N-Doped Cationic PAHs by Rh(III)-Catalyzed Double C-H Activation and Annulation of 2-Arylbenzimidazoles with Alkynes

Article abstract of DOI:10.1021/acs.orglett.7b00478

A novel class of N-doped cationic PAHs (polycyclic aromatic hydrocarbons) bearing the benzo[c,d]fluoranthene scaffold has been synthesized by the Rh(III)-catalyzed double-oxidative annulation of 2-arylbenzimidazoles with alkynes. The overall process involves a double C-N bond formation through a double C-H/N-H functionalization.The solid-state structures and electronic properties of the new N-doped PAHs were analyzed. These cationic azapolycycles were readily reduced in the presence of LiAlH₄ or by the addition of PhLi to give interesting phenyl and diphenylmethanediamine derivatives.

Full text of DOI:10.1021/acs.orglett.7b00478

Letter
pubs.acs.org/OrgLett
N‑Doped Cationic PAHs by Rh(III)-Catalyzed Double C−H Activation
and Annulation of 2‑Arylbenzimidazoles with Alkynes
Jose M. Villar, Jaime Suarez, Jesus A. Varela, and Carlos Saa*
́
́
́
́
́ ́ ́
Centro Singular de Investigacion en Química Bioloxica e Materiais Moleculares (CIQUS) e Dpto. de Química Organica, Universidade
de Santiago de Compostela, 15782 Santiago de Compostela, Spain
S
* Supporting Information
ABSTRACT: A novel class of N-doped cationic PAHs (polycyclic
aromatic hydrocarbons) bearing the benzo[c,d]fluoranthene scaffold has
been synthesized by the Rh(III)-catalyzed double-oxidative annulation of
2-arylbenzimidazoles with alkynes. The overall process involves a double
C−N bond formation through a double C−H/N−H functionalization.The
solid-state structures and electronic properties of the new N-doped PAHs
were analyzed. These cationic azapolycycles were readily reduced in the
presence of LiAlH4 or by the addition of PhLi to give interesting phenyl
and diphenylmethanediamine derivatives.
oped polycyclic aromatic hydrocarbons (doped PAHs)1
Dare considered to be a very important class of molecules in
materials science due to their wide-ranging applications in
electronic devices, semiconductors, solar cells, and fluorescent
materials, among others. The incorporation of heteroatoms such
as boron,2 nitrogen,3 phosphorus,4 oxygen,5 or sulfur5 in the
aromatic framework of PAHs can modulate their physical,
chemical, and supramolecular properties. Transition-metal-
catalyzed aromatic C−H activation between arenes/heteroar-
enes and alkynes has proven to be a powerful synthetic
methodology to access different polycyclic aromatic/hetero-
aromatic molecules (PAHs).6−8 Undoubtedly, nitrogen-contain-
ing derivatives are among the most abundant doped PAHs.
Focusing our attention in those containing the interesting
cyclopenta[c,d]phenalene unit, either neutral N-doped9 or
cationic derivatives have been synthesized by Wang,7m
Choudhury,8c and Macgregor7l using Rh(III)-catalyzed double
C−H activation−annulation reactions with imidazole, NHC-
carbenes, and pyrazole as directing groups (Scheme 1a).10
Encouraged by these results and our interest in the behavior of
amidines and guanidines as directing groups in metal-catalyzed
single/multiple C−H bond activation processes,11 we report
herein the synthesis of new N-doped cationic benzo[c,d]-
fluoranthene (benzimidazo[c,d]phenalene) derivatives by an
efficient Rh(III)-catalyzed double-oxidative annulation of 2-
arylbenzimidazoles and alkynes which involves a double C−N
bond formation (Scheme 1b).
We initially tested the catalytic conditions previously reported
by Miura and Satoh for the single C−H activation of 2-
arylbenzimidazoles to give imidazoisoquinolines,7a but in the
presence of 2 equiv of diphenylacetylene 2a (Table 1).12
However, after 24 h at 80 °C only the starting materials were
recovered (Table 1, entry 1). Gratifyingly, the use of polar protic
solvents had a dramatic beneficial effect on the course of the
reaction since heating the mixture in MeOH at 100 °C (entry 2)
led to a mixture of two products, the monocyclized
imidazoisoquinoline 4aa7a (66%) and the novel benzo-fused
azafluoranthenium salt 3aa (21%, air stable solid), a product
derived from a double C−H/N−H functionalization that was
fully characterized by single-crystal X-ray diffraction, ESI-HRMS,
and NMR spectroscopy.13 The reaction conditions were
optimized to increase the selectivity of the process (entries 3−
5). Thus, replacement of the oxidant Cu(OAc)2 by the mixture
H2O2/NaOAc led to a slight increase in the yield of 3aa (entry 3).
To our delight, total selectivity toward 3aa (99%) was achieved
on using AgOAc as oxidant (entry 4). Furthermore, high
conversions were obtained at room temperature without
Scheme 1. N-Doped Cyclopenta[c,d]phenalenes via Rh(III)-
Catalyzed Double C−H Activation and Oxidative Annulation
compromising the yield of the reaction (entry 5).14
A
comparison between different polar protic and aprotic solvents
confirmed that MeOH was the best solvent for this reaction
(entries 4 and 5).15 Other alcohols such as iPrOH or chlorinated
Received: February 17, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00478
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Organic Letters
Letter
a
groups led to the corresponding N-doped benzo[cd]-
fluoranthenium salts in excellent yields (3aa−af). The meta-
substituted aromatic alkynes such as 1,2-bis(3-bromophenyl)-
ethyne furnished the azafluoranthenium salt 3ag in 91% yield.17
Heteroaromatic alkynes such as 1,2-di(thiophene-2-yl)ethyne
participate as the cycloaddition partners. One representative
product, 3ah, was formed in very good yield. Aliphatic alkynes
were also successful partners under standard conditions,
although moderate yields of 3ai and 3aj13 were isolated since
extended reaction times were required. Pleasingly, complete
regioselectivity was observed with asymmetric alkynes, e.g., 1-
phenyl-1-propyne, which afforded 3ak in 74% yield.
We next analyzed the influence of substitution on the C2-
phenyl ring of the benzimidazole ring. Both electron-rich and
electron-poor substituents in the para-position allowed efficient
double cycloaddition to provide the corresponding benzofused
azafluoranthenium salts 3ba−ha in good to excellent yields.18
Interestingly, the reaction also tolerates halogenated substitu-
ents, i.e., Br and I, giving excellent yields of the functionalized 3da
and 3ea, which could allow further metal-catalyzed trans-
formations to be carried out. In addition, the reaction is also
compatible with aryl groups bearing sp- and sp2-hybridized
nitrogen atoms. Thus, the nitrile derivative 3ha could be isolated
in a 74% yield, whereas the pyrido-fused azafluoranthenium salt
3ia was obtained in 67% yield by double activation of the
pyridine ring. These interesting results could allow extension of
the above functionalization to other combinations of hetero-
cycles, thus making this methodology particularly attractive for
the synthesis of valuable heteroatom-doped charged PAHs.
As in related references,7l,m,8c,d,10 we anticipated a similar two-
step mechanism for the present catalytic reaction.19 Thus, the
reaction of 1a with 2 equiv of 2a in tert-amyl alcohol for 48 h
stopped at the monocyclized imidazoisoquinoline 4aa (Scheme
3). The yield of the dicyclized fluoranthenium salts 3 increased
Table 1. Optimization of the Reaction Conditions
b
entry
oxidant
solvent
temp (°C) time (h) yield (%)
1
2
3
4
5
6
7
Cu(OAc)2
Cu(OAc)2
H2O2/NaOAc
AgOAc
DMF
80
100
100
100
25
24
24
24
5
c
c
MeOH
MeOH
MeOH
MeOH
iPrOH
DCE
21
40
99
87
62
67
AgOAc
84
24
24
AgOAc
50
AgOAc
50
a
Reaction conditions: 1a (0.4 mmol), 2a (0.8 mmol), [RhCp*Cl2]2
(2.5 mol %), oxidant (1.68 mmol), solvent (2.0 mL) in an air
atmosphere unless otherwise stated. Isolated yields. Imidazoisoqui-
noline 4aa (Scheme 3) was isolated in 66% yield (entry 2) and 55%
yield (entry 3).
b
c
solvents such as 1,2-dichloroethane (DCE) gave only moderate
yields (entries 6 and 7).16 Finally, a catalyst screening showed
that other metal complexes such as [Co(III)], [Ir(III)], [Pd(II)],
or [Ru(II)] were totally inactive in this transformation.15 In
addition, a multigram-scale reaction was carried out with 1a (4
mmol) to give 3aa (2.4 g) in quantitative yield, and the catalyst
loading could be reduced to 1 mol % with full conversion of the
starting materials after 15 h at 100 °C.
Having identified the optimal reaction conditions, we
proceeded to explore the scope of the reaction (Scheme 2). It
was found that para-substituted aromatic alkynes were well
tolerated. Both electron-donating and electron-withdrawing
Scheme 2. Substrate Scope of the RhIII-Catalyzed Double-
Oxidative Annulation
Scheme 3. Mechanistic Studies: Double-Oxidative Annulation
a
along the series tAmOH < iPrOH < MeOH and was zero in the
first solvent and quantitative in the last solvent (see Table 1 and
ref 16). This result suggests a positive solvation effect for the
second C−H activation, probably due to coordination of the
solvent to the Rh(III) center.7l On the other hand, careful
monitoring of the reaction between 1a and 2a (2 equiv) by TLC,
at short reaction times, indicated that appreciable amounts of 4aa
were not formed during the catalysis. This result is consistent
with a faster reaction rate for the second C−H activation process.
In an attempt to confirm the existence of 4aa as a reaction
intermediate, this compound was subjected to the optimized
reaction conditions in the presence of 1 equiv of 2a. Full
conversion of 4aa to 3aa was observed by 1H NMR spectroscopy
in less than 5 h, and the product could be isolated in 99% yield
a
Unless otherwise stated, all reactions were carried out using 1 (0.40
mmol), 2 (0.80 mmol), [RhCp*Cl2]2 (2.5 mol %), AgOAc (1.68
mmol), and MeOH (2 mL) at 100 °C for 5 h. 12 h. 9 h.
b
c
B
DOI: 10.1021/acs.orglett.7b00478
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Organic Letters
Letter
(Scheme 3).20 Finally, two different samples of either 1a or 4aa
were charged with 2a (2 equiv) and subjected to the optimized
conditions but without the rhodium catalyst loading. After 5 h at
100 °C, only starting materials were recovered, which rules out
any silver-catalyzed C−H activation process.21
The azafluoranthenium cations are stable with a wide variety of
anions. Thus, treatment of 3·OAc salts with saturated NaCl(aq)
solutions and subsequent chromatography on silica gel (MeOH/
CH2Cl2, 2%) afforded the corresponding chloride salts 3·Cl in
quantitative yield as pure microcrystalline solids. In addition,
treatment of 3·Cl with different silver salts AgX (X = PF6, SbF6,
OTf, BArf4) resulted in rapid anion exchange. Single crystals of
3aa·OAc and 3aj·Cl suitable for XRD analysis were obtained by
slow diffusion of hexane into saturated solutions in methanol or
dichloromethane/diethyl ether, respectively.
The cations present in the two salts have a pentacyclic planar
structure for 3aa·OAc and a quasiplanar structure for 3aj·Cl
(mean deviation 5.56°) (Figure 1). To the best of our
Figure 2. Electronic absorption (solid line) and electronic emission
(dotted line) spectra of 3(a−i)a (top) and 3a(a−k) (bottom) in
CH2Cl2.
Table 2. Influence of the Anion on the Molar Extinction
Coefficient
3aa·X
OAc−
77000
SbF6
56800
PF6
59200
BArf4
OTf−
Cl−
−
−
−
Figure 1. (a) Solid-state structures (diamond plots) of 3aa·OAc (left)
and 3aj·Cl (right). Hydrogen atoms are omitted for clarity. Ellipsoids are
drawn at the 50% probability level. 3D-dimeric packing structure viewed
along the c axis (b) and a axis (c).
ε(285)
54060
53800
47100
cm−1) than 3aa·Cl. This parameter was also affected by the
counteranion, and the maximum value was obtained for acetate.
A gradual red shift in the emission peak was observed from 415
to 470 nm as the electron-withdrawing strength of the functional
group increased from 3ca·Cl to 3fa·Cl (Figure 2, top). The
opposite effect was observed with the substitution in the para-
position of the aromatic ring of the alkyne. Thus, a red shift from
410 to 448 nm was observed on increasing the electron-donating
strength from 3af·Cl to 3ac·Cl (Figure 2, bottom).15
Interestingly, the azafluoranthenium salt 3aa·Cl could be
reduced in the presence of LiAlH4 or PhLi to give phenyl- and
diphenylmethanediamine derivatives 5aaa and 5aab13 (Scheme
4). The former compound was extremely unstable during
manipulation and gave rise to an unidentified species. In contrast,
suitable crystals of 5aab, which was stable, could be grown and
knowledge, this is the first symmetrical N-doped PAH with
20π-electrons.1c The two C2−N distances of 1.35 (3aa·OAc) and
1.36 (3aj·Cl) Å, which are typical in benzofused azaheterocycles,
show the high symmetry of these molecules. Crystallization of
the crude material after quenching the reaction between 1a and
2a gave a compound with a dimeric packing of two neatly stacked
cations with the acetate anion, one acetic acid molecule, and a
water molecule interacting within the cationic layers by hydrogen
bonding. By contrast, the solid-state structure of pure 3aj·Cl
showed a dimeric packing of two cationic offset layers (interlayer
space 3.33 Å)22 with the hydrophobic propyl groups located as
far as possible from one another and the chloride outside the
interlayer space.
The UV−vis absorption and emission spectra of species 3 in
CH2Cl2 are shown in Figure 2. The solutions were all pale yellow
with strong blue-light emission under irradiation at 254 nm. In
the electronic absorption spectrum, these salts showed an
absolute maximum centered at around 290 nm with molar
extinction coefficients that were strongly dependent on the
substitution in the para position (Table 2). As an example, the
iodo derivative 3ea·Cl displayed a 3-fold larger ε (130000 M−1
Scheme 4. Reduction of Azafluoranthenium Salt 3aa·Cl
C
DOI: 10.1021/acs.orglett.7b00478
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Organic Letters
Letter
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characterized by X-ray crystallography. Formation of a
tetrahedral carbon atom was accompanied by a significant
modification of the electronic spectrum of 3aa·Cl.
In summary, we have successfully developed an efficient
rhodium(III)-catalyzed double-oxidative annulation between
arylbenzimidazoles and alkynes to form novel N-doped benzo-
[cd]fluoranthenium salts via double C−H activation and double
C−N bod formation. The new skeleton exhibits intense
fluorescence, which is indicative that these compounds could
have promising applications in optoelectronic materials. Further
electronic studies and applications of these interesting materials
are currently under investigation 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.7b00478.
Experimental procedures and spectral data (PDF)
NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: carlos.saa@usc.es.
ORCID
Jesus A. Varela: 0000-0001-8499-4257
́
Carlos Saa: 0000-0003-3213-4604
́
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work has received financial support from Spanish MINECO
(project CTQ2014-59015R), the Conselleria de Cultura,
■
(10) For the synthesis of the fluorescent quinolinium phenalene
(pyrene-type) derivatives from arylpyridinium salts, see: Ge, Q.; Hu, Y.;
Li, B.; Wang, B. Org. Lett. 2016, 18, 2483.
(11) Cajaraville, A.; Suarez, J.; Lopez, S.; Varela, J. A.; Saa, C. Chem.
Commun. 2015, 51, 15157.
́
Educacion
́
e Ordenacion
́
Universitaria (project GRC2014/
n de Galicia,
032), and Centro singular de investigacio
́
accreditation 2016-2019, ED431G/09 and ERDF. We also
thank the ORFEO-CINQA network (CTQ2014-51912REDC).
J.M.V. and J.S. thank the Xunta de Galicia for predoctoral and
postdoctoral contracts, respectively.
(12) Reaction carried out in the absence of C5H2Ph4.
(13) CCDC 1523743 (3aa·OAc), 1523744 (3aj·Cl), and 1523745
(5aab) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge
Crystallographic Data Centre. For ORTEP diagrams of complexes 3aa·
OAc, 3aj·Cl, and 5aab, see the Supporting Information.
REFERENCES
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D
DOI: 10.1021/acs.orglett.7b00478
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