A facile route to benzo[a]fluorenes via a palladium-catalyzed reaction of 2-alkynylbromobenzene with 2-(2-alkynylphenyl)malonate

Article abstract of DOI:10.1002/adsc.201200606

A palladium-catalyzed reaction of 2-alkynylbromobenzenes with 2-(2-alkynylphenyl)malonates gives rise to benzo[a]fluorenes in good yields. This tandem process is efficient with the formation of three bonds from easily available starting materials. Copyright

Full text of DOI:10.1002/adsc.201200606

FULL PAPERS
DOI: 10.1002/adsc.201200606
A Facile Route to Benzo[a]fluorenes via a Palladium-Catalyzed
Reaction of 2-Alkynylbromobenzene with 2-(2-Alkynylphenyl)-
malonate
Yong Luo,a Xiaolin Pan,a and Jie Wua,b,*
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, Peopleꢀs Republic of China
Fax : (+86)-216-564-1740; e-mail: jie_wu@fudan.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, Shanghai 200032, Peopleꢀs Republic of China
Received: July 11, 2012; Revised: September 14, 2012; Published online: November 4, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200606.
Abstract:
A
palladium-catalyzed reaction of Keywords: 2-alkynylbromobenzenes; 2-(2-alkynyl-
2-alkynylbromobenzenes with 2-(2-alkynylphenyl)- phenyl)malonates; benzo[a]fluorenes; palladium cat-
malonates gives rise to benzo[a]fluorenes in good alyst; tandem reactions
yields. This tandem process is efficient with the for-
mation of three bonds from easily available starting
materials.
Introduction
plied in the preparation of polyheterocyclic or poly-
carbocyclic compounds.[6] Prompted by this result and
The development of novel routes for the construction the achievement of tandem reactions, we envisioned
of carbocyclic units through a transition metal-cata- that the benzo[a]fluorene derivatives could be con-
lyzed process has attracted much attention by organic structed via a palladium-catalyzed reaction of 2-alk-
chemists. Although there are developed pathways for
ACHTUNGTRENyNGNU nylbromobenzenes with 2-(2-alkynylphenyl)malo-
the synthesis of carbocycles,[1] utilizing tandem reac- nates. The proposed synthetic route is illustrated in
tions for the generation of polycarbocycles in a one- Scheme 1.
pot procedure from simple and readily available start-
ing materials is still rare. Among the polycarbocycles, alkACHTUNGTRENNUNG
We hypothesized that an oxidative addition of 2-
ynylbromobenzene 1 to Pd(0) would occur first to
the benzo[a]fluorene core as a privileged substructure generate a Pd(II) species A. On the basis of our pre-
is attractive. This scaffold (including its reduced and vious work,[6b,c] we believed that the dimethyl malo-
oxidized forms) which has a tetracyclic backbone, can nate group would act as the coupling partner as well
be found widely in natural products[2] and biologically as a directing group for control of the regioselectivity.
active pharmaceuticals.[3] However, the reported Thus, the regioselectivity of insertion into the triple
methods for the preparation of this structure typically bond would depend on the coordination of the palla-
required multiple steps and toxic reagents.[3a] The lack dium center with the dimethyl malonate functional
of a simple, straightforward and efficient synthetic group. An impact of the electronic properties of the
procedure for these polycarbocycles prevents their substitutions is not observed. Therefore, the subse-
broader and further applications in chemical biology quent coordination and insertion to the triple bond of
and medicinal chemistry.[4] Thus, the development of 2-(2-alkynylphenyl)malonate 2 would result in the for-
methods for the efficient construction of benzo[a]- mation of intermediate B. Then the intramolecular in-
fluorenes is highly desirable.
sertion of the triple bond would take place to produce
À
A tandem reaction would be the choice for the gen- intermediate C, which would undergo a C C coupling
eration of molecular complexity and diversity.[5] This to afford the desired benzo[a]fluorene 3. However,
approach has been successfully utilized in the synthe- there are several significant challenges. Firstly, the
sis of natural product-like compounds. Recently, generation of indene compounds would be a competi-
a powerful strategy using intramolecular or intermo- tive pathway for the reaction of 2-(2-alkynylphenyl)-
lecular double insertion of triple bonds has been ap- malonate 2 in the presence of 2-alkynylbromobenzene
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Scheme 1. A proposed pathway for the generation of benzo[a]fluorenes.
1 and a palladium catalyst.[7] For instance, Liang re- Results and Discussion
ported the preparation of substituted indenes via
a palladium-catalyzed carboannulation of 2-[2-(1-alk- To efficiently assemble the benzo[a]fluorene scaffold,
ynyl)phenyl]malonate with aryl, benzylic, and alkenyl we first evaluated the reaction using 1-bromo-2-
halides.[7a] Larock described the synthesis of substitut- (phen
ylethynyl)benzene 1a and dimethyl 2-(2-
ed indenes through a palladium-catalyzed cyclization (phenylethynyl)phenyl)malonate 2a. To identify the
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
of diethyl 2-[2-(1-alkynyl)phenyl]malonate with or- optimal reaction conditions for this reaction,
ganic halides.[7b] Secondly, the coordination between a number of ligands was examined initially in the
dimethyl malonate and the palladium center is presence of PdACTHNUTRGNEG(UN OAc)2 (5 mol%) and K2CO3 in tolu-
weaker and more complicated compared to other het- ene under reflux (Table 1). However, for most cases,
eroatom nucleophiles, which might hamper the pro- the direct carboannulation product 4 dominated, and
cess of insertion of the triple bond. To achieve the only a trace amount of benzo[a]fluorene 3a was de-
proposed synthetic route shown in Scheme 1, we start- tected (Table 1, entries 1–5). To our delight, the addi-
ed to explore the feasibility for the construction of tion of alkane-tethered bidentate phosphine ligands
benzo[a]fluorenes.
was proven to be efficient in the reaction, providing
the desired product 3a in low yields (Table 1, en-
tries 6–9). DPPM was the best choice and the corre-
sponding benzo[a]fluorene 3a was isolated in 43%
yield (Table 1, entry 9). We further screened various
organic and inorganic bases (Table 1, entries 10–13).
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A Facile Route to Benzo[a]fluorenes via a Palladium-Catalyzed Reaction
Table 1. Initial studies for the palladium-catalyzed reaction of 1-bromo-2-(phenylethynyl)benzene 1a with dimethyl 2-(2-
(phenylethynyl)phenyl)malonate 2a.[a]
Entry
[Pd]
Ligand
PCy3
Base
Solvent
Yield [%][b]
3a
4
1
2
3
4
5
6
7
8
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
G
E
E
R
R
N
N
R
N
R
ACHTUNGTRENNUNG
E
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
K3PO4
iPr2NEt
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1,4-dioxane
DMF
trace
trace
trace
trace
trace
30
64
48
30
25
33
20
A
(Æ)-BINAP
XPhos
PPh3
DPPB
DPPP
24
25
43
25
17
13
DPPE
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
DPPM
9
10
11
12
13
14
15
16
17
18
19
20
21
22[c]
23[c,d]
24[e]
N.R.
40
trace
trace
trace
trace
21
55
nr
30
N
R
N
R
trace
trace
trace
trace
trace
trace
20
30
DMSO
PhCN
trace
trace
20
32
17
ACHTUNGTRENNUNG
G
toluene
toluene
toluene
toluene
toluene
toluene
toluene
E
N
R
N
T
A
15
64
80
trace
trace
trace
trace
[a]
Reaction conditions: 1-bromo-2-(phenylethynyl)benzene 1a (0.3 mmol), dimethyl 2-(2-(phenylethynyl)phenyl)malonate 2a
(1.2 equiv.), palladium catalyst (5 mol%), phosphine ligand (10 mol%), base (2.0 equiv.), solvent (2.0 mL), 1108C.
Isolated yield based on 1-bromo-2-(phenylethynyl)benzene 1a.
1.5 equiv. of dimethyl 2-[2-(phenylethynyl)phenyl]malonate 2a were used.
6.0 mL of toluene were used.
[b]
[c]
[d]
[e]
The reaction was performed at 908C.
The transformation worked efficiently in the presence the reaction was run at 908C (Table 1, entry 24). The
of K3PO4, leading to the product in 55% yield structure of benzo[a]fluorene 3a was unambiguously
(Table 1, entry 12). Further investigation indicated identified by X-ray diffraction analysis (Figure 1).
that toluene was the best solvent (Table 1, entries 14–
After establishing the optimal conditions, we then
17). Other palladium catalysts were examined subse- explored the scope of this palladium-catalyzed
quently, however, the yield was decreased dramatical- tandem reaction of 2-alkynylbromobenzenes 1 with 2-
ly (Table 1, entries 18–21). Interestingly, the benzo[a]- (2-alkynylphenyl)malonates 2. The results are pre-
fluorene 3a was obtained in 80% yield when the reac- sented in Scheme 2. All the reactions proceeded
tion occurred in toluene at a lower concentration smoothly to afford the benzo[a]fluorenes 3 in moder-
(Table 1, entry 23). The efficiency was retarded when ate to good yields. Different substituents including
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Experimental Section
General Procedure of the Palladium-Catalyzed
Reaction of 2-Alkynylbromobenzene 1 with 2-(2-
Alkynylphenyl)malonate 2
2-Alkynylbromobenzene 1 (0.3 mmol), 2-(2-alkynylphenyl)-
malonate
2 (0.45 mmol), PdACHTUNTGERNUN(G OAc)2 (5 mol%), DPPM
(5 mol%) and K3PO4 (0.6 mmol) were placed in the test
tube under N2. Toluene (6.0 mL) was added via a syringe.
The mixture was stirred under reflux. After completion of
the reaction as indicated by TLC (usually 10 h), the mixture
was cooled to room temperature and the solvent was evapo-
rated. The residue was purified immediately by flash column
chromatography on silica gel to give the desired product 3.
Dimethyl
6,11-diphenyl-5H-benzo[a]fluorene-5,5-dicar-
boxylate (3a): yellow solid; mp 175–1768C; 1H NMR
(400 MHz, CDCl3): d=7.54–7.47 (m, 9H), 7.39 (m, 3H),
7.19–7.03 (m, 3H), 6.97 (d, J=7.2 Hz, 1H), 6.86–6.83 (m,
1H), 6.12 (d, J=7.2 Hz, 1H), 3.61 (s, 6H); 13C NMR
(100 MHz, CDCl3): d=168.9, 146.3, 139.0, 138.8, 137.5,
136.5, 136.0, 133.5, 132.4, 129.8, 129.2, 129.13, 129.07, 128.9,
128.7, 128.1, 128.05, 127.95, 127.6, 127.0, 125.9, 125.6, 123.5,
120.2, 67.0, 52.8; HR-MS (ESI): m/z=485.1743, calcd. for
C33H25O4 [M+H]+: 485.1753. IR (thin film): n=3060, 2950,
2918, 2849, 1769, 1745, 1596, 1493, 1432, 1218, 1051 cmÀ1.
Dimethyl 11-phenyl-6-(p-tolyl)-5H-benzo[a]fluorene-5,5-
dicarboxylate (3b): yellow solid; mp 203–2048C; 1H NMR
(400 MHz, CDCl3): d=7.53–7.49 (m, 6H), 7.37 (d, J=
7.8 Hz, 1H), 7.26 (m, 4H), 7.17–7.09 (m, 2H), 7.06–7.02 (m,
1H), 6.96 (d, J=7.2 Hz, 1H), 6.88–6.84 (m, 1H), 6.23 (d, J=
7.2 Hz, 1H), 3.61 (s, 6H), 2.44 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=168.9, 146.2, 138.8, 138.6, 138.5, 136.8, 136.0,
134.4, 133.6, 132.5, 129.7, 129.5, 129.1, 129.0, 128.7, 128.0,
127.9, 127.6, 126.9, 125.8, 125.5, 123.5, 120.1, 67.0, 52.8, 21.4;
HR-MS (ESI): m/z=499.1916, calcd. for C34H27O4 [M+H]+:
499.1909; IR (thin film): n=3060, 2950, 2926, 1769, 1745,
1591, 1448, 1213, 1051 cmÀ1.
Figure 1. ORTEP illustration of benzo[a]fluorene 3a (30%
probability ellipsoids).
aryl and alkyl groups attached to the triple bond were
all tolerated under the standard conditions. For in-
stance, the 4-acetylphenyl group could be compatible
in the reaction, which furnished the expected product
3d in 88% yield. The thienyl-substituted 2-alkynylbro-
mobenzene was a good reactant as well, although the
corresponding product 3g was formed in 44% yield.
Various substrates bearing electron-withdrawing and
electron-donating substituents on the aromatic back-
bone were then examined. As expected, the nature of
the substituents did not hamper the efficiency of the
conversion.
Dimethyl 6-(4-methoxyphenyl)-11-phenyl-5H-benzo[a]-
fluorene-5,5-dicarboxylate (3c): yellow solid; mp 219–
1
2208C; H NMR (400 MHz, CDCl3): d=7.53–7.48 (m, 6H),
7.38–7.36 (m, 1H), 7.32–7.30 (m, 2H), 7.18–7.10 (m, 2H),
7.06–7.00 (m, 4H), 6.90–6.87 (m, 1H), 6.29 (d, J=7.2 Hz,
1H), 3.88 (s, 3H), 3.61 (s, 6H); 13C NMR (100 MHz,
CDCl3): d=169.0, 159.8, 146.2, 138.9, 136.7, 136.0, 133.6,
132.5, 130.5, 129.7, 129.5, 129.1, 128.8, 128.0, 127.9, 127.6,
126.9, 125.8, 125.6, 123.5, 120.1, 114.1, 67.1, 55.2, 52.8; HR-
MS (ESI): m/z= 515.1846, calcd. for C34H27O5 [M+H]+:
515.1858; IR (thin film): n=2957, 2911, 2839, 1776, 1745,
1606, 1509, 1242, 1170, 1052 cmÀ1.
Dimethyl 6-(4-acetylphenyl)-11-phenyl-5H-benzo[a]fluor-
ene-5,5-dicarboxylate (3d): yellow solid; mp 223–2248C;
1H NMR (400 MHz, CDCl3): d=8.08 (d, J=6.8 Hz, 2H),
7.55–7.49 (m, 8H), 7.38 (d, J=7.8 Hz, 1H), 7.20–7.04 (m,
3H), 6.97 (d, J=7.2 Hz, 1H), 6.86–6.82 (m, 1H), 6.12 (d, J=
7.2 Hz, 1H), 3.62 (s, 6H), 2.69 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=197.6, 168.7, 146.3, 142.6, 139.5, 139.0, 137.0,
135.6, 135.0, 133.1, 132.0, 129.8, 129.5, 129.1, 128.9, 128.6,
128.4, 128.1, 128.0, 127.4, 127.0, 125.8, 125.7, 123.3, 120.3,
66.9, 52.9, 26.7; HR-MS (ESI): m/z=527.1858, calcd. for
C35H27O5 [M+H]+: 527.1858; IR (thin film): n=3061, 2951,
2926, 1745, 1686, 1602, 1475, 1448, 1400, 1264, 1050 cmÀ1.
Conclusions
In summary, we have described an efficient route for
the generation of benzo[a]fluorenes via a palladium-
catalyzed tandem reaction of 2-alkynylbromoben-
zenes with 2-(2-alkynylphenyl)malonates. A tetracy-
clic backbone could be constructed in a one-pot pro-
À
cedure with the formation of three C C bonds. A
double insertion of triple bonds is the key step, and
the molecular complexity could be easily introduced
during the transformation.
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A Facile Route to Benzo[a]fluorenes via a Palladium-Catalyzed Reaction
Scheme 2. Investigationof scope for the palladium-catalyzed reaction of 2-alkynylbromobenzenes 1 with 2-(2-alkynylphenyl)-
malonates 2.
Dimethyl 6-butyl-11-phenyl-5H-benzo[a]fluorene-5,5-di-
carboxylate (3e): yellow solid; mp 157–1588C; 1H NMR
(400 MHz, CDCl3): d=7.67 (d, J=6.8 Hz, 1H), 7.51–7.43
(m, 6H), 7.32–7.23 (m, 3H), 7.15–7.13 (m, 1H), 7.04–7.01
(m, 2H), 3.69 (s, 6H), 2.91–2.90 (m, 2H), 1.59–1.57 (m, 4H),
1.02–1.00 (m, 3H); 13C NMR (100 MHz, CDCl3): d=169.6,
146.4, 146.4, 139.5, 137.2, 136.7, 136.2, 132.9, 131.9, 129.7,
129.2, 129.1, 128.7, 127.8, 127.7, 127.6, 126.8, 125.80, 125.75,
123.8, 120.4, 66.3, 53.0, 33.0, 30.9, 23.4, 13.8; HR-MS (ESI):
m/z=465.2040, calcd. for C31H29O4 [M+H]+: 465.2066; IR
(thin film): n=3061, 2954, 2871, 1762, 1736, 1644, 1601,
1451, 1213, 1047 cmÀ1.
(m, 3H), 7.13 (s, 1H), 7.09–7.02 (m, 2H), 3.78 (s, 6H);
13C NMR (100 MHz, CDCl3): d=169.7, 146.1, 140.3, 139.1,
135.7, 133.3, 130.2, 130.1, 129.7, 129.1, 128.9, 128.8, 128.1,
126.9, 126.4, 125.8, 125.7, 121.5, 120.3, 120.1, 61.7, 53.5; HR-
MS (ESI): m/z=409.1425, calcd. for C27H21O4 [M+H]+:
409.1440; IR (thin film): n=3059, 2952, 2924, 2849, 1735,
1601, 1493, 1474, 1451, 1228, 1041 cmÀ1.
Dimethyl 11-phenyl-6-(thiophen-3-yl)-5H-benzo[a]fluor-
ene-5,5-dicarboxylate (3g): yellow solid; mp 204–2058C;
1H NMR (400 MHz, CDCl3): d=7.54–7.45 (m, 8H), 7.37 (m,
2H), 7.19–7.13 (m, 2H), 7.09–7.05 (m, 2H), 6.99–6.94 (m,
2H), 6.36 (d, J=7.8 Hz, 1H), 3.63 (s, 6H); 13C NMR
(100 MHz, CDCl3): d=169.1, 146.2, 139.3, 139.2, 137.3,
135.9, 133.4, 132.2, 132.1, 129.7, 129.1, 129.0, 128.3, 128.07,
127.96, 127.4, 126.9, 125.8, 125.1, 123.3, 120.2, 66.8, 53.0;
Dimethyl 11-phenyl-5H-benzo[a]fluorene-5,5-dicarboxy-
late (3f): yellow solidmp 150–1518C; 1H NMR (400 MHz,
CDCl3): d=7.73–7.71 (m, 2H), 7.53–7.42 (m, 6H), 7.24–7.21
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HR-MS (ESI): m/z=491.1304, calcd. for C31H23O4S [M+
H]+: 491.1317; IR (thin film): n=3065, 2952, 2916, 1766,
1740, 1653, 1596, 1452, 1211, 1052 cmÀ1.
2952, 2916, 1766, 1745, 1596, 1483, 1442, 1432, 1216,
1047 cmÀ1.
Dimethyl 11-(4-(methoxycarbonyl)phenyl)-6-phenyl-5H-
benzo[a]fluorene-5,5-dicarboxylate (3m): yellow solid; mp
189–1908C; 1H NMR (400 MHz, CDCl3): d=8.22 (d, J=
7.4 Hz, 2H), 7.60 (d, J=7.4 Hz, 2H), 7.53–7.47 (m, 4H),
7.38 (m, 2H), 7.31–7.04 (m, 4H), 6.94–6.84 (m, 2H), 6.14 (d,
J=7.4 Hz, 1H), 3.98 (s, 3H), 3.61 (s, 6H); 13C NMR
(100 MHz, CDCl3): d=168.8, 166.9, 145.7, 141.1, 138.6,
137.6, 137.4, 133.4, 132.5, 130.4, 129.8, 129.3, 129.1, 129.0,
128.82, 128.77, 128.2, 128.1, 127.2, 125.8, 123.6, 119.9, 67.1,
52.9, 52.2; HR-MS (ESI): m/z=543.1807, calcd. for
C35H27O6 [M+H]+: 543.1808; IR (thin film): n=3065, 2952,
2849, 1766, 1724, 1606, 1437, 1278, 1221, 1057 cmÀ1.
Dimethyl 11-butyl-6-phenyl-5H-benzo[a]fluorene-5,5-di-
carboxylate (3n): yellow solid; mp 121–1228C; 1H NMR
(400 MHz, CDCl3): d=7.96 (d, J=7.8 Hz, 1H), 7.53 (d, J=
7.8 Hz, 1H), 7.41 (m, 4H), 7.30–7.16 (m, 5H), 6.83–6.79 (m,
1H), 6.03 (d, J=7.4 Hz, 1H), 3.55 (s, 6H), 3.00 (t, J=
7.8 Hz, 2H), 1.75–1.73 (m, 2H), 1.60–1.55 (m, 2H), 1.02 (t,
J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=169.1,
145.8, 140.0, 138.9, 137.6, 134.3, 133.8, 132.1, 130.7, 129.3,
129.1, 128.61, 128.55, 128.48, 127.9, 126.50, 126.46, 125.5,
125.4, 123.3, 118.7, 67.0, 52.7, 30.0, 26.6, 23.3, 14.0; HR-MS
(ESI): m/z=465.2076, calcd. for C31H29O4 [M+H]+:
465.2066; IR (thin film): n=3075, 2952, 2865, 1766, 1740,
1591, 1447, 1216, 1047 cmÀ1.
Dimethyl
9-methyl-6,11-diphenyl-5H-benzo[a]fluorene-
5,5-dicarboxylate (3h): yellow solid; mp 206–2078C;
1H NMR (400 MHz, CDCl3): d=7.54–7.45 (m, 9H), 7.37–
7.35 (m, 3H), 7.17–7.13 (m, 1H), 7.05–7.01 (m, 1H), 6.77 (s,
1H), 6.66 (d, J=7.2 Hz, 1H), 6.01 (d, J=7.2 Hz, 1H), 3.60
(s, 6H), 2.22 (s, 3H); 13C NMR (100 MHz, CDCl3): d=
169.0, 146.6, 138.9, 138.6, 138.3, 137.6, 136.1, 135.6, 132.4,
130.9, 129.8, 129.2, 129.12, 129.07, 128.8, 128.7, 128.6, 128.0,
127.9, 126.8, 126.3, 125.8, 123.3, 120.9, 66.9, 52.8, 21.5; HR-
MS (ESI): m/z=491.1895; calcd. for C34H27O4 [M+H]+:
499.1909; IR (thin film): n=3055, 3024, 2942, 1771, 1745,
1601, 1483, 1437, 1206, 1052 cmÀ1.
Dimethyl
9-fluoro-6,11-diphenyl-5H-benzo[a]fluorene-
1
5,5-dicarboxylate (3i): yellow solid; mp 193–1948C; H NMR
(400 MHz, CDCl3): d=7.54–7.48 (m, 9H), 7.38 (m, 3H),
7.23–7.17 (m, 1H), 7.08–7.04 (m, 1H), 6.67 (d, J=8.0 Hz,
1H), 6.54–6.49 (m, 1H), 6.05–6.02 (m, 1H), 3.62 (m, 6H);
13C NMR (100 MHz, CDCl3): d=168.8, 163.3
ACTHNUTRGENN(UG d, J HCATUNGTRENN(UGN C,F)=
245.0 Hz), 148.6 (d, J (C,F)=8.6 Hz), 137.9, 137.8, 137.2,
136.6, 135.4, 132.6, 129.4, 129.3, 129.2, 128.98, 128.94, 128.85,
128.79, 128.3, 128.0, 127.3, 126.0, 124.6 (d, JC,F =8.6 Hz),
111.9 (d, JC,F =22.9 Hz), 107.4 (d, JC,F =23.8 Hz), 67.0, 52.9;
HR-MS (ESI): m/z=503.1658, calcd. for C33H24FO4 [M+
H]+: 503.1659; IR (thin film): n=3070, 2947, 2916, 1771,
1730, 1596, 1463, 1216, 1144, 1052 cmÀ1.
Dimethyl
11-butyl-6-(4-methoxyphenyl)-5H-benzo[a]-
fluorene-5,5-dicarboxylate (3o): yellow solid; mp 206–
Dimethyl
8-chloro-6,11-diphenyl-5H-benzo[a]fluorene-
1
2078C; H NMR (400 MHz, CDCl3): d=7.97 (d, J=7.8 Hz,
5,5-dicarboxylate (3j): yellow solid; mp 230–2318C;
1H NMR (400 MHz, CDCl3): d=7.53–7.48 (m, 8H), 7.37 (m,
3H), 7.20–7.16 (m, 2H), 7.08–7.06 (m, 2H), 6.87 (d, J=
7.8 Hz, 1H), 6.01 (s, 1H), 3.62 (s, 6H); 13C NMR (100 MHz,
CDCl3): d=168.7, 144.6, 138.3, 138.10, 138.06, 136.9, 135.5,
134.9, 132.3, 131.4, 129.5, 129.2, 129.1, 129.0, 128.9, 128.3,
128.0, 127.9, 127.7, 127.2, 125.8, 123.91, 123.87, 120.8, 67.1,
52.9; HR-MS (ESI): m/z=519.1362, calcd. for C33H24ClO4
[M+H]+: 519.1363. IR (thin film): n=3060, 2951, 2849,
1769, 1746, 1601, 1444, 1217, 1047 cmÀ1.
1H), 7.54 (d, J=7.8 Hz, 1H), 7.44–7.41 (m, 1H), 7.32–7.21
(m, 5H), 6.95 (d, J=8.2 Hz, 2H), 6.89–6.85 (m, 1H), 6.20
(d, J=7.2 Hz, 1H), 3.86 (s, 3H), 3.58 (s, 6H), 3.02 (t, J=
6.8 Hz, 2H), 1.77 (m, 2H), 1.60–1.59 (m, 2H), 1.04 (d, J=
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=169.2, 159.7,
145.7, 139.9, 139.1, 134.4, 133.9, 132.1, 130.7, 130.6, 129.7,
129.0, 128.4, 127.8, 126.6, 126.4, 125.45, 125.38, 123.3, 118.6,
114.0, 67.0, 55.1, 52.7, 30.0, 26.6, 23.3, 14.0; HR-MS (ESI):
m/z=495.2163, calcd. for C32H31O5 [M+H]+: 495.2171; IR
(thin film): n=3060, 2952, 2870, 1771, 1745, 1601, 1509,
1477, 1288, 1242, 1052 cmÀ1.
Dimethyl
8-chloro-6-(4-methoxyphenyl)-11-phenyl-5H-
benzo[a]fluorene-5,5-dicarboxylate (3k): yellow solid; mp
202–2038C; 1H NMR (400 MHz, CDCl3): d=7.52–7.47 (m,
6H), 7.36–7.29 (m, 3H), 7.18–7.15 (m, 1H), 7.09–7.01 (m,
4H), 6.87 (d, J=7.8 Hz, 1H), 6.23 (s, 1H), 3.88 (s, 3H), 3,61
(s, 6H); 13C NMR (100 MHz, CDCl3): d=168.8, 160.1, 144.5,
138.3, 138.1, 138.0, 135.5, 135.0, 132.4, 131.3, 130.5, 129.5,
129.2, 129.0, 128.9, 128.2, 128.0, 127.8, 127.1, 125.8, 123.84,
123.80, 120.8, 114.2, 67.2, 55.3, 52.9; HR-MS (ESI): m/z=
549.1469, calcd. for C34H26ClO5 [M+H]+: 549.1469; IR (thin
film): n=2955, 2925, 2854, 1770, 1730, 1607, 1509, 1445,
1289, 1250, 1046 cmÀ1.
Dimethyl 6-phenyl-11-(p-tolyl)-5H-benzo[a]fluorene-5,5-
dicarboxylate (3l): yellow solid; mp 194–1958C; 1H NMR
(400 MHz, CDCl3): d=7.51–7.46 (m, 5H), 7.38–7.33 (m,
6H), 7.18–7.04 (m, 3H), 7.00–6.98 (m, 1H), 6.85–6.81 (m,
1H), 6.12 (d, J=7.4 Hz, 1H), 3.60 (s, 6H), 2.47 (s, 3H);
13C NMR (100 MHz, CDCl3): d=169.0, 146.4, 139.2, 138.8,
137.8, 137.6, 136.3, 133.5, 132.8, 132.3, 129.9, 129.8, 129.2,
128.9, 128.8, 128.7, 128.1, 127.9, 127.4, 126.9, 125.9, 125.5,
123.4, 120.2, 67.0, 52.8, 21.4; HR-MS (ESI): m/z=499.1905,
calcd. C34H27O4 [M+H]+: 499.1909; IR (thin film): n=3065,
Dimethyl 6-(4-acetylphenyl)-11-butyl-5H-benzo[a]fluor-
ene-5,5-dicarboxylate (3p): yellow solid; mp 180–1818C;
1H NMR (400 MHz, CDCl3): d=8.05–7.97 (m, 3H), 7.55–
7.43 (m, 4H), 7.33–7.19 (m, 3H), 6.84–6.81 (m, 1H), 6.05 (d,
J=7.2 Hz, 1H), 3.59 (s, 6H), 3.02 (t, J=7.2 Hz, 2H), 2.67 (s,
3H), 1.77 (m, 2H), 1.62–1.57 (m, 2H), 1.04 (t, J=6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3): d=197.7, 168.9, 145.8,
142.7, 140.6, 139.2, 136.8, 133.4, 132.7, 131.7, 130.5, 129.9,
129.1, 128.6, 128.5, 128.3, 126.5, 126.3, 125.5, 125.4, 123.2,
118.9, 66.8, 52.8, 29.9, 26.6, 23.3, 13.9; HR-MS (ESI); m/z=
507.2164, calcd. for C33H31O5 [M+H]+: 507.2171; IR (thin
film): n=3060, 2957, 2859, 1771, 1745, 1596, 1452, 1401,
1267, 1216, 1047 cmÀ1.
Dimethyl 2-methoxy-6,11-diphenyl-5H-benzo[a]fluorene-
5,5-dicarboxylate (3q): yellow solid; mp 191–1928C;
1H NMR (400 MHz, CDCl3): d=7.55–7.37 (m, 11H), 7.14–
7.10 (m, 1H), 6.99–6.97 (m, 1H), 6.89–6.83 (m, 2H), 6.74 (d,
J=8.3 Hz, 1H), 6.12 (d, J=7.8 Hz, 1H), 3.61 (s, 6H), 3.33
(s, 3H); 13C NMR (100 MHz, CDCl3): d=169.1, 158.8, 146.2,
139.0, 138.6, 137.6, 136.8, 136.1, 133.5, 130.8, 130.0, 129.3,
129.2, 129.1, 128.7, 128.13, 128.05, 127.9, 125.6, 124.8, 123.6,
3076
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 3071 – 3077

A Facile Route to Benzo[a]fluorenes via a Palladium-Catalyzed Reaction
120.2, 115.4, 108.6, 66.6, 54.5, 52.8; HR-MS (ESI): m/z=
515.1849, calcd. for C34H27O5 [M+H]+: 515.1858; IR (thin
film): n=3057, 2993, 2951, 2835, 1766, 1745, 1604, 1484,
1244, 1049 cmÀ1.
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Dimethyl
2-phenyl-3-(2-(phenylethynyl)phenyl)-1H-
indene-1,1-dicarboxylate (4): white solid; mp 56–578C;
1H NMR (400 MHz, CDCl3): d=7.69 (m, 1H), 7.61–7.59 (m,
1H), 7.30–7.14 (m, 14H), 6.94–6.93 (m, 2H), 3.75 (s, 3H),
3.28 (s, 3H); 13C NMR (100 MHz, CDCl3): d=169.0, 168.6,
145.1,144.8, 141.3, 140.4, 137.5, 134.3, 131.9, 131.3, 129.9,
129.5, 128.6, 128.5, 128.0, 127.9, 127.8, 127.6, 127.4, 126.4,
123.9, 123.3, 123.0, 121.8, 93.8, 88.3, 72.3, 53.0, 52.5; HR-MS
(ESI): m/z=485.1749, calcd. for C33H25O4 [M+H]+:
485.1747; IR (thin film): n=3055, 3029, 2947, 2212, 1740,
1596, 1493, 1463, 1226, 1052 cmÀ1.
Crystallographic data for the structure 3a has been depos-
ited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 887903. These data
can be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif or on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK [fax (internat.): +44-1223/336-033;
e-mail: deposit@ccdc.cam.ac.uk].
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Supporting Information
Experimental procedures, characterization data, 1H and
13C NMR spectra of compounds 3 and 4 re available in the
Supporting Information.
Acknowledgements
Financial support from National Natural Science Foundation
of China (No. 21032007) is gratefully acknowledged.
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Adv. Synth. Catal. 2012, 354, 3071 – 3077
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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