γ-selective cross-coupling of potassium allyltrifluoroborates with aryl and 1-alkenyl bromides catalyzed by a Pd(OAc)2/D-t-BPF complex

Article abstract of DOI:10.1246/cl.2006.704

Cross-coupling reactions of [RCH=CHCH₂BF₃]K with aryl or 1-alkenyl bromides occurred at the γ-carbon of an allylborane moiety with perfect regioselectivities (>99%) in the presence of a palladium/D-t-BPF complex and K₂CO

Full text of DOI:10.1246/cl.2006.704

704
Chemistry Letters Vol.35, No.7 (2006)
ꢀ-Selective Cross-coupling of Potassium Allyltrifluoroborates
with Aryl and 1-Alkenyl Bromides Catalyzed by a Pd(OAc)2/D-t-BPF Complex
Yasunori Yamamoto,ꢀ Shingo Takada, and Norio Miyauraꢀ
Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628
(Received March 14, 2006; CL-060308; E-mail: yasu@org-mc.eng.hokudai.ac.jp, miyaura@org-mc.eng.hokudai.ac.jp)
Cross-coupling reactions of [RCH=CHCH2BF3]K with aryl
sized by treatment of allylboronic acids or esters with KHF2,
were advantageous over triallylboranes, allylboronic acids or
esters in preparation and handling of pure and water-stable crys-
talline materials.6 Although these Kþ salts are highly insoluble
in common organic solvents, the reaction smoothly proceeded
at refluxing temperature of THF in the presence of K2CO3 and
a palladium catalyst prepared in situ from Pd(OAc)2 and 1,10-
bis(di-t-butylphosphino)ferrocene (D-t-BPF).7
or 1-alkenyl bromides occurred at the ꢀ-carbon of an allylborane
moiety with perfect regioselectivities (>99%) in the presence of
a palladium/D-t-BPF complex and K2CO3 in refluxing THF.
Transition metal-catalyzed cross-coupling reactions have
proved to be one of the most powerful methods for selective
C–C bond formation.1 Among the possible combinations of elec-
trophiles and nucleophiles, coupling reactions of allylic metals
with aryl, alkenyl, and allyl electrophiles or their reversed
combination provide an important class of compounds due to
the frequent occurrence of these fragments in natural products.1c
Although there have been few attempts at employing allylboron
compounds for this purpose,2,3 no systematic study on selective
coupling at the ꢁ- or ꢀ-carbon of allylic boron reagents. Perfect
control of the coupling position by phosphine ligands was first
achieved by Hiyama et al. by using allyltrifluorosilanes.4 They
found that palladium-catalyzed coupling selectively occurs at
the ꢀ-carbon when using PPh3 or bisphosphines possessing a
large bite angle such as dppb, and the reaction proceeds at the
ꢁ-carbon with bisphosphines possessing a relatively small angle
such as dppp.4c Such an effect of phosphine ligands was also
demonstrated by Tsuji in the regioselective Stille coupling of
aryl halides with Me3SiCH2CH=CHCH2SnBu3 at the ꢁ- or ꢀ-
carbon.5
The yields and regioselectivities of the coupling position
were highly sensitive to phosphine ligands employed for palladi-
um acetate in the cross-coupling reaction between 4-bromoani-
sole and potassium crotyltrifluoroborate (1b) (Table 1). Since
the reaction was very slow in the absence of a base, it was carried
out in a basic solution as was previously reported in related
palladium-catalyzed cross-coupling reactions of potassium aryl-
and 1-alkenyltrifluoroborates.6d The use of K2CO3 (3 equiv.)
gave the best results, but stronger bases, K3PO4 and KOH,
resulted in yields of 9 and 30%, respectively. Dppm and dppe
possessing a relatively small bite angle gave a mixture of two
isomers (Entries 1 and 2), but bisphosphines that have a bite an-
gle larger than dppf yielded a ꢀ-coupling product 3 as the sole
product (Entries 3–7). However, these catalysts suffered from
low yields of the coupling products mainly due to formation of
anisole via base-assisted ꢂ-hydride elimination from ꢃ-allylpal-
ladium(II) intermediate 5, which was generated by transmetala-
tion between an oxidative adduct R2PdXꢁL2 and 1b by an SE20
mechanism (eq 2).8 Among the ligands screened for optimiza-
tion of the catalyst, D-t-BPF was found to be the best ligand
to achieve high yields and high ꢀ-selectivities for 4-bromoani-
sole (Entry 8).
In this paper, we report ꢀ-selective cross-coupling reactions
of potassium allyltrifluoroborates with aryl and 1-alkenyl bro-
mides (Scheme 1). Air- and water-stable allylborates 1, synthe-
R2X (2)
R2
R1
BF3K
R1
R2
+
R1
Pd(OAc)2
D-t-BPF
K2CO3
Table 1. Effect of ligandsa
1a: R1=H
3
4
Entry
Ligand
Yield/%b
3/4
1b: R1=Me
1c: R1=c-C6H11
P(t-Bu)2
1
2
dppm
dppe
35
17
78/22
37/63
Fe
D-t-BPF=
3
4
5
6
7
8
9c
10
dppp
dppf
37
68
21
10
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
78/22
Br
P(t-Bu)2
2a:
2b:
2c:
2d:
2e:
2f:
2g:
2h:
2i:
2j:
2k:
2l:
2m:
2n:
2o:
FG=4-NH2
FG
FG=4-NHBz
FG=4-MeO
FG=3-MeO
FG=2-MeO
FG=4-t-Bu
FG=2,6-Me2
FG=4-CO2Me
FG=3-CO2Me
FG=2-CO2Me
FG=4-COMe
FG=4-CN
DPEphos
Xantphos
DBFphos
D-t-BPF
D-t-BPF
10
Br
(87)
(85)
42
2p:
2q:
d
PPh3
aAll reactions were carried out at reflux in THF–H2O (10/1)
for 20 h in the presence of Pd(OAc)2 (3 mol %), a ligand
(3 mol %), 4-bromoanisole (0.5 mmol), 1b (0.75 mmol), and
K2CO3 (1.5 mmol) unless otherwise noted. bNMR yields
and isolated yield are shown in parentheses. The reaction
was conducted in dry THF. Pd(PPh3)4 (3 mol %) was used.
Br
PhCH2O
FG=4-CF3
FG=4-NO2
FG=2-naphthyl
2r:
Br
c
d
Scheme 1. ꢀ-Selective cross-coupling of 1 giving 3.
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.7 (2006)
Table 2. ꢀ-Selective cross-coupling of 1a
705
electron-rich bromoarenes possessing a 4-NH2 group and 4-
NHBz group (Entries 2 and 3) and tolerated amino, ester, cyano,
and nitro groups. It was also interesting that the steric hindrance
of ortho-substituents did not affect the yields and regioselectiv-
ities (Entries 6, 8, and 11). Coupling with bromoalkenes resulted
in lower yields than those in the case of coupling with bromoar-
enes, but the reactions again provided ꢀ-coupling products with
perfect regioselectivities (Entries 16–18).
Tetracoordinated allylborates such as 1b are inert to carbon-
yl compounds, but their decomposition into tricoordinated allyl-
boron species may allow their addition to aldehydes or ketones
as was previously reported in BF3-catalyzed allylboration of al-
dehydes with 1b.6a–6c The coupling reaction of 4-bromoaceto-
phenone (2k) with 1b (3 equivalents) was faster than addition
to the carbonyl group (eq 3, Entry 1). The allylboration product
7 was only obtained under forced conditions using 5 equiv. of 1b
for 22 h (Entry 2).
Entry
1
2
Yield/%b
3/4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1cc
2i
38
80
96
90
85
84
88
87
92
92
92
77
83
80
93
75
66
65
98
—
2a
2b
2c
2d
2e
2f
2g
2h
2i
>99/1
>99/1
>99/1
>99/1
>99/1
98/2
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
>99/1
2j
2l
2m
2n
2o
2p
2q
2r
2i
1b
HO
(3)
+
Br
O
O
Pd(OAc)2
D-t-BPF
THF, reflux
2k
6
7
Entry 1b/2k
Time/h
3.5
Yield 6/%
Yield 7/%
aAll reactions were carried out at reflux in THF for 22 h in
the presence of Pd(OAc)2 (3 mol %), D-t-BPF (3.6 mol %),
bromoarene (1 mmol), 1 (2.5 mmol), and K2CO3 (3 mmol).
bIsolated yield by chromatography. cA mixture of E=Z ¼
80=20.
1
2
3
5
94
55
0
22
45
The ꢀ-coupling products thus synthesized are synthetically
equivalent to 2-arylpropionic acids via oxidative cleavage of
the C=C bond as is shown in the synthesis of ibuprofen (eq 4).4a
L2
KF3B
R2
R2
R2
Pd
1b
(4)
(1)
Pd·L2
X
+ Pd(0)L2
CH3
Pd(OAc)2
D-t-BPF
K2CO3
KMnO4
NaIO4
(Ref. 4a)
CH3
CH3
5
Br
HO2C
base
THF, reflux
91% (α
/
γ
= 0/100)
ibuprofen
L2
R2H + Pd(0)L2
+
CH2=CHCH=CH2
Pd R2
base
References
(2)
1
a) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed., ed. by A.
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CH2
H
This catalyst worked well in aqueous K2CO3, but a hetero-
geneous system using K2CO3 and 1b, both suspended in dry
THF, was a better system (Entry 9). By using such a heterogene-
ous system that minimizes contact between the base and 5 (eq 2),
the formation of anisole was reduced to a negligible amount. The
bulkiness and strong electron-donating property of the di-t-
butylphosphino group in D-t-BPF may serve to accelerate both
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other hand, Pd(PPh3)4, a ꢀ-selective catalyst for allyltrifluoro-
silanes,4a,4b resulted in 42% yield due to the formation of anisole
(Entry 10).
The cross-couplings of potassium allyltrifluoroborates
(1, 2.5 equiv.) and aryl or 1-alkenyl bromides in the presence
of Pd(OAc)2/D-t-BPF (3 mol %) and K2CO3 in anhydrous
THF are summarized in Table 2. Potassium allyltrifluoroborate
(1a) unexpectedly resulted in a low yield (Entry 1), but (E)-
crotylborate (1b, Entries 2–18) and (E)-3-cyclohexyl-2-propen-
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products 3 with high regioselectivities (>99%) for representa-
tive aryl bromides (Entries 2–15).
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The reaction proceeded smoothly at reflux in THF even for
Published on the web (Advance View) May 30, 2006; doi:10.1246/cl.2006.704