Pd-catalyzed tandem homocoupling-aldol-dehydration of ortho-acylphenyl iodides

Article abstract of DOI:10.1039/c4ra02055c

A Pd-catalyzed cascade Ullmann coupling-aldol-dehydration reaction of ortho-acylphenyl iodides has been explored. This transformation provides a concise access to colchino analogues in moderate to good yields with wide functional group tolerance.

Full text of DOI:10.1039/c4ra02055c

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Pd-catalyzed tandem homocoupling–aldol–
dehydration of ortho-acylphenyl iodides†
Cite this: RSC Adv., 2014, 4, 23595
Meiqin Fu,a Dongen Lin,a Yuanfu Deng,a Xiao-Qi Zhang,b Yanchu Liu,a Chunsong Laia
a
*
and Wei Zeng
Received 9th March 2014
Accepted 19th May 2014
A Pd-catalyzed cascade Ullmann coupling–aldol–dehydration reaction of ortho-acylphenyl iodides has
been explored. This transformation provides a concise access to colchino analogues in moderate to
good yields with wide functional group tolerance.
DOI: 10.1039/c4ra02055c
www.rsc.org/advances
reaction steps and harsh reaction conditions. Considering
that colchicine derivatives possesses potent anti-tumour
Introduction
properties, the development of a concise approach to
these compounds therefore is desirable. In order to further
richen the colchinol library, herein we described a Pd-cata-
lyzed tandem Ullmann homocoupling–aldol–dehydration of
ortho-acylphenyl iodides14 to rapidly construct colchinol
analogues.
Transition-metal catalyzed homocoupling of aryl halides, as
a powerful tool to construct aryl carbon (sp2)–aryl carbon
(sp2) bonds, provides an efficient route to biaryl motifs
which are frequently encountered in the elds of optical
materials,1 molecular devices2 and natural products.3
Since the Ullmann coupling was rst reported one century
ago,4 much signicant progress on various transition-
metal catalyzed homocoupling reactions of aryl halides has
already been achieved.5 In contrast, there have been rare
reports about the transition-metal catalyzed cascade Ull-
mann coupling reaction of aryl halides, which possibly
provides a concise approach to construct complex organic
compounds.6
On the other hand, rapid assembly of dibenzo-seven-
memebered-ring system has attracted growing interesting
in synthetic and medicinal eld due to that this
macrocyclic system belongs to an important core structure
of many biologically active molecules such colchicine deriv-
atives.7 Therefore, various methodologies including the ring
expansion of phenanthrene derivatives,8 Diels–Alder reac-
tions,9 direct arylations10 and Nicholas reactions,11 Suzuki–
Miyaura coupling–aldol condensation reaction12 were
successively developed to make these compounds. Never-
theless, the number and range of examples disclosed in
the above-mentioned methods to date is still limited. More-
over, Leonard ever reported an elegant synthetic process to
Results and discussion
The Pd(OAc)2-catalyzed cascade cyclization of ortho-bro-
moacetophenone 1b (0.20 mmol) in the presence of NaHCO3
(1.5 equiv.) and PPh3 (10 mol%) was rst investigated in
DMF (1.0 mL) at 150 ꢀC for 3 h (Table 1, entry 1), and
we quickly found that this transformation could provide
us the 7-membered-ring product 2a (23% yield) and the
by product 3a (16% yield) which was derived from the further
C–H functionalization reaction of 2a, and the chemical
structure of 3a was also unambiguously conrmed by its
single crystal X-ray analysis (see Fig. 1 and ESI† for more
details).
Although the competitive C–H arylation led to lower yield
of the desired dibenzo-cycloheptenone 2a, this positive
result still encouraged us to conduct further optimization of
the reaction conditions for achieving excellent selectivity.
Then, we found the PdCl2/PPh3/K2CO3 system could afford
2a and 3a in 78% overall yield, but the reaction specication
is still very poor (2a/3a z 1, entry 7). Subsequently, we had
to switch our focus to the substrate and ligand screening for
improving the reaction selectivity (entries 8–17). To our
delight, ortho-iodo-substituted acetophenone (1c) could
high-specically give the desired product 2a in 80% yield
using 1,3-bis (diphenylphosphino) propane (DPPP) (L3) as
ligand, and only trace amounts of 3a (<5% yield) was
observed (entry 17). Notably, the Pd-catalyzed cascade
cyclization of ortho-chloro-substituted acetophenone (1a)
could not furnish 2a or 3a under PdCl2/L3/K2CO3 condi-
tions, and the starting material 1a was recovered completely
construct dibenzo-cycloheptenone core via
a
six-step
protocol including Ullmann coupling and aldol condensa-
tion, etc.13 However, this procedure suffered from tedious
aSchool of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou 510641, P. R. China. E-mail: zengwei@scut.edu.cn
bCollege of Pharmacy, Jinan University, Guangzhou 510632, P. R. China
† Electronic supplementary information (ESI) available: Detailed experimental
procedures and characterization of products. CCDC 998466. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c4ra02055c
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23595–23603 | 23595

View Article Online
RSC Advances
Paper
Table 1 Optimisation of the Pd-catalyzed cascade cyclization of Table
2
Pd-catalyzed cascade cyclization of ortho-acylphenyl
ortho-haloacetophenonea
iodidesa
Entry
X
Pd salts
L
Base
2a/3a yieldb (%)
Entry
1
Substrate
Product
Yieldb (%)
80
1
2
3
4
5
6
7
8
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
I
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
Pd(MeCN)2Cl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L6
L7
L3
L1
L2
L3
L4
L3
L3
NaHCO3
K2CO3
Cs2CO3
NEt3
23/16
32/32
14/10
0/16
28/37
32/32
41/37
41/42
42/39
32/18
0/22
0/0
0/0
0/0
14/28
60/4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
2
3
4
72
80
64
9
10
11
12
13
14
15
16
17
18
19
20
I
I
I
I
80/<5
46/18
71/4c
68/<5d
I
PdCl2
5
72
6
7
35
30
a
Unless otherwise noted, ortho-haloacetophenone (0.20 mmol) was
treated with Pd catalyst (5 mol%) in the presence of ligand (L) (10
mol%) and base (1.5 equiv.) in DMF (1.0 mL) at 150 ꢀC for 3 h under
Ar condition in a sealed tube, followed by ash chromatography on
8
9
0
b
c
d
SiO2. Isolated yield. The reaction temperature was 140 ꢀC. 2.5
mol% of PdCl2 was used.
46
10
62
11
12
66
80
Fig. 1 Single crystal structure of 3a.
(entry 14). Further optimization of this reaction conditions
demonstrated that lowering the reaction temperature or
reducing the Pd catalyst loading led to poorer yield of 2a
13
61
23596 | RSC Adv., 2014, 4, 23595–23603
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 2 (Contd.)
(compare entries 17 with 19 and 20) (see ESI for more
details†).
Having established an efficient reaction protocol that
enables the smooth cascade homocoupling cyclization of
ortho-iodoacetophenone, we next investigated the effect of
substituents on this tandem reaction. As shown in Table 2,
although the various functional group-substituted phenyl-
ketones (1) could smoothly homocouple and cyclize to
Entry
14
Substrate
Product
Yieldb (%)
furnish dibenzo-cycloheptenone
2 under the optimized
conditions, the substituted group on the benzene ring
showed signicant electronic effects. The electron donating
group including 5-MeO, 5-Me, 5-NH2, 5-NHAc, 5-aryl, 5-
alkynyl, 4-Me, 4-MeO, 4-NH2 and 4-AcNH on the phenyl ring
afforded the dibenzo-7-membered-ring compounds in
moderate to excellent yields (48–80%) (entries 1–5, 10–19).15
On the contrary, the electron withdrawing group such as 5-
Cl and 5-CO2Et on the phenyl ring gave the desired product
in poorer yields (30–46%) (entries 6 and 9). It is worth
noting that the 5-bromo-substituted phenylketone 1i led to
the formation of 3-acetylphenanthrene instead of 7-
membered ring product (entry 7). Moreover, no cascade
homocoupling/cyclization product from the electon-poor 5-
nitro-substituted phenylketone 1j was observed (entry 8). To
further explore the substrate scope, we also investigated the
effect of the acyl substituent (R1CH2CO–) on this cascade
reaction, and found the ortho-propionyl phenyl iodide (1v)
and ortho-phenyl acetyl phenyl iodide (1w) could also
provide the expected polysubstituted dibenzo-cyclo-
heptenone 2t and 2u (entries 20 and 21). Unfortunately,
ortho-bromoactyl phenyl iodide (1x) only led to the forma-
tion of 2a in which bromo group was reductively removed.
In addition, we tried to use the 1-(2-iodo-3-methyl-phenyl)-
ethanone (1y) as a substrate, but no desired product 2v was
obtained possibly due to the “ortho-substitutent” effect
(entry 23).
To further investigate the reaction mechanism, we con-
ducted the Pd(II)-catalyzed cascade cyclization of ortho-
iodoacetophone (1c) at lower reaction temperature (130 ꢀC)
in order to trap some possible byproducts and intermedi-
ates (Scheme 1a). Aer the reaction was carried out for
0.5 h, we observed the formation of alcohol intermediate
3b (18% isolated yield) which could be further converted
into the desired product 2a in 82% yield under our
standard conditions (Scheme 1b). Considering that aryl
halides (1c) could easily convert to symmetric biaryl
ketone (3c) using palladium catalysts via a Ullmann proc-
ess,5d,16 and the alcohol intermediate 3b is also
possibly derived from the ketone 3c via an intramolecular
aldol reaction (Scheme 1c), we tried to use 3c as a substrate
under our standard conditions. As expected, we also
obtained the 7-membered-ring product 2a in 81% yield
(Scheme 1d).
48
15
16
74
75
17
18
19
20
72
68
78
34
21
22
40
48
23
0
a
Unless otherwise noted, ortho-acylphenyl iodides 1 (0.20 mmol) was
treated with PdCl2 (5 mol%) in the presence of ligand (DPPP) (10
mol%) and K2CO3 (1.5 equiv.) in DMF (1.0 mL) at 150 ꢀC for 3 h
Although the exact reaction mechanism about Pd-cata-
lyzed homocoupling of aryl halides is not still clear,17 on the
basis of the above-mentioned control experimental results,
we proposed two plausible reaction pathways (see Fig. 2).
At rst, the organic phosphine ligand (DPPP) or DMF18
under Ar condition in
a
sealed tube, followed by ash
chromatography on SiO2. b Isolated yield.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23595–23603 | 23597

View Article Online
RSC Advances
Paper
Conclusions
In summary, we have developed an efficient Pd-catalyzed
cascade homocoupling–aldol–dehydration reaction of ortho-
acylphenyl iodides to rapidly construct colchinol analogues in
moderate to good yields, and the further biological activity
evaluation for these compounds is currently underway in our
laboratory.
Experimental
General information
Unless otherwise noted, all reagents including 1a, 1b and 1c
were purchased from commercial suppliers and used without
purication, and all reactions were carried out under argon
atmosphere in ame-dried sealed tubes with magnetic stirring.
Scheme 1 Control reactions.
˚
Solvents were treated with 4 A molecular sieves or sodium and
distilled prior to use. Flash chromatography was performed on
silica gel (40–63 mm) by standard technique. H and 13C NMR
1
reduces Pd(II) to Pd(0), followed by the oxidative addition
with Ar–I (1c) to form Pd(II) intermediate A.15 Then the
second oxidative addition of Pd(II) intermediate A with
another ortho-iodoacetophenone molecule (1c) via Pathway I
leads to the formation of the Pd(IV) intermediate B,15,19
spectra were recorded on a 400 MHz spectrometer at room
temperature with tetramethylsilane (TMS) as internal standard.
Chemical shis are reported in parts per million (ppm) and
coupling constants are reported as Hertz (Hz). Splitting patterns
are designated as singlet (s), doublet (d), triplet (t), quartet (q).
Splitting patterns that could not be interpreted or easily visu-
alized are designated as multiple (m). High resolution exact
mass measurements (HR-MS) were performed on a TOF spec-
trometer (Micromass). Infrared spectra (IR) were reported as
wavelength numbers (cmꢁ1). Infrared spectra were recorded
by preparing a KBr pellet containing the title compound.
Crystal data were obtained by employing graphite mono-
and
subsequent
reductive
elimination
affords
homocoupling product 3c which can further lead to the
formation of the nal dibenzo-cycloheptenone 2a via
cascade intramolecular aldol–dehydration process;20 in
addition to Pathway I, an alternative reaction Pathway II can
not be ruled out in the absence of strong oxidizing agents, in
which the disproportionation between two Ar–Pd(II)–I (A)
molecules can lead to Ar–Pd(II)–Ar (C) and Pd(II)I2.21 The
resulting bisarylpalladium(II) C will be subjected to reductive
elimination to afford the corresponding coupling product 3c
and Pd(0).
˚
chromated Mo-Ka radiation (l ¼ 0.71073 A) at 293(2) K and
operating in the 4–u scan mode. The structure was solved by
direct methods SHELXS-97; 1-(2-amino-5-methylphenyl)etha-
none,20 1-(2-amino-5-chlorophenyl)ethanone,22 2-amino-5-nitro-
acetophenone,23 1-(2-amino-5-bromophenyl)ethanone,24 1-(4-
amino-[1,10-biphenyl]-3-yl)ethanone,24 1-(2-amino-5-(thiophen-
3-yl)phenyl)ethanone,24 1-(2-amino-5-(furan-2-yl)phenyl)etha-
none,24 1-(2-amino-5-(phenylethynyl)phenyl)ethanone,24 ethyl-3-
acetyl-4-aminobenzoate,25 1-(2-amino-4,5-dimethylphenyl)etha-
none,26 1-(2-amino-3-methylphenyl)ethanone27 and 1,10-([1,10-
biphenyl]-2,20-diyl)diethanone,28 1-(2-iodo-5-methoxyphenyl)-
ethanone (1e),29 1-(2-iodo-4-methylphenyl)ethanone (1q),30 1-(2-
iodo-4-methoxyphenyl)ethanone (1r),30 1-(2-iodophenyl)propan-
1-one (1v),29 1-(2-iodophenyl)-2-phenyl-1-ethanone (1w),31 2-
bromo-1-(2-iodophenyl)ethanone (1x)32 and 2-iodo-3-methyl-
acetophenone (1y)33 were prepared using the previous reported
procedure. Procedures for the preparation of ortho-acylphenyl
iodides.
Procedure A: general procedure for the preparation of 1d, 1f,
1h–1p and 1u
To a stirred solution of p-toluenesulfonic acid monohydrate
(3.8 g, 20.1 mol) in acetonitrile (24 mL) was added corre-
sponding 4- or 5-substituted-2-acyl-anilines (6.7 mmol). The
resulting suspension of protonated amine was cooled to 10 ꢀC.
Fig. 2 The proposed reaction mechanism.
23598 | RSC Adv., 2014, 4, 23595–23603
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
To this mixture was carefully added an aqueous solution (4 mL) NMR (101 MHz, CDCl3) d 200.2, 145.6, 142.1, 134.8, 131.2, 122.5,
of potassium iodide (2.78 g, 16.75 mmol) and sodium nitrite 88.9, 29.4; IR (KBr): 3542, 2987, 1695, 1447, 1338, 1142, 1019,
(0.92 g, 13.4 mmol). The resulting brown solution was warmed 754, 548 cmꢁ1; HRMS (EI) calcd for [M]+: C8H6IBrO 323.8641,
to room temperature aer N2 gas evolution ceased. Aer 4.5 found 323.8640.
hours, 55 mL of water was added, the mixture was brought to
1-(2-Iodo-5-nitrophenyl)ethanone (1j). Yellow solid; 36%
pH ¼ 9 by saturated sodium bicarbonate solution and adding 6 yield; mp 145–147 ꢀC; 1H NMR (400 MHz, CDCl3) d 8.27 (d, J ¼
mL of a saturated aqueous solution of sodium thiosulfate. 2.4 Hz, 1H), 8.17 (d, J ¼ 8.6 Hz, 1H), 7.96 (dd, J ¼ 8.6, 2.5 Hz,
The resulting light yellow solution was extracted with ether (3 ꢂ 1H), 2.69 (s, 3H); 13C NMR (101 MHz, CDCl3) d 199.5, 147.8,
50 mL) and washed with brine, dried over anhydrous magne- 145.0, 142.3, 125.6, 122.6, 99.3, 29.3; IR (KBr): 3779, 3538, 3082,
sium sulphate, and concentrated under reduced pressure to 2916, 1704, 1567, 1415, 1264, 1113, 1014, 752, 494 cmꢁ1; HRMS
afford the aryl iodides aer purication via ash column (EI) calcd for [M]+: C8H6INO3 290.9387, found 290.9388.
1
chromatography.
Ethyl-3-acetyl-4-iodobenzoate (1k). Yellow oil; 54% yield; H
1-(2-Iodo-5-methylphenyl)ethanone (1d). Yellow oil; 48% NMR (400 MHz, CDCl3) d 8.11 (d, J ¼ 2.0 Hz, 1H), 8.05 (d, J ¼ 8.2
yield; 1H NMR (400 MHz, CDCl3) d 7.76 (dd, J ¼ 7.9, 3.2 Hz, 1H), Hz, 1H), 7.76 (dd, J ¼ 8.2, 2.0 Hz, 1H), 4.42 (q, J ¼ 7.1 Hz, 2H),
7.26 (s, 1H), 6.93 (d, J ¼ 7.9 Hz, 1H), 2.59 (s, 3H), 2.33 (s, 3H); 13
C
2.67 (s, 3H), 1.42 (t, J ¼ 7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) d
NMR (101 MHz, CDCl3) d 202.0, 143.9, 140.5, 138.2, 132.8, 129.1, 200.9, 165.3, 144.0, 141.3, 132.1, 130.6, 128.9, 97.0, 61.6, 29.4,
86.8, 29.5, 20.9; IR (KBr): 3680, 2979, 2924, 1699, 1562, 1467, 14.2; IR (KBr): 3782, 3542, 1695, 1447, 1338, 1142, 1019, 754, 548
1268, 1175, 1120, 1014, 756 cmꢁ1; HRMS (EI) calcd for [M]+: cmꢁ1; HRMS (EI) calcd for [M]+: C11H11IO3 317.9747, found
C9H9IO 259.9693, found 259.9692.
317.9749.
1-(6-Iodobenzo[d][1,3]dioxol-5-yl)ethanone (1l). Yellow solid;
1-(5-Amino-2-iodophenyl)ethanone (1f). Yellow solid; 52%
1
1
yield; mp 276–278 ꢀC; H NMR (400 MHz, CDCl3) d 7.60 (d, J ¼ 65% yield; mp 93–94 C; H NMR (400 MHz, CDCl3) d 7.37 (s,
8.4 Hz, 1H), 6.75 (d, J ¼ 2.5 Hz, 1H), 6.48 (dd, J ¼ 8.4, 2.5 Hz, 1H), 7.06 (s, 1H), 6.05 (s, 2H), 2.58 (s, 3H); 13C NMR (101 MHz,
1H), 3.86 (s, 2H), 2.57 (s, 3H); 13C NMR (101 MHz, CDCl3) d CDCl3) d 199.5, 150.3, 148.2, 136.6, 120.6, 109.1, 102.3, 81.3,
202.4, 146.6, 145.0, 141.0, 118.6, 114.7, 75.3, 29.5; IR (KBr): 29.2; IR (KBr): 2992, 2906, 1690, 1607, 1482, 1375, 1239, 1128,
ꢀ
3541, 2955, 1631, 1528, 1484, 1242, 1125, 1010, 754, 536 cmꢁ1
HRMS (EI) calcd for [M]+: C8H8INO 260.9645, found 260.9646.
.
1034, 930, 863, 754 cmꢁ1; HRMS (EI) calcd for [M]+: C9H7IO3
289.9434, found 289.9435.
1-(4-Iodo-[1,10-biphenyl]-3-yl)ethanone (1m). Yellow solid;
61% yield; mp 87–89 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.96 (d, J ¼
8.2 Hz, 1H), 7.62 (d, J ¼ 2.1 Hz, 1H), 7.57–7.52 (m, 2H), 7.45 (t, J
¼ 7.4 Hz, 2H), 7.38 (t, J ¼ 7.2 Hz, 1H), 7.32 (dd, J ¼ 8.2, 2.0 Hz,
Procedure B: general procedure for the preparation of 1g and
1t
A solution of 1-(5-amino-2-iodophenyl)ethanone (1f) or 1-(4- 1H), 2.65 (s, 3H); 13C NMR (101 MHz, CDCl3) d 201.9, 144.7,
amino-2-iodophenyl)ethanone (1s) (3.7 mmol) in dichloro- 141.4, 141.2, 139.1, 130.4, 129.1, 128.2, 126.9, 126.9, 89.5, 29.6;
methane (15 mL) at room temperature was treated with trieth- IR (KBr): 3120, 2920, 2767, 1692, 1452, 1355, 1224, 1010, 755,
ylamine (4 mmol) and acetyl chloride (4.5 mmol). The reaction 690 cmꢁ1; HRMS (EI) calcd for [M]+: C14H11IO 321.9849, found
mixture was stirred at room temperature for 3 h. The reaction 321.9848.
mixture was diluted with EtOAc and washed with water. The
1-(2-Iodo-5-(thiophen-3-yl)phenyl)ethanone (1n). Yellow
aqueous layer was extracted with ethyl acetate. The combined solid; 57% yield; mp 67–68 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.92
extracts were washed with brine, dried over MgSO4, and (d, J ¼ 8.2 Hz, 1H), 7.62 (d, J ¼ 1.9 Hz, 1H), 7.49 (d, J ¼ 1.4 Hz,
concentrated to provide the desired product 1g or 1t aer 1H), 7.42 (dd, J ¼ 4.7, 3.1 Hz, 1H), 7.33 (dd, J ¼ 12.1, 3.7 Hz, 2H),
purication via ash column chromatography.
2.65 (s, 3H); 13C NMR (101 MHz, CDCl3) d 202.0, 144.9, 141.1,
N-(3-Acetyl-4-iodophenyl)acetamide (1g). Yellow solid; 82% 140.2, 136.0, 129.5, 127.0, 126.1, 125.9, 121.4, 88.7, 29.6; IR
yield; mp 223–225 ꢀC; 1H NMR (400 MHz, CDCl3) d 8.11 (d, J ¼ (KBr): 3463, 2922, 2889, 1701, 1625, 1458, 1352, 1256, 1014, 780,
18.9 Hz, 1H), 7.84–7.76 (m, 2H), 7.27 (d, J ¼ 9.2 Hz, 1H), 2.60 (s, 691 cmꢁ1; HRMS (EI) calcd for [M]+: C12H9IOS 327.9413, found
3H), 2.18 (s, 3H); 13C NMR (101 MHz, CDCl3) d 202.6, 169.6, 327.9412.
144.2, 140.9, 138.7, 123.2, 119.7, 83.4, 29.6, 24.4; IR (KBr): 3601,
1-(5-(Furan-2-yl)-2-iodophenyl)ethanone (1o). Yellow solid;
2999, 1718, 1588, 1268, 1115, 1024, 755, 561 cmꢁ1; HRMS (EI) 52% yield; mp 94–96 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.90 (d, J ¼
calcd for [M + Na]+: C10H10INO2Na 325.9648, found 325.9655.
8.3 Hz, 1H), 7.72 (d, J ¼ 2.0 Hz, 1H), 7.48 (d, J ¼ 8.2 Hz, 1H), 7.37
1-(5-Chloro-2-iodophenyl)ethanone (1h). Yellow oil; 40% (dd, J ¼ 8.3, 2.0 Hz, 1H), 6.71 (d, J ¼ 3.3 Hz, 1H), 6.49 (dd, J ¼ 3.3,
yield; 1H NMR (400 MHz, CDCl3) d 7.83 (d, J ¼ 8.4 Hz, 1H), 7.41 1.7 Hz, 1H), 2.65 (s, 3H); 13C NMR (101 MHz, CDCl3) d 201.7,
(d, J ¼ 2.4 Hz, 1H), 7.11 (dd, J ¼ 8.4, 2.4 Hz, 1H), 2.60 (s, 3H); 13
C
151.9, 144.5, 142.9, 141.1, 130.9, 126.6, 123.3, 112.0, 106.6, 88.7,
NMR (101 MHz, CDCl3) d 200.3, 145.4, 141.9, 134.7, 131.8, 128.3, 29.5; IR (KBr): 3119, 2922, 2855, 1766, 1695, 1555, 1356, 1293,
88.0, 29.4; IR (KBr): 3618, 2936, 1700, 1548, 1447, 1270, 1229, 1090, 961, 820 cmꢁ1; HRMS (EI) calcd for [M]+: C12H9IO2
1011, 814, 754, 670 cmꢁ1. HRMS (EI) calcd for [M]+: C8H6IClO 311.9642, found 311.9644.
279.9146, found 279.9147.
1-(2-Iodo-5-(phenylethynyl)phenyl)ethanone (1p). Yellow
1-(5-Bromo-2-iodophenyl)ethanone (1i). Yellow oil; 53% solid; 63% yield; mp 82–84 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.78
yield; 1H NMR (400 MHz, CDCl3) d 7.77 (d, J ¼ 8.4 Hz, 1H), 7.55 (d, J ¼ 8.2 Hz, 1H), 7.48 (d, J ¼ 2.0 Hz, 1H), 7.46–7.39 (m, 2H),
(d, J ¼ 2.3 Hz, 1H), 7.25 (dd, J ¼ 8.4, 2.4 Hz, 1H), 2.60 (s, 3H); 13
C
7.27–7.20 (m, 3H), 7.11 (dd, J ¼ 8.2, 2.0 Hz, 1H), 2.50 (s, 3H); 13
C
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23595–23603 | 23599

View Article Online
RSC Advances
Paper
NMR (101 MHz, CDCl3) d 200.8, 143.9, 141.0, 134.3, 131.7, 131.1,
128.8, 128.5, 123.6, 122.5, 91.8, 90.7, 87.6, 29.4; IR (KBr): 3120,
2957, 2764, 1695, 1447, 1356, 1131, 1009, 754, 685 cmꢁ1; HRMS
(EI) calcd for [M]+: C16H11IO 345.9849, found 345.9850.
7-Methyl-5H-dibenzo[a,c][7]annulen-5-one (2a). Yellow oil;
80% yield; 1H NMR (400 MHz, CDCl3) d 7.71 (dd, J ¼ 6.7, 5.0 Hz,
2H), 7.69–7.61 (m, 2H), 7.55 (t, J ¼ 7.6 Hz, 1H), 7.49–7.33 (m,
3H), 6.53 (s, 1H), 2.36 (s, 3H). 13C NMR (101 MHz, CDCl3) d
194.0, 144.8, 142.0, 137.5, 137.3, 135.7, 133.2, 131.9, 131.2,
130.0, 128.6, 128.1, 127.8, 127.3, 127.1, 24.4; IR (KBr): 3067,
2983, 2890, 1724, 1636, 1595, 1445, 1222, 1147, 1104, 989, 881,
750 cmꢁ1. HRMS (EI) calcd for [M]+: C16H12O 220.0883, found
220.0883.
1-(4-Amino-2-iodophenyl)ethanone (1s). 3-Iodo-phenylamine
(6.4 mmol), AlCl3 (1.07 g, 8.0 mmol), and anhydrous CS2 (15 mL)
were added to a 50 mL ask under argon atmosphere. To the
mixture was dropwise added a solution of acetyl chloride (0.628 g,
8.05 mmol) in anhydrous CS2 (2.5 mL) at 0 ꢀC. The resulting
mixture was allowed to warm to room temperature and stirred for
1 h. Then the mixture was heated to reux for 12 h. Aer being
cooled to room temperature, the resulting mixture was poured
out to ice water and extracted with CH2Cl2 (3 ꢂ 30 mL). The
organic layer was washed with saturated aqueous Na2CO3 (20
mL) and brine (20 mL) and then dried over Na2SO4. Aer evap-
oration of the solvent under vacuum, the residue was puried by
column chromatography on silica gel to give the desired
compounds 1s. Yellow solid; 32% yield; mp 143–145 ꢀC; 1H NMR
(400 MHz, CDCl3) d 7.53 (d, J ¼ 8.0 Hz, 1H), 7.29 (s, 1H), 6.64–6.61
(m, 1H), 4.07 (br, 2H), 2.56 (s, 3H); 13C NMR (101 MHz, CDCl3) d
197.6, 150.2, 132.1, 130.0, 127.5, 113.2, 94.2, 28.3; IR (KBr): 3700,
2917, 2849, 1674, 1581, 1370, 1264, 754, 538 cmꢁ1; HRMS (EI)
calcd for [M]+: C8H8INO 260.9645, found 260.9646.
3,7,9-Trimethyl-5H-dibenzo[a,c][7]annulen-5-one
(2b).
1
Yellow oil; 72% yield; H NMR (400 MHz, CDCl3) d 7.70 (d, J ¼
8.1 Hz, 1H), 7.67–7.61 (m, 2H), 7.52 (s, 1H), 7.43 (d, J ¼ 8.1 Hz,
1H), 7.29 (d, J ¼ 8.1 Hz, 1H), 6.61 (s, 1H), 2.46 (s, 6H), 2.44 (s,
3H). 13C NMR (101 MHz, CDCl3) d 193.0, 143.8, 140.4, 136.9,
136.2, 134.2, 133.8, 133.8, 131.9, 131.1, 130.5, 128.8, 128.5,
126.4, 126.4, 23.5, 20.2, 19.8; IR (KBr): 3635, 2997, 2951, 1731,
1643, 1445, 1268, 1191, 1150, 986, 840, 752 cmꢁ1. HRMS (EI)
calcd for [M + H]+: C18H17O 249.1273, found 249.1274.
3,9-Dimethoxy-7-methyl-5H-dibenzo[a,c][7]annulen-5-one
(2c). Yellow oil; 80% yield; 1H NMR (400 MHz, CDCl3) d 7.68 (dd,
J ¼ 10.9, 8.9 Hz, 2H), 7.30 (d, J ¼ 2.8 Hz, 1H), 7.23–7.16 (m, 2H),
7.04 (dd, J ¼ 8.8, 2.7 Hz, 1H), 6.62 (s, 1H), 3.90 (d, J ¼ 2.5 Hz,
6H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3) d 193.5, 159.0,
158.4, 144.7, 142.3, 136.3, 132.9, 132.8, 131.2, 130.5, 130.4,
119.4, 114.5, 112.2, 109.8, 55.5, 55.4, 24.6; IR (KBr): 3547, 3002,
2839, 1702, 1602, 1483, 1271, 1001, 755 cmꢁ1. HRMS (EI) calcd
for [M + H]+: C18H17O3 281.1172, found 281.1172.
N-(4-Acetyl-3-iodophenyl)acetamide (1t). A solution of 1-(4-
amino-2-iodophenyl)ethanone (1s) (3.7 mmol) in dichloro-
methane (15 mL) at room temperature was treated with triethyl-
amine (4 mmol) and acetyl chloride (4.5 mmol). The reaction
mixture was stirred at room temperature for 3 h. The reaction
mixture was diluted with EtOAc and washed with water. The
aqueous layer was extracted with ethyl acetate. The combined
extracts were rinsed with brine, dried over MgSO4, and
concentrated to provide the desired product 1t aer purication
via ash column chromatography. Yellow solid; 76% yield; mp
3,9-Diamino-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2d).
Yellow solid; 64% yield; mp 155–156 ꢀC; 1H NMR (400 MHz,
CDCl3) d 7.50 (d, J ¼ 8.5 Hz, 1H), 7.45 (d, J ¼ 8.5 Hz, 1H), 7.00 (d, J
¼ 2.2 Hz, 1H), 6.88 (d, J ¼ 1.9 Hz, 1H), 6.85 (dd, J ¼ 8.5, 2.2 Hz,
1H), 6.75–6.71 (m, 1H), 6.49 (s, 1H), 3.79 (s, 4H), 2.31 (s, 3H). 13
C
NMR (101 MHz, CDCl3) d 193.9, 145.7, 145.0, 144.8, 141.8, 135.9,
132.4, 132.3, 130.8, 128.9, 118.7, 116.2, 112.5, 112.0, 24.7; IR
1
ꢀ
168–170 C; H NMR (400 MHz, CDCl3) d 8.88 (s, 1H), 8.04 (s,
1H), 7.65 (d, J ¼ 8.0 Hz, 1H), 7.44 (d, J ¼ 8.0 Hz, 1H), 2.51 (s, 3H),
2.13 (s, 3H). 13C NMR (101 MHz, CDCl3) d 200.35, 169.7, 141.5,
137.2, 131.9, 130.1, 118.9, 92.0, 29.1, 24.6; IR (KBr): 3652, 2934,
1719, 1584, 1356, 1238, 1013, 754, 542 cmꢁ1. HRMS (EI) calcd
for [M + H]+: C10H11INO2 302.3053, found 302.3077.
(KBr): 3781, 3662, 3005, 2919, 1666, 1485, 1267, 1018, 754 cmꢁ1
.
HRMS (EI) calcd for [M + H]+: C16H15N2O 251.1178, found
251.1179.
N,N0-(7-Methyl-5-oxo-5H-dibenzo[a,c][7]annulene-3,9-diyl)-
1
ꢀ
diacetamide (2e). Yellow solid; 72% yield; mp 129–131 C; H
NMR (400 MHz, DMSO) d 10.26 (d, J ¼ 19.1 Hz, 2H), 8.04 (s, 1H),
7.94 (d, J ¼ 10.4 Hz, 2H), 7.84 (d, J ¼ 7.0 Hz, 2H), 7.77 (d, J ¼ 8.7
Hz, 1H), 6.65 (s, 1H), 2.40 (s, 3H), 2.11 (s, 6H). 13C NMR (101
MHz, DMSO) d 192.6, 168.7, 144.5, 141.2, 139.0, 138.7, 135.0,
132.4, 131.9, 131.2, 130.5, 122.1, 119.6, 116.9, 116.0, 24.0, 24.0,
23.9; IR (KBr): 3700, 3462, 3008, 2922, 1662, 1268, 1022, 999,
825, 755 cmꢁ1. HRMS (EI) calcd for [M + Na]+: C20H19N2O3Na
357.1209, found 357.1204.
1-(2-Iodo-4,5-dimethylphenyl)ethanone (1u). Yellow oil; 60%
yield; 1H NMR (400 MHz, CDCl3) d 7.72 (s, 1H), 7.28 (s, 1H), 2.60
(s, 3H), 2.24 (s, 6H); 13C NMR (101 MHz, CDCl3) d 201.0, 141.8,
141.7, 140.8, 136.8, 130.2, 87.8, 29.2, 19.3, 19.2; IR (KBr): 3662,
3006, 2919, 2849, 1690, 1590, 1354, 1267, 754, 537 cmꢁ1; HRMS
(EI) calcd for [M]+: C10H11IO 273.9849, found 273.9850.
General procedure for the Pd-catalyzed tandem
homocoupling–aldol–dehydration of ortho-acylphenyl iodides
3,9-Dichloro-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2f).
Yellow solid; 35% yield; mp 141–142 ꢀC; 1H NMR (400 MHz,
CDCl3) d 7.76 (d, J ¼ 2.2 Hz, 1H), 7.70 (dd, J ¼ 5.3, 3.2 Hz, 2H),
7.65 (d, J ¼ 8.6 Hz, 1H), 7.60 (dd, J ¼ 8.5, 2.3 Hz, 1H), 7.46 (dd, J
¼ 8.6, 2.1 Hz, 1H), 6.63 (s, 1H), 2.44 (s, 3H). 13C NMR (101 MHz,
CDCl3) d 191.0, 143.10, 141.7, 136.0, 134.0, 133.9, 133.7, 133.3,
132.7, 132.0, 130.4, 130.2, 127.8, 126.2, 23.3; IR (KBr): 3680,
2921, 2854, 1730, 1647, 1460, 1260, 1091, 1023, 804 cmꢁ1. HRMS
(EI) calcd for [M + H]+: C16H11Cl2O 289.0181, found 289.0181.
To the solution of ortho-acylphenyl iodides 1 (0.2 mmol) in DMF
(1.0 mL) were added PdCl2 (5 mol%), K2CO3 (1.5 equiv.) and
DPPP (10 mol%) in a sealed tube under Ar atmosphere. The
reaction mixture was stirred at 150 ꢀC for 3 h, then cooled down
to room temperature and ltered, and the corresponding ltrate
was concentrated under vacuum and further puried by ash
column chromatography on silica gel to furnish the target
products 2.
23600 | RSC Adv., 2014, 4, 23595–23603
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
1
126.3, 123.9, 122.4, 122.2, 111.9, 111.9, 106.5, 106.2, 24.6. IR
1-Phenanthren-3-yl-ethanone (2g). Yellow oil; 35% yield; H
NMR (400 MHz, CDCl3) d 8.11 (s, 1H), 7.86 (d, J ¼ 7.7 Hz, 1H),
7.72 (d, J ¼ 7.7 Hz, 1H), 7.55 (d, J ¼ 7.3 Hz, 2H), 7.47 (t, J ¼ 7.7
Hz, 1H), 7.40 (t, J ¼ 7.5 Hz, 2H), 7.31 (t, J ¼ 7.3 Hz, 1H), 2.59 (s,
3H). 13C NMR (101 MHz, CDCl3) d 197.1, 140.7, 139.1, 136.6,
130.7, 128.0, 127.9, 126.8, 126.1, 126.1, 125.9, 25.7; IR (KBr):
3009, 2947, 2852, 1680, 1622, 1501, 1324, 1233, 1009, 870, 765
cmꢁ1. MS (EI, 70 eV): m/z¼ 220.09 [M]+.
(KBr): 3546, 3402, 2922, 1642, 1428, 1359, 1054, 742 cmꢁ1
.
HRMS (EI) calcd for [M + Na]+: C24H16O3Na 375.0991, found
375.1001.
7-Methyl-3,9-bis(phenylethynyl)-5H-dibenzo[a,c][7]annulen-
1
5-one (2n). Yellow solid; 48% yield; mp 174–175 ꢀC; H NMR
(400 MHz, CDCl3) d 7.96 (d, J ¼ 1.2 Hz, 1H), 7.89 (d, J ¼ 1.4 Hz,
1H), 7.78 (dd, J ¼ 8.7, 4.9 Hz, 2H), 7.74 (d, J ¼ 8.2 Hz, 1H), 7.63
(dd, J ¼ 8.3, 1.5 Hz, 1H), 7.57 (ddd, J ¼ 9.2, 6.6, 3.0 Hz, 4H), 7.42–
7.34 (m, 6H), 6.65 (d, J ¼ 0.7 Hz, 1H), 2.48 (s, 3H). 13C NMR (101
MHz, CDCl3) d 192.9, 144.4, 141.8, 136.6, 136.3, 135.9, 133.8,
133.5, 131.8, 131.7, 131.7, 131.4, 130.6, 130.5, 130.0, 128.7,
128.6, 128.4, 128.4, 123.8, 123.3, 122.8, 122.8, 91.8, 91.2, 88.5,
88.2, 24.5. IR (KBr): 3480, 3120, 2922, 2780, 1750, 1690, 1510,
1440, 1358, 1120, 864, 687 cmꢁ1. HRMS (EI) calcd for [M]+:
Diethyl-7-methyl-5-oxo-5H
dibenzo[a,c][7]annulene-3,9-
1
ꢀ
dicarboxylate (2i). Yellow solid; 46% yield; mp 122–124 C; H
NMR (400 MHz, CDCl3) d 8.44 (d, J ¼ 1.6 Hz, 2H), 8.30 (dd, J ¼
8.3, 1.9 Hz, 1H), 8.13 (dd, J ¼ 8.3, 1.7 Hz, 1H), 7.89 (d, J ¼ 8.3 Hz,
1H), 7.84 (d, J ¼ 8.3 Hz, 1H), 6.66 (d, J ¼ 1.0 Hz, 1H), 4.45 (dd, J ¼
14.1, 7.0 Hz, 4H), 2.52 (d, J ¼ 1.0 Hz, 3H), 1.44 (td, J ¼ 7.1, 6.0 Hz,
6H). 13C NMR (101 MHz, CDCl3) d 192.8, 165.7, 165.5, 144.6,
142.2, 140.4, 140.1, 136.1, 133.7, 132.2, 131.8, 130.8, 130.4,
129.1, 128.9, 128.7, 61.5, 24.4, 14.3; IR (KBr): 3462, 2923, 2855,
1718, 1650, 1285, 1252, 1196, 1115, 754, 685 cmꢁ1. HRMS (EI)
calcd for [M + Na]+: C22H20O5Na 387.1202, found 387.1219.
2,3,9,10-Bis(di-1,3-benzodioxol)-7-methyl-5H-dibenzo[a,c][7]-
annulen-5-one (2j). Yellow solid; 62% yield; mp 222–224 ꢀC; 1H
NMR (400 MHz, CDCl3) d 7.26 (d, J ¼ 3.8 Hz, 1H), 7.14 (d, J ¼ 5.4
Hz, 3H), 6.54 (s, 1H), 6.06 (d, J ¼ 7.2 Hz, 4H), 2.38 (s, 3H). 13C
NMR (101 MHz, CDCl3) d 191.8, 150.5, 148.0, 147.9, 147.2, 143.6,
137.0, 133.7, 132.7, 131.6, 130.3, 110.9, 109.2, 106.8, 106.4,
102.0, 101.8, 24.9; IR (KBr): 3838, 3581, 3008, 2923, 1668, 1591,
1482, 1267, 1037, 754, 537 cmꢁ1. HRMS (EI) calcd for [M]+:
C
32H20O 420.1509, found 420.1509.
2,7,10-Trimethyl-5H-dibenzo[a,c][7]annulen-5-one (2o).
1
Yellow oil; 74% yield; H NMR (400 MHz, CDCl3) d 7.74 (d, J ¼
7.9 Hz, 1H), 7.64 (d, J ¼ 8.0 Hz, 2H), 7.59 (s, 1H), 7.37 (d, J ¼ 7.9
Hz, 1H), 7.31 (d, J ¼ 8.1 Hz, 1H), 6.60 (s, 1H), 2.53 (s, 3H), 2.49 (s,
3H), 2.45 (s, 3H). 13C NMR (101 MHz, CDCl3) d 193.6, 144.7,
141.5, 139.7, 138.5, 137.5, 137.4, 133.2, 132.7, 132.3, 130.5,
129.1, 128.6, 127.6, 127.1, 24.5, 21.6, 21.3; IR (KBr): 3441, 2921,
2855, 1644, 1577, 1445, 1358, 1301, 1035, 823, 743 cmꢁ1. HRMS
(EI) calcd for [M + Na]+: C18H16ONa 271.1093, found 271.1093.
2,10-Dimethoxy-7-methyl-5H-dibenzo[a,c][7]annulen-5-one
(2p). Yellow oil; 75% yield; 1H NMR (400 MHz, CDCl3) d 7.73 (d, J
¼ 8.7 Hz, 1H), 7.58 (d, J ¼ 8.9 Hz, 1H), 7.17 (s, 2H), 6.99 (d, J ¼
8.7 Hz, 1H), 6.94 (dd, J ¼ 8.8, 2.0 Hz, 1H), 6.44 (s, 1H), 3.83 (s,
3H), 3.81 (s, 3H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3) d
192.4, 161.7, 159.2, 144.1, 139.3, 139.2, 135.5, 131.9, 130.1,
129.0, 116.8, 114.9, 114.2, 113.7, 55.5, 55.4, 24.6; IR (KBr): 3454,
2936, 2854, 1637, 1594, 1454, 1359, 1298, 1237, 1028, 857, 820
cmꢁ1. HRMS (EI) calcd for [M + H]+: C18H17O3 281.1172, found
281.1174.
C
18H12O5 308.0679, found 308.0680.
7-Methyl-3,9-diphenyl-5H-dibenzo[a,c][7]annulen-5-one (2k).
Yellow solid; 66% yield; mp 164–166 ꢀC; 1H NMR (400 MHz,
CDCl3) d 8.07 (s, 1H), 7.98–7.82 (m, 4H), 7.69 (d, J ¼ 8.1 Hz, 3H),
7.65 (d, J ¼ 7.5 Hz, 2H), 7.47 (dd, J ¼ 15.5, 7.7 Hz, 4H), 7.38 (dt, J ¼
12.3, 6.3 Hz, 2H), 6.68 (s, 1H), 2.51 (s, 3H). 13C NMR (101 MHz,
CDCl3) d 193.8, 144.9, 142.2, 140.9, 140.7, 140.1, 139.4, 136.1,
136.1, 136.0, 133.4, 132.3, 130.6, 129.8, 129.0, 129.0, 127.9, 127.9,
127.4, 127.2, 127.1, 125.9, 125.8, 24.6. IR (KBr): 3638, 3005, 2919,
2848, 1722, 1665, 1455, 1268, 754, 696 cmꢁ1. HRMS (EI) calcd for
[M]+: C28H20O 372.1509, found 372.1507.
2,10-Diamino-7-methyl-5H-dibenzo[a,c][7]annulen-5-one (2q).
Yellow solid; 72% yield; mp 202–204 ꢀC; 1H NMR (400 MHz,
DMSO) d 7.47 (dd, J ¼ 10.0, 8.6 Hz, 2H), 6.95 (d, J ¼ 2.3 Hz, 1H),
6.89 (d, J ¼ 2.0 Hz, 1H), 6.73 (ddd, J ¼ 8.4, 4.3, 2.3 Hz, 2H), 6.25 (s,
1H), 5.87 (s, 4H), 2.30 (s, 3H). 13C NMR (101 MHz, DMSO) d 190.0,
151.7, 149.1, 143.5, 139.6, 139.2, 130.3, 129.5, 128.7, 123.8, 115.4,
113.9, 113.6, 113.2, 24.3; IR (KBr): 3781, 3636, 2922, 1665, 1590,
1315, 1117, 995, 754 cmꢁ1. HRMS (EI) calcd for [M + H]+:
C16H15N2O 251.1178, found 251.1178.
7-Methyl-3,9-di(thiophen-3-yl)-5H dibenzo[a,c][7]annulen-5-
one (2l). Yellow solid; 80% yield; mp 226–227 ꢀC; 1H NMR (400
MHz, CDCl3) d 7.94 (s, 1H), 7.82 (s, 1H), 7.76–7.70 (m, 2H), 7.67
(d, J ¼ 8.2 Hz, 1H), 7.56 (d, J ¼ 8.3 Hz, 1H), 7.49 (d, J ¼ 1.1 Hz,
1H), 7.43 (s, 1H), 7.38 (d, J ¼ 4.9 Hz, 1H), 7.32 (dd, J ¼ 9.0, 5.9
Hz, 3H), 6.57 (s, 1H), 2.39 (s, 3H). 13C NMR (101 MHz, CDCl3) d
193.7, 144.8, 142.1, 141.2, 140.7, 136.0, 135.9, 135.8, 135.6,
135.3, 133.3, 132.2, 130.5, 129.1, 126.7, 126.7, 126.6, 126.2,
126.1, 125.0, 124.9, 121.3, 121.2, 24.6. IR (KBr): 3464, 2901,
2778, 1640, 1425, 1358, 1147, 1036, 780, 664 cmꢁ1. HRMS (EI)
calcd for [M + H]+: C24H17OS2 385.0715, found 385.0740.
3,9-Di(furan-2-yl)-7-methyl-5H dibenzo[a,c][7]annulen-5-one
(2m). Yellow solid; 61% yield; mp 188–189 ꢀC; 1H NMR (400
MHz, CDCl3) d 8.11 (s, 1H), 8.04 (s, 1H), 7.93 (d, J ¼ 8.3 Hz, 1H),
7.83 (d, J ¼ 8.3 Hz, 1H), 7.76 (q, J ¼ 8.6 Hz, 2H), 7.55 (s, 2H), 6.80
(d, J ¼ 15.9 Hz, 2H), 6.68 (s, 1H), 6.54 (s, 2H), 2.53 (s, 3H). 13C
NMR (101 MHz, CDCl3) d 193.5, 152.9, 152.7, 144.9, 142.8, 142.7,
142.0, 136.0, 136.0, 135.8, 133.2, 132.0, 130.7, 130.3, 130.2,
N,N0-(7-Methyl-5-oxo-5H-dibenzo[a,c][7]annulene-2,10-diyl)
1
ꢀ
diacetamide (2r). Yellow solid; 68% yield; mp 132–134 C; H
NMR (400 MHz, DMSO) d 10.42 (s, 1H), 10.32 (s, 1H), 8.15 (s,
1H), 8.07 (s, 1H), 7.89–7.73 (m, 3H), 7.65 (d, J ¼ 8.5 Hz, 1H), 6.53
(s, 1H), 2.40 (s, 3H), 2.12 (d, J ¼ 9.2 Hz, 6H). 13C NMR (101 MHz,
DMSO) d 191.4, 169.0, 168.8, 144.3, 142.1, 139.6, 137.6, 137.4,
136.5, 131.8, 130.1, 128.4, 128.2, 120.9, 119.1, 118.8, 118.7, 24.1,
24.0, 23.9; IR (KBr): 3636, 2923, 1722, 1667, 1489, 1324, 1268,
1021, 755, 537 cmꢁ1. HRMS (EI) calcd for [M + Na]+:
C
20H18N2O3Na 357.1209, found 357.1215.
2,3,7,9,10-Pentamethyl-5H-dibenzo[a,c][7]annulen-5-one (2s).
Yellow oil; 78% yield; 1H NMR (400 MHz, CDCl3) d 7.58 (d, J ¼ 7.1
Hz, 2H), 7.54 (s, 1H), 7.47 (s, 1H), 6.57 (d, J ¼ 0.9 Hz, 1H), 2.42
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23595–23603 | 23601

View Article Online
RSC Advances
Paper
(d, J ¼ 1.0 Hz, 3H), 2.41 (s, 3H), 2.38 (s, 3H), 2.36 (d, J ¼ 2.3 Hz, CDCl3) d 7.66 (dd, J ¼ 6.2, 1.9 Hz, 2H), 7.59 (td, J ¼ 7.7, 1.3 Hz,
6H). 13C NMR (101 MHz, CDCl3) d 193.6, 144.7, 140.4, 139.5, 1H), 7.46–7.32 (m, 5H), 3.17 (q, J ¼ 19.1 Hz, 2H), 2.80 (s, 1H),
137.4, 136.8, 136.1, 135.3, 135.1, 133.3, 132.6, 132.6, 130.9, 128.3, 1.54 (s, 3H); 13C NMR (101 MHz, CDCl3) d 202.6, 143.9, 140.2,
128.1, 24.6, 20.0, 19.7, 19.6, 19.2; IR (KBr): 3436, 2920, 2854, 1640, 137.7, 136.4, 132.9, 131.8, 129.7, 128.5, 128.3, 128.3, 127.8, 71.0,
1587, 1452, 1360, 1054, 742 cmꢁ1. HRMS (EI) calcd for [M + Na]+: 61.2, 28.2; HRMS (EI) calcd for [M]+: C16H14O2 238.0988, found
C20H20ONa 299.1406, found 299.1423.
238.0989; IR (KBr): 3686, 2975, 2865, 1722, 1669, 1543, 1458,
7-Ethyl-6-methyl-5H-dibenzo[a,c][7]annulen-5-one
(2t). 1269, 1052, 754 cmꢁ1
.
1
Yellow oil; 34% yield; H NMR (400 MHz, CDCl3) d 7.76 (d, J ¼
7.9 Hz, 1H), 7.68–7.65 (m, 1H), 7.64–7.57 (m, 2H), 7.53–7.45 (m,
2H), 7.39 (ddt, J ¼ 14.9, 7.3, 3.7 Hz, 2H), 2.76 (q, J ¼ 7.5 Hz, 2H),
Acknowledgements
2.18 (s, 3H), 1.08 (t, J ¼ 7.5 Hz, 3H). 13C NMR (101 MHz, CDCl3) d We thank the NSFC (no. 21372085) for nancial support.
201.3, 143.5, 142.2, 138.5, 136.9, 136.8, 136.7, 130.9, 130.7,
128.3, 127.7, 127.5, 127.3, 127.0, 125.8, 27.0, 17.3, 13.1; IR (KBr):
Notes and references
3439, 2919, 2852, 1649, 1457, 1359, 1054, 987, 741 cmꢁ1. HRMS
(EI) calcd for [M + Na]+: C18H16ONa 271.1093, found 271.1103.
1 Selected examples: (a) X. Zhan, S. Wang, Y. Liu, X. Wu and
D. Zhu, Chem. Mater., 2003, 15, 1963–1969; (b)
S. Lightowler and M. Hird, Chem. Mater., 2005, 17, 5538–
5549; (c) M. Kertesz, C. H. Choi and S. Yang, Chem. Rev.,
2005, 105, 3448–3481.
7-Benzyl-6-phenyl-5H-dibenzo[a,c][7]annulen-5-one
(2u).
Yellow solid; 40% yield; mp 75–77 ꢀC; 1H NMR (400 MHz,
CDCl3) d 7.69 (d, J ¼ 7.8 Hz, 1H), 7.64 (dt, J ¼ 8.7, 3.8 Hz, 1H),
7.60–7.51 (m, 2H), 7.44 (dd, J ¼ 13.7, 5.4 Hz, 1H), 7.37 (dd, J ¼
7.6, 1.2 Hz, 1H), 7.29–7.19 (m, 7H), 7.02–6.91 (m, 3H), 6.76 (d, J
¼ 6.9 Hz, 2H), 3.96 (s, 2H). 13C NMR (101 MHz, CDCl3) d 199.1,
145.9, 144.8, 139.3, 138.6, 137.6, 137.5, 136.5, 135.5, 131.1,
130.9, 129.1, 128.5, 128.4, 128.2, 128.0, 128.0, 127.7, 127.7,
127.5, 125.8, 125.2, 39.1. IR (KBr): 3572, 2441, 2922, 2853, 1644,
1434, 1359, 1067, 737, 696 cmꢁ1. HRMS (EI) calcd for [M + Na]+:
2 X. Mei and C. Wolf, J. Am. Chem. Soc., 2006, 128, 13326–
13327.
3 (a) G. Bringmann, C. Gunther, M. Ochse, O. Schupp and
S. Tasler, in Progress in the Chemistry of Organic Natural
Products, ed. W. Herz, H. Falk, G. W. Kirby and R. E.
Moore, Sprong, New York, 2001, vol. 82, pp. 1–293; (b)
O. Baudoin and F. Gueritte, Stud. Nat. Prod. Chem., 2003,
29, 355–417.
C
28H20ONa 395.1465, found 395.1438.
4 F. Ullmann, Justus Liebigs Ann. Chem., 1904, 332, 38–81.
5 Selected examples: (a) B. J. Gallon, R. W. Kojima, R. B. Kaner
and D. L. Diaconescu, Angew. Chem., Int. Ed., 2007, 46, 7251–
7254; (b) B. Yuan, Y. Pan, Y. Li, B. Yin and H. Jiang, Angew.
Chem., Int. Ed., 2010, 49, 4054–4058; (c) G. Cahiez,
A. Moyeux, J. Buendia and C. Duplais, J. Am. Chem. Soc.,
2007, 129, 13788–13789; (d) Y. Wan, H. Wang, Q. Zhao,
M. Klingstedt, O. Terasaki and D. Zhao, J. Am. Chem. Soc.,
2009, 131, 4541–4550; (e) R. N. Dhital, C. Kamonsatikul,
E. Somsook, K. Bobuatong, M. Ehara, S. Karanjit and
H. Sakurai, J. Am. Chem. Soc., 2012, 134, 20250–20253; (f)
A. Monopoli, V. Calo, F. Ciminale, P. Cotugno, C. Angelici,
N. Cioffi and A. Nacci, J. Org. Chem., 2010, 75, 3908–3911;
(g) L. Wang and W. Lu, Org. Lett., 2009, 11, 1079–1082.
6 (a) K. Pericherla, A. Jha, B. Khungar and A. Kumar, Org. Lett.,
2013, 15, 4304–4307; (b) Q. Cai, J. Yan and K. Ding, Org. Lett.,
2012, 14, 3332–3335; (c) J. Yan, F. Zhou, D. Qin, T. Cai,
K. Ding and Q. Cai, Org. Lett., 2012, 14, 1262–1265; (d)
L. Mahendar, J. Krishna, A. G. K. Reddy, B. V. Ramulu and
G. Satyanarayana, Org. Lett., 2012, 14, 628–631; (e)
M. Nagamochi, Y. Q. Fang and M. Lautens, Org. Lett., 2007,
9, 2955–2958; (f) N. Aljaar, C. C. Malakar, J. Conrad,
S. Strobel, T. Schleid and U. Beifuss, J. Org. Chem., 2012,
77, 7793–7803; (g) Z. Y. Ge, X. D. Fei, T. Tang, Y. M. Zhu
and J. K. Shen, J. Org. Chem., 2012, 77, 5736–5743; (h)
L. Cio, A. Trabocchi, C. Lalli, G. Menchi and A. Guarna,
Org. Biomol. Chem., 2012, 10, 2780–2786.
Mechanistic studies about this transformation
4-(2-Acetylphenyl)-7-methyl-5H-dibenzo[a,c][7]annulen-5-
one (3a). To the solution of ortho-acylphenyl bromide 1 (0.2
mmol) in DMF (1.0 mL) were added PdCl2 (5 mol%), K2CO3 (1.5
equiv.) and DPPP (10 mol%) in a sealed tube under Ar atmo-
sphere. The reaction mixture was stirred at 150 ꢀC for 3 h, then
cooled down to room temperature and ltered, and the corre-
sponding ltrate was concentrated under vacuum and further
puried by ash column chromatography on silica gel to
furnish the target products 3a. Yellow solid; 39% yield; mp 125–
126 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.73–7.63 (m, 3H), 7.58 (dd,
J ¼ 5.9, 3.4 Hz, 1H), 7.49 (t, J ¼ 7.8 Hz, 1H), 7.39 (ddd, J ¼ 9.3,
4.2, 1.6 Hz, 3H), 7.37–7.32 (m, 1H), 7.21 (dd, J ¼ 7.5, 0.9 Hz, 1H),
7.15–7.13 (m, 1H), 6.30 (d, J ¼ 1.0 Hz, 1H), 2.29 (d, J ¼ 1.0 Hz,
3H), 2.19 (s, 3H); 13C NMR (101 MHz, CDCl3) d 202.1, 195.6,
141.7, 140.7, 140.0, 138.5, 137.2, 137.1, 136.1, 133.4, 132.0,
130.6, 130.2, 129.7, 129.4, 128.2, 128.1, 127.9, 127.4, 126.5, 29.5,
23.3; HRMS (EI) calcd for [M + Na]+: C24H18O2Na 361.1199,
found 361.1207; IR (KBr): 3700, 2918, 2846, 1758, 1669, 1481,
1385, 1266, 1128, 755 cmꢁ1
.
7-Hydroxy-7-methyl-6,7-dihydro-5H-dibenzo[a,c][7]annulen-
5-one (3b). To the solution of ortho-acylphenyl iodide (1c) (0.2
mmol) in DMF (1.0 mL) were added PdCl2 (5 mol%), K2CO3 (1.5
equiv.) and DPPP (10 mol%) in a sealed tube under Ar atmo-
sphere. The reaction mixture was stirred at 150 ꢀC for 1.5 h, then
cooled down to room temperature and ltered, and the corre-
sponding ltrate was concentrated under vacuum and further
puried by ash column chromatography on silica gel to
7 (a) Y. C. Chia, H. C. Yeh, Y. T. Yeh and C. Y. Chen, Chem. Nat.
Compd., 2011, 47, 220–222; (b) J. Y. Sanceau, R. Dhal and
E. Brown, Tetrahedron, 1994, 50, 3363–3380; (c) C. Y. Chen,
1
furnish the target products 3b. Yellow oil; H NMR (400 MHz,
23602 | RSC Adv., 2014, 4, 23595–23603
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
W. L. Yang and Y. R. Hsui, Nat. Prod. Res., 2010, 24, 423–427;
RSC Advances
C. Hathroubi, C. Gozzi and M. Lemaire, Tetrahedron, 2001,
57, 7845–7855; (d) I. Cepanec, M. Litvic, J. Udikovic,
I. Pogorelic and M. Lovric, Tetrahedron, 2007, 63, 5614–5621.
(d) J. Y. Sanceau, R. Dhal and E. Brown, Nat. Prod. Lett., 1992,
1, 221; (e) K. Nakagawa-Goto, M. K. Jung, E. Hamel, C. C. Wu,
K. F. Bastow, A. Brossi, S. Ohta and K. H. Lee, Heterocycles, 20 J. Hu, Y. Cheng, Y. Yang and Y. Rao, Chem. Commun., 2011,
2005, 65, 541–550; (f) F. Graening and H. G. Schmalz,
Angew. Chem., Int. Ed., 2004, 43, 3230–3256.
8 W. M. Seganism and P. Deshong, Org. Lett., 2006, 8, 3951–
3954.
47, 10133–10135.
21 M. Kotora and T. Takahashi, in Handbook of
Organopalladium Chemistry for Organic Synthesis, ed. E. I.
Negishi, Wiley-Interscience, New York, 2002, vol. 1, pp.
973–993.
9 (a) A. V. Vorogushin, A. V. Predeus, W. D. Wulff and
H. J. Hansen, J. Org. Chem., 2003, 68, 5826–5831; (b) 22 S. Zhao, Y. He, D. Wum and Z. Guan, J. Fluorine Chem., 2010,
F. D. Boyer and I. Hanna, Org. Lett., 2007, 9, 715–718.
10 M. Leblanc and K. Fagnou, Org. Lett., 2005, 7, 2849–2852.
11 S. Djurdjevic and J. R. Green, Org. Lett., 2007, 9, 5505–5507.
131, 597–605.
23 N. J. Leonard and S. N. Boyd Jr, J. Org. Chem., 1946, 11, 405–
418.
12 Y. L. Choi, C. M. Yu, B. T. Kim and J. N. Heo, J. Org. Chem., 24 Z. Huang, Y. Yang, Q. Xiao, Y. Zhang and J. B. Wang, Eur.
2009, 74, 3948–3951. J. Org. Chem., 2012, 33, 6586–6593.
13 S. D. Broady, M. D. Golden, J. Leonard, J. C. Muir and 25 D. L. Boger, M. Yasuda, L. A. Mitscher, S. D. Drake,
M. Maudet, Tetrahedron Lett., 2007, 48, 4627–4630.
14 Satyanarayana reported a Pd-catalyzed cascade cyclization of
P. A. Kitos and S. C. Thompson, J. Med. Chem., 1987, 30,
1918–1928.
ortho-acyl phenyl bromides. Unfortunately, this method 26 T. Nittoli, K. Curran, S. Insaf, M. DiGrandi, M. Orlowski,
suffered from a limited range of substrates (only seven
examples) and poor yields (41–50%), see: J. Krishna,
A. G. K. Reddy and G. Satyanarayana, Synlett, 2013, 24,
967–972.
R. Chopra, A. Agarwal, A. Y. M. Howe, A. Prashad,
M. B. Floyd, B. Johnson, A. Sutherland, K. Wheless,
B. Feld, J. O'Connell, T. S. Mansour and J. Bloom, J. Med.
Chem., 2007, 50, 2108–2116.
15 S. Nadri, E. Azadi, A. Ataei, M. Joshaghani and E. Raee, 27 M. S. Juan, B. Eduardo, G. F. Vicente and G. Vicente, Org.
J. Organomet. Chem., 2011, 696, 2966–2970. Lett., 2012, 14, 1444–1447.
16 L. K. Sharma, K. B. Kim and G. I. Elliott, Green Chem., 2011, 28 N. Kirai and Y. Yamamoto, Eur. J. Org. Chem., 2009, 12, 1864–
13, 1546–1549. 1867.
17 (a) C. Amatore, E. Carrc, A. Jutand, H. Tanaka, Q. Ren and 29 J. Takaya, K. Sangu and N. Iwasawa, Angew. Chem., Int. Ed.,
S. Torii, Chem.–Eur. J., 1996, 2, 957–966; (b) 2009, 48, 7090–7093.
S. Mukhopadhyay, G. Rothenberg, D. Gitis, H. Wiener and 30 X. Jia, D. A. Petrone and M. Lautens, Angew. Chem., Int. Ed.,
Y. Sasson, J. Chem. Soc., Perkin Trans. 2, 1999, 2, 2481– 2012, 51, 9870–9872.
2484; (c) L. Wang, Y. Zhang, L. Liu and Y. Wang, J. Org. 31 F. Gasparrini, S. Grilli, R. Leardini, L. Lunazzi, A. Mazzanti,
Chem., 2006, 71, 1284–1287.
D. Nanni, M. Pierini and M. Pinamonti, J. Org. Chem., 2002,
18 I. Pastoriza-Santos and L. M. Liz-marzan, Pure Appl. Chem.,
2000, 72, 83–90.
67, 3089–3095.
32 J. J. Richards and C. Melander, J. Org. Chem., 2008, 73, 5191–
19 (a) A. T. Canty, Acc. Chem. Res., 1992, 25, 83–90; (b)
5193.
J. M. Brunel, M. H. Hirlemann, A. Heumann and 33 U. H. Hirt, M. F. H. Schuster, A. N. French, O. G. Wiest and
G. Buono, Chem. Commun., 2000, 1869–1870; (c) J. Hassan,
T. Wirth, Eur. J. Org. Chem., 2001, 8, 1569–1579.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 23595–23603 | 23603