Palladium-catalyzed cyclocoupling of 2-halobiaryls with isocyanides via the cleavage of carbon-hydrogen bonds

Article abstract of DOI:10.1021/jo1009728

(Figure Presented) To demonstrate the utility of isocyanides in catalytic C-H bond functionalization reactions, a palladium-catalyzed cyclocoupling reaction of 2-halobiaryls with isocyanides was developed. The reaction afforded an array of fluorenone imine derivatives via the cleavage of a C-H bond at the 2′-position of 2-halobiaryls. The use of 2,6-disubstituted phenyl isocyanide was crucial for this catalytic cyclocoupling reaction to proceed. The reaction was applicable to heterocyclic and vinylic substrates, allowing the construction of a wide range of ring system. The large kinetic isotope effect observed (k_H/k_D = 5.3) indicates that C-H bond activation was the turnover-limiting step in this catalysis.

Full text of DOI:10.1021/jo1009728

pubs.acs.org/joc
Palladium-Catalyzed Cyclocoupling of 2-Halobiaryls with Isocyanides
via the Cleavage of Carbon-Hydrogen Bonds
Mamoru Tobisu,† Shinya Imoto, Sana Ito, and Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan.
†Frontier Research Base for Global Young Researchers, Graduate School of Engineering, Osaka University,
Suita, Osaka 565-0871, Japan.
chatani@chem.eng.osaka-u.ac.jp
Received May 18, 2010
To demonstrate the utility of isocyanides in catalytic C-H bond functionalization reactions, a
palladium-catalyzed cyclocoupling reaction of 2-halobiaryls with isocyanides was developed. The
reaction afforded an array of fluorenone imine derivatives via the cleavage of a C-H bond at the
20-position of 2-halobiaryls. The use of 2,6-disubstituted phenyl isocyanide was crucial for this catalytic
cyclocoupling reaction to proceed. The reaction was applicable to heterocyclic and vinylic substrates,
allowing the construction of a wide range of ring system. The large kinetic isotope effect observed
(kH/kD = 5.3) indicates that C-H bond activation was the turnover-limiting step in this catalysis.
Introduction
isocyanides in organic synthesis and demonstrated that they
serve not simply as a carbon monoxide equivalent but also as
a unique C1 source, enabling transformations that could not
be achieved with carbon monoxide.5 On the basis of these
findings, it may be possible to use isocyanides as a C1
component in C-H bond functionalization reactions. To
date, such transition-metal-catalyzed incorporation of iso-
cyanides into C-H bonds has met with limited success. Jones
reported that the isomerization of 2,6-xylyl isocyanide to
The development of transition-metal-catalyzed methods
for the direct functionalization of C-H bonds is currently a
vibrant research area, and progress is being made.1 With
respect to C-C bond formation, various carbon-based
substituents, such as aryl, alkenyl, and alkyl groups, can be
introduced through the catalytic C-H bond functionaliza-
tion reactions. The installation of carbonyl functionalities
has attracted increasing attention, since such methods could
serve as atom-efficient and potentially useful pathways to
ketones and esters.2-4 We2 and others3 have demonstrated
that carbon monoxide can be utilized as an effective carbonyl
source in the catalytic C-H bond carbonylation reactions.
On the other hand, we have been exploring the utility of
(2) (a) Chatani, N.; Fukuyama, T.; Kakiuchi, F.; Murai, S. J. Am. Chem.
Soc. 1996, 118, 493. (b) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Org.
Chem. 1997, 62, 2604. (c) Fukuyama, T.; Chatani, N.; Kakiuchi, F.; Murai, S.
J. Org. Chem. 1997, 62, 5647. (d) Ishii, Y.; Chatani, N.; Kakiuchi, F.; Murai,
S. Organometallics 1997, 16, 3615. (e) Ishii, Y.; Chatani, N.; Kakiuchi, F.;
Murai, S. Tetrahedron Lett. 1997, 38, 7565. (f ) Fukuyama, T.; Chatani, N.;
Tatsumi, J.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc. 1998, 120, 11522.
(g) Chatani, N.; Ishii, Y.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Org. Chem. 1998,
63, 5129. (h) Chatani, N.; Asaumi, T.; Ikeda, T.; Yorimitsu, S.; Ishii, Y.;
Kakiuchi, F.; Murai, S. J. Am. Chem. Soc. 2000, 122, 12882. (i) Ie, Y.;
Chatani, N.; Ogo, T.; Marshall, D. R.; Fukuyama, T.; Kakiuchi, F.; Murai,
S. J. Org. Chem. 2000, 65, 1475. ( j) Chatani, N.; Fukuyama, T.; Tatamidani,
H.; Kakiuchi, F.; Murai, S. J. Org. Chem. 2000, 65, 4039. (k) Chatani, N.;
Asaumi, T.; Yorimitsu, S.; Ikeda, T.; Kakiuchi, F.; Murai, S. J. Am. Chem.
Soc. 2001, 123, 10935. (l) Chatani, N.; Yorimitsu, S.; Asaumi, T.; Kakiuchi,
F.; Murai, S. J. Org. Chem. 2002, 67, 7557. (m) Asaumi, T.; Chatani, N.;
Matsuo, T.; Kakiuchi, F.; Murai, S. J. Org. Chem. 2003, 68, 7538. (n)
Asaumi, T.; Matsuo, T.; Fukuyama, T.; Ie, Y.; Kakiuchi, F.; Chatani, N.
J. Org. Chem. 2004, 69, 4433. (o) Chatani, N.; Uemura, T.; Asaumi, T.; Ie, Y.;
Kakiuchi, F.; Murai, S. Can. J. Chem. 2005, 83, 755. (p) Imoto, S.; Uemura,
T.; Kakiuchi, F.; Chatani, N. Synlett 2007, 170. (q) Inoue, S.; Shiota, H.;
Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc. 2009, 131, 6898.
(1) Representative recent reviews on C-H bond functionalization: (a)
Godula, K.; Sames, D. Science 2006, 312, 67. (b) Dick, A. R.; Sanford, M. S.
Tetrahedron 2006, 62, 2439. (c) Alberico, D.; Scott, M. E.; Lautens, M. Chem.
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Kochi, T. Synthesis 2008, 3013. (i) Topics in Organometallic Chemistry;
Chatani, N., Ed.; Springer-Verlag: Berlin, 2007; Vol 24. ( j) Daugulis, O.; Do,
H.-Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074. (k) Chen, X.; Engle,
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DOI: 10.1021/jo1009728
r
Published on Web 06/15/2010
J. Org. Chem. 2010, 75, 4835–4840 4835
2010 American Chemical Society

Tobisu et al.
JOCArticle
SCHEME 1. Catalytic C-H Bond Functionalization through
Acyl and Imidoyl Metal Species
TABLE 1. Palladium-Catalyzed Cyclocoupling of 2-Bromobiphenyl
(1a) with Isocyanide 2aa
entry
variations from “standard” conditions
yield of 3aa (%)b
1
2
3
4
5
6
7
8
none
95
94
86
54
80
42
trace
45
PCy3 as ligand
PdCl2 as catalyst precursor
Cs2CO3 as base
K2CO3 as base
toluene as solvent
dioxane as solvent
80 °C for 20 h
aReaction conditions: 1a (0.25 mmol), 2a (0.30 mmol), Pd(OAc)2
(0.0125 mmol), PPh3 (0.025 mmol), and CsOPiv (0.30 mmol) in DMF
(2.0 mL) at 100 °C for 5 h. bIsolated yield based on 1a.
7-methyl-1H-indole is catalyzed by a ruthenium complex via
the insertion of an isocyanide moiety into the C-H bond of
methyl groups.6 Tanaka and Jones independently reported
the catalytic insertion of isocyanides into a C-H bond of
benzene under photochemical conditions.7 The palladium-
catalyzed cascade coupling of aryl isocyanides with 6-iodo-
N-propargylpyridones was reported by Curran.8 Despite
these precedents, there remains a need to develop more
general catalytic reactions to assess the utility of isocyanides
in C-H bond functionalization reactions.
In the present study, Larock’s palladium-catalyzed cyclo-
carbonylation of 2-halobiaryls A, in which fluoren-9-one
derivatives C are formed through C-H bond cleavage, was
chosen as a model reaction (Scheme 1a).3j,k The hypothesis is
that replacing carbon monoxide with isocyanides in this
reaction would lead to the formation of the corresponding
imine derivatives E if an imidoyl palladium intermediate D
possesses a reactivity comparable to acyl palladium B toward
the C-H bonds nearby (Scheme 1b). The feasibility of the
hypothesis is supported, in part, by Larock’s report that
imidoyl palladium D that is generated by unique aryl-to-
imidoyl palladium migration can undergo cyclization to
afford imine E (Scheme 1c).9 This report documents the
development of palladium-catalyzed cyclocoupling of 2-
halobiaryls with isocyanides, as in Scheme 1b, demonstrat-
ing that isocyanides can be utilized as a C1 component in
C-H bond functionalization reactions.
Results and Discussion
A palladium-catalyzed reaction of 2-bromobiphenyl (1a)
with isocyanide 2a was initially examined to test the ability of
isocyanides to work in Larock’s cyclocarbonylation.3j,k The
expected imine 3aa was obtained in high yield (Table 1). In
reactions using carbon monoxide, PCy3 has been the optimal
ligand and the use of PPh3 has reduced the yield of the
product.3j,k However, both PPh3 and PCy3 served as an
(4) Carbonyl sources other than CO have also been utilized in transition-
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E.; Sato, M.; Kakiuchi, F. J. Am. Chem. Soc. 2009, 131, 2792. Isocyanates
and ketenes: (d) Hong, P.; Yamazaki, H.; Sonogashira, K.; Hagihara, N.
Chem. Lett. 1978, 8, 535. (e) Kuninobu, Y.; Tokunaga, Y.; Kawata, A.;
Takai, K. J. Am. Chem. Soc. 2005, 128, 202. CO2: (f) Sugimoto, H.; Kawata,
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J.-C.; Kobayashi, Y.; Sakakura, T. J. Org. Chem. 2001, 66, 5262. Formic
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Zhou, Z. Y.; Chan, A. S. C. J. Am. Chem. Soc. 2008, 130, 3304.
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Chem. Soc. 2003, 125, 7812. (b) Oshita, M.; Yamashita, K.; Tobisu, M.;
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Tobisu, M.; Chatani, N. Org. Lett. 2005, 7, 3697. (d) Tobisu, M.; Oshita, M.;
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Tobisu, M.; Yamaguchi, S.; Chatani, N. Org. Lett. 2007, 9, 3351. (f) Tobisu,
M.; Kitajima, A.; Yoshioka, S.; Hyodo, I.; Oshita, M.; Chatani, N. J. Am.
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N. Org. Lett. 2008, 10, 5223.
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TABLE 2. Scope of Isocyanidesa
TABLE 3. Palladium-Catalyzed Cyclocoupling of 2-Bromobiphenyls
with Isocyanide 2aa
aReaction conditions: 1a (0.25 mmol), isocyanide (0.30 mmol),
Pd(OAc)2 (0.0125 mmol), PPh3 (0.025 mmol), and CsOPiv (0.30 mmol) in
DMF (2.0 mL) at 100 °C for 5 h. bIsolated yield based on 1a. cRun for 10 h.
effective ligand (entries 1 and 2). PdCl2 can be used as a
palladium source in place of Pd(OAc)2 (entry 3). CsOPiv
proved to be the optimal base (entries 4 and 5). The solvent
employed had a major effect on the yield, and DMF was the
solvent of choice (entries 6 and 7). Lowering the reaction
temperature below 100 °C resulted in a significant loss of the
efficiency of the catalysis (entry 8).
The effect of the structure of isocyanides on the palladium-
catalyzed cyclocoupling of 1a was then examined (Table 2).
We found that 2,6-xylyl isocyanide (2b), which is less bulky
than 2a, required a longer reaction time (10 h) to complete
the reaction (entry 2). Other phenyl isocyanides bearing 2,6-
substituents, such as ethyl (entry 3) and aryl (entry 5), and
asymmetrically substituted phenyl isocyanide 2f (entry 6) all
furnished the corresponding cyclocoupling product in good
yield, whereas the introduction of highly congested tert-butyl
groups had a detrimental effect on the reaction (entry 4). The
substituents at the 2,6-positions were crucial for this cyclo-
coupling reaction to proceed: no corresponding product was
observed when phenyl isocyanide (2g) was used (entry 7).
This is presumably due to the decomposition of 2g under the
catalytic conditions in the present study, through polymeri-
zation,10 for example, and/or catalyst deactivation by multiple
coordination of 2g to a palladium center.11 Aliphatic isocya-
nides 2h and 2i were unable to undergo this cyclocoupling
aReaction conditions: 2-halobiaryl (0.25 mmol), 2a (0.30 mmol),
Pd(OAc)2 (0.0125 mmol), PPh3 (0.025 mmol), and CsOPiv (0.30 mmol)
in DMF (2.0 mL) at 100 °C for 5 h. bIsolated yield based on 2-halobiaryl.
cPCy3 was used in place of PPh3. dRun for 20 h. eDetermined by 1H NMR.
reaction under these conditions (entries 8 and 9). On the basis of
these results, isocyanide 2a was used for the subsequent studies.
The reaction conditions optimized for the palladium-cata-
lyzed reaction of 1a with 2a have successfully been applied to a
wide range of 2-halobiphenyls (Table 3). In addition to bro-
mides (entry 1), iodides (entry 2) and triflates (entry 3) serve
as good substrates, whereas the corresponding chlorides
(10) Reviews on the polymerization of isocyanides: (a) Millich, F. Chem.
Rev. 1972, 72, 101. (b) Millich, F. J. Polym. Sci. Macromol. Rev. 1980, 15,
207. (c) Suginome, M.; Ito, Y. Adv. Polym. Sci. 2004, 171, 77.
(11) Pd(CNR)n are known to aggregate into higher nuclearity clusters.
See: Yamamoto, Y. Coord. Chem. Rev. 1980, 32, 193.
J. Org. Chem. Vol. 75, No. 14, 2010 4837

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TABLE 4. Palladium-Catalyzed Cyclocoupling of 2-Bromohetero-
biaryls with Isocyanide 2aa
TABLE 5. Palladium-Catalyzed Cyclocoupling of 2-Bromostyrene
Derivatives with Isocyanide 2aa
aReaction conditions: substrate (0.25 mmol), 2a (0.30 mmol),
Pd(OAc)2 (0.0125 mmol), PPh3 (0.025 mmol), and CsOPiv (0.30 mmol)
in DMF (2.0 mL) at 100 °C for 5 h. bIsolated yield based on the substrate.
aReaction conditions: 2-halobiaryl (0.25 mmol), 2a (0.30 mmol),
Pd(OAc)2 (0.0125 mmol), PPh3 (0.025 mmol), and CsOPiv (0.30 mmol) in
DMF (2.0 mL) at 100 °C for5 h. bIsolated yield based on 2-haloheterobiaryl.
30-position was examined next. However, the cyclocoupling
reaction proceeded exclusively at the less-hindered position,
indicating that the steric bulkiness of the acetyl group was
dominant over the directing effect (entry 13).
2-Halobiaryl bearing a substituent at the 4-position also
underwent a cyclocoupling reaction to afford the corre-
sponding imine 3la in good yield (entry 14). The selective
formation of 3la provides an insight into the reaction me-
chanism (vide infra). Introduction of a methyl group at the
20-position did not interfere with the cyclocoupling reaction,
and the corresponding imine 3oa was efficiently furnished
(entry 15).
To further investigate the reactivity of the postulated
imidoyl palladium intermediate, as in D in Scheme 1, toward
an aromatic C-H bond, heteroaromatic substrates were
then applied to this catalytic cyclocoupling reaction (Table 4).
C-H bonds in electron-rich heteroaryls, including pyrroles
(entry 1), furans (entry 2), and thiophenes (entries 3 and 4),
successfully participated in the cyclocoupling reaction to
form the corresponding products with unique ring systems.
Especially noteworthy was the effective construction of a
strained ring system 12, in which three five-membered rings
were fused (entry 4). In the case of furans and thiophenes
(entries 2-4), the reaction selectively proceeded at the 2-po-
sition of the heteroaryls, rather than at the 3-position. The
remained intact even in the presence of an electron-rich PCy3
ligand.12 Functional group compatibility was assessed by the
reactions of a series of 2-bromobiphenyls bearing a substituent
at the 40-position (entries 5-10). Both electron-donating and -
withdrawing groups were tolerated, and even a reactive formyl
group survived (entry 9).
The regioselectivity of the present cyclocoupling was inves-
tigated next using a 30-substituted system in which two different
C-H bonds could participate in the reaction. When methyl-
substituted substrate 1k was subjected to the catalytic condi-
tions, the cyclocoupling reaction occurred almost exclusively at
the less-hindered site (entry 11). However, both regioisomers
3la and 4la were obtained in a ratio of 2.1:1 in the case of
methoxy-substituted substrate 1l (entry 12). The relatively
facile formation of the sterically demanding isomer 4la, com-
pared to 4ka, might be attributed to the coordinating ability of
an oxygen atom of the methoxy group, which directs a
palladium catalyst to the congested C-H bond.2i In anticipa-
tion of regioselective formation of the hindered isomer by using
such directing effect, a substrate bearing an acetyl group at the
(12) PCy3 is one of the effective ligands for the activation of Ar-Cl bonds.
For a leading reference, see: Fu, G. C. Acc. Chem. Res. 2008, 41, 1555.
4838 J. Org. Chem. Vol. 75, No. 14, 2010

Tobisu et al.
JOCArticle
observed regioselectivity agreed with that observed in other
palladium-catalyzed C-H bond functionalization reactions
through electrophilic substitution1e and concerted metala-
tion/deprotonation mechanism.13 In addition to electron-
rich heteroaryls, the C-H bond in electron-deficient pyri-
dines could also be used in the present cyclocoupling reaction
(entry 5).
aryl-palladium bond. Activation of a C-H bond at the 20-
position by imidoyl palladium D0 then affords a palladacycle
J, presumably either through electrophilic aromatic substi-
tution, as in I,1e or through a concerted metalation-depro-
tonation mechanism, as in H,13 analogous to the C-H bond
activation by aryl palladium species. The final product E0 is
released from J by reductive elimination, and Pd(0) is
regenerated.
We next turned our attention to the issue of whether a vinylic
system can be applied to the present cyclocoupling reaction in
place of an aromatic one (Table 5). Commercially available
2-bromo-1,1,2-triphenylethylene (15a) was initially examined as
a substrate for palladium-catalyzed cyclocoupling with 2a. The
expected indenone imine 1614 was obtained in 80% yield under
conditions optimized for 2-halobiaryl substrates (entry 1). The
use of the corresponding triflate 15b significantly decreased the
yield of 16, although 15b was consumed completely (entry 2).
Bromide 17 did not afford the cyclocoupling product, however,
indicating that a vinylic C-H bond cannot participate in the
catalytic reaction (entry 3). When triflate 19 was subjected to
the catalytic conditions, the corresponding product 18 was not
formed, but diphenylacetylene (20, 83% yield) was obtained
instead through the elimination of TfOH (entry 4). Thus, the
presence of two substituents at the β-position of vinyl halides
(or triflates) is required to suppress the undesired elimination
pathway. For example, halides and triflates connected to
unsaturated cyclic systems, as in 21 and 23, underwent the
cyclocoupling reaction, allowing isocyanide 2a to be incorpo-
rated into polycyclic systems (entries 5 and 6).
It is widely recognized that aryl palladium G can also
activate the C-H bond at the 20-position, leading to 1,4-
migration of a palladium center.15,16 Even if such a migration
process is involved in the present cyclocoupling reaction, the
reaction would afford an identical product with all substrates
shown in Table 3 except for 1n. As shown in Scheme 3, aryl
palladium 25 initially formed from 1n could rapidly isomer-
ize to 26 via the 1,4-migration. The involvement of the
intermediate 26 would lead to the formation of a mixture
of isomeric products 3la and 4la, on the basis of the fact that
2-bromobiaryl 1l afforded 3la and 4la (entry 12 in Table 3).
However, the isomerized product 4la was not detected at all
in the palladium-catalyzed reaction of 1n (entry 14 in Table 3).
This observation indicates that insertion of isocyanide into aryl
palladium G and the subsequent C-H bond activation by the
resultant imidoyl palladium D0 are relatively fast processes
compared with 1,4-palladium migration.
To gain further insight into the C-H bond activation
process by imidoyl palladium species, an intramolecular
kinetic isotope effect was investigated by conducting a cata-
lytic reaction of 29 (Scheme 4). The observed product dis-
tribution suggests that a C-H bond is activated significantly
faster than a C-D bond (kH/kD = 5.3). This observation does
not serve to discriminate among the possible mechanisms for
the C-H bond activation step (SEAr17 or concerted metala-
tion-deprotonation18) but does indicate that C-H bond
activation is a turnover-limiting step in the present catalysis.
SCHEME 2. Possible Mechanism
Conclusions
In summary, we have demonstrated the utility of isocya-
nides in catalytic C-H bond functionalization reactions by
developing a palladium-catalyzed cyclocoupling of 2-halo-
biaryls with isocyanides. The use of 2,6-disubstituted phenyl
isocyanides is crucial for efficient catalysis. Scope and
limitation studies revealed that the postulated imidoyl
palladium species exhibited reactivity in aromatic C-H
bond activation comparable to that observed for the corre-
sponding acyl palladium species.3j,k Although the precise
mechanism for the C-H bond activation by imidoyl palla-
dium remains elusive, the process proved to be a turnover-
limiting step in the present catalysis. We expect that the
A possible mechanism for the palladium-catalyzed cyclo-
coupling of 2-halobiaryls with isocyanides, found in the
present study, is depicted in Scheme 2. Oxidative addition
of 2-halobiaryl A to Pd(0), followed by the ligand exchange
from halide to pivalate, affords aryl palladium intermediate
G. The aryl palladium G subsequently forms imidoyl palla-
dium species D0 via the insertion of isocyanide into an
(15) (a) Karig, G.; Moon, M.-T.; Thasana, N.; Gallagher, T. Org. Lett.
2002, 4, 3115. (b) Campo, M. A.; Larock, R. C. J. Am. Chem. Soc. 2002, 124,
14326. (c) Campo, M. A.; Huang, Q.; Yao, T.; Tian, Q.; Larock, R. C. J. Am.
Chem. Soc. 2003, 125, 11506. (d) Huang, Q.; Campo, M. A.; Yao, T.; Tian,
Q.; Larock, R. C. J. Org. Chem. 2004, 69, 8251. (e) Campo, M. A.; Zhang, H.;
Yao, T.; Ibdah, A.; McCulla, R. D.; Huang, Q.; Zhao, J.; Jenks, W. S.;
Larock, R. C. J. Am. Chem. Soc. 2007, 129, 6298.
(16) For 1,4-migration of other metals, see: Ma, S.; Gu, Z. Angew. Chem.,
Int. Ed. 2005, 44, 7512.
ꢀ
(13) Liegault, B.; Lapointe, D.; Caron, L.; Vlassova, A.; Fagnou, K. J.
Org. Chem. 2009, 74, 1826.
(17) For discussion on large kinetic isotope effect in SEAr process, see:
Zhao, X.; Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132, 5837and
references therein.
(18) For discussion on large kinetic isotope effect in concerted metala-
tion-deprotonation process, see: Campeau, L.-C.; Parisien, M.; Jean, A.;
Fagnou, K. J. Am. Chem. Soc. 2005, 128, 581.
(14) For other catalytic methods for the synthesis of indenone imine
derivatives via C-H bond cleavage, see: (a) Hu, Q.; Lu, J.; Wang, C.; Wang,
C.; Xi, Z. Tetrahedron 2007, 63, 6614. (b) Fukutani, T.; Umeda, N.; Hirano,
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J. Org. Chem. Vol. 75, No. 14, 2010 4839

Tobisu et al.
SCHEME 3. Fate of Aryl Palladium Intermediate: Formation and Cyclization of Imidoyl Palladium versus 1,4-Migration
JOCArticle
SCHEME 4. Intramolecular Kinetic Isotope Effect
fundamental knowledge gained in the present study will aid
the further development of new catalytic reactions using
isocyanides, particularly those that cannot be achieved with
carbon monoxide. Related studies are underway in our
laboratory.
(d, J = 7.3 Hz, 1H). 13C NMR (CDCl3): δ 23.2, 23.3, 28.4, 119.5,
120.0, 123.1, 123.2, 123.9, 126.4, 127.8, 128.3, 131.57, 131.64,
135.2, 137.2, 141.8, 143.0, 147.0, 162.9. IR (KBr): 3060 m, 2962
s, 2868 m, 2360 w, 1651 s, 1606 m, 1450 s, 1382 m, 1361 m, 1328 m,
1306 s, 1253 m, 1190 m, 1144 m, 1103 m, 1059 w, 1043 w, 941 m,
908 m, 795 m, 771 m, 734 s, 656 m, 434 w. MS m/z (relative
intensity, %): 340 (Mþ, 28), 339 (Mþ - 1, 100), 325 (14), 324 (54),
310 (20), 309 (70), 294 (24), 282 (27), 281 (26), 280 (40), 279 (12),
278 (21), 267 (16), 175 (13), 174 (89), 165 (46), 161 (25), 147 (13),
146 (46), 139 (11), 132 (50), 117 (11), 115 (10), 77 (10). Exact mass
calcd for C25H25N 339.1987, found 339.1991.
Experimental Section
General Procedure for the Palladium-Catalyzed Cyclocoupling
of 2-Halobiaryls. To a flame-dried 10 mL two-necked flask were
added 2-halobiaryl (0.25 mmol), isocyanide (0.30 mmol),
Pd(OAc)2 (0.0125 mmol), PPh3 (0.025 mmol), CsOPiv (0.30
mmol), and DMF (2 mL) under a gentle stream of nitrogen. The
mixture was stirred at 100 °C for 5 h under N2 atmosphere. The
reaction mixture was then cooled to room temperature, diluted
with diethyl ether, and washed with brine. The organic layer was
dried (MgSO4). After removing the volatiles in vacuo, the
residue was subjected to column chromatography on silica gel
to afford the desired product.
N-(9H-Fluoren-9-ylidene)-2,6-diisopropylaniline (3aa). Yellow
solid. Mp = 101-102 °C. Rf = 0.43 (hexane/EtOAc = 4:1). 1H
NMR (CDCl3): δ 0.94 (d, J = 7.0 Hz, 6H), 1.17 (d, J = 6.5 Hz,
6H), 2.82-2.92 (m, 2H), 6.41 (d, J = 7.6 Hz, 1H), 6.89 (td, J = 7.8
Hz, 0.8 Hz, 1H), 7.18-7.50 (m, 6H), 7.58 (t, J = 8.4 Hz, 2H), 8.03
Acknowledgment. This work was carried out, in part, by the
Program of Promotion of Environmental Improvement to
Enhance Young Researchers’ Independence, the Special
Coordination Funds for Promoting Science and Technology,
Ministry of Education, Culture, Sports, Science and Techno-
logy (MEXT), Japan. We also thank the Instrumental Analysis
Center, Faculty of Engineering, Osaka University, for assis-
tance with the MS, HRMS, and elemental analyses.
Supporting Information Available: Detailed experimental
procedures and characterization of products. This material is
available free of charge via the Internet at http://pubs.acs.org.
4840 J. Org. Chem. Vol. 75, No. 14, 2010