Connecting a carbonyl and a π-conjugated group through a: P-phenylene linker by (5+1) benzene ring formation

Article abstract of DOI:10.1039/c9cc04012a

A benzene ring was formed to connect a carbonyl group of various methyl ketones with a π-conjugated group through a p-phenylene linker. Methyl ketones and streptocyanines were used as the C1 and C5 sources, respectively, in the (5+1) annulation, which could form donor-π-acceptor molecules.

Full text of DOI:10.1039/c9cc04012a

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Connecting a carbonyl and a p-conjugated group
through a p-phenylene linker by (5+1) benzene
ring formation†
Cite this:DOI: 10.1039/c9cc04012a
Received 24th May 2019,
Accepted 12th June 2019
Tatsuya Morofuji, * Hanae Kinoshita and Naokazu Kano
*
DOI: 10.1039/c9cc04012a
rsc.li/chemcomm
A benzene ring was formed to connect a carbonyl group of various
methyl ketones with a p-conjugated group through a p-phenylene
linker. Methyl ketones and streptocyanines were used as the C1 and
C5 sources, respectively, in the (5+1) annulation, which could form
donor–p–acceptor molecules.
Connecting two different molecules with a linker is a funda-
mental design principle of functional organic molecules such as
organic devices,1 supramolecular materials,2 bioactive compounds,3
and ligands for metal–organic frameworks.4 The p-phenylene group
is one of the most widely used linkers for the following reasons:
(1) the rigid structure of the benzene ring defines the relative
position of two substituents on the benzene ring,5 and (2) the
p-phenylene group can connect two substituents with p-conjugation,
which affects the electronic state of the molecule.6 Compared with
o- or m-phenylene groups, (3) the p-phenylene group can extend
p-conjugation more effectively because of steric or electronic
reasons, and (4) the planar structure and p-electrons of the
benzene ring induce p–p stacking, which can affect the secondary
structure of the molecules.7
Fig. 1 Strategies for synthesis of carbonyl-p-phenylene-p molecules.
Utilizing these characteristics, various p-phenylene-containing
molecules were designed and synthesized as functional organic
molecules. Particularly, carbonyl-p-phenylene-p molecules (Fig. 1a)
are used for a wide range of applications such as receptor benzene ring bearing a carbonyl group via cross-coupling
antagonists,8 aggregation-induced emission luminogens,9 and reactions13 (Fig. 1b). Another method is the connection of a
photoinitiators for free radical polymerization.10 In addition, carbonyl group to a benzene ring to form a ketone (Fig. 1c). The
when a p-conjugated substituent acts as a donor, such a carbonyl-p- most popular classical approach with respect to the latter
phenylene-p molecule could be regarded as a donor–acceptor method is the Friedel–Crafts reaction of acid chlorides and
molecule, which is an important core structure of thermally acti- electron-rich aromatic compounds.14 The reaction of the
vated delayed fluorescent emitters11 and photocatalysts mediating Weinreb amide or its analogues with organometallic reagents
proton-coupled electron transfer.12
is an alternative method for ketone formation.15 Transition-
One approach to synthesizing carbonyl-p-phenylene-p mole- metal-catalyzed ketone formation is also popular.16 These
cules is the introduction of a p-conjugated substituent to a approaches are valuable, but the scope of the Friedel–Crafts
reaction is limited and some aromatic substrates show undesired
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro,
regioselectivity.
Toshima-ku, Tokyo 171-8588, Japan. E-mail: tatsuya.morofuji@gakushuin.ac.jp,
The introduction of a p-conjugated group needs to use both
naokazu.Kano@gakushuin.ac.jp; Tel: +81-3-5904-9394
aryl halides and arylmetal reagents that require multistep
preparation in most cases. A more convenient regiospecific
† Electronic supplementary information (ESI) available: Experimental procedures
and NMR data. See DOI: 10.1039/c9cc04012a
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method for synthesizing carbonyl-p-phenylene-p molecules is
still highly desired.
Benzene ring formation would be an alternative approach to
synthesize benzene-containing molecules. Various approaches
for [2+2+2] and [4+2] benzene ring formation have been developed
in the past up to the present.17 However, it is difficult to synthesize
carbonyl-p-phenylene-p molecules using the [2+2+2] and [4+2]
annulation because of their inherent 1,4-disubstitution pattern.
In contrast, (5+1) benzene ring formation18,19 could be expected to
give 1,4-disubstituted benzene derivatives regioselectively.
Based on this background, we envisioned that (5+1) benzene
ring formation using a methyl ketone 1 as the C1 source and a
C5 source bearing a p-conjugated substituent would be an
attractive approach to obtaining carbonyl-p-phenylene-p mole-
cules because starting methyl ketone 1 is readily available
(Fig. 1d). This approach would give the p-phenylene-linked
products regiospecifically. In relation to the approach, conver-
sion of an acetyl group into an unsubstituted benzoyl group
using a conjugated methine compound (streptocyanine) as a C5
source was reported by Jutz.20 However, the mere formation of
an unsubstituted phenyl group, which restricted applicability of
this reaction, has not been applied to connecting two fragments
through the benzene ring formed. We report here a new
method for connecting a carbonyl and a p-conjugated group
through a p-phenylene linker by benzene ring formation using
a methyl ketone as the C1 source and a streptocyanine bearing
a p-conjugated substituent as the C5 source (eqn (1)).
Scheme 1 Proposed reaction mechanism of (5+1) benzene ring formation.
Table 1 Optimization of the reaction conditionsa
Entry
R0, R0
Base
Temp. (1C)
Yieldb (%)
(1)
1
2
3
4
5
6
Me, Me
Me, Me
Me, Me
–(CH2)2O(CH2)2–
–(CH2)5–
–(CH2)5–
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
NaOtBu
80
30
53
84
29
100
120
120
120
120
89
99 (94)c
A working hypothesis is that the (5+1) annulation proceeds
following a pathway such as that shown in Scheme 1. The
enolate generated from methyl ketone 1 and a base attacks an
iminium group in streptocyanines 2, and following the elimi-
nation of an amine gives triene intermediate 3. Triene 3 could
be converted thermally to E/Z isomer 4 because of the push–pull
a
Acetophenone (1a) (0.2 mmol), streptocyanine 2 (1.5 equiv.), and base
(1.5 equiv.) were stirred at the indicated temperature in THF (4 mL)
for 10 h. Yield of the products was determined by 1H NMR analysis
b
c
using 1,1,2,2-tetrachloroethane as an internal standard. Isolated yield.
electronic structure.21 Then, 6p electrocyclization22 of 4 gives benzene ring formation was achieved in one pot without isolating
cyclohexadiene 5, and following the second elimination of the intermediates 3.
amine produces the desired carbonyl-p-phenylene-p molecule 6.
Next, we prepared streptocyanines bearing a p-conjugated
It follows that the base, nitrogen substituents, and reaction substituent at the 3-position, 2, for the (5+1) annulation
temperature could be critical for the successful (5+1) annulation. synthesizing carbonyl-p-phenylene-p molecules. The procedure
We first optimized the reaction conditions for the (5+1) for synthesizing streptocyanines 2 is illustrated in Fig. 2.23
annulation using streptocyanines bearing no internal substituent N-Arylation of 4-substituted pyridine 7 with 2,5-dinitrochloro-
(Table 1).20 Acetophenone (1a), streptocyanine 2, and KOtBu were benzene gave the corresponding N-arylpyridinium salt 8 (Fig. 2, A).
mixed and stirred in THF at 80 1C for 10 h in a pressure tube to The resulting N-arylpyridinium 8 was treated with piperidine,
give benzophenone (6a) in a 30% yield (entry 1). Higher reaction and following salt exchange gave the desired streptocyanine 2
temperatures increased the yield of the product (entries 2 and 3). (Fig. 2, B). Streptocyanines bearing a p-conjugated substituent
The nitrogen substituent in streptocyanine 2 was found to affect such as a phenyl group, a biphenyl group, a naphthyl group,
the yield, and the piperidinyl substituent turned out to be the best a benzothiophenyl group, and a pyrenyl group were prepared
(entries 3–5). The use of NaOtBu instead of KOtBu as a base gave (2b–2f). Streptocyanines bearing a diphenylamino group, a carba-
the product in an almost quantitative yield (entry 6). The (5+1) zolyl group, and a tert-butyl group were also synthesized in the
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Fig. 2 Synthesis of streptocyanines bearing a substituent. a NH4PF6 was
used. b KPF6 was used. c NaSbF6 was used.
same manner (2g–2i). It should be noted that streptocyanines
2a–2i could be purified by filtration and washing and did not
require purification by column chromatography.
The synthesized streptocyanines 2 were used for (5+1) annu-
lation under the optimized reaction conditions described in
Table 1. Some of the scope of the reaction is shown in Fig. 3.
The functional group compatibility of the present transformation
is remarkable. Acetophenones bearing an electron-donating group
and an electron-withdrawing group gave the corresponding
Fig. 3 Scope of (5+1) benzene ring formation. Aryl methyl ketone 1
(0.5 mmol), streptocyanine 2 (1.5–6 equiv.), and NaOtBu (1.5–18 equiv.)
were stirred at 120 1C in THF for 10 h. a Reaction run on 0.2 mmol scale.
b Reaction run on a gram scale (12 mmol scale). See ESI† for details.
products (6b–6h) in excellent to moderate yields. Particularly, carried out. Biphenyl-, naphthyl-, and 2-benzothiophenyl-
iodo- or bromo-substituted products (6e, 6f) are valuable substituted streptocyanines were found to be good substrates
because further transformation of the products is easy using for the annulation (6n–6p). Use of pyrenyl-substituted strepto-
a transition-metal catalyst. Additionally, benzylacetone, which cyanine 2f gave corresponding product 6q, which was used as a
is an aliphatic ketone, could also be used for (5+1) annulation photoinitiator.10 Using diphenylamino- or carbazolyl-substituted
to give the corresponding product 6i.
streptocyanines (2g, 2h), the present method could be applied
This annulation reaction was applied to the synthesis of to the synthesis of carbonyl-p-phenylene-donor molecules (6r, 6s,
carbonyl-p-phenylene-p molecules. Reactions of acetophenone respectively). The reaction of acetophenone with tert-butyl-
(1a) with streptocyanines bearing a phenyl substituent 2b gave substituted streptocyanine 2i gave p-tert-butylphenyl phenyl
corresponding product 6j in excellent yield. The reaction also ketone (6t).
worked well on a gram scale. Sterically hindered o-methylaceto-
An advantage of this method is the availability of versatile
phenone was also a good substrate for (5+1) annulation (6k). acetyl compounds as a counterpart to streptocyanines. Even
Heteroaryl methyl ketones such as 2-acetyl thiophene and 1-methyl- di- or tri-acetyl-substituted compounds are also readily available.
3-acetylindole gave the corresponding heteroaryl–carbonyl-p- By using such compounds as a starting material, we applied
phenylene-p molecules (6l, 6m).
this method to the synthesis of symmetric molecules bearing
(5+1) benzene ring formation using acetophenone and p-phenylene groups connecting the triphenylamine moiety as
streptocyanines bearing various p-conjugated substituents was the donor and carbonyl groups as the acceptor. C2h symmetric
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donor–acceptor molecule 6u was synthesized from 4,40-diacetyl-
biphenyl and 2g via double (5+1) benzene ring formation. Using
4,40,400-triacetyltriphenylamine and 2b as starting materials, triple-
p-phenylene group formation was achieved to give the corres-
ponding C3 symmetric donor–acceptor molecule 6v. The reaction
of 1,3,5-triacetylbenzene with 2g also gave the C3 symmetric
donor–acceptor molecule 6w.
In conclusion, we have developed an efficient method for
synthesizing carbonyl-p-phenylene-p molecules from readily avail-
able methyl ketones and easily synthesized streptocyanines in one
pot. This convenient method was applied to the synthesis of
symmetric donor–acceptor molecules that have two or three such
linkages.
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