Palladium-catalyzed esterification of aryl halides using aryl formates without the use of external carbon monoxide

Article abstract of DOI:10.1039/c2cc33944g

Aryl formates are efficient carbon monoxide sources in palladium-catalyzed esterification of aryl halides. The carbonylation readily proceeds at ambient pressure without the use of external carbon monoxide to afford the corresponding esters in high yields.

Full text of DOI:10.1039/c2cc33944g

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COMMUNICATION
Palladium-catalyzed esterification of aryl halides using aryl formates
without the use of external carbon monoxidew
Tetsuaki Fujihara, Tomoya Hosoki, Yuko Katafuchi, Tomohiro Iwai, Jun Terao and
Yasushi Tsuji*
Received 1st June 2012, Accepted 22nd June 2012
DOI: 10.1039/c2cc33944g
Aryl formates are efficient carbon monoxide sources in palladium-
catalyzed esterification of aryl halides. The carbonylation readily
proceeds at ambient pressure without the use of external carbon
monoxide to afford the corresponding esters in high yields.
Scheme 1
only one equivalent of aryl formates is enough to afford the
Carbonylation processes using carbon monoxide (CO) as a
carbonylated products in high yields.7
carbonyl source constitute industrial core technologies for
First, the reaction of 4-bromotoluene (1a) with 1.5 equivalent
of phenyl formate (2a) was carried out in the presence of a
catalytic amount of PdCl2(PhCN)2 in a 10 mL glass flask
equipped with a standard ground glass joint (Table 1).8 Without
any ligand, phenyl 4-methylbenzoate (3a) was not obtained at all
(entry 1). With an addition of monodentate phosphines such
as PPh3, P(o-tol)3, or PCy3,9 3a was obtained in low yields
(entries 2–4). The use of a bidentate phosphine such as dppe,
dppp, dppf, or binap9 improved the catalytic activity (entries 5–8),
although yields of the product were not satisfactory. Among the
ligands examined, xantphos9,10 gave the best result, affording 3a
in 99% yield (entry 9). As a base, (i-Pr)2EtN, DBU, and K2CO3
afforded 3a in 82%, 70%, and 57% yields, respectively, while
pyridine and KOH did not provide 3a at all. Under the same
reaction conditions as in entry 9, alkyl formates (benzyl formate,
converting various bulk chemicals into functionalized useful
products.1 Despite large-scale applications in industry, carbonyla-
tions with CO are not comparatively used for more complex
organic syntheses. This might be due to general reluctance to use
the toxic gas as a reagent and frequent use of a high-pressure
reactor. Therefore, carbonylation reactions without the use of
external CO is highly desirable.2 As for the CO source, formic
acid and its esters are industrially produced from CO. Thus,
formate esters may be regarded as liquid condensates and
expedient alternative sources of CO. Actually, much effort has
been made to realize carbonylation reaction employing formate
esters as CO sources.3,4 However, the CO generation from usual
formate esters is not efficient and required relatively high reaction
temperature,3a co-catalysts,3b or strong bases.3c Recently,
Skrydstrup et al. reported ex situ generation of carbon monoxide
utilizing several CO sources by the aid of palladium catalysts.5
Although efficient CO generation and the carbonylation of
aryl halides proceeded, a two-chamber system must be used to
separate CO generation and carbonylation processes.
Table 1 Effect of ligands on the palladium-catalyzed esterification of
4-bromotoluene (1a) with phenyl formate (2a)a
We have recently found that aryl formates, not alkyl formates,
are very efficient CO sources under relatively mild reaction condi-
tions in the Pd–xantphos catalyzed hydroesterification of alkynes.6
However, in the reactions, an excess amount (4 or 10 equiv.) of
aryl formates must be indispensable for high yields of products.
Herein, we report the Pd-catalyzed esterification of aryl halides
employing aryl formates as CO sources (Scheme 1). By simply
mixing an aryl halide, an aryl formate, and a Pd catalyst in a
usual glass flask (no pressure bottle is required), highly efficient
esterification of the aryl halide was realized. Noteworthy is that
Entry
Ligand
Yieldb (%)
1
2
3
4
5
6
7
8
9
None
PPh3
P(o-tol)3
PCy3
dppe
dppp
dppf
rac-binap
Xantphos
0
27
0
0
12
37
15
50
99 (94)c
a
Reaction conditions: 4-bromotoluene (1a, 0.50 mmol), phenyl
formate (2a, 0.75 mmol), PdCl2(PhCN)2 (0.025 mmol, 5.0 mol%),
phosphine (0.025 mmol), Et3N (1.0 mmol) in DMF (0.5 mL) at 60 1C
Department of Energy and Hydrocarbon Chemistry,
Graduate School of Engineering, Kyoto University, Kyoto 615-8510,
Japan. E-mail: ytsuji@scl.kyoto-u.ac.jp; Fax: +81-75-383-2514;
Tel: +81-75-383-2515
b
for 20 h. Yield based on the GC internal standard technique.
c
Isolated yield of 3a.
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c2cc33944g
c
8012 Chem. Commun., 2012, 48, 8012–8014
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Table 2 Conversion of phenyl formate (2a) to phenol and carbon
monoxide
Table 3 Carbonylation of various substrates under the optimum
reaction conditionsa
Entry Reaction conditionsa
Yield of phenolb (%)
99
Yieldb
(%)
Entry 1
2
3
1
2
PdCl2(PhCN)2 (2.5 mol%),
xantphos (2.5 mol%), Et3N (1.0 equiv.)
PdCl2(PhCN)2 (2.5 mol%),
xantphos (2.5 mol%)
o5
3
4
5
Et3N (1.0 equiv.)
Et3N (1.0 equiv.) at 40 1C
Et3N (10 mol%)
99
24
o5
1c
2d
3
4
5
6
7
8
1b: R1 = OMe
1c: R1 = NMe2
1d: R1 = Cl
2a
3b: R1 = OMe
3c: R1 = NMe2
3d: R1 = Cl
91
83
96
89
92
1e: R1 = CF3
1f: R1 = Ac
3e: R1 = CF3
3f: R1 = Ac
a
Reaction conditions: 2a (1.0 mmol) in DMF (0.5 mL) at 60 1C
for 20 h. Yield based on the GC internal standard technique.
b
1g: R1 = COOMe
1h: R1 = NO2
1i: R1 = CHO
3g: R1 = COOMe 88
3h: R1 = NO2
3i: R1 = CHO
72
88
hexyl formate, and 2-phenylethyl formate) in place of 2a did not
convert and the corresponding esters were not provided at all.
Thus, 2a is a unique carbonyl source in the present carbonylation.
The conversion of 2a was monitored under various reaction
conditions (Table 2). In the presence of a catalytic amount
(2.5 mol%) of PdCl2(PhCN)2 and xantphos with 1.0 equiv. of
Et3N (the same catalytic conditions as in entry 9 in Table 1),8
phenol was obtained quantitatively with evolution of carbon
monoxide (entry 1). Removal of Et3N from the entry 1 resulted in
low conversion of 2a and phenol was obtained only in low yield
(entry 2). However, with 1.0 equiv. of Et3N alone, 2a was fully
converted and phenol was obtained in 99% yield (entry 3). Thus,
Et3N is responsible for the conversion of 2a. The reaction was slow
at 40 1C (entry 4) and 2a was not almost converted in the presence
of a catalytic amount of Et3N (entry 5). Under the reaction
conditions in entry 3, alkyl formates such as benzyl formate, hexyl
formate, and 2-phenylethyl formate were not converted at all,
which is very reminiscent of the catalytic reaction (vide supra).
Various aryl bromides (1b–n) reacted with 2a under the stan-
dard reaction conditions (Table 3). Aryl bromides bearing both
electron-rich (entries 1 and 2) and electron-poor (entries 3–8)
phenyl moieties gave the corresponding esters (3b–j) in high yields.
Nitro (entry 7), formyl (entry 8) and cyano (entry 9) functionalities
on the aryl ring tolerated the reaction conditions. Gratifyingly, 1l
bearing an ethynyl moiety afforded the corresponding ester (3l)
without hydroesterification6 at the alkyne moiety (entry 11).
Heterocycles such as pyridine and thiophene were also adapted
(entries 12 and 13). Besides 2a, the reaction of bromobenzene (1o)
with aryl formates (2b–e) bearing electron-rich (entries 14 and 15)
and electron-poor (entry 16) phenyl moieties gave the corres-
ponding esters (3o–q) in good to high yields. A sterically
demanding aryl formate (2e) also afforded 3r in high yield.
An alkenyl bromide (1p) reacted with 2a under the standard
reaction conditions to give phenyl cinnamate (3s) in 66% yield
(Scheme 2a). Iodobenzene (4) and phenyl triflate (5) also
afforded phenyl benzoate 3t in 85% and 88% yields, respectively
(Scheme 2b). Although a chloro moiety on the aryl ring was intact
under the standard reaction conditions (entry 3 in Table 3), an
aryl chloride bearing an acetyl moiety (6) gave the corresponding
ester 3f in 86% yield at the elevated temperature with (i-Pr)2EtN
as a base (Scheme 2c). In addition, benzyl bromide (7) was
smoothly converted to the corresponding phenyl ester (3u) by
using P(OPh)3 as a ligand11 at 120 1C (Scheme 2d).
9c
2a
84
10e
11e
12
2a
2a
2a
2a
89
87
91
92
13
14c
15
1o
1o
1o
2b: R2 = Me 3o: R2 = Me
2c: R2 = OMe 3p: R2 = OMe
77
92
97
16
2d: R2 = Cl
3q: R2 = Cl
17
1o
89
a
Reaction conditions: aryl bromide (1, 0.50 mmol), aryl formate
(2, 0.75 mmol), PdCl2(PhCN)2 (0.025 mmol, 5.0 mol %), xantphos
(0.025 mmol, 5.0 mol %), Et3N (1.0 mmol) in DMF (0.50 mL) at 60 1C
b
c
d
e
for 20 h. Isolated yields. At 70 1C. At 80 1C. At 90 1C.
Noteworthy is that the present catalytic system realizes
highly atom-efficient carbonylation. The reaction of 1a with
1 equiv. of 2a in DMF (0.1 mL) smoothly proceeded and 3a
was obtained in 93% isolated yield (Scheme 3).8 The yield was
almost comparable to that described in entry 9 in Table 1.
Other reactions employing 1d, 1e and 1f with 1.0 equiv. of
2a afforded the corresponding products in high yield. The
equimolar mixture of 1o and 2c in the presence of the Pd
catalyst also gave 3p in high yield.
In conclusion, the carbonylation of aryl halides using aryl
formates occurred at ambient pressure in the presence of a
Pd–xantphos catalyst system to afford aryl esters in good to
high yields. The reaction can be carried out without the use of
c
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Chem. Commun., 2012, 48, 8012–8014 8013

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(c) C. Godard, B. K. Munoz, A. Ruiz and C. Claver, Dalton Trans.,
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D. J. Thompson and M. V. Twigg, Carbonylation: Direct Synthesis
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2 For carbonylation utilizing in situ generated carbon monoxide, see:
T. Morimoto and K. Kakiuchi, Angew. Chem., Int. Ed., 2004, 43,
5580–5588 and references sited therein.
3 (a) T. Schareina, A. Zapf, A. Cotte, M. Cotta and M. Beller, Adv.
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4 Palladium-catalyzed esterification employing potassium oxalate
monoesters was reported: R. Shang, Y. Fu, J. Li, S. Zhang,
Q. Guo and L. Liu, J. Am. Chem. Soc., 2009, 131, 5738–5739.
5 (a) S. D. Friis, R. H. Taaning, A. T. Lindhardt and T. Skrydstrup,
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A. T. Lindhardt, R. H. Taaning, K. Bjerglund, D. Lupp and
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(c) P. Hermange, T. M. Gøgsig, A. T. Lindhardt, R. H. Taaning
and T. Skrydstrup, Org. Lett., 2011, 13, 2444–2447.
Scheme 2 Palladium-catalyzed carbonylation of various electrophiles
with 2a.
6 Y. Katafuchi, T. Fujihara, T. Iwai, J. Terao and Y. Tsuji, Adv.
Synth. Catal., 2011, 353, 475–482.
7 (a) Very recently, Manabe et al. reported the Pd-catalyzed carbo-
nylation with phenyl formate.7b This publication prompted us to
report our independent study7c,d featuring atom-efficient carbonyla-
tion with only 1 equiv. of phenyl formate; (b) T. Ueda, H. Konishi
and K. Manabe, Org. Lett., 2012, 14, 3100–3103; (c) T. Hosoki,
Y. Katafuchi, T. Iwai, T. Fujihara, J. Terao and Y. Tsuji, 58th
Symposium on Organometallic Chemistry, Japan, 2011, P3B-12,
presented on September 9, Nagoya, Japan; (d) T. Hosoki,
Y. Katafuchi, T. Iwai, T. Fujihara, J. Terao and Y. Tsuji, Interna-
tional Symposium on Catalysis and Fine Chemicals 2011
(C&FC2011), 2011, P1-35, presented on December 5, Nara, Japan.
8 See ESI for detailw.
9 Abbreviation: o-tol = 2-methylphenyl, Cy = cyclohexyl, dppe = 1,2-
bis(diphenylphosphino)ethane, dppp = 1,2-bis(diphenylphosphino)-
propane, dppf = 1,2-bis(diphenylphosphino)ferrocene, rac-binap =
bis(diphenylphosphino)-1,10-binaphthyl, xantphos: 4,5-bis(diphenyl-
phosphino)-9,9-dimethylxanthene.
Scheme 3 Highly efficient esterification of 1 with 2 catalyzed by the
palladium–xantphos system.
external carbon monoxide, and no directing group is required.
During the reaction aryl formates were converted to carbon
monoxide and the corresponding phenols by the aid of a base.
This work was supported by Grant-in-Aid for Scientific
Research on Innovative Areas (‘‘Organic synthesis based on
reaction integration’’ and ‘‘Molecular activation directed toward
straightforward synthesis’’) from MEXT, Japan. T. F. is acknowl-
edged to The Sumitomo Foundation for financial support.
Notes and references
10 J. R. Martinelli, D. A. Watson, D. M. M. Freckmann, T. E. Barder
and S. L. Buchwald, J. Org. Chem., 2008, 73, 7102–7107.
11 A. M. Trzeciak, H. Bartosz-Bechowski, Z. Ciunik, K. Niesyty and
J. J. Ziolkowski, Can. J. Chem., 2001, 79, 752–759.
1 For reviews, see: (a) A. Brennfuhrer, H. Neumann and M. Beller,
Angew. Chem., Int. Ed., 2009, 48, 4114–4133; (b) A. Bennfuhrer,
H. Neumann and M. Beller, ChemCatChem, 2009, 1, 28–41;
c
8014 Chem. Commun., 2012, 48, 8012–8014
This journal is The Royal Society of Chemistry 2012