Indium-mediated Barbier-type allylation reaction in PEG400 and PEG400/H2O

Article abstract of DOI:10.3184/030823410X12813608471242

A green method for the allylation of aldehydes with allyl bromide mediated by indium in polyethylene glycol 400 (PEG400) and PEG400/H2O is described. Aldehydes with different substituents afforded the corresponding homoallylic alcohols in good to excellen

Full text of DOI:10.3184/030823410X12813608471242

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 475
AUGUST, 475–477
Indium-mediated Barbier-type allylation reaction in PEG400 and
PEG400/H2O
Zhengyin Du*, Fen Wang, Wanwei Zhou and Jin-Xian Wang
Key Laboratory of Eco-Environment Related Polymer Materials of Ministry of Education; Key Laboratory of Polymer Materials of Gansu
Province & College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, P. R. China
A green method for the allylation of aldehydes with allyl bromide mediated by indium in polyethylene glycol 400
(PEG400) and PEG400/H2O is described. Aldehydes with different substituents afforded the corresponding homo-
allylic alcohols in good to excellent yields. Comparative studies show that water promoted this reaction in PEG 400.
Keywords: indium, allylation, homoallyl alcohols, PEG400, aqueous reaction, green synthesis
Recently there has been interest in developing organometallic
reactions in water amongst which allylation of aldehydes to
give homoallylic alcohols has received the most attention.1
This reaction has been carried out by using metals such as
Mn,2 Fe,3 Sb,4 Ga,5 Sn,6 Mg.7 Most reactions required an
activator such as ammonium chloride, hydrobromic acid and
trimethyl chlorosilane (TMSCl), and used a volatile organic
compound (VOC) as a cosolvent. In comparison with those
metals, indium offers a number of advantages, including its
low toxicity, tolerance towards air and moisture and low ioni-
sation potential.8,9 For these reasons, indium metal-mediated
carbon-carbon bond formation reactions, including the
Barbier-type allylation of carbonyl compounds, have become
a major topic in organic synthesis. The previous reports of
indium-mediated allylation reaction used the volatile organic
solvent tetrahydrofuran (THF),10,11 an aqueous organic media
(THF/H2O),12,13 and water,14,15 which caused environmental
contamination and health problems.
Polyethylene glycol 400 (PEG400) has the advantages of
low vapour pressure and nonflammability. The workup is easy
and it is a non-toxic, good reaction medium that is inexpensive
and eco-friendly.16,17 However, there are no examples of the
allylation of carbonyl compounds in PEG400 which have been
reported. We report here a simple and convenient method for
the preparation of homoallylic alcohol from aldehydes and
allyl bromide by using PEG400 and PEG400/H2O as green
reaction medium and indium as the promoting metal reagent
(Scheme 1).
Table 1 Optimisation of allylation reaction conditionsa
Entry
Reaction media (V/V)
Time/h
Yield/%b
1
2
3
4
5
6
H2O
12
12
12
12
12
12
53
57
75
88
97
84
PEG/H2O (1/1)
PEG/H2O (2/1)
PEG/H2O (3/1)
PEG/H2O (4/1)
PEG
a Reaction conditions: 2-bromobenzaldehyde 1 mmol, allyl
bromide 2 mmol, r.t., TLC tracking.
b Isolated yield after flash column chromatography.
of the product demonstrate that PEG/H2O (V/V=4/1) is the
best choice for the reaction media affording the homoallylic
alcohol in a high yield of 97% (entry 5). It is clear that water
can promote the allylation of 4-bromobenzaldehyde with allyl
bromide in PEG400 whereas large amount of water is dis-
advantageous to this reaction. This might be ascribed to the
acceleration of electron transfer from indium metal to organic
substrates when a small quantity of water is added and a
decrease of solubility of substrates when large amount of
water is used in PEG400 although PEG400 and water can be
miscibility with random ratios.
In order to explore the scope of this reaction, a variety of
aldehydes with different substituents were investigated in both
PEG and PEG/H2O (V/V=4/1) at room temperature based on
the optimised conditions. The reactions were followed with
thin layer chromatography until aldehydes disappeared. The
results shown in Table 2 reveal that all the aldehydes that were
used were converted smoothly to give the corresponding
homoallylic alcohols in good to excellent yields either in
PEG400 or in PEG400/H2O (V/V=4/1). Overall, the reactions
in PEG400/H2O gave similar or higher yields in shorter
reaction times than in pure PEG400. Among the substituted
aromatic aldehydes, those with a 2-bromo and 4-bromo sub-
stituent gave higher yields of 88% and 97%, respectively
(entries 9 and 10). Other substituents, including electron-
donating groups and electron-withdrawing groups, have no
demonstrable effect on the yield of products (entries 1–8,
11 and 12). It is noteworthy that for the same substituent, 2-
substituted aromatic aldehydes gave lower yields of products
than 4-substituted ones. This may be attributable to the larger
steric hindrance of the 2-substituent. For example, 2-methoxy-
and 4-methoxybenzaldehyde gave yields of 81 and 84%,
respectively (entries 2 and 3). Two aliphatic aldehydes were
also explored in this reaction. Fortunately, they gave the cor-
responding homoallylic alcohols in good yields (entries 13
and 14). These indicate that indium-mediated allylation of
aldehydes has a wide range of substrates, which can be used
for large-scale synthesis of homoallylic alcohols. These are
important organic synthesis and as medicinal intermediates.
Results and discussion
The reaction of 4-bromobenzaldehyde with allyl bromide was
chosen as the model to define the optimum reaction conditions
for this indium-mediated allylation reaction. The results are
shown in Table 1. From Table 1, it could be seen that only 53%
of yield was obtained when the reaction was conducted in pure
water for 12 hours (entry 1). This indicates that pure water is
not the ideal medium for the reaction. When PEG400 was used
as the reaction medium, however, a good yield of 84% was
obtained (entry 6). This comparison shows that PEG400 as a
reaction medium is better than pure water. In order to clarify
the effect of water in this reaction, mixtures of PEG400 and
water with different volume ratios were examined as he reac-
tion media under the same conditions (entries 2–5). The yields
Scheme 1 Indium-mediated synthesis of homoallylic
alcohols in PEG400.
* Correspondent. E-mail: Zhengyin Du - clinton_du@126.com

476 JOURNAL OF CHEMICAL RESEARCH 2010
Table 2 Synthesis of homoallylic alcohols from various aldehydesa
PEG400
PEG400/H2O
Entry
1
R
Time/h
14
Yield/%
79
Time/h
Yield/%
Productb
4-CH3C6H4
16
84
2
3
2-CH3OC6H4
4-CH3OC6H4
15
14
73
79
13
16
81
84
4
2-HOC6H4
16
76
14
73
5
6
4-HOC6H4
2-ClC6H4
18
13
79
82
15
13
81
83
7
8
4-ClC6H4
14
13
82
75
14
14
83
80
4-CNC6H4
9
2-BrC6H4
4-BrC6H4
2,4-Cl2C6H4
14
12
16
83
84
73
12
12
15
88
97
83
10
11c
12
3,4-Cl2C6H4
15
69
14
78
13
14
CH3(CH2)3
CH3(CH2)5
14
15
78
77
14
13
78
83
a Reactions conditions: indium 1 mmol, aldehyde 1 mmol, allyl bromide 2 mmol, PEG400 4mL or PEG400 3.2 mL and water 0.8 mL,
r. t., TLC tracked.
1
b Isolated yield after flash column chromatography; all products are known compounds and characterised thoroughly by H and
13C NMR, which were consistent with the literature data.
c The melting point of this product is 59–60oC (lit.21, 59.5 oC).

JOURNAL OF CHEMICAL RESEARCH 2010 477
Conclusion
Gansu Province (No. zd-06-18) and Yong Teachers Research
Foundation of NWNU (No. NWNU-QN-06-27) is acknowl-
edged.
In summary, a simple and green protocol for the synthesis of
homoallylic alcohols by the allylation of aldehydes with allyl
bromide mediated by indium in PEG400 and PEG400/H2O has
been developed. In comparison with previous reports, this
method has some notable advantages, such as using a green
medium, which is more environmentally acceptable. It has a
wide application, simple reaction conditions giving good
to excellent yields, which can be applied for the scale-up
synthesis of these compounds.
Electron Supplementary Information
Electron supplementary information includes the experimen-
tal, spectroscopic data and spectra of the products and is
available via http://www.ingentaconnect.com/content/stl/jcr
Received 29 May 2010; accepted 16 July 2010
Paper 1000162 doi: 10.3184/030823410X12813608471242
Published online: 30 August 2010
Experimental
All reagents were used as obtained from commercial sources except
where mentioned. PEG400 was AR grade and used directly. Indium
granules with a purity of 99.999% were pressed into flakes and
then cut into small pieces prior to use. Allyl bromide was redistilled
for use. Melting points were determined on an XT-4 electrothermal
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1
(4-Methylphenyl)-3-buten-1-ol (1a): a colourless viscous liquid. H
NMR (400 MHz, CDCl3) (δ, ppm): δ = 7.18 (dd, J = 8.0 Hz, J = 4.8
Hz, 4H, ArH), 5.81–5.75 (m, 1H, =CH), 5.15–5.09 (m, 2H, =CH2),
4.69–4.65 (m, 1H, CH), 2.49–2.46 (m, 2H, CH2), 2.35 (s, 3H, CH3),
2.15–2.13 (m, 1H, OH); 13C NMR (100 MHz, CDCl3): δ = 140.9,
137.1, 134.6, 129.1, 125.7, 118.1 (all unsaturated CH2 and CH), 73.2
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