Regioselective Synthesis of 2- or 2,7-Functionalized Pyrenes via Migration

Article abstract of DOI:10.1021/acs.orglett.8b03270

A simple method for the preparation of 2- or 2,7-functional pyrenes from 1- or 1,6-substituted derivatives is reported. The synthesis involves the unexpected 1,2-phosphinyl migration in an AlCl₃/NaCl melt. The structure of the product has been unambiguously confirmed by X-ray crystallography. We also demonstrated that further functionalization of pyrene through C-P bond activation is possible. These 2,7-positions are difficult to derivatize otherwise.

Full text of DOI:10.1021/acs.orglett.8b03270

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Regioselective Synthesis of 2- or 2,7-Functionalized Pyrenes via
Migration
Liqi Qiu, Wei Hu, Di Wu, Zheng Duan,* and Francois 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, P. R. China
S
* Supporting Information
ABSTRACT: A simple method for the preparation of 2- or 2,7-functional pyrenes from 1- or 1,6-substituted derivatives is
reported. The synthesis involves the unexpected 1,2-phosphinyl migration in an AlCl3/NaCl melt. The structure of the product
has been unambiguously confirmed by X-ray crystallography. We also demonstrated that further functionalization of pyrene
through C−P bond activation is possible. These 2,7-positions are difficult to derivatize otherwise.
Scheme 1. Proposed Synthesis of Pyrene-Fused
Phosphacycle
ubstituting pyrene at the 2- or 2,7-positions is challenging
Sbecause of the presence of the nodal plane in the HOMO
and LUMO, which lies perpendicular to the molecule and passes
through the 2- and 7-positions. These sites are less activated
toward electrophilic substitution than the 1-, 3-, 6-, and 8-
positions, except sterically driven regioselective Friedel−Crafts
tert-butylation.1 Indirect and multistep synthetic methods were
developed for the regioselective synthesis of 2- and 7-substituted
pyrenes from tetrahedropyrene,2 pyrene−Cr(CO)3 complex,3
or well-designed biphenyl derivatives.4 Very recently, Ir-
catalyzed borylation provided a direct method to functionalize
pyrene at these positions.5
The similar reactions were performed with other 1-pyrenyl-
phosphine oxides. Both the open chain and cyclized phosphinyl
moieties could migrate from 1- to 2-position of the pyrenyl
moiety, and dimethyl-2-pyrenylphosphine oxide 4bO (50%),
bis(4-methylphenyl) (2-pyrenyl)-phosphine oxide 4dO (48%),
and 5-(2-pyrenyl)benzo[b]phosphindole 4eO (63%) were
obtained, respectively. 2-Pyrenylphenylphosphine oxide 4cO
can also be prepared from the corresponding 1-pyrenyl
derivative. Pyrene (5−7%) was isolated from all the afore-
mentioned reactions, but the similar reaction with tervalent
phosphine 1a (X = lone pair) provided 2-pyrenylphosphine 4a
in low yield (5%). No migration product 4aS was obtained with
1-pyrenylphosphine sulfide (X = S) (Scheme 2). Although the
reaction mechanism is unclear, involvement of an acid-
promoted migration is presumed. Mechanistic study for this
migration is under way.
Here we would like to report an unprecedented method to
prepare 2- and 2,7-substituted pyrenes from 1- and 1,6-
substituted pyrenes, respectively.
Pyrene is an important and well-studied polycyclic aromatic
hydrocarbon (PAH) unit, the unique electronic and photo-
physical properties have led to its use in a wide variety of
applications.6 The fusion of a pyrene moiety to a π-conjugated
system causes a significant alteration of physical properties.7 Our
interest in novel π-expanded organophosphorus materials and
new reaction with phosphine derivatives8 promoted us to
investigate the possibility of preparation of phosphorus
incorporated PAHs 2 and/or 39 from an intramolecular Scholl
reaction10 with pyrene-substituted triarylphosphine 1 (Scheme
1).
To our surprise, under N2 atmosphere, treatment of 1-
pyrenylphosphine oxide 1aO with an AlCl3/NaCl melt (2.9:1)
at 160 °C for 1 h gave pyrene (7%) and an unexpected 2-
pyrenylphosphine oxide 4aO, whose structure was assigned
unambiguously based on the NMR spectroscopy, X-ray
crystallography (see SI, Figure S1), elemental analysis, and
mass spectrometry measurements. After the optimization of
reaction conditions (see SI), 4aO could be isolated in 70% yield.
It should be mentioned that the dual migrations are also
possible. 1,6-Diphosphinylpyrene 1fO was converted into 2,7-
diphosphinylpyrene 4fO (66%) efficiently in this molten salts
system. However, the reaction with 1gO provided the dual
Received: October 13, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b03270
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Synthesis of 2-Pyrene Derivatives
Figure 1. X-ray crystal structure of 5aO. The level set for thermal
ellipsoids of all atoms is 50%. Main bond lengths (Å) and angles (deg):
P1−O1 1.484(2), C14−P1 1.813(3), C1−P1 1.822(3), C13−C14
1.392(4), C7−P1−C14 105.14(14), C1−P1−C14 107.08(13). CCDC
reference number: 1830073.
Scheme 5. Synthesis of Pyrene-fused Seven-membered
Phosphacycle
migrated product 4gO in low yield (12%), and pyrene was
isolated as a major product (35%) (Scheme 3).
Scheme 3. Synthesis of 2,7-Functionalized Pyrene and Bis(2-
pyrenyl)-substituted Phosphine Oxide via Migration
Interestingly, when bulky alkyl-substituted 1hO and 1iO were
used, besides the desired 4hO and 4iO, the dimerized products
5aO and 5bO were obtained, which were formed through the
intermolecular Scholl reaction, respectively (Scheme 4). The
Figure 2. X-ray crystal structure of 6. The level set for thermal ellipsoids
of all atoms is 50%. Main bond lengths (Å) and angles (deg): P1−O1
1.461(2), P1−O2 1.5964(18), P1−O3 1.588(2), C1−O2 1.407(3),
C7−O3 1.401(3), C2−C1−O2 122.3(2), C1−O2−P1 125.86(16),
O1−P1−O3 110.32(12), P1−O3−C7 118.34(15). CCDC reference
number: 1830074.
Scheme 4. Reactions with Bulky Alkyl-substituted Phosphine
Oxides
The absorption spectra of migrated products show blue shifts in
comparison to the precursors, while the emission spectra are
slightly red-shifted. Compared with 4hO, a significant red shift
was observed in 5aO, indicating that the π-conjugation is
significantly extended via dimerization. The fluorescence
quantum yields (Φf) of these compounds range from 0.37 to
0.93. Higher luminescence efficiencies were observed with 1-
pyrenylphosphine oxides than the corresponding migrated
products (Table 1).
It should be noticed that 2-pyrenylphosphine derivatives can
be used as a 2-pyrenyl building block to synthesize various 2-
pyrenyl-substituted compounds via C−P bond cleavage.11 For
example, 4a and 8 could be synthesized easily from 4aO (see SI).
2-Alkenylpyrene 7 was prepared through the Pd-catalyzed C−P
cleavage of 4a.12 2-Arylpyrene 9 and 2-pyrenemethanol 10 were
synthesized through Pd-catalyzed13 or CsCO3-mediated14 C−P
bond activation of 2-pyrenylphosphonium 8, respectively
(Scheme 6).
structure of 5aO was confirmed by X-ray crystallographic
analysis (Figure 1). The reaction with purified 4hO or 4iO did
not provide 5aO or 5bO, respectively. The formation of 5aO
and 5bO might go through dimerization of the 1-pyrene
derivative, followed by migration. Additional studies on the
reaction mechanism are underway.
The intramolecular coupling reaction was realized with
diphenyl(1-pyrenyl)phosphonate 1jO. The reaction took place
between one of the phenoxy groups and position C10 of the
pyrenyl moiety to give a pyrene-fused seven-membered
phosphacycle 6 (Scheme 5, Figure 2).
The resulting 2-pyrenylphosphine derivatives were used to
synthesize π-conjugated phosphacycles, which might be
interesting for material science.9 2-Pyrenylphenylphosphine
oxide 4cO was converted into a pyrene-fused phosphole oxide
The UV−vis absorption and fluorescence spectra of
representative precursors and the corresponding migrated
products in CH2Cl2 are summarized in Figure 3 and Table 1.
B
DOI: 10.1021/acs.orglett.8b03270
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 7. Synthesis of Pyrene-fused π-Conjugated
Phosphacycles
Figure 3. (a) UV−vis absorption and fluorescence spectra of the 1aO
and 4aO in CH2Cl2 at rt. (b) UV−vis absorption and fluorescence
spectra of the 1eO and 4eO in CH2Cl2 at rt. (c) UV−vis absorption and
fluorescence spectra of the 1fO and 4fO in CH2Cl2 at rt. (d) UV−vis
absorption and fluorescence spectra of the 1hO, 4hO, and 5aO in
CH2Cl2 at rt.
Table 1. Photophysical Data
a
a
a
b
compd
λabs (nm)
λex (nm)
λem (nm)
Φf
1aO
4aO
1eO
4eO
1fO
4fO
1hO
4hO
5aO
323,337,352
312,325,341
345,355,360,379
312,325,341
349,357,366,375,384
313,327,342
320,333,350
352
341
345
341
357
342
333
338
379,398,420
386,406,428
382,401
389,409,432
386,406,427
396,418,442
379,398,420
382,403,424
498,535
0.93
0.76
0.70
0.37
0.72
0.60
0.57
0.41
0.56
309,322,338
325,432,461,494
Figure 4. X-ray crystal structure of 13. The level set for thermal
ellipsoids of all atoms is 50%. Main bond lengths (Å) and angles (deg):
P1−C5 1.775(2), P1−C6 1.7822(19), P1−C8 1.791(2), C5−P1−C6
106.80(9), C5−P1−C8 108.57(9), C5−P1−C13 109.32(9). CCDC
reference number: 1857706.
432
b
a
Measured in CH2Cl2 (5 × 10−6 M). Measured relative to quinine
sulfate (H2SO4, 0.1 M), 15%.
Scheme 6. Synthesis of 2-Pyrenyl Compounds via C−P Bond
Cleavage
In conclusion, the regioselective synthesis of 2- or 2,7-
substituted pyrenes was achieved through the migration of
related 1 or 1,6-substituted derivatives, respectively. The further
C−P bond cleavage provides considerable utility for pyrene
functionalizations. The further elucidation of the migration
mechanism and the development of π-conjugated organo-
phosphorus functional materials using this method are under-
way in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b03270.
Experimental procedure and characterization of all new
compounds (PDF)
11 (for crystal structure, see SI, Figure S4) directly through
silver-mediated oxidative C−H/P-H functionalization.15 Fol-
lowing Wang’s Cu-mediated annulation,16 4a was transformed
into a pyrene-fused phosphindolium 12 (for crystal structure,
see SI, Figure S5). For the comparison, under the same
conditions, the reaction with 1a gave a six-membered phospha-
cycle 13 (Scheme 7, Figure 4). This selectivity might be due to
the inertness of position C2.1
Accession Codes
CCDC 1586367, 1830073−1830074, 1857706, 1861056, and
1866548 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
C
DOI: 10.1021/acs.orglett.8b03270
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
G. Y.; Cai, W. H.; Cao, J.; Duan, Z.; Mathey, F. Org. Lett. 2018, 20,
Crystallographic Data Centre, 12 Union Road, Cambridge CB2
1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: duanzheng@zzu.edu.cn.
*E-mail: frmathey@yahoo.fr.
ORCID
Di Wu: 0000-0001-8293-4859
Zheng Duan: 0000-0002-0173-663X
Francois Mathey: 0000-0002-1637-5259
̋
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Inorg. Chem. 2016, 2016, 768. (i) Szucs, R.; Bouit, P.-A.; Nyulaszi, L.;
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
We are grateful to the National Science Foundation of China
(No. 21672193, 21272218) and Zhengzhou University of China
for financial support of this research.
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Org. Lett. XXXX, XXX, XXX−XXX