PPh3-catalyzed unexpected α-addition reaction of 1-(o-hydroxyaryl)-1,3-diketones to terminal alkynoates: A straightforward synthesis of multifunctional vinylesters

Article abstract of DOI:10.1039/b909279j

PPh₃-catalyzed α-addition reactions of 1-(o-hydroxyaryl)-1,3-diketones to terminal alkynoates involving carbon-carbon bond cleavage to give multifunctional vinylesters are described.

Full text of DOI:10.1039/b909279j

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PPh3-catalyzed unexpected a-addition reaction of
1-(o-hydroxyaryl)-1,3-diketones to terminal alkynoates:
a straightforward synthesis of multifunctional vinylestersw
Ling-Guo Meng,b Bin Hu,a Quan-Ping Wu,a Mao Lianga and Song Xue*a
Received (in Cambridge, UK) 11th May 2009, Accepted 3rd August 2009
First published as an Advance Article on the web 26th August 2009
DOI: 10.1039/b909279j
PPh3-catalyzed a-addition reactions of 1-(o-hydroxyaryl)-1,3-
diketones to terminal alkynoates involving carbon–carbon bond
cleavage to give multifunctional vinylesters are described.
at room temperature for 12 h afforded a colorless solid in
59% yield that was characterized as compound 3a by
NMR and HRMS spectra. The structure of 3a was further
confirmed unambiguously using single crystal X-ray analysis
(Fig. 1 in ESIw).
Vinylesters are important intermediates in organic synthesis.
They have served as key building blocks in the preparation of
nitrogen-containing molecules and used as monomers in
polymerization.1,2 Moreover, they have also been used as
valuable synthetic intermediates in total synthesis3 and as
versatile building blocks for many functionalized molecules.4
Recently, the carbon–carbon bond-forming reaction, using
electron-deficient alkynes as a source of carbon nucleophiles,
has been a useful method in organic synthesis.5 Trost, Taran
and co-workers have reported the phosphine-catalyzed
a-addition of activated methylenes to deficient-electronic
alkynes for the preparation of vinylesters.6
The amount of PPh3 catalyst has a slight effect on this
reaction. Desired product 3a was obtained in 51% yield when
20 mol% PPh3 was used. The yield of the product was not
improved by further increasing the amount of PPh3. The yield
of 3a was unsuccessfully improved under reflux conditions but
decreased sharply when the reaction was stirred at 0 1C.
PPh3 as a catalyst was crucial for the course of this reaction.
The use of other organic bases, such as tributylphosphine,
1,4-diazabicyclo[2,2,2]-octane (DABCO), triethylamine (Et3N)
and pyridine, did not give the desired product. The choice of
Et2O and toluene as solvents gave the desired product 3a in
58 and 59% yields, respectively. With tetrahydrofuran (THF),
acetone or dimethylformamide (DMF), 3a was produced in a
relatively low yield.
Recently, we have also described the PPh3-catalyzed
a-addition of 1,3-dicarbonyl compounds to acetylenic ketones
and the a-addition of aromatic aldehydes to terminal
alkynoates to provide various vinylesters.7 In continuation
of our interest in developing new addition reactions, we
further investigate the possibility of a-addition reactions of
1-(o-hydroxyaryl)-1,3-diketones to terminal alkynoates in the
presence of PPh3. Fortunately, an unexpected a-addition
reaction occurred, involving carbon–carbon bond cleavage.
Chemical transformations via carbon–carbon bond cleavage
have received much attention in recent years because new
skeletons can be constructed directly by such reactions.8
However, most of those reactions rely on transition metal
catalysis. Herein, we report the PPh3-catalyzed a-addition of
1-(o-hydroxyaryl)-1,3-diketones to terminal alkynoates,
involving carbon–carbon bond cleavage, for the synthesis of
multifunctional vinylesters.
With the reaction conditions optimized for the formation of
3a, subsequently we investigated the scope and limitations of
this reaction. Various 1-(o-hydroxyaryl)-1,3-diketones were
subjected to the reaction under the standard conditions;
representative results are shown in Table 2. When R1 was an
aromatic group, the reaction worked smoothly, giving the
Table 1 The reaction of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-
dione (1a) with ethyl propiolate (2a)
Our studies were initiated by the addition of 0.3 equiv. of
PPh3 to a solution of 1-(2-hydroxyphenyl)-3-phenylpropane-
1,3-dione (1a) and 1.1 equiv. of ethyl propiolate (2a) under
various reaction conditions; the results are shown in Table 1.
The reaction of 1a with 2a in the presence of PPh3 in CH2Cl2
Entry
Equiv. 1a
Equiv. 2a
Solvent
Yield (%)a
1
2
3
4
5
6
7
8
1.0
1.0
1.0
1.0
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.1
1.1
1.5
1.0
1.1
1.1
1.1
1.1
1.1
1.1
1.1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Et2O
Toluene
THF
Acetone
DMF
59
51b
60c
59
58
o5d
61e
58
a Department of Applied Chemistry, Tianjin University of Technology,
Tianjin 300384, P. R. China. E-mail: xuesong@ustc.edu.cn;
Fax: +86 22-60214252; Tel: +86 22-60214250
9
59
49
30
15
b Department of Chemistry, University of Science and Technology of
China, Hefei 230026, P. R. China
10
11
12
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and characterization data for all products,
and X-ray data for 3a. CCDC 711329. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/b909279j
a
b
Isolated yield. 20 mol% of PPh3 was used. 40 mol% of PPh3 was
c
d
e
used. At 0 1C. At reflux.
ꢀc
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Table 2 Reactions of 1-(2-hydroxyphenyl)-3-aryl-1,3-diones with 2a
catalyzed by PPh3 (30 mol%)
Table 3 Reactions of multi-substituted 1-(2-hydroxyaryl)-3-aryl-1,3-
diones 4 with terminal alkynoates 2 catalyzed by PPh3 (30 mol%)
Entry
1
Substrate
Product
Yield (%)a
Et
Et
Et
Et
78
Entry
R1
Product
Yield (%)a
1
2
3
4
5
6
7
8
9
C6H5
3a
3b
3c
3d
3e
3f
3g
—
3h
59
70
82
61
40
45
48
Trace
41
2
3
4
46
51
50
4-CH3OC6H4
3,4-(CH3O)2C6H3
4-CH3C6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-NO2C6H4
1-Thiophenyl
a
Isolated yield.
desired multifunctional vinylesters 3 in moderate to good
yields. Clearly, the substituents on the aromatic ring had an
effect on the reaction yield. Substrates with an electron-
donating group on the aromatic ring gave better yields
than those with an electron-withdrawing group on the
aromatic ring. For example, substrates with 4-methoxy and
3,4-dimethoxy groups on the aromatic ring afforded the
corresponding products 3b and 3c in 70 and 82% yields,
respectively. However, the substrate with a nitro group in
the para-position of the aromatic ring gave only a trace
amount of the desired product under the same conditions.
5
6
7
Et
Et
Et
26
33
45
Notably, when
a heteroaromatic 1,3-diketone, such as
8
9
Et
Me
NRb
—
46
55
1-(2-hydroxyphenyl)-3-(thiophen-2-yl) propane-1,3-dione, was
subjected to this reaction, the corresponding product, 3h, was
obtained in 41% yield.
To further evaluate the scope of this reaction, multi-
substituted 1-(2-hydroxyaryl)-3-aryl-1,3-diones 4a–h were
synthesized and tested under the standard conditions; these
results are summarized in Table 3. The treatment of substrates
4a–c with 2a in the presence of 30 mol% PPh3 afforded
the corresponding products 5a–c in 78, 46 and 51% yield,
respectively. Substrates 4d–g could be converted into the
corresponding products, albeit with lower yields. However,
no reaction was observed under the same conditions when
a-substituted b-diketone 4h was submitted to this reaction,
which might be due to steric hindrance of the methyl group.
On the other hand, terminal methyl and benzyl propiolates
could also be transformed into the corresponding products 5h
and 5i in moderate yields. In many cases, the moderate
yields obtained in the reaction could be accounted for by the
formation of other by-products, which could not be isolated
by column chromatography.
10
C6H5CH2
a
b
Isolated yield. NR = no reaction.
derivative in 49% yield, which was characterized as compound
7a by NMR and HRMS spectra. The yield of 7a increased to
59% when the reaction was performed at 0 1C for 24 h.
Various multi-substituted 1-(2-hydroxyaryl)-3-alkyl-1,3-diones
were also reacted smoothly with 2a to give chromone
derivatives in moderate yields; the experimental results are
summarized in Table 4.
On the basis of these experiments and previous investigations,6
a mechanistic pathway for this unexpected PPh3-catalyzed
a-addition reaction of 1-(o-hydroxyaryl)-1,3-diketones to ethyl
propiolates is proposed in Scheme 1. The reaction could be
triggered by the nucleophilic addition of PPh3 to the electron-
deficient multiple bond to produce zwitterion 8, which then
deprotonates the 1-(o-hydroxyaryl)-1,3-diketone to generate 9
and 10. Intermediate 10 could give enolate 11 through
a proton transfer step. Enolate 11 could then undergo a
We next extended the reaction to 1-(2-hydroxyaryl)-3-alkyl-
1,3-dione substrates 6. The desired multifunctional vinylesters
3 or 5 were not formed, but a new product was found when the
reaction was carried out under the above standard conditions.
For example, the exposure of 1-(2-hydroxyphenyl)butane-1,3-
dione 6a to 2a in the presence of PPh3 (30 mol%) at room
temperature for 12 h gave a new structure of a chromone
ꢀc
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Table 4 Reactions of 1-(2-hydroxyaryl)-3-alkyl-1,3-diones with ethyl
propiolate catalyzed by PPh3 (30 mol%)
Entry
1
Substrate
Product
Yield (%)a
Et
Et
59
2
3
4
46
38
40
Et
Et
Scheme 1 A plausible mechanism for the reaction of 1-(o-hydroxyaryl)-
1,3-diketones with 2a.
5
Et
39
bond cleavage. Meanwhile, 1-(2-hydroxyphenyl)-3-alkyl-1,3-
diones resulted in the formation of chromone derivatives in
moderate yields.
a
Isolated yield.
This work was supported by the NNSFC (20772116) and
the state 863 project (2009AA05Z421).
a-C-addition to 9 to afford 12, with the subsequent generation
of 13 through another proton transfer step. Intermediate 13
might then undergo an intramolecular nucleophilic addition
reaction to form intermediate 14, which is the key intermediate
of the reaction. When R is an aryl group, intermediate 14
would undergo a carbon–carbon bond cleavage to give 15,
followed by proton transfer and the elimination of PPh3 to
generate the desired product 3 or 5. On the other hand, when
R is an alkyl group, intermediate 14 would be transformed
into 16 by proton transfer and the elimination of PPh3.
Subsequently, elimination of a molecule of water from 16
affords product 7. A different product is obtained when R is
varied from an aryl to an alkyl group, which might be ascribed
to the more stabilized structure of an aromatic carbonyl group
than that of an alkyl carbonyl group. When R is an aromatic
group, the oxygen anion of intermediate 14 prefers to form a
carbonyl group, which is well stabilized by the aromatic
system. However, the mechanistic details for the formation
of these products need further investigation.
Notes and references
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In conclusion, we have described unexpected a-addition
reactions of 1-(o-hydroxyaryl)-1,3-diketones to terminal
alkynoates by means of PPh3. The reaction of 1-(2-hydroxy-
phenyl)-3-aryl-1,3-diones with terminal alkynoates afforded
multifunctional vinylesters in moderate to good yields under
mild conditions. The unexpected transformation is proposed
to proceed via an a-addition reaction and carbon–carbon
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 6089–6091 | 6091