Facile Construction of Benzofulvene Scaffold from Tetraaryl[3]cumulene Through Electrophilic Iodocyclization

Article abstract of DOI:10.1002/ejoc.202001200

We found that the reaction of tetraaryl[3]cumulenes with N-iodosuccinimide afforded the corresponding iodinated triarylbenzofulvenes with high yields under mild reaction conditions. Unsymmetrical tetraaryl[3]cumulenes underwent regioselective reactions to

Full text of DOI:10.1002/ejoc.202001200

Communication
doi.org/10.1002/ejoc.202001200
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European Journal of Organic Chemistry
Iodocyclization
Facile Construction of Benzofulvene Scaffold from
Tetraaryl[3]cumulene Through Electrophilic Iodocyclization
Fumitoshi Yagishita,*[a,b] Keita Hoshi,[a] Yasushi Yoshida,[c] Shoko Ueta,[a] Keiji Minagawa,[a]
Yasushi Imada,[a] and Yasuhiko Kawamura[a]
Abstract: We found that the reaction of tetraaryl[3]cumulenes pending on the aryl substituents. The obtained iodinated
with N-iodosuccinimide afforded the corresponding iodinated benzofulvene was successfully used as aryl iodide for common
triarylbenzofulvenes with high yields under mild reaction condi- cross-coupling reactions, and the corresponding tetrasubsti-
tions. Unsymmetrical tetraaryl[3]cumulenes underwent regio- tuted benzofulvenes was easily accessed via Suzuki–Miyaura
selective reactions to give a single isomer of benzofulvenes de- and Sonogashira cross-coupling reactions, respectively.
Benzofulvenes are found in natural compounds[1] as the core
structure and have potential applications as versatile scaffolds
for medicinal chemistry,[2] polymer chemistry,[3] organic synthe-
sis,[4] and organometallics.[5] Due to huge importance in various
research fields, many synthetic methodologies have been devel-
oped to construct a benzofulvene scaffold. Among them, the
cyclization reactions of aryldiynes[6] and aryleneynes[7] are
recognized as one of the promising strategies. For example, pal-
ladium-catalyzed cyclization of 1,2-bis(arylethynyl)benzene has
been developed by Lee and Wu.[6d] They proposed that benzo-
fulvenes were formed via the generation of vinyl palladium in-
termediates followed by 5-exo-dig cyclization. On the other
hand, Martinelli and co-workers reported the construction of
benzofulvene core from the 1,2-bis(arylethynyl)benzene via
5-exo-dig cyclization under transition-metal-free conditions.[6h]
Their method using iodine affords the diiodobenzofulvenes as
E/Z mixture with high yields. Saunthwal and co-workers also
demonstrated 5-end-dig iodocyclization of symmetrical and un-
symmetrical enediynes under mild reaction conditions.[6i]
Cumulenes have attracted intense attention due to the
unique reactivity affording various hydrocarbons through di-
merization,[8] trimerization,[9] intermolecular cycloaddition,[10]
or related cyclization reactions.[11] To construct a benzofulvene
scaffold, the allene structure has also been used.[12] For exam-
ple, Cordier and co-workers reported that α-hydroxyallenes
bearing aryl groups were transformed into aryl-substituted
benzofulvenes via Nazarov reaction under catalytic condi-
tions.[12a] Regarding of the use of higher cumulative bond, a
few examples including [3]cumulenes as key components were
reported. For example, Dyker and co-workers reported the pro-
duction of tetraarylbenzofulvenes in the palladium-catalyzed
arylation of butadiynes through the formation of the
[3]cumulene intermediate followed by cyclopalladation at high
temperature (Figure 1a).[13] Furuta and co-workers also reported
the synthesis of benzofulvenes from [3]cumulenes via similar
palladacycles under Heck reaction conditions (Figure 1b).[14]
However, these successful examples based on [3]cumulenes re-
quire both transition metals and high reaction temperature.
Herein, we describe the facile preparation of triarylated iodo-
benzofulvenes, 1-(diarylmethylene)-3-aryl-2-iodo-1H-indenes,
from tetraaryl[3]cumulenes via iodocyclization under metal-free
and mild reaction conditions (Figure 1c). The vinyl iodide
moiety of the benzofulvenes can be used for common cross-
[a] Dr. F. Yagishita, K. Hoshi, Dr. S. Ueta, Prof. Dr. K. Minagawa,
Prof. Dr. Y. Imada, Prof. Dr. Y. Kawamura
Department of Applied Chemistry, Tokushima University
2-1 Minamijosanjima, Tokushima 770-8506, Japan
E-mail: yagishitaf@tokushima-u.ac.jp
[b] Dr. F. Yagishita
Department of Post-LED Photonics Research,
Institute of Post-LED Photonics, Tokushima University
2-1 Minamijosanjima, Tokushima 770-8506, Japan
[c] Dr. Y. Yoshida
Department of Applied Chemistry and Biotechnology,
Graduate School of Engineering, Chiba University
1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.202001200.
Figure 1. Preparation of benzofulvenes from [3]cumulenes.
1 © 2020 Wiley-VCH GmbH
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coupling reactions, and the benzofulvene can be easily con-
verted to tetraarylated benzofulvenes under Suzuki–Miyaura re-
action conditions.
Table 2. Scope and limitation of iodocyclization of tetraaryl[3]cumulenes 1.
We initially investigated the optimized reaction conditions
for the construction of benzofulvene using tetraphenyl[3]-
cumulene (1a) as a model substrate. The results are summa-
rized in Table 1.
Table 1. Optimization of reaction conditions.[a]
Entry
R1
R2
Time [h]
Product
Yield
[%][a]
1
2
3
4
5
6
H
Me
OMe
Cl
OMe
OMe
H
3
3
2
72
3
2a
2b
2c
2d
2e
2f
96
Me
OMe
Cl
H
Me
> 99
> 99
trace
81
Entry
Solvent
[I+] source
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
9
MeNO2
MeCN
DCM
Benzene
Toluene
MeNO2
MeNO2
MeNO2
MeNO2
NIS
NIS
NIS
NIS
NIS
I2
NIS
NIS
NIS
2
2
2
3
2
2
0.5
1
3
86
7
8
trace
trace
24
36
52
2
88
[a] Isolated yields.
for X-ray crystallographic analysis were successfully prepared by
recrystallization from the chloroform solution of each com-
pound. Therefore, we conducted X-ray analysis and found that
the triarylated iodobenzofulvenes tend to crystallize in twisted
conformation through C–C bonds between the benzofulvene
framework and substituted three aryl rings (Figure 2). In addi-
tion, we also confirmed that the cyclization of unsymmetrical
tetraaryl[3]cumulenes occurred at the p-methoxyphenyl ring.
96
[a] All reactions were conducted using 0.1 mmol of tetraphenyl[3]cumulene
(1a), 0.12 mmol of [I+] source, and 1 mL of solvent at room temperature.
[b] Isolated yields.
When 1 mL of MeNO2 solution containing 0.1 mmol of tetra-
phenyl[3]cumulene (1a) and 0.12 mmol of N-iodosuccinimide
(NIS) was stirred for 2 hours at room temperature, the iodinated
triarylbenzofulvene 2a, 1-(diphenylmethylene)-2-iodo-3-phenyl-
1H-indene, was isolated in 86 % yield (Entry 1). The use of other
solvents such as MeCN, dichloromethane (DCM), benzene, and
toluene was ineffective for this reaction (Entries 2–5). The reac-
tion using molecular iodine instead of NIS afforded 2a in lower
yield (Entry 6). The yields of desired product 2a increased as
the reaction time became longer, and it reached 96 % after 3
hours (Entries 1 and 7–9). As a result, we found that the reaction
of tetraaryl[3]cumulene with NIS for 3 hours in MeNO2 is the
optimized condition for this reaction (Entry 9).
Next, we investigated the substrate scope using various
tetraaryl[3]cumulenes under the optimized reaction conditions
(Table 2). The reaction of symmetrical tetraaryl[3]cumulenes 1
possessing electron-donating groups with NIS proceeded
smoothly and gave the corresponding benzofulvenes 2 with
quantitative yields (Entries 2 and 3). On the other hand, the
desired benzofulvene could not be obtained by the reaction
using tetra-(p-chlorophenyl)[3]cumulene (1d) (Entry 4). Al-
though the trace amount of benzofulvene 2d was detected by
1H NMR spectroscopy of the crude mixture after the reaction
for 72 hours, we could not isolate the sufficient amount of prod-
uct for the characterization. It was found that the use of unsym-
metrical tetraaryl[3]cumulenes gave the corresponding benzo-
fulvenes as a sole product in good yields (Entries 5 and 6).
Figure 2. ORTEP views of a) three independent molecules of 2a in the unit
cell and b) 2e showing the atoms and thermal ellipsoids at 50 % probability,
respectively.[15]
To explain the formation of the benzofulvene 2, we proposed
the mechanism involving the generation of iodonium cation
(Scheme 1). Initially, the iodonium intermediate A was preferen-
tially formed by the reaction between the cationic iodine atom
and the centered cumulative double bond of 1, which is the
shortest double bond of the [3]cumulne and is slightly longer
than a typical triple bond.[16] Next, the nucleophilic attack of
the aryl group into the iodonium intermediate A gave the
benzofulvene 2. Based on the result of X-ray analysis of 2e, it
was indicated that the regioselective iodocyclization occurred
from the electron rich aromatic ring to iodonium cation. On the
basis of this mechanism, we consider that the N-bromosuccin-
The structures of all products 2 were determined by NMR imide (NBS) is also used for the transformation of tetraaryl[3]-
spectroscopy. Fortunately, single crystals of 2a and 2e suitable cumulene to construct a brominated benzofulvene scaffold.
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Scheme 1. Plausible mechanism for the iodocyclization of tetraaryl[3]cumulenes.
When the reaction of 1a with NBS instead of NIS under the indene skeleton are 58.6° for 2-substituted p-methoxyphenyl
optimized condition, the corresponding brominated triphenyl- ring (C3–C2–C9–C10) and 51.9° 3-substituted phenyl ring (C2–
benzofulvene 3 was successfully obtained in 62 % yield C3–C11–C12), respectively.
(Scheme 2).
Scheme 2. The reaction of tetraphenyl[3]cumulene (1a) with NBS.
Finally, we evaluated the utility of 1-(diarylmethylene)-3-aryl-
2-iodo-1H-indenes 2 as a coupling partner for the transition
metal catalyzed cross-coupling reaction. The reaction of benzo-
fulvene 2a with p-methoxyphenylboronic acid gave the corre-
sponding tetraarylated benzofulvene 4 in 95 % yield under the
Suzuki–Miyaura cross-coupling condition (Scheme 3a). The
Sonogashira cross-coupling reaction of 2a with 4-ethynylanis-
ole was also demonstrated and gave the corresponding benzo-
fulvene 5 in 38 % yield (Scheme 3b). The X-ray analysis of 4
revealed that the substituted four aryl rings twisted against the
benzofulvene plane to avoid the steric hindrance of each other
(Figure 3). The torsion angles between the benzofulvene core
and the aryl rings tethered to 1-methylene moiety are 53.9°
(C1–C4–C5–C6) and 57.8° (C1–C4–C7–C8), respectively. Those
values between the benzofulvene core and the aryl rings on
Figure 3. ORTEP view of 4 showing the atoms and thermal ellipsoids at 50 %
probability.[15]
In conclusion, we have demonstrated the facile synthesis of
benzofulvene scaffold from tetraaryl[3]cumulene under metal-
free and mild conditions. Because the iodocyclization of the
unsymmetrical iodonium intermediate occurred exclusively
from an electron rich aromatic ring, a sole benzofulvene was
formed in all cases. In addition, the obtained benzofulvene 2a
was successfully used as aryl iodide for common cross-coupling
reactions, and corresponding tetrasubstituted benzofulvenes
were easily accessed via Suzuki–Miyaura and Sonogashira cross-
coupling reactions, respectively.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgments
We thank the Research Clusters program of Tokushima Univer-
sity (Nos. 1802001, 1802003, and 2003006) for partial financial
support.
Keywords: Benzofulvenes · [3]Cumulenes ·
Iodocyclization · N-Iodosuccinimide
Scheme 3. The use of benzofulvene 2a as a coupling partner for a) Suzuki–
Miyaura cross-coupling reaction and b) Sonogashira cross-coupling reaction,
respectively.
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Received: September 3, 2020
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European Journal of Organic Chemistry
Iodocyclization
F. Yagishita,* K. Hoshi, Y. Yoshida,
S. Ueta, K. Minagawa, Y. Imada,
Y. Kawamura ....................................... 1–5
Facile Construction of Benzofulvene
Scaffold from Tetraaryl[3]cumulene
Through Electrophilic Iodocycliza-
tion
The reaction of tetraaryl[3]cumulenes philic iodocyclization. The iodinated
with N-iodosuccinimide afforded the benzofulvene was successfully used as
corresponding iodinated triarylbenzo- versatile precursor for common cross-
fulvenes with high yields under mild coupling reaction.
reaction conditions through electro-
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