Decarbonylative Heck olefination of enol esters: Salt-free and environmentally friendly access to vinyl arenes

Article abstract of DOI:10.1002/anie.200352357

Thank you, no salt on the side. In this variant of the Heck olefination, enol esters serve as environmentally friendly synthetic equivalents of aryl halides. These reactants, in turn, are available from a waste-free synthesis from carboxylic acids and propyne. Thus, a salt-free overall process has been devised for preparing vinyl arenes from a variety of aromatic carboxylic acids.

Full text of DOI:10.1002/anie.200352357

Angewandte
Chemie
Pd-Catalyzed Couplings
Herein, we report on a novel strategy for the introduction
of carbon chains to arenes that fulfills these requirements in
an excellent way (Scheme 1). Aromatic carboxylic acids 1 are
initially converted into the isopropenyl esters 3 in a waste-free
Decarbonylative Heck Olefination of Enol Esters:
Salt-Free and Environmentally Friendly Access to
Vinyl Arenes**
Lukas J. Gooßen* and Jens Paetzold
Dedicated to Prof. Dr. Manfred Reetz
on the occasion of his 60th birthday
The Mizoroki–Heck reaction, one of the most elegant
methods for the attachment of carbon chains onto
aromatic rings, has found many applications in both
academic and industrial laboratories.[1] The standard
process starting from aryl halides,[2] triflates,[3] diazo-
nium salts,[4] aroyl-[5] and arylsulfonyl halides[6] suffers
from the requirement of stoichiometric amounts of base to
neutralize the acid released in the reaction. The large
quantities of salts inevitably formed must then be separated
and disposed of in an environmentally acceptable way—a
complex procedure, particularly on an industrial scale.
The reduction of the salt load of Heck reactions has
previously been approached in two ways: In the first,
nonfunctionalized arenes are used for the oxidative coupling
with olefins.[7] In analogy to the Friedel–Crafts reaction, this
reaction is regioselective for very few substrates; usually
product mixtures are obtained that can be hard to separate.
The second, more generally applicable approach makes use of
carboxylic acids as the source of the aryl residue.[8–10] These
are first converted into the corresponding anhydrides or
p-nitrophenyl esters, which are then used in a palladium-
catalyzed decarbonylative olefination step. The substitution
pattern on the aromatic ring is determined by the position of
the carboxylate group. Along with the desired vinyl arenes,
the corresponding carboxylic acid or p-nitrophenol is pro-
duced as the by-product, which can be converted back into the
starting material with fresh carboxylic acid. In the overall
process, the only by-products eliminated are hence CO and
water. However, the technical realization of such a cyclic
process would be rather difficult, and the ecological advan-
tage of a salt-free reaction might not balance the energy
required for the separation and recycling of the by-products.
Based on both economical and ecological considerations,
there is still a high demand for alternative processes that start
from environmentally benign compounds, produce no waste
salts, and require no energetically demanding material
streams.
Scheme 1. Salt-free synthesis of vinyl arenes from carboxylic acids.
and atom-economical fashion by coupling to propyne (2a) or
allene (2b), which are available from the C3 fraction from the
steam cracker.[11a] These intermediates 3 then react further to
give the vinyl arenes 5 in a newly developed decarbonylative
Heck olefination. The only by-products, CO and acetone (6),
can be burned in an environmentally neutral way, potentially
providing some of the energy required for the reaction.
While a number of active catalyst systems are available for
the first reaction step,[11] metal-catalyzed coupling reactions of
enol esters are still unknown. This second step in the process
would require metal complexes with enough activity to insert
À
into the C O bond of the poorly reactive enol esters. Such
catalysts could undergo a cycle consisting of the oxidative
addition of the enol ester to give an acyl–metal enolate,
decarbonylation to give the aryl complex, insertion of the
olefin into the metal–aryl bond, b-hydride elimination, and
protonation of the enolate with formation of the correspond-
ing ketone.[12]
Using the model reaction depicted in Scheme 2, a
conversion of isopropenyl benzoate (3a, R’ = Me) with
styrene (4a) to yield trans-stilbene (5a), we investigated the
catalytic activity of various combinations of palladium
precursors, additives, and ligands (Table 1). While barely
any conversion was observed for palladium acetate or
[Pd2(dba)3] (dba = dibenzylideneacetone) modest catalytic
activity for the desired reaction was displayed by palladium(ii)
[*] Dr. L. J. Gooßen, J. Paetzold
Max-Planck-Institut für Kohlenforschung
Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr (Germany)
Fax. (+49)208-306-2985
E-mail: goossen@mpi-muelheim.mpg.de
[**] We thank Prof. Dr. M. T. Reetz for generous support and constant
encouragement, D. Neis for technical assistance, and the DFG, the
FCI, and the BMBF for financial support.
Scheme 2. Decarbonylative Heck olefination of vinyl benzoates.
Angew. Chem. Int. Ed. 2004, 43, 1095 –1095
DOI: 10.1002/anie.200352357
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Communications
Table 1: Optimization of the catalyst system for the reaction in
Scheme 2.[a]
No. Pd source
Additive
R’
Solvent
Conv. Sel.[b]
1
2
3
4
Pd(OAc)2
(dba)3Pd2
PdCl2
PdBr2
PdCl2
PdCl2
PdCl2
PdCl2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
–
–
–
–
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
DMF
0
0
45
50
60
38
10
70
75
80
70
100
95
100
100
100
100
100
100
35
n.d.[c]
n.d.[c]
80
90
5
LiCl
LiCl
LiCl
LiBr
NaBr
KBr
LiBr
>95
95
6[d]
7[e]
8
n.d.[c]
>95
70
(entries 14–16).[13] With this additive, the catalyst load could
be reduced to 0.5 mol% without losses in the yield (entry 17).
The catalyst was recycled successfully following the
method of de Vries (entries 18, 19).[14] Thus, celite was
added to the reaction mixture, and palladium in reduced
form precipitated on it over the course of the reaction. After
complete conversion, the solid was removed by centrifugation
and treated with the corresponding amount of Br2 and 8b as
solutions in N-methylpyrrolidone (NMP). The resulting
mixture displayed the same catalytic activity as the original
catalyst.
9
10
11
12
13
14
15
16
>95
>95
90
(nBu)4N+BrÀ Me
(nOct)4P+BrÀ Me
90
8a
8b
8c
8b
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
>95
>95
75
95
95
17[f] PdBr2
18
19[g] PdBr2/celite 8b
20
21
22
23
24
25
26
27
PdBr2/celite 8b
95
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
PdBr2
8b
8b
8b
8b
8b
8b
8b
8b
50[h]
55
o-C6H4Cl2 40
sulfolane 90
–
N-Methylpyrrolidone proved to be a particularly suitable
solvent (entries 15, 20–22). In contrast to traditional Heck
reactions, the dilution can be significantly reduced since there
is no longer a necessity to dissolve stoichiometric amounts of
inorganic salts (entry 17). Notable product yields are obtained
even in the absence of a solvent—a major advantage of the
new protocol from an ecological perspective (entry 23).
Besides isopropenyl esters, other enol esters with terminal
double bonds, for example, vinyl benzoate (3b, R’ = H), 1-
(tert-butyl)vinylbenzoate (3c, R’ = tBu), and 1-phenylvinyl
benzoate (3d, R’ = Ph) were successfully olefinated
(entries 24–26). In the reaction of 2-hex-1-enyl benzoate
(3e, R’ = nBu), however, mainly isomerization to a mixture of
(E)- and (Z)-2-hex-2-enyl benzoate was observed (entry 27).
In the model reaction of the relatively unreactive styrene,
the principal product was trans-stilbene (5a); under opti-
mized conditions, 1,1-diphenylethylene (7a) was formed in
less than 10% yield. The only side-product observed was
triphenylethylene, at levels of around 2%. In analogy to the
traditional Heck olefination, yet higher selectivities were
obtained with activated olefins such as acrylates (Table 2, 5p).
The general applicability of the new reaction was inves-
tigated with a series of isopropenyl carboxylates 3a,f–r,
previously prepared from the corresponding carboxylic acids
and propyne gas,[11c] and with the olefins 4a–c following
Scheme 3. Table 2 shows the broad applicability of the new
Heck reaction variant. Electron-rich and electron-deficient
aryl, heteroaryl, and vinyl carboxylic acid esters were coupled
to various olefins in good yields. The reaction tolerates many
functionalities, including esters, ethers, nitro, keto, trifluoro-
methyl, and even formyl groups.
50
80
80
90
90
40
80
90
100
NMP
tBu NMP
Ph NMP
nBu NMP
90
<10[i]
[a] Reaction conditions: 1.00 mmol vinyl benzoate (3), 2.00 mmol
styrene (4a), 0.03 mmol Pd source, 0.03 mmol additive, 0.03 mmol
ligand, 4 mL solvent, 16 h, 1608C. Conversions and selectivities (both in
%) were determined by GC analysis with n-tetradecane as the internal
standard. The ratio 5a/7a was around 10:1 in all conversions. [b] Main
side products: benzoic acid and benzoic anhydride. [c] n.d.: not
determined. [d] With isoquinoline as a ligand. [e] With PPh3 as a
ligand. [f] 0.5 mL solvent, 0.005 mmol PdBr2, and additive. [g] Experi-
ment conducted with regenerated catalyst. [h] Side product: N,N-
dimethylbenzamide. [i] Isomerization to the product with the internal
=
C C bond.
halides (entries 1–4). In analogy to decarbonylative olefina-
tions of anhydrides and p-nitrophenyl esters, the conversion
could be improved by adding metal halides (entries 5, 8–11);
however, early precipitation of metallic palladium could not
totally be prevented by these additives. Coordinating ligands,
such as amines or phosphanes, succeeded in stabilizing the
palladium in solution, but at the same time decreased its
catalytic activity (entries 6, 7). Hence, only unsatisfactory
yields could be obtained when the catalytic systems optimal
for anhydrides[8d] or p-nitrophenyl esters[8b] were applied to
isopropenyl esters (entries 5, 6).
A combination of palladium bromide and tetraalkylam-
monium or tetraalkylphosphonium bromides proved to be
active and selective catalysts for these substrates (entries 12,
13). Finally, the hydroxy-substituted ammonium salts N-
dodecyl-N-methylephedrinium bromide (8a) and tri-n-
butyl(2-hydroxyethyl)ammonium bromide (8b) were found
to stabilize the palladium in solution for sufficient time to give
quantitative conversion along with high selectivity
The workup is particularly easy since only volatile side
products are formed: the celite is removed by filtration or
centrifugation together with the precipitated palladium(0),
the solvent is evaporated under high vacuum along with
excess olefin, then the vinyl arene is purified by distillation.
Overall, for the first time an efficient and selective catalyst
system for the decarbonylative Heck olefination of enol esters
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Table 2: Conversion of various isopropenyl carboxylates with olefins (Scheme 3).[a]
Cmpd.
Structure
Yield [%][b]
5:7[c]
Cmpd.
Structure
Yield [%][b]
92
5:7[c]
5a
95
10:1
5i
8:1
5b
5c
5d
85
78
92
9:1
5j
5k
5l
75
98
77
9:1
9:1
9:1
13:1
13:1
5e
5 f
96
75
10:1
10:1
5m
5n
95
87
15:1
15:1
5g
5h
99
63
15:1
9:1
5o
5p
67
98
5:1[d]
>50:1
[a] Reaction conditions: 1.00 mmol isopropenyl benzoate, 2.00 mmol olefin, 0.03 mmol PdBr2, 0.03 mmol 8b, 4 mL NMP, 16 h, 1608C. [b] Overall
yield [%] of vinyl arenas as isolated products. [c] The relative amounts of 1,2- and 1,1-substituted vinyl arenes were determined by gas chromatography.
[d] Mixture of double-bond isomers.
Experimental Section
5p: A 20-mL flask was charged with PdBr2 (8.00 mg, 0.03mmol), 8b
(9.30 mg, 0.03 mmol), and celite (200 mg). The flask was then heated to
1408C under vacuum for 15 min and flushed with argon. Subsequently,
3a (162 mg, 1.00 mmol), 4c (175 mL, 1.20 mmol), and NMP (4.00 mL)
were added by syringe. The resulting mixture was then stirred for 16 h
at 1608C. After filtration of Pd0/celite and removal of the volatiles
under high vacuum, the residue was fractionally distilled to give 5p
(195 mg, 95%) as a colorless liquid. The spectroscopic data of the
product correspond to those of (E)-3-phenyl-2-propenoic acid 1-
butylester, CAS registry number [538-65-8]. The Pd0/celite mixture was
dried under vacuum then treated with Br2 (2.00 mL, 0.037 mmol) in
NMP (1 mL) and stirred for 15 min. Following addition of 8b (9.30 mg,
0.03mmol), the mixture can be reused as the catalyst.
Scheme 3. Decarbonylative Heck olefination of isopropenyl
carboxylates.
has been developed. In contrast to traditional Heck reactions,
the addition of both base and solvent can be avoided, and
instead of waste salts, only volatile, flammable by-products
are formed. This reaction combined with a waste-free syn-
thesis of the isopropenyl ester substrates by addition of a
carboxylic acid onto propyne results in a salt-free, environ-
mentally benign overall process. This is the first example of a
palladium-catalyzed coupling reaction of the poorly reactive
enol esters and could open up new perspectives for related
reactions, such as ketone syntheses or reductions.[15]
The experiments in Table 2 were carried out analogously. The
products were purified by column chromatography and characterized
by NMR, MS, and HRMS.
Received: July 11, 2003
Revised: October 27, 2003[Z52357]
Published Online: January 29, 2004
Angew. Chem. Int. Ed. 2004, 43, 1095 –1095
www.angewandte.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1097

Communications
Keywords: alkenes · enol esters · Heck reaction · homogeneous
.
catalysis · palladium
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1098
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