Catalytic reactions of bis-π-allylpalladium generated from allyltrifluoroborate

Article abstract of DOI:10.1016/j.tetlet.2010.11.082

Bis-π-allylpalladium-catalyzed nucleophilic allylations to aldehydes 2 and imines 3 have been achieved by replacing allylstannanes with allyltrifluoroborate. Amphiphilic bisallylation of activated olefins 6 with allyltrifluoroborate and allyl acetate also proceeded smoothly in the presence of Pd₂(dba)₃·CHCl₃ and tricyclohexylphosphine catalysts.

Full text of DOI:10.1016/j.tetlet.2010.11.082

Tetrahedron Letters 52 (2011) 426–429
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Tetrahedron Letters
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Catalytic reactions of bis-p-allylpalladium generated from allyltrifluoroborate
⇑
Hiroyuki Nakamura , Kazuki Shimizu
Department of Chemistry, Faculty of Science, Gakushuin University, Mejiro, Toshima-ku, Tokyo 171-8588, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Bis-p-allylpalladium-catalyzed nucleophilic allylations to aldehydes 2 and imines 3 have been achieved
Received 19 October 2010
Revised 11 November 2010
Accepted 15 November 2010
Available online 18 November 2010
by replacing allylstannanes with allyltrifluoroborate. Amphiphilic bisallylation of activated olefins 6 with
allyltrifluoroborate and allyl acetate also proceeded smoothly in the presence of Pd2(dba)3ÁCHCl3 and tri-
cyclohexylphosphine catalysts.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Bis-p-allylpalladium
Allylation
Amphiphilic
Allyltrifluoroborate
Since the discovery of carbon–carbon bond formation in
p
-allyl-
tion can be applied to the synthesis of medium-sized carbocycles.14
Wallner and Szabó demonstrated the detailed regio- and stereose-
palladium complexes1 with carbon nucleophiles,2–4 palladium has
become one of the most useful metals in organic synthesis.5,6 The
-allylpalladium complexes are key electrophilic intermediates
in the Tsuji–Trost allylation reaction and react with various
nucleophiles.
lectivity of bis-p-allylpalladium complexes by density functional
p
calculations.15,16 Recently, Itami and co-workers discovered the
regioselective unsymmetrical tetraallylation of C60 using the cata-
lytic amphiphilic bis-
allylpalladium complexes but also pincer-type
plexes display nucleophilic allylation to electrophiles.18,19
In general, in addition to bis- -allylpalladium formation from
the dimerization of butadienes,20 bis-
-allylpalladium complexes
utilized for nucleophilic allylation and amphiphilic bisallylation
may be generated by the transmetalation of -allylpalladium com-
p p-
-allylpalladium reaction.17 Not only bis-
In previous studies, we found that bis-
p
-allylpalladium com-
p-allyl-Pd–Ar com-
plexes7 react with electrophiles, such as aldehydes8 and imines,9,10
in a nucleophilic manner (Fig. 1). The presence or absence of li-
p
gands controls the reactivity of the bis-
p
-allylpalladium com-
p
plexes,11 and they undergo chemoselective allylic addition to
aldehydes or imines in the absence of phosphine ligands.12 Fur-
p
thermore, bis-
p
-allylpalladium complexes display amphiphilic
plexes with allylstannanes in a catalytic cycle. However, there are
disadvantages to the use of organostannanes because of their tox-
icity as well as their byproducts. We focused on the use of allyltri-
reactivity with activated olefins to give the bisallylated products
1,7-octadienes in high yields.13 This catalytic amphiphilic bisallyla-
fluoroborate in catalytic bis-p-allylpalladium reactions. Since the
discovery of the Suzuki–Miyaura coupling reaction,21 much atten-
tion has been paid to organoboranes. The most interesting feature
of organoboranes and their byproducts is that they are less toxic
compared to other organometallic reagents, in particular, org-
anostannanes. Recently, potassium trifluoroborates, among the
other organoboranes, have been utilized widely as equivalents to
the corresponding organoboronic acids for Suzuki–Miyaura-type
coupling reactions due to their stability, achieved without decreas-
ing their high reactivity.22 Malinakova and co-workers demon-
strated palladium-catalyzed bisfunctionalization of allenyl esters
Pd(II)
Pd(II)
BF3K
SnBu3
Pd
EWG
EWG
RCH=NR'
RCHO
R"
NHR'
OH
EWG
EWG
R
R
R"
nuclephilic
allylation
amphiphilic
bisallylation
for synthesis of unsaturated
c
-lactines.23 Furthermore, Lewis
acid24 or palladium-catalyzed25 allylations and the allylation in a
biphasic medium (CH2Cl2/H2O)26 of carbonyl compounds have
been developed by using allylic boranes and/or borates. In this Let-
Figure 1. Catalytic reactions of bis-p-allylpalladium.
ter, we describe an alternative catalytic system of bis-
dium complexes generated from allyltrifluoroborate.
p-allylpalla-
⇑
Corresponding author.
E-mail address: hiroyuki.nakamura@gakushuin.ac.jp (H. Nakamura).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.11.082

H. Nakamura, K. Shimizu / Tetrahedron Letters 52 (2011) 426–429
427
We first examined the reaction of allyltrifluoroborate 127 and
Table 2
Allylation of various imines 4
benzaldehyde 2a in the presence of PdCl2(PPh3)2 (10 mol %) in
THF at 70 °C. The corresponding homoallylalcohol 3a was obtained
in 67% yield. Although the use of a palladium(0) catalyst, such as
Pd(PPh3)4, afforded a lower yield of 3a (43% yield), the use of
Cl
Cl
Pd
Pd
R3
H
R3
(10 mol%)
HN
R2
N
p
-allylpalladium chloride dimer gave the best result, and the
BF3K
R2
allylation reaction proceeded in 86% yield at room temperature
(Table 1, entry 1). Previously, we found that the use of platinum
catalysts was more suitable for the nucleophilic allylation of
aldehydes with allyltributylstannanes.8,9 We examined this
nucleophilic allylation with various aldehydes. As shown in Table
1 , 4-bromobenzaldehyde underwent nucleophilic allylation very
smoothly to give the corresponding homoallylic alcohol 3b quanti-
tatively, without giving any allylated product at a bromo-substi-
tuted position obtained by the Suzuki–Miyaura-type coupling
reaction (entry 2).28,29 Not only aromatic aldehydes 2a–c (entries
1–3) but also aliphatic aldehydes 2d–f underwent the nucleophilic
THF, rt.
1
4a-g
5a-g
Entry
4
R2
R3
Time (h)
Yielda (%)
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
Ph
Ph
24
7
7
24
24
24
24
93
85
98
97
66
85
84
4-CO2MeC6H4
4-OMeC6H4
Ph
2-Py
4-OMeC6H4
4-OMeC6H4
Ph
4-MeC6H4
PhCH@CH2
4g
a
Isolated yield based on imine 4.
allylation reaction in the presence of the p-allylpalladium chloride
dimer catalyst in THF at room temperature. Cyclohexycarboxalde-
hyde 2d gave a lower yield of the homoallylic alcohol 3d due to the
steric hindrance of the cyclohexyl group, while the less hindered
n-heptanal afforded the corresponding homoallylic alcohol 3d in
94% yield (entry 4 vs 5). The nucleophilic allylation also proceeded
with the conjugated aldehyde 2g to give 3g in 65% yield (entry 7).
We then examined the nucleophilic allylation of various imines
under palladium(II)-catalyzed conditions. The results are summa-
rized in Table 2. The aromatic imines 4a, 4b, and 4c derived from
4-nitrobenzaldehyde reacted with potassium allyltrifluoroborate
1 to give the corresponding homoallylamines 5a, 5b, and 5c,
respectively, in high yields (Table 2, entries 1–3). The aromatic imi-
nes 4c and 4d derived from benzaldehyde also gave the corre-
sponding homoallylamines 5c and 5d in 97% and 66% yields,
respectively (entries 4 and 5). The pyridyl moiety substituted on
the N-atom of imine 4d was expected to co-ordinate with the pal-
ladium catalyst to accelerate the reaction rate. However, this pyr-
idyl moiety was not effective in this reaction. The reactions of 4f,
derived from 4-tolaldehyde and 4-methoxyaniline, and 4g, derived
from cinnamaldehyde and 4-methoxyaniline, also proceeded
smoothly to give the corresponding homoallylamines 5f and 5g
in 85% and 84% yields, respectively (entries 6 and 7).
results are shown in Table 3. The reaction of phenylidene malono-
nitrile 6a (1 equiv), allyltrifluoroborate 1 (1.5 equiv), and allyl ace-
tate (1.5 equiv) in THF proceeded in the presence of Pd(PPh3)4
(10 mol %) in an Ar atmosphere at 70 °C to give the corresponding
bisallylated product 7a in 71% yield (entry 1). However, the use of
allyl chloride, which was considered the most appropriate for the
amphiphilic bisallylation with allyltributylstannane, was less
effective (entry 2). Palladium(II) catalysts, such as Pd(OAc)2 and
PdCl2(PPh3)2, were not effective in this reaction. Therefore, we
examined the effect of phosphine ligands on the amphiphilic bisal-
lylation using Pd2(dba)3ÁCHCl3 (5 mol %). Although tri-n-butyl-
phosphine was more effective than triphenylphosphine (entry 1
vs 3), other trialkylphosphines, such as tri-tert-butylphosphine
and tri-n-propylphosphine, afforded low yields of 7a (entries 4
and 5). The best result was observed in the case of tricyclohexyl-
phosphine, in which 7a was obtained quantitatively (entry 6). Trip-
henylphosphite was also a suitable ligand for the reaction (entry
7); however, bidentate phosphines, such as 1,2-bis(diphenylphos-
phino)ethane (dppe) and bis(diphenylphosphino)ferrocene (dppf),
tripentafluorophenylphosphine, and X-phos30 were not effective
in this reaction (entries 8–11).
The aldehydes and imines underwent the palladium-catalyzed
nucleophilic allylation and the corresponding homoallylic alcohols
and imines were obtained in good-to-high yields. We investigated
the amphiphilic bisallylation of activated olefins 6 in the presence
of palladium catalysts. We first examined the optimization of pal-
ladium catalysts and ligands for the amphiphilic bisallylation. The
Table 3
Effect of various ligands on catalytic amphiphilic bisallylation
CN
OAc
BF3K
Ph
CN
1
6a
Table 1
Pd-cat./Ligand
Allylation of various aldehydes 2
CN
CN
Ph
THF, 70 o
C
Cl
Pd
Pd
7a
Cl
O
OH
Entry
Pd-cat. (mol %)/ligand (mol %)a
Time (h)
Yieldb (%)
(10 mol%)
BF3K
R1
H
R1
1
2c
3
4
5
6
7
8
9
Pd(PPh3)4 (10)
Pd(PPh3)4 (10)
18
18
24
24
24
4
12
24
24
24
24
71
38
85
42
30
>99
80
38
3
THF, rt.
3a-g
1
2a-g
Pd2(dba)3ÁCHCl3 (5)/P(n-Bu)3 (10)
Pd2(dba)3ÁCHCl3 (5)/P(t-Bu)3 (10)
Pd2(dba)3ÁCHCl3 (5)/P(n-Pr)3 (10)
Pd2(dba)3ÁCHCl3 (5)/PCy3 (10)
Pd2(dba)3ÁCHCl3 (5)/P(OPh)3 (10)
Pd2(dba)3ÁCHCl3 (5)/dppe (5)
Pd2(dba)3ÁCHCl3 (5)/dppf (5)
Pd2(dba)3ÁCHCl3 (5)/P(C6F5)3 (10)
Pd2(dba)3ÁCHCl3 (5)/X-Phos (10)
Entry
2
R1
Time (h)
Yielda (%)
1
2b
3
4
5
2a
2b
2c
2d
2e
2f
Ph
12
6
86
>99
67
53
94
4-BrC6H4
2-Naphtyl
c-Hexyl
n-Hexyl
PhCH2CH2
PhCH@CH
18
24
24
11
9
10
11
4
30
6
7
70
65
2g
a
b
c
Amount of catalyst and ligand are indicated in the parenthesis.
a
Yield was determined by GC analysis using n-dodecane as an internal standard.
Isolated yield based on aldehyde 2.
The reaction was carried out using PdCl2(PPh3)2 (10 mol %).
b
Allyl chloride was used instead of ally acetate.

428
H. Nakamura, K. Shimizu / Tetrahedron Letters 52 (2011) 426–429
Table 4
Catalytic amphiphilic bisallylation of various activated olefins 6a
Entry
Olefin 6
Time (h)
24
Product 7
Yieldb (%)
CN
CN
CN
CN
1
75
7b
Br
6b
Br
CN
CN
CN
CN
2
3
24
24
94
71
7c
MeO2C
6c
MeO2C
CN
CN
CN
CN
7d
MeO
O
6d
MeO
O
CN
CN
CN
CN
4
5
6
1
1
1
97
>99
77
6e
7e
CN
CN
CN
S
CN
S
6f
7f
CN
CN
CN
CN
6g
N
N
7g
a
The reactions of olefin 6 (0.65 mmol) with potassium allyltrifluoroborate 1 (1.5 equiv) and allyl acetate (1.5 equiv) were carried out in the presence of Pd2(dba)3ÁCHCl3
(5 mol %) and tricyclohexylphosphine (10 mol %) at 70 °C in THF.
b
Isolated yield based on olefin 6.
A suitable condition for the amphiphilic bisallylation of acti-
vated olefin 6a was established, and then we examined the scope
of the reaction by using various activated olefins. The results are
summarized in Table 4. The activated olefin 6b, which has a bromo
group substituted at the para position of aromatic ring, underwent
the amphiphilic bisallylation under standard palladium-catalyzed
conditions to give the corresponding product 7b in 75% yield (entry
1). The reactions of other aromatic olefins 6c and 6d, which have
an electron-withdrawing group such as methoxycarbonyl and an
electron-donating group such as methoxy at the para position gave
the corresponding 1,7-octadienes 7c and 7d in 94% and 71% yields,
respectively (entries 2 and 3). The current bisallylation also pro-
ceeded not only with benzene ring-substituted activated olefins
but also with heteroaromatic group-substituted activated olefins,
such as 2-furyl (6e), 2-thiofuryl (6f), and 3-pyridyl (6g) substitu-
ents. The reactions were complete within an hour and the desired
1,7-octadienes 7e, 7f, and 7g were obtained in good to high yields
(entries 4–6). The acceleration of the reaction rate may be because
of the co-ordination between palladium and both CN and heteroar-
omatic groups. In all the above cases, monoallylated products were
not obtained.
OAc
EWG
EWG
Pd(0)Ln
R"
7
EWG
GWE
Ln
Pd
Pd
AcO
R"
8
10
BF3K
EWG
EWG
Pd
1
R"
9
KBF3OAc
6
Scheme 1. Plausible mechanism for amphiphilic bisallylation.
produce bis-
p
-allylpalladium complex 9, which would react with
-allylpalladium intermediate 10. Fi-
nally, the reductive elimination from 10 would give the correspond-
activated olefins 6 to give the
p
ing bisallylated products 7, and palladium(0) species would be
regenerated in the catalytic cycle. The
p-allyl group reacts with a
nucleophilic carbon center in the palladium complex 10.
In summary, we developed nucleophilic allylations of aldehydes
and imines and amphiphilic bisallylation of activated olefins
The plausible mechanism for this amphiphilic bisallylation is
shown in Scheme 1. The oxidative addition of allyl acetate to palla-
dium(0) gives
the allyl trifluoroborate 1 to the
p
-allylpalladium acetate 8. The transmetalation of
by generating bis-
p-allylpalladium complexes from allyltrifluorob-
p-allylpalladium acetate 8 would
orate.31 Because toxic organostannanes pollute the environment,

H. Nakamura, K. Shimizu / Tetrahedron Letters 52 (2011) 426–429
429
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30. Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006,
45, 3484–3488.
the replacement of allylstannanes by allyltrifluoroborates achieved
in our study can have many applications in organic synthesis
involving a catalytic bis-p-allylpalladium reaction system.
References and notes
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8. Nakamura, H.; Asao, N.; Yamamoto, Y. J. Chem. Soc., Chem. Commun. 1995,
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31. Representative procedures for the palladium(II)-catalyzed nucleophilic allyla-
tion of an aldehyde and the palladium(0)-catalyzed amphiphilic bisallylation of
an activated olefin are presented here.
1-Phenyl-3-buten-1-ol (3).
A
mixture of allyltrifluoroborate
1 (104 mg,
0.7 mmol), benzaldehyde 2a (51 mL, 0.5 mmol), and
p-allylpalladium chloride
dimer (18 mg, 0.05 mmol) was dissolved in THF (3 mL) and stirred at room
temperature for 12 h. The reaction mixture was heterogeneous all the while.
Precipitates were removed through a Celite pad and the solvent was evaporated.
Theresiduewaspurifiedby silicagelcolumnchromatography withhexane/ethyl
acetate (20:1) to give 3a (63 mg, 0.43 mmol, 86% yield) as a colorless liquid: 1
H
NMR (400 MHz; CDCl3) d 7.25–7.36 (m, 5H), 5.76–5.85 (m, 1H), 5.13–5.19 (m,
2H), 4.72–4.76 (m, 1H), 2.46–2.57 (m, 2H), 2.02 (d, J = 2.8 Hz, 1H).
4,4-Dicyano-5-phenyl-1,7-octadinene (7a). Allyl acetate (105 mL, 0.98 mmol)
was added to a mixture of phenylidene malononitrile 6a (100 mg, 0.65 mmol),
allyltrifluoroborate
1
(145 mg, 0.98 mmol), Pd2(dba)3ÁCHCl3 (35 mg,
0.033 mmol), and tricyclohexylphosphine (18 mg, 0.066 mmol), in THF (3 mL)
in an Ar atmosphere and the mixture was stirred at 70 °C for 4 h. The reaction
mixture was heterogeneous all the while. Precipitates were removed through a
Celite pad and the solvent was evaporated. The residue was purified by silica gel
column chromatography with hexane/ethyl acetate (50:1) to give 7a (158 mg,
0.65 mmol, quant) as a colorless liquid: 1H NMR (400 MHz; CDCl3) d 7.26–7.42
(m, 5H), 5.83–5.93 (m, 1H), 5.43–5.54 (m, 1H), 5.40 (d, J = 9.2 Hz, 1H), 5.31 (d,
J = 16.4 Hz, 1H), 5.08 (d, J = 18.8 Hz, 1H), 4.98 (d, J = 8.8 Hz, 1H), 3.08 (dd,
J = 4.4 Hz, 1H), 2.84–2.96 (m, 2H), 2.47–2.52 (m, 1H), 2.35–2.41 (m, 1H).