A new organic transformation by introducing crotyl/allyltrifluoroborates in cross-coupling reaction with aroyl chlorides

Article abstract of DOI:10.1016/j.tetlet.2011.07.107

Microwave irradiated PdCl₂(d^tbpf) catalyzed direct cross-coupling reaction of aroyl chlorides with potassium crotyl/ allyltrifluoroborates has been developed. Regioselectivity of the cross-coupling product is varied from crotyltrifluoroborate to allyltrifluoroborate.

Full text of DOI:10.1016/j.tetlet.2011.07.107

Tetrahedron Letters 52 (2011) 5090–5093
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A new organic transformation by introducing crotyl/allyltrifluoroborates
in cross-coupling reaction with aroyl chlorides
⇑
Mohammad Al-Masum , Kwei-Yu Liu
Tennessee State University, Department of Chemistry, 3500 John A Merritt Blvd., Boswell 201, Nashville, TN 37209, USA
a r t i c l e i n f o
a b s t r a c t
Microwave irradiated PdCl2(dtbpf) catalyzed direct cross-coupling reaction of aroyl chlorides with potas-
sium crotyl/allyltrifluoroborates has been developed. Regioselectivity of the cross-coupling product is
varied from crotyltrifluoroborate to allyltrifluoroborate.
Article history:
Received 30 June 2011
Revised 21 July 2011
Accepted 22 July 2011
Available online 29 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Cross-coupling
Potassium crotyl- and allyltrifluoroborates
Aroyl chlorides
Crotonophenones
The major development and extensively used methods in
organic synthesis for carbon–carbon bond formation reactions
are palladium-catalyzed allylation reactions.1 Our interest is to
introduce crotyl- and allyltrifluoroborates in a new organic trans-
formation. Compared to highly reactive, less stable allylboronic
acid and allylboronic ester, potassium allyltrifluoroborate is an
air- and water-stable unique solid compound. Its use in organic
transformations is increasing dramatically.2 Recently, potassium
allyltrifluoroborate is successfully applied in Michael type reac-
tion.3 In addition to this, cross-coupling reaction of potassium
allyltrifluoroborate and aryl halides is developed very recently.4
The oxidative addition of aroyl chloride to a palladium (0) complex
yielding ArCO-Pd-Cl is a new entity for cross-coupling chemistry.
Very few reports demonstrated the direct cross-coupling reaction
of aryl metals with aroyl chloride in the presence of a palladium-
catalyst.5 But, palladium catalyzed cross-coupling reaction of allyl
metals with aroyl halides is yet to be known. In this communica-
tion, we demonstrate the palladium-catalyzed microwave irradi-
ated cross-coupling reaction of potassium crotyltrifluoroborate
with aroyl chlorides and potassium allyltrifluoroborate with aroyl
chlorides as well (Scheme 1). The results of this new cross-coupling
process, which facilitates smooth organic transformation, are pre-
sented in Tables 2 and 3.
applied the same palladium-catalyst system that we had previ-
ously found effective for trans-b-methyl styrene synthesis4a and
no promising transformation was observed. Changing the molar
ratio and solvent system with the same palladium complex mer-
ited the successful cross-coupling of potassium allyltrifluoroborate
and aroyl chlorides (Table 1). Both microwave and conventional
heating systems are almost equally effective and we explore the
transformation under microwave heating for minute reaction.
When aroyl chloride treated with crotyltrifluoroborate 1a in the
presence of palladium-catalyst, major cross-coupling products ob-
tained in
chloro-aroyl chloride, potassium crotyltrifluoroborate gave a mix-
ture of -adduct and -adduct (Table 2, entry 5). The reaction suc-
cess of crotyltrifluoroborate with aroyl chloride is mixed. Yields are
moderate and aroyl group coupling at the -position of the allyl
moiety is interesting which we thought could proceed with
selectivity (Table 2, entry 5). Probably, the electron donating
methyl group enhances -selectivity. In the case of potassium
a-selectivity (Table 2, entries 1–4). In the case of 4-
a
c
a
c-
a
allyltrifluoroborate, a more selective transformation was observed.
The best successful conditions leading to the formation of croton-
ophenone 5a from the cross-coupling of potassium allyltrifluorob-
orate 1b and aroyl chloride 2a is shown as a representative
procedure. A dry microwave pyrex tube was purged with argon.
Potassium allyltrifluoroborate, 73.0 mg (0.5 mmol), anhydrous
potassium carbonate, 414 mg (3.0 mmol), PdCl2(dtbpf) catalyst,
In earlier works of palladium-catalyzed cross-coupling reaction
of potassium allyltrifluoroborate with aryl halides reported by
Yamamoto group4b and Al-Masum group4a, 2.5 equiv of potassium
allyltrifluoroborate gave best results. In the initial experiments, we
9.9 mg (0.015 mmol), benzoyl chloride, 114 lL (1.0 mmol), and a
magnetic bar were packed in a microwave tube. The reactants were
then flushed with argon for 1–2 min to prevent the presence of air
from causing the decomposition of the Pd catalyst followed by the
addition of 2.0 mL of dry 1,4-dioxane from a sure-seal bottle. The
⇑
Corresponding author.
E-mail address: malmasum@tnstate.edu (M. Al-Masum).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.107

M. Al-Masum, K.-Y. Liu / Tetrahedron Letters 52 (2011) 5090–5093
5091
O
O
t
3 mole % PdCl (d bpf)
2
BF K
3
+
Cl
K CO , 1,4-Dioxane
140 C, 20 min
2
3
Potassium crotyltrifluoroborate
0
3
Aroyl chloride
α-selectivity
1a
2
O
O
t
3 mole % PdCl (d bpf)
2
BF K
+
3
Cl
K CO , 1,4-Dioxane
H
2
3
Potassium allyltrifluoroborate
0
140 C, 20 min
4
Aroyl chloride
1b
2
O
1,3-migration
5
β-selectivity
Scheme 1.
Table 3
Table 1
Palladium-catalyzed cross-coupling reaction of allyltrifluoroborate 1b and aroyl
chlorides 2a
Microwave versus thermal heating
Method Molar ratio of
Heating
Product
Yields
(%)
Entry Aroyl chlorides 2
Aryl propenyl ketone 5
Yields
(%)
1b:2
1
2.5:1
MW, 20 min
Mixed
65
O
O
regioisomers
5 (selective)
5 (selective)
1
96
95
95
88
90
90
24b
5a
2a
2
3
1:2
1:2
MW, 20 min
140 °C, 12 h
thermal
95
90
Ph
Cl
Ph
O
O
2b
5b
2
3
4
5
6
7
4
1:1
MW, 20 min
Mixed
regioisomers
<50
p-Me-C6H4
Cl
p-Me-C6H4
O
O
2c
5c
p-MeO-C6H4
Cl
p-MeO-C6H4
O
O
Table 2
2d
5d
Palladium-catalyzed cross-coupling reaction of crotyltrifluoroborate 1a and aroyl
m-MeO-C6H4
O
Cl
2e
m-MeO-C6H4
O
chlorides 2a
5e
Entry
1
Aroyl chlorides 2
a
-Selectivity product 3
Yields (%)
26
p-F-C6H4
O
Cl
p-F-C6H4
O
O
O
5f
2f
2g
Ph
Cl
Ph
p-Cl-C6H4
O
Cl
p-Cl-C6H4
O
2a
3a
5g
O
O
p-Br-C6H4
Cl
p-Br-C6H4
O
O
O
p-Me-C6H4
Cl
p-Me-C6H4
3b
2
3
4
85
90
25
+
8
88
p-O2N-C6H4
Cl
Ar
Ar
2b
8
O
O
5h
2h
O
O
p-MeO-C6H4
Cl
p-MeO-C6H4
Cl
5i
2i
3c
2c
9
95
75
O
O
Cl
Cl
Cl
Cl
m-MeO-C6H4
Cl
m-MeO-C6H4
O
O
2d
3d
O
2j
5j
10
Cl
O
p-Cl-C6H4
Cl
p-Cl-C6H4
a
Yields are isolated pure products by column chromatography.
4,40-Dibromobenzil (7) was the major product.
b
3f
5
67b
2f
O
power) and heated at 140 °C for 20 min. After removal from the
microwave, the product mixture was extracted with diethyl ether
and separated from the inorganic byproducts through filtration.
The crude product was subjected to silica gel chromatography or
preparative thin layer chromatography with hexane/ethyl acetate
(50:1, 25:1, 10:1) as eluents and the pure product was isolated,
dried, and characterized by GC/MS (Saturn 2200 Benchtop GC/
MS) and NMR (Varian 300 MHz).
p-Cl-C6H4
6
a
Yields are isolated pure products by column chromatography.
b
Major product was 6 (c-selectivity).
resulting mixture in the microwave tube was subsequently in-
serted into the microwave (CEM, Discover microwave 300 W

5092
M. Al-Masum, K.-Y. Liu / Tetrahedron Letters 52 (2011) 5090–5093
In case of potassium crotyltrifluoroborate
O
C
Base
Z
BF K
3
+
ClPd
Pd
Z
Transmetallation
C
1a
O
O
+
Pd(0)
Z
3
In case of potassium allyltrifluoroborate
O
Base
Z
C
BF K
3
+
ClPd
Pd
Z
Transmetallation
C
1b
O
O
O
− Pd(0)
1,3-migration
Z
H
Z
5
4
OR
O
Z
− Pd(0)
Pd
Pd
C
Z
O
O
O
H
isomerization
Z
Z
5
Scheme 2. Probable mechanism.
By adding potassium allyltrifluoroborate, the scope of this new
transformation was established with a variety of different aroyl
chlorides. On changing the electron-rich or electron-deficient
groups in the phenyl ring of the aroyl chlorides, the reaction
proceeded essentially in the same rate affording the corresponding
aryl propenyl ketones (crotonophenones) in good to high yields
(Table 3, entries 1–6, 9 and 10). In the case of para-bromo-aroyl
chloride and allyltrifluoroborate, the cross-coupling product 5g
was formed as a minor product (Table 3, entry 7) and homo-
coupling product 4,40-dibromobenzil (7) was the major one.
Probably, possible palladium insertion to bromide inhibits the
transmetallation process and led to the homo-coupling product.
Interestingly, when 4-nitro-aroyl chloride reacted with potassium
allyltrifluoroborate under the same reaction conditions, a 50:50
the case of 4-nitro-aroyl chloride and allyltrifluoroborate (Table
3, entry 8) convinces us to propose that the nucleophile may attack
the terminal carbon of the
p-allyl intermediate and subsequently
isomerizes to the more stable
a,b-unsaturated ketone (Scheme 2).
The application of potassium crotyltrifluoroborate cross-coupled
with aroyl chlorides and potassium allyltrifluoroborate cross-
coupled with aroyl chlorides has been successfully established. Fur-
ther synthetic and mechanistic studies of these new processes will
be explored in due course.
Acknowledgment
Financial support from the US department of education Title III
grant, Tennessee State University is thankfully acknowledged.
mixture of b-adduct and
c-adduct was obtained (Table 3, entry
8) in good yields. Compared to other bases, potassium carbonate
was the most effective for this transformation. This new cross-cou-
pling reaction requires an excess amount of potassium carbonate.
Control experiments without potassium carbonate did not give
any product. Also, adding a stoichiometric amount of potassium
carbonate had very little effect on the formation of the desired
product. The palladium inserted aroyl chloride, ArCO-Pd-Cl dis-
plays excellent chemoselectivity in cross-coupling reaction when
treated with potassium allyltrifluoroborate. Initially, we specu-
lated that central carbon selectivity appears to be accomplished
through palladacycle. But the mixture of products observed in
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.07.107.
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