Silver-catalyzed decarboxylative acylfluorination of styrenes in aqueous media

Article abstract of DOI:10.1039/c4cc02800g

A mild catalytic decarboxylative acylfluorination of styrenes with α-oxocarboxylic acids and Selectfluor is reported. This operationally simple and efficient method provides a fundamentally novel approach toward the synthesis of β-fluorinated 3-aryl ketones with a wide range of substrate scope.

Full text of DOI:10.1039/c4cc02800g

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Silver-catalyzed decarboxylative acylfluorination
of styrenes in aqueous media†
Cite this: Chem. Commun., 2014,
50, 7382
Hua Wang, Li-Na Guo and Xin-Hua Duan*
Received 16th April 2014,
Accepted 19th May 2014
DOI: 10.1039/c4cc02800g
www.rsc.org/chemcomm
A mild catalytic decarboxylative acylfluorination of styrenes with tandem decarboxylative fluorination process.1 Encouraged by our
a-oxocarboxylic acids and Selectfluor is reported. This operationally recent success in the oxidative coupling of a-oxocarboxylic acids7
simple and efficient method provides a fundamentally novel approach and in the oxidative difunctionalization of activated alkenes,8 we
toward the synthesis of b-fluorinated 3-aryl ketones with a wide range turned our attention to much more challenging oxidative difunction-
of substrate scope.
alization of unactivated alkenes with a-oxocarboxylic acids. Herein,
we report a mild catalytic decarboxylative acylfluorination of styrenes
The development of C–F bond forming reactions is one of the into the corresponding benzylic fluorides. This novel method pro-
most important research fields in organic chemistry because it vides a complementary approach to synthesize b-fluorinated 3-aryl
provides an appealing way for the synthesis of valuable organo- ketones,4d which have widespread applications in pharmaceuticals,
fluorine compounds.1 In this field, the catalytic site-specific con- fine chemicals and materials.9
struction of C(sp3)–F bonds is among the most challenging of the
Initially, we investigated the reaction of styrene (1a) and
C–F bond forming reactions, and some efficient methods have phenylglyoxylic acid (2a) with Selectfluor. Treatment of 1a, 2a and
been developed in the past few years.2 One of the most common Selectfluor with 20 mol% AgNO3 in EtOAc/H2O (1 : 1) at 50 1C for
methods is the fluorination of unsaturated carbon–carbon bonds, 12 h led to the desired 3-fluoro-1,3-diphenylpropanone (3a) in 23%
such as oxyfluorination,3a–c aminofluorination,3d–i hydrofluorina- yield (Table 1, entry 1). Among the homogeneous reaction solvents,
tion,3j–l carbofluorination,3m,n phosphonofluorination3o and azido- such as CH3CN/H2O, DMF/H2O and acetone/H2O, acetone/H2O
fluorination3p of alkenes. Recently, another important progress gave the best yield (entries 2–4). When the reaction was carried out
has also been made in the formation of C(sp3)–F bonds based on
the direct fluorination of unactivated sp3 C–H bonds.4 Although
some great advances have been achieved in this field, exploitation
Table 1 Optimization of the reaction conditionsa
of the new catalytic C(sp3)–F bond forming reaction still remains a
significant challenge for synthetic chemists. Especially, a catalytic
reaction capable of utilizing environmentally friendly and inexpen-
sive substrates and proceeding under mild conditions is still
Yieldb (%)
highly desirable.2
Entry
Additive (equiv.)
Solvent
In recent years, transition metal-catalyzed decarboxylative cross-
coupling reactions have received much attention, owing to the
prospects of the use of stable and readily available carboxylic acids
and CO2 as the sole waste product.5 Very recently, several decarbox-
ylative fluorination reactions of carboxylic acids and anhydrides to
construct C(sp3)–F bonds have been developed.6 However, there are
no reports for the formation of C(sp3)–F bonds via an intermolecular
1
2
3
4
5
6
7
8
—
—
—
—
EtOAc/H2O (1 : 1)
CH3CN/H2O (1 : 1)
DMF/H2O (1 : 1)
23c
18c
45c
47c
57
68
53
46
53
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
Acetone/H2O (1 : 1)
—
Na2SO4 (1)
K2SO4 (1)
(NH4)2SO4 (1)
BaSO4 (1)
MgSO4 (1)
CuSO4 (1)
NaHCO3 (1)
9
10
11
12
52
n.r.d
40 (41)e
Department of Chemistry, School of Science and MOE Key Laboratory for
Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi’an Jiaotong
University, Xi’an 710049, China. E-mail: duanxh@mail.xjtu.edu.cn
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c4cc02800g
a
Reaction conditions: AgNO3 (20 mol%), 1a (0.2 mmol, 1 equiv.), 2a
(0.3 mmol, 1.5 equiv.), Selectfluor (0.3 mmol, 1.5 equiv.), solvent (1 mL), rt,
12 h. Yields of isolated products. 50 1C. n.r. = no reaction. Yield of
chalcone (3a0) is given in parentheses.
b
c
d
e
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Table 3 Scope of unactivated terminal alkenes
at room temperature, the yield was increased to 57% (entry 5). To
our delight, using 1 equiv. of Na2SO4 as an additive improved the
yield of 3a to 68% (entry 6). Other sulfate additives proved to be less
efficient (entries 7–10), and no coupling product was observed in
the presence of CuSO4 (entry 11). However, when NaHCO3 was
added, 3a was isolated in 40% yield along with a considerable
amount of chalcone 3a0 as a byproduct (41%, entry 12).10
To probe the scope and limitations of the reaction, we first
investigated the reactions of 1a and Selectfluor with different
a-oxocarboxylic acids (Table 2). As shown in Table 2, both electron-
rich and electron-poor p-substituents on the phenylglyoxylic acid
gave the desired products in moderate to good yields (3b–g). Notably,
the formation of b-fluorinated 3-aryl ketones 3 was also found to be
compatible with synthetically valuable functional groups on the aryl
moiety of the a-oxocarboxylic acids (3d–g). To further explore the
generality of this transformation, we carried out the reaction using
2-thienylglyoxylic acid and b-naphthyloxoacetic acid, and the desired
products 3h and 3i were isolated in 39% and 52% yields, respectively.
Unfortunately, only trace amounts of the desired products were
observed when o-methyl phenylglyoxylic acid and a-naphthyloxo-
acetic acid were used, probably due to steric hindrance.
We then extended this reaction to a wide variety of commer-
cially available styrene derivatives 1 (Table 3). Styrene derivatives,
bearing an electron-donating and -withdrawing group at either the
4-, 3- or 2-position of the aromatic ring, afforded the corresponding
products 4a–f in moderate to good yields. In the cases of 4d–f, the
low yields were obtained which were attributed to the low conver-
sion of 1 and other unidentified byproducts were also detected.
Gratifyingly, a-methylstyrene derivatives 1g–j having a methyl
The Ag-catalyzed decarboxylation of a-keto acids, leading to
or halogen atom on the aromatic ring, gave the corresponding acyl radicals in the presence of persulfates, and coupling with
b-fluorinated 3-aryl ketones in moderate yields (4g–j). However, other partners have previously been reported in the literature.11
aliphatic terminal alkenes, such as 1k and 1l were not compatible The reaction of 1a and 2a with Selectfluor could also be inhibited
with the reaction conditions.
by addition of radical scavengers, such as TEMPO and BHT
(eqn (1) and (2)), which implies that the reaction probably
proceeded via a free radical process. Furthermore, the coupling
of 1a and 2a was conducted with AgNO3 (20 mol%), K2S2O8
(2 equiv.) and KF (2 equiv.) in actone/H2O, no desired product
3a was detected (for details see the ESI†), suggesting that a new
reaction pathway other than the one involving a common Ag(II)
intermediate11 might be involved. Based on these results, a
plausible mechanism was proposed as shown in Scheme 1. Firstly,
the oxidation of Ag(I) by Selectfluor generates an Ag(III)–F inter-
mediate.3h,o,6b Secondly, a-keto acids are converted into the
corresponding nucleophilic acyl radicals in the presence of
Ag(III),6b,11 and then the acyl radical attacks the CQC double
bond of styrenes 1 to afford the alkyl radical. Finally, the fluorine
atom transfers from Ag(II)–F to the radical to give the fluoride
products and regenerates the Ag(I) catalyst.
Table 2 Scope of a-oxocarboxylic acids
(1)
(2)
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In summary, we have developed a novel Ag-catalyzed decarboxyl-
ative acylfluorination of styrenes for the synthesis of b-fluorinated
3-aryl ketones from a-oxocarboxylic acids and Selectfluor under
mild conditions. This method provides ready access to benzylic
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7384 | Chem. Commun., 2014, 50, 7382--7384
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