Copper-Catalyzed Carboxylation of Alkenylzirconocenes with Carbon Dioxide Leading to α,β-Unsaturated Carboxylic Acids

Article abstract of DOI:10.1021/acs.orglett.5b02619

A variety of alkenylzirconocenes were efficiently carboxylated by CO₂ utilizing the (IMes)CuCl catalyst yielding the corresponding α,β-unsaturated carboxylic acids in good yields. This reaction could be carried out in a one-pot operation via sequential carbozirconation of alkynes and carboxylation using CO₂ as starting materials under room temperature.

Full text of DOI:10.1021/acs.orglett.5b02619

Letter
pubs.acs.org/OrgLett
Copper-Catalyzed Carboxylation of Alkenylzirconocenes with
Carbon Dioxide Leading to α,β-Unsaturated Carboxylic Acids
Sheng Wang,† Peng Shao,† Chao Chen,† and Chanjuan Xi*,†,‡
†Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry,
Tsinghua University, Beijing 100084, China
‡State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
S
* Supporting Information
ABSTRACT: A variety of alkenylzirconocenes were efficiently
carboxylated by CO2 utilizing the (IMes)CuCl catalyst yielding the
corresponding α,β-unsaturated carboxylic acids in good yields. This
reaction could be carried out in a one-pot operation via sequential
carbozirconation of alkynes and carboxylation using CO2 as starting
materials under room temperature.
α,β-Unsaturated carboxylic acids are important scaffolds widely
existing in pharmacologically and biologically active molecules.1
In addition, α,β-unsaturated carboxylic acids have also been
employed as useful building blocks in organic synthesis.2 Owing
to the importance of the α,β-unsaturated carboxylic acids,
various synthetic methodologies for their synthesis have been
developed. Traditional methods to yield the α,β-unsaturated
carboxylic acids include utilization of named reactions such as
the Doebner−Knoevenagel reaction,3 Wittig reaction, and
Horner−Wadsworth−Emmons reaction.4 Although significant
contributions have been made, use of a strong base or the
formation of a considerable amount of organophosphorous
byproducts such as phosphine oxides and phosphate salts in
these reactions are unavoidable. Recently, the α,β-unsaturated
acids have also been yielded from aldehydes and dibromoacetic
acid with the assistance of an excess amount of SmI2.5 Most of
the above-mentioned reactions are noncatalytic and less
stereoselective.
Carbon dioxide (CO2) is an attractive, abundant, inex-
pensive, and nontoxic one-carbon source. The utilization of
CO2 as a starting material in organic synthesis has received
much attention.6 In concept, addition of CO2 to alkynes could
serve as an efficient synthetic route for construction of the α,β-
unsaturated carboxylic acids. Recently, transition-metal-medi-
ated hydrocarboxylation of alkynes with CO2 have been widely
reported to provide disubstituted α,β-unsaturated carboxylic
acids.7,8 However, carbocarboxylation of alkynes with CO2 to
afford trisubstituted α,β-unsaturated carboxylic acids has been
rarely reported, although methylcarboxylations and allylcarbox-
ylation of alkynes with CO2 have been reported.9
α-methylene-γ-butyrolactone through a methylzincation/car-
boxylation tandem reaction.10 More recently, Hou and co-
worker reported that a combination of the methylalumination
of alkynes with carboxylation of the resulting alkenylaluminum
species with CO2 provides a useful protocol for the synthesis of
a variety of the α,β-unsaturated carboxylic acids.8b All of these
reactions are still limited for introduction of a methyl group to
the β-position of the α,β-unsaturated carboxylic acids. On the
other hand, Rh-, Ni-, Cu-, and Ag-catalyzed carboxylation of
alkenylboronic esters with CO2 have been developed.11 As part
of our studies involving alkenylzirconocene chemistry,12 we
herein describe a sequential carbozirconation of various alkynes
through zirconacycles and subsequent copper-catalyzed carbox-
ylation of the resulting alkenylzirconocenes with CO2 to afford
a wide range of trisubstituted α,β-unsaturated carboxylic acids
(Scheme 1).
Scheme 1. Formal Carbocarboxylation of Alkyne by a
Tandem Carbozirconation/Carboxylation
As we have known, the transmetalation of the C−Zr bond
into the C−Cu bond has been reported and numerous C−C
bond formation reactions have been developed.13 These results
encouraged us to examine the carboxylation of alkenylzircono-
cene species with CO2 utilizing copper catalysts. At first, we
examined exclusive CuCl-catalyzed carboxylation of the
alkenylzirconocene species 2a, prepared by the ethanolysis of
the corresponding zirconacyclopentene generated from 3-
hexyne 1a and Cp2ZrEt2,14 with CO2 (1 atm). The desired
It is well-known that the carbometalation reaction of alkynes
can be achieved in a regio- and stereospecific fashion. Various
alkenylmetal species with well-controlled configurations could
be generated in this way, which can serve as carbon
nucleophiles for further formation of functionalized olefins.
Recently, Ma and co-workers reported the Ni-catalyzed
methylcarboxylation of alkynes with ZnMe2 and CO2 to afford
Received: September 10, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02619
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Organic Letters
Letter
reaction did not proceed, even at 50 °C (Table 1, entries 1−2).
When a copper complex (IPr)CuCl prepared by the reaction of
Table 2. (IMes)CuCl-Catalyzed Carboxylation of
Alkenylzirconocenes with CO2
a
Table 1. Carboxylation of Alkenylzirconocene 2a with CO2
a
by Various Cu Catalysts
b
entry
catalyst
CuCl
temp/°C
yield/%
1
2
3
4
rt
−
−
60
CuCl
50
rt
(IPr)CuCl
(IMes)CuCl
rt
86 (70)
a
Reaction conditions: alkenylzirconocene 2 prepared in situ from
alkyne (0.5 mmol), Cu-catalyst (0.05 mmol), room temperature, 24 h.
b
NMR yield; isolated yield was shown in parentheses.
CuCl and IPr (IPr = 1,3-bis(2,6-diisopropenyl)imidazol-2-
ylidene)15 was used as a catalyst, the carboxylation of 2a with
CO2 proceeded smoothly at room temperature for 24 h to
afford the carboxylic acid product 3a in 60% yield (Table 1,
entry 3). Furthermore, the use of the (IMes)CuCl (IMes = 1,3-
dimesitylimidazol-2-ylidene) catalyst instead of (IPr)CuCl led
to a higher yield (86%) of 3a (Table 1, entry 4). Notably, in
contrast with the transition-metal-catalyzed carboxylation of
alkenylboron compounds,11 this carboxylation of alkenyl-
zirconocene did not require an additional base. It is also
noteworthy that no carboxylated product was observed in the
absence of any copper catalyst in this reaction.
We then examined the carbocarboxylation of a variety of the
alkenylzirconocene species with CO2 by using (IMes)CuCl.
Representative results are summarized in Table 2. The
alkenylzirconocenes 2a−2m, which were prepared by alcohol-
ysis of in situ generated zirconacyclopentenes,16 can tolerate
various substituents such as alkyl, aryl, alkynyl, thienyl, and
cyclopropyl groups. In all cases, the corresponding β-alkyl-α,β-
unsaturated carboxylic acids 3a−3m were formed in 49% to
77% isolated yields (entries 1−13).
Various preparative methods of alkenylzirconocenes are now
available, such as allylzirconation and alkenylzirconation of
alkynes.17 For example, when alkenylzirconocene 2n and 2o
generated from zirconocene−alkyne complexes and diallyl ester
were adopted, skipped diencarboxylic acids 3n and 3o were
yielded, respectively (Table 3, entries 1−2). When dienylzirco-
nocene ethanolyzed from the corresponding zirconacyclopen-
tadiene was employed, tetrasubstituted diencarboxylic acid 3p
was obtained (entry 3). Furthermore, when alkenylzirconocene
2q and 2r produced by the reaction of the zirconacyclopentene
with ethoxyethene were employed, disubstituted diencarboxylic
acid 3q and 3r were afforded, respectively (entries 4−5). When
alkenylzirconocene 2s and 2t yielded from the zirconocene−
alkyne complex and 4-bromobut-1-ene or 3-chlorobut-1-ene
were subjected, the corresponding α,β-unsaturated carboxylic
acid 3s and 3t were obtained in 65% and 58% yields,
respectively (entries 6−7). In addition, the vinylzirconocene
species 2u resulting from the hydrozirconation of alkynes
employing Schwartz’ reagent18 could also proceed in a
carboxylation with CO2 under the optimized conditions to
afford the corresponding α,β-unsaturated carboxylic acid 3u
(entry 8).
a
Reaction conditions: alkenylzirconocene 2 prepared in situ from
alkyne (0.5 mmol), (IMes)CuCl (0.05 mmol).
On the basis of the results, a possible reaction mechanism of
the present catalytic carboxylation of alkenylzirconocene
species with CO2 is illustrated in Scheme 2. First, trans-
metalation from the Zr−C bond to the Cu−C bond occurs to
yield alkenylcopper species 4. Then nucleophilic addition of the
alkenylcopper 4 to CO2 produces copper carboxylate 5, which
upon metathesis with the alkenylzirconocene species 2 could
regenerate alkenylcopper 4 and release zirconocene salt 6. The
zirconocene salt 6 would generate the α,β-unsaturated
carboxylic acid 3 after hydrolysis.
B
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Table 3. (IMes)CuCl-Catalyzed Carboxylation of
Alkenylzirconocenes with CO2
Full experiment procedure, spectra data, and NMR charts
(PDF)
a
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: cjxi@tsinghua.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (21472106 and 21272132) and the
National Key Basic Research Program of China (973 program)
(2012CB933402).
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ASSOCIATED CONTENT
* Supporting Information
■
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The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.5b02619.
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