Gadolinium(III) chloride: a novel and an efficient reagent for the synthesis of homoallylic alcohols

Article abstract of DOI:10.1016/j.tetlet.2006.04.124

Carbonyl compounds efficiently undergo nucleophilic addition reactions with allylstannanes in the presence of GdCl₃·6H₂O in acetonitrile under extremely mild reaction conditions to give the corresponding homoallylic alcohols in excellent yields and with high chemoselectivity.

Full text of DOI:10.1016/j.tetlet.2006.04.124

Tetrahedron Letters 47 (2006) 4315–4318
Gadolinium(III) chloride: a novel and an efficient reagent for
the synthesis of homoallylic alcoholsI
B. Venkat Lingaiah, G. Ezikiel, T. Yakaiah, G. Venkat Reddy and P. Shanthan Rao*
Fluoroorganic Division, Indian Institute of Chemical Technology, Hyderabad 500 007, AP, India
Received 20 March 2006; revised 13 April 2006; accepted 26 April 2006
Abstract—Carbonyl compounds efficiently undergo nucleophilic addition reactions with allylstannanes in the presence of
GdCl3Æ6H2O in acetonitrile under extremely mild reaction conditions to give the corresponding homoallylic alcohols in excellent
yields and with high chemoselectivity.
ꢀ 2006 Elsevier Ltd. All rights reserved.
In recent years the synthesis of homoallylic alcohols has
been an intense research area.1 Homoallylic alcohols are
useful tools for the construction of complex molecules
and can be easily converted into many important build-
ing blocks for natural products synthesis.2 Lewis acid
catalyzed C–C bond forming reactions have gained
much importance in organic synthesis because of their
mild reaction conditions and high selectivity.3 Lewis
acid promoted nucleophilic addition of allyltin reagents
to carbonyl compounds is one of the straightforward
methods for the synthesis of homoallylic alcohols.4–6
Lewis acids such as Et2OÆBF3, TiCl4, SnCl4, etc. are ex-
tremely moisture sensitive, which causes inconvenience
in handling and manipulating. Thus, there is an interest
in development of a new catalyst which has advantages
with respect to mild reaction conditions, cleaner reac-
tions, shorter reaction times, high yields of products,
lower catalytic loading and simple isolation procedures.7
Consequently, several methods have been reported for
the allylation of carbonyl compounds. Generally, strong
Lewis acids8–10 are required to promote the addition of
allyltributylstannane to a carbonyl function. Recently,
GdCl3Æ6H2O has become an attractive candidate as a
powerful Lewis acid in C–C bond forming transforma-
tions,11 which would extend the scope and generality
of these allylation reactions.
In continuation of our studies aimed to develop new
methodologies for organic transformations,12,13 here
we report GdCl3Æ6H2O as a mild and efficient catalyst
for the allylation of carbonyl compounds with allyl
stannanes under mild and neutral conditions.
We chose allyltributylstannane, which is inexpensive,
readily available and does not require rigorously dry
conditions or an inert atmosphere in comparison with
most metal reagents, as our allyl reagent. We first exam-
ined the reaction of allyltributylstannane with benzalde-
hyde using 5 mol % of GdCl3Æ6H2O in acetonitrile by
TLC monitoring and observed the total disappearance
of starting material after 3 h. It was found that GdCl3Æ
6H2O acts as an excellent promoter leading to the
formation of 1-phenyl-3-buten-1-ol in excellent yield
(95%) after extractive work-up and purification. This
methodology was extended to a variety of aldehydes to
determine the scope and reactivity of the procedure
and the results are summarized in Table 1. The results
suggest that GdCl3Æ6H2O is an efficient promoter for
the allylation of aldehydes and can be extended to a
broad range of aldehydes (Scheme 1). In all cases, the
reaction proceeded efficiently at ambient temperature
with high chemoselectivity. Enolizable aldehydes also
produced the corresponding homoallylic alcohols in
good yield. No bis-allylated products were obtained with
3,4,5-trimethoxybenzaldehyde, which are normally ob-
served in allylation reactions using allyltrimethylsilane.14
Acid sensitive aldehydes such as furfural and cinnam-
aldehydes also smoothly reacted to afford the correspond-
ing homoallylic alcohols in excellent yields. Encouraged
by these results we extended our method to ketones and
Keywords: Gadolinium chloride; Allylstannanes; Allylation; Carbonyl
compounds; Homoallylic alcohols.
q IICT Communication No. 060324.
*
Corresponding author. Tel.: +91 40 9885223425; e-mail:
shanthanpp@yahoo.co.in
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.04.124

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B. V. Lingaiah et al. / Tetrahedron Letters 47 (2006) 4315–4318
Table 1. Synthesis of homoallylic alcohols from aldehydes
Entry
a
Aldehyde
CHO
Homoallylic alcohola
Time (h)
3.0
Yieldb (%)
95
OH
OH
CHO
CHO
b
c
3.0
2.5
3.0
95
92
94
Cl
Cl
OH
H3C
H3CO
H3C
OH
CHO
d
H3CO
OH
CHO
e
f
3.0
3.5
89
87
O2N
O2N
OH
CHO
NO2
NO2
OH
CHO
g
3.5
3.0
87
94
CF3
CF3
OH
CHO
h
OH
OH
i
j
2.5
2.5
90
92
CHO
CHO
OH
CHO
k
l
3.0
3.0
86
88
OH
CHO
OH
CHO
CHO
m
n
3.0
3.5
3.0
92
90
93
OH
MeO
MeO
MeO
MeO
OMe
OMe
o
O
CHO
O
OH
a All the products were characterized by 1H NMR, IR and mass spectrometry.
b Isolated yields.

B. V. Lingaiah et al. / Tetrahedron Letters 47 (2006) 4315–4318
4317
OH
O
HO
R
GdCl3.6H2O
CH3CN, r.t.
GdCl3.6H2O
CH3CN, r.t.
4
R'
R
+
R'
Sn
Bu3Sn
CHO +
R
R
3
2
1
5
6
4
Scheme 1.
Scheme 2.
the presence of a ketone. The most interesting result
was observed for aryl aldehydes with electron withdraw-
ing and releasing groups which underwent allylation
at the same rate, suggesting that the reactivity of the
carried out the reaction using acetophenone, cyclohexa-
none and a b-ketoester. None of the ketones gave homo-
allylic alcohols even after longer reaction times, thus
providing a chemoselective allylation of aldehydes in
GdCl3
GdCl3.6H2O
SnBu3
O
OSnBu3
OH
SnBu3
O
H2O
R
H
R
R
R
Bu3SnOH
GdCl3
Figure 1.
Table 2. Synthesis of homoallylic alcohols from ketones
Entry
Ketone
Homoallylic alcohola
Time (h)
3.0
Yieldb (%)
94
OH
COMe
COPh
a
OH
Ph
b
c
3.0
3.5
88
86
OH
COMe
Cl
Cl
OH
COMe
d
e
f
3.0
3.0
3.0
3.5
90
85
88
90
F
F
OH
COMe
O2N
Me
O2N
OH
COMe
COMe
Me
OH
g
MeO
O
MeO
HO
i
j
2.5
2.5
86
88
O
HO
The experimental procedure is included in Ref. 16.
a All the products were characterized by 1H NMR, IR and mass spectrometry.
b Isolated yields.

4318
B. V. Lingaiah et al. / Tetrahedron Letters 47 (2006) 4315–4318
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The high coordinating ability of gadolinium(III) towards
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drives the reaction towards the product. We propose the
mechanism as depicted in Figure 1.
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Allylation of ketones is a challenging task due to the
lower electrophilicity of the carbonyl group and steric
hindrance present in ketones. After successful allylation
of aldehydes we studied the allylation of ketones using
GdCl3Æ6H2O as a catalyst and tetraallyltin as the allylat-
ing agent. The reaction of acetophenone proceeded
smoothly and gave the corresponding homoallylic
alcohol. Encouraged by this result, this method was
extended to various ketones such as aryl, alkyl, cyclic
heterocyclic and a,b-unsaturated ketones (Scheme 2).
In all cases the reaction proceeded smoothly and gave
the corresponding homoallylic alcohols in good to excel-
lent yields. The results are summarized in Table 2. The
usage of hydrated form of catalyst is having an advan-
tage in reduced reaction timings compared to the reac-
tion carried out in methanol.15
In conclusion, we have demonstrated a simple, conve-
nient and efficient protocol for the synthesis of homo-
allylic alcohols from carbonyl compounds and
allylstannanes using GdCl3Æ6H2O under mild and neu-
tral conditions. This catalyst offers several advantages
including mild conditions, clean reactions, shorter reac-
tion times, high yields of products and lower catalytic
loading.
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Acknowledgements
The authors are thankful to Dr. J. S. Yadav, Director,
IICT and Shri. S. Narayan Reddy, Head, Fluoroorganic
Division, IICT, Hyderabad for their constant encour-
agement and financial support from an industry-spon-
sored project.
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16. Experimental procedure: A mixture of aldehyde (2 mmol),
allyltributylstannane (2 mmol) or [1 mmol of tetraallyltin
for the allylation of 2 mmol of ketone] and gadolinium
chloride hexahydrate (5 mol %) in acetonitrile (2 mL) was
stirred at ambient temperature for an appropriate time
(see Tables 1 and 2). After completion of the reaction,
as indicated by TLC, the reaction mixture was diluted
with water (20 mL) and extracted with ethyl acetate
(2 · 15 mL). The combined organic layers was washed
with brine, dried over anhydrous Na2SO4 and concen-
trated in vacuo, and the resulting product was purified by
column chromatography on silica gel (Merck, 60–120
mesh, ethyl acetate–hexane, 2:8) to afford pure homo-
allylic alcohol.
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