Gallium-mediated allylation of carbonyl compounds in water

Article abstract of DOI:10.1016/S0040-4039(02)00995-4

Ga-mediated allylation of aldehydes or ketones in distilled or tap water generated the corresponding homoallyl alcohols in high yields without the assistance of either acidic media or sonication.

Full text of DOI:10.1016/S0040-4039(02)00995-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5097–5099
Gallium-mediated allylation of carbonyl compounds in water
Zhiyong Wang,a,* Shizhen Yuana and Chao-Jun Lib
aDepartment of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, China
bDepartment of Chemistry, University of Tulane, New Orleans, LA 70118, USA
Received 26 February 2002; revised 15 May 2002; accepted 24 May 2002
Abstract—Ga-mediated allylation of aldehydes or ketones in distilled or tap water generated the corresponding homoallyl alcohols
in high yields without the assistance of either acidic media or sonication. © 2002 Published by Elsevier Science Ltd.
The importance of organometallic reactions in organic
synthesis is well recognized. Recently, there has been a
considerable interest in developing organometallic reac-
tions in water of which allylation of aldehydes and
ketones to give homoallylic alcohols has received the
most attention.1 This reaction has been achieved by
using metals such as Mn/Cu,2 Sn,3 Zn,4 Bi,5 In,6 Mg,7
or organometallic compounds such as diallylmercury,
allylmercurybromide,8 allyltributylstannanes9 and tetra-
allylgermane.10 Nevertheless, it is necessary for most of
these reactions to be carried out with acidic co-reagents
such as ammonium chloride, hydrobromic acid, or
co-solvents such as a mixture of THF and water.
Herein, we wish to report a simple allylation of car-
bonyl compounds mediated by gallium in distilled or
tap water without the help of acidic co-reagents (e.g.
HBr, AcOH) or an organic co-solvent (e.g. THF,
Et2O).
Our initial study was carried out by reacting benzalde-
hyde with allyl bromide in the presence of gallium
under various conditions. The results are summarized
in Table 1.
It was found that at room temperature no significant
formation of the desired product was observed even
after prolonged stirring. When the reactions were per-
formed under acidic conditions, the addition of 1N HCl
or saturated NH4Cl led to the generation of compli-
cated mixtures. Subsequently, it was found that allyla-
tion of benzaldehyde proceeded smoothly at 45°C in
either distilled water or tap water. Subsequently, a
variety of aldehydes and ketones were examined using
this allylation method (Scheme 1). The results are listed
in Table 2.
Most of the reactions proceeded smoothly in good yield
and side reactions such as reduction and coupling were
not observed (entries 1–7). An acid sensitive acetal
survived the reaction conditions (entry 3) whereas the
acetal can be hydrolyzed in 0.1N HCl at 45°C. Aro-
matic aldehydes can be allylated in high yields (entries
1, 2, 3 and 6). The allylation of acetophenone also gave
the corresponding product in 61% yield (entry 8).
Aliphatic aldehydes or ketones were also allylated
smoothly under the current conditions (entries 10 and
11). p-N,N-Dimethylamino-benzaldehyde also provided
the corresponding product in 42% yield (entry 9).
Previously Li and Chan reported the use of indium to
mediate Barbier–Grignard type reactions in water.6
Subsequently, indium has been used widely in organic
synthesis in aqueous media. After comparing the first
ionization and reduction potentials of gallium with
those of indium (Ga: FIP, 5.99 eV, E0, Ga3+/Ga=
−0.56 V; In: FIP, 5.79 eV, E0, In3+/In=−0.345 V), we
expected similar properties between the two metals. As
in the case of indium, the reduction potential of gallium
is not too negative, and thus it is not sensitive to water
and does not form oxides readily in air.
The diastereoselectivity of the allylation catalyzed by
gallium was studied. Allylation of 2,3-dihydroxy-
propanal with allyl bromide gave the corresponding
product with the diastereoselectivity depending on the
solvent. When the reaction was carried out in water, the
* Corresponding author. Tel.: 86-551-3603544; fax: 86-551-3631760;
e-mail: zwang3@ustc.edu.cn
0040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(02)00995-4

5098
Z. Wang et al. / Tetrahedron Letters 43 (2002) 5097–5099
Table 1. Allylation of benzaldehyde mediated by gallium under various conditions
Entry
Mediator
Reaction temperature (°C)
Reaction time (h)
Allylation yield (%)a,b
1
2
3
4
5
H2O
rt
rt
rt
rt
45
12
4
4
4
6
41
59
82
71
76
1N HCl
0.1N HCl
NH4Cl (aq. satd)
H2O
a The isolated yields are reported.
b The pure product was identified by IR, 1H, 13C NMR and HRMS.
OH
H(Me)
dominant product was the syn-isomer. In contrast, the
anti-isomer was the dominant product when THF was
employed as the reaction solvent, see Table 3. The
syn-isomer may be regarded as the chelation-controlled
product, due to the hydrogen bond between the two
hydroxyl groups. The aqueous environment favors
chelation of the a-hydroxyl. Moreover, it was found
that steric hindrance around the carbonyl group had an
influence on the diastereoselectivity of the allylation.
For example, benzaldehyde reacted with ethyl 4-bro-
mobutenoate in water (entry 3, Table 3) to give rise to
the anti-isomer as the dominant product. It is likely
that steric hindrance governed this diastereoselectivity
because of the bulk of the phenyl group. Here the
assignment of syn and anti stereochemistry were based
on chemical shift values.11
O
Ga
Mediator
Br
R
+
R
H(Me)
Scheme 1.
Table 2. Allylation reactions mediated by Ga in water
Yield (%)b
76
Entry
Producta
OH
Substrate
1
CHO
OH
82
79
H3CO
2 H
CHO
3CO
In conclusion, gallium was found to be an effective
metal for mediating allylation of carbonyl compounds
in water at 45°C. The reaction conditions are mild in
that no acidic additives are required. This method
provides a useful alternative to the other presently used
procedures.
OH
O
O
CHO
3
O
O
OH
CHO
CHO
CHO
4
64
73
OH
A typical experimental procedure is as follows:
5
6
Cl
Cl
OH
Distilled water or tap water (5 ml), a gallium ingot (2
mmol), the carbonyl compound (1 mmol) and allyl
bromide (1.7 mmol) were placed in a round-bottomed
flask then the reaction mixture was stirred vigorously
for 6 h at 45°C. Subsequently, the reaction mixture was
extracted with ether and the organic phase washed with
saturated brine, dried over anhydrous magnesium sul-
fate and concentrated in vacuo. The pure products were
obtained by flash chromatography on silica gel eluting
with petroleum ether/EtOAc (4:1), and identified by IR,
1H, 13C NMR and HRMS.
H3C
80
68
H3C
OH
7
8
CHO
O
O
OH
O
CCH3
61
OH
(H3C)2N
CHO
42
57
9
(H3C)2N
OH
OH
Acknowledgements
10 OHC
CHO
The authors are grateful to the National Nature Science
Foundation of China (No. 50073021) and the Green
Chemistry Fund, University of Science and Technol-
ogy, China, for support.
11
46
HO
O
a. Products were identified by IR, 1H NMR, 13C NMR and HRMS. b. Isolated yields.

Z. Wang et al. / Tetrahedron Letters 43 (2002) 5097–5099
5099
Table 3. The diastereoselectivity of allylations catalyzed by Ga in different solvents
Reaction
conditions
Syn:Anti
Product (syn : anti)a
Entry
Halide
Aldehyde
Yield(%)b
OH
OH
Ga/H2O
45 C/16 h
8.3:1
86
HO
HO
HO
HO
Br
Br
CHO
OH
CHO
OH
1
HO
HO
OH
OH
OH
OH
Ga/THF
45 C/16 h
1:4.2
74
2
OH
CO2C2H5
OH
CO2C2H5
CO2C2H5
Ga/H2O
45 C/16 h
Ph
1:2.2
67
Ph
CHO
3
Br
OH
OH
a. The products were identified by IR, 1H NMR, 13C NMR and HRMS. b. Isolated yields.
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