Palladium-catalyzed aerobic oxidative allylic C-H arylation of alkenes with polyfluorobenzenes

Article abstract of DOI:10.1039/c4cc02023e

An aerobic oxidative cross-coupling reaction of alkenes with polyfluorobenzenes, through palladium-catalyzed allylic C-H activation, is reported. This attractive route provides a new way to forge allylic C-C bonds of valuable products, in good yields, with high regioselectivity.

Full text of DOI:10.1039/c4cc02023e

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Palladium-catalyzed aerobic oxidative allylic C–H
arylation of alkenes with polyfluorobenzenes†
Cite this: Chem. Commun., 2014,
50, 7202
Huanfeng Jiang,* Wanfei Yang, Huoji Chen, Jianxiao Li and Wanqing Wu
Received 18th March 2014,
Accepted 15th April 2014
DOI: 10.1039/c4cc02023e
www.rsc.org/chemcomm
An aerobic oxidative cross-coupling reaction of alkenes with poly-
fluorobenzenes, through palladium-catalyzed allylic C–H activation, is
reported. This attractive route provides a new way to forge allylic C–C
bonds of valuable products, in good yields, with high regioselectivity.
Palladium-catalyzed oxidation reactions of alkenes continue to be an
active area of research. Representative reactions include Wacker-type
oxidation1 and oxidative difunctionalization.2,3 These reactions
proceed through an alkylpalladium(II) intermediate that forms
via nucleopalladation (Scheme 1a).4 In contrast to traditional
palladium-catalyzed oxidation of alkenes, a different reaction
selectivity involving oxidative allylic C–H bond functionalization
of alkenes has been developed and plays a vital role in organic
synthesis.5–11 The reaction is thought to proceed via substitution
of allylpalladium intermediates generated through allylic C–H
Scheme 1 Pd-catalyzed oxidative alkene functionalization.
Scheme 2 Palladium-catalyzed aerobic oxidative allylic C–H arylation.
cleavage (Scheme 1b).12 In this case, how to control the selectivity of oxygen as the sole oxidant, which avoids the environmentally
the palladium catalysts in oxidative alkene functionalization hazardous by-products obtained with other oxidants.15
remains challenging and rewarding.
At the outset of this study, allylcyclohexane (1a) and penta-
We have recently reported a new regioselective palladium- fluorobenzene (2a) were used as substrates to optimize the reaction
catalyzed oxidative allylic C–H oxygenation5d and carbonylation8 of conditions. To our delight, when 1a and 2a were treated with
alkenes with water and carbon monoxide (CO) as nucleophiles, Pd(OAc)2 (10 mol%) under a dioxygen atmosphere (1 atm) in DMSO
respectively. On the basis of these preliminary studies, we hypothe- at 100 1C for 24 h, this reaction produced a 28% NMR yield of 3a and
sized that electron-deficient polyfluoroarenes could be chosen as the Wacker oxidation product 4a was observed (Table 1, entry 1).
nucleophiles for the allylpalladium species, which would provide a Further screening of the solvents indicated that a mixed solvent
straightforward approach for direct allylic C–H arylation of alkenes system of DMSO–DMF (1 : 1) was found to benefit the reaction
for traditional Tsuji–Trost reaction protocols.13 Furthermore, poly- (Table 1, entries 6–16). Encouraged by this result, Ag2O and pivalic
fluoroarenes are key structural motifs found in various functional acid (PivOH) were selected as the additive because it was shown to be
molecules, such as pharmaceuticals, agrochemicals, liquid crystals, beneficial for the aerobic dehydrogenative cross-coupling reaction of
and electronic devices.14 Herein we describe the first example of pentafluorobenzene.16 Gratifyingly, treatment of 1a and 2a with
direct palladium-catalyzed aerobic oxidative allylic C–H arylation of Pd(OAc)2 under a dioxygen atmosphere (1 atm) in the presence of
alkenes with polyfluorobenzenes via twofold C–H functionalization 0.1 equiv. of Ag2O and 0.5 equiv. of PivOH afforded the desired C1
(Scheme 2). Moreover, the reaction proceeds by using molecular arylation 3a in 75% isolated yield with high regioselectivity (Table 1,
entry 7), while the absence of either Ag2O or PivOH gave unsatis-
School of Chemistry and Chemical Engineering, South China University of
factory results (Table 1, entries 8 and 9). The replacement of Ag2O
with other silver salts, such as Ag2CO3, AgF and AgOAc, could also
result in 3a, albeit in lower yields (Table 1, entries 10–12). Further-
more, the reaction temperature was also varied, and 120 1C gave the
best yield (entry 13). A lower yield of 3a was obtained when O2
Technology, Guangzhou 510640, China. E-mail: jianghf@scut.edu.cn;
Fax: +86 20-87112906; Tel: +86 20-87112906
† Electronic supplementary information (ESI) available: Experimental section,
characterization of all compounds, copies of 1H, 19F and 13C NMR spectra for
selected compounds. See DOI: 10.1039/c4cc02023e
7202 | Chem. Commun., 2014, 50, 7202--7204
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Table 1 Optimization of the reaction conditionsa
and 1-dodecene, underwent direct oxidative arylation at the C1
position to generate the corresponding linear (E)-allylpentafluoro-
benzene derivatives in moderate to high yields (3a–3c). More-
over, a variety of allyl arenes bearing electron-withdrawing or
electron-donating groups afforded the desired products in
moderate to good yields with high regioselectivity, and the
substituents at the para and ortho positions of the arene ring
did not affect the efficiencies (3d–3i).
Heteroaryl-substituted propenes such as 5-allylbenzo[d][1,3]-
dioxole and 2-allylthiophene also produced the desired products
in good yields (3k, 3j). Interestingly, 2-naphthylpropene gave the
corresponding product in 81% yield (3l). It is noteworthy that
2,3-disubstituted propene performed well in this transformation,
leading to the corresponding trisubstituted product being produced
in good yields (3m). Unexpectedly, a-methyl styrene and its derivatives
proceeded efficiently under the optimized conditions by affording
double bond isomerization products as major products (3n–3q).
Next, the scope of polyfluoroarenes was examined in this
reaction (Table 3). Variations of fluoroarenes containing 2–4 fluor-
ines were investigated, comparable yields of compounds 3r, 3s and
3t were provided at 120 1C with use of 3.0 equiv. of fluoroarenes.
Furthermore, other fluoroarenes, such as 1,2,4,5-tetrafluoro-3-(tri-
fluoromethyl)benzene, were also good coupling partners under the
present reaction conditions; thus a good yield was obtained as well.
Notably, the tetrafluoroarene bearing a –OMe group was tested with
Yieldb (%)
T (1C) (3a : 4a)
Entry Solvent
Additive (equiv.)
1
2
3
4
DMSO
CH3CN
Dioxane
Toluene
DMF
—
—
—
—
—
100
100
100
100
100
100
100
100
100
28(83 : 17)
17(30 : 70)
21(12 : 88)
23(10 : 90)
31(60 : 40)
42(85 : 15)
75(99 : 1)
44(95 : 5)
63(84 : 16)
46(92 : 8)
28(93 : 7)
29(95 : 5)
88(99 : 1)
72(98 : 2)c
21(98 : 2)d
N.D.e
5
6
7
8
9
DMSO–DMF (1 : 1) —
DMSO–DMF (1 : 1) Ag2O (0.1), PivOH (0.5)
DMSO–DMF (1 : 1) PivOH (0.5)
DMSO–DMF (1 : 1) Ag2O (0.1)
10
11
12
13
14
15
16
DMSO–DMF (1 : 1) Ag2CO3 (0.1), PivOH (0.5) 100
DMSO–DMF (1 : 1) AgF (0.1), PivOH (0.5) 100
DMSO–DMF (1 : 1) AgOAc (0.1), PivOH (0.5) 100
DMSO–DMF (1 : 1) Ag2O (0.1), PivOH (0.5)
DMSO–DMF (1 : 1) Ag2O (0.1), PivOH (0.5)
DMSO–DMF (1 : 1) Ag2O (0.1), PivOH (0.5)
DMSO–DMF (1 : 1) Ag2O (0.1), PivOH (0.5)
120
140
120
120
a
Reaction conditions (unless otherwise specified): 1a (0.5 mmol),
2a (3.0 equiv.), DMF–DMSO (v/v = 1 : 1, 2 mL, DMSO must be stored
b
with the powder of 4 Å molecular sieves), O2 (1 atm), 24 h. Determined
by 1H NMR or GC analysis of the crude product. Pentafluorobiphenyl
c
d
e
was detected. Under air. In the absence of Pd(OAc)2.
(1 atm) was replaced with air (entry 15). Finally, the absence of a several allyl arenes, and comparable yields of the desired products
Pd-catalyst did not give any desired product (Table 1, entry 16).
With the optimized conditions established, the scope of the
were obtained (3v–3y).
Experimental support for an allylic C–H activation mechanism
terminal alkenes was first examined. As summarized in Table 2, was obtained by preparing p-allylpalladium complex 7 and investi-
terminal alkyl alkenes such as 4-phenyl-1-butene, allylcyclohexane gating its reactivity with fluorobenzene 2a (Scheme 3). When the
reaction was performed in the presence of PivOH (1.5 equiv.) and
Ag2O (1.2 equiv.), product 3c was formed in 53% yield. In the
absence of Ag2O/PivOH or Ag2O, a trace amount of 3c was observed,
while 3c was only obtained in 17% yield for the reaction without
PivOH. This demonstrates that the silver salt plays a pivotal role in
the catalytic cycle. These results are consistent with a mechanism
involving p-allylpalladium intermediates and suggest that PivOH
facilitates nucleophilic attack on the p-allylpalladium species.13b
Table 2 Substrate scope of alkenesa
Table 3 Substrate scope of fluoroarenesa
a
a
Reaction conditions:
1 (0.5 mmol), 2a (1.5 mmol), Pd(OAc)2
Reaction conditions: 1 (0.5 mmol), 2 (1.5 mmol), Pd(OAc)2 (10 mol%),
(10 mol%), Ag2O (0.1 equiv.) and PivOH (0.5 equiv.) in DMSO–DMF
(2 mL, 1 : 1) under O2 (1 atm) at 120 1C for 24 h; isolated yield; the ratio
of the two isomers was determined by 1H NMR.
Ag2O (0.1 equiv.) and PivOH (0.5 equiv.) in DMSO–DMF (2 mL, 1 : 1)
under O2 (1 atm) at 120 1C for 24 h; isolated yield; the ratio of the two
isomers was determined by 1H NMR.
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S2012040007088), and the Fundamental Research Funds for
the Central Universities (2014ZP0004 and 2014ZZ0046).
Notes and references
1 (a) J. Smidt, W. Hahner, R. Jira, J. Sedlmeier, R. Sieber and
R. Ru¨ttingger, Angew. Chem., 1959, 71, 176; (b) J. Tsuji, Synthesis,
1984, 369; (c) J. M. Takacs and X. T. Jiang, Curr. Org. Chem., 2003,
7, 369; (d) J. Tsuji, Palladium Reagents and Catalysts, Wiley, Chiche-
ster, 2004; (e) R. Jira, Angew. Chem., Int. Ed., 2009, 48, 9034;
( f ) J. A. Keith and P. M. Henry, Angew. Chem., Int. Ed., 2009, 48, 9038.
2 For selected review articles: (a) R. I. McDonald, G. Liu and S. S. Stahl,
Scheme 3 Experiments for mechanistic studies.
˜
Chem. Rev., 2011, 111, 2981; (b) K. Munz, Angew. Chem., Int. Ed.,
2009, 48, 9412; (c) K. H. Jensen and M. S. Sigman, Org. Biomol.
˜
Chem., 2008, 6, 4083; (d) A. Minatti and K. Munz, Chem. Soc. Rev.,
2007, 36, 1142; (e) V. Kotov, C. C. Scarborough and S. S. Stahl, Inorg.
˜
Chem., 2007, 46, 1910; ( f ) B. Jacques and K. Munz, in Catalyzed
Carbon-Heteroatom Bond Formation, ed. A. K. Yudin, Wiley-VCH,
Weinheim, 2010, pp. 119–135.
3 For our contributions to the palladium-catalyzed oxidative defunc-
tionalization of alkenes, see: (a) A. Wang, H. Jiang and H. Chen,
J. Am. Chem. Soc., 2009, 131, 3846; (b) A. Wang and H. Jiang, J. Org.
Chem., 2010, 75, 2321; (c) A. Wang, H. Jiang and X. Li, J. Org. Chem.,
2011, 76, 6958; (d) X. Ji, H. Huang, W. Wu, H. Jiang and H. Chen,
J. Am. Chem. Soc., 2013, 135, 5286.
4 For reviews, see: (a) P. M. Henry, in Palladium Catalyzed Oxidation of
Hydrocarbons, ed. D. Reidel, The Netherlands, Dordrecht, 1980, vol. 2;
¨
(b) J. E. Backvall, Acc. Chem. Res., 1983, 16, 335; (c) E. Negishi, in
Scheme 4 Plausible reaction mechanism.
Handbook of Organopalladium Chemistry for Organic Synthesis, ed.
E. Negishi, Wiley, New York, vol. 2, 2002; (d) R. Jira, in Applied Homo-
geneous Catalysis with Organometallic Compounds, ed. B. Cornils and
W. A. Herrmann, Wiley-VCH, Weinheim, Germany, 2nd edn, 2002,
p. 386; (e) M. S. Sigman and M. J. Schultz, Org. Biomol. Chem., 2004,
2, 2551; ( f ) B. M. Stoltz, Chem. Lett., 2004, 33, 362; (g) L. F. Tietze, H. Ila
and H. P. Bell, Chem. Rev., 2004, 104, 3453; (h) E. M. Beccalli, G. Broggini,
M. Martinelli and S. Sottocornola, Chem. Rev., 2007, 107, 5318;
(i) K. M. Gligorich and M. S. Sigman, Chem. Commun., 2009, 3854.
5 (a) E. M. Stang and M. C. White, Nat. Chem., 2009, 1, 547;
(b) A. N. Campbell, P. B. White, L. A. Guzei and S. S. Stahl, J. Am. Chem.
Soc., 2010, 132, 15116; (c) N. A. Vermeulen, J. H. Delcamp and
M. C. White, J. Am. Chem. Soc., 2010, 132, 11323; (d) H. Chen,
H. Jiang, C. Cai, J. Dong and W. Fu, Org. Lett., 2011, 13, 992;
(e) P. E. Gormisky and M. C. White, J. Am. Chem. Soc., 2011, 133, 12584.
6 (a) S. Lin, C. X. Song, G. X. Cai, W. H. Wang and Z. J. Shi, J. Am.
According to the experimental results and by referring to the
leading references (12,13b and 16) the mechanism is proposed in
Scheme 4. First, intermediate I is formed through the coordination
of olefin to palladium. Then, there is a competition between allylic
C–H activation and the Wacker process in the following step. The
addition of PivOH affects the selectivity and facilitates the allylic C–H
activation, leading to p-allylpalladium species II via an electrophilic
allylic C–H cleavage by the Pd(II) catalyst. Then, p-allylpalladium
intermediate II reacts with intermediate III, which was formed by the
deprotonation of polyfluoroarene with silver salts, by metal exchange
to generate a Pd–(polyfluoroaryl) complex IV. Finally, reductive
elimination and reoxidation by O2 regenerate the active Pd(II)Ln
species.
In conclusion, we have developed an efficient and straightforward
regioselective Pd-catalyzed method for aerobic oxidative allylic C–H
direct arylation of alkenes with polyfluorobenzenes, which represents
the most atom-efficient approach for the creation of allyl–aryl bonds,
and the preparation of allylic polyfluoroarene derivatives of interest
in both life and materials science. Various aryl and heteroaryl
¨
Chem. Soc., 2008, 130, 12901; (b) A. K. Persson and J.-E. Backvall,
Angew. Chem., Int. Ed., 2010, 49, 4624; (c) A. J. Young and
M. C. White, J. Am. Chem. Soc., 2008, 130, 14090; (d) A. J. Young
and M. C. White, Angew. Chem., Int. Ed., 2011, 50, 6824; (e) L. Li,
Q.-Y. Chen and Y. Guo, Chem. Commun., 2013, 49, 8764.
7 (a) G. Liu, G. Yin and L. Wu, Angew. Chem., Int. Ed., 2008, 47, 4733;
(b) S. A. Reed, A. R. Mazzotti and M. C. White, J. Am. Chem. Soc.,
2009, 131, 11701; (c) G. Yin, Y. Wu and G. Liu, J. Am. Chem. Soc.,
2010, 132, 11978; (d) C. Jiang, D. J. Covell, A. F. Stepan,
M. S. Plummer and M. C. White, Org. Lett., 2012, 14, 1386.
8 H. Chen, C. Cai, X. Liu, X. Li and H. Jiang, Chem. Commun., 2011,
47, 12224.
´
9 J. M. Larsson, T. S. N. Zhao and K. J. Szabo, Org. Lett., 2011, 13, 1888.
alkenes, as well as aliphatic alkenes, produced the expected allylated 10 E. M. Stang and M. C. White, J. Am. Chem. Soc., 2011, 133, 14892.
11 M.-G. Braun and A. G. Doyle, J. Am. Chem. Soc., 2013, 135, 12990.
12 C. Engelin, T. Jensen, S. Rodriguez-Rodriguez and P. Fristrup, ACS
polyfluoroarenes. Undoubtedly, this is a valuable complementary
method to the well-known Tsuji–Trost reaction, from an atom-
Catal., 2013, 3, 294.
economic and environmental perspective. Further investigations 13 (a) S. Fan, F. Chen and X. Zhang, Angew. Chem., Int. Ed., 2011, 50, 5918;
(b) Y.-B. Yu, S. Fan and X. Zhang, Chem. – Eur. J., 2012, 18, 14643.
14 (a) K. Muller, C. Faeh and F. Diederich, Science, 2007, 317, 1881;
are focused on expanding the scope of this transformation and
elucidating the detailed mechanism.
(b) H. Amii and K. Uneyama, Chem. Rev., 2009, 109, 2119.
We are grateful to the National Natural Science Foundation 15 For general reviews see: (a) T. Punniyamurthy, S. Velusamy and
J. Iqbal, Chem. Rev., 2005, 105, 2329; (b) Z. Shi, C. Zhang, C. Tang
and N. Jiao, Chem. Soc. Rev., 2012, 41, 3381; (c) W. Wu and H. Jiang,
Acc. Chem. Res., 2012, 45, 1736.
of China (21172076 and 21202046), the National Basic Research
Program of China (973 Program) (2011CB808600), the Guang-
dong Natural Science Foundation (10351064101000000 and 16 C.-Y. He, Q.-Q. Min and X. Zhang, Organometallics, 2012, 31, 1334.
7204 | Chem. Commun., 2014, 50, 7202--7204
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