Efficient palladium-catalyzed C(sp2)-H activation towards the synthesis of fluorenes

Article abstract of DOI:10.1039/c6nj02033j

A facile protocol for the synthesis of fluorene derivatives has been developed through palladium-catalyzed cyclization of 2′-halo-diarylmethanes via activation of arylic C-H bonds. The reactions occurred smoothly and allowed both electron-rich and electron-deficient substrates to convert into their corresponding fluorenes in good to excellent yields. Studies revealed that this Pd-catalyzed cyclization was also available for the substrates of 2′-chloro-diarylmethanes and no catalyst poisoning occurred for 2′-iodo-diphenylmethane.

Full text of DOI:10.1039/c6nj02033j

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Efficient palladium-catalyzed C(sp2)–H activation
towards the synthesis of fluorenes†
Cite this:DOI: 10.1039/c6nj02033j
Juan Song,*a Yali Li,a Wei Sun,b Chenglong Yi,a Hao Wu,a Haotian Wang,a
Keran Ding,a Kang Xiaoa and Chao Liu*b
Received (in Montpellier, France)
29th June 2016,
Accepted 22nd September 2016
DOI: 10.1039/c6nj02033j
www.rsc.org/njc
A facile protocol for the synthesis of fluorene derivatives has been
developed through palladium-catalyzed cyclization of 20-halo-
diarylmethanes via activation of arylic C–H bonds. The reactions
occurred smoothly and allowed both electron-rich and electron-
deficient substrates to convert into their corresponding fluorenes in
good to excellent yields. Studies revealed that this Pd-catalyzed
cyclization was also available for the substrates of 20-chloro-
diarylmethanes and no catalyst poisoning occurred for 20-iodo-
diphenylmethane.
Scheme 1 Different intermediates formed in Pd-catalyzed cyclization to
construct fluorene derivatives via C–H bond activation.
The utility of methylene-bridged polyarenes in materials science,
such as light-emitting diodes, field-effect transistors and so on,1–3
has prompted intense research directed at discovering efficient a new C(sp2)–C(sp3) bond will be formed via intermediate A22 or
and high-yielding methods for their preparation. Among this B23 in the reaction. 2-Methyl-20-palladabiphenyl (intermediate A)
class of compounds, fluorene, as an excellent scaffold for organic undergoes cyclization through benzylic C–H bond activation
photoelectric materials, is the most representative structural (type I), and alternatively, intermediate B through aryl C–H bond
motif.4–9 The traditional strategies to synthesize fluorene derivatives activation. The crowded environment and the short distance
include Friedel–Crafts-type reactions,10–14 radical cyclization,15–18 between the palladium moiety and the methyl group or the aryl
and transition metal-mediated cyclization.19–26 Comparatively, group cause these processes to be more efficient. However, if a
because of its simplicity, cleanliness and atom economy, transi- diphenylmethane type compound is used as the reactant, the
tion metal-catalyzed cyclization, through a C–H bond activation reaction proceeds via aryl C–H bond activation via intermediate
with subsequent C–C bond formation,27–29 has emerged as the C.24–26 Differing from intermediate A and B, in intermediate C,
most efficient strategy and palladium is the most widely used due to the existence of a methylene group between two phenyl
catalyst which has been extensively investigated. Of these syn- rings, the distance between the palladium moiety and the aryl
thetic procedures, closing the central five-membered ring is the group is stretched which makes the C–H bond activation more
key step in most employed strategies. As shown in Scheme 1, challenging without a directing group or atom.
according to different intermediates, Pd-catalyzed cyclizations
To date, most of the research studies have focused on
which proceed via C–H bond activation can be classified into biphenyl type reactants. Only a few examples were reported for
three types. If biphenyl type compounds are used as reactants, diphenylmethane type substrates in the literature. In 2010, Wu
and co-workers reported only the unexpected product (1-methyl-
a Key Laboratory for Organic Electronics and Information Displays,
Institute of Advanced Materials, Nanjing University of Posts and Telecommunications,
Nanjing, 210023, P. R. China. E-mail: iamjsong@njupt.edu.cn
b State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP),
Chinese Academy of Sciences, Lanzhou, 730000, P. R. China.
E-mail: chaoliu@licp.cas.cn
fluorene) by the treatment of (2-bromophenyl)-2-tolylmethane
with Pd(OAc)2 in the presence of a bulk NHC ligand (IPr) for
the activation of benzylic C–H bonds.22 Furthermore, Fagnou and
co-workers developed a new palladium catalyzed direct arylation
reaction with an aryl halide in 2006. In his report, also as a special
case, fluorene was obtained when 20-iodo-diphenylmethane was
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nj02033j used as the substrate in the presence of Pd(OAc)2, PCy3-HBF4,
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Ag2CO3, and K2CO3 in DMA.24–26 Herein, we report our newly PivOCs in THF (2 mL) at 120 1C for 12 h. This procedure provided
developed palladium-catalyzed direct arylation via C–H activa- fluorene (2a) in 90% isolated yield.
tion adopting diphenylmethane type reactants for the synthesis
of fluorene derivatives.
The scope of the cyclization with 20-halo-diarylmethanes was
outlined in Table 2. All the employed substrates bearing either
In the previously reported work of Fagnou’s group, 0.5 equiv. electron-withdrawing groups such as –F (1c, 1l, 1w), –Cl (1e,
of Ag2CO3 was necessary in the intramolecular cyclization of 1i, 1m), and –CF3 (1f) or electron-donating groups such as –Me
20-iodo-diphenylmethane catalyzed by Pd(OAc)2. They established (1d, 1g, 1n) and –OMe (1b, 1h, 1k, 1v) were well tolerated and
that the catalyst poisoning occurred with the accumulation of proceeded smoothly to afford their corresponding products
iodide anions in the reaction mixture and could be overcome by in good to excellent yields. This reaction was also effective for
the addition of silver salts. Then, was the silver salt necessary 2-(2-bromobenzyl) thiophene (1j) and produced the desired
if the aryl iodide was replaced by aryl bromide? Accordingly, fluorene (2j) in moderate yield (Table 2, entry 10). These experi-
under the reaction conditions described in Fagnou’s work, mental results indicated that there was only a weak electronic
20-bromo-diphenylmethane was treated with Pd(OAc)2, PCy3, effect and steric effect for the transformation in the reaction.
and K2CO3 in DMA at 130 1C. Disappointedly, the yield of However, for 20-bromo-300-substituted-diphenyl methanes (1k, 1l,
fluorene was only 35%. This result prompted us to initiate 1m, 1n), the electronic effect and steric effect had a great influence
our efforts on a new efficient palladium-catalyzed cyclization of on selectivity for this transformation. 20-Bromo-300-methoxy-
20-halo-diarylmethanes for the synthesis of fluorene derivatives. diphenyl methane (1k) and 20-bromo-300-methyl-diphenyl methane
Solvent screens were first performed with 20-bromo-diphenyl- (1n) gave more 2-substituted fluorene than 4-substituted fluorene
methane in the presence of 3 mol% Pd(OA)2, 6 mol% of PCy3, (Table 2, entries 11 and 14). In contrast, 20-bromo-300-fluoro-
3.0 equiv. of K2CO3 and 1.0 equiv. of PivOH at 120 1C. The results diphenyl methane (1l) and 20-bromo-300-chloro-diphenyl methane
were outlined in Table 1; DMF (Table 1, entry 1) and toluene (1m) afforded more 4-substituted fluorine unexpectedly (Table 2,
(Table 1, entry 2) gave inferior results in the reaction. The optimal entries 12 and 13). The selectivity was improved by increasing the
solvent was THF (Table 1, entry 4) and gave the product fluorene steric hindrance of the substituent at the 300-position. For example,
in 96% yield (determined by 1H NMR analysis) which was better 2s could be synthesized with high efficiency and high selectivity
than 1,4-dioxane (Table 1, entry 3). The influence of the base by the cyclization of 1s (Table 2, entry 19). A more challenging
was also examined (Table 1). It was revealed that both Cs2CO3 double annulation of this palladium method was also attempted
and Na2CO3 were ineffective (Table 1, entries 6 and 7) for this using 1t as a substrate and an enhanced p-conjugation compound
cyclization reaction. PivOCs provided a comparable result to 2t was synthesized conveniently (Table 2, entry 20). They were
K2CO3/PivOH and a slightly higher yield (98%) could be obtained useful molecules in organic electronic materials. The reactivity of
(Table 1, entry 8). However, the reaction was obviously sluggish at aryl C–Cl is generally considered to be inferior in coupling
lower temperature (Table 1, entries 10 and 11). We reasoned that reaction and use of aryl chlorides is rare despite the fact that
the elevated reaction temperature could facilitate the C–H activa- aryl chlorides are more readily available and less expensive.
tion processes. The optimum reaction conditions thus far being In subsequent studies, we were glad to discover that aryl C–Cl
developed employed 1.0 equiv. of 20-bromo-diphenylmethane (1a) (1u, 1v, 1w) also reacted smoothly to afford their corresponding
(0.5 mmol), 3 mol% of Pd(OAc)2, 6 mol% of PCy3, and 3.0 equiv. of products in good to excellent yields (Table 2, entries 1–3).
Interestingly, the C–Cl bond was tolerated in the substrates of
20-bromo-diarylmethanes (1e, 1i, 1m, 1o, 1p, 1q, 1r), and more
Table 1 Optimization of conditions for palladium catalyzed direct aryla-
tion via C–H activationa
significantly, the preservation of C–Cl bonds offered the oppor-
tunity for further functionalizations. More wonderfully, 20-iodo-
diphenylmethane (1y) was also well tolerated and afforded
fluorene (2a) in 83% yield (Table 2, entry 1) which indicated
that no catalyst poisoning occurred in our reaction system.
In summary, a facile protocol for the synthesis of fluorene
Entry
Base
Solventd
T (1C)
Yieldb (%)
derivatives has been developed through palladium-catalyzed
cyclization of 20-halo-diarylmethanes via activation of aryl C–H
bonds. The reactions occurred smoothly and allowed both
electron-rich and electron-deficient substrates to convert into
their corresponding fluorenes in good to excellent yields. Studies
revealed that this Pd-catalyzed cyclization was also available
for the substrates of 20-chloro-diarylmethanes and no catalyst
poisoning occurred for 20-iodo-diphenylmethane in our reac-
tion system. This approach could afford a diversity of fluorene-
based molecular architectures and therefore would provide more
opportunity for research on the properties of material molecules.
Further investigation on the application of this chemistry is
currently underway in our laboratory.
1
2
3
4
5
6
7
8
K2CO3/PivOH
K2CO3/PivOH
K2CO3/PivOH
K2CO3/PivOH
K3PO4/PivOH
Cs2CO3/PivOH
Na2CO3/PivOH
PivOCs
DMF
120
120
120
120
120
120
120
120
120
100
80
48
31
85
96
Toluene
1,4-Dioxane
THF
THF
THF
THF
THF
THF
THF
51
Trace
25
98 (90c)
81
9
10
11
PivOK
PivOCs
PivOCs
94
54
THF
a
Reaction conditions: 1 (0.5 mmol, 1.0 equiv.), 3 mol% of Pd(OAc)2,
6 mol% of PCy3, base (1.5 mmol, 3.0 equiv.), PivOH (0.3 mmol, 1.0 equiv.),
solvent (2 mL). Yields were determined by 1H NMR. Isolated yield.
b
c
d
DMF = N,N-dimethylformamide, THF = tetrahydrofuran.
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Table 2 Synthesis of fluorenes by palladium-catalyzed C(sp2)–H activationa
Yield
(%)
Entry Substrate
1
Product
Entry Substrate
Product
Yield (%)
94
90/85/83 11
2ka/2kb =
5.4 : 4.6
84
2la/2lb =
1 : 9
2
90/64
94/90
64
12
87
2ma/2mb
=
2.8 : 5
3
13c
14c
78
2na/2nb
=
4b
2.3 : 1
5
6
91
99
15
16
81
88
7b
56
93
93
17
18
19
84
89
99
8
9
10
65
20
99
a
Reaction was conducted with 1 (0.50 mmol), Pd(OAc)2 (3 mol%), PCy3 (6 mol%), PivOCs (3.0 equiv.) and THF (2 mL) at 120 1C for 12 h. Isolated
yield. Yields were determined by 1H NMR. A mixture of the cyclization product and the hydrodebromination byproduct. A mixture of two
b
c
regioisomers (the ratio of the products was determined by 1H NMR).
8.4 mg) was added in a glove box under an argon atmosphere.
Experimental section
1-Benzyl-2-bromobenzene (0.50 mmol, 124.0 mg) and THF
To an oven dried sealed tube containing PivOCs (1.5 mmol, (2.0 mL) were injected into the reaction tube via a syringe. The
349.0 mg) and Pd(OAc)2 (0.015 mmol, 3.4 mg), PCy3 (0.030 mmol, mixture was allowed to stir at room temperature for 5 minutes
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