Palladium catalyzed atom-economic synthesis of functionalized 9-(diarylmethylene)-9H-fluorenes using triarylbismuths in one-pot bis-coupling process

Article abstract of DOI:10.1016/j.tetlet.2011.10.156

An efficient palladium catalyzed atom-economic synthesis of functionalized 9-(diarylmethylene)-9H-fluorenes has been accomplished in one-pot bis-coupling process using triarylbismuths as organometallic reagents. These bis-couplings in 1 hour short reactio

Full text of DOI:10.1016/j.tetlet.2011.10.156

Tetrahedron Letters 53 (2012) 162–165
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Tetrahedron Letters
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Palladium catalyzed atom-economic synthesis of functionalized
9-(diarylmethylene)-9H-fluorenes using triarylbismuths
in one-pot bis-coupling process
⇑
Maddali L. N. Rao , Priyabrata Dasgupta
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient palladium catalyzed atom-economic synthesis of functionalized 9-(diarylmethylene)-9H-
fluorenes has been accomplished in one-pot bis-coupling process using triarylbismuths as organometallic
reagents. These bis-couplings in 1 hour short reaction time afforded various 9-(diarylmethylene)-9H-
fluorenes in good to high yields.
Received 3 October 2011
Revised 28 October 2011
Accepted 30 October 2011
Available online 6 November 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
Triarylbismuths
9-(Diarylmethylene)-9H-fluorenes
Bis-couplings
9-(Diarylmethylene)-9H-fluorenes or diarylmethylidenefluo-
renes are novel structural components useful in various material
applications.1 Metal catalyzed reactions are indispensable for facile
synthesis of organic skeletons useful in materials chemistry.2 Var-
ious synthetic methods are reported recently for the synthesis of 9-
(diarylmethylene)-9H-fluorenes under palladium catalyzed condi-
tions.3 These reactions include: (i) couplings of oxime ether with
aryl iodide involving long hours heating,3a (ii) 5-exo-dig cyclization
of 2-bromo-20-(phenylethynyl)biphenyl with arylboronic acids,3b
(iii) double cross-coupling reaction of 9-stannafluorenes with
1,1-dibromoalkenes,3c (iv) 5-exo-dig annulations of o-alkynylbiar-
yls with aryl halides,3d and (v) double cross-couplings of 9-(dibro-
momethylene)-9H-fluorene with arylboronic acids3e reported by
Ramana et al. A few other synthetic methods are also available.4
For example, the 9-(diphenylmethylene)-9H-fluorene was also
prepared through the addition–elimination protocol involving flu-
orenyl lithium addition to diphenyl ketone4a or diphenylmethyl
lithium addition to 9-fluorenone.5 However, some of these meth-
ods involve cumbersome procedures.
one palladium catalyzed protocol involving double bis-couplings
of 9-(dibromomethylene)-9H-fluorene with aryl boronic acids
was reported so far.3e This prompted us to expand the scope and
general utility of this bis-couplings with triarylbismuths, as these
reagents demonstrated an excellent multi-coupling ability as orga-
nometallic nucleophiles under palladium catalysis.7 Advantage of
using BiAr3 reagents is that they serve three aryl groups efficiently
in an atom-economic manner and this reduces the organometallic
loadings to one third in such couplings.8 In tune with the growing
importance of the utility of diarylmethylidenefluorenes, we report
here a facile palladium catalyzed atom-economic synthesis of func-
tionalized 9-(diarylmethylene)-9H-fluorenes in one-pot bis-cou-
pling process using triarylbismuth reagents.
Synthesis of 9-(dibromomethylene)-9H-fluorene (1) was car-
ried out using Ramirez gem-dibromoolefination with Horner–
Wadsworth–Emmons modification reported for aldehydes and ke-
tones.9 This reaction using 9-fluorenone in combination with tetr-
abromomethane and triethylphosphite afforded the desired 9-
(dibromomethylene)-9H-fluorene in an 86% yield after treating
with mixture of acids under reflux condition (Scheme 1).10
As three aryl groups are available, 1 equiv of triarylbismuths
was chosen to couple with 1.5 equiv of 9-(dibromomethylene)-
9H-fluorene to afford 1.5 equiv of 9-(diarylmethylene)-9H-fluo-
renes (Scheme 2).
The double Suzuki coupling process3e is of special interest as
this provides the desired flexibility in the synthesis of various func-
tionalized diarylmethylidenefluorenes.
The required 9-(dibromomethylene)-9H-fluorenes6 and several
aryl organometallic reagents are readily available and these factors
bestow this process an edge over other methods. However, only
To establish a viable palladium catalyzed protocol for efficient
bis-couplings, a systematic screening was carried out using 9-
(dibromomethylene)-9H-fluorene (1) and BiPh3 as model sub-
strates to obtain 9-(diphenylmethylene)-9H-fluorene (1a) product.
⇑
Corresponding author. Tel./fax: +91 512 2597532.
E-mail address: maddali@iitk.ac.in (M.L.N. Rao).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.156

M.L.N. Rao, P. Dasgupta / Tetrahedron Letters 53 (2012) 162–165
163
and 7, Table 1), whereas K2CO3 and KOAc proved to be more effi-
cient with 78–79% yields (entries 6 and 8, Table 1). Reaction with
PdCl2(PPh3)2 as catalyst precursor furnished a 76% yield of the de-
sired product (entry 9, Table 1). Thus, additional scrutiny was car-
ried out with low catalyst loadings of Pd(PPh3)4 using 0.04 and
0.02 equiv and KOAc base. These reactions provided 82% and 77%
yields, respectively (entries 10 and 11, Table 1). Different KOAc
loadings using 1–4 equiv revealed that bis-coupling process is
more effective with either 4 or 3 equiv (entries 12 and 13, Table 1).
However, moderate yields were obtained with 2 and 1 equiv of
base (entries 14 and 15, Table 1). Reaction checked for optimum
reaction time with 3 and 1 h revealed a marginal improvement
in yield with longer reaction time (entries 16 and 17, Table 1).
Two control reactions carried out without base and catalyst (en-
tries 18 and 19, Table 1) amply indicated their importance for
effective bis-couplings. Triarylbismuths are thermally labile to give
biaryls in the presence of palladium catalyst.11 This resulted in the
formation of biphenyl as a minor side product in all screening reac-
tions. In some cases, the mono phenylated product 9-benzylidene-
9H-fluorene was also formed in minor amounts.3d From this study,
it was realized that Pd(PPh3)4 (0.02 equiv), KOAc (4 equiv) in DMF
at 110 °C and 1 hour reaction time as an optimum condition to ob-
tain high coupling yield (entry 17, Table 1).
Br
Br
O
(1) CBr4 / P(OEt)3
CH2Cl2, 0 oC to rt
(2) Conc. HCl / AcOH
reflux
1
86%
Scheme 1. Synthesis of 9-(dibromomethylene)-9H-fluorene.10
Br
Br
Ar
Ar
Ar
Bi
[Pd]
+
Ar
Ar
1
(1 equiv)
(1.5 equiv)
(1.5 equiv)
Scheme 2. Bis-couplings with dibromide and BiAr3.
The coupling reaction carried out using Pd(PPh3)4 catalyst and
K3PO4 base in N,N-dimethylformamide (DMF) at 90 °C afforded
bis-coupled product 1a in a 36% yield (entry 1, Table 1). This reac-
tion at 110 °C afforded a marginal change in yield up to 45% (entry
2, Table 1). Other solvents such as N,N-dimethylacetamide (DMA),
N-methylpyrrolidinone (NMP) did not improve the yield under
similar coupling conditions (entries 3 and 4, Table 1). The effect
of various bases was studied to check their efficacy. For example,
Cs2CO3 and Na2CO3 bases furnished 41% and 54% yields (entries 5
With optimized condition in hand, generality of this one-pot
bis-coupling process was checked using electronically different
BiAr3 reagents12 (Table 2). It is fascinating to see that the bis-cou-
plings using various BiAr3 reagents are facile to furnish a variety of
functionalized 9-(diarylmethylene)-9H-fluorenes in good to high
yields. For example, BiAr3 reagents substituted with various alkoxy
and methyl substituents furnished high product yields in short
Table 1
Screening conditionsa,b,c,d
Br
Br
[Pd]
Bi
+
3
(1 equiv)
(1.5 equiv)
(1.5 equiv)
1
1a
Entry
Catalyst (equiv)
Base (equiv)
Solvent
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
Pd(PPh3)4 (0.09)
PdCl2(PPh3)2 (0.09)
Pd(PPh3)4 (0.04)
Pd(PPh3)4 (0.02)
Pd(PPh3)4 (0.02)
Pd(PPh3)4 (0.02)
Pd(PPh3)4 (0.02)
Pd(PPh3)4 (0.02)
Pd(PPh3)4 (0.02)
Pd(PPh3)4 (0.02)
Pd(PPh3)4
K3PO4 (6)
K3PO4 (6)
K3PO4 (6)
K3PO4 (6)
Cs2CO3 (6)
K2CO3 (6)
Na2CO3 (6)
KOAc (6)
KOAc (6)
KOAc (6)
KOAc (6)
KOAc (4)
KOAc (3)
KOAc (2)
KOAc (1)
KOAc (4)
KOAc (4)
none
DMF
DMF
DMA
NMP
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
1
1
1
36e
45
35
34
41
78
54
79
76
82
77
82
81
55
52
81
79
35
–
none
KOAc
a
b
c
Coupling conditions: 9-(dibromomethylene)-9H-fluorene (0.375 mmol, 1.5 equiv), BiPh3 (0.25 mmol, 1 equiv), base, catalyst, solvent (3 mL), 110 °C.
Isolated yields.
Biphenyl as a minor side homo-coupling product was formed in all the reactions.
Mono phenylated product 9-benzylidene-9H-fluorene was also formed in some reactions in minor amounts.
At 90 °C.
d
e

164
M.L.N. Rao, P. Dasgupta / Tetrahedron Letters 53 (2012) 162–165
Table 2
One-pot bis-couplings with different triarylbismuthsa,b,c,d,e
Br
Br
R
R
Pd(PPh3)4 (0.02 equiv)
Bi
+
(1a-1o)
KOAc (4 equiv)
3
DMF, 110 oC, 1 h
R
1
(1 equiv)
(1.5 equiv)
(1.5 equiv)
Entry
1
Triarylbismuth
Product
Yield (%)
79
Entry
9
Triarylbismuth
Product
-PrO
Yield (%)
84
i
O
i-Pr
Bi
Bi
O
i-Pr
3
3
1a
1i
OMe
OMe OMe
s-BuO
MeO
Os-Bu
Bi
O
s-Bu
3
Bi
3
1j
2
69
10
62
1b
Me
Me
OMe
Bi
Bi
Me
F
Bi
Bi
Bi
OMe
3
3
3
4
93
66
11
12
87
76
1c
1k
F
F
n-BuO
On-Bu
O
O
n-Bu
3
3
1d
1l
F
F
F
3
Bi
O
O
3
5
6
59
44
13
73
1e
1f
1m
Cl
Cl
Cl
i
-BuO
O
i-Bu
Bi
Bi
O
i-Bu
3
Bi
Bi
3
1n
14
15
84
71
Cl
Cl
Me
Me
Me
Cl
3
1g
3
7
8
51
79
1o
EtO
OEt
Bi
OEt
3
1h
a
Coupling conditions: 9-(dibromomethylene)-9H-fluorene (0.375 mmol, 1.5 equiv), BiAr3 (0.25 mmol, 1 equiv), KOAc (1 mmol, 4 equiv), Pd(PPh3)4 (0.005 mmol,
0.02 equiv), DMF (3 mL), 110 °C, 1 h.
b
Isolated yields.
c
Biaryls as a minor side homo-coupling products were formed in all the reactions.
d
Mono arylated product 9-benzylidene-9H-fluorene was formed in some reactions in minor amounts.
e
All the product were identified by 1H NMR, 13C NMR, EI-HRMS and IR spectroscopic analyses.
reaction time. Triarylbismuths substituted with electron-with-
drawing halo substituents provided moderate yields. It is impor-
tant to note that electronically rich aryl boronic acids did not
fare well in the reported double Suzuki coupling process.3e How-
ever, it is highly satisfying to note that similar couplings with BiAr3
afforded good yields in an atom-efficient manner under present
conditions.
In summary, we have demonstrated a facile palladium cata-
lyzed protocol for an efficient synthesis of various functionalized
9-(diarylmethylene)-9H-fluorenes using triarylbismuths as multi-
coupling organometallic nucleophiles under palladium catalyzed
condition. These one-pot bis-couplings are fast and completed in
1 hour reaction time furnishing good to high yields. Given the
importance of 9-(diarylmethylene)-9H-fluorenes, this method is

M.L.N. Rao, P. Dasgupta / Tetrahedron Letters 53 (2012) 162–165
165
4. (a) Luisa, M.; Franco, T. M. B.; Herold, B. J.; Evans, J. C.; Rowlands, C. C. J. Chem.
Soc., Perkin Trans. 2 1988, 443–449; (b) Other references cited in 3e
5. Banerjee, M.; Emond, S. J.; Lindeman, S. V.; Rathore, R. J. Org. Chem. 2007, 72,
8054–8061.
expected to provide an easy access to a plethora of these molecular
entities in a facile manner.
6. (a) Donovan, P. M.; Scott, L. T. J. Am. Chem. Soc. 2004, 126, 3108–3112; (b) Paul,
G. C.; Gajewski, J. J. Synthesis 1997, 524–526.
Acknowledgments
7. Rao, M. L. N.; Jadhav, D. N.; Dasgupta, P. Org. Lett. 2010, 12, 2048–2051. and
references cited therein.
8. (a) Rao, M. L. N.; Venkatesh, V.; Banerjee, D. Synfacts 2008, 4, 406; (b) Rao, M. L.
N.; Banerjee, D.; Dhanorkar, R. J. Synfacts 2010, 8, 928.
We are greatful to the Department of Science and Technology
(DST), New Delhi for funding this work through Green Chemistry
programme (DST No. SR/S5/GC-11/2008). P.D. acknowledges the
Council of Scientific and Industrial Research (CSIR), New Delhi for
a research fellowship. We also thank Deepak N. Jadhav for a few
initial experiments.
9. Fang, Y.-Q.; Lifchits, O.; Lautens, M. Synlett 2008, 413–417.
10. Synthesis of 9-(dibromomethylene)-9H-fluorene, 1: to
a solution of 9-
fluorenone (2.0 g, 11.1 mmol) and CBr4 (5.5 g, 16.7 mmol) in CH2Cl2 (20 mL)
was added dropwise P(OEt)3 (5.6 mL, 33.3 mmol) in CH2Cl2 (10 mL) at 0 °C
under nitrogen atmosphere. The reaction was continued at 0 °C for 1 h
followed by rt, stirring for 3 h. The reaction mixture was diluted with CH2Cl2
(20 mL) and washed with water and extracted with CH2Cl2 (2 ꢀ 15 mL). The
organic layer was dried over anhydrous MgSO4 and concentrated. The crude
product thus obtained was treated with conc. HCl (8 mL) and glacial acetic acid
(8 mL) at 100 °C for 12 h. Reaction mixture was cooled to rt, and quenched with
saturated ice cold Na2CO3 solution. After neutralization, the reaction mixture
was extracted following usual procedure. The crude product was purified by
silica gel column chromatography with pet ether as eluent to afford product as
pure yellow crystalline solid (3.2 g, 86%).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.10.156.
References and notes
11. Barton, D. H. R.; Ozbalik, N.; Ramesh, M. Tetrahedron 1988, 44, 5661–5668.
12. Representative procedure: to an oven-dried 50 mL Schlenk tube, 9-
(dibromomethylene)-9H-fluorene (0.126 g, 0.375 mmol, 1.5 equiv), BiPh3
(0.110 g, 0.25 mmol, 1.0 equiv), KOAc (0.098 g, 1.0 mmol, 4.0 equiv),
Pd(PPh3)4 (0.0058 g, 0.005 mmol, 0.02 equiv) and DMF (3 mL) were added
under nitrogen atmosphere. The reaction mixture was stirred in a pre-heated
oil bath at 110 °C for 1 h. The contents were cooled to rt, and extracted with
ethyl acetate (15 mL ꢀ 3). The combined extract was treated with water, brine
and dried over anhydrous MgSO4 and concentrated. The crude mixture was
purified by silica gel column chromatography using petroleum ether as an
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eluent to obtain pure 9-(diphenylmethylene)-9H-fluorene in
a 79% yield
(0.098 g). The product was identified by 1H NMR, 13C NMR, EI-HRMS and IR
spectroscopic methods. In all the cases, isolated yields are calculated
considering 0.375 mmol of product as a 100% yield.