Synthesis of α-pyrones by catalytic oxidative coupling of terminal alkynes and carbon dioxide

Article abstract of DOI:10.1016/j.jorganchem.2016.12.033

The use of the complex [(dippe)Ni(μ-H)]₂(1) as a catalyst precursor (10?mol%) in the presence of a variety of terminal alkynes and CO₂allowed the production of substituted α–pyrones. This reaction occurs using relatively mild conditions (50?°C, 150 psi of CO₂) with good to modest yields, depending on the nature of the substituents in the corresponding alkyne. The produced α–pyrones were characterized by different analytical methods and spectroscopic techniques.

Full text of DOI:10.1016/j.jorganchem.2016.12.033

Journal of Organometallic Chemistry 831 (2017) 18e22
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of
a
-pyrones by catalytic oxidative coupling of terminal
alkynes and carbon dioxide
*
ꢀ
Saray Oliveros-Cruz, Alma Arevalo, Juventino J. García
ꢀ
ꢀ
ꢀ
Facultad de Química, Universidad Nacional Autonoma de Mexico, Mexico D. F. 04510, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of the complex [(dippe)Ni(
of terminal alkynes and CO2 allowed the production of substituted
m
-H)]2 (1) as a catalyst precursor (10 mol%) in the presence of a variety
epyrones. This reaction occurs using
relatively mild conditions (50 ꢀC, 150 psi of CO2) with good to modest yields, depending on the nature of
Received 4 December 2016
Received in revised form
30 December 2016
Accepted 30 December 2016
Available online 3 January 2017
a
the substituents in the corresponding alkyne. The produced
analytical methods and spectroscopic techniques.
a
epyrones were characterized by different
© 2017 Elsevier B.V. All rights reserved.
Keywords:
Pyrones
Alkynes
Carbon dioxide
Nickel
Catalysis
Oxidative coupling
1. Introduction
synthesis, reported by Limbach and co-workers, using ethylene and
CO2 catalyzed by Ni(0) [10], later improved on by other groups [11].
The increasing amount of atmospheric CO2 from anthropogenic
sources is a concerning issue of global proportions [1]; therefore,
transforming this pollutant gas into useful products, such as fuels
[2] and co-polymers [3], among many others, is still a pending task.
There are several chemical strategies to use CO2 as a building block
toward more complex materials, e.g., the partial hydrogenation to
yield formates [4], the reduction to CO for further use in a variety of
processes [5], and the incorporation of CO2 into alkenes, dienes,
allenes, and alkynes [6].
Similarly, dienes have also been used to produce corresponding
pyrones with CO2 catalyzed by palladium [12].
a-
Regarding the coupling of alkynes and CO2 catalyzed by nickel,
reports from 1977 by Inoue et al. indicate the use of [Ni(COD)2] and
bidentate aromatic phosphines to produce corresponding 2-pyrone
or alkyne cyclotrimerization products [13]. Tsuda and co-workers
reported on the co-polymerization of diynes with CO2 catalyzed
by [Ni(COD)2] using monodentate alkyl phosphines to produce
poly-(2-pyrones) [14] and, with a closely related method, bicyclic a-
The insertion reaction of CO2 into M-C bonds has been reported,
and Allen and co-workers have documented some relevant exam-
ples for Ru [7] and Fe [8]; in these cases, the single or double
insertion of CO2 gives acetates, depending on the pressure of CO2
used.
The oxidative coupling of alkenes with CO2 mediated by nickel
to yield carboxylic acids, via the formation of nickela-lactone in-
termediates followed by hydrolysis, was reported by Hoberg and
co-workers [9]. A closely related process is the sodium acrylate
pyrones [15]. Also worthy to mention are the contributions from
Walther [16] and Saegusa [17] using low-valent nickel complexes
and alkyl-substituted alkynes to yield pyrones with low to mod-
erate yields. Other relevant reports on that field include the use of
nickel (0) catalysts and CO2 along with organo-zinc compounds to
produce acrylic acid derivatives [18], recently expanded to the
hydrocarboxylation of alkynes using alcohols as proton sources [19]
and the production of maleic acid by the double insertion of CO2
using Zn powder and MgBr2 [20].
In recent years, our group has been interested in a variety of
methods for CO2 activation and transformations catalyzed by
nickel, including the characterization of intermediates in the
reduction of CO2 [21]; these methods includes catalytic
* Corresponding author.
E-mail address: juvent@unam.mx (J.J. García).
http://dx.doi.org/10.1016/j.jorganchem.2016.12.033
0022-328X/© 2017 Elsevier B.V. All rights reserved.

S. Oliveros-Cruz et al. / Journal of Organometallic Chemistry 831 (2017) 18e22
19
applications in the hydroesterification of styrenes [22], hydro-
sililation to yield formic acid and formates [23], and the production
of aliphatic N-methylamines [24].
Here, we want to disclose our findings in the study of the
oxidative coupling of a variety of substituted terminal alkynes with
CO2 (99.998%) to produce aepyrones catalyzed by nickel with good
to low yields, depending on the electronic donor/withdrawing
characteristic of the substituents at the alkyne moiety.
cyclotrimerization and homo-coupling products; this was probably
due to the high electronegativity of the fluorine atom and the
decreasing electronic density in the aromatic ring, compared to
simple phenyl acetylene.
To further explore this behavior, we decided to assess the
reactivity of trifluoromethyl-substituted phenylacetylenes (entries
10e12); similarly, we observed high conversion of the starting
material but with a poor selectivity to the corresponding pyrones,
along with an increased preference towards the production of
homocoupling and cyclotrimerization products, i.e., products
where CO2 was not incorporated.
2. Results and discussion
Inspired in the mechanistic reports in the literature [13] [25],
and the current observations, a mechanistic proposal for the for-
mation of aepyrones is depicted in Scheme 2.
The optimized reaction conditions were established using
phenylacetylene as a model substrate and [(dippe)Ni(m-H)]2 (1) as a
catalyst precursor with variations of reaction time, solvent, catalyst
load, temperature, and CO2 pressure; thus, we found that the use of
69 h, toluene, 10 mol% of 1, 50 ꢀC, and 150 psi of CO2 were the best
reaction conditions to achieve a 100% conversion of the substrate,
with the best selectivity towards the production of the corre-
As represented in Scheme 2, we envisage the formation of the
five-membered nickelacycle (A) where the incoming CO2 can be
inserted to yield the corresponding seven-membered metalla-
lactone (B), and ultimately giving the corresponding pyrone by
having electron-donating substituents at the aromatic ring in the
alkyne; this favors a nucleophilic attack at the electrophilic
carbon of the incoming CO2. On the other hand, the cyclo tri-
merization pathway, which yields the seven-membered metal-
lacycle (C) leading to the production of benzenic products, would
be favored, with electron-withdrawing substituents at the
aromatic ring in the alkyne by insertion of a third alkyne instead
of CO2. A similar scenario might be expected in the case of homo-
coupling products; however, this would occur by a different
mechanistic proposal, see SI section. Thus, the proposal for the
formation of (A) as a key intermediate instead of a nickela-
lactone proposed by Hoberg [26] is consistent with the elec-
tronic properties of the substituents in the aromatic ring, to
produce (B) or (C) having (A) as a common intermediate. How-
ever, we do not discard at all the formation of the above-
mentioned metalla-lactone.
sponding
Scheme 1.
aepyrone (4,6-diphenyl-2-pyrone), as represented in
The produced 4,6-diphenyl-2-pyrone was isolated from the re-
action mixture by column chromatography and then fully charac-
terized by a variety of analytical techniques, including 1H, 13C{1H},
COSY, and HETCOR; see SI section.
Considering that a 100% transformation of phenylacetylene was
achieved under the reaction conditions (vide supra), the scope of
the reaction was extended to closely related alkynes, some of which
had electron donor or electron withdrawing substituents or small
structural variations; the corresponding results are summarized in
Table 1.
As seen in Table 1, the use of terminal phenyl-acetylenes with
electron donor substituents in the para position (entry 2) of the
benzenic ring produce a high conversion and selectivity (91%) to-
wards the production of the corresponding 2-pyrone, compared to
the unsubstituted phenyl alkyne (entry 1). A sharp contrast can be
seen in entry 3 for the p-methoxyphenylalkyne, but this result was
due to the low solubility of this alkyne in toluene; efforts to over-
come that by using solvent mixtures of toluene/THF did not in-
crease the conversion rate. The use of another electron donor
substituent, such as an amino group in the ortho position, mostly
favored the homocoupling products (96%) and the production of
small amounts (2%) of indole as a product of internal cyclization.
Closely related structural variations, like adding a methylene
between the triple bond and the phenyl ring, decreased the yield,
probably due to increased system flexibility and a lack of conju-
gation. The use of an internal alkyne yielded a dramatic drop in
reactivity (entry 6) to barely produce only 5% hydrogenation; thus,
the use of internal akynes was not further assessed.
The use of 1 mol% of additives, such as BEt3 and NaBPh4, did not
increased the observed yields; only in the case of NaBPh4 could the
nickel catalyst load be reduced from 10 to 5 mol%, with a very
similar product distribution. Last but not least, the cinnamaldehyde
formation may be due to a competing reaction of reduction of CO2
to yield CO, as previously reported by our group [21], along with the
hemi-reduction of the corresponding alkyne, followed by CO
insertion and reductive elimination.
3. Conclusions
The oxidative coupling of terminal aromatic alkynes with CO2
catalyzed with nickel to yield aepyrones (lactones) was achieved in
good yields on electron-donating substituents in the aromatic ring.
However, the substitution with electron-withdrawing substituents
favors the production of cyclotrimerization and homocoupling
products instead.
The use of mono-fluorinated phenyl alkynes gave a complete
conversion (entries 7e9), but with a low selectivity to the corre-
sponding pyrone and an increasing preference for the
Scheme 1. Optimized reaction conditions with phenylacetylene.

20
S. Oliveros-Cruz et al. / Journal of Organometallic Chemistry 831 (2017) 18e22
4. Experimental section
Table 1
4.1. General considerations
CO2 oxidative coupling with aromatic alkynesa.
Entry
1
Alkyne
Conversion (%)
Yield (%)
Unless otherwise noted, all manipulations were performed
using standard Schlenk techniques in an inert-gas/vacuum double
manifold or under an argon atmosphere (Praxair 99.998) in an
MBraun UniLab glovebox (<1 ppm H2O and O2). All liquid reagents
were purchased as reagent grade and degassed before use. All
alkynes and NiCl2 were purchased from Aldrich and stored in a
a
b
c
d
1
e
100
100
5
65
10
20
4
2
91
3
6
0
0
3
0
0
2
0
0
0
glovebox for their use. The complex [(dippe)Ni(m-H)]2 (1) was
prepared from a n-hexane slurry of [(dippe)NiCl2] using Super-
Hydride (LiHBEt3), according to the reported procedure [27]. The
solvents were dried using standard techniques and stored in the
glove box before use. Deuterated solvents were purchased from
Cambridge Isotope Laboratories and stored under 4 Å molecular
sieves for 24 h before use. NMR spectra were recorded at room
temperature on a 300 MHz Varian Unity spectrometer unless
3
2
4b
100
0
96
otherwise noted. 1H NMR spectra (
d parts per million) are re-
ported relative to the residual protio-solvent. 13C{1H} spectra give
the characteristic carbon signal of each solvent. 31P{1H} NMR
5
45
14
17
10
4
0
chemical shifts (
d parts per million) are reported relative to
external 85% H3PO4. Coupling constants (J values) are given in Hz.
The following abbreviations are used for the NMR data:
s ¼ singlet; d ¼ doublet; t ¼ triplet, m ¼ multiplet; and br ¼ broad.
GC-MS determinations were performed using an Agilent Tech-
nologies G3171A equipped with the following column: 5% phe-
6
7
5
0
0
4
0
5
0
0
nylmethylsilicone, 30 m * .25 mm * .25 mm
1H and 13C{1H} NMR
spectra of the reduction products were obtained in CDCl3. Cata-
lytic experiments were carried out in a 100-mL stainless steel Parr
T315SS reactor. Elemental analyses (EAs) were performed by
USAII-FQ-UNAM or USAI-UNAM using a PerkinElmer micro-
analizer 2400.
100
50
17
29
4.2. Catalytic experiments
8
100
25
8
49
0
18
4.2.1. General procedure for the catalytic production of
aepyrones
[(dippe)Ni( -H)]2 (1) (0.031 mmol) and the corresponding
m
alkyne (0.311 mmol) and toluene (10 mL) were charged in a
100-mL Parr reactor. On reacting 1 with all acetylenes, a color
change from wine red to brown was observed with a light
bubbling; the reactor was immediately closed and then pres-
surized out of the dry box with CO2 (150 psi). Afterward, the
reaction vessel was heated up to 50 ꢀC for 69 h. After this time,
the reactor was cooled down to room temperature and vented
into a hood; the reaction mixture was directly analyzed by GC-
MS.
9
100
47
9
15
0
29
10
11
100
100
14
11
3
3
32
23
7
7
44
56
4.2.2. General procedure for the catalytic production of
with additives
aepyrones
For these reactions, a similar experimental procedure as above
was followed but included adding BEt3 or NaBPh4 (0.0031 mmol)
before closing the reactor. NaBPh4 was handled by protecting this
reagent from light using aluminum foil.
12
100
10
0
65
5
20
4.2.3. Isolation and purification of 4,6-diphenyl-2-pyrone
The reaction mixture obtained was evaporated to dryness with
silica gel and then eluted in a silica-gel column (0.2e0.5 mm,
Merck), using a mixture of 80% hexane and 20% ethyl acetate (V/V)
as the eluting agent; the desired fraction was concentrated in the
rotary evaporator and further dried in high vacuum for 2 h.
Elemental Analysis: calc. for C17H12O2, %C 82.24, %H 4.87; exp. %C
82.31, %H 4.83, m/z ¼ 248.1. Relevant NMR spectra are included in
the SI section.
a
Reaction conditions according to Scheme 1.
Additional 2% of indole was observed.
b

S. Oliveros-Cruz et al. / Journal of Organometallic Chemistry 831 (2017) 18e22
21
Scheme 2. Mechanistic proposal for the aepyrone production vs. cyclotrimerization.
ꢀ
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Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
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