Solvent-free synthesis of 2-pyrones from alkynes and carbon dioxide catalyzed by Ni(1,5-cyclooctadiene)2/trialkylphosphine catalysts

Article abstract of DOI:10.1055/s-2005-872266

Solvent-free, efficient, and mild 2-pyrone synthesis by the cycloaddition of alkynes with CO₂ has been achieved under compressed CO₂ with a Ni(cod)₂/P(C₄H₉)₃ or Ni(cod)₂/P(C₈H₁₇)₃ catalyst; both high yields (up to 98%) and selectivities (up to 99%) are attained. One attractive aspect of these catalysts is their high efficiency at low CO ₂ pressures (4 MPa). The applicability of this reaction to a broad range of alkyne substrates and the ease of handling the phosphine ligands are additional merits of the present new catalytic systems in comparison to the previously reported Ni(cod)₂/P(CH₃)₃ catalyst in supercritical CO₂. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872266

LETTER
2141
Solvent-Free Synthesis of 2-Pyrones from Alkynes and Carbon Dioxide
Catalyzed by Ni(1,5-cyclooctadiene)2/Trialkylphosphine Catalysts
S
olvent-Free Synth
a
esis of 2-P
s
yrone
s
fro
u
m
A
lkynes
a
h
nd Carbon D
i
ioxidesa Kishimoto,a Ikuko Mitani*b
a
The General Environmental Technos Co., Ltd., 3-3-1 Higashi-Kuraji, Katano, Osaka 576-0061, Japan
b
Environmental Research Center, The Kansai Electric Power Company, Inc., 1-7 Hikaridai, Seika-cho, Souraku-gun, Kyoto
619-0237, Japan
Fax +81(774)932894; E-mail: mitani.ikuko@b2.kepco.co.jp
Received 13 April 2005
second is related to the role of scCO2 as a substrate, which
may improve the reaction rate and the product selectivity.
Abstract: Solvent-free, efficient, and mild 2-pyrone synthesis by
the cycloaddition of alkynes with CO2 has been achieved under
compressed CO2 with a Ni(cod)2/P(C4H9)3 or Ni(cod)2/P(C8H17)3
catalyst; both high yields (up to 98%) and selectivities (up to 99%)
are attained. One attractive aspect of these catalysts is their high ef-
ficiency at low CO2 pressures (4 MPa). The applicability of this re-
action to a broad range of alkyne substrates and the ease of handling
the phosphine ligands are additional merits of the present new cata-
lytic systems in comparison to the previously reported Ni(cod)2/
P(CH3)3 catalyst in supercritical CO2.
To the best of our knowledge, only two studies on the
Ni(cod)2/phosphine-catalyzed cycloaddition of 1 with
CO2 in scCO2 have been reported and both indicate a re-
markable phosphine ligand effect together with a very
limited scope of applicable alkyne substrates. Reetz et al.
reported that 2a is formed in 35% yield and ca. 90% selec-
tivity by Ni(cod)2/(C6H5)2P(CH2)4P(C6H5)2 catalysis in
scCO2.8,9 Walther et al. used trialkylphosphine ligands in-
stead of (C6H5)2P(CH2)4P(C6H5)2 and reported the forma-
tion of 2a in yields of 99% [P(CH3)3], 53% [P(C2H5)3],
and 3% [P(C3H7)3].10 The ligand P(CH3)3 was highly ef-
fective for the reaction of 1a, but was ineffective for the
reaction of 2-butyne (4% yield). The result of the reaction
of 4-octyne (1b) with the Ni(cod)2/P(C2H5)3 catalyst was
also unsatisfactory (8% yield).
Key words: 2-pyrone derivatives, alkynes, carbon dioxide, Ni(0)
complex, solvent-free
The cycloaddition of alkynes 1 with CO2 to afford 2-py-
rones 21 has drawn much attention from the viewpoints of
the utility of 2-pyrone derivatives2–4 and the chemical fix-
ation of CO2. Typically a combination of Ni(cod)2
(cod = 1,5-cyclooctadiene) and various phosphines PR¢3
(3) are used as catalysts. Two procedures have been re-
ported to be useful for producing 2-pyrones in high yields
by catalysis: the first involves a reaction in finely-tuned
organic solvents and the second is a reaction in supercrit-
ical CO2 (scCO2) without organic solvents.
We have studied further the effect of phosphine ligand 3
on the Ni(0)-catalyzed cycloaddition of alkynes 1 with
CO2 to produce 2-pyrones 2 under compressed CO2 with-
out organic solvents along with improving the substrate
scope of the reaction. This communication reports that a
catalyst generated from Ni(cod)2 and P(C4H9)3 (3a) or
P(C8H17)3 (3b) bearing a long primary alkyl chain, i.e., a
Ni(cod)2/P(C4H9)3 or Ni(cod)2/P(C8H17)3 catalyst, effects
the solvent-free and efficient synthesis of 2 by the cy-
cloaddition of 1 with CO2 under compressed CO2. This
solvent-free 2-pyrone synthesis is also characterized by
being widely applicable to a range of alkyne substrates
(Scheme 1).
Concerning the former approach, Walther et al. reported
that the Ni(cod)2/P(C2H5)3 catalyst effects the cycloaddi-
tion of 3-hexyne (1a) with CO2 to give tetraethyl-2-py-
rone (2a) quantitatively in THF–acetonitrile.1b The
presence of acetonitrile is indispensable and plays a criti-
cal role in the efficient formation of 2a. Another charac-
teristic result is the effect of the phosphine ligand: the
sterically small trialkylphosphine ligand, P(C2H5)3, was
effective, but the sterically bulky P(c-C6H11)3 was much
less effective.
R
Ni(cod)2
R
R
R
The second approach involves the use of scCO2 both as a
solvent and as a substrate. This approach has two signifi-
cant advantages. The first concerns the role of scCO2 as a
suitable ‘environmentally benign’ alternative for a variety
of solvents5,6 because there is a need to reduce or elimi-
nate toxic chemical wastes and by-products that arise in
the course of chemical synthesis and manufacture.7 The
PR'3 (3)
2
R
R
CO2
+
O
compressed CO2
1
O
R = alkyl
2
R' = C4H9, C8H17
Scheme 1
The effect of phosphine ligands on the Ni(0)-catalyzed cy-
cloaddition of 3-hexyne (1a) with CO2 is listed in Table 1.
A catalyst generated from Ni(cod)2 (10 mol% with respect
to 1a) and P(C8H17)3 (3b) (20 mol% with respect to 1a)
SYNLETT 2005, No. 14, pp 2141–2146
Advanced online publication: 03.08.2005
DOI: 10.1055/s-2005-872266; Art ID: U10805ST
© Georg Thieme Verlag Stuttgart · New York
0
2
.0
9
.2
0
0
5

2142
Y. Kishimoto, I. Mitani
LETTER
a
Table 1 The Ni(0)-Catalyzed Cycloaddition of 3-Hexyne (1a) with CO2 under Compressed CO2
R
R
Ni(cod)2
PR'3 (3)
R
R
R
R
R
R
R
R
R
R
CO2
R
+
R
+
+
O
1a
(R = C2H5)
R
R
R
O
2a
4a
5a
Entry PR¢3 (3)
Medium
CO2 Pressure
(MPa)
Conversion
(%)b
Yield (%)b
2a
4a
<1
49
1
5a
<1
<1
<1
<1
<1
1
2
3
4
5
P(C4H9)3 (3a)
P(c-C6H11)3
P(C8H17)3 (3b)
3b
CO2
CO2
15
15
5d
99
61
97
10
THF–CH3CNc
CO2
100
100
72
99
15
20
95 (91)
48
1
P(CH3)2(C6H5)
CO2
13
a Conditions: 1a (2 mmol), Ni(cod)2 (0.2 mmol), 3 (0.4 mmol), 120 °C, 20 h.
b Determined by GC analysis on the basis of the alkyne 1.13 Isolated yield is shown in parentheses.
c THF (5 mL), CH3CN (5 mL).
d CO2 pressure at 20 °C.
gave tetraethyl-2-pyrone (2a) in 99% yield in THF–aceto- tivity.13 In all cases, 1a was completely consumed, and 2a
nitrile (1:1) at 120 °C under CO2 pressure (5 MPa at was obtained in quantitative yield. In particular, it is of
20 °C) (Table 1, entry 3). As by-products, the cyclopenta- great interest that the reaction at 4 MPa gave 2a in excel-
diene-type trimers 4a were produced in 1% yield and the lent yield (Table 2, entry 2). The reaction at 2 MPa result-
benzene-type trimer 5a was barely detected by GC; this ed in a slightly lower but satisfactory selectivity (ca. 90%)
result is consistent with a previous report.1b Quite interest- (Table 2, entry 1). At temperatures as low as 80 °C and
ingly, when this reaction was carried out under com- 100 °C, the same reaction afforded 2a in high yields
pressed CO2 (15 MPa) in the absence of both THF and irrespective of the CO2 pressure (4 and 12 MPa) (Table 2,
acetonitrile, 2a was obtained nearly quantitatively (95% entries 7–10), where ≥95% selectivity for 2a was main-
yield; Table 1, entry 4).11,12 The alkyne trimers 4a were tained. A reduction in catalyst loading to 5 mol% resulted
formed in very small amounts (1%), and the benzene de- in a lower reaction rate, but 2a was obtained in good yield
rivative 5a was detected only in trace amounts. A reaction (Table 2, entry 11). The necessity of relatively high cata-
employing P(C4H9)3 (3a) as the ligand also gave 2a in lyst loading to ensure the quantitative formation of 2a,
97% yield (Table 1, entry 1). In contrast, the use of the may be partly correlated with the formation of inactive
P(CH3)2(C6H5) as the ligand1b resulted in both lower yield nickel carbonyl phosphine complexes, as Walther et al.
and selectivity (Table 1, entry 5). The sterically bulky demonstrated for the Ni(cod)2/P(C2H5)3 catalyst under
P(c-C6H11)3 gave 4a as the main product (49%; Table 1, scCO2 conditions.10 The Ni(cod)2/3a catalyst also gave 2a
entry 2). These results show that the trialkylphosphine in high yields over a wide range of CO2 pressures
ligands bearing a long primary alkyl chain such as 3a and (Table 2, entries 12 and 13). Noteworthy was the high se-
3b are effective ligands for the solvent-free Ni(0)-cata- lectivity (ca. 95%) for 2a at a CO2 pressure of 4 MPa,
lyzed cycloaddition of 1a with CO2 under compressed which was similar to 3b.
CO2. This ligand effect is new and noteworthy because
Thus, the findings herein demonstrate that the use of 3a
and 3b as ligands for Ni(cod)2 enables the solvent-free and
highly efficient cycloaddition of 1a with CO2 under mild
reaction conditions. A CO2 pressure of 4 MPa is sufficient
Walther et al. reported a different ligand effect in scCO2,10
where the order of decreasing ligand efficiency was
P(CH3)3 > P(C2H5)3 > P(C3H7)3.
Table 2 shows the effect of reaction conditions on the for achieving ≥95% selectivity for 2a. An additional
Ni(cod)2/3a- and Ni(cod)2/3b-catalyzed cycloaddition of advantage of the new catalytic systems is the ease of
1a with CO2 under compressed CO2. The effect of the CO2 handling 3a and 3b in comparison to the reported P(CH3)3
pressure on the reaction employing ligand 3b at 120 °C is and P(C2H5)3 ligands,10 since the latter two smell horrible
shown (Table 2, entries 1–6). CO2 pressures of 4–15 MPa and have pyrophoricity and/or a poorer stability toward
had no significant effect on the yield of 2a and the selec- oxygen.14,15
Synlett 2005, No. 14, 2141–2146 © Thieme Stuttgart · New York

LETTER
Solvent-Free Synthesis of 2-Pyrones from Alkynes and Carbon Dioxide
2143
a
Table 2 The Effect of Reaction Conditions on the Ni(0)-Catalyzed Cycloaddition of 3-Hexyne (1a) with CO2 under Compressed CO2
Entry
PR¢3
(3)
Ni(cod)2
(mol%)
Temp
(°C)
CO2 Pressure Time
Conversion
(%)b
Yield (%)b
(MPa)
2
(h)
5
2a
4a
13
4
5a
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
<1
1
2
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
3a
3a
10
10
10
10
10
10
10
10
10
10
5
120
120
120
120
120
120
100
100
80
96
99
100
99
99
98
94
99
95
90
72
97
99
76
90
93
95
97
92
86
98
85
88
70
91
97
4
5
3
7
5
4
4
9
5
1
5
11
15
4
5
1
6
5
4
7
5
5
8
12
4
5
<1
6
9
5
10
11
12
13
80
12
15
4
5
<1
1
100
120
120
20
5
10
10
5
12
5
<1
a Conditions: 1a (2 mmol), 3/Ni(cod)2, 2:1.
b Determined by GC analysis on the basis of the alkyne 1.13
a
Table 3 The Effect of Alkynes on Ni(0)-Catalyzed 2-Pyrone Formation under Compressed CO2
R
Ni(cod)2
R
R
R
PR'3 (3)
R
R
CO2
2
+
O
CO2
1
O
2
Entry
R in 1
PR¢3 (3)
CO2 Pressure
(MPa)
Conversion
(%)b
2-Pyrone 2
Yield (%)b
Selectivity (%)b,c
1
2
3d
4
5
6
7
8
9
C3H7 (1b)
3b
3b
3b
3a
3a
3b
3b
3b
3b
4
12
12
4
99
99
76
96
99
61
86
0
91
91
>99
>99
69
98 (96)
76
66
12
12
18
17
12
95
96
C4H9 (1c)
52
88
CH2OCH3 (1e)
CH2OCOCH3 (1f)
Si(CH3)3 (1g)
78 (44)
94e
17
0
a Conditions: 1 (2 mmol), Ni(cod)2 (0.2 mmol), 3 (0.4 mmol), 120 °C, 5 h.
b Determined by GC analysis on the basis of the alkyne 1.13 Isolated yields are shown in parentheses.
c The selectivity for 2.13
d At 100 °C.
e Hexa(methoxymethyl)benzene (5e) was isolated as the sole by-product (7%).
Synlett 2005, No. 14, 2141–2146 © Thieme Stuttgart · New York

2144
Y. Kishimoto, I. Mitani
LETTER
Ni(cod)2
3b
Visual inspection of the reaction mixtures using Ni(cod)2/
3a or Ni(cod)2/3b catalyst (3/Ni(cod)2, 2:1) revealed that
the reaction does not proceed homogeneously and a dark
brown liquid phase is present under the compressed CO2
phase (2–15 MPa) throughout the reaction. Its volume
was approximately equal to the volume sum of the com-
bined Ni(cod)2, 3, and 2. In a separate experiment, the sol-
ubility of the reaction components and 2-pyrone products
in scCO2 was examined. The alkyne substrates were mis-
cible with scCO2 while 3b and the 2-pyrones obtained
were not completely soluble in scCO2; Ni(cod)2 and
Ni(cod)2/3b were insoluble in scCO2. These results indi-
cate that the dark brown liquid phase possibly contains an
active Ni(0) catalytic species. The efficient 2-pyrone for-
mation at a low CO2 pressure of 4 MPa where CO2 exists
in the gaseous phase also suggests participation of the
above-mentioned liquid phase in the 2-pyrone formation.
2 CH3
C2H5
CO2
+
CO2 (12 MPa)
120 °C, 5 h
1d
74% conv.
CH3
CH3
C2H5
other three possible
regioisomers
O
+
C2H5
O
2d' (38%)
2d: 65% (in total)
Scheme 2
ity. Hexa(methoxymethyl)benzene (5e) was obtained as
the sole by-product (7%),19 and cyclopentadiene-type
alkyne trimers (4e) were not observed. However, 1,4-di-
acetoxy-2-butyne (1f) and bis(trimethylsilyl)acetylene
(1g) were essentially unreactive under the reaction condi-
tions employed, and these alkynes were recovered from
the reaction mixtures (Table 3, entries 8 and 9). The low
reactivity of 1f and 1g may be due to their electronic na-
ture and the steric bulk of the functional groups, respec-
tively.
As is described in the introductory section, the substrate
scope of the 2-pyrone formation by the previously report-
ed Ni(cod)2/P(CH3)3 and Ni(cod)2/P(C2H5)3 catalysts in
scCO210 was very limited: the yields of 2-pyrones from 4-
octyne (1b) and 2-butyne, having a sterically small methyl
substituent, were 8% [Ni(cod)2/P(C2H5)3 catalyst] and 4%
[Ni(cod)2/P(CH3)3 catalyst], respectively. Therefore, the
substrate scope of the solvent-free 2-pyrone formation
with Ni(cod)2/3a and Ni(cod)2/3b catalysts was examined
(Table 3).
Thus, the combined results of 1a, 1b, 1c, 1d, and 1e re-
vealed that the solvent-free 2-pyrone synthesis with
Ni(cod)2/3b catalyst under compressed CO2 can be ap-
plied to a broader scope of substrates compared with pre-
viously reported Ni(cod)2/P(CH3)3 and P(C2H5)3 catalysts
in scCO2.10
The reaction of 1b with CO2 (12 MPa) in the presence of
Ni(cod)2/3b (120 °C, 5 h) gave the corresponding 2-py-
rone 2b in 98% yield and >99% selectivity (Table 3, entry
2). The formation of 2b was confirmed by GC-MS and 1H
NMR spectroscopic analyses.1a The same reaction at 4
MPa produced 2b in excellent yield with a slight decrease
in selectivity (Table 3, entry 1). Lowering the reaction
temperature to 100 °C reduced the yield of 2b, but the
high selectivity was maintained (Table 3, entry 3). On the
other hand, the Ni(cod)2/3a-catalyzed reaction of 1b at
120 °C was found to be sensitive to CO2 pressure. The re-
action at 12 MPa proceeded cleanly with 96% selectivity
(2b), whereas a remarkably decreased selectivity (69%)
was observed at 4 MPa (Table 3, entries 4 and 5). 5-De-
cyne (1c) reacted with CO2 (12 MPa) more slowly than 1a
or 1b, and gave the corresponding 2-pyrone 2c16 with 88%
selectivity (Table 3, entry 6).
The reaction path is reasonably assumed to involve an ini-
tial [2 + 2] cycloaddition of the first alkyne molecule with
CO2 (Scheme 3).10,20 Subsequent insertion of the second
alkyne molecule followed by reductive elimination would
then release the 2-pyrone product 2 and regenerate the ac-
tual catalytic species. Nickel(0) complexes having an
electron-rich metal center may promote the coordination
of alkynes,10 the reductive elimination1d and, hence, the
formation of 2. The effectiveness of phosphines 3a and 3b
as ligands, especially at low CO2 pressure, may be partly
attributed to their high electron-donating ability.21,22
In summary, solvent-free, efficient, and mild 2-pyrone
synthesis by the cycloaddition of alkynes with CO2 has
been achieved under compressed CO2 with a Ni(cod)2/
P(C4H9)3 or Ni(cod)2/P(C8H17)3 catalyst; both high yields
(up to 98%) and selectivities (up to 99%) are attained. One
attractive aspect of these catalysts is their high efficiency
at low CO2 pressures (4 MPa). The applicability of this re-
action to a broad range of alkyne substrates and the ease
of handling the phosphine ligands are additional merits of
the present new catalytic systems in comparison to the
previously reported Ni(cod)2/P(CH3)3 catalyst in scCO2.
Expanding the substrate scope and enhancing the per-
formance of the catalyst are currently underway in our
laboratory.
The Ni(cod)2/3b catalyst afforded 2-pyrone 2d from 2-
pentyne (1d) having a sterically small methyl substituent
with reasonable yield (65%) and satisfactory selectivity
(93%) (Scheme 2). 2-Pyrone 2d obtained consists of four
possible regioisomers, among which 3,6-diethyl-4,5-di-
methyl-2-pyrone (2d¢) was found to be the main product
(38% yield) following careful isolation by column chro-
matography and by spectral characterization.17
The tolerance of the Ni(cod)2/3b catalyst to functionality
on the alkynes was briefly examined. The reaction of 1,4-
dimethoxy-2-butyne (1e) with CO2 (18 MPa) gave 2e in
78% yield and 94% selectivity (Table 3, entry 7),18 indi-
cating that the catalyst tolerates the methoxy functional-
Synlett 2005, No. 14, 2141–2146 © Thieme Stuttgart · New York

LETTER
Solvent-Free Synthesis of 2-Pyrones from Alkynes and Carbon Dioxide
2145
Ni(cod)2 (0.2 mmol) was placed in a stainless steel autoclave
containing a magnetic stirring bar, and, to this, was added the
above mixture via a dry syringe. CO2 (ca. 5 MPa) was
quickly introduced, and the autoclave was immersed in an
oil bath at 120 °C. When the temperature of the reactor
reached the desired temperature (typically after about 10
min), more CO2 was added to achieve the desired pressure of
15 MPa. The time of the second addition of CO2 was
considered to be the start of the reaction. The mixture was
allowed to stir for 20 h. Then, the vessel was removed from
the oil bath, immersed in an ice bath for ca. 1 h, and allowed
to cool to ca. 0 °C. Excess CO2 was then slowly vented at ca.
0 °C. The remaining organic liquid was diluted with acetone.
The GC analysis of the solution indicated the conversion of
1a and the yield of 2a were 100% and 95%, respectively.
Acetone was removed by evaporation, and the residue was
chromatographed on silica gel (hexanes–EtOAc, 15:1) to
give analytically pure 2a in 91% isolated yield. The product
was identified by 1H NMR and GC-MS analyses. The 1H
NMR spectrum was identical to the spectral data reported in
ref. 1a.
R
R
R
Ni(PR'3)n
R
R
1
+
O
R
CO2
O
2
R
Ni(PR'3)n
R
O
R
O
R
R
R
Ni(PR'3)n
O
O
R
R
1
Scheme 3
Acknowledgment
(12) CAUTION: Certain alkynes turn immediately brown when
they are mixed with trialkylphosphines and the use of such
alkynes does not give desired results. The reason for this is
unclear at this time, but we recommend the use of the
alkynes that cause no color change.
The authors wish to thank Dr. Tetsuo Tsuda of the Aichi Institute of
Technology for helpful discussions and valuable comments. The
authors are grateful to Professor Naoto Chatani of Osaka University
for the HRMS analysis and measurement of NMR spectra.
(13) The product yield was determined by GC analysis on the
basis of the alkyne 1 employed. Thus, the yield (%) of 2-
pyrone 2 = 100 ꢀ [(mmol of alkyne component in 2) / (mmol
of 1)] = 100 ꢀ [(2 ꢀ mmol of 2) / (mmol of 1)]; and the yield
(%) of alkyne trimer 4 or 5 = 100 ꢀ [(mmol of alkyne
component in 4 or 5) / (mmol of 1)] = 100 ꢀ [(3 ꢀ mmol of 4
or 5) / (mmol of 1)].
References
(1) (a) Inoue, Y.; Itoh, Y.; Kazama, H.; Hashimoto, H. Bull.
Chem. Soc. Jpn. 1980, 53, 3329. (b) Walther, D.;
Schönberg, H.; Dinjus, E.; Sieler, J. J. Organomet. Chem.
1987, 334, 377. (c) Tsuda, T.; Morikawa, S.; Sumiya, R.;
Saegusa, T. J. Org. Chem. 1988, 53, 3140. (d) Louie, J.;
Gibby, J. E.; Farnworth, M. V.; Tekavec, T. N. J. Am. Chem.
Soc. 2002, 124, 15188.
(2) For a discussion of the chemistry of 2-pyrone, see: Stauton,
J. In Comprehensive Organic Chemistry, Vol. 4; Samnes, P.
G., Ed.; Pergamon Press: Oxford, 1979, 629.
The selectivity for 2 is defined as the mol% of 2 in all of the
reaction products and is calculated from the yields of 2, 4,
and 5 by using the above equations. Thus, the selectivity (%)
for 2 = 100 ꢀ [(mmol of 2) / (mmol of 2 + mmol of 4 + mmol
of 5)] = 100 ꢀ [(% yield of 2) / 2] / {[(% yield of 2) / 2] + [(%
yield of 4) / 3] + [(% yield of 5) / 3]}.
(3) (a) Kvita, V.; Fischer, W. Chimia 1992, 46, 457. (b) Kvita,
V.; Fischer, W. Chimia 1993, 47, 3.
(14) For safety data for P(CH3)3, see: (a) Sigma-Aldrich Library
of Chemical Safety Data, Vol. 2; Lenga, R. E., Ed.; Sigma-
Aldrich Corp.: Milwaukee, 1995, 3435C. (b)Sigma-Aldrich
Library of Regulatory & Safety Data, Vol. 1; Lenga, R. E.;
Votoupal, K. L., Eds.; Sigma-Aldrich Corp.: Milwaukee,
1993, 1087E.
(15) For safety data for P(C2H5)3, see: Sigma-Aldrich Library of
Regulatory & Safety Data, Vol. 1; Lenga, R. E.; Votoupal,
K. L., Eds.; Sigma-Aldrich Corp.: Milwaukee, 1993, 1087C.
(16) Selected data for compound 2c: 1H NMR (CDCl3, 270
MHz): d = 2.36–2.49 (m, 6 H, CH2), 2.24–2.29 (t, J = 7.3 Hz,
2 H, CH2), 1.59–1.70 (m, 2 H, CH2), 1.30–1.45 (m, 14 H,
CH2), 0.91–1.00 (m, 12 H, CH3). 13C NMR (CDCl3, 67.5
MHz): d = 163.7 (C=O), 158.1 (Cvinyl), 154.5 (Cvinyl), 123.2
(Cvinyl), 115.4 (Cvinyl), 33.4 (CH2), 32.1 (CH2), 31.2 (CH2),
30.7 (CH2), 30.1 (CH2), 29.3 (CH2), 27.1 (CH2), 26.6 (CH2),
23.3 (CH2), 23.1 (CH2), 23.0 (CH2), 22.6 (CH2), 14.1 (CH3),
13.93 (CH3), 13.90 (CH3), 13.8 (CH3). HRMS (EI): m/z
calcd for C21H36O2: 320.2715. Found: 320.2729.
(17) Through careful column chromatography on silica gel
(hexanes–EtOAc, 30:1), analytically pure 2d¢ could be
isolated from the reaction mixture as a colorless oil (15 mg,
8%). 1H NMR (CDCl3, 270 MHz): d = 2.54 (t, J = 7.6 Hz, 2
H, CH2), 2.53 (t, J = 7.6 Hz, 2 H, CH2), 2.09 (s, 3 H, CH3),
1.94 (s, 3 H, CH3), 1.19 (t, J = 7.6 Hz, 3 H, CH3), 1.07 (t,
J = 7.6 Hz, 3 H, CH3). 13C NMR (CDCl3, 67.5 MHz): d =
163.4 (C=O), 157.9 (Cvinyl), 150.8 (Cvinyl), 124.4 (Cvinyl),
110.8 (Cvinyl), 24.6 (CH2), 20.5 (CH2), 16.3 (CH3), 13.0
(4) For a synthesized 2-pyrone with anti-HIV activity, see: Vara
Prasad, J. V. N.; Para, K. S.; Lunney, E. A.; Ortwine, D. F.;
Dunbar, J. B. Jr.; Ferguson, D.; Tummino, P. J.; Hupe, D.;
Tait, B. D.; Domagala, J. M.; Humblet, C.; Bhat, T. N.; Liu,
B.; Guerin, D. M. A.; Baldwin, E. T.; Erickson, J. W.;
Sawyer, T. K. J. Am. Chem. Soc. 1994, 116, 6989.
(5) Benign by Design. Alternative Synthetic Design for
Pollution Prevention, Vol. 577; Anastas, P. T.; Farris, C. A.,
Eds.; American Chemical Society: Washington DC, 1994.
(6) Eckert, C. A.; Knutson, B. L.; Debenedetti, P. G. Nature
(London, U.K.) 1996, 383, 313.
(7) Chemical Synthesis Using Supercritical Fluids; Jessop, P.
G.; Leitner, W., Eds.; Wiley-VCH: Weinheim, 1999.
(8) Reetz, M. T.; Könen, W.; Strack, T. Chimia 1993, 47, 493.
(9) It has been suggested that this reaction might occur as a
multiphase reaction (i.e. between CO2 and catalyst both
dissolved in liquid 3-hexyne) and not in scCO2: Dinjus, E.
COST/Dechema Workshop; Lahnstein Germany, April
1995.
(10) Kreher, U.; Schebesta, S.; Walther, D. Z. Anorg. Allg. Chem.
1998, 624, 602.
(11) Typical procedure for the Ni(0)-catalyzed cycloaddition
of alkynes with CO2: All manipulations were carried out
under a nitrogen or argon atmosphere. Alkyne 1a (2 mmol),
phosphine 3b (0.4 mmol), and o-xylene (40 mL, internal
standard for GC analysis) were mixed in a Schlenk tube.
Synlett 2005, No. 14, 2141–2146 © Thieme Stuttgart · New York

2146
Y. Kishimoto, I. Mitani
LETTER
(19) Selected data for compound 5e: 1H NMR (CDCl3, 270
(CH3), 12.8 (CH3), 12.1 (CH3). 1H NMR: NOE enhancement
(2.8%) between the methyl protons at 1.94 ppm and the
methyl protons at 2.09 ppm was observed. HRMS (EI): m/z
calcd for C11H16O2: 180.1146. Found: 180.1144.
MHz): d = 4.60 (s, 12 H, CH2O), 3.41 (s, 18 H, CH3O). MS
(EI): m/z (%) = 310 (38) [M+ – 32], 295 (100), 265 (42), 233
(30), 203 (23).
(18) Selected data for compound 2e: 1H NMR (CDCl3, 270
MHz): d = 4.47 (s, 2 H, CH2O), 4.45 (s, 2 H, CH2O), 4.37 (s,
2 H, CH2O), 4.33 (s, 2 H, CH2O), 3.42 (s, 3 H, CH3O), 3.41
(20) (a) Walther, D.; Bräunlich, G.; Kempe, R.; Sieler, J. J.
Organomet. Chem. 1992, 436, 109. (b) Hoberg, H.;
Schaefer, D.; Burkhardt, G.; Kruger, C.; Romao, M. J.
Organomet. Chem. 1984, 266, 203.
(s, 3 H, CH3O), 3.40 (s, 3 H, CH3O), 3.37 (s, 3 H, CH3O). 13
C
NMR (CDCl3, 67.5 MHz): d = 162.1 (C=O), 158.6 (Cvinyl),
152.1 (Cvinyl), 123.7 (Cvinyl), 115.4 (Cvinyl), 68.6 (CH2O), 67.0
(CH2O), 65.6 (CH2O), 65.1 (CH2O). HRMS (EI): m/z calcd
for C13H20O6: 272.1260. Found: 272.1257.
(21) Bartik, T.; Himmler, T.; Schulte, H.-G.; Seevogel, K. J.
Organomet. Chem. 1984, 272, 29.
(22) Bodner, G. M.; May, M. P.; McKinney, L. E. Inorg. Chem.
1980, 19, 1951.
Synlett 2005, No. 14, 2141–2146 © Thieme Stuttgart · New York