Nickel-catalyzed double carboxylation of alkynes employing carbon dioxide

Article abstract of DOI:10.1021/ol502538r

The nickel-catalyzed double carboxylation of internal alkynes employing carbon dioxide (CO₂) has been developed. The reactions proceed under CO₂ (1 atm) at room temperature in the presence of a nickel catalyst, Zn powder as a reducing reagent, and MgBr₂ as an indispensable additive. Various internal alkynes could be converted to the corresponding maleic anhydrides in good to high yields. DFT calculations disclosed the indispensable role of MgBr₂ in the second CO₂ insertion.

Full text of DOI:10.1021/ol502538r

Letter
pubs.acs.org/OrgLett
Nickel-Catalyzed Double Carboxylation of Alkynes Employing
Carbon Dioxide
Tetsuaki Fujihara,† Yuichiro Horimoto,† Taiga Mizoe,† Fareed Bhasha Sayyed,‡ Yosuke Tani,† Jun Terao,†
Shigeyoshi Sakaki,*,‡ and Yasushi Tsuji*,†
†Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto
615-8510, Japan
‡Fukui Institute for Fundamental Chemistry, Kyoto University, Nishihiraki-Cho-34-4, Sakyo-ku, Kyoto 606-8103, Japan
S
* Supporting Information
ABSTRACT: The nickel-catalyzed double carboxylation of
internal alkynes employing carbon dioxide (CO2) has been
developed. The reactions proceed under CO2 (1 atm) at room
temperature in the presence of a nickel catalyst, Zn powder as a
reducing reagent, and MgBr2 as an indispensable additive.
Various internal alkynes could be converted to the corresponding maleic anhydrides in good to high yields. DFT calculations
disclosed the indispensable role of MgBr2 in the second CO2 insertion.
Scheme 1. Catalytic Double Carboxylation Using CO2
arbon dioxide (CO2) is a readily available, nontoxic, and
1
Crenewable carbon source. Its environmental impact due
to its overabundance makes it especially attractive as a raw
material in carbon−carbon bond−forming reactions.2 Recently,
the highly efficient transition-metal catalyzed monocarboxyla-
tions of arylboranes,3a−d organozincs,3e,f organic halides,4
esters,5 and C−H bonds6 using CO2 have been reported.
Furthermore, the transition-metal catalyzed hydrocarboxylation
of styrenes,7a allenes,7b alkynes,7c,d and 1,3-dienes7e as well as
heterocarboxylations of alkynes8 have also been explored. In all
these reactions, only one CO2 was incorporated into the
unsaturated substrates.
By extension, double carboxylation, in which two CO2
molecules are introduced simultaneously into a substrate,
would be very promising for the efficient synthesis of
dicarboxylic acids. However, to date, such methods have not
been extensively developed. Electrochemical double carbox-
ylation was reported,9 but disappointingly, it was not efficient at
all in terms of applicable substrates and/or product selectivity.
Other than the electrochemical reactions, stoichiometric Ni
complexes have been used to facilitate the double carboxylation
of 1,3-butadienes, although the reaction did not proceed
catalytically.10 The single reported catalytic double carbox-
ylation used 1-(trimethylsilyl)-3-alkyl-substituted allenes as
substrates (Scheme 1a).11 Unfortunately, the substrate scope
was limited and the trimethylsilyl moiety was necessary for the
double carboxylation. Herein, we report the Ni-catalyzed
double carboxylation of internal alkynes with CO2, affording
highly versatile maleic anhydrides12 as products (Scheme 1b).
The reactions proceed selectively under CO2 at 1 atm and
room temperature in the presence of Zn powder as a reducing
reagent and MgBr2 as an indispensable additive.
reagent, and MgBr2 (2.0 equiv) as an additive, in the presence
of molecular sieves 3 Å (MS 3 Å, powder) in dimethylforma-
mide (DMF) at room temperature under a CO2 pressure of 1
atm (Table 1). The yield of the double-carboxylated product
(2a) was determined by gas chromatography (GC) after
acidification. Under these conditions, the double-carboxylated
product 2a was obtained in 74% yield (entry 1). A small
amount of a hydrocarboxylated product (3a), which was
analyzed by GC after derivatization to the corresponding
methyl ester, was also detected. With Ni(acac)2 as the catalyst
(i.e., without the bpy ligand), the reaction did not proceed
(entry 2). In the absence of MgBr2, 2a was not detected (entry
3). The Zn powder was indispensable for the reaction (entry
4). Without MS 3 Å, the yield of 2a was slightly reduced while
4c
that of 3a increased (entry 5). Employing MgCl2 in place of
MgBr2, the yield of 2a considerably decreased and 3a was
obtained in 23% yield (entry 6). ZnBr2 and ZnCl2 in place of
MgBr2 suppressed the double carboxylation (entries 7 and 8).
Initially, the reaction of 5-decyne (1a) was surveyed with
Ni(acac)2(bpy) (10 mol %, acac = acetylacetonate; bpy =
bipyridine) as a catalyst, zinc powder (3.0 equiv) as a reducing
Received: August 28, 2014
Published: September 8, 2014
© 2014 American Chemical Society
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Letter
Table 1. Optimization of Reaction Conditions on the Nickel-
Catalyzed Double Carboxylation of 5-Decyne (1a)
Table 2. Nickel-Catalyzed Double Carboxylation of Various
Internal Alkynes
a
a
catalyst system: alternation from the
reaction conditions
yield of 2a yield of 3a
b
b
entry
(%)
(%)
1
without any change
without bpy
74
3
2
0
0
3
without MgBr2
0
0
4
without Zn powder
without MS 3 Å
0
0
5
62
24
0
6
6
MgCl2 in place of MgBr2
ZnBr2 in place of MgBr2
ZnCl2 in place of MgBr2
MeObpy in place of bpy
phen in place of bpy
Mn in place of Zn
23
0
7
8
0
0
9
37
48
66
4
2
10
11
12
13
trace
2
Mg in place of Zn
trace
2
c
MgBr2 (3.0 equiv), DMF (2.0 mL)
78 (71)
a
Reaction conditions: 5-Decyne (1a, 0.50 mmol), Ni(acac)2(bpy)
(0.050 mmol, 10 mol %), Zn powder (1.5 mmol, 3.0 equiv), MgBr2
(1.0 mmol, 2.0 equiv), molecular sieves 3 Å (MS 3 Å, powder, 100
mg), under CO2 (1 atm), in DMF (2.5 mL), at room temperature for
b
c
20 h. Determined by GC analysis. Isolated yield of 2a.
The use of other ligands such as 4,4′-dimethoxybipyridine
(MeObpy) and 1,10-phenanthroline (phen) in place of bpy
decreased the yield of 2a (entries 9 and 10). Regarding the
ligand, PPh3, PCy3 (tricyclohexylphosphine), and dppe
(diphenylphosphinoethane) were not effective.13 Other reduc-
ing agents such as Mn powder or Mg turnings gave the product
in moderate or low yields (entries 11 and 12). In 1,3-dimethyl-
2-imidazolidinone (DMI) as the solvent in place of DMF, 2a
was obtained in 52% yield, whereas THF and toluene were not
good solvents, giving trace amounts of 2a. Under the optimal
reaction conditions, 2a was obtained in 78% GC yield and in
71% isolated yield as shown in entry 13.
The double carboxylations of various internal alkynes (1b−i)
were carried out (Table 2). With 3-hexyne (1b) and 2,9-
dimethyl-5-decyne (1c) as substrates, the corresponding
products (2b and 2c) were obtained in good isolated yields
(entries 1 and 2). 2-Octyne (1d) and 5-phenyl-2-pentyne (1e)
reacted smoothly, giving the corresponding products (entries 3
and 4). Alkynes with secondary alkyl groups on the sp-carbons
(1f and 1g) also provided the double-carboxylated products in
good yields (entries 5 and 6). An alkyne having an olefin
substituent (1h) was converted to the corresponding product
with the CC bond intact (entry 7). A cyclic internal alkyne
(1i) also took part in the reaction, giving the corresponding
product in 79% yield (entry 8). In Table 2, 1b−i were fully
converted, but side products other than a small amount of
monocarboxylated products were not detected by GC and GC-
MS analyses. Unfortunately, terminal alkynes and aromatic
internal alkynes did not afford the corresponding double
carboxylated products.
a
Reaction conditions: 1 (0.50 mmol), Ni(acac)2(bpy) (0.050 mmol,
10 mol %), MgBr2 (1.5 mmol, 3.0 equiv), Zn powder (1.5 mmol, 3.0
equiv), molecular sieves 3 Å (powder, 100 mg), under CO2 (1 atm), in
DMF (2.0 mL), at 25 °C for 20 h. Isolated yield. A mixture of
DMA/hexane (1.5 mL/0.75 mL) was used as a solvent.
b
c
Scheme 2, the reaction of commercially available 1-hexadecyne
with methyl iodide afforded 1j quantitatively. The treatment of
1j under the optimized reaction conditions provided the
desired product (2j) in 70% isolated yield. To the best of our
knowledge, this is the shortest and most efficient synthetic
route to Chaetomellic acid A anhydride among the known
procedures.11,15
The present reaction was applied to the fast and highly
efficient synthesis of Chaetomellic acid A anhydride, which is
isolated from the coelomycete Chaetomella acutiseta. The
dianionic form of this compound is a potent and selective
inhibitor of ras farnesyl protein transferase.14 As shown in
In terms of a mechanism, it is well-known both
experimentally16a,b and theoretically16c,d that the oxidative
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Letter
Scheme 2. Synthesis of Chaetomellic Acid A Anhydride
cyclization of Ni0, CO2, and alkynes gives oxanickelacyclo-
pentenones (4). Actually, the reaction of 1a with Ni(COD)2
(COD = 1,5-cyclooctadiene) in the presence of bpy under CO2
(1 atm) gave the corresponding complex 4a in 75% yield (eq
1).16b The double carboxylation of 1a to 2a proceeded in the
Figure 2. Gibbs energy profile for the second CO2 insertion (path c).
interacts with the nickel carboxylate moiety of 4b to afford A2.
Then, CO2 is inserted into the NiII−C bond of A2 via TSA2‑A3
to afford A3 with a ΔG°‡ value of 17.4 kcal/mol. In sharp
contrast, in path c (Figure 2), after the one-electron reduction
of 4b to B, the insertion of CO2 into the NiI−C bond of B1 is
quite facile (ΔG°‡ = 5.0 kcal/mol) as compared with paths a
and b (cf. 21.9 and 17.4 kcal/mol in Figure 1). In the one-
electron reduction, MgBr2 plays a crucial role to provide a
bromide anion to Zn2+. During the CO2 insertion, the resulting
MgBr coordinates with both the carboxylate moiety and the
incoming CO2 in B1 and TSB1−C to facilitate the second
carboxylation. Thus, MgBr2 makes the one-electron reduction
of 4b possible and accelerates the CO2 insertion in B1. These
crucial roles of MgBr2 have not been previously recognized.
Based on the experimental results (eqs 1 and 2) and DFT
calculations (Figures 1 and 2), a plausible catalytic cycle is
suggested in Scheme 3. The active catalyst species must be
presence of a catalytic amount (10 mol %) of 4a in 63% yield
(eq 2). Hence, nickelacycle (4) must be involved in the
catalytic cycle.
After the formation of nickelacycle (4), three possible paths
(a−c) may follow for the second carboxylation. In path a, direct
CO2 insertion into the NiII−C bond of 4 occurs without any
help by MgBr2. In path b, 4 forms an adduct with MgBr2
followed by the insertion of CO2 into the NiII−C bond. Finally,
in path c, a one-electron reduction of 4 by Zn in the presence of
MgBr2 occurs first to afford a NiI intermediate, followed by the
insertion of CO2 into the NiI−C bond.5b These three possible
paths were examined by density functional theory (DFT)
calculations (Figures 1 and 2).
Scheme 3. Plausible Reaction Mechanism
Direct CO2 insertion into the NiII−C bond of 4b (4: R1 = R2
= CH3) proceeds via TS4b‑A1 with a large ΔG°‡ value of 21.9
kcal/mol (path a, Figure 1). In path b (Figure 1), MgBr2 first
Ni0(bpy)16d which is formed via reduction of the NiII catalyst
precursor by Zn (step a). Then, the oxidative cyclization of
Ni0(bpy) with 1 and CO2 affords the NiII metallacycle 4 (step
b). The reduction of 4 with Zn and MgBr2 provides NiI species
B (step c). B must be a key intermediate in this double
carboxylation, since the carboxylation of B to C (step d) is
much easier due to the higher nucleophilicity of B and the
coordinative participation of the MgBr moiety (Figure 2).
Figure 1. Gibbs energy profile for the second CO2 insertion (paths a
and b).
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In conclusion, we developed a new nickel-catalyzed double
carboxylation of alkynes under CO2 (1 atm) at room
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AUTHOR INFORMATION
Corresponding Authors
■
(11) Takimoto, M.; Kawamura, M.; Mori, M.; Sato, Y. Synlett 2005,
2019−2022.
*E-mail: ytsuji@scl.kyoto-u.ac.jp.
*E-mail: sakaki.shigeyoshi.47e@st.kyoto-u.ac.jp.
Notes
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(13) See the Supporting Information for details.
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas (“Organic synthesis based on
reaction integration” and “Molecular activation directed toward
straightforward synthesis”) and for Specially Promoted Science
and Technology (No. 22000009) from MEXT, Japan. T.F.
acknowledges financial support from a Grant-in-Aid for Young
Scientists (A) (No. 25708017) from JSPS.
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