Pd-catalysed direct dehydrogenative carboxylation of alkenes: Facile synthesis of vinyl esters

Article abstract of DOI:10.1039/c2cc37779a

A novel Pd-catalysed oxidative coupling reaction methodology using readily available carboxylic acids and alkenes for the preparation of vinyl esters has been developed. A broad range of vinyl esters were successfully synthesised. The reactions have demonstrated good efficiency as well as excellent chemo- and regio-selectivity.

Full text of DOI:10.1039/c2cc37779a

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Pd-catalysed direct dehydrogenative carboxylation of
alkenes: facile synthesis of vinyl esters†
Cite this: DOI: 10.1039/c2cc37779a
Dan Yang, Shixuan Ding, Jianhui Huang* and Kang Zhao*
Received 26th October 2012,
Accepted 20th December 2012
DOI: 10.1039/c2cc37779a
www.rsc.org/chemcomm
A novel Pd-catalysed oxidative coupling reaction methodology direct intra- and intermolecular dehydrogenative coupling reac-
using readily available carboxylic acids and alkenes for the pre- tions of carboxylic acids and alkenes have been reported.7
paration of vinyl esters has been developed. A broad range of vinyl
Herein, we report our latest discovery of Pd-catalysed oxida-
esters were successfully synthesised. The reactions have demon- tive coupling of carboxylic acids and alkenes for the synthesis of
strated good efficiency as well as excellent chemo- and regio- vinyl esters (Scheme 1c).
selectivity.
Our reaction condition optimization began with the reaction of
benzoic acid with butyl acrylate in the presence of 10 mol% of Pd
Vinyl esters present a class of useful organic building blocks catalyst. MeCN showed to be the best solvent when compared with
which have been utilized in polymer chemistry, chemical other solvents such as DMA, dioxane, butanol, toluene and H2O
industry and pharmaceutical sciences.1 Various traditional during the solvent screening. The addition of halogen salts8,9 did
processes for the synthesis of these motifs have been estab- not change the reactivity and the reaction conversions are rather
lished. Only recently, with the development of modern organo- low (Table 1, entries 2–4). When Cu salts were used as additives,
metallic chemistry, transition metal-catalysed reactions of our desired product was only obtained in poor yield. We pleasingly
carboxylic acids addition onto alkynes for the synthesis of found that under an O2 atmosphere10 when Ag2CO3 was employed
unsaturated esters have entered the chemical world. In hydro- the reaction speed increased rapidly and under these conditions,
carboxylation under Rh,2 Ru,3 Ag4 and Pd5-catalysed condi- the reaction gave our desired vinyl ester 3a in an excellent 91%
tions, carboxylic acids can be introduced onto alkynes to form yield. The reaction in the absence of O2 was sluggish, only
vinyl esters in an anti-Markovnikov’s fashion (Scheme 1a). resulting in 50% of conversion after 24 hours. While the combi-
In addition, the Stambuli group observed the oxidative coupling nation of O2 and K2CO3 instead of Ag2CO3 gave rise to total
of alkenes with carboxylic acids in a Markovnikov’s manner
(Scheme 1b).6 However, only a few transition metal-catalysed
Table 1 Reaction conditions screening
Entry
Catalyst
Additive
Yield (%)
Ratio (E : Z)
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
—
NaCl
NaBr
12
11
5
0
6
92 : 8
93 : 7
93 : 7
—
92 : 8
—
92 : 8
92 : 8
92 : 8
92 : 8
85 : 15
NaIÁ2H2O
Cu(OAc)2
CuBr2
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
0
Scheme 1 The synthesis of vinyl esters.
91
75
73
56
34
9
10
11
Pd(MeCN)2Cl2
Pd(PPh3)2Cl2
Pd2dba3
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of
Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
E-mail: jhuang@tju.edu.cn, kangzhao@tju.edu.cn; Fax: +86-22-27404031;
Tel: +86-22-27405316
Reaction conditions: benzoic acid 1a (37 mg, 0.3 mmol), butyl acrylate
2a (192 mg, 1.5 mmol), Pd catalyst (10 mol%), additive (2.0 equiv.) at
reflux in MeCN (1.5 mL, 0.2 M), 7–36 h.
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c2cc37779a
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Table 2 Unsaturated ester synthesis
Entry
1
Carboxylic acid 1
Unsaturated ester 3
Yield (E : Z)
Entry
9
Carboxylic acid 1
Unsaturated ester 3
Yield (E : Z)
91%
(92 : 8)
65%
(>98 : 2)
93%a
(93 : 7)
83%
(93 : 7)
2
3
4
10
11
12
92%a
(91 : 9)
68%a
(94 : 6)
78%
(92 : 8)
42%
(>98 : 2)
53%
(94 : 6)
47%a
(93 : 7)
5
6
13
14
88%
(91 : 9)
64%
(96 : 4)
80%
(92 : 8)
41%
(>98 : 2)
7
8
15
16
52%a
(93 : 7)
42%
(94 : 6)
Standard reaction conditions: benzoic acid 1 (0.3 mmol), butyl acrylate 2a (192 mg, 1.5 mmol), Pd(OAc)2 (10 mol%), Ag2CO3 (2.0 equiv.) at reflux under
1 atm O2, in MeCN (1.5 mL, 0.2 M), 7–36 h. a When 10 mol% was used, reactions did not go to completion, 20 mol% of Pd(OAc)2 was used instead.
decarboxylation of benzoic acid. These results suggest that the Ag Sterically hindered ortho-substituted benzoic acids are also
salt acted as both base and co-oxidant where O2 is the terminal demonstrated to be efficient substrates for the synthesis of
oxidant in the reaction. Other Pd sources, PdCl2, Pd(PPh3)2Cl2 and corresponding vinyl esters 3j and 3k. In addition, the attempts
Pd(MeCN)2Cl2, for instance, facilitated vinyl ester 3a in moderate on heteroaromatic and alkenyl carboxylic acids were all suc-
to good yields (entries 8–10). Interestingly, however, a Pd(0) source, cessful which gave rise to the desired corresponding vinyl esters
Pd2dba3, also provided our desired product in 34% yield albeit in good yields with excellent selectivity (entries 11–14). More-
with slightly lower (85 : 15) selectivity. In most of the cases, there is over, aliphatic carboxylic acids were also tolerated in this
1
only a trace amount of branched alkene detected in the H NMR reaction and secondary as well as tertiary substituted carboxylic
spectra of the crude reaction mixture.
With the optimal conditions in hand, a wide range of carboxylic esters 3o and 3p in useful 41% and 42% yields respectively.
acids as well as terminal alkenes were evaluated. When benzoic acid On the other hand, a group of alkenes were also investi-
acids were both working well to give the corresponding vinyl
reacted with butyl acrylate, our desired vinyl ester 3a was isolated in gated. We were pleased to find that when benzoic acid reacts
an excellent 91% yield with a good 92 : 8 E/Z ratio. Good reactivity with acrylamide 2b, our desired amide 3q was isolated exclu-
and regioselectivity were also observed for electron deficient sub- sively as the E alkene in a good 76% yield (Table 3, entry 2). The
stituted benzoic acids although 20 mol% Pd(OAc)2 was used in reaction with unsaturated ketones also worked and the vinyl
terms of pushing the reaction into high conversion. When electron ester 3r was isolated in 33% yield with greater than 98 : 2 E/Z
rich benzoic acids 1d and 1e were subjected to the reaction, the selectivity. The low yield was due to the rapid polymerization of
corresponding vinyl esters 3d and 3e were isolated in good 78% and reactive alkene 2c under these reaction conditions. Unactivated
53% yields respectively. meta-Substituted benzoic acids were also alkene 2d reacts fluently to provide vinyl esters in a good 58% yield
tolerated well in this type of transformation (Table 2, entries 5–8). with 36% of a mixture of C–H activation products 4 and 511,12
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Table 3 Reactions with various alkenes
presence of a Pd(II) catalyst as a Lewis acid. The resulting
8-membered palladacycle C was then tautomerized to give a
6-membered intermediate D where a Pd–C bond formed
instead of a Pd–O bond. After further bond rotation and
b-hydride elimination, the desired product 3a favouring a
thermodynamically stable E-isomer was formed with the elimi-
nation of HPdX. Further reductive elimination and reoxidation
of HPdX would give rise to active Pd(II) species which can be
used for the next catalytic cycle (Fig. 1).
Entry
1
2
3
Yield (E/Z)
91%
(92 : 8)
In conclusion, we have developed an efficient Pd-catalysed
dehydrogenative coupling approach for the synthesis of vinyl
esters from carboxylic acids and alkenes. As a good alternative
to hydrocarboxylation of terminal alkynes, this methodology is
suitable for the synthesis of a broad range of di-substituted vinyl
esters with good yields and excellent chemo- and regio-selectivity.
The financial support from the Cultivation Foundation for
the New Faculties from Tianjin University (No. 60302010) is
gratefully acknowledged.
76%
(>98 : 2)
2
3
4
33%
(>98 : 2)
58%
(67 : 33)
Notes and references
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65%
(>98 : 2)
5
6
72%
(>95 : 5)
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with only 4% of Z-stilbene.13 Alkene 2e with an adjacent sp3
hybridized carbon gave the corresponding allyl ester 3t in a good
65% yield (>98 : 2 E/Z) with the double bond migration. This is
consistently in agreement with White’s discovery of the allylic
ester synthesis.6,14 Compared to Stambuli’s results with AcOH
(60% yield with >95% E/Z selectivity), reaction of benzoic acid with
4-phenyl-1-butene 2f under our conditions gave ester 3u in 72%
yield with similar (>95 : 5 E/Z) selectivity (Table 3, entry 6).
A catalytic reaction pathway was then proposed. Similar to
Wacker oxidation,15,16 is the deprotonation of benzoic acid by
Ag2CO3 to facilitate the Ag salt A which can be added onto the
terminal side of the alkene without decarboxylation in the
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11 A 64 : 36 mixture of compounds 4 and 5 was isolated in 36% yield.
12 M. Miura, T. Tsuda, T. Satoh, S. Pivsa-art and M. Nomura, J. Org.
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Fig. 1 Proposed catalytic cycle.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun.