Palladium-catalysed carbonylative cross-coupling reactions of aryl iodides and vinyl boron derivatives as a straightforward route to aryl vinyl ketones

Article abstract of DOI:10.1055/s-0029-1217379

The carbonylative cross-coupling of potassium vinyl trifluoroborate or 2,4,6-trivinyltricycloboroxane with aryl iodides under mild conditions affords aryl vinyl ketones. The optimisation of the reaction conditions leads to the targeted enones in good yiel

Full text of DOI:10.1055/s-0029-1217379

LETTER
A
Palladium-Catalysed Carbonylative Cross-Coupling Reactions of Aryl Iodides
and Vinyl Boron Derivatives as a Straightforward Route to Aryl Vinyl Ketones
Cross-Coupling R
y
eactions of
r
A
ryl Iod
i
ides an
l
d Vinyl Boron
P
D
erivatives irez, Julien Dheur, Mathieu Sauthier,* Yves Castanet,* André Mortreux
Université des Sciences et Technologies de Lille 1, Unité de Catalyse et Chimie du Solide, UMR CNRS 8181, ENSCL,
B.P. 90108, 59652 Villeneuve dAscq Cedex, France
Fax +33(3)20436585; E-mail: mathieu.sauthier@univ-lille1.fr; E-mail: yves.castanet@ensc-lille.fr
Received 11 February 2009
O
[Pd]
Abstract: The carbonylative cross-coupling of potassium vinyl tri-
fluoroborate or 2,4,6-trivinyltricycloboroxane with aryl iodides un-
der mild conditions affords aryl vinyl ketones. The optimisation of
the reaction conditions leads to the targeted enones in good yields
in the case of the aryl substrates bearing donor substituents in meta
or para position. Much more moderate yields were observed with
aryl substrates bearing withdrawing substituents.
I
+
+
CO, base
[B]
1
2
O
B
B
B
or
=
BF3K
[B]
⋅pyridine
O
O
Key words: carbonylation, cross-coupling, palladium, vinyl boron
derivatives, enones.
Scheme 1
in a pure form9,10 and have been recently used in noncar-
bonylative Suzuki reactions.10,11
Among the methods to produce oxygenated compounds
with high efficiency, carbonylation that leads to the intro-
duction of a carbonyl functionality in the final product
represents a straightforward method accessing this class
of compounds.1 Transition-metal-catalysed carbonylation
reactions have thus become an important tool in modern
organic synthesis allowing the formation of a wide range
of functionalities such as aldehydes, ketones, and carbox-
ylic acid derivatives.1
Preliminary investigations were carried out using potassi-
um vinyl trifluoroborate and iodobenzene as an aryl halide
model (see Scheme 1). Table 1 shows that under the con-
ditions classically used in carbonylative Suzuki reactions,
the expected enone 1 was obtained but with modest yields
(32%, entry 1). Moreover, styrene 2 resulting from the
noncarbonylative process was also formed.
The feasibility of the reaction having been established, we
have tried to optimize the reaction conditions. Various
monodentate and bidentate phosphines [P(o-Tol)3,
PPh2(o-MeOPh), dppe, dppp, dppb, dppf]12 have been
tested (although the results are not reported here). It ap-
peared that no significant improvement in terms of con-
version or selectivity was observed in comparison with
Ph3P. The influence of the nature of the solvent and the
base was much more marked. When the reaction was car-
ried out in toluene (entry 2) no reaction occurred and in
DMF (entry 3) or dioxane (entry 4) the yields significantly
dropped. Using Na2CO3 instead of K2CO3 led to an impor-
tant increase of the yield (entry 5) whereas others bases
such NaOAc, KF, or KOt-Bu were less efficient. It should
also be noted that when Na2CO3 was used as a base, the
yield passed through a maximum for about 1 to 1.2 equiv-
alents of base per PhI and dramatically dropped for higher
ratios (compare entries 12, 15, and 16). As this finding
could be due to the decomposition of the boron derivative
(or its polymerisation), we checked the influence of the
amount of this compound on the reaction. The best results
were obtained for a vinyltrifluoroborate/PhI ratio of about
1.4. Increasing this ratio had only a slight effect on the
yield but a decrease of about 20% is observed for a ratio
going from 1.4 to 1.
For our part, we recently reported the rhodium-catalysed
carbonylative 1,4-addition of aryl boronic acids to vinyl
ketones giving 1,4-diketones.2 To expand the scope of this
new reaction, we had to synthesise various aryl vinyl ke-
tones, which are in addition useful reagents in various
metal-catalysed reactions such as Heck,3 Diels–Alder, or
Michael-type reactions.4,5 They can also be used as mono-
mers in polymerisation reactions for the synthesis of func-
tionalised polymers.6 Unfortunately, the synthetic
strategies reported for the preparation of aryl vinyl ke-
tones is quite limited, and the procedures are often te-
dious. In view of our current interest in the palladium-
catalyzed carbonylative Suzuki cross-coupling reaction
between halogenated substrates, carbon monoxide and
aryl boronic acids,7 we envisioned one such reaction in-
volving an aryl halide and a vinyl boron derivative as a
general, straightforward route toward the targeted com-
pounds. However, due to the lack of stability of vinyl bo-
ronic acid under the reaction conditions,8 we focused our
attention toward more stable synthetic equivalents such as
potassium vinyltrifluoroborate or 2,4,6-trivinyltricyclo-
boroxane-pyridine complex which can be easily obtained
SYNLETT 2009, No. x, pp 000A–000D
x
x
.xx.
2
0
0
9
Advanced online publication: xx.xx.2009
DOI: 10.1055/s-0029-1217379 ; Art ID: D05009ST
© Georg Thieme Verlag Stuttgart · New York

B
C. Pirez et al.
LETTER
Table 1 Carbonylative Cross-Coupling of Iodobenzene and Potassium Vinyl Trifluoroboratea
Entry
Solvent
Base
VinylBF3K vs PCO
Temp
(°C)
Conversion
(%)b
Yield (%)c Yield (%)c
PhI (equiv)
(bar)
20
20
20
20
20
20
20
20
20
40
5
of 1
32
–
of 2
1
2
THF
toluene
DMF
dioxane
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
NaOAc
KF
1.2
80
80
80
80
80
80
80
80
80
80
80
80
100
120
80
80
80
100
0
2
1.2
–
3
1.2
100
100
100
52
22
21
59
34
8
2
4
1.2
2
5
1.2
2
6
1.2
5
7
1.2
10
2
8
KOt-Bu
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
1.2
100
100
100
89
0
9
9
1.4
69
62
86
88
62
41
57
38
78
3
10
11
12
13
14
15
16
17
1.2
2
1.2
1
1.2
2
90
1
1.2
20
20
5
100
98
2d
3d
2
1.2
1.2
96
1.2
5
96
4
1.2
5
80
1
a Conditions: PhI (1 mmol, 0.204 g), Pd(OAc)2 (0.022 mmol, 5 mg), Ph3P (0.07 mmol, 18 mg except entry 17: 0.21 mmol, 54 mg), base (1.1
equiv/PhI except entries 15 and 16, respectively, 2 and 3 equiv/PhI), solvent (8 mL), 20 h (the reaction time was not necessarily optimized).
b Conversion of PhI determined by GC analysis based on its disappearance.
c Determined by quantitative GC analysis.
d Yields of compound 3: 6% and 10% (entries 13 and 14).
Surprisingly, high CO pressure had a rather detrimental case of potassium vinyltrifluoroborate salts with Pd cata-
effect on the efficiency of the reaction. Indeed the yields lysts.13
increased from 62% to 88% when the CO pressure was
Varying the Ph3P/Pd ratio between 3 and 6 had only a
lowered from 40 bar to 2 bar (compare entries 10 and 12).
slight effect, however, higher ratios led to lower conver-
This is quite uncommon with this type of reaction, as the
sions (entry 17).
selectivities are generally improved in favor of the ketone
Moreover, as important differences were found between
versus the noncarbonylated product at higher CO pres-
conversions and yields, and as it is well known that
enones are easily polymerised, we checked the stability of
the product formed in the reaction mixture. Under the re-
action conditions (i.e., in the reaction medium) only mod-
erate degradation was observed at 80 °C after three days
(about 30% of the quantity which was present after 24 h).
However, if pure phenyl vinyl ketone was dissolved in
THF and heated at 80 °C only 25% of the initial quantity
remained after three days, showing that the reaction medi-
um is acting as a stabiliser.
sures.7
Higher temperatures than 80 °C induced, as expected,
higher activities but at the expense of the selectivity.
Above 80 °C the formation of the byproduct 3 resulting
from the subsequent noncarbonylative 1,4 addition of the
potassium vinyltrifluoroborate on the enone 1 markedly
increased (Scheme 2). This addition reaction is known to
proceed with arylbronic acids catalysed either by rhodium
or palladium but is not reported, to our knowledge, in the
O
It is also noteworthy that no Heck-type reaction occurred
between the enone 1 formed at the early stage of the main
reaction and the remaining iodobenzene.3 This is in agree-
ment with the fact that, to our knowledge, no carbonyla-
tive Heck reaction has been reported.
O
[Pd]
base
+
BF3K
1
3
Scheme 2
Synlett 2009, No. x, A–D © Thieme Stuttgart · New York

LETTER
Cross-Coupling Reactions of Aryl Iodides and Vinyl Boron Derivatives
C
Table 2 Carbonylative Cross-Coupling of Various Aryl Halides and Potassium Vinyl Trifluoroboratea
Entry
Substrate
Product
Conversion (%)b Yield (%)b,c of enone
1
2
2-iodotoluene
2-methylphenyl vinyl ketone
3-methylphenyl vinyl ketone
4-methylphenyl vinyl ketone
4-bromophenyl vinyl ketone
4-chlorophenyl vinyl ketone
3,4-dichlorophenyl vinyl ketone
4¢-acetylacrylophenone
86
91
80
71
55
74
85
85
90
2
45 (40)
76 (70)
78 (72)
48 (45)
46 (42)
67 (60)
44 (40)
72 (68)
39 (35)
0
3-iodotoluene
3
4-iodotoluene
4
1-bromo-4-iodobenzene
1-chloro-4-iodobenzene
1,2-dichloro-4-iodobenzene
4-iodoacetophenone
ethyl 4-iodobenzoate
1-iodonaphtalene
bromobenzene
5
6
7
8
ethyl-4-(2-propenoyl) benzoate
1-(1-naphthalenyl)-2-propen-1-one
phenyl vinyl ketone
9
10
a Conditions: aryl halide (1 mmol), VinylBF3K (1.2 mmol), Pd(OAc)2 (0.022 mmol, 5 mg), Ph3P (0.07 mmol, 18 mg), Na2CO3 (1.1 mmol, 0.117
g), THF (8 mL), 20 h.
b Yield determined by GC analysis.
c Numbers in parentheses are isolated yields of >95% pure product.
Table 3 Carbonylative Cross-Coupling of Iodobenzene and 2,4,6-Trivinyltricycloboroxanea
Entry
Base
Vinyl[B] (equiv) vs. PhI PCO (bar)
Conversion (%)(b)
Yield (%)b of 1
1
2
3
4
5
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
0.34
0.34
0.34
0.34
1
5
5
25
95
17
67
64
65
53
10
2
94
96
5
100
a Conditions: PhI (1 mmol, 0.204 g), Pd(OAc)2 (0.022 mmol, 5 mg), Ph3P (0.07 mmol, 18 mg), base 1.12 mmol, THF (8 mL), 20 h.
b Yield determined by GC analysis.
Taking into account the good results obtained with iodo- In summary we have described a facile method for the
benzene, the study was extended to other aryl halides in synthesis of various arylvinyl ketones via a carbonylative
order to determine the scope and limitations of the reac- Suzuki cross coupling reaction between an aryl iodide and
tion (Table 2). Good results were generally obtained with a stable vinyl boron derivative.
aryl iodides bearing donor substituents (entries 2, 3) al-
though steric hindrance due to ortho substituent can im-
pede the reaction efficiency (entries 1 and 9) as observed
in Suzuki coupling.14 On the other hand, with iodo aryls
bearing withdrawing substituents the reaction was less ef-
ficient, and the desired ketones were obtained only with
moderate yields (entries 4–7). Other aryl halides were in-
effective under these reaction conditions.
Typical Procedure (Table 1, Entry 12)
A suspension of iodobenzene (0.204 g, 1.0 mmol), potassium vinyl-
trifluoroborate (0.134 g, 1.0 mmol), Na2CO3 (0.120 g, 1.12 mmol),
Pd(OAc)2 (0.005 g, 0.022 mmol), and Ph3P (0.018 g, 0.07 mmol) in
THF (8 mL) and undecane (0.12 mL as internal standard for GC an-
alyzes) was charged under nitrogen into a 50 mL stainless-steel au-
toclave equipped with a magnetic stirrer bar. After sealing, the
Finally, 2,4,6-trivinyltricycloboroxane was tested under reactor was purged with N2 and pressurized to 5 bar with CO and
then heated to 80 °C. At the end of the reaction, the reactor was
the similar conditions to the one optimised with potassium
cooled to r.t. and the reaction mixture was analyzed by GLC to de-
vinyltrifluoroborate and the results are reported Table 3.
termine conversion and selectivities. The reaction mixture was con-
centrated under vacuum, and the crude residue was
chromatographed on silica using Et2O–PE (1:9) as eluent, to yield
analytically pure phenyl vinyl ketone.
In this case, it was found that K2CO3 was the best base and
that the CO pressure had only a slight influence on the re-
sults. Interestingly all of the vinyl moieties of 2,4,6-tri-
vinyltricycloboroxane are incorporated in the reaction
product.
All of the reaction products described in this paper were character-
1
ized by H NMR, 13C NMR, and MS, and gave data in full accor-
dance with the proposed structures.
Synlett 2009, No. x, A–D © Thieme Stuttgart · New York

D
C. Pirez et al.
LETTER
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Synlett 2009, No. x, A–D © Thieme Stuttgart · New York