Iron-catalyzed annulation reaction of arylindium reagents and alkynes to produce substituted naphthalenes

Article abstract of DOI:10.1016/j.tet.2012.04.004

We report here an iron-bisphosphine complex-catalyzed annulation reaction of an arylindium reagent and two alkyne molecules that affords a substituted naphthalene derivative in moderate to good yield. The reaction represents a new example of iron-catalyzed C-C bond forming reactions via C-H bond functionalization.

Full text of DOI:10.1016/j.tet.2012.04.004

Tetrahedron 68 (2012) 5167e5171
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Iron-catalyzed annulation reaction of arylindium reagents and alkynes to produce
substituted naphthalenes
*
Laksmikanta Adak, Naohiko Yoshikai
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
We report here an ironebisphosphine complex-catalyzed annulation reaction of an arylindium reagent
and two alkyne molecules that affords a substituted naphthalene derivative in moderate to good yield.
The reaction represents a new example of iron-catalyzed CeC bond forming reactions via CeH bond
functionalization.
Received 27 January 2012
Received in revised form 30 March 2012
Accepted 1 April 2012
Available online 7 April 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Iron catalysis
Organoindium reagent
Alkyne
CeH bond functionalization
Naphthalene
1. Introduction
(a)
R
R
H
X
R
R
Pd, Rh, Ir etc.
Efficient and selective construction of naphthalenes and
other polycyclic aromatic hydrocarbons has been an important
subject in organic synthesis because of their potential utility as
+
2
R
R
-conjugated functional materials.1 Among various synthetic
X = I, COCl, CO2H, B(OH)2 etc.
p
methods for naphthalenes,2 metal-mediated or -catalyzed annu-
lation of a mono- or difunctionalized aromatic substrate with two
alkyne molecules has attracted significant attention because of
flexible and modular nature of the approach.3e5 The use of
monofunctionalized aromatic substrates is not only synthetically
attractive from atom economy and structural diversity points of
view but also mechanistically intriguing because the reaction in-
volves functionalization of the ortho CeH bond.6 Thus far, a variety
of monofunctionalized aromatic substrates have been shown to
participate in such annulation reactions, including iodoarenes,3c-e
aroyl chlorides,3f benzoic acids,3gei and arylboronic acids,3n,o
while in all cases expensive transition metals, such as palladium,
rhodium, and iridium have been used as catalysts (Scheme 1a).
Recently, we developed a preparative method for arylindium
reagents from the corresponding aryl bromides and indium metal
using a cobaltebathophenanthroline complex and LiCl as a catalyst
and a promoter, respectively (Scheme 1b).7e9 The thus-formed
arylindium reagents participate in palladium-catalyzed biaryl
(b)
cat. [Co]
In LiCl
R
R
THF, 80 100 °C
Br
+
InX2
(c)
R
R
R
H
R
R
cat. [Fe]
2
In
R
Scheme 1.
cross-coupling reactions without interference from the cobalt cat-
alyst. On our way to expand the scope of synthetic applications of
the arylindium reagents, we became interested in their use in an
iron-catalyzed reaction with alkynes because of the prominent
reactivity of iron catalysts in carbometalation of alkynes.10 Contrary
to our initial expectation, we have found an iron-catalyzed annu-
lation reaction of an arylindium reagent and two alkyne molecules
to afford a naphthalene derivative, which is reported herein
* Corresponding author. Tel.: þ65 6592 7768; fax: þ65 6791 1961; e-mail
address: nyoshikai@ntu.edu.sg (N. Yoshikai).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.04.004

5168
L. Adak, N. Yoshikai / Tetrahedron 68 (2012) 5167e5171
(Scheme 1c). The reaction represents an interesting new example of
None of other bidentate phosphine ligands including dppe, dppp,
dppf, DPEphos, and Xantphos exhibited comparable catalytic ac-
tivity (entries 4e8).14 Other types of ligands, such as PCy3, 1,10-
phenanthroline, and IPrꢀHCl14 were also ineffective (entries
9e11). The metal/ligand ratio of 2 was crucial as the use of 5 mol %
of dppbz resulted in a significant decrease in the product yield
(entry 12). Fe(acac)3 was an inferior precatalyst compared with
FeCl3 (entry 13). The use of a smaller amount of Me3SiCH2MgCl led
to exclusive formation of the alkenylation product 4aa (entry 14).
Note that aryl Grignard and zinc reagents did not produce the an-
nulation product at all under the optimized conditions shown in
entry 3.
With the optimized catalytic system in hand, we explored the
scope of the present annulation reaction (Scheme 2). Arylindium
reagents bearing electron-neutral or electron-donating sub-
stituents at the para position participated smoothly in the reaction
with 1a to afford naphthalene derivatives 3abe3ae in 66e78%
yields, except that a strongly donating dimethylamino substituent
caused adverse effects (see 3af). On the other hand, electron-
withdrawing fluoro and trifluoromethyl groups at the para posi-
tion slowed down the reaction, resulting in modest yields of
products 3ag and 3ah, respectively. The reaction of meta-
fluorophenylindium reagent afforded an annulation product 3ai via
regioselective functionalization of the CeH bond ortho to the
fluorine atom. The same sense of regioselectivity has been observed
for rhodium-catalyzed annulation of meta-fluorophenylboronic
acid and diphenylacetylene,3o which may be ascribed to the ability
of fluorine to strengthen a metalecarbon bond at the ortho
iron-catalyzed CeC bond formation via CeH bond cleavage.11,12
2. Results and discussion
At the outset of our investigation, we examined the reaction of
4-octyne 1a with a 4-tert-butylphenylindium reagent prepared by
our indium insertion reaction of 1-bromo-4-tert-butylbenzene.
After initial experiments using a few different iron catalysts, it
became clear that the as prepared indium reagent is too unreactive
to give any addition products. In analogy to the reactivity of arylzinc
reagents in iron-catalyzed cross-coupling reactions,13 we envi-
sioned that the reactivity of the arylindium reagent might be en-
hanced by transmetalation with
a Grignard reagent bearing
a nontransferable trimethylsilylmethyl group. Thus, systematic
screening experiments were performaed on the reaction of 1a with
an arylindium reagent 2a, which was generated from the 4-tert-
butylphenylindium reagent (3 equiv) and Me3SiCH2MgCl (6 equiv)
(Table 1). With FeCl3 (5 mol %) as the precatalyst, we obtained
a naphthalene derivative 3aa and an olefin product 4aa (E/Z¼ca.
6:4) albeit in low yields (entry 1), whereas none of those products
was obtained in the absence of FeCl3 (entry 2).
Table 1
Screening of reaction conditionsa
nPr
tBu
tBu
nPr
nPr
tBu
H
FeCl3 (5 mol %)
ligand
nPr
nPr
3aa
InX2
nPr
nPr
nPr
(3 equiv)
+
+
+
nPr
nPr
nPr
nPr
Me
nPr
nPr
Ph
nPr
nPr
THF, 60 °C, 14 h
Me3SiCH2MgCl
(6 equiv)
1a
nPr
nPr
nPr
nPr
3ad, 72%
nPr
2a
4aa
3ab, 78%
3ac, 66%
nPr
nPr
Entry
Ligand (mol %)
Yield (%)b
MeO
nPr
Me2N
nPr
F
nPr
nPr
3aa
4aac
nPr
nPr
1
d
3
0
5
0
0
3
2
9
8
12
7
2d
3
d
nPr
3ae, 71%
nPr
3af, 28%
nPr
dppbz (10)
dppe (10)
dppp (10)
dppf (10)
DPEphos (10)
Xantphos (10)
PCy3 (20)
80e
20
5
3ag, 49%
4
5
6
7
8
9
nPr
F
nPr
H(Cl) nPr
7
3
3
3
F3C
nPr
nPr
nPr
nPr
nPr
nPr
(H)Cl
R
10
11
12
13f
14g
1,10-Phenanthroline (10)
IPrꢀHCl (20)
5
0
27
55
0
8
5
0
0
nPr
nPr
nPr
3ah, 22%
3ai, 35%
3aj, 42% (1:1)
dppbz (5)
dppbz (10)
dppbz (10)
F
nPr
R
Ph
41
nPr
nPr
tBu
R
R
Ph
Ph
a
Reaction was performed on a 0.3 mmol scale.
b
c
d
e
f
Determined by GC using n-tridecane as an internal standard.
The E/Z ratio was 6:4 as determined by GC and 1H NMR.
FeCl3 was omitted from the reaction.
Isolated yield.
Fe(acac)3 was used instead of FeCl3.
3 equiv of Me3SiCH2MgCl was used.
Cl
R
nPr
R
Ph
3ak, 40%
3ba (R = Et), 83%
3ca (R = nBu), 76%
3da (R = tBu), 33%
3db (R = H), 25%
g
Me
Et
Me
Ph
Ph
Ph
tBu
nPr
Me
Subsequent screening of ligands led us to find that a diphos-
Ph
Et
phine ligand 1,2-bis(diphenylphosphino)benzene (dppbz) (10 -
mol %) significantly promotes the annulation reaction to afford
3aa in 80% yield with no formation of 4aa (entry 3). It is interesting
to note that no external oxidant is necessary for the catalytic
turnover, while the overall transformation appears to be an
oxidative coupling of the arylindium reagent and the alkyne.
Me
nPr
3ga + three regiosiomers
85% (ratio = ca. 1:1:1:1)
3ea (R = tBu), 38%
3eb (R = H), 52%
3fb, 46%
Scheme 2. Scope of iron-catalyzed annulation of arylindium reagents and alkynes. The
bond indicated by a bold line refer to the CeC bond formed via CeH bond cleavage.

L. Adak, N. Yoshikai / Tetrahedron 68 (2012) 5167e5171
5169
position.15 In contrast, no regioselectivity in the CeH bond func-
3. Conclusion
tionalization was observed for the reaction of meta-chlor-
ophenylindium reagent (see 3aj). When both chloro and fluoro
substituents were present at the meta positions, exclusive func-
tionalization of the CeH bond proximal to the fluorine atom took
place (see 3ak).
In summary, we have developed an iron-catalyzed annulation
reaction of arylindium reagents and internal alkynes to afford
substituted naphthalene derivatives. The reaction represents an
intriguing new example of iron-catalyzed aromatic CeH bond
functionalization. Further effort will focus on the investigation
of mechanistic details including the origin of the ligand effect,16 and
the extension of iron catalysis of organoindium reagents.
Not unexpectedly, other dialkylacetylenes, such as 3-hexyne
and 5-decyne took part in the annulation reaction to afford prod-
ucts 3ba and 3ca in good yields. On the other hand, the reaction of
diphenylacetylene was rather sluggish, and the corresponding an-
nulation products were obtained only in modest yields (3da and
3db). 1-Phenyl-1-propyne and 1-phenyl-1-butyne regioselectively
afforded 1,4-dialkyl-2,3-diphenylnaphthalene derivatives 3ea, 3eb,
and 3fb in moderate yields. Note that this regioselectivity is the
same as that observed for rhodium-catalyzed annulation reactions
using phenylpyrazole and phenylboronic acid.3k,o On the other
hand, the reaction of 2-hexyne was efficient but not regioselective,
producing an equimolar mixture of four regioisomers including 3ga
in 85% overall yield.
4. Experimental section
4.1. General
All reactions dealing with air- and moisture-sensitive com-
pounds were performed by standard Schlenk techniques in oven-
dried reaction vessels under nitrogen atmosphere. Analytical
thin-layer chromatography (TLC) was performed on Merck 60 F254
silica gel plates. Flash chromatography was performed using
While the mechanism of the present reaction is not clear at
present, we may suggest a possible catalytic cycle as illustrated in
Scheme 3. The iron precatalyst and the arylindium reagent would
generate an aryliron species A, which would undergo insertion of
the alkyne to give an alkenyliron species B.10 The subsequent
reaction pathway of the species B may be relevant to that of
a putative 2-biarylliron species proposed for the iron-catalyzed
reaction of a 2-biaryl Grignard reagent with an alkyne to pro-
duce a phenanthrene derivative by Nakamura et al.12c Thus, it
may undergo intramolecular ortho CeH bond activation to give
a ferracycle C followed by insertion of the second alkyne mole-
cule to afford the naphthalene product 3. An alternative route to
3 may involve insertion of the second alkyne molecule to the
species B to form a dienyliron species D, which then undergoes
intramolecular CeH bond functionalization. Judging from the
regioselectivity observed for the reactions of 1-phenyl-1-propyne
(3ea and 3eb) and 1-phenyl-1-butyne (3fb), the former pathway
appears more likely. The formation of naphthalene 3 is formally
accompanied by generation of an iron hydride species E. Because
the present reaction does not require an external oxidant, we
speculate that the aryliron species A is regenerated through
transmetalation between the iron hydride species E and the
arylindium reagent.
40e63 mm silica gel (Si 60, Merck). 1H and 13C nuclear magnetic
resonance (NMR) spectra were recorded on a JEOL ECA-400
(400 MHz) spectrometer, and are reported in parts per million
(ppm) downfield from an internal standard, tetramethylsilane
(0 ppm) and CHCl3 (77 ppm), respectively. Gas chromatographic
(GC) analysis was performed on a Shimadzu GC-2010 system
equipped with an FID detector and a capillary column, DB-5 (Agi-
lent J&W, 0.25 mm i.d.ꢁ30 m, 0.25
mm film thickness). High-
resolution mass spectra (HRMS) were recorded with a Q-TOf Pre-
mier LC HR mass spectrometer. Unless otherwise noted, commer-
cial reagents were purchased from Aldrich, Alfa Aesar, and other
commercial suppliers and were used as received. Cobalt(II) bro-
mide (99%) and indium powder (99.99% trace metals basis;
contain w1% Mg as anticaking agent) were purchased from
Aldrich. Bathophenanthroline, iron(III) chloride (>98%), and 1,2-
bis(diphenylphosphino)benzene were purchased from Alfa Aesar,
Merck, and Strem Chemicals, respectively. THF was distilled
over Na/benzophenone before use.
4.2. General procedure for iron-catalyzed annulation of
arylindium reagents and alkynes
An arylindium reagent was prepared in a 10 mL Schlenk tube
according to our procedure (typically 0.90 mmol in 1 mL THF).7 The
reagent solution was carefully transferred to another Schlenk tube
via cannula while leaving insoluble materials including excess in-
dium powder. To the arylindium solution was added
Me3SiCH2MgCl (0.90 M in THF, 2 mL, 1.8 mmol) over 5 min at 0 ꢂC.
After stirring for 1 h at 0 ꢂC and 45 min at room temperature, 1,2-
bis(diphenylphosphino)benzene (13.4 mg, 0.030 mmol), 4-octyne
FeCl3/L
Ar In
2
H
H
(44 mL, 0.30 mmol), and FeCl3 (2.5 mg, 0.015 mmol) were sequen-
[Fe]
R
R
tially added. The resulting mixture was stirred at 60 ꢂC for 14 h, and
then allowed to room temperature, diluted with ethyl acetate
(5 mL), and quenched with H2O (1 mL). The aqueous layer was
extracted with ethyl acetate (3 x 10 mL), and the combined organic
layer was dried over Na2SO4 and concentrated under reduced
pressure. The residue was purified by silica gel chromatography
(eluent: hexane) to afford the naphthalene product.
[Fe]
H
In
R
1
A
C
R
Ar In
2
or
H
[Fe]
H [Fe]
R
[Fe]
H
R
E
B
R
R
4.2.1. 6-(tert-Butyl)-1,2,3,4-tetrapropylnaphthalene (3aa). Colorless
R
R
R
R
D
liquid; Rf 0.65 (hexane); 1H NMR (400 MHz, CDCl3):
d 1.12e1.20 (m,
R
R
R
R
12H), 1.46 (s, 9H), 1.58e1.65 (m, 4H), 1.70e1.79 (m, 4H), 2.75e2.80
(m, 4H), 3.02e3.09 (m, 4H), 7.49 (dd, J¼6.8, 3.2 Hz, 2H), 8.09 (dd,
1
J¼6.6, 3.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 15.1, 15.2, 15.3 (2C),
24.7, 24.8, 25.2 (2C), 31.5 (5C), 32.7, 32.9, 35.0, 119.8, 123.4, 124.5,
3
Scheme 3. A possible catalytic cycle.
129.5, 131.0, 134.1, 134.2, 136.4, 137.1, 146.8; HRMS (ESIþ) Calcd for

5170
L. Adak, N. Yoshikai / Tetrahedron 68 (2012) 5167e5171
C26H40 [MþH]þ 353.3208, found 353.3209. The 1H and 13C NMR
d 1.09e1.15 (m, 12H), 1.56e1.62 (m, 4H), 1.64e1.71 (m, 4H),
spectra were in agreement with the literature data.3f
2.73e2.77 (m, 4H), 3.00e3.05 (m, 4H), 7.56 (dd, J¼9.2, 1.8 Hz, 1H),
8.08 (d, J¼9.2 Hz, 1H), 8.27 (s, 1H), 13C NMR (100 MHz, CDCl3):
4.2.2. 1,2,3,4-Tetrapropylnaphthalene (3ab). Colorless liquid; Rf
d 15.0, 15.1, 15.3 (2C), 24.8, 24.9, 25.1 (2C), 31.3, 31.4, 32.8, 32.9, 120.1
0.64 (hexane); 1H NMR (400 MHz, CDCl3):
d
1.18e1.24 (m, 12H),
(q, 3JCꢃF¼2.9 Hz), 122.4 (q, 3JCꢃF¼4.1 Hz), 125.1 (q, 1JCꢃF¼270.6 Hz),
2
1.66e1.72 (m, 4H), 1.74e1.82 (m, 4H), 2.81e2.86 (m, 4H),
125.8, 126.3 (q, JCꢃF¼31.0 Hz), 130.4, 132.7, 134.6, 135.4, 138.7,
3.09e3.13 (m, 4H), 7.47e7.50 (m, 2H), 8.07e8.10 (m, 2H); 13C NMR
139.6; HRMS (ESIþ) Calcd for C23H31F3 [MþH]þ 365.2456, found
(100 MHz, CDCl3):
d
15.2 (2C), 15.3 (2C), 24.8 (2C), 25.2 (2C), 31.5
365.2452.
(2C), 32.8 (2C), 124.7 (2C), 124.8 (2C), 131.4 (2C), 134.4 (2C), 137.1
(2C); HRMS (ESIþ) Calcd for C22H32 [MþH]þ 297.2582, found
297.2581. The 1H and 13C NMR spectra were in agreement with the
literature data.3f
4.2.9. 5-Fluoro-1,2,3,4-tetrapropylnaphthalene (3ai). Colorless liq-
uid; Rf 0.75 (hexane); 1H NMR (400 MHz, CDCl3):
d 1.02e1.13 (m,
12H), 1.50e1.69 (m, 8H), 2.45e2.49 (m, 2H), 2.70e2.74 (m, 4H),
2.95e3.00 (m, 1H), 3.08 (br, 1H), 6.99e7.06 (m, 1H), 7.25e7.31 (m,
4.2.3. 6-Methyl-1,2,3,4-tetrapropylnaphthalene (3ac). Colorless liq-
1H), 7.76 (d, J¼8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 15.1,
uid; Rf 0.67 (hexane); 1H NMR (400 MHz, CDCl3):
d
1.07e1.14 (m,
15.2, 15.3, 15.5, 24.5, 25.0, 25.1, 25.7 (d, JCꢃF¼4.8 Hz), 32.1, 32.4
5
5
4
12H), 1.53e1.60 (m, 4H), 1.62e1.71 (m, 4H), 2.50 (s, 3H), 2.69e2.73
(m, 4H), 2.96e3.00 (m, 4H), 7.23 (d, J¼8.7 Hz,1H), 7.73 (s,1H), 7.88 (d,
(d, JCꢃF¼12.4 Hz), 33.0, 33.8 (d, JCꢃF¼14.4 Hz), 110.5 (d,
4 3
2JCꢃF¼25.9 Hz), 120.8 (d, JCꢃF¼3.8 Hz), 122.1 (d, JCꢃF¼9.6 Hz),
J¼8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
15.1, 15.2, 15.3 (2C), 22.2,
124.3 (d, JCꢃF¼10.5 Hz), 133.4 (d, JCꢃF¼5.8 Hz), 134.1 (d,
2
3
1
24.7, 24.8, 25.1, 25.2, 31.4, 31.5, 32.7, 32.9, 123.8, 124.7, 126.8, 129.6,
131.5, 133.7, 133.9, 134.2, 136.1, 137.2; HRMS (ESIþ) Calcd for C23H34
[MþH]þ 311.2739, found 311.2730. The 1H and 13C NMR spectra were
in agreement with the literature data.3f
3JCꢃF¼4.8 Hz), 136.9, 138.2, 138.7, 160.6 (d, JCꢃF¼253.9 Hz);
HRMS (ESIþ) Calcd for C22H31
F
[MþH]þ 315.2488, found
315.2489.
4.2.10. 6-Chloro-1,2,3,4-tetrapropylnaphthalene (3aj) and 5-chloro-
1,2,3,4-tetrapropylnaphthalene (3aj0). Colorless liquid; Rf 0.72
4.2.4. 6-Phenyl-1,2,3,4-tetrapropylnaphthalene (3ad). Colorless liq-
uid; Rf 0.59 (hexane); 1H NMR (400 MHz, CDCl3):
d
1.09e1.15 (m,
(hexane); 1H NMR (400 MHz, CDCl3):
d 1.03e1.14 (m, 24H),
12H), 1.57e1.63 (m, 4H), 1.68e1.76 (m, 4H), 2.73e2.77 (m, 4H),
3.00e3.08 (m, 4H), 7.36 (t, J¼7.6 Hz, 1H), 7.48 (t, J¼7.8 Hz, 2H), 7.65
(dd, J¼9.1, 1.8 Hz, 1H), 7.71 (dd, J¼8.2, 1.4 Hz, 2H), 8.06 (d, J¼9.1 Hz,
1.53e1.71 (m, 16H), 2.70e2.77 (m, 8H), 2.93e3.00 (m, 8H),
7.21e7.25 (m, 2H), 7.32 (dd, J¼9.3, 2.0 Hz, 1H), 7.49 (d, J¼7.4 Hz, 1H),
7.90e7.94 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 14.9, 15.1 (3C), 15.3
1H), 8.17 (d, J¼1.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d
15.1, 15.2,
(4C), 24.6, 24.7, 24.8, 24.9, 25.1 (2C), 26.3 (2C), 31.4, 31.5, 32.2, 32.5,
32.7, 32.8, 32.9, 33.1, 123.7, 124.1, 124.4, 125.3, 126.6, 129.2, 129.4,
129.7,130.6,131.1,132.4, 133.7,134.2, 134.5,134.9,135.0, 137.5,138.0,
138.5, 140.2; HRMS (ESIþ) Calcd for C22H31Cl [MþH]þ 331.2193,
found 331.2188. The 1H NMR spectra indicated ca. 1:1 ratio of the
two regioisomers.
15.3 (2C), 24.8, 24.9, 25.2 (2C), 31.5 (2C), 32.8, 32.9, 123.0, 124.3,
125.4, 127.2, 127.7 (2C), 129.0 (2C), 130.6, 131.5, 134.3, 134.6, 137.2,
137.4, 137.7, 142.2; HRMS (ESIþ) Calcd for C28H36 [MþH]þ 373.2895,
found 373.2894.
4.2.5. 6-Methoxy-1,2,3,4-tetrapropylnaphthalene
(3ae). Colorless
liquid; Rf 0.54 (hexane/EtOAc¼99/1); 1H NMR (400 MHz, CDCl3):
4.2.11. 7-Chloro-5-fluoro-1,2,3,4-tetrapropylnaphthalene
(3ak). Colorless liquid; Rf 0.75 (hexane); 1H NMR (400 MHz,
d
1.07e1.14 (m, 12H), 1.54e1.61 (m, 4H), 1.63e1.72 (m, 4H), 2.67e2.73
(m, 4H), 2.94e2.99 (m, 4H), 3.92 (s, 3H), 7.09 (dd, J¼9.2, 2.7 Hz,1H), 7.28
CDCl3): d 1.08e1.15 (m, 12H), 1.55e1.68 (m, 8H), 2.69e2.75 (m, 4H),
(d, J¼2.3 Hz, 1H), 7.91 (d, J¼9.2 Hz, 1H); 13C NMR (100 MHz, CDCl3):
2.91e2.95 (m, 2H), 3.04e3.07 (br, 2H), 7.05 (dd, J¼14.2, 2.3 Hz, 1H),
d
15.1, 15.2, 15.3 (2C), 24.2, 24.9, 25.1, 25.2, 31.6, 31.7, 32.6, 32.9, 55.4,
7.74 (d, J¼1.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 15.0, 15.1, 15.3
5
104.1, 116.3, 126.5, 126.8, 132.5, 133.2, 134.4, 134.9, 137.8, 156.7; HRMS
(2C), 24.5, 24.9, 25.1, 25.7 (d, JCꢃF¼3.8 Hz), 31.9, 32.2 (d,
1
(ESIþ) Calcd for C23H34O [MþH]þ 327.2688, found 327.2681. The H
5JCꢃF¼11.5 Hz), 33.0, 33.6 (d, 4JCꢃF¼13.4 Hz), 111.7 (d, 2JCꢃF¼30.5 Hz)
and 13C NMR spectra were in agreement with the literature data.3f
120.0 (d, JCꢃF¼3.8 Hz), 120.7 (d, JCꢃF¼9.5 Hz), 129.4 (d,
3
3
2JCꢃF¼12.4 Hz), 133.6, 133.7, 134.4 (d, JCꢃF¼5.7 Hz), 139.1, 139.6,
3
1
4.2.6. N,N-Dimethyl-5,6,7,8-tetrapropylnaphthalen-2-amine
160.5 (d, JCꢃF¼255.6 Hz); HRMS (ESIþ) Calcd for C22H30ClF
(3af). Pale yellow liquid; Rf 0.29 (hexane/EtOAc¼99/1); 1H NMR
[MþH]þ 349.2098, found 349.2099.
(400 MHz, CDCl3):
d 1.05e1.13 (m, 12H), 1.54e1.71 (m, 8H),
2.65e2.71 (m, 4H), 2.88e2.97 (m, 4H), 3.02 (s, 6H), 7.06 (d, J¼2.3 Hz,
4.2.12. 6-(tert-Butyl)-1,2,3,4-tetraethylnaphthalene (3ba). Colorless
1H), 7.11 (dd, J¼9.6, 2.3 Hz, 1H), 7.86 (d, J¼9.2 Hz, 1H); 13C NMR
liquid; Rf 0.65 (hexane); 1H NMR (400 MHz, CDCl3):
d 1.25e1.29 (m,
(100 MHz, CDCl3):
d
15.1, 15.3 (3C), 23.9, 24.9, 25.2, 25.3, 31.5, 31.7,
6H), 1.32e1.39 (m, 6H), 1.46 (s, 9H), 2.84e2.91 (m, 4H), 3.10e3.19 (m,
32.6, 32.9, 41.4 (2C), 104.8, 115.5, 124.8, 125.7, 127.1, 132.4, 132.5,
134.1, 137.4, 147.9; HRMS (ESIþ) Calcd for C24H38N [MþH]þ
340.3004, found 340.3008.
4H), 7.55 (dd, J¼9.2, 1.8 Hz, 1H), 8.01e8.03 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 15.6,15.8,16.1 (2C), 21.9 (2C), 22.9, 23.0, 31.6 (3C),
35.0, 119.8, 123.4, 124.4, 129.3, 130.9, 135.3, 135.4, 137.3, 137.9, 146.9;
HRMS (ESIþ) Calcd for C22H32 [MþH]þ 297.2582, found 297.2589.
4.2.7. 6-Fluoro-1,2,3,4-tetrapropylnaphthalene (3ag). Colorless liq-
uid; Rf 0.72 (hexane); 1H NMR (400 MHz, CDCl3):
d
1.11e1.16 (m,
4.2.13. 6-(tert-Butyl)-1,2,3,4-tetrabutylnaphthalene (3ca). Colorless
12H), 1.56e1.71 (m, 8H), 2.71e2.76 (m, 4H), 2.93e3.03 (m, 4H),
7.17e7.21 (m,1H), 7.59 (dd, J¼11.9, 2.7 Hz,1H), 7.99 (dd, J¼9.2, 5.9 Hz,
liquid; Rf 0.70 (hexane); 1H NMR (400 MHz, CDCl3):
d 1.00e1.07 (m,
12H), 1.42 (s, 9H), 1.53e1.67 (m, 16H), 2.73e2.78 (m, 4H), 2.99e3.07
1H); 13C NMR (100 MHz, CDCl3):
d 15.1(2C),15.3 (2C), 24.5, 24.8, 25.1,
(m, 4H), 7.50 (dd, J¼9.2, 1.8 Hz, 1H), 7.94e7.96 (m, 2H); 13C NMR
2
25.2, 31.7 (2C), 32.7, 32.9, 108.2 (d, JCꢃF¼20.0 Hz), 114.5 (d,
2JCꢃF¼24.8 Hz),127.2 (d, 3JCꢃF¼8.6 Hz),128.4,132.5 (d, 3JCꢃF¼8.6 Hz),
133.8 (d, 4JCꢃF¼5.7 Hz),134.6,136.4,138.5,160.4 (d, 1JCꢃF¼242.3 Hz);
HRMS (ESIþ) Calcd for C22H31F [MþH]þ 315.2488, found 315.2483.
(100 MHz, CDCl3): d 14.1 (2C), 14.3 (2C), 23.7 (2C), 23.8 (2C), 28.8,
28.9, 30.0, 30.1, 31.5 (3C), 33.5, 33.7, 34.0 (2C), 35.0, 119.8, 123.3,
124.5, 129.5, 131.0, 134.1, 134.2, 136.4, 137.1, 146.8; HRMS (ESIþ)
Calcd for C30H48 [MþH]þ 409.3834, found 409.3838.
4.2.8. 1,2,3,4-Tetrapropyl-6-(trifluoromethyl)naphthalene (3ah). Co-
lorless liquid; Rf 0.72 (hexane); 1H NMR (400 MHz, CDCl3):
4.2.14. 6-(tert-Butyl)-1,2,3,4-tetraphenylnaphthalene (3da). Yellow
solid; Mp¼250e251 ꢂC; Rf 0.22 (hexane/EtOAc¼99/1); 1H NMR

L. Adak, N. Yoshikai / Tetrahedron 68 (2012) 5167e5171
5171
(400 MHz, CDCl3):
d
1.18 (s, 9H), 6.74e6.79 (m, 10H), 7.09e7.17 (m,
Supplementary data
10H), 7.41 (dd, J¼8.9, 2.0 Hz, 1H), 7.51e7.54 (m, 2H); 13C NMR
(100 MHz, CDCl3):
d
31.3 (3C), 35.1, 122.3, 124.9, 125.4 (2C), 126.5
Copies of 1H and 13C NMR spectra for all the naphthalene
products. Supplementary data related to this article can be found
online at doi:10.1016/j.tet.2012.04.004.
(2C), 126.7 (4C), 126.9, 127.6 (2C), 127.7 (2C), 130.4, 131.5 (4C), 131.6
(4C), 132.0, 138.2, 138.4, 138.6, 139.1, 139.8, 139.9, 140.8, 140.9,
148.7; HRMS (ESIþ) Calcd for C38H32 [MþH]þ 489.2582, found
489.2581.
References and notes
1. Anthony, J. E. Angew. Chem., Int. Ed. 2008, 47, 452.
4.2.15. 1,2,3,4-Tetraphenylnaphthalene
(3db). Yellow
solid;
2. de Koning, C. B.; Rousseau, A. L.; van Otterlo, W. A. L. Tetrahedron 2003, 59, 7.
3. (a) Herwig, W.; Metlesics, W.; Zeiss, H. J. Am. Chem. Soc. 1959, 81, 6203; (b)
Whitesides, G. M.; Ehmann, W. J. J. Am. Chem. Soc. 1970, 92, 5625; (c) Sakaki-
bara, T.; Tanaka, Y.; Yamasaki, S.-I. Chem. Lett. 1986, 797; (d) Wu, G.; Rheingold,
A. L.; Geib, S. J.; Heck, R. F. Organometallics 1987, 6, 1941; (e) Kawasaki, S.; Satoh,
T.; Miura, M.; Nomura, M. J. Org. Chem. 2003, 68, 6836; (f) Yasukawa, T.; Satoh,
T.; Miura, M.; Nomura, M. J. Am. Chem. Soc. 2002, 124, 12680; (g) Ueura, K.;
Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362; (h) Yamashita, M.; Hirano, K.;
Satoh, T.; Miura, M. Org. Lett. 2009, 11, 2337; (i) Yamashita, M.; Horiguchi, H.;
Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 7481; (j) Uto, T.; Shimizu,
M.; Ueura, K.; Tsurugi, H.; Satoh, T.; Miura, M. J. Org. Chem. 2008, 73, 298; (k)
Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2008, 47,
4019; (l) Umeda, N.; Hirano, K.; Satoh, T.; Shibata, N.; Sato, H.; Miura, M. J. Org.
Chem. 2011, 76, 13; (m) Wu, Y.-T.; Huang, K.-H.; Shin, C.-C.; Wu, T.-C. Chem.
dEur. J 2008, 14, 6697; (n) Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2009, 11, 5198; (o) Fukutani, T.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem.
2011, 76, 2867.
Mp¼201e203 ꢂC; Rf 0.21 (hexane/EtOAc¼99/1); 1H NMR (400 MHz,
CDCl3):
d
6.82e6.86 (m, 10H), 7.16e7.25 (m, 10H), 7.39 (dd, J¼6.6,
3.4 Hz, 2H), 7.64 (dd, J¼6.6, 3.4 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
125.5 (2C), 126.1 (2C), 126.6 (2C), 126.8 (4C), 127.2 (2C), 127.7 (4C),
127.8 (2C), 131.5 (6C), 132.2 (2C), 138.6 (2C), 139.1 (2C), 139.8 (2C),
140.7 (2C); HRMS (ESIþ) Calcd for C34H24 [MþH]þ 433.1956, found
433.1955. The 1H and 13C NMR spectra were in agreement with the
literature data.3n
4.2.16. 6-(tert-Butyl)-1,4-dimethyl-2,3-diphenylnaphthalene
(3ea). White solid; Mp¼157e159 ꢂC; Rf 0.27 (hexane); 1H NMR
(400 MHz, CDCl3): d 1.47 (s, 9H), 2.42 (s, 3H), 2.44 (s, 3H), 6.94e6.97
(m, 4H), 7.06e7.14 (m, 6H), 7.69 (dd, J¼8.9, 2.0 Hz, 1H), 8.08e8.10
4. (a) Huang, W.; Zhou, X.; Kanno, K.-I.; Takahashi, T. Org. Lett. 2004, 6, 2429; (b)
Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122,
(m, 2H); 13C NMR (100 MHz, CDCl3):
d
16.9, 17.0, 31.6 (3C), 35.3,
120.2, 124.7, 125.0, 125.9 (2C), 127.4 (4C), 129.3, 129.4, 130.3, 130.6
(2C), 130.7 (2C), 131.9, 139.0, 139.7, 142.0, 142.1, 148.6; HRMS (ESIþ)
Calcd for C28H28 [MþH]þ 365.2269, found 365.2263.
~
~
ꢀ
ꢀ
ꢀ
7280; (c) Pena, D.; Perez, D.; Guitian, E.; Castedo, L. J. Org. Chem. 2000, 65,
ꢀ
6944; (d) Pena, D.; Perez, D.; Guitian, E.; Castedo, L. J. Am. Chem. Soc. 1999, 121,
5827.
5. For annulation reactions using zirconacyclopentadiene as a surrogate for two
alkyne molecules, see: Takahashi, T.; Li, Y.; Stepnicka, P.; Kitamura, M.; Liu, Y.;
Nakajima, K.; Kotora, M. J. Am. Chem. Soc. 2002, 124, 576.
4.2.17. 1,4-Dimethyl-2,3-diphenylnaphthalene (3eb). White solid;
Mp¼166e167 ꢂC; Rf 0.26 (hexane); 1H NMR (400 MHz, CDCl3):
6. For selected recent reviews on CeH bond functionalization, see: (a) Wencel-
€
Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740; (b) Satoh,
d
2.43 (s, 6H), 6.95e6.97 (m, 4H), 7.06e7.14 (m, 6H), 7.57 (dd, J¼6.4,
T.; Miura, M. Chem.dEur. J. 2010, 16, 11212; (c) Colby, D. A.; Bergman, R. G.;
Ellman, J. A. Chem. Rev. 2010, 110, 624; (d) Lyons, T. W.; Sanford, M. S. Chem.
Rev. 2010, 110, 1147; (e) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 677;
(f) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem. Int. Ed. 2009, 48,
9792; (g) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem. Int. Ed.
2009, 48, 5094; (h) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013.
7. Adak, L.; Yoshikai, N. J. Org. Chem. 2011, 76, 7563.
8. (a) Chen, Y. H.; Knochel, P. Angew. Chem. Int. Ed. 2008, 47, 7648; (b) Papoian, V.;
Minehan, T. J. Org. Chem. 2008, 73, 7376.
9. For recent reviews on organoindium chemistry, see: (a) Auge, J.; Lubin-Ger-
3.2 Hz, 2H), 8.13 (dd, J¼6.4, 3.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
17.1 (2C), 125.2 (2C), 125.9 (2C), 126.0 (2C), 127.4 (4C), 129.6 (2C),
130.6 (4C), 132.2 (2C), 139.6 (2C), 141.9 (2C); HRMS (ESIþ) Calcd for
C24H20 [MþH]þ 309.1643, found 309.1640. The 1H and 13C NMR
spectra were in agreement with the literature data.3n
ꢀ
4.2.18. 1,4-Diethyl-2,3-diphenylnaphthalene (3fb). Colorless viscous
liquid; Rf 0.33 (hexane); 1H NMR (400 MHz, CDCl3):
d 1.17 (t,
main, N.; Uziel, J. Synthesis 2007, 1739; (b) Araki, S.; Hirashita, T. In Compre-
hensive Organometallic Chemistry III; Crabtree, R., Mingos, M., Eds.; Pergamon:
Oxford, 2007; vol. 9, pp 649e751; (c) Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, S. H.;
Kim, J. N. Tetrahedron 2010, 66, 7065.
J¼7.6 Hz, 6H), 2.86 (q, J¼7.6 Hz, 4H), 6.99 (d, J¼6.8 Hz, 4H),
7.05e7.13 (m, 6H), 7.55e7.58 (m, 2H), 8.16e8.19 (m, 2H); 13C NMR
10. (a) Hojo, M.; Murakami, Y.; Aihara, H.; Sakuragi, R.; Baba, Y.; Hosomi, A. Angew.
Chem. Int. Ed. 2001, 40, 621; (b) Shirakawa, E.; Yamagami, T.; Kimura, T.; Ya-
maguchi, S.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 17164; (c) Zhang, D.; Ready,
J. M. J. Am. Chem. Soc. 2006, 128, 15050; (d) Yamagami, T.; Shintani, R.; Shir-
akawa, E.; Hayashi, T. Org. Lett. 2007, 9, 1045; (e) Shirakawa, E.; Ikeda, D.;
Ozawa, T.; Watanabe, S.; Hayashi, T. Chem. Commun. 2009, 1885; (f) Shirakawa,
E.; Masui, S.; Narui, R.; Watabe, R.; Ikeda, D.; Hayashi, T. Chem. Commun. 2011,
9714.
(100 MHz, CDCl3):
d 15.9 (2C), 23.5 (2C), 125.4 (2C), 125.8 (2C),
126.0 (2C), 127.4 (4C), 130.3 (4C), 131.5 (2C), 135.9 (2C), 139.3 (2C),
141.7 (2C); HRMS (ESIþ) Calcd for C26H25 [MþH]þ 337.1956, found
337.1943.
4.2.19. 6-(tert-Butyl)-2,4-dimethyl-1,3-dipropylnaphthalene
(3ga)
11. (a) Nakamura, E.; Yoshikai, N. J. Org. Chem. 2010, 75, 6061; (b) Sun, C.-L.; Li, B.-J.;
Shi, Z.-J. Chem. Rev. 2011, 111, 1293.
and its three regioisomers. Colorless liquid; Rf 0.64 (hexane); GC
analysis indicated the presence of four regioisomers in an ap-
12. For recent examples of iron-catalyzed CeH bond functionalization, see: (a)
Yoshikai, N.; Asako, S.; Yamakawa, T.; Ilies, L.; Nakamura, E. Chem.dAsian J.
2011, 6, 3059; (b) Ilies, L.; Asako, S.; Nakamura, E. J. Am. Chem. Soc. 2011, 133,
7672; (c) Matsumoto, A.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2011, 133, 6557;
(d) Yoshikai, N.; Mieczkowski, A.; Matsumoto, A.; Ilies, L.; Nakamura, E. J. Am.
Chem. Soc. 2010, 132, 5568.
proximate ratio of 1:1:1:1; 1H NMR (400 MHz, CDCl3):
d 1.08e1.17
(m), 1.46 (s), 1.55e1.61 (m), 1.66e1.75 (m), 2.43 (s), 2.44 (s), 2.47
(s), 2.48 (s), 2.65 (s), 2.68 (s), 2.79e2.88 (m), 3.05e3.13 (m),
7.53e7.58 (m), 7.98e8.02 (m); 13C NMR (100 MHz, CDCl3):
d 14.8,
14.9, 15.0, 15.1, 15.2, 16.4, 16.6, 17.1, 17.2, 23.6, 23.8, 23.9, 24.5,31.5,
31.6, 33.0, 33.1, 33.3, 33.4, 35.0, 35.1, 119.6, 119.7, 123.2, 123.3,
123.5, 123.6, 124.2, 124.3, 124.4, 128.7, 128.8, 129.0, 129.2, 129.9,
130.0, 130.6, 130.8, 131.5, 131.6, 131.7, 132.2, 132.3, 132.9, 133.7,
133.9, 134.0, 134.2, 136.7, 137.2, 137.5, 137.9, 146.7, 146.9, 147.0,
147.2; HRMS (ESIþ) Calcd for C22H33 [MþH]þ 297.2582, found
297.2581.
13. Nakamura, M.; Ito, S.; Matsuo, K.; Nakamura, E. Synlett 2005, 1794.
14. Abbreviations: dppe¼1,2-bis(diphenylphosphino)ethane, dppp¼1,3-bis(diphe-
nylphosphino)propane, dppf¼1,10-bis(diphenylphosphino)ferrocene, DPEph-
os¼bis[2-(diphenylphosphino)phenyl]ether,
Xantphos¼4,5-bis(diphenylph-
osphino)-9,9-dimehtylxanthene, IPrꢀHCl¼1,3-bis(2,6-diisopropylphenyl)imi-
dazolium chloride.
ꢀ
15. (a) Clot, E.; Megret, C.; Eisenstein, O.; Perutz, R. N. J. Am. Chem. Soc. 2009,
131, 7817; (b) Clot, E.; Eisenstein, O.; Jasim, N.; Macgregor, S. A.; Mcgrady,
J. E.; Perutz, R. N. Acc. Chem. Res. 2011, 44, 333 and references cited
therein..
16. For the use of dppbz-type ligands in iron catalysis, see: (a) Hatakeyama, T.;
Okada, Y.; Yoshimoto, Y.; Nakamura, M. Angew. Chem. Int. Ed. 2011, 50, 10973;
(b) Ito, S.; Itoh, T.; Nakamura, M. Angew. Chem. Int. Ed. 2011, 50, 454; (c)
Hatakeyama, T.; Hashimoto, T.; Kondo, Y.; Fujiwara, Y.; Seike, H.; Takaya, H.;
Tamada, Y.; Ono, T.; Nakamura, M. J. Am. Chem. Soc. 2010, 132, 10674; (d)
Hatakeyama, T.; Kondo, Y.; Fujiwara, Y. I.; Takaya, H.; Ito, S.; Nakamura, E.;
Nakamura, M. Chem. Commun. 2009, 1216; (e) Bedford, R. B.; Huwe, M.;
Wilkinson, M. C. Chem. Commun. 2009, 600.
Acknowledgements
We thank the Singapore National Research Foundation (NRF-RF-
2009-05), Nanyang Technological University, and JST, CREST for fi-
nancial support.