Silver-Catalyzed Decarboxylative Allylation of Aliphatic Carboxylic Acids in Aqueous Solution

Article abstract of DOI:10.1021/acs.orglett.6b00802

Direct decarboxylative radical allylation of aliphatic carboxylic acids is described. With K₂S₂O₈ as the oxidant and AgNO₃ as the catalyst, the reactions of aliphatic carboxylic acids with allyl sulfones in aqueous CH₃CN solution gave the corresponding alkenes in satisfactory yields under mild conditions. This site-specific allylation method is applicable to all primary, secondary, and tertiary alkyl acids and exhibits wide functional group compatibility.

Full text of DOI:10.1021/acs.orglett.6b00802

Letter
pubs.acs.org/OrgLett
Silver-Catalyzed Decarboxylative Allylation of Aliphatic Carboxylic
Acids in Aqueous Solution
†
‡
‡
,§
Lei Cui, He Chen, Chao Liu, and Chaozhong Li*
†
Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
‡
Key Laboratory of Organofluorine Chemistry and Collaborative Innovation Center of Chemistry for Life Sciences, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
§
School of Chemical Engineering, Ningbo University of Technology, No. 89 Cuibai Road, Ningbo 315016, China
S Supporting Information
*
ABSTRACT: Direct decarboxylative radical allylation of
aliphatic carboxylic acids is described. With K S O as the
2
2
8
oxidant and AgNO as the catalyst, the reactions of aliphatic
3
carboxylic acids with allyl sulfones in aqueous CH CN solution
3
gave the corresponding alkenes in satisfactory yields under
mild conditions. This site-specific allylation method is
applicable to all primary, secondary, and tertiary alkyl acids and exhibits wide functional group compatibility.
adical allylation has been demonstrated to be a versatile
method for the construction of C(sp )−allyl bonds. It
of application (Figure 1). It is certainly highly desirable to
develop a one-step method for this type of transformation,
3
R
generally takes place between a carbon-centered radical and a
suitable allylic reagent via radical addition/fragmentation
processes. A variety of allylating agents have been developed
1
2
for this purpose, including allyl sulfides, allyl sulfoxides, allyl
3
4
5
sulfones, allyltrimethylsilanes, allyltributylstannanes, allyl
halides/chalcolides, and allylmetallic (Co, Zr, Ga) complexes.
6
7
Meanwhile, a number of organic compounds can be employed as
radical precursors to participate in this type of transformation,
8
9
such as alkyl halides/chalcolides, boronates, xanthates,
1
0
11
enamines, active methylene compounds, and even aliphatic
1
2
hydrocarbons. However, many radical allylation reactions also
suffer from either the use of toxic organotin initiators or the use
of excess transition metals or limited substrate scopes. The
discovery of general and efficient methods under mild and
transition-metal-catalyzed conditions remains a challenging task.
Herein we report the silver-catalyzed decarboxylative radical
allylation of aliphatic carboxylic acids in aqueous solution,
providing an efficient and convenient entry to site-specific
Figure 1. Decarboxylative allylation of aliphatic carboxylic acids.
especially in a catalytic manner. As a continuation of our interest
in silver-catalyzed decarboxylative functionalization reac-
17,18
tions,
we set out to explore this possibility (Figure 1).
Thus, 2-ethyltetradecanoic acid (1a) was used as the model
substrate for the optimization of reaction conditions (Table 1).
3
3
C(sp )−C(sp ) bond formations.
With AgNO (20 mol %) as the catalyst and K S O (1.5 equiv)
Aliphatic carboxylic acids are promising raw materials for
chemical synthesis due to their high stability, ready availability,
3
2
2
8
as the oxidant, reaction of 1a with ethyl 2-(tosylmethyl)acrylate
2a, 2 equiv) in aqueous CH Cl solution at 40 °C for 24 h gave
1
3
(
and low cost. In particular, the Hunsdiecker-type reactions
2
2
3
no expected product while all the acid 1a was recovered (entry 1,
involving the cleavage of C(sp )−CO H bonds allow the
2
Table 1). Changing the solvents to acetone/H O did not offer
introduction of various functional groups in a site-specific
2
1
4
any product either (entry 2, Table 1). However, when the
manner. The decarboxylative allylation was first introduced by
Barton and Crich in which carboxylic acids were converted into
the corresponding pyridine-2-thione-N-oxycarbonyl esters fol-
lowed by reaction with an allylating agent such as allyl phenyl
selenide. More recently, Chen and Hu reported the visible-
light-induced, ruthenium-catalyzed decarboxylative allylation of
N-acyloxyphthalimides with allyl sulfones. However, these two
methods require the prior conversion of carboxylic acids into
esters and suffer from the low overall efficiency or limited scope
reaction was carried out in aqueous CH CN solution, we found
3
that the expected product 3a was obtained in 42% yield (entry 3,
Table 1). Increasing the temperature increased the product yield
1
5
(
entries 4 and 5, Table 1). The highest yield (89%) was achieved
when the reaction was performed at 50 °C for 12 h (entry 6,
16
Received: March 18, 2016
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b00802
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Letter
Table 1. Optimization of Reaction Conditions
a
b
entry
catalyst (mol %)
solvent
temp/time (°C/h)
yield (%)
1
2
3
4
5
6
7
8
9
AgNO (20)
CH Cl /H O (1:1)
40/24
40/24
40/24
50/24
60/24
50/12
50/12
50/12
50/12
50/12
50/12
50/12
0
0
3
2
2
2
AgNO (20)
Me CO/H O (1:1)
2 2
3
AgNO (20)
CH CN/H O (1:1)
42
73
62
89
78
64
67
0
3
3
2
AgNO (20)
CH CN/H O (1:1)
3 2
3
AgNO (20)
CH CN/H O (1:1)
3 2
3
AgNO (20)
CH CN/H O (1:1)
3 2
3
AgBF (20)
CH CN/H O (1:1)
3 2
4
AgOTf (20)
AgOAc (20)
none
CH CN/H O (1:1)
3 2
CH CN/H O (1:1)
3
2
1
0
CH CN/H O (1:1)
3 2
c
1
1
AgNO (20)
CH CN/H O (1:1)
0
3
3
2
12
AgNO (20)
CH CN/H O/CH Cl (2:4:1)
58
3
3
2
2
2
a
b
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), K S O (0.3 mmol), Ag(I) catalyst (0.04 mmol), solvent (2 mL). Isolated yield based on 1a.
2
2
8
c
No K S O was added.
2
2
8
Table 1). The reaction was clean, and no radical−radical
coupling byproduct (13,14-diethylhexacosane) could be de-
tected. Switching the catalyst to other Ag(I) salts such as AgBF4
or AgOTf resulted in a lower yield of 2a (entries 7−9, Table 1).
Control experiments indicated that Ag(I) and persulfate were
necessary for the transformation (entries 10 and 11, Table 1).
When K S O was replaced by (NH ) S O as the oxidant, the
unchanged. This phenomenon in combination with the results in
Scheme 1 parallels our observations in other AgNO -catalyzed
3
17
decarboxylative functionalization reactions, which in turn
clearly indicates that an oxidative radical decarboxylation
mechanism is involved in the above reactions. Thus, chemo-
selective decarboxylative allylation reactions could be designed
based on this assumption. Indeed, diacid 4 underwent chemo-
selective decarboxylation to afford exclusively the monoallylation
product 5 in 54% yield (eq 1). Similarly, the tertiary alkylic
2
2
8
4 2
2
8
product yield was decreased to 60%. However, only a trace
amount of 3a could be detected when either (diacetoxy)-
iodobenzene or [bis(trifluoroacetoxy)]iodobenzene was used as
the oxidant (not shown in Table 1). It should be mentioned that
the use of CH CN/CH Cl /H O as the mixed solvents lowered
3
2
2
2
the yield of 2a (entry 12, Table 1). However, this biphasic solvent
system turned out to be advantageous in some cases (vide infra)
presumably because the addition of CH Cl inhibited the
2
2
decomposition of product alkenes.
With the optimized conditions in hand, we next examined the
scope and imitation of this new decarboxylative allylation
method with allyl sulfone 2a as the allylating reagent. As
shown in Scheme 1, secondary alkyl carboxylic acids underwent
efficient decarboxylative allylation, furnishing the corresponding
products 3a−3j in high yields. Reactions of tertiary alkyl
carboxylic acids also proceeded smoothly, leading to the
formations of acrylates 3k−3q in satisfactory yields. α-Oxy or
α-amino acids could also be used as substrates, as exemplified by
the synthesis of 3r−3t. Allylation was also applicable to primary
alkyl carboxylic acids, albeit in moderate efficiency (46% for 3u).
Interestingly, formation of acrylate 3v as the mixture of two
stereoisomers in an 85:15 ratio was observed if trans- (trans-1v)
or cis-2-benzoylcyclohexanecarboxylic acids (cis-1v) was used as
the starting material. The results in Scheme 1 also showed the
excellent tolerance of the decarboxylation toward a variety of
functional groups, including amide, sulfonamide, ester, ether,
nitro, and alkyl or aryl halides. This should allow the late-stage
allylation of complex molecules. For example, decarboxylative
allylation of dehydrolithocholic acid (1w) under the above
optimized conditions afforded the corresponding product 3w in
carboxyl group in 2,2-dimethylpentanedioic acid (6) was
selectively removed, producing the acrylate 7 in 60% yield
while the primary alkylic carboxyl group remained safe (eq 2).
We then examined the generality of this catalytic allylation
toward different allylating agents. The above reaction conditions
were directly used without further optimization, and the results
are summarized in Scheme 2. With 2-cyanoallyl sulfone 2b as the
reagent, the decarboxylative allylation of acids 1a and 1s
proceeded nicely to give the expected products 8 and 11,
respectively. Other than 2a and 2b, which are electron-deficient
alkenes, electron-rich alkenes such as 2-methylallyl sulfone 2c
and allyl sulfone 2d also served as good allylating agents in the
decarboxylative allylation, as exemplified by the synthesis of
electron-rich alkenes 9, 10, 12, and 13 in moderate to high yields.
These results significantly expand the scope of application of the
new method. Nevertheless, our attempt to use 1-fluoroallyl
sulfone 2e as the allylating agent failed. Reaction of acid 1a with
2e did not offer the expected product 14. Instead, vinyl fluoride
15 was obtained in 70% yield as the rearrangement product of 2e
(eq 3).
80% yield.
Treatment of aromatic acids such as 4-chlorobenzoic acid
under the above reaction conditions failed to give any
decarboxylative allylation products, while all the acids remained
As indicated above, a radical mechanism can be drawn for this
catalytic decarboxylative allylation. To provide further evidence,
B
DOI: 10.1021/acs.orglett.6b00802
Org. Lett. XXXX, XXX, XXX−XXX

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Letter
Scheme 1. Silver-Catalyzed Decarboxylative Allylation
Scheme 2. Decarboxylative Allylation with Different Allylating
Agents
a
Reaction conditions: carboxylic acid (0.2 mmol), allylating agent (0.4
mmol), K S O (0.3 mmol), AgNO (0.04 mmol), CH CN (1 mL),
2
2
8
3
3
b
H O (1 mL), 50 °C, 12 h. Isolated yield based on the corresponding
carboxylic acid. Solvent: CH CN/CH Cl /H O (2:4:1).
2
c
3
2
2
2
the cyclized product 17 in 46% yield as the mixture of four
stereoisomers in 9:14:26:51 ratio determined by GC−MS (eq 4).
A plausible mechanism was thus proposed, as shown in Figure
2
. The Ag(I) is first oxidized by persulfate to give the highly
Figure 2. Proposed mechanism of decarboxylative allylation.
reactive Ag(II) intermediate, which in turn oxidizes a carboxylate
19
to produce the carboxyl radical via single-electron transfer. The
carboxyl radical then undergoes fast decarboxylation to generate
the alkyl radical. The addition of the alkyl radical onto an allyl
sulfone followed by β-elimination leads to the product alkene
and a tosyl radical. Finally, oxidation of the tosyl radical gives rise
to TsOH.
In summary, we have successfully developed the one-step
decarboxylative allylation of aliphatic carboxylic acids in aqueous
solution. This transformation is not only efficient and chemo-
selective but also silver catalytic. In addition, it possesses a broad
substrate scope and wide functional group compatibility. In view
of its operational simplicity and mild experimental conditions,
this method should find important applications in organic
synthesis.
a
Reaction conditions: carboxylic acid (0.2 mmol), 2a (0.4 mmol),
K S O (0.3 mmol), AgNO (0.04 mmol), CH CN (1 mL), H O (1
mL), 50 °C, 12 h. Isolated yield based on the corresponding
carboxylic acid. Solvent: CH CN/CH Cl /H O (2:4:1). Reaction
2
2
8
3
3
2
b
c
d
3
2
2
2
e
f
g
time: 5 h. Reaction time: 10 h. trans/cis = 85:15. dr = 1:1.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b00802.
Full experimental details, characterizations of new
1
13
compounds, and copies of H and C NMR spectra
PDF)
(
AUTHOR INFORMATION
Corresponding Author
substrate 16 was designed as the probe for the mechanism.
Reaction of 16 with allylating agent 2c underwent the
decarboxylation/5-exo cyclization/allylation sequence to give
■
*E-mail: clig@mail.sioc.ac.cn.
C
DOI: 10.1021/acs.orglett.6b00802
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This project was supported by the National Natural Science
Foundation of China (Grants 21272259, 21290180, 21472220,
■
2
1532008, and 21361140377).
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DOI: 10.1021/acs.orglett.6b00802
Org. Lett. XXXX, XXX, XXX−XXX