Monocarboxylation and intramolecular coupling of butenylated arenes via palladium-catalyzed C-H activation process

Article abstract of DOI:10.1021/acs.orglett.5b00376

A novel and practical reaction for the direct intramolecular oxidative coupling of butenylated arenes is reported. With the catalysis of Pd(OAc)₂, reactions of various butenylated arenes and carboxylic acids with Selectfluor reagent in CH₃CN solution afforded the corresponding monocarboxylation/cyclization products in good yields under mild conditions. This research demonstrated an economic method with the synthesis of 2-tetralyl carboxylic esters, a valuable class of bioactive compounds.

Full text of DOI:10.1021/acs.orglett.5b00376

Letter
pubs.acs.org/OrgLett
Monocarboxylation and Intramolecular Coupling of Butenylated
Arenes via Palladium-Catalyzed C−H Activation Process
†
†
†
†
,†,‡
Rui Liu, Ze-Hai Lu, Xiao-Hui Hu, Jun-Li Li, and Xian-Jin Yang*
†Key Lab for Advanced Materials & Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong
Road, Shanghai 200237, China
‡
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, China
*
S Supporting Information
ABSTRACT: A novel and practical reaction for the direct
intramolecular oxidative coupling of butenylated arenes is
reported. With the catalysis of Pd(OAc) , reactions of various
2
butenylated arenes and carboxylic acids with Selectfluor
reagent in CH CN solution afforded the corresponding
3
monocarboxylation/cyclization products in good yields under
mild conditions. This research demonstrated an economic method with the synthesis of 2-tetralyl carboxylic esters, a valuable
class of bioactive compounds.
arboxylic ester is a ubiquitous functional group of organic
molecules. The classical strategy for the formation of an
Scheme 1. Strategies for Monocarboxylation and Direct
Intramolecular Coupling
C
ester relies on the condensation of an alcohol with a carboxylic
acid. Often, the catalytic addition of carboxylic acids to alkenes,
as an alternative method for the generation of esters, provides a
1
more direct and simple route, although photolytic, and
2
3
4
5
Bronsted acid and transition metals such as Pd, Au, Ag,
6
Ru, etc., are usually required as a catalyst.
Transition-metal-catalyzed direct cross-coupling via C−H
bond activation is another important research topic and has
7
been extensively studied. In comparison with traditional
8
indirect cross-couplings, this direct cross-coupling method is
more challenging but advantageous for its atom economy and
eco-friendliness. In particular, some Pd-catalyzed direct
coupling reactions between arenes and olefins have been
9
reported.
On the basis of the above facts, we note that the Pd-catalyzed
tandem reactions including hydrocarboxylation and intra-
molecular direct cross-coupling of butenylated arenes to
construct a useful tetralyl carboxylic ester should be reasonable
(
Scheme 1). Recently, Toste and co-workers described a gold-
10
catalyzed oxidative coupling of 2-butenylated aryltrimethylsi-
1
1
12
lane using Selectfluor as an oxidant (Scheme 1). 2-
Butenylated arylsilanes are necessary for the conversion.
From an academic point of view, it would be highly desirable
to directly use an unactivated, instead of activated, coupling
partner. Meanwhile, 2-tetralyl carboxylic esters are revealed to
be present in numerous biologically active natural products and
Figure 1. Synthetically and naturally occurring 2-tetralyl carboxylic
esters or their derivatives.
13
synthetic molecules, such as isofregenedadiol, ficuselastic
1
4
15
16
acid, taepeenin D, epigallocatechingallate analogues,1 25-
7
Nor-D:C-friedooleana-5,7,9-triene-3α-29-diol diacetates, and
18
rotigotine (Figure 1). Therefore, we were interested in
developing a more convenient protocol for the synthesis of the
compounds.
Received: February 5, 2015
Published: March 12, 2015
©
2015 American Chemical Society
1489
DOI: 10.1021/acs.orglett.5b00376
Org. Lett. 2015, 17, 1489−1492

Organic Letters
Letter
a
We started our investigations using 4-phenyl-1-butene 1a as
Scheme 2. Substrate Scope of Carboxylic Acids
the model substrate. Initially, while Pd(OAc) (150 mol %) was
2
used to catalyze the reaction of 4-phenyl-1-butene (1 equiv)
and acetic acid (70 equiv) in MeCN under ambient
temperature, no target product was detected. The reaction
afforded an addition mixture of acetic acid and the C−C double
19
bond of 1a (Table 1, entry 1). Then, we used Cu(OAc) (10
2
Table 1. Oxidant Screening for Monocarboxylation and
a
Direct Intramolecular Coupling
entry
Pd(OAc) (mol %)
oxidant (equiv)
result
2
b
1
2
3
4
5
6
150
10
10
10
10
10
nd
nd
nd
nd
nd
b
b
b
b
Cu(OAc) (0.1)
2
Cu(OAc) (2.5)
2
H O (2.5)
2
2
NaIO (2.5)
4
c
Selectfluor (2.5)
3a (68%)
a
Conditions: a mixture of 1a (1.0 mmol), 2a−l (60 equiv), Selectfluor
a
Conditions: a mixture of 1a (0.5 mmol), HOAc (2 mL), and
(2.8 equiv), and Pd(OAc) (5 mol %) in MeCN was stirred at room
2
Pd(OAc) in MeCN was stirred, and then oxidant was added; the
temperature overnight. Isolated yield after column chromatography.
2
b
mixture was stirred at room temperature overnight. No target
1
c
product was detected as determined by H NMR analysis. Isolated
yield after column chromatography.
mol %) with Pd(OAc) (10 mol %) as catalyst to catalyze the
2
reaction of 1a (1 equiv) with 2a (70 equiv) in CH CN (Table
3
1
, entry 2). This reaction also failed to give the product,
19c
affording a mixture of adducts.
Subsequently, excess
Cu(OAc) (2.5 equiv) did not give a positive result (Table 1,
2
entry 3). It was also unsuccessful when H O or NaIO was
2
2
4
used as oxidant (Table 1, entries 4 and 5). By referring to
1
1
Toste’s report, we attempted to use Selectfluor as the oxidant
to accomplish this reaction. To our delight, use of Selectfluor
eventually gave the target product 3a in 68% yield (Table 1,
entry 6).
Figure 2. X-ray structure and structure cell of 3h.
On the basis of the above results, we chose Selectfluor as the
oxidant to optimize the reaction conditions. After a series of
experiments, we found that, among the tested solvents, MeCN
was the best, and the amount of acetic acid significantly affected
the yield. When HOAc was added in 2 equiv, 3a was obtained
with low yield. With the increase of acetic acid 2a, the yield was
gradually increased until 2a reached 60 equiv. Then, we
identified the following as the optimal reaction condition:
Pd(OAc) (5 mol %)/Selectfluor (2.8 equiv)/CH CN/ambient
To broaden the range of substrates, various butenylated
arenes with formic acid 2b were tested under the optimized
conditions (Table 2). Notably, the presence of substituents on
aryls gave a mixture of 4 and 5. Neutral or electron-rich
butenylated arenes 1a−e gave 4a−e and 5a−e in high yields
(Table 2, entries 1−4). The substitution position of methyl
group in 1b−d had no significant effect on the yield (Table 2,
entries 1−3). Reactions with electron-withdrawing substrates
1f−i also gave the desired products 4f−i and 5f−i in moderate
yields (Table 2, entries 5−8). Particularly, 1c gave a mixture of
4c and 5c in an almost 1:1 ratio (Table 2, entry 2). This result
shows that the reaction of 1c is regioselective and gives
compounds 4c (coupling with an ortho-aromatic carbon of
methyl and isomerization) and 5c (coupling with para-aromatic
carbon of methyl). Meanwhile, for 1i, only 4i was isolated from
the reaction mixture (Table 2, entry 8). Reasonably, 1j gave 4j
as a single isomer in moderate yield (Table 2, entry 9).
2
3
2
0
temperature.
With the optimized conditions in hand, we first examined the
substrate scope by treatment of various carboxylic acids with 4-
phenyl-1-butene. As shown in Scheme 2, a variety of carboxylic
acids 2a−l were tolerant, affording the products in moderate to
good yields. While formic acid 2b, a small ligand of palladium,
gave the product 3b in 85% yield, the bulky butyric acid 2d and
isobutyric acid 2e showed low reactivity and gave products 3d
and 3e in 65 and 60% yield, respectively. Nevertheless, for
aromatic acids 2f−l, yields were moderate, except for phenyl
acetic acid 2k with a yield of 82%. We were surprised to find
that 3f and 3h were in the solid state, whereas others were oil.
From the X-ray structure of 3h (Figure 2), a special
intermolecular π−π stacking between the phenyl ring of
carboxylic acid and that of tetralyl was observed.
On the basis of the obtained results, we therefore propose a
plausible mechanism for monocarboxylation and direct intra-
molecular coupling. A Pd(II)/Pd(IV) process was supposed,
and the formation pathway of 4 and 5 is depicted in Scheme 3.
In this process, intermediate B gave the mixture of 4 and 5
through path a and path b, respectively. Pd(IV) intermediates E
1
490
DOI: 10.1021/acs.orglett.5b00376
Org. Lett. 2015, 17, 1489−1492

Organic Letters
Letter
a
Table 2. Substrate Scope of Butenylated Arene
Scheme 3. Plausible Mechanism for Monocarboxylation and
Direct Intramolecular Coupling
In conclusion, we have developed a novel and useful
approach for the construction of 2-tetralyl carboxylic ester.
This reaction features Pd-catalyzed tandem carboxylation and
direct intramolecular coupling with Selectfluor as an oxidant. A
series of substrates were tolerated, including various carboxylic
acids and differently substituted butenylated arenes. The
reaction conditions are mild, and the products were obtained
with acceptable yields. Further mechanistic studies are
underway and will be demonstrated in due course.
ASSOCIATED CONTENT
Supporting Information
■
*
S
a
Experimental procedures, new compound characterization, and
crystal structure data. This material is available free of charge
via the Internet at http://pubs.acs.org.
Conditions: a mixture of 1b−j (1.0 mmol), 2b (60 equiv), Selectfluor
(
2.8 equiv), and Pd(OAc) (5 mol %) in MeCN was stirred at room
2
temperature overnight. Isolated yield after column chromatography.
The ratio of 4/5 was determined by 13C NMR.
AUTHOR INFORMATION
■
Corresponding Author
*
E-mail: yxj@ecust.edu.cn.
and E′ promoted C−H activation of arenes to form transition
2
1,22
Notes
state F and F′.
Key intermediate K was considered to
The authors declare no competing financial interest.
originate from the Pd(IV)-catalyzed Claisen rearrangement of
intermediate H. Finally, K and K′ followed by reductive
elimination gave isomers 4 and 5, respectively. The absence of
the generation of pentacyclic compound 6 may be due to the
fact that the β-H elimination of G to give H was more feasible
than the reductive elimination of F to give 6.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (NSFC) (Grant Number 21372077) for financial
support.
1
491
DOI: 10.1021/acs.orglett.5b00376
Org. Lett. 2015, 17, 1489−1492

Organic Letters
Letter
(
19) (a) Kitching, W.; Rappoport, Z.; Winstein, S.; Young, W. G. J.
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DOI: 10.1021/acs.orglett.5b00376
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