Synthesis of allylarenes via catalytic decarboxylation of allyl benzoates

Article abstract of DOI:10.1002/adsc.201400624

A catalyst system consisting of the palladium(0) complex Pd₂(dba)₃ and tri(p-tolyl) phos-phine was found to efficiently promote the decarboxylation of allyl benzoates with formation of allylarenes. This catalytic C-O activation followed by extrusion of carbon dioxide and C-C bond formation represents a sustainable alternative to traditional waste-intensive cross-couplings. The scope of the transformation includes allyl and cinnamyl esters of various ortho-substituted benzoic acids. For particularly activated substrates, the palladium catalyst can optionally be replaced by an inexpensive nickel complex.

Full text of DOI:10.1002/adsc.201400624

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DOI: 10.1002/adsc.201400624
Synthesis of Allylarenes via Catalytic Decarboxylation of Allyl
Benzoates
Kai F. Pfister,a Matthias F. Grꢀnberg,a and Lukas J. Gooßena,*
a
Department of Chemistry, University of Kaiserslautern, 67663 Kaiserslautern, Germany
Fax : (+49)-631-205-3921; e-mail: goossen@chemie.uni-kl.de
Received: June 26, 2014; Revised: July 24, 2014; Published online: September 24, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400624.
Abstract: A catalyst system consisting of the palla-
dium(0) complex Pd2A(dba)3 and tri(p-tolyl)phos-
phine was found to efficiently promote the decar-
halides by ethers or carboxylates as the carbon elec-
trophiles. Prominent examples include Tsuji–Trost al-
lylations of allyl esters,[6] as well as Ni-catalyzed cross-
couplings of anisoles or aryl pivalates with organome-
tallic reagents.[7]
G
ACHTUNGTRENNUNG
boxylation of allyl benzoates with formation of
À
allyl
arenes. This catalytic C O activation followed
À
À
by extrusion of carbon dioxide and C C bond for-
mation represents a sustainable alternative to tradi-
tional waste-intensive cross-couplings. The scope of
the transformation includes allyl and cinnamyl
esters of various ortho-substituted benzoic acids.
For particularly activated substrates, the palladium
catalyst can optionally be replaced by an inexpen-
sive nickel complex.
The two innovative concepts of C O activation and
decarboxylative coupling are combined in the catalyt-
ic decarboxylation of allyl carboxylates (Scheme 1,
top). This reaction type was pioneered by the groups
of Tsuji[8] and Saegusa,[9] and advanced to synthetic
maturity by Tunge,[2c,10] Stoltz,[11] and others. However,
its scope has long remained limited to activated struc-
tures that, upon decarboxylation, lead to stabilized
carbanions, for example, enolates.[9] Such carboxylate
substrates, for example, a-oxo esters or dialkyl malo-
nates, readily extrude CO2 even without a catalyst.
Just recently, the reaction concept was extended to
a class of non-activated carboxylates. Thus, a combina-
tion of palladium and nucleophilic organocatalysts
was shown to catalyze the conversion of allyl a-oxo-
Keywords: allylation; decarboxylation; homogene-
ous catalysis; nickel; palladium
Over the past decades, transition metal-catalyzed carboxylates into the corresponding a,b-unsaturated
cross-coupling reactions have become established as ketones in a decarboxylation/isomerization sequence
À
powerful tools for the regioselective formation of C
(Scheme 1, center).[12]
C bonds.[1] In redox-neutral transformations, coupling
It would be highly desirable to use a related reac-
occurs between a carbon electrophile and a carbon tion concept also for the decarboxylative allylation of
nucleophile, usually an organometallic reagent. How- non-activated carboxylic acids, for example, simple
ever, the synthetic value of such transformations de- benzoic acids. The allylbenzene scaffold is a common
pends on the availability and stability of the starting structural motif,[13] and the allyl moiety is a versatile
materials, which are normally synthesized in addition- anchor for further derivatization.[14] However, the
al, waste-intensive steps. In recent years, the interest only example of an allylarene synthesis via decarbox-
in sustainable and salt-free alternatives has grown ylative coupling is the reaction of dimethoxyben-
considerably, and the use of cheap and easily avail- zoates with allyl halides reported by Liu et al., which
able carboxylic acids as coupling partners has re- calls for an elaborate palladium/copper catalyst
ceived tremendous attention.[2]
system and three equivalents of silver carbonate.[5a]
We herein present the first example of a decarboxy-
In decarboxylative couplings, organometallic re-
agents are replaced by simple carboxylates as the nu- lative allylation of benzoates that requires only a cata-
cleophilic coupling partner. This concept has found lytic amount of metal and no stoichiometric additive,
application in the synthesis of biaryls[3] and aryl ke- thus generating volatile CO2 as the only by-product.
tones,[4] and for introducing allyl and benzyl groups.[5]
The catalytic activation of C O bonds has allowed pentafluorobenzoate as a model substrate, since this
the replacement of ecologically questionable organo- benzoic acid decarboxylates easily in the presence of
We started the catalyst development by using allyl
À
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Synthesis of Allylarenes via Catalytic Decarboxylation
Scheme 1. Decarboxylative allylation of allyl esters.
Table 1. Optimization of the reaction conditions.[a]
palladium catalysts that are also known to efficiently
[15]
À
insert into allyl-C O bonds.
With Liuꢂs catalyst
system, the allylbenzene was observed in only 31%
yield, along with pentafluorobenzene. The monome-
tallic palladium catalyst that had been employed in
the decarboxylative allylation of a-oxocarboxylates
[2.5 mol% Pd
7% yield (Table 1, entry 1).
However, the yields increased when lowering the
amount of P(p-Tol)3, so that with 2.5 mol%, 42% of
2a were obtained. Even lower phosphine amounts
gave inferior results (Table 1, entries 1–5). Systematic
2ACHTUNGTRENNUNG(dba)3/25 mol% PACHTUNGTREN(NGUN p-Tol)3] gave only
#
Catalyst
PR3 (mol%)
Solvent
Yield [%][b]
ACHTUNGTRENNUNG
1
2
3
4
5
6
7
8
Pd
Pd
Pd
Pd
Pd
Pd
Pd
G
P
T
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
anisole
1,4-dioxane 73
diglyme
NMP
DMSO
1,4-dioxane 35
1,4-dioxane 27
7
P
N
29
34
42
29
7
28
0
0
PACHTUNGTRENNUNG
PACHTUNGTRENNUNG
–
–
variation of the Pd catalyst revealed that Pd
2ACHTUNGTNER(NUNG dba)3 is
optimal, although Pd(PPh3)4 and Pd(OAc)2 are also
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
A
active (Table 1, entries 6–9). Control experiments con-
firmed that the reaction does not take place in the ab-
sence of palladium (Table 1, entry 23).
Changing the solvent to 1,4-dioxane gave a decisive
step-up in the yields, whereas other solvents were less
effective (Table 1, entries 10–14). In comparison to
other triarylphosphines (Table 1, entries 15–18) and
P
R
PdCl2
PACHTUNGTRENNUNG
9
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
G
P
E
10
11
12
13
14
15
16
17
18
19
20
E
E
R
R
R
R
U
P
N
50
P
G
P
U
34
43
21
PACHTUNGTRENNUNG
PH
trialkylphosphines (Table 1, entries 19 and 20), PACTHNUTRGNEUNG(p-
Tol)3 gave the best results. The reaction temperature
also has a profound influence on the reaction out-
come. At the optimum temperature of 1108C, 2a was
obtained in near quantitative yield (Table 1, entry 21).
It is remarkable that double bond migration, as
occurs quantitatively in the case of a-oxocarboxylates,
is not observed.
Having thus identified an efficient catalytic system,
we next investigated the scope of the new reaction.
As can be seen from Table 2, various substituted allyl
benzoates could be converted to the corresponding al-
lylbenzenes in good to excellent yields. It is not sur-
prising that the scope with regard to the benzoic acids
remains limited to substrates that can be easily decar-
boxylated with palladium catalysts.[15] ortho-Nitroben-
PACHTUNGTRENNUNG
CTHUGNTRENNUN(G dba)3 P(p-MeO-C6H4)3 1,4-dioxane 25
E
CTHUNGTRENNUNG
C
PN
1,4-dioxane 58
1,4-dioxane 15
1,4-dioxane 9
1,4-dioxane 99
1,4-dioxane 13
1,4-dioxane 0
PACHTUNGTRENNUNG
PACHTUNGTRENNUNG
PACHTUNGTRENNUNG
PACHTUNGTRENNUNG
21[c] Pd
22[d] Pd
23
N
R
–
[a]
Reaction conditions: 1a (0.50 mmol), palladium
(5 mol%), PR3 (2.5 mol% unless otherwise specified),
solvent (2.5 mL), N2 atmosphere, 1008C, 24 h.
Yields were determined by GC analysis using n-tetrade-
cane as internal standard.
[b]
[c]
[d]
1108C.
908C.
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Table 2. Scope of the decarboxylation.[a]
Product
Yield [%] (2:3)
Product
Yield [%] (2:3)
88 (99:1)
99 (99:1)
68[b] (99:1)
76[c] (97:3)
92 (98:2)
97 (99:1)
92 (99:1)
22 (96:4)
87 (99:1)
61[d] (99:1)
99[b] (97:3)
66[e] (97:3)
99[f] (98:2)
97[f] (98:2)
87 (99:1)
trace[f]
0
90 (99:1)
84 (99:1)
95 (98:2)
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Synthesis of Allylarenes via Catalytic Decarboxylation
zoates and other substrates bearing only one substitu- Experimental Section
ent in the ortho-position were unreactive. Polyfluo-
rinated arenes gave particularly high yields, and me- General Procedure for the Palladium-Catalyzed
thoxy-substituted arenes were also smoothly convert- Decarboxylative Allylation
ed (2f, g).
A 20-mL vessel was charged with Pd2ACTHNUGTRNE(UNG dba)3 (22.9 mg,
On the allyl side, several substituents were tolerat-
ed both in the 2- and 3-positions. Bulky substituents
such as 3-cyclohexyl groups (2n, r) seem to hamper
the reaction, whereas 3-phenyl groups lead to even
better yields.
Double bond migration with formation of 3 was ob-
served in less than 4% yield for substrate 2n, which
bears a cyclohexyl-substituted allyl group, and in even
smaller amounts for all other products.
0.025 mmol) and tri-p-tolylphosphine (7.76 mg, 0.025 mmol)
and the vessel was brought under an atmosphere of dry ni-
trogen. 1,4-Dioxane (4 mL) and allyl 2,3,4,5,6-pentafluoro-
benzoate (1a, 252 mg, 1.00 mmol) were added via syringe
and the mixture was stirred at 1108C for 24 h. After cooling
to room temperature, the mixture was diluted with n-pen-
tane (20 mL), washed with aqueous 1N NaOH (3ꢃ20 mL),
water (20 mL) and brine (20 mL), dried over MgSO4 and fil-
tered. The solvent was removed at ambient pressure and the
products 2a–t were isolated from the residue by flash
column chromatography (SiO2, Et2O/n-pentane gradient).
We next investigated whether this transformation is
restricted to palladium catalysts only. Nickel(0) com-
plexes appeared to be promising candidates, since
they had successfully been used in C O activation.
Synthesis of Allyl 2,3,4,5,6-Pentafluorobenzene (2a)
[7]
À
Indeed, a systematic survey revealed that allyl penta-
fluorobenzoate can efficiently be decarboxylated by
a Ni(0) catalyst generated in situ from nickel(II) chlo-
ride, BINAP, and zinc powder (see the Supporting In-
formation, Table S1). With this system, 2a was ob-
tained in 82% yield at 1008C in NMP (Scheme 2).
For the 2,6-difluorobenzoate, the allylarene 2d was
obtained in 39% yield after 16 h at 1508C using
a dppe ligand. For even less activated substrates such
as 1g or 1k, the product was obtained only in traces
using this prototypical nickel catalyst.
Following the general procedure, compound 2a [CAS: 1736-
60-3] was synthesized from allyl 2,3,4,5,6-pentafluoroben-
zoate (1a, 252 mg, 1.00 mmol). The product was obtained as
1
a colorless liquid; yield: 183 mg (879 mmol, 88%). H NMR
(400 MHz, CDCl3): d=5.82–5.96 (m, 1H), 5.03–5.16 (m,
2H), 3.45 (dt, J=6.4, 1.7 Hz, 2H); 13C NMR (101 MHz,
CDCl3): d=145.1 (m), 139.8 (m), 137.2 (m), 132.9 (s), 116.8–
117.2 (m), 112.8–113.4 (m), 26.3 (d, J=1.47 Hz); 19F NMR
(376 MHz, CDCl3): d=À144.23 to À144.05 (m, 1F),
À157.73 to À157.38 (m, 1F), À163.04 to À162.75 (m, 1F);
IR (NaCl): n=1655, 1643, 1503, 1443, 1415, 1315, 1299,
1219, 1123, 1011, 983, 911, 895, 752, 692, 624 cmÀ1; HR-MS-
EI (TOF): m/z=208.0319 [M+], calcd. for C9H5F5: 208.0311;
anal. calcd. for C9H5F5: C 51.94, H 2.42; found: C 52.20, H
2.59.
In conclusion, the advantageous concept of forming
À
C C bonds by catalytic ester decarboxylation was
successfully employed for benzoic acid substrates. In
the presence of a Pd2ACTHNUGTRNENUG(dba)3/PACHTUGNTREN(NUNG p-Tol)3 catalyst, various
Nickel-Catalyzed Decarboxylative Allylation of 1a
allylarenes were synthesized in good yields, along
with CO2 as the only by-product. Particularly activat-
ed substrates can also be converted by inexpensive
nickel catalysts. Further catalyst development aiming
at extending this sustainable transformation to the
A crimp-cap reaction vessel was charged with nickel(II)
chloride (13.0 mg, 0.10 mmol), BINAP (76.2 mg, 0.12 mmol)
and zinc powder (65.4 mg, 1.00 mmol). Under an inert at-
mosphere, degassed NMP (2 mL) and 1a (252 mg,
entire range of allyl benzoates is currently underway. 1.00 mmol, 183 mL) were added via syringe. The reaction
Scheme 2. Nickel-catalyzed decarboxylative allylation of pentafluorobenzoates.
[a]
Reaction conditions: Allyl ester 1a–t (1.00 mmol), Pd
2CAHUTTNGREN(NGU dba)3 (2.5 mol%), PACHUTNTGRNE(NUGN p-Tol)3 (2.5 mol%), 1,4-dioxane (4 mL), N2 at-
mosphere, 1108C, 24 h, isolated yields, product ratios were determined by 19F NMR and GC analysis.
[b]
[c]
[d]
[e]
[f]
4 mol% P
ACHTUNGTRENNUNG
5 mol% PACHTUNGTRENNUNG
3.75 mol% PACHTUNGTRENNUNG
5 mol% Pd
N
ACHTUNGTNER(NUNG p-Tol)3.
1308C.
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COMMUNICATIONS
Kai F. Pfister et al.
mixture was stirred at 1008C for 16 h and then cooled to
room temperature. The slight pressure build-up caused by
the partially dissolved CO2 was carefully released by pierc-
ing the septum with a syringe needle before uncapping. Pen-
tane (20 mL) was added, and the mixture was washed with
water (2ꢃ20 mL) and brine (20 mL), dried over MgSO4, fil-
tered and concentrated (408C). The crude product was fur-
ther purified by flash chromatography (SiO2, pentane),
yielding the allylbenzene 2a as colorless liquid; yield:
171 mg (0.82 mmol, 82%). The analytical data matched
those described for allyl 2,3,4,5,6-pentafluorobenzene [CAS:
1736-60-3].
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Acknowledgements
We thank NanoKat and Saltigo GmbH for financial support
and Umicore for the generous donation of catalyst metals.
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