Palladium-catalyzed decarbonylative and decarboxylative cross-coupling of acyl chlorides with potassium perfluorobenzoates affording unsymmetrical biaryls

Article abstract of DOI:10.1039/d1cc00202c

This paper describes the synthesis of unsymmetrical biaryls by the palladium-catalyzed cross-coupling reaction of acyl chlorides with potassium perfluorobenzoates. This transformation is unique in that it involves simultaneous decarbonylation and decarbox

Full text of DOI:10.1039/d1cc00202c

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Palladium-catalyzed decarbonylative and
decarboxylative cross-coupling of acyl chlorides
with potassium perfluorobenzoates affording
Cite this: Chem. Commun., 2021,
57, 3696
Received 12th January 2021,
Accepted 11th March 2021
unsymmetrical biaryls†
b
Liyan Fu,a Jingwen Youa and Yasushi Nishihara
*
DOI: 10.1039/d1cc00202c
rsc.li/chemcomm
This paper describes the synthesis of unsymmetrical biaryls by the
Based on our previous studies on palladium-catalyzed decarbo-
palladium-catalyzed cross-coupling reaction of acyl chlorides with nylative cross-coupling reactions9 and related mechanisms,5,7d,10 we
potassium perfluorobenzoates. This transformation is unique in hypothesized the possible scenario of biaryl synthesis via decarbo-
that it involves simultaneous decarbonylation and decarboxylation nylation and decarboxylation (Scheme 2). First, the acylpalladium(II)
under redox-neutral conditions. Compared to conventional cross- complex A is formed by oxidative addition of benzoic acid derivatives
coupling protocols for the synthesis of unsymmetrical biaryls, the 1 to the Pd(0) catalyst. In Path a, decarbonylation occurs prior to
two reactants in this synthetic strategy can be readily prepared transmetalation, affording the arylpalladium(II) species B, which
from abundant and inexpensive aromatic carboxylic acids.
reacts with benzoates 2 to yield the intermediate C. After decar-
boxylation, the diarylpalladium(II) complex D is formed from C.
Over the past few decades, carboxylic acids and their derivatives Finally, reductive elimination of D yields the desired unsymmetrical
have aroused wide interest in organic synthesis due to their biaryls 3, and regeneration of palladium(0) completes the catalytic
ready availability, abundance, and environmental friendliness.1 cycle. On the other hand, in Path b, transmetalation between A and
In this context, benzoic acids and their derivatives have been benzoates 2 gives the intermediate B0. Thus, the loss of CO2 in B0
developed as convenient surrogates for conventional coupling produces complex C0, and subsequent decarbonylation gives the
partners through the loss of CO or CO2, known as decar- same intermediate D, while ketone 4 is a by-product from the direct
bonylative2 and decarboxylative3 couplings, respectively. reductive elimination of C0. Compared to previously reported
Among these protocols, the development of synthetic methods
for biaryls, one of the most versatile units of organic molecules,
is of great importance (Scheme 1a).4–7 As a pioneering example,
Gooßen and co-workers developed the Pd/Cu-cocatalyzed inter-
molecular decarboxylative coupling of benzoic acids or benzoates
with aryl (pseudo)halides.4 In 2018, Sanford and co-workers
reported the nickel-catalyzed decarbonylative couplings of acyl
fluorides with arylboronic acids under base-free conditions.7c
Although these synthetic methods utilize substrates derived from
naturally abundant carboxylic acids, either organic (pseudo)
halides or organometallic reagents are still required. Therefore,
a method for the synthesis of unsymmetrical biaryls from benzoic
acid derivatives alone via redox-neutral decarbonylative and de-
carboxylative couplings has not yet been developed (Scheme 1b).8
a Graduate School of Natural Science and Technology, Okayama University,
3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
b Research Institute for Interdisciplinary Science, Okayama University,
3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
E-mail: ynishiha@okayama-u.ac.jp
† Electronic supplementary information (ESI) available: Experimental proce-
dures, spectroscopic data, and copies of 1H and 19F{1H} NMR spectra. See DOI:
Scheme 1 Biaryl synthesis via decarboxylation or/and decarbonylation.
10.1039/d1cc00202c
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Table 1 Optimization of the reaction conditionsa
Entry
1
2
3
4
Catalyst
Pd(OAc)2
PdCl2(cod)
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
—
Ligand
3aab (%)
4b (%)
5
3
4
10
2
3
0
5
4
PCy3ꢀHBF4
PCy3ꢀHBF4
PCy3ꢀHBF4
PPh3
72
62
74
10
15
26
1
71
48
68
49
0
5
DCYPE
6c
PCy3ꢀHBF4
PCy3ꢀHBF4
PCy3ꢀHBF4
PCy3ꢀHBF4
PCy3ꢀHBF4
PCy3ꢀHBF4
PCy3ꢀHBF4
—
7d
8e
9 f
10 g
11h
12
13
14i
7
5
3
9
Scheme 2 A working hypothesis for the synthesis of biaryl from benzoic
acid derivative 1 and benzoate 2.
Pd(dba)2
Pd(dba)2
0
PCy3ꢀHBF4
74 (69)
4
couplings involving decarboxylation or decarbonylation, this process
poses a greater challenge since both processes should occur prior to
reductive elimination.
a
Reactions were carried out with catalyst (0.02 mmol, 10 mol%), ligand
(0.04 mmol, 20 mol%), 1a (0.2 mmol, 1.0 equiv.) and 2a (0.3 mmol,
1.5 equiv.) in toluene (1 mL) at 150 1C for 20 h under Ar. GC
b
yields using n-tetradecane as an internal standard and an isolated yield
Acyl chlorides, one of the most fundamental and commercially
available carboxylic acid derivatives, have been widely used as
electrophiles in organic synthesis.11 However, despite their wide-
spread existence, there are relatively few reports on the use of acyl
chlorides as aryl sources via decarbonylative cross-coupling
c
is shown in parentheses. C6F5COONa instead of C6F5COOK.
d
f
e
C6F5COOLi instead of C6F5COOK. Toluene/1,4-dioxane (10 : 1).
g
h
Toluene/diglyme (10 : 1). 140 1C. Pd(dba)2 (0.01 mmol, 5 mol%),
i
PCy3ꢀHBF4 (0.02 mmol, 10 mol%). 12 h.
reactions.12 As a recent example, Szostak and co-workers reported ligand resulted in a decrease in the yield of the desired product
a decarbonylative Suzuki–Miyaura-type cross-coupling reaction of
acyl chlorides using arylboronic acids as the nucleophiles.7d On
the other hand, perfluorophenyl groups present unique reactivity
and properties.13 Due to the widespread use of the biaryl skeleton
with perfluorophenyl moieties in pharmaceutical14 and materials15
chemistry, a series of decarboxylative cross-coupling reactions of
(entries 4 and 5), indicating that the ligand properties have a
significant effect on the present reaction. The similar trend was
observed for the variation from potassium pentafluorobenzoate
to lithium and sodium salts, leading to lower yields (entries
6 and 7). The employment of co-solvent also reduced the yield
of 3aa (entries 8 and 9). Furthermore, decreasing the tempera-
perfluorobenzoates with aryl (pseudo)halides have been developed ture (entry 10) and the amount of catalyst loading (entry 11)
under copper, palladium, and nickel catalysis.5 Recently, we also resulted in the product yields of 68% and 49%, respectively.
reported that spontaneous decarboxylation occurs in transition-
metal-free cross-coupling reactions of acyl fluorides with potassium
perfluorobenzoates, leading to unsymmetrical ketones.16 Although
this method is an efficient and environmentally friendly route to
the synthesis of perfluorinated ketones, the synthesis of perfluori-
nated biaryls from perfluorobenzoates and benzoic acid derivatives
The control experiments indicated both the palladium precursor
and the phosphine ligand were necessary for the formation of the
target product (entries 12 and 13). Fortunately, the yield of 3aa was
still 74% in the 12 h reaction, providing a 69% isolated yield
(entry 14).
With optimized conditions in hand, a range of acyl chlorides
still poses a major challenge. Hence, we herein report the were examined in reactions with potassium pentafluorobenzoate
palladium-catalyzed cross-coupling reaction of acyl chlorides with (2a) (Scheme 3). Both 2- and 1-naphthoyl chlorides afforded the
potassium perfluorobenzoates, involving both decarbonylation and
decarboxylation.
desired products 3aa and 3ba in good yields. The use of benzoyl
chloride (1c) also generated the corresponding product 3ca in
49% yield. Substrates bearing electron-donating groups such as
3-methyl, 4-methyl, 4-tert-butyl, and 4-phenyl moieties could also
be applicable to provide coupling products 3da, 3ea, 3fa, and 3ga
in moderate yields. In addition, the ester group and the electron-
Our investigation was initiated using 2-naphthoyl chloride
(1a) and potassium pentafluorobenzoate (2a), which is not only
a coupling partner, but also a base to generate PCy3 from
PCy3ꢀHBF4. After extensive optimization, the use of Pd(OAc)2
(10 mol%) and PCy3ꢀHBF4 (20 mol%) in toluene at 150 1C for withdrawing trifluoromethyl group furnished the desired products
20 h was found to be the optimal condition, providing a 72% 3ha and 3ia in 61% and 48% yields, respectively. The highly
GC yield of the desired product 3aa and 5% ketone 4 as a
by-product (Table 1, entry 1). Notably, no ester product was
observed, suggesting that the decarboxylation proceeded suffi-
ciently. When PdCl2(cod) was employed instead of Pd(OAc)2,
the yield of 3aa decreased to 62% (entry 2), but when Pd(dba)2
was used, the yield increased to 74% (entry 3). Changing the
reactive chlorobenzene moiety was also tolerated in this manner,
providing 3ja in 34% yield. Finally, the probenecid-derived acyl
chloride 1k underwent decarbonylation and decarboxylation
to give the desired product 3ka in 52% yield, demon-
strating the synthetic potential of this protocol for late-stage
functionalization.
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Scheme 5 Mechanistic study.
Reaction of 1c with Pd(dba)2 in the presence of stirred PCy3 at room
temperature gave complex 5, corresponding to intermediate A in
Scheme 2, and reaction at 140 1C for 3 h yielded complex 6,
corresponding to intermediate B in Scheme 2.7d Reaction with 2a
using the separately prepared and isolated palladium complex 6
gave the product 3ca in 77% GC yield, with no esters observed
(Scheme 5b). These results suggest that Path a is a plausible reaction
pathway. However, the possibility of Path b cannot be ruled out at
this stage. Although the decarboxylation of potassium perfluoro-
benzoates 2 could proceed under transition-metal-free conditions,
we propose that the decarboxylation in this transformation is caused
by palladium, since Liu’s work5b and our previous reports16 indicate
that decarboxylation cannot proceed in toluene without palladium,
and that only a small amount of ketone 4 was obtained in the
absence of palladium catalyst, as shown in entry 12 of Table 1.
In summary, we have developed the palladium-catalyzed
cross-coupling reaction of acyl chlorides with potassium
perfluorobenzoates to synthesize perfluorinated biaryls. This
protocol realized the first cross-coupling involving simulta-
neous decarbonylation and decarboxylation under redox-
neutral conditions, and both starting materials can be prepared
directly from carboxylic acids, providing an environmentally
friendly and sustainable cross-coupling reaction. We are currently
conducting experiments to achieve a wide substrate scope under
even milder conditions.
a
Scheme 3 Substrate scope of acyl chlorides.
Reaction conditions:
Pd(dba)2 (0.02 mmol, 10 mol%), PCy3ꢀHBF4 (0.04 mmol, 20 mol%), acyl
chlorides 1 (0.2 mmol, 1.0 equiv.), potassium pentafluorobenzoate 2a
(0.3 mmol, 1.5 equiv.), toluene (1 mL), 150 1C, 12 h. Isolated yields.
In a further study, the reactions of various potassium per-
fluorobenzoates 2 with 1a was investigated (Scheme 4). As a
result, two fluorine atoms located in the ortho-position of
benzoates 2 appeared to be the key point in this reaction.17
Decarbonylative and decarboxylative couplings of potassium
2,6-difluorobenzoate (2b) and 2,4,6-trifluorobenzoate (2c) pro-
ceeded smoothly to give the desired products 3ab and 3ac in
63% and 42% yields, respectively. While 2,3,5,6-tetrafluoro-4-
methylbenzoates (2d) afforded the corresponding product 3ad
in 54% yield, no coupling product 3ae was observed when
2,3,4,5-tetrafluorobenzoate (2e) was employed. Only 20% of
the desired product 3af was obtained, probably due to competi-
tion from the C–H bond activation reaction at the 2,3,5,
6-tetrafluorobenzene moiety.18
To gain insights into the mechanism of this reaction, the
reaction was conducted without perfluorobenzoates 2 (Scheme 5a).
The authors gratefully thank the SC-NMR Laboratory of
Okayama University for the NMR spectral measurements. Dedi-
cated to Professor Tamotsu Takahashi on the occasion of his
retirement.
Conflicts of interest
There are no conflicts to declare.
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