Cyclization-carbonylation-cyclization coupling reactions of N-propargylanilines and o-alkynylphenols with palladium(II)-bisoxazoline catalysts

Article abstract of DOI:10.1055/s-0031-1290805

Cyclization-carbonylation-cyclization coupling reactions (CCC-coupling reactions) of N-propargylanilines and o-alkynylphenols catalyzed by (box)Pd(II) complexes afforded symmetrical bis(quinolin-3-yl) and bis(benzofuran-3-yl) ketones, respectively, in mod

Full text of DOI:10.1055/s-0031-1290805

SPECIAL TOPIC
▌1825
sCpeyciaclltoipzication–Carbonylation–Cyclization Coupling Reactions of N-Propargyl-
anilines and o-Alkynylphenols with Palladium(II)–Bisoxazoline Catalysts
Cyclization–Carbonylation–Cyclization Coupling Reactions
Taichi Kusakabe,a Emika Sekiyama,a Yukari Ishino,a Satoshi Motodate,a Shigeki Kato,b Tomoyuki Mochida,c
Keisuke Kato*a
a
Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan
Fax +81(474)721805; E-mail: kkk@phar.toho-u.ac.jp
b
Department of Respiratory Medicine, Kawasaki Medical School, 577, Matsushima, Kurashiki, Okayama 701-0192, Japan
c
Department of Chemistry, Faculty of Sciences, Kobe University, Rokkodai, Nada, Kobe 657-8501, Japan
Received: 11.02.2012; Accepted after revision: 05.03.2012
O
HO
Abstract: Cyclization–carbonylation–cyclization coupling reac-
tions (CCC-coupling reactions) of N-propargylanilines and o-al-
kynylphenols catalyzed by (box)Pd(II) complexes afforded
symmetrical bis(quinolin-3-yl) and bis(benzofuran-3-yl) ketones,
respectively, in moderate to excellent yields.
O
S
S
O(CH2)2N
CO2H
Key words: palladium, tandem reaction, carbonylation, alkynes,
dimerization
suprofen
O
OH
raloxifene
O
Br
I
Quinolines and benzofurans occur in numerous natural
products, many of which display important biological ac-
tivity.1 Diaryl ketones are also frequently found in natural
products and pharmaceuticals2 [e.g., suprofen (a nonste-
roidal anti-inflammatory drug), raloxifene (a selective
estrogen receptor modulator for the treatment of osteopo-
rosis), benzbromarone (an antipodagric drug), and amiod-
arone (an antiarrhythmic drug)]. In addition, they are good
precursors for nonsteroidal antiestrogen drugs (e.g.,
tamoxifen3) and diarylmethyl compounds4a [e.g., car-
binoxamine (an antihistamic drug), antitubercular com-
pounds,4b and tubulin polymerization inhibitors4c] (Figure
1).
O
O
OH
O(CH2)2NEt2
Et
n-Bu
Br
I
benzbromarone
amiodarone
NMe2
O
N
Cl
carbinoxamine
Figure 1 Some drugs with diaryl ketones and related structures
produce the acylpalladium intermediate A. Coordination
of the triple bond of a second molecule induces the second
cyclization. Reductive elimination then leads to the for-
mation of a ketone bearing two heterocyclic groups. We
believe that the box ligand enhances the π-electrophilicity
of palladium(II),7 and thus promotes coordination of the
second triple bond to the acylpalladium intermediate A,
leading to the dimerization reaction. To extend our con-
cept of the CCC-coupling reaction, we investigated the
[Pd(II)(tfa)2(box)]-catalyzed carbonylation reaction of N-
propargylanilines 1 and o-alkynylphenols 4 (Tables 1–3).
A variety of heterocycles can be synthesized by transition-
metal-catalyzed cyclization of unsaturated systems.5
Among them, N-propargylanilines are good precursors for
the synthesis of quinoline derivatives.6 If these intramo-
lecular cyclization reactions could be expanded to include
carbonylative coupling reactions, the process would be a
synthetically valuable method for the direct preparation of
ketones bearing two heterocyclic groups. Recently, we re-
ported a cyclization–carbonylation–cyclization-coupling
reaction (CCC-coupling reaction) of propargylic acetates
and amides catalyzed by palladium(II)–bisoxazoline
(box) complexes (Scheme 1).
Initially, we selected 1a as a standard substrate in a search
for potential catalysts (Table 1). The reaction of 1a with
PdCl2(MeCN)2 (5 mol%) in the presence of p-benzoqui-
none (2 equiv) in methanol under a carbon monoxide at-
mosphere (balloon) generated the dimeric ketone 2a in
14% yield along with a 12% yield of monomeric ester 3a
(entry 1).
Symmetrical ketones possessing two cyclic orthoesters,
furanones, oxazoles, and oxabicyclic derivatives were ob-
tained in moderate to excellent yields.7a,f In this transfor-
mation, the triple bond of the substrate coordinates to
palladium(II) and undergoes nucleophilic attack by the in-
tramolecular nucleophile X followed by CO insertion to
The use of palladium(II) trifluoroacetate [Pd(tfa)2],
PdCl2(PPh3)2, and (–)-sparteine/Pd(tfa)2 generated 3a as
the sole product in 12–58% yields (entries 2–4). (2,2′-Bi-
pyridine)dichloropalladium(II) did not show catalytic ac-
tivity (entry 5). Next, we used the box ligands depicted in
SYNTHESIS 2012, 44, 1825–1832
Advanced online publication: 11.04.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1290805; Art ID: SS-2012-C0129-ST
© Georg Thieme Verlag Stuttgart · New York

1826
T. Kusakabe et al.
SPECIAL TOPIC
O
L2(box)Pd
Pd(box)L
cyclization
Pd(box)
A
cyclization
carbonylation
X
X = oxygen atom of amides or acetates
methanolysis
X
O
O
Pd(box)
coupling
heterocycles
(reductive elimination)
O
O
R
R
O
N
O
N
O
R
R
O
O
O
O
R
OMe
R
O
R
R
MeO
R
O
R
O
O
R
O
R
O
O
R2
R2
O
O
R2
R2
O
N
N
O
R1
R1
O
O
O
O
R
R
O
O
Scheme 1 Our concept of a cyclization–carbonylation–cyclization-coupling reaction (CCC-coupling reaction) of propargylic compounds, and
previous synthesized bis(hetaryl) ketones
Table 1 The Effect of Different Palladium Sources and Ligandsa
O
O
HN
N
N
N
OMe
palladium source
(5 mol%)
+
ligand (7.5 mol%)
p-benzoquinone
(2 equiv)
3a
1a
2a
CO, MeOH, r.t.
Entry
Pd source
Ligand
Time (h)
Yield (%)
2a
3a
1
2
3
4
5
6
7
8
PdCl2(MeCN)2
–
1
2
14
–
12
12
30
58
–
Pd(tfa)2
–
PdCl2(PPh3)2
Pd(tfa)2
–
21
21
18
1
–
(–)-sparteine
–
PdCl2(2,2′-bipy)b
Pd(tfa)2
–
c
c
box L1
box L2
box L3
54
34
89
3
Pd(tfa)2
19
1
3
Pd(tfa)2
5
a Reaction conditions: Pd source (5 mol%), ligand (7.5 mol%), p-benzoquinone (2 equiv), CO, MeOH, r.t.
b 5 mol% of palladium complex was employed.
c 1a was recovered (34%).
Synthesis 2012, 44, 1825–1832
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Cyclization–Carbonylation–Cyclization Coupling Reactions
1827
an increased yield of 2 (entries 5 and 6); the structure of
2e was determined by X-ray crystallographic analysis
(Figure 3). However, steric hindrance in the acylpalladi-
um intermediate also seemed to play an important role in
the dimerization.7a The reaction of 1g (R1 = SiEt3) afford-
ed monomeric ester 3g in 57% yield together with a small
amount of dimeric ketone 2g (entry 7). Unsubstituted sub-
strate 1h and p-methyl substrate 1i (R3 = Me) showed no
reactivity (entries 8 and 9).
O
O
N
N
R
R
L1 R = i-Pr (S)-i-Prbox
L2 R = Bn (S)-Bnbox
L3 R = Ph ( )-Phbox
Figure 2 Box ligands
Figure 2 according to our previous report.7a Although the
use of (S)-i-Prbox L1 and (S)-Bnbox L2 resulted in the
formation of 2a in 34–54% yield together with a small
amount of 3a (entries 6 and 7), (±)-Phbox accelerated the
reaction, and the yield improved to 89% (entry 8). Dichlo-
romethane, acetonitrile, and toluene were not suitable as
solvents.
Having optimized the reaction conditions, we examined
the reaction of various N-propargylanilines 1a–k with the
box ligand (±)-Phbox L3 (Table 2). The substrates 1a–d
bearing alkyl groups at both ortho- and meta-positions (R1
+ R2 or R1 + R4) were transformed in 70–89% yields (en-
tries 1–4). In most cases, small amounts (3–5%) of mono-
meric ester 3 were obtained as a byproduct. Replacement
of the methyl group 1e (R1 = Me) at the ortho-position
with the bulkier isopropyl group 1f (R1 = i-Pr) resulted in
Figure 3 X-ray crystal structure of 2e
However, introduction of a methyl group at the propargyl-
ic position (R5) was found to be important for this reac-
tion. The reaction of 1j (R3 = R5 = Me) gave 2j in 50%
yield (entry 10). In addition, the substrate 1k having two
bulky substituents at the meta-positions (R2 = R4 = t-Bu)
Table 2 CCC-Coupling Reaction of N-Propargylanilines 1a
R5
R5
O
R5
HN
N
N
Pd(tfa)2 (5 mol%)
L3 (7.5 mol%)
R1
R2
R1
R2
R1
+ 3
p-benzoquinone
(2 equiv)
CO, MeOH, r.t.
R4
R4
2a–k
R4
R2
R3
1a–k
R3
R3
R1
R2
R3
R4
R5
Entry
Time (h)
Product
Yield (%)
1
2
-(CH=CH)2-
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
1
1
2a
2b
2c
2d
2e
2f
89
77
71
70
55
76
10b
–
-(CH2)4-
Me
Me
Me
i-Pr
SiEt3
H
H
3
Me
H
H
2
4
H
Me
H
1
5
H
H
4
6
H
H
H
1
7
H
H
H
3
2g
2h
2i
8
H
H
H
12
24
63
48
9
H
H
Me
Me
H
H
–
10
11
H
H
H
2j
50
47
H
t-Bu
t-Bu
2k
a Reaction conditions: Pd(tfa)2 (5 mol%), L3 (7.5 mol%), p-benzoquinone (2 equiv), CO, MeOH, r.t.
b The monomeric ester 3g was obtained in 57% yield.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1825–1832

1828
T. Kusakabe et al.
SPECIAL TOPIC
gave 2k in 47% yield. Although we do not have a clear ex- ingly changed the course of the reaction,7b,c yielding the
planation for the observed substituent effects at this stage, desired dimeric ketones 5 by the CCC-coupling reaction
we tentatively propose the following. An equilibrium (entries 2, 4, 6, 8, and 10). For substrates 4a–e with hydro-
mixture of B and C should be formed by coordination of carbon substituents (R1), the reaction proceeded well (85–
the substrate 1 to palladium(II)8 (Scheme 2). The steric re- 93% yields) (entries 2, 4, 6, 8, and 10). Steric hindrance in
pulsion present in B may allow the formation of the prod- the acylpalladium intermediate seemed to play an impor-
ucts 2 and 3 through intermediate C.
tant role in the dimerization.7a The reaction of phenylacet-
ylene 4f afforded benzofuran-3-carboxylate 6f
exclusively (entry 11).
R5
R5
+ X–
L2XPd
PdXL2
In conclusion, we have presented a CCC-coupling reac-
tion of N-propargylanilines 1 and o-alkynylphenols 4 cat-
alyzed by (box)Pd(II) complexes. Symmetrical
bis(quinolin-3-yl) ketones 2 and bis(benzofuran-3-yl) ke-
tones 5 were obtained in moderate to excellent yields. We
believe that the box ligand enhances the π-electrophilicity
of palladium(II),7 and thus promotes coordination of the
triple bond (second molecule) to the acylpalladium inter-
mediate A, leading to the dimerization reaction. We are
currently investigating other new cascade reactions based
on the cyclization–carbonylation–cyclization strategy
presented here for the synthesis of other types of ketones
containing two heterocyclic groups.
N
HN
R1
R1
HX
+
B
–
C
X = CF3CO2
Scheme 2 Coordinated intermediates B and C
The palladium-catalyzed carbonylative cyclization of o-
alkynylphenols has proven to be a useful method for the
synthesis of benzofuran-3-carboxylates.9a–d Recently,
many successful examples based on cascade cyclization
coupling reactions of o-alkynylphenols have been report-
ed.9e–i To investigate the generality of the CCC-coupling
reaction, we next attempted the carbonylation of o-al-
kynylphenols 4 (Table 3). In the absence of the box li-
gand, carbonylative dimerization was not observed and
the benzofuran-3-carboxylates 6 were obtained exclusive-
ly (entries 1, 3, 5, 7, and 9). The use of box ligands strik-
All melting points were measured on a Yanaco MP-3S micromelt-
1
ing point apparatus and are uncorrected. H and 13C NMR and
HMBC spectra were recorded on Jeol AL 400 and Jeol Lambda 500
spectrometers in CDCl3 with TMS as internal reference. In the case
of CD3CN, solvent peaks were used as a reference (δ = 1.93 for 1H,
Table 3 CCC-Coupling Reaction of o-Alkynylphenols 4a
O
R
catalyst (5 mol%)
CO2Me
p-benzoquinone
+
(1.5 equiv)
CO, MeOH, r.t.
O
O
O
R
OH
R
R
4
5
6
Entry
R
Catalyst
Time (h)
Yield (%)
5
6
1
2
(CH2)2Ph
(CH2)2Ph
(CH2)3Ph
(CH2)3Ph
(CH2)5Me
(CH2)5Me
(CH2)7Me
(CH2)7Me
(CH2)2i-Pr
(CH2)2i-Pr
Ph
Pd(tfa)2
29
6.5
48
5a: –
6a: 89
6a: 10
6b: 88
6b: 2
[Pd(tfa)2(L3)]
Pd(tfa)2
5a: 90
5b: –
5b: 93
5c: –
3
4
[Pd(tfa)2(L3)]
Pd(tfa)2
5
48
6
6c: 91
6c: 6
6
[Pd(tfa)2(L3)]
Pd(tfa)2
5c: 86
5d: –
5d: 85
5e: –
7
48
6d: 73
6d: 5
8
[Pd(tfa)2(L3)]
Pd(tfa)2
9
6e: 80
6e: 10
6f: 82
10
11
[Pd(tfa)2(L3)]
[Pd(tfa)2(L3)]
6.5
30
5e: 85
5f: –
a Reaction conditions: catalyst (5 mol%), p-benzoquinone (1.5 equiv), CO, MeOH, r.t.
Synthesis 2012, 44, 1825–1832
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Cyclization–Carbonylation–Cyclization Coupling Reactions
1829
and δ = 118.2 for 13C). 13C NMR spectra were recorded at 100 MHz.
HRMS were obtained with Jeol GC Mate II, JMS-SX102 and Jeol
JMS 600H spectrometer. IR spectra were recorded with Jasco
FT/IR-300 spectrophotometer. All reagents were purchased from
commercial sources and used without purification. All evaporations
were performed under reduced pressure. For column chromatogra-
phy, silica gel (Kieselgel 60) was employed.
1H NMR (CDCl3): δ = 1.86–1.97 (m, 4 H), 2.93 (t, J = 6.0 Hz, 2 H),
3.32 (t, J = 6.0 Hz, 2 H), 3.99 (s, 3 H), 7.28 (d, J = 8.4 Hz, 1 H), 7.61
(d, J = 8.4 Hz, 1 H), 8.70 (d, J = 2.4 Hz, 1 H), 9.39 (d, J = 2.4 Hz, 1
H).
13C NMR (CDCl3): δ = 22.7 (2 C), 24.8, 30.6, 52.3, 121.9, 125.0,
125.9, 129.8, 134.9, 138.6, 141.2, 148.7, 148.8, 166.2.
HRMS (EI): m/z [M+] calcd for C15H15NO2: 241.1103; found:
Cyclization–Carbonylation–Cyclization Coupling Reaction of 1
or 4; General Procedure
241.1104.
A 30-mL 2-necked round-bottomed flask containing a magnetic
stirring bar, Pd(tfa)2 (0.025 mmol), ligand (0.038 mmol or 0.05
mmol), p-benzoquinone (0.75 mmol or 1 mmol), and MeOH (4 mL)
was fitted with a rubber septum and a 3-way stopcock connected to
a balloon filled with CO. The apparatus was purged with CO by
pump-filling via the 3-way stopcock. A MeOH soln (1 mL) of sub-
strate 1 or 4 (0.5 mmol) was added to the stirred soln via syringe at
an appropriate temperature. The remaining substrate was washed
with MeOH (2 × 1 mL). After stirring for a period of time (see Ta-
bles 2 and 3) at r.t., the mixture was diluted with CH2Cl2 (50 mL)
and washed with 3% NaOH (40 mL). The aqueous layer was ex-
tracted with CH2Cl2 (2 × 50 mL) and the combined organic layers
were dried (MgSO4) and concentrated in vacuo. The crude product
was purified by column chromatography (silica gel). The fraction
eluted with hexane–EtOAc afforded dimeric ketone 2 or 5 and mo-
nomeric ester 3 or 6. In some cases, the dimeric ketones were then
precipitated from the reaction mixture and the resulting precipitate
was collected by filtration and washed with cold MeOH (2 × 1 mL).
The filtrate was reprocessed via the above procedure to provide ad-
ditional product after column chromatography.
Bis(7,8-dimethylquinolin-3-yl)methanone (2c)
Eluent: hexane–EtOAc, 40:1; pale yellow needles; yield: 60.4 mg
(71%); mp 178–180 °C (hexane–EtOAc, 1:1).
IR (KBr): 2919, 1654, 1597, 1272, 855 cm–1.
1H NMR (CDCl3): δ = 2.56 (s, 6 H), 2.81 (s, 6 H), 7.46 (d, J = 8.4
Hz, 2 H), 7.67 (d, J = 8.4 Hz, 2 H), 8.55 (d, J = 2.4 Hz, 2 H), 9.37
(d, J = 2.4 Hz, 2 H).
13C NMR (CDCl3): δ = 13.4 (2 C), 21.0 (2 C), 124.9 (2 C), 126.2 (2
C), 128.6 (2 C), 130.7 (2 C), 134.9 (2 C), 139.1 (2 C), 140.6 (2 C),
148.7 (2 C), 148.9 (2 C), 193.6.
HRMS (EI): m/z [M+] calcd for C23H20N2O: 340.1576; found:
340.1575.
Methyl 7,8-Dimethylquinoline-3-carboxylate (3c)
Eluent: hexane–EtOAc, 50:1; pale yellow needles; yield: 3.2 mg
(3%); mp 91 °C (hexane).
IR (KBr): 2948, 1715, 1609, 1340, 1278, 1114 cm–1.
1H NMR (CDCl3): δ = 2.51 (s, 3 H), 2.75 (s, 3 H), 3.99 (s, 3 H), 7.39
(d, J = 8.2 Hz, 1 H), 7.62 (d, J = 8.2 Hz, 1 H), 8.70 (d, J = 2.4 Hz, 1
H), 9.39 (d, J = 2.4 Hz, 1 H).
13C NMR (CDCl3): δ = 13.4, 20.9, 52.3, 121.6, 125.1, 126.0, 130.3,
134.7, 138.8, 140.1, 148.7, 148.8, 166.2.
HRMS (EI): m/z [M+] calcd for C13H13NO2: 215.0946; found:
215.0941.
Bis(benzo[h]quinolin-3-yl)methanone (2a)
Eluent: hexane–EtOAc, 50:1; pale yellow needles; yield: 85.5 mg
(89%); mp 218–220 °C.
IR (KBr): 3047, 1639, 1591, 1326, 739 cm–1.
1H NMR (CDCl3): δ = 7.74–7.96 (m, 10 H), 8.67 (d, J = 2.4 Hz, 2
H), 9.34–9.36 (m, 2 H), 9.74 (d, J = 2.4 Hz, 2 H).
13C NMR (CDCl3): δ = 125.2 (2 C), 125.2 (2 C), 125.5 (2 C), 127.7
(2 C), 128.0 (2 C), 129.1 (2 C), 129.5 (2 C), 130.4 (2 C), 131.0 (2
C), 134.7 (2 C), 137.9 (2 C), 148.9 (2 C), 149.1 (2 C), 193.4.
HRMS (EI): m/z [M+] calcd for C27H16N2O: 384.1263; found:
384.1269.
Bis(5,8-dimethylquinolin-3-yl)methanone (2d)
Eluent: hexane–EtOAc, 30:1; pale yellow needles; yield: 59.6 mg
(70%); mp 188–189 °C (hexane–EtOAc, 1:1).
IR (KBr): 2915, 1644, 1279, 824 cm–1.
1H NMR (CDCl3): δ = 2.68 (s, 6 H), 2.84 (s, 6 H), 7.39 (d, J = 7.5
Hz, 2 H), 7.62 (d, J = 7.5 Hz, 2 H), 8.82 (d, J = 2.0 Hz, 2 H), 9.40
(d, J = 2.0 Hz, 2 H).
13C NMR (CDCl3): δ = 18.2 (2 C), 18.7 (2 C), 126.3 (2 C), 128.1 (2
C), 129.0 (2 C), 132.2 (2 C), 134.1 (2 C), 135.5 (2 C), 135.8 (2 C),
148.6 (2 C), 149.2 (2 C), 194.1.
Methyl Benzo[h]quinoline-3-carboxylate (3a)
Eluent: hexane–EtOAc, 50:1; yield: 5.9 mg (5%). The spectroscop-
ic data were identical to those reported in the literature.6p
Bis(7,8,9,10-tetrahydrobenzo[h]quinolin-3-yl)methanone (2b)
Eluent: hexane–EtOAc, 30:1; pale yellow needles; yield: 75.6 mg
(77%); mp 224–225 °C (hexane).
IR (KBr): 2932, 2855, 1639, 1609, 782 cm–1.
1H NMR (CDCl3): δ = 1.91–2.02 (m, 8 H), 2.99 (t, J = 5.6 Hz, 4 H),
3.38 (t, J = 5.6 Hz, 4 H), 7.36 (d, J = 8.4 Hz, 2 H), 7.65 (d, J = 8.4
Hz, 2 H), 8.54 (d, J = 2.4 Hz, 2 H), 9.36 (d, J = 2.4 Hz, 2 H).
13C NMR (CDCl3): δ = 22.7 (4 C), 24.8 (2 C), 30.6 (2 C), 124.9 (2
C), 126.0 (2 C), 128.8 (2 C), 130.2 (2 C), 135.2 (2 C), 138.9 (2 C),
141.7 (2 C), 148.7 (2 C), 148.9 (2 C), 193.6.
HRMS (EI): m/z [M+] calcd for C23H20N2O: 340.1576; found:
340.1577.
Methyl 5,8-Dimethylquinoline-3-carboxylate (3d)
Eluent: hexane–EtOAc, 50:1; pale yellow needles; yield: 4.3 mg
(4%); mp 108 °C (hexane).
IR (KBr): 2924, 1721, 1278, 823 cm–1.
1H NMR (CDCl3): δ = 2.66 (s, 3 H), 2.75 (s, 3 H), 4.01 (s, 3 H), 7.26
(d, J = 7.0 Hz, 1 H), 7.49 (d, J = 7.0 Hz, 1 H), 8.90 (d, J = 2.2 Hz, 1
H), 9.41 (d, J = 2.2 Hz, 1 H).
HRMS (EI): m/z [M+] calcd for C27H24N2O: 392.1889; found:
392.1883.
13C NMR (CDCl3): δ = 18.0, 18.5, 52.4, 122.0, 126.2, 127.5, 131.6,
133.8, 135.1, 135.2, 148.2, 149.2, 166.2.
HRMS (EI): m/z [M+] calcd for C13H13NO2: 215.0946; found:
215.0947.
Methyl 7,8,9,10-Tetrahydrobenzo[h]quinoline-3-carboxylate
(3b)
Eluent: hexane–EtOAc, 50:1; pale yellow needles; yield: 3.6 mg
(3%); mp 93–94 °C (hexane).
Bis(8-methylquinolin-3-yl)methanone (2e)
Eluent: hexane–EtOAc, 20:1; pale yellow needles; yield: 42.9 mg
(55%); mp 138–139 °C (hexane).
IR (KBr): 2934, 1715, 1435, 1254, 784 cm–1.
IR (KBr): 2918, 1651, 1280, 782 cm–1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1825–1832

1830
T. Kusakabe et al.
SPECIAL TOPIC
Methyl 8-(Triethylsilyl)quinoline-3-carboxylate (3g)
Eluent: hexane–EtOAc, 150:1, colorless needles; yield: 85.9 mg
(57%); mp 58 °C.
1H NMR (CDCl3): δ = 2.87 (s, 6 H), 7.55 (dd, J = 7.0, 8.0 Hz, 2 H),
7.72 (d, J = 7.0 Hz, 2 H), 7.77 (d, J = 8.0 Hz, 2 H), 8.59 (d, J = 2.0
Hz, 2 H), 9.40 (d, J = 2.0 Hz, 2 H).
IR (KBr): 2955, 2871, 1721, 1608, 1266, 789 cm–1.
13C NMR (CDCl3): δ = 18.1 (2 C), 126.6 (2 C), 127.3 (2 C), 127.6
(2 C), 129.4 (2 C), 132.4 (2 C), 137.6 (2 C), 139.2 (2 C), 148.8 (2
C), 148.9 (2 C), 193.5.
HRMS (EI): m/z [M+] calcd for C21H16N2O: 312.1263; found:
312.1260.
1H NMR (CDCl3): δ = 0.92–0.96 (m, 9 H), 1.01–1.07 (m, 6 H), 3.99
(s, 3 H), 7.56 (dd, J = 8.0, 6.8 Hz, 1 H), 7.89 (dd, J = 8.0, 1.2 Hz, 1
H), 7.95 (ddd, J = 6.8, 1.2, 0.4 Hz, 1 H), 8.79 (d, J = 2.4 Hz, 1 H),
9.46 (dd, J = 2.4, 0.4 Hz, 1 H).
13C NMR (CDCl3): δ = 4.0 (3 C), 7.7 (3 C), 52.3, 122.4, 126.2,
126.8, 130.0, 138.8, 139.2, 139.7, 148.5, 154.6, 166.2.
HRMS (EI): m/z [M+] calcd for C17H23NO2Si: 301.1498; found:
301.1497.
X-ray crystallographic analysis of 2e: X-ray diffraction data were
collected on a Bruker SMART APEX CCD diffractometer
equipped with a graphite crystal and incident beam monochromator
using MoKα radiation (λ = 0.71073 Å) at 223 K. The structure was
solved by direct method. The non-hydrogen atoms were refined an-
isotropically. Crystallographic parameters: C21H26N2O, MW
=
Bis(2,6-dimethylquinolin-3-yl)methanone (2j)
Eluent: hexane–EtOAc, 100:1; pale yellow needles; yield: 42.6 mg
(50%); mp 147–149 °C.
322.44, monoclinic, space group P21/c, with unit cell a =
11.8081(10) Å, b = 18.5799(16) Å, c = 7.3619(6) Å, β = 94.238(2)°
and V = 1610.7(2) Å3; Z = 4, Dcalcd = 1.330 g cm–3, R1[I > 2σ(I)] =
0.0659, wR2 = 0.2010, 2407 independent reflections [R(int) =
0.0249], 219 parameters refined on F2. Crystallographic data (ex-
cluding structure factors) for the structure have been deposited with
the Cambridge Crystallographic Data Centre as supplementary pub-
lication No. 847693.
IR (KBr): 2956, 2924, 1660, 1615, 1575, 1424, 1271, 1245, 1187,
845 cm–1.
1H NMR (CDCl3): δ = 2.84 (s, 6 H), 2.89 (s, 6 H), 7.38–7.42 (m, 2
H), 7.55 (d, J = 8.0 Hz, 2 H), 7.63 (d, J = 7.2 Hz, 2 H), 8.09 (s, 2 H).
13C NMR (CDCl3): δ = 17.8 (2 C), 25.2 (2 C), 125.3 (2 C), 126.3 (2
C), 126.5 (2 C), 131.8 (2 C), 131.8 (2 C), 136.9 (2 C), 139.2 (2 C),
147.5 (2 C), 156.2 (2 C), 198.1.
Methyl 8-Methylquinoline-3-carboxylate (3e)
Eluent: hexane–EtOAc, 50:1; pale yellow needles; yield: 4.0 mg
(4%); mp 98–99 °C (hexane).
IR (KBr): 2966, 1724, 1284, 785 cm–1.
HRMS (EI): m/z [M+] calcd for C23H20N2O: 340.1576; found:
340.1576.
1H NMR (CDCl3): δ = 2.83 (s, 3 H), 4.01 (s, 3 H), 7.49 (dd, J = 7.2,
8.0 Hz, 1 H), 7.66 (dt, J = 7.2, 1.2 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1
H), 8.78 (d, J = 2.2 Hz, 1 H), 9.45 (d, J = 2.2 Hz, 1 H).
Methyl 2,6-Dimethylquinoline-3-carboxylate (3j)
Eluent: hexane–EtOAc, 100:1; pale yellow needles; yield: 18.3 mg
(17%); mp 112–115 °C.
IR (KBr): 2956, 2920, 1720, 1272, 1251, 1100, 786 cm–1.
13C NMR (CDCl3): δ = 18.1, 52.4, 122.7, 126.8, 127.1, 127.2, 132.0,
1H NMR (CDCl3): δ = 2.80 (s, 3 H), 3.00 (s, 3 H), 3.97 (s, 3 H),
7.39–7.43 (m, 1 H), 7.61 (d, J = 6.8 Hz, 1 H), 7.68 (d, J = 8.0 Hz, 1
H), 8.70 (s, 1 H).
13C NMR (CDCl3): δ = 17.7, 26.0, 52.3, 123.1, 125.6, 126.2, 126.4,
131.7, 136.7, 140.2, 147.8, 157.3, 167.2.
HRMS (EI): m/z [M+] calcd for C13H13NO2: 215.0946; found:
215.0945.
137.4, 138.9, 148.8, 148.9, 166.0.
HRMS (EI): m/z [M+] calcd for C12H11NO2: 201.0790; found:
201.0790.
Bis(8-isopropylquinolin-3-yl)methanone (2f)
Eluent: hexane–EtOAc, 100:1, colorless needles; yield: 70.0 mg
(76%); mp 114–115 °C (hexane).
IR (KBr): 2936, 1646, 1574, 783 cm–1.
1H NMR (CDCl3): δ = 1.43 (d, J = 6.8 Hz, 12 H), 4.41 (septet, J =
6.8 Hz, 2 H), 7.63 (dd, J = 7.2, 8.0 Hz, 2 H), 7.76–7.80 (m, 4 H),
8.62 (d, J = 2.4 Hz, 2 H), 9.42 (d, J = 2.4 Hz, 2 H).
13C NMR (CDCl3): δ = 23.5 (4 C), 27.4 (2 C), 126.7 (2 C), 127.0 (2
C), 127.8 (2 C), 128.1 (2 C), 129.3 (2 C), 139.4 (2 C), 147.6 (2 C),
147.8 (2 C), 148.8 (2 C), 193.6.
Bis(5,7-di-tert-butylquinolin-3-yl)methanone (2k)
Eluent: hexane–EtOAc, 10:1, colorless needles; yield: 59.8 mg
(47%); mp 256–258 °C (hexane–EtOAc, 10:1).
IR (KBr): 2964, 1657, 1594, 1288, 763 cm–1.
1H NMR (CDCl3): δ = 1.48 (s, 18 H), 1.64 (s, 18 H), 7.77 (d, J = 2.2
Hz, 2 H), 8.07 (dd, J = 0.7, 1.9 Hz, 2 H), 9.29 (d, J = 2.2 Hz, 2 H),
9.35 (dd, J = 0.7, 1.9 Hz, 2 H).
HRMS (EI): m/z [M+] calcd for C25H24N2O: 368.1889; found:
13C NMR (CDCl3): δ = 31.0 (6 C), 32.3 (6 C), 35.6 (2 C), 36.5 (2
C), 123.3 (2 C), 123.8 (2 C), 124.0 (2 C), 127.8 (2 C), 137.4 (2 C),
147.8 (2 C), 148.7 (2 C), 151.9 (2 C), 154.8 (2 C), 193.7.
368.1883.
Methyl 8-Isopropylquinoline-3-carboxylate (3f)
Not isolated.
HRMS (EI): m/z [M+] calcd for C35H44N2O: 508.3454; found:
Bis[8-(triethylsilyl)quinolin-3-yl]methanone (2g)
Eluent: hexane–EtOAc, 150:1, colorless needles; yield: 12.8 mg
(10%); mp 146–148 °C (hexane).
IR (KBr): 2951, 2873, 1650, 1604, 728 cm–1.
1H NMR (CDCl3): δ = 0.95–0.99 (m, 18 H), 1.04–1.10 (m, 12 H),
7.61 (dd, J = 8.0, 6.8 Hz, 2 H), 7.92 (dd, J = 8.0, 1.2 Hz, 2 H), 8.01
(dd, J = 6.8, 1.2 Hz, 2 H), 8.58 (d, J = 2.4 Hz, 2 H), 9.38 (d, J = 2.4
Hz, 2 H).
508.3454.
Methyl 5,7-Di-tert-butylquinoline-3-carboxylate (3k)
Eluent: hexane–EtOAc, 25:1; brown oil; yield: 6.0 mg (4%).
IR (neat): 2956, 1724, 1283, 1249, 768 cm–1.
1H NMR (CDCl3): δ = 1.44 (s, 9 H), 1.65 (s, 9 H), 4.01 (s, 3 H), 4.03
(s, 3 H), 7.70 (d, J = 1.6 Hz, 1 H), 7.99 (d, J = 0.8 Hz, 1 H), 9.37 (d,
J = 1.6 Hz, 1 H), 9.45 (t, J = 0.8 Hz, 1 H).
13C NMR (CDCl3): δ = 31.0 (3 C), 32.2 (3 C), 35.5, 36.5, 52.5,
120.6, 123.3, 123.5, 123.8, 137.2, 147.5, 148.5, 154.4, 155.3, 166.3.
HRMS (EI): m/z [M+] calcd for C19H25NO2: 299.1885; found:
299.1886.
13C NMR (CDCl3): δ = 3.9 (6 C), 7.7 (6 C), 125.9 (2 C), 127.1 (2
C), 129.3 (2 C), 130.2 (2 C), 139.0 (2 C), 139.6 (2 C), 139.9 (2 C),
148.6 (2 C), 154.4 (2 C), 194.0.
HRMS (EI): m/z [M+] calcd for C31H40N2OSi2: 512.2679; found:
512.2678.
Synthesis 2012, 44, 1825–1832
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Cyclization–Carbonylation–Cyclization Coupling Reactions
1831
Bis(2-phenethylbenzofuran-3-yl)methanone (5a)
Eluent: hexane–EtOAc, 400:1; yellow oil; yield: 105.9 mg (90%).
IR (KBr): 3028, 2927, 2857, 1720, 1637, 1574, 1453, 749 cm–1.
1H NMR (CDCl3): δ = 3.01–3.17 (m, 8 H), 6.99–7.01 (m, 2 H),
7.08–7.15 (m, 7 H), 7.20–7.29 (m, 7 H), 7.48–7.51 (m, 2 H).
13C NMR (CDCl3): δ = 30.0 (2 C), 34.0 (2 C), 110.0 (2 C), 118.9 (2
C), 121.2 (2 C), 123.6 (2 C), 124.6 (2 C), 125.9 (2 C), 126.2 (2 C),
128.3 (4 C), 128.4 (4 C), 140.3 (2 C), 153.7 (2 C), 163.4 (2 C),
185.9.
Methyl 2-Hexylbenzofuran-3-carboxylate (6c)
Eluent: hexane–EtOAc, 500:1; yellow liquid; yield: 118.5 mg
(91%).
IR (KBr): 2954, 2931, 2859, 1716, 1591, 1062, 751 cm–1.
1H NMR (CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.25–1.40 (m, 6 H),
1.73–1.81 (m, 2 H), 3.18 (t, J = 7.6 Hz, 2 H), 3.94 (s, 3 H), 7.24–
7.30 (m, 2 H), 7.41–7.45 (m, 1 H), 7.93–7.97 (m, 1 H).
13C NMR (CDCl3): δ = 14.1, 22.5, 27.9, 28.1, 29.0, 31.5, 51.3,
108.4, 110.9, 121.9, 123.7, 124.3, 126.2, 153.6, 164.9, 167.8.
HRMS (EI): m/z [M+] calcd for C33H26O3: 470.1882; found:
470.1881.
HRMS (EI): m/z [M+] calcd for C16H20O3: 260.1413; found:
260.1414.
Methyl 2-Phenethylbenzofuran-3-carboxylate (6a)
Eluent: hexane–EtOAc, 400:1, yellow solid; yield: 124.7 mg (89%);
mp 40–42 °C.
Bis(2-octylbenzofuran-3-yl)methanone (5d)
Eluent: hexane–EtOAc, 500:1; yellow liquid; yield: 103.4 mg
(85%).
IR (KBr): 3028, 2951, 2884, 1708, 1590, 1061, 747 cm–1.
IR (KBr): 2926, 2855, 1638, 1573, 1454, 749 cm–1.
1H NMR (CDCl3): δ = 3.09 (t, J = 8.0 Hz, 2 H), 3.49 (t, J = 8.0 Hz,
2 H), 3.92 (s, 3 H), 7.18–7.32 (m, 7 H), 7.43–7.46 (m, 1 H), 7.96–
7.98 (m, 1 H).
13C NMR (CDCl3): δ = 30.2, 34.1, 51.4, 108.9, 110.9, 121.9, 123.8,
124.5, 126.1, 126.3, 128.4 (2 C), 128.5 (2 C), 140.6, 153.7, 164.7,
166.2.
1H NMR (CDCl3): δ = 0.85 (t, J = 6.8 Hz, 6 H), 1.21–1.27 (m, 20
H), 1.74 (quint, J = 7.2 Hz, 4 H), 2.91 (t, J = 7.6 Hz, 4 H), 7.11–7.15
(m, 2 H), 7.23–7.28 (m, 2 H), 7.35–7.38 (m, 2 H), 7.46–7.48 (m, 2
H).
13C NMR (CDCl3): δ = 14.1 (2 C), 22.6 (2 C), 28.0 (2 C), 28.1 (2
C), 29.1 (2 C), 29.2 (2 C), 29.3 (2 C), 31.8 (2 C), 111.1 (2 C), 118.6
(2 C), 121.1 (2 C), 123.6 (2 C), 124.4 (2 C), 126.2 (2 C), 153.7 (2
C), 164.8 (2 C), 186.3.
HRMS (EI): m/z [M+] calcd for C18H16O3: 280.1099; found:
280.1101.
HRMS (EI): m/z [M+] calcd for C33H42O3: 486.3134; found:
486.3136.
Bis[2-(3-phenylpropyl)benzofuran-3-yl]methanone (5b)
Eluent: hexane–EtOAc, 300:1; colorless oil; yield: 115.9 mg (93%).
IR (KBr): 3026, 2933, 2859, 1635, 1572, 1453, 749 cm–1.
Methyl 2-Octylbenzofuran-3-carboxylate (6d)
Eluent: hexane–EtOAc, 500:1; yellow liquid; yield: 144.2 mg
(73%).
IR (KBr): 2953, 2928, 2885, 1717, 1591, 1067, 751 cm–1.
1H NMR (CDCl3): δ = 0.87 (t, J = 7.0 Hz, 3 H), 1.26–1.41 (m, 10
H), 1.77 (quint, J = 7.6 Hz, 2 H), 3.17 (t, J = 7.6 Hz, 2 H), 3.94 (s,
3 H), 7.27–7.29 (m, 2 H), 7.42–7.44 (m, 1 H), 7.95–7.97 (m, 1 H).
1H NMR (CDCl3): δ = 2.06 (quint, J = 7.6 Hz, 4 H), 2.60 (t, J = 7.6
Hz, 4 H), 2.92 (t, J = 7.6 Hz, 4 H), 7.07–7.28 (m, 14 H), 7.37 (d,
J = 7.6 Hz, 2 H), 7.49 (d, J = 8.4 Hz, 2 H).
13C NMR (CDCl3): δ = 27.7 (2 C), 29.6 (2 C),35.4 (2 C), 110.1 (2
C), 118.8 (2 C), 121.1 (2 C), 123.7 (2 C), 124.5 (2 C), 125.9 (2 C),
126.1 (2 C), 128.3 (4 C), 128.4 (4 C), 141.3 (2 C), 153.7 (2 C), 164.2
(2 C), 186.1.
13C NMR (CDCl3): δ = 14.1, 22.7, 27.9, 28.1, 29.2, 29.3, 29.4, 31.9,
51.3, 108.4, 110.9, 121.9, 123.7, 124.3, 126.2, 153.6, 164.9, 167.8.
HRMS (EI): m/z [M+] calcd for C18H24O3: 288.1726; found:
HRMS (EI): m/z [M+] calcd for C35H30O3: 498.1295; found:
498.1296.
288.1729.
Methyl 2-(3-Phenylpropyl)benzofuran-2-carboxylate (6b)
Eluent: hexane–EtOAc, 300:1; white oil; yield: 129.5 mg (88%).
Bis[2-(3-methylbutyl)benzofuran-3-yl]methanone (5e)
Eluent: hexane–EtOAc, 1000:1; yellow oil; yield: 85.5 mg (85%).
IR (KBr): 2956, 2927, 2870, 1637, 1573, 1456, 748 cm–1.
1H NMR (CDCl3): δ = 0.84 (d, J = 6.4 Hz, 12 H), 1.48–1.67 (m, 6
H), 2.91 (t, J = 7.8 Hz, 4 H), 7.11–7.15 (m, 2 H), 7.23–7.28 (m, 2
H), 7.36–7.38 (m, 2 H), 7.45–7.48 (m, 2 H).
13C NMR (CDCl3): δ = 22.1 (4 C), 26.1 (2 C), 27.8 (2 C), 36.9 (2
C), 111.0 (2 C), 118.5 (2 C), 121.0 (2 C), 123.6 (2 C), 124.4 (2 C),
126.2 (2 C), 153.7 (2 C), 164.9 (2 C), 186.3.
IR (KBr): 3028, 2949, 1714, 1590, 1237, 751 cm–1.
1H NMR (CDCl3): δ = 2.12 (quint, J = 7.6 Hz, 2 H), 2.72 (t, J = 7.6
Hz, 2 H), 3.22 (t, J = 7.6 Hz, 2 H), 3.90 (s, 3 H), 7.19–7.43 (m, 8 H),
7.96–7.97 (m, 1 H).
13C NMR (CDCl3): δ = 27.7, 29.4, 35.4, 51.3, 108.7, 110.8, 121.8,
123.7, 124.4,125.9, 126.1, 128.3 (2 C), 128.4 (2 C), 141.5, 153.6,
164.7, 166.9.
HRMS (EI): m/z [M+] calcd for C19H18O3: 294.1256; found:
294.1257.
HRMS (EI): m/z [M+] calcd for C27H30O3: 402.2195; found:
402.2196.
Bis(2-hexylbenzofuran-3-yl)methanone (5c)
Eluent: hexane–EtOAc, 500:1; yellow liquid; yield: 92.6 mg (86%).
Methyl 2-(3-Methylbutyl)benzofuran-3-carboxylate (6e)
Eluent: hexane–EtOAc, 1000:1; yellow liquid: yield: 98.5 mg
(80%).
IR (KBr): 2955, 2929, 2871, 1716, 1591, 1062, 751 cm–1.
1H NMR (CDCl3): δ = 0.97 (d, J = 6.0 Hz, 6 H), 1.62–1.68 (m, 3 H),
3.19 (t, J = 7.6 Hz, 2 H), 3.95 (s, 3 H), 7.24–7.30 (m, 2 H), 7.41–
7.44 (m, 1 H), 7.93–7.97 (m, 1 H).
IR (KBr): 2957, 2929, 2857, 1638, 1574, 1454, 749 cm–1.
1H NMR (CDCl3): δ = 0.83 (t, J = 6.8 Hz, 6 H), 1.22–1.28 (m, 12
H), 1.71–1.78 (m, 4 H), 2.91 (t, J = 7.6 Hz, 4 H), 7.11–7.15 (m, 2
H), 7.23–7.28 (m, 2 H), 7.36–7.38 (m, 2 H), 7.47–7.49 (m, 2 H).
13C NMR (CDCl3): δ = 14.0 (2 C), 22.5 (2 C), 28.0 (4 C), 28.9 (2
C), 31.4 (2 C), 111.0 (2 C), 118.6 (2 C), 121.1 (2 C), 123.6 (2 C),
124.4 (2 C), 126.2 (2 C), 153.7 (2 C), 164.8 (2 C), 186.3.
13C NMR (CDCl3): δ = 22.3 (2 C), 26.2, 27.9, 36.8, 51.3, 108.3,
110.8, 121.8, 123.7, 124.3, 126.2, 153.6, 164.9, 167.9.
HRMS (EI): m/z [M+] calcd for C15H18O3: 246.1256; found:
HRMS (EI): m/z [M+] calcd for C29H34O3: 430.2508; found:
430.2509.
246.1254.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1825–1832

1832
T. Kusakabe et al.
SPECIAL TOPIC
Methyl 2-Phenylbenzofuran-3-carboxylate (6f)
Tetrahedron Lett. 2011, 52, 1783. (e) Majumdar, K. C.;
Nandi, R. K.; Ganai, S.; Taher, A. Synlett 2011, 116. (f) See
also: Fei, N.; Yin, H.; Wang, S.; Wang, H.; Yao, Z.-J. Org.
Lett. 2011, 13, 4208. (g) Zhang, X.; Yao, T.; Campo, M. A.;
Larock, R. C. Tetrahedron 2010, 66, 1177. (h) Imase, H.;
Suda, T.; Shibata, Y.; Noguchi, K.; Hirano, M.; Tanaka, K.
Org. Lett. 2009, 11, 1805. (i) Kuninobu, Y.; Inoue, Y.;
Takai, K. Chem. Lett. 2007, 36, 1422. (j) Watanabe, T.;
Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2007, 9, 4821.
(k) Nevado, C.; Echavarren, A. M. Chem.–Eur. J. 2005, 11,
3155. (l) Sangu, K.; Fuchibe, K.; Akiyama, T. Org. Lett.
2004, 6, 353. (m) Abbiati, G.; Arcadi, A.; Bianchi, G.;
Giuseppe, S. D.; Marinelli, F.; Rossi, E. J. Org. Chem. 2003,
68, 6959. (n) Martín-Matute, B.; Nevado, C.; Cárdenas, D.
J.; Echavarren, A. M. J. Am. Chem. Soc. 2003, 125, 5757.
(o) Williamson, N. M.; March, D. R.; Ward, A. D.
Yield: 103.4 mg (82%).
The spectroscopic data were identical to those reported in the liter-
ature.9l
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.omnoinfrtIangiomnSionurpoatfrInt
giSutpor
References
(1) (a) Michael, J. P. Nat. Prod. Rep. 2001, 18, 543.
(b) Balasubramanian, M.; Keay, J. G. In Comprehensive
Heterocyclic Chemistry II, Vol. 5; Katritzky, A. R.; Rees, C.
W.; Scriven, E. F. V., Eds.; Pergamon Press: Oxford, 1996,
245. (c) Donnelly, D. M. X.; Meegan, M. J. In
Tetrahedron Lett. 1995, 36, 7721. (p) O’Dell, D. K.;
Nicholas, K. M. J. Org. Chem. 2003, 68, 6427.
Comprehensive Heterocyclic Chemistry, Vol. 4; Katritzky,
A. R.; Rees, C. W., Eds.; Pergamon Press: Oxford, 1984,
657.
(7) (a) Yasuhara, S.; Sasa, M.; Kusakabe, T.; Takayama, H.;
Kimura, M.; Mochida, T.; Kato, K. Angew. Chem. Int. Ed.
2011, 50, 3912; Angew. Chem. 2011, 123, 3998 . (b) Kato,
K.; Teraguchi, R.; Yamamura, S.; Mochida, T.; Akita, H.;
Peganova, T. A.; Vologdin, N. V.; Gusev, O. V. Synlett
2007, 638. (c) Kato, K.; Teraguchi, R.; Motodate, S.;
Uchida, A.; Mochida, T.; Peganova, T. A.; Vologdin, N. V.;
Akita, H. Chem. Commun. 2008, 3687. (d) Kato, K.;
Motodate, S.; Mochida, T.; Kobayashi, T.; Akita, H. Angew.
Chem. Int. Ed. 2009, 48, 3326; Angew. Chem. 2009, 121,
3376 . (e) Motodate, S.; Kobayashi, T.; Fujii, M.; Mochida,
T.; Kusakabe, T.; Katoh, S.; Akita, H.; Kato, K. Chem. Asian
J. 2010, 5, 2221. (f) Kusakabe, T.; Kawai, Y.; Shen, R.;
Mochida, T.; Kato, K. Org. Biomol. Chem. 2012, 10, DOI:
10.1039/c2ob07016b. (g) Recently, we reported the CCC-
coupling reaction of allenyl ketones without box ligand. The
reactivity of allenyl compounds is high enough to induce
dimer formation: Kato, K.; Mochida, T.; Takayama, H.;
Kimura, M.; Moriyama, H.; Takeshita, A.; Kanno, Y.; Inoue,
Y.; Akita, H. Tetrahedron Lett. 2009, 50, 4744.
(2) (a) Neumann, H.; Brennführer, A.; Beller, M. Chem.–Eur. J.
2008, 14, 3645; and references cited therein. (b) Chaplin, J.
H.; Flynn, B. L. Chem. Commun. 2001, 1549; and references
cited therein.
(3) (a) Nguyen, A.; Top, S.; Pigeon, P.; Vessières, A.; Hillard,
E. A.; Plamont, M.-A.; Huché, M.; Rigamonti, C.; Jaouen,
G. Chem.–Eur. J. 2009, 15, 684. (b) Chao, E. Y. H.; Collins,
J. L.; Gaillard, S.; Miller, A. B.; Wang, L.; Orband-Miller,
L. A.; Nolte, R. T.; McDonnell, D. P.; Willson, T. M.;
Zuercher, W. J. Bioorg. Med. Chem. Lett. 2006, 16, 821.
(4) (a) Álvarez, C.; Álvarez, R.; Corchete, P.; López, J. L.;
Pérez-Melero, C.; Peláez, R.; Medarde, M. Bioorg. Med.
Chem. 2008, 16, 5952. (b) Das, S. K.; Panda, G.; Chaturvedi,
V.; Manju, Y. S.; Gaikwad, A. K.; Sinha, S. Bioorg. Med.
Chem. Lett. 2007, 17, 5586. (c) Schmidt, F.; Stemmler, R.
T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev. 2006, 35, 454.
(5) (a) Handbook of Organopalladium Chemistry for Organic
Synthesis, Vol. II; Negishi, E., Ed.; Wiley: New York, 2002,
2309. For recent reviews, see: (b) Vlaar, T.; Ruijter, E.;
Orru, R. V. A. Adv. Synth. Catal. 2011, 353, 809. (c) Grigg,
R.; Mutton, S. P. Tetrahedron 2010, 66, 5515. (d) See also:
Majumdar, K. C.; Chattopadhyay, B.; Maji, P. K.;
Chattopadhyay, S. K.; Samanta, S. Heterocycles 2010, 81,
795. (e) Majumdar, K. C.; Debnath, P.; Roy, B. Heterocycles
2009, 78, 2661. (f) Asao, N. Synlett 2006, 1645. (g) Muzart,
J. Tetrahedron 2005, 61, 5955. (h) Ma, S. Chem. Rev. 2005,
105, 2829. (i) Nakamura, I.; Yamamoto, Y. Chem. Rev.
2004, 104, 2127. (j) Zeni, G.; Larock, R. C. Chem. Rev.
2004, 104, 2285. (k) Soderberg, B. C. G. Coord. Chem. Rev.
2004, 248, 1085. (l) Vizer, S. A.; Yerzhanov, K. B.; Al Aziz
Al Quntar, A.; Dembitsky, V. M. Tetrahedron 2004, 60,
5499. For palladium-catalyzed carbonylative coupling
reaction, see: (m) Brennführer, A.; Neumann, H.; Beller, M.
ChemCatChem 2009, 1, 28. (n) Torborg, C.; Beller, M. Adv.
Synth. Catal. 2009, 351, 3027. (o) Barnard, C. F. J.
Organometallics 2008, 27, 5402. (p) Wu, X.-F.; Neumann,
H.; Beller, M. Angew. Chem. Int. Ed. 2009, 48, 4114;
Angew. Chem. 2009, 121, 4176.
(8) Palladium(II) complexes of anilines were reported, see:
(a) Yang, E.; Kang, Y.; Chen, G.-Y. Acta Crystallogr., Sect.
E 2006, 62, m1368. (b) Chen, Y. B.; Li, Z. J.; Qin, Y. Y.;
Kang, Y.; Wu, L.; Yao, Y. G. Chin. J. Struct. Chem. 2002,
21, 530; and references cited therein.
(9) (a) Liao, Y.; Reitman, M.; Zhang, Y.; Fathi, R.; Yang, Z.
Org. Lett. 2002, 4, 2607. (b) Arcadi, A.; Cacchi, S.;
Giuseppe, S. D.; Fabrizi, G.; Marinelli, F. Org. Lett. 2002, 4,
2409. (c) Kondo, Y.; Shiga, F.; Murata, N.; Sakamoto, T.;
Yamanaka, H. Tetrahedron 1994, 50, 11803. (d) Kondo, Y.;
Shiga, F.; Murata, N.; Sakamoto, T.; Yamanaka, H.
Tetrahedron 1994, 50, 11803. For carbonylative coupling,
see: (e) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Moro, L. Eur. J.
Org. Chem. 1999, 1137. (f) Chaplin, J. H.; Flynn, B. L.
Chem. Commun. 2001, 1594. (g) Luo, Y.; Wu, J. Org. Lett.
2011, 13, 5858. For coupling reactions, see: (h) Hachiya,
H.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2011, 13,
3076. (i) Luo, Y.; Hong, L.; Wu, J. Chem. Commun. 2011,
47, 5298. (j) Álvarez, R.; Martínez, C.; Madich, Y.; Denis, J.
G.; Aurrecoechea, J. M.; De Lera, Á. R. Chem.–Eur. J. 2010,
16, 12746. (k) Lütjens, H.; Scammells, P. J. Synlett 1999,
1079. (l) Liu, Y.; Qian, J.; Lou, S.; Xu, Z. J. Org. Chem.
2010, 75, 6300.
(6) For selected reviews, see: (a) Yamamoto, Y.; Gridnev, I. D.;
Patil, N. T.; Jin, T. Chem. Commun. 2009, 5075.
(b) Kitamura, T. Eur. J. Org. Chem. 2009, 1111. (c) Nevado,
C.; Echavarren, A. M. Synthesis 2005, 1067. For selected
examples, see: (d) Gurunathan, S.; Perumal, P. T.
Synthesis 2012, 44, 1825–1832
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