Cobalt-catalyzed annulation of aryl iodides with alkynes

Article abstract of DOI:10.1016/j.tetlet.2013.07.133

A cobalt-catalyzed approach for the concise synthesis of naphthalenes by the annulation of aryl iodides with alkynes is disclosed. In the reaction, manganese reductant and MeCN solvent are necessary to proceed efficiently, which tolerates various functional groups, for example, boronate ester. Mechanistic investigation indicates that the transformation employs electrophilic aromatic substitution (S_EAr) in the aromatic C-H bond replacement step.

Full text of DOI:10.1016/j.tetlet.2013.07.133

Tetrahedron Letters 54 (2013) 5659–5662
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Tetrahedron Letters
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Cobalt-catalyzed annulation of aryl iodides with alkynes
⇑
⇑
Kimihiro Komeyama , Tetsuya Kashihara, Ken Takaki
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima City, Hiroshima 739-8527, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A cobalt-catalyzed approach for the concise synthesis of naphthalenes by the annulation of aryl iodides
with alkynes is disclosed. In the reaction, manganese reductant and MeCN solvent are necessary to pro-
ceed efficiently, which tolerates various functional groups, for example, boronate ester. Mechanistic
investigation indicates that the transformation employs electrophilic aromatic substitution (SEAr) in
the aromatic C–H bond replacement step.
Received 2 July 2013
Revised 23 July 2013
Accepted 26 July 2013
Available online 2 August 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Cobalt catalyst
Annulation
C–H replacement
Carbocobaltation
Naphthalene
Selective and practical construction of naphthalenes and other
polyaromatic hydrocarbons has been an important subject in or-
reductive elimination via B to afford naphthalenes (Scheme 2, bot-
tom). On the other hand, inexpensive and abundant cobalt salts
have been extensively used as catalysts in the C(sp2)–C(sp2) cou-
plings,9 wherein the generation of the aryl-Co by the oxidative
addition is involved as a key step. Furthermore, the aryl-Co is
known to be an active species for the alkyne insertion to give a vi-
nyl-Co similarly to the carbozincation,10 cyclotrimerization,11 and
other related reactions.12 But, the generated aryl-Co and vinyl-Co
are quickly transmetalated to give thermally more stable vinyl-
zinc complexes by the residual salts or organozinc reagents during
the reaction.13 In contrast, manganese (Mn) powder works
effectively as a reductant in the aryl-Co generation step;14 note-
worthy, the transmetalation of the generated aryl-Co with residual
manganese salts does not occur.14c Based on these results, we
envisaged that Co/Mn system might induce the annulation (route
d). Herein, we would like to report a cobalt-catalyzed annulation
ganic synthesis because of their potential utility as
p-conjugated
materials.1 Among several synthetic methods for naphthalenes,
transition metal-catalyzed annulation of aromatic compounds
with two alkynes has attracted much attention due to its simplic-
ity, flexibility, and modularity. Among them, the double-function-
alization of 1,2-dihaloarenes with alkynes using Pd- and Ni
catalysts has been demonstrated (Scheme 1, route a).2 In contrast,
a similar annulation of mono-functionalized aromatic substrates
such as aryl iodides,3 aroyl chlorides,4 benzoic acids,5 arylboronic
acids,6 and simple arenes having a directing group (DG),7 has also
been reported (route b). These methods are not only synthetically
attractive from atom economy and structural diversity points of
view, but also mechanistically intriguing because the reaction in-
volves the C–H bond replacement. However, these procedures
use expensive and rare transition metal catalysts such as Pd, Rh,
and Ir. As the improved method, Yoshikai recently developed the
Fe-catalyzed annulation of arylindiums with alkynes (route c).8
However, the method requires a large excess of arylindiums and
Grignard reagents, which would restrict the use of some reactive
substituents in the annulation reaction.
In consideration of the background and related information, we
noticed that vinyl-transition metal species A or A0 are common key
intermediates in routes b and c, which were followed by the
second alkyne insertion and sequential C–H replacement, and/or
⇑
Corresponding authors. Tel.: +82 82 424 7747; fax: +82 82 424 5494 (K.K.); tel.:
+82 82 424 7744; fax: +82 82 424 5494 (K.T.).
E-mail addresses: kkome@hiroshima-u.ac.jp (K. Komeyama), ktakaki@hiroshima-u.
ac.jp (K. Takaki).
Scheme 1. Transition metal-catalyzed annulations of mono- and bi-functionalized
arenes with alkynes.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.133

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K. Komeyama et al. / Tetrahedron Letters 54 (2013) 5659–5662
4). An N-heterocyclic carbene ligand {IMes: 1,3-bis(mesityl)-imi-
dazol-2-ylidene}, which was generated in situ from the reaction
of its salt with Cs2CO3, did not take effect (entry 5), but Cs2CO3
did not control the reaction progress (entry 6). In contrast, mono-
dentate phosphine ligands, P(n-Bu)3, P(t-Bu)3, P(Mes)3, and PPh3
were totally more effective than bidentate ones because of
restraining the formation of hydroarylation products (entries
7–10). Finally, simple and ubiquitous PPh3 was proved to be the
most effective ligand (entry 10). 20 mol % of PPh3 led to the similar
result (entry 11). In contrast, the absence of PPh3 caused a slightly
lower yield (entry 12). In the Co-catalyzed annulation, Mn reduc-
tant was necessary to effect the annulation efficiently, that is, Zn
powder mainly gave the hydroarylation product (entry 13). Other
cobalt complexes such as CoCl2 and CoI2 showed the similar cata-
lytic activity (entries 14 and 15), but Co(acac)2 and other transition
metal complexes, NiCl2 and FeCl2, did not convert both substrates
to the products at all (entries 16–18). Additionally, we found that
CoBr2/PPh3 complex could effect the annulation under ambient
temperature (25 °C) for 6 h, giving rise to the corresponding naph-
thalene 3aa in 70% yield (entry 19). The metal salt catalyst, reduc-
tant, and MeCN solvent were crucial in the transformation. Other
Scheme 2. Common key intermediates in the transition metal-catalyzed
annulation.
of aryl iodides with 2 equiv of unactivated alkynes in the presence
of Mn powder.
To prove the feasibility of the hypothesis, we first examined the
reaction of 4-iodotoluene (1a) with 4-octyne (2a) under various
reaction conditions (Table 1). When 1a was treated with 2.2 equiv
of 2a in the presence of CoBr2 (10 mol %), 1,2-bis(diphenylphos-
phino)ethane (DPPE, 10 mol %) and Mn powder (2.0 equiv) in
MeCN for 3 h at 50 °C, the desired adduct 3aa was obtained in
52% yield, along with hydroarylation product 4 in 11% yield (entry
1).15 The similar bidentate phosphine ligand such as 1,10-
bis(diphenylphosphino)ferrocene (DPPF) was also an effective li-
gand (entry 2), but xantphos completely prevented the reaction
(entry 3). 2,20-Bipyridine (Bipy) afforded the lower yield (entry
Table 2
Scope of aryl iodides 1 and alkynes 2 in the co-catalyzed annulationa
Table 1
Screening of reaction conditions
Entry
Catalyst
Ligand
Reductant
Yielda (%)
3aa
4b
1
2
3
4
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoBr2
CoCl2
CoI2
DPPE
DPPF
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Mn
Zn
Mn
Mn
Mn
Mn
Mn
Mn
52
53
11
14
Xantphos
Bipy
No reaction
40
No reaction
51
49
56
52
69
62
54
12
60
24
5c
6e
7
IMesꢀHCld
DPPE
10
5
5
4
8
14
4
25
9
P(n-Bu)3
P(t-Bu)3
P(Mes)3
8
9
f
10
11
12
13
14
15
16
17
18
19h
PPh3
PPh3
g
—
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
62
13
Co(acac)2
NiCl2
FeCl2
No reaction
No reaction
No reaction
70 (68)
CoBr2
4
a
Determined by GC using decane as an internal standard. Value in parenthesis
indicates isolated yield.
b
Hydroarylation products were formed with ca. 50:50 E/Z ratio.
With Cs2CO3 (15 mol %).
N,N0-Bis(2,4,6-trimethylphenyl)imidazolium hydrochloride.
With Cs2CO3 (100 mol %).
Tris(2,4,6-trimethylphenyl)phosphine.
20 mol % of PPh3 was used.
The reaction was carried out at 25 °C for 6 h.
c
d
e
f
g
a
The indicated yields were isolated yields. Gray color indicates the minor isomer
h
and its ratio.

K. Komeyama et al. / Tetrahedron Letters 54 (2013) 5659–5662
5661
solvents such as THF, DMF, DMAc, DMI, DMSO, and toluene
afforded sluggish product yields.16 In all screening, no homo-cou-
pling (4,40-dimethoxy-1,10-biphenyl) and dehalogenated product
(anisole) were observed.
Co(II) halides initially would be reduced by Mn to low valent
cobalt species C, which could be oxidized by aryl iodides to afford
Ar–[Co]–I (D). Then the double alkyne insertion to the Ar–[Co]
bond would provide the intermediate F via the formation of E.
According to the labeling-experiment {eq (1)}, F would undergo
the intramolecular SEAr reaction to produce the intermediate G,
which would be followed by reductive elimination to afford the
naphthalene 3 and C.
In conclusion, we have developed the cobalt-catalyzed annula-
tion of aryl iodides with alkynes to lead to various naphthalene
derivatives. In the annulation, a diverse set of aryl iodides possess-
ing several functional groups were converted to the corresponding
naphthalenes; particularly the tolerance of boronate ester unit
represents a unique reactivity of the cobalt catalyst. The substrate
scope and labeling-experiment supported that the C–H replace-
ment would be induced by intramolecular SEAr reaction of Co–I
with the aryl group. Further studies for the mechanism and syn-
thetic application of the cobalt-catalyzed transformation based
on these finding are currently underway in our laboratory.
Next, with optimized conditions in hand, we explored the scope
and limitation of substrates in the cobalt-catalyzed annulation.
These results are summarized in Table 2.17 Phenyl iodide (1b)
could be converted to the corresponding a 1:2 adduct 3ba in 50%
yield. The annulation favored electron-rich aryl iodides 1c rather
than electron-deficient ones 1d, 1e, 1g, and 1h. In the latter cases,
the alkyne and the corresponding hydroarylated products were not
detected, whereas aryl iodides remained after the reaction. Inter-
estingly, an aryl iodide possessing a boronate ester 1f participated
in the annulation,6b,18 giving rise to the corresponding naphthalene
skeleton in good yield without a loss of the boron function. meta-
Substituted unsymmetic aryl iodides, 1i, 1k, 1m, and 1n, were also
tolerated in the annulation. The C–H functionalization selectively
occurred at the less-hindered position unlike the previously re-
ported Rh- and Fe-catalyzed annulations.6b,8 These regio-selectiv-
ity might indicate that the reaction employs a different reaction
pathway from the oxidative addition of the C–H bond. Aryl bro-
mide such as 4-bromo anisole also participated in the reaction to
give 3ca, albeit in lower yield (32% for 12 h at 25 °C). Additionally,
the Co-catalyzed annulation could be extended to the reaction
with 5-dodecyne (2b) and 1,4-diphenyl-2-butyne (2c) to give the
corresponding products 3cb and 3cc in good yields.
Acknowledgment
This work was partially supported by a Grant-in-Aid for Scien-
tific Research from the ministry of Education, Culture, Sports, Sci-
ence and Technology of Japan.
To gain insight into the reaction mechanism, a labeling-exper-
iment was carried out {eq (1)}. A reaction of 1c–d1 with 4-octyne
afforded a mixture of 3ca and 3ca-d1 with 1:1.18 ratio in 82%
yield. This result clearly shows that the reaction does not involve
an oxidative addition of the aryl C–H bond to the cobalt center.19
In addition, the efficiency of the annulation strongly depended
on the electronic circumstance of aromatic ring on the aryl
iodides; electron-rich aryl iodides were superior to electron-defi-
cient ones (Table 2). These findings suggested that the cobalt-cat-
alyzed annulation might employ an electrophilic aromatic
substitution (SEAr reaction) in the C–H bond replacement as well
recognized in the palladium chemistry3b,20 (Scheme 3). Thus, the
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.07.
133.
References and notes
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15. .A pretreatment of a mixture of CoBr2 and Mn powder with heat-gun (400 °C)
under vacuum conditions was very important for the annulation to proceed
efficiently; otherwise it caused
a longer reaction (20 h) with lower yield
(>20%). 3aa and 4 were easily separated by silica-gel column chromatography.
16. Solvent (yields of 3aa and 4): THF: tetrahydrofuran (2%, 10%); DMF: N,N-
Dimethylformamide (1%, 8%); DMAc: N,N-Dimethylacetamide (0%, 5%), DMI
(1,3-Dimethyl-2-imidazolidinone), DMSO: Dimethyl sulfoxide (1%, 7%);
Scheme 3. Plausible reaction mechanism.

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K. Komeyama et al. / Tetrahedron Letters 54 (2013) 5659–5662
toluene (0%, 0%). Similar solvent effect was pointed out in the cobalt-catalyzed
reaction. See: Ref. 10a.
and ether. Aqueous phase was extracted with ether. The combined ethereal
phases were dried over anhydrous MgSO4, filtered, and concentrated to afford
crude product. Silica-gel column purification of the crude product provided the
corresponding naphthalenes.
17. General procedure of cobalt-catalyzed annulation of aryl iodides with alkynes:
Anhydrous CoBr2 (5.5 mg, 0.025 mmol) and Mn (27.5 mg, 0.5 mmol) were
placed in a 20-mL Schlenk tube and heated with heat-gun (400 °C) under the
vacuum conditions for 30 min. After cooling to room temperature, the tube
was filled with N2 gas, and then PPh3 (6.6 mg, 0.025 mmol), aryl iodide
(0.25 mmol), and acetonitrile (0.5 mL) were sequentially added. Alkyne
(0.55 mmol) was successively added to the mixture. After stirring at 25 °C
for several hours, the reaction mixture was poured saturated NH4Cl solution
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