields. Next, we
Experimental procedure and characterization of all new
compounds (PDF)
Accession Codes
CCDC 1515639 (3), 1524758 (4), 1539284 (5), 1546555
(6b),1546556 (trans-6d), 1562501 (trans-6e), 1569257 (6g),
and 1571295 (6h) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_
request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, U.K.; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: caojing73@126.com (J. Cao).
*E-mail: duanzheng@zzu.edu.cn (Z. Duan).
*E-mail: frmathey@yahoo.fr (F. Mathey).
Table 1. Luminescent Properties of
Diazadiphosphafulvalenes
ORCID
compound
λmax (nm)
λF,max (nm)
φ
Franco̧ is Mathey: 0000-0002-1637-5259
6f
442
426
424
474
536
532
0.53
0.58
0.70
Notes
6g
6h
The authors declare no competing financial interest.
C
DOI: 10.1021/acs.orglett.7b03971
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
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ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation (Nos. 21672193, 21272218, 81671091) and
Zhengzhou University of China.
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