Rapid access to homoallylic alcohols via Pd(OAc)2 catalyzed Barbier type allylation in presence of DMAP

Article abstract of DOI:10.1016/j.tetlet.2013.09.038

DMAP was found to accelerate significantly the rate of Pd(OAc)₂ catalyzed Barbier type allylation of carbonyl compounds by allylbromide using SnCl₂·2H₂O as reducing agent. Both aldehyde as well as ketones produced excellent yields within a short reaction time in the presence of 3 mol % of Pd(OAc)₂ and 12 mol % of DMAP at room temperature. Aldehydes could be allylated within 5-10 min whereas, in case of ketones, the reaction completes in 45-120 min.

Full text of DOI:10.1016/j.tetlet.2013.09.038

Tetrahedron Letters 54 (2013) 6324–6327
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rapid access to homoallylic alcohols via Pd(OAc)2 catalyzed Barbier
type allylation in presence of DMAP
⇑
Bishwapran Kashyap, Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati 781014, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
DMAP was found to accelerate significantly the rate of Pd(OAc)2 catalyzed Barbier type allylation of car-
bonyl compounds by allylbromide using SnCl2Á2H2O as reducing agent. Both aldehyde as well as ketones
produced excellent yields within a short reaction time in the presence of 3 mol % of Pd(OAc)2 and
12 mol % of DMAP at room temperature. Aldehydes could be allylated within 5–10 min whereas, in case
of ketones, the reaction completes in 45–120 min.
Received 2 August 2013
Revised 8 September 2013
Accepted 11 September 2013
Available online 19 September 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Barbier allylation
Allyl bromide
SnCl2
Pd(OAc)2
DMAP
OH
Allylation of carbonyl compound is a significant carbon–carbon
bond forming transformation in organic chemistry which leads to
the formation of a very important synthetic intermediate homoal-
lylic alcohol.1 A common approach for carbonyl allylation is the use
of various allylic organometallic reagents such as allylsilanes,2 all-
ylstannanes,3 allyl indium,4 and allylboranes.5 However, most of
these allyl transfer reagents are moisture sensitive and highly
active. This makes these reagents unpractical for large scale
production of homoallylic alcohols.
O
Pd(OAc)2, DMAP
Br
R1
+
R2
R1
R2
SnCl2.2H2O, DMF, rt
Scheme 1. Palladium catalyzed allylation of carbonyl compounds.
To the best of our knowledge there are only a very few reports
of palladium catalyzed, one-pot Barbier-type allylations using an
allyl halide. Guo and co-workers have put forward a SnCl2/PdCl2
mediated Barbier type allylation of aldehyde.22 Although good
yield of the expected product was observed, long reaction time
makes the procedure unsuitable. Moreover, high amount of cata-
lyst loading is required to carry out the reaction. Till date, the scope
of 4-(NN-dimethylamino)pyridine (DMAP) as ligand for palladium
catalyzed reaction has not been studied explicitly. In continuation
of our investigations on various allylation reactions,23 we report
herein an expeditious, one pot method for the synthesis of homo-
allylic alcohols using allyl bromide and SnCl2Á2H2O in the presence
of a catalytic system composed of Pd(OAc)2 and DMAP (Scheme 1).
Initially the reaction was optimized by varying the solvent, con-
centration of the catalyst, reducing agent, and allylbromide taking
benzaldehyde as a model substrate. In a typical reaction Pd(OAc)2
(0.01 mmol) and DMAP (0.04 mmol) were dissolved in DMF and
waited for ten minutes. Then aldehyde (1 mmol), allylbromide
(1 mmol), and SnCl2Á2H2O (1 mmol) were added successively at
room temperature. The reaction was monitored by thin layer chro-
matography (TLC). The results are given in Table 1. Initial reaction
without Pd(OAc)2 failed to produce any product even after 24 h of
Recently, Barbier reaction6 has gained interest among chemists
in the field of allylation reaction. Due to its operational simplicity
and the fact that it does not require strictly anhydrous condition,
the one-pot Barbier type allylation reaction is becoming popular.
However, limited attempts have been made to develop an effective
multicomponent Barbier allylation process, which is due to low
reactivity of allyl halides. Over the years a few methods have been
reported for the Barbier type allylation of carbonyl compounds.
These include the use of ionic liquid,7 clay catalyst,8 organic cata-
lyst,9 ultrasonic irradiation,10 and electrochemical allylation.11
One of the most common approaches for Barbier type allylation
is the use of a catalyst derived from transition metals such as
indium,12 zinc,13 bismuth,14 chromium,15 titanium,16 cadmium,17
aluminum,18 tin,10,19 magnesium,20 and gallium.21 However, most
of the above methods have the disadvantages of long reaction time
and low yield of the allylated product.
⇑
Corresponding author.
E-mail address: pphukan@yahoo.com (P. Phukan).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.09.038

B. Kashyap, P. Phukan / Tetrahedron Letters 54 (2013) 6324–6327
6325
Table 1
Allylation of benzaldehyde using Pd(OAc)2 and DMAP
Entry
Solvent
Allylbromide (mmol)
SnCl2Á2H2O (mmol)
Pd(OAc)2 (mmol)
DMAP (mmol)
Time
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
Toluene
DMSO
H2O
1
1
1
1
1
1
1
1
1.1
1.2
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1
—
1
1
1
1
1
1
1
1
1.5
2
2.5
2.5
2.5
2.5
2.5
2.5
—
—
0.04
—
24 h
24 h
5 h
0
0
0.01
0.01
0.01
0.02
0.03
0.04
0.05
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
70
70
74
80
80
81
83
83
88
95
95
30
0
0.04
0.08
0.12
0.16
0.2
0.12
0.12
0.12
0.12
0.12
0.12
0.12
0.12
0.12
0.12
15 min
15 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
2 h
24 h
24 h
24 h
24 h
0
0
10
CH2Cl2
a
Isolated yield.
reaction (Table 1, Entry 1). Similarly the reaction was not success-
ful in the absence of SnCl2Á2H2O (Table 1, Entry 2). Next, the
reaction was carried out using 0.01 mmol of Pd(OAc)2 and 1 mmol
of SnCl2Á2H2O and 70% of yield was observed after 5 h of reaction.
However, addition of 0.04 mmol of DMAP to the reaction mixture
could produce a similar result with significant reduction of reac-
tion time to 15 min (Table 1, Entry 4). Further increment of catalyst
amount up to 0.03 mmol and DMAP amount up to 0.12 mmol did
improve the result. A slight increase in the yield was observed on
increasing the amount of allylbromide to 1.1 mmol (Table 1, Entry
9). However, amount of SnCl2Á2H2O had a greater effect on the
reaction yield. The yield of the desired product goes up to 95% on
doubling the amount of SnCl2Á2H2O (Table 1, Entry 12). The reac-
tion was further examined using different solvents such as H2O,
CH3CN, DCM, toluene, and DMSO. Use of DCM and CH3CN produced
10% and 30% of yield of the product respectively. All the other sol-
vents failed to give the desired product even after 24 h of reaction
time. In all the above cases, DMAP was taken as 4:1 ratio with
Pd(OAc)2. Finally the use of 0.03 mmol of Pd(OAc)2, 0.12 mmol of
DMAP, 1.1 mmol of allylbromide, and 2 mmol of SnCl2Á2H2O in
DMF was taken as optimum condition for the reaction.
After optimization, the method was extended to a variety of
aldehydes. The results are depicted in Table 2. It was observed that
both aromatic as well as aliphatic aldehydes react efficiently under
the reaction condition.24 Most of the reactions were completed
within 5 min of reaction time with excellent yield of the desired
product. However, 2-nitrobenzaldehyde, 2-bromobenzaldehyde,
4-methylbenzalldehyde, 4-ethylbenzaldehyde, 2-naphthaldehyde,
and octanaldehyde took slightly longer time for completion with
excellent yields.
The success of the method with aldehyde encouraged us to
extend the reaction to ketones (Table 3). Initial reaction with
acetophenone was encouraging. The reaction was completed in
50 min with 88% yield of the desired product in the presence of
3 mol % of the catalyst and 12 mol % of DMAP. Then the reaction
was extended to a variety of ketones and the results are summa-
rized in Table 3.
It was observed that both aromatic as well as aliphatic ketones
undergo this reaction efficiently. In all the cases, the reaction takes
45 min to 2 h for completion with high yield. It was observed that
aromatic ketones (Table 3, Entries 1,3,4) react much faster than
aliphatic ketones (Table 3, Entries 5–10). Among aromatic ketones,
4-fluoro acetophenone took slightly longer time to produce the
respective homoallylic alcohol (Table 3, Entry 2).
We believe, the enhancement in the reaction rate after addition
of DMAP is due to ligand acceleration effect.25 It has been
established that Pd(II) has a tendency to form four coordinated
26
complexes with DMAP such as Pd(DMAP)4(OH)2
and
PdCl2(DMAP)4.27 Hain and co-workers have established during
their study on DMAP-stabilized palladium nanoparticles that the
formation of such type of Pd(II) complexes results in the increase
in the efficiency of the palladium catalyst.26a
We have carried out a cyclic voltammetry experiment to
examine the role of DMAP in enhancing the reaction rate
(Fig. 1). The present electrochemical experiment shows a signifi-
cant change in the cyclic voltammogram of Pd(OAc)2 in the pres-
ence of DMAP (Fig. 1b and c). This change might be associated
with the formation of Pd(II) complex with DMAP. It has been
observed that Pd(OAc)2 shows a cathodic peak at À0.464 V. This
peak shifts to À0.529 V after addition of DMAP to the solution
of Pd(OAc)2. Moreover, the characteristic peak of DMAP (Fig. 1a)
disappears during complexation with palladium. This indicates
a strong complexion of DMAP with Pd(II) and therefore the reac-
tion rate increases due to the ligand acceleration effect. Detailed
study in this effect of DMAP in the rate enhancement is in
progress.
In summary, an expeditious method has been established for
the synthesis of homoallylic alcohols via a Barbier type allylation
of aldehydes and ketones using allyl bromide in the presence of
SnCl2Á2H2O under the influence of a catalytic amount of Pd(OAc)2
at room temperature. Significant rate enhancement of the reaction
was observed by the presence of DMAP. In case of aldehydes, the
reaction completes very rapidly to produce the corresponding
homoallylic alcohols in 5–10 min, whereas ketones take a maxi-
mum of 2 h for completion of the reaction.
Acknowledgments
Financial support from DST (Grant No. SR/S1/OC-43/2011) is
gratefully acknowledged. B.K. thanks CSIR for Senior Research
Fellowship.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.
09.038.

6326
B. Kashyap, P. Phukan / Tetrahedron Letters 54 (2013) 6324–6327
Table 2
Table 2 (continued)
Allylation of aldehyde using Pd(OAc)2 and DMAPa
Entry Substrate
Product
Time (min) Yieldb
Entry Substrate
Product
Time (min) Yieldb
O
OH
O
OH
16
10
5
81
79
86
86
H
1
5
5
5
5
95
95
93
90
H
3p
OH
3a
O
O
O
O
OH
17
18
19
H
H
H
3q
OH
2
3b
OH
Cl
Cl
Cl
5
H
3r
Cl
3
3c
O
OH
O
OH
Cl
10
H
3s
H
O
4
3d
a
Reaction condition: aldehyde (1 mmol), allylbromide (1.1 mmol), SnCl2Á2H2O
Cl
(2 mmol), Pd(OAc)2, (0.03 mmol), DMAP (0.12 mmol), DMF (2 mL), rt.
OH
b
Isolated yield.
H
5
6
5
5
94
87
3e
OH
F
F
Table 3
O
Allylation of ketone using Pd(OAc)2 and DMAPa
H
Entry
1
Substrate
Product
Time (min)
50
Yieldb
88
3f
O2N
O2N
O
OH
O
OH
H
5a
OH
7
8
5
5
5
8
5
5
85
90
85
82
80
88
90
3g
O
NO2
NO2
O
OH
2
3
120
45
79
82
5b
H
F
8
F
3h
O
OH
OH
MeO
MeO
O
OH
5c
H
OH
9
3i
O
OH
OMe
OMe
4
5
50
90
82
84
O
OH
5d
H
H
10
11
12
13
O
O
HO
HO
3j
Br
Br
5e
O
OH
H
3k
Br
Br
6
120
85
O
OH
5f
O
O
HO
3l
Cl
Cl
Cl
Cl
O
7
8
120
90
80
76
OH
5g
MeO
MeO
MeO
MeO
H
HO
3m
5h
O
OH
O
HO
14
15
10
10
84
80
H
9
120
120
77
79
5i
3n
OH
O
O
HO
10
5j
H
3o
a
Reaction condition: aldehyde (1 mmol), allylbromide (1.1 mmol), SnCl2Á2H2O
(2 mmol), Pd(OAc)2, (0.03 mmol), DMAP (0.12 mmol), DMF (2 mL), rt.
b
Isolated yield.

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