Aqueous Barbier allylation of aldehydes mediated by tin

Article abstract of DOI:10.3390/12092089

The aqueous tin-mediated Barbier reaction affords good to excellent yields and moderate syn diastereoselectivity under basic and acidic conditions. The high yields and stereoselectivity observed in the case of o-substituted aldehydes suggest a cyclic orga

Full text of DOI:10.3390/12092089

Molecules 2007, 12, 2089-2105
molecules
ISSN 1420-3049
© 2007 by MDPI
www.mdpi.org/molecules
Full Paper
Aqueous Barbier Allylation of Aldehydes Mediated by Tin
Ricardo L. Guimarães 1,2,†, Dimas J. P. Lima 2, Maria Ester S. B. Barros 2, Lívia N. Cavalcanti 2,
Fernando Hallwass 2, Marcelo Navarro 2, Lothar W. Bieber 2 and Ivani Malvestiti 2,*
1
Instituto de Ciências Ambientais e Desenvolvimento Sustentável, Universidade Federal da Bahia -
Campus Universitário Reitor Edgar Santos, Rua Professor José Seabra S/N - Barreiras - BA - 47805-
100, Brazil; †E-mail: riclima@ufba.br
2
Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade
Universitária, Recife-PE 50670- 901, Brazil
*Author to whom correspondence should be addressed; E-mail: ivani@ufpe.br,
imalvestiti@gmail.com
Received: 16 June 2007; in revised form: 25 August 2007 / Accepted: 25 August 2007 / Published: 29
August 2007
Abstract: The aqueous tin-mediated Barbier reaction affords good to excellent yields and
moderate syn diastereoselectivity under basic and acidic conditions. The high yields and
stereoselectivity observed in the case of o-substituted aldehydes suggest a cyclic organotin
intermediate or transition state in K2HPO4 solution. A practical and efficient aqueous tin
allylation of methoxy- and hydroxybenzaldehydes can be carried out in HCl solution in 15
minutes to afford the corresponding homoallylic alcohols in high yields. Aliphatic
aldehydes give moderate to excellent yields with reaction times ranging from 30 to 60
minutes. Under these conditions, crotylation gives exclusively the γ-product and the syn
isomer is formed preferentially. For 2-methoxybenzaldehyde, an equilibration of the
isomers to a syn/anti ratio of 1:1 can be observed after several hours. Control experiments
with radical sources or scavengers give no support for radical intermediates. NMR studies
suggest a mechanism involving an organotin intermediate. The major organotin species
formed depends on the reaction medium and the reaction time. The use of acidic solution
reduces the reaction times, due to the acceleration of the formation of the allyltin(IV)
species.
Keywords: Fast Barbier reaction; hydroxy and methoxy benzaldehydes; aqueous; tin.

Molecules 2007, 12
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Introduction
Carbonyl allylation is an important synthetic transformation in organic and pharmaceutical
chemistry because the homoallylic alcohols produced are valuable synthetic intermediates [1]. The
study of organometallic reactions using water as (co)-solvent has attracted renewed interest [1-2],
mainly due to the increasing importance of environmentally friendly methodologies [3]. The Barbier
reaction mediated by several metals such as zinc [4], tin [5], indium [6], manganese [7] and others [8],
historically performed in anhydrous solvents, has been widely studied in aqueous media. Moreover,
the use of water, an economically and environmentally benign solvent, reduces the need to handle
flammable and anhydrous solvents and protection and deprotection processes are often unnecessary.
Although several groups have reported Barbier allylations of hydroxylated aldehydes, specially
carbohydrates, in water [9], and a systematic study of hydroxy and methoxy aldehydes and ketones
with tetrallyltin in toluene has been published [10], no data are available about the behavior of hydroxy
and methoxy benzaldehydes in aqueous Barbier allylations. In general, tin-mediated allylation of
carbonyl compounds has been reported as being a slow reaction, with reaction times ranging between 1
and 24 hours, depending on the substrate and reaction conditions [11]. Some attempts to improve yield
and selectivity or to reduce the reaction time with the use of tin nanoparticles in water [12] or of an
electrochemical process in water [13] have been reported.
In this work, we report the Barbier reaction mediated by tin in basic and acidic aqueous media with
reaction times ranging from 15 minutes to 24 hours, according to the medium (Scheme 1).
Scheme 1. The Barbier type reaction in aqueous medium.
CHO
OH
Sn
+
OR
R'
Br
H2O
R'
OR
R = H or CH3; R' = H or CH3
Results and Discussion
The initial tests were performed with 2-hydroxy and 2-methoxybenzaldehydes in water and basic
solution (K2HPO4), varying the reaction time. The best yields were achieved in 24 hours. Due to the
importance of metallic salts in aqueous organometallic reactions [14] and previous unpublished results
with the zinc mediated reaction, the catalyst, namely Pb(OAc)2, and solvents, alkaline solution
(K2HPO4) and pure water, were tested in the reaction with tin and allyl and crotyl bromide (Table 1).

Molecules 2007, 12
Table 1. Tin-mediated allylation of oxy-substituted benzaldehydes in aqueous media.
2091
Entry
1
Aldehyde
Halide
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C3H5Br
C4H7Br
C4H7Br
C4H7Br
C4H7Br
C4H7Br
C4H7Br
Salt added
—
Additive
Yield (%) Syn/antia
2-CH3O-C6H4CHO
2-CH3O-C6H4CHO
4-CH3O-C6H4CHO
3-CH3O-C6H4CHO
3-CH3O-C6H4CHO
2-HO-C6H4CHO
2-HO-C6H4CHO
3-HO-C6H4CHO
3-HO-C6H4CHO
4-HO-C6H4CHO
4-HO-C6H4CHO
2-CH3O-C6H4CHO
3-CH3O-C6H4CHO
4-CH3O-C6H4CHO
2-HO-C6H4CHO
3-HO-C6H4CHO
4-HO-C6H4CHO
—
73
94
80
72
84
61
85
43
60
25
71
98
98
80
84
88
72
—
—
2
K2HPO4
K2HPO4
K2HPO4
—
—
3
—
—
4
—
—
5
—
—
6
—
—
—
7
K2HPO4
—
—
b
8
K2HPO4
—
—
b
9
K2HPO4
Pb(OAc)2
—
b
10
11
12
13
14
15
16
K2HPO4
—
—
b
K2HPO4
Pb(OAc)2
—
K2HPO4
K2HPO4
—
—
—
—
—
—
—
65:35
50:50
50:50
70:30
55:45
57:43
K2HPO4
K2HPO4
K2HPO4
17
a
The syn:anti ratio was determined using the ¹H-NMR signal areas for the methyl group of the
homoallylic alcohols. b Dioxane (0.2 mL) was used as co-solvent.
The Barbier reaction afforded good yields with 2-methoxybenzaldehyde and 2-hydroxy-
benzaldehyde in water (entries 1 and 6), which increased in alkaline solution (entries 2 and 7). With 4-
methoxybenzaldehyde the best result was achieved in K2HPO4 solution (entry 3), while 3-methoxy-
benzaldehyde, on the other hand, yielded better results in pure water (entries 4 and 5).
The hydroxylated aldehydes, except for 2-hydroxybenzaldehde (entry 7), gave best yields using
Pb(OAc)2 as a catalyst (entries 9 and 11). Other metallic salts were also tested, but their presence only
decreased the reaction yields. The next step was the Barbier reaction with crotyl bromide (Table 1),
where, in addition to the reactivity, the diastereoselectivity was analyzed. In these reactions, both 2-
and 3-methoxybenzaldehyde gave excellent yields in alkaline media (entries 12 and 13), and 4-
methoxybenzaldehyde gave 80% of addition product (entry 14) in pure water. A similar behavior was
observed for hydroxybenzaldehydes, with yields ranging between 72 – 88% (entries 15 – 17). In all
these cases, no additive was necessary. Regarding the diastereoselectivity, only low syn selectivity was
observed with ortho substituted aldehydes, affording ratios of 65:35 for 2-methoxybenzaldehyde (entry
12) and 70:30 for 2-hydroxybenzaldehyde (entry 15). The use of additives did not improve the yields
or the diastereoselectivity. Even though the literature explained the syn diastereoselectivity via an
acyclic intermediate [15, 16], in these particular cases the presence of a coordinating group in the
ortho position could favor a cyclic transition state (Figure 1), as previously proposed in the literature
[17]. This could explain the observed increase in the diastereoselectivity only with the ortho
substituted aldehydes, suggesting a probable allyltin species as intermediate.

Molecules 2007, 12
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Figure 1. A cyclic transition state.
R
O
Sn
L3
H
O
L = crotyl or X
The experimental conditions developed afforded good yields for the Barbier reaction, but the
diastereoselectivity was still low and observed only with ortho substituted benzaldehydes, therefore
new conditions were pursued in order to reduce the reaction times and increase the diastereoselectivity.
Initially, it was suggested that use of acidic conditions might be beneficial due to enhancement of
carbonyl reactivity. Hydrochloric acid solution, normally used for quenching the reaction, was tested
and it reduced the reaction times to only one minute. When no acid solution was added, almost all the
aldehyde was recovered. The allylation of aromatic and aliphatic aldehydes with allyl bromide using
tin in acid solution at room temperature are shown in Table 2.
Table 2. Allylation of aromatic and aliphatic aldehydes with allyl bromide mediated by tin
in acid solution at room temperature.
O
OH
Sn
Br
+
C
H3O+
R
H
R
Entry
1 a
Aldehyde
Acid solution
HCl
Time (min)
Yield (%)
97
2-OCH3-C6H4CHO
2-OCH3-C6H4CHO
2-OCH3-C6H4CHO
2-OCH3-C6H4CHO
C6H5CHO
5
5
2 a
H2SO4
HNO3
CF3CO2H
HCl
98
3 a
5
94
4 a
5
78
5 a
5
93
6 a
3-OCH3-C6H4CHO
2-OH-C6H4CHO
3-OH-C6H4CHO
3-OH-C6H4CHO
3,4-(OCH3)2-C6H3CHO
3-OH-4-OCH3-C6H3CHO
n-C6H13CHO
HCl
5
98
7 a
HCl
5
98
8 a
HCl
5
41
9a, b
10 a
11 a
12 a
13 a
14c
15 c
16 c
HCl
60
5
54
HCl
99
HCl
5
60
HCl
30
60
15
15
15
90
(CH3)2CHCHO
HCl
30
C6H5CHO
HCl
92
2-OCH3-C6H4CHO
3-OCH3-C6H4CHO
HCl
95
HCl
96

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Table 2. Cont.
Acid solution
Entry
17 c
18 c
19 c
20 c
21 c
22 c
23 c
Aldehyde
Time (min)
Yield (%)
4-OCH3-C6H4CHO
4-F-C6H4CHO
HCl
HCl
HCl
HCl
HCl
HCl
HCl
15
15
15
15
15
15
15
86
88
70
80
85
92
65
2-OH-C6H4CHO
2-OH-3-OCH3-C6H3CHO
3-OH-4-OCH3-C6H3CHO
3,4-(OCH3)2-C6H3CHO
C6H5(CH2)2CHO
a Aldehyde (0.2 mmol), allyl bromide (0.75 mmol), tin (0.5 mmol) in 1.0 mol L-1 HCl (2.0 mL).
c
b Dioxane was used as co-solvent. Aldehyde (0.5 mmol), allyl bromide (0.6 mmol), tin (0.5
mmol) in 0.25 mol L-1 HCl (2.0 mL).
Other acid solutions, such as H2SO4, HNO3, HBr and CF3CO2H, were tested at several
concentrations and volumes, as well as several stirring times and all of them showed similar results,
probably due to a general acid catalysis or acid activation of the metal surface. Allylation of
benzaldehyde and methoxybenzaldehydes afforded homoallylic alcohols in excellent yields (entries 1
– 6). Allylation of 2-hydroxybenzaldehyde and 3,4-dimethoxybenzaldehyde produced also excellent
yields (entries 7 and 10). 3-Hydroxy-4-methoxybenzaldehyde gave only a moderate yield (entry 11).
For 3-hydroxybenzaldehyde, even after 1 hour of reaction, only a moderate yield was obtained (entries
8 and 9). Under the same conditions, 4-hydroxybenzaldehyde afforded only traces of product.
Aliphatic aldehydes needed longer reaction times – 30 minutes for heptanaldehyde, with excellent
yield (entry 12), and 1 hour for isobutyraldehyde, giving a low yield (entry 13). No aldehyde was
recovered in any of the reactions. In these heterogeneous reactions efficient stirring was an important
parameter for their success and reproducibility.
The initial tests were performed using excess of halide (3.2 equivalents) and concentrated acid
solutions (1.0 mol L-1, entries 1 – 13) with excellent yields and 5 minutes reaction times. In order to
reduce the waste of starting materials the ratio of aldehyde, halide and metal was modified. The best
results were obtained in 15 minutes and using aldehyde, halide and tin in the ratio of 1:1.2:1 (entries
14 – 23), except for the aliphatic aldehydes and for 3-OH and 4-OH-benzaldehyde, whose yields
decreased significantly. In order to evaluate the regio- and stereoselectivity, we also studied these
conditions using crotyl bromide. The results of allylation of aromatic and aliphatic aldehydes with
crotyl bromide using tin in HCl solution at room temperature are presented in Table 3. Crotylation
occurred exclusively in the γ-position, with excellent yields with all aromatic aldehydes (entries 1 – 8).
The aliphatic heptanaldehyde afforded a good yield after 1 hour (entry 9). Reducing the excess of
crotyl halide and tin led to a significant decrease of the reaction yields, except with 3-phenylpropanal,
benzaldehyde, 4-fluorbenzaldehyde, 2-methoxy and 2-hydroxybenzaldehyde, where excellent results
were obtained (entries 10 –14).
It was observed that the syn/anti selectivity improved in comparison with some results published in
the literature, in either organic or aqueous media [4b, 16b, 18]. Some examples on the literature had

Molecules 2007, 12
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diastereoselectivity higher than 7:3, but in some cases the anti isomer was the major product [1b, 16a,
19].
Table 3. Allylation of aromatic and aliphatic aldehydes with crotyl bromide
mediated by tin in HCl solution at room temperature.
OH
O
Sn
Br
+
R
C
H3O+
R
H
Entry
1 b
Aldehyde
Time (min) Yield (%)
Syn/Antia
70 : 30
75 : 25
60 : 40
65 : 35
65 : 35
70 : 30
70 : 30
65 : 35
60 : 40
70 : 30
65 : 35
75 : 25
65 : 35
75 : 25
60 : 40
50 : 50
C6H5CHO
5
5
90
93
93
74
94
98
93
85
93
98
93
95
80
90
91
67
2 b
2-OCH3-C6H4CHO
3-OCH3-C6H4CHO
4-OCH3-C6H4CHO
2-OH-C6H4CHO
3,4-(OCH3)2-C6H3CHO
3-OH-4-OCH3-C6H3CHO
4-F-C6H4CHO
3 b
5
4 b
5
5 b
5
6 b
5
7 b
5
8 b
5
9 b
n-C6H13CHO
60
15
15
15
15
30
60
240
10 c
11 c
12 c
13 c
14 c
15 b
16 b
C6H5CHO
4-F-C6H4CHO
2-OCH3-C6H4CHO
2-OH-C6H4CHO
C6H5(CH2)2CHO
2-OCH3-C6H4CHO
2-OCH3-C6H4CHO
a
The syn:anti ratio was determined by ¹H-NMR. b Aldehyde (0.2 mmol), crotyl bromide
c
(0.75 mmol), tin (0.5 mmol) in 1.0 mol L-1 HCl (2.0 mL). Aldehyde (0.5 mmol), crotyl
bromide (0.6 mmol), tin (0.5 mmol) in 0.25 mol L-1 HCl (2.0 mL).
Other experiments were performed in 1.0 mol L–1 HCl solution with 2-methoxybenzaldehyde,
where the reaction time was increased and a decrease of the diastereoselectivity was observed (entries
2, 15 and 16), suggesting the presence of an equilibration process under these reaction conditions. This
equilibration could be explained by a symmetric oxonia-Cope type rearrangement or a solvolysis
process [20, 21].
Comparing the two sets of data, the reaction in acid medium presents good to excellent yields with
reduced reaction times for aromatic and aliphatic aldehydes and moderated syn diastereoselectivity for
all cases. The reaction performed in basic medium presents good yields and moderated syn
diastereoselectivity only for aldehydes containing the ortho chelating group. Therefore the reaction
pathways should be distinct in basic and acidic conditions.

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Regarding the mechanism of the Barbier reaction, the literature proposes three different
mechanisms involving a single electron transfer (SET), a radical-anion formation or an organometallic
reagent [1a]. The prevailing mechanism usually depends upon the metal, substrates and reaction
conditions. Moyano and co-workers have described a theoretical study of the Barbier reaction, where
the proposed mechanism involves a SET process [22]. This transference will be dependent upon the
electron affinities (EA) of the reactants, since the radical anion preferably formed will be that derived
from the species with higher EA [22-23]. In the Barbier reaction, the aromatic carbonyl compounds
will have the largest EA, thus forming a radical anion. In addition, the reduction potential (E) of the
aldehyde can influence its reactivity [7]. The measured reduction potential of the aldehydes and the
calculated EA’s are presented in Table 4.
Table 4. Reduction potential (E) and electron affinity (EA) of substituted
benzaldehydes and allyl bromide.
Entry
Reagent
EA (kcal mol-1)
E (V)
–1.36
–1.48
–1.68
–2.14
–1.55
–1.50
–1.64
–1.73a
1
2
3
4
5
6
7
8
C6H5CHO
24.7
28.8
27.8
26.1
27.4
28.3
26.3
3.21
2-HO-C6H4CHO
3-HO-C6H4CHO
4-HO-C6H4CHO
2-CH3O-C6H4CHO
3-CH3O-C6H4CHO
4-CH3O-C6H4CHO
CH2=CHCH2Br
a See reference [23].
Considering the results shown in Tables 1 through 4, there is no direct correlation between the
observed yields and the reduction potentials or the electron affinities. Nevertheless, the reduction
potential can be used to rationalize the reactivity of the aromatic aldehydes, as lower reaction yields
were obtained with 3-OH and 4-OH-benzaldehydes, which have the more negative reduction potentials
(entries 3 and 4), which suggest a lower reactivity of the carbonyl compound. However, in acid
medium, the lower yields could also be related to the fact that these two aldehydes are solids and
almost insoluble in water, requiring dioxane as co-solvent. In basic medium, the yields with 3-OH and
4-OH-benzaldehydes were moderated to good (Table 1, entries 9, 11, 16 and 17), and in these cases
the solubility should increase due to the formation of anionic species.
In order to obtain some mechanistic information, additional tests were performed with a radical
initiator, dibenzoyl peroxide, and radical scavengers, phenol and 2,2,6,6-tetramethylpiperidine-N-oxyl
(TEMPO) in K2HPO4 solution. For all the aldehydes examined, including unsubstituted benzaldehyde,
very small variations, within the reproducibility of the reaction, were observed with all addictives.
These results turn a radical and anion-radical chain mechanism less probable because neither radical
initiators (peroxide) nor scavengers (phenol, TEMPO) had significant influence in the reaction [24].
In addition to these results, that are the unchanged behavior in the presence of radical initiators and
inhibitors, the observation of small amounts of tetrallyltin at the end of our reactions in basic medium

Molecules 2007, 12
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and the syn diastereoselectivity only for 2-substituted benzaldehydes, suggest that the mechanism
involves organometallic species.
A mechanism involving an organometallic intermediate was already proposed by Whitesides,
Marshall and Chan [9, 25, 26]. Recently, Chan et al. carried out a theoretical study of hydrolysis and
carbonyl additions reactions for a series of allylmetals in gas phase [27]. The divalent metal allyl
complexes of group 14 have similar reactivity toward hydrolysis and carbonyl addition. On the order
hand, tetravalent group 14 metals form σ-complexes with allyl ligands and these complexes are less
reactive toward hydrolysis than toward allylation. These results indicated that allyl complexes of
tetravalent metals, such as allyl-SnBr3, are suitable for allylation in aqueous media.
Establishing a mechanism involving organotin species in aqueous medium is a challenging task,
since only SnX4, with X = halides, in water yields a complex equilibrium whose species and
concentrations depend upon the pH and halide nature.[28] For organotin species, these equilibria
should be even more complex, since they can undergo hydrolysis and ligand exchanges [29].
As a result, an effort was undertaken to identify and characterize the predominant species
responsible for the observed results. Initially the progress of the reaction of allyl bromide, metallic tin
1
and benzaldehyde in pure water was monitored by extracting samples with CDCl3, followed by H-
NMR analysis.
1
Figure 2. Partial H-NMR spectra in CDCl3 of the reaction of allyl bromide and tin in water after
extraction. a) 15 minutes; b) 30 minutes; c) 1 h, d) 4 h and e) 8 h. Assignments: allyl bromide (I);
tetrallyltin (II); triallyltin bromide (III); diallyltin dibromide (IV) and propene (V).
(IV)
(IV)
V)
(
e)
d)
(III)
c)
b)
(II)
(I)
a)

Molecules 2007, 12
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Nonetheless, organotin species were observed only after the benzaldehyde was consumed.
Consequently, the monitoring was also carried out in the absence of aldehyde, and the formation of
organotin was observed in water, acidic and basic conditions. The reaction was carried out at room
temperature in K2HPO4 solution and samples of the reaction mixture (1 mL) were extracted with
CDCl3 (containing anisole as internal standard) at different time intervals and monitored by 1H-NMR.
The only species observed in low concentration at 1.9ppm and 2JH-Sn = 63 Hz was characterized based
1
upon the literature H-NMR data as tetrallyltin [30]. The allylation reaction was also tested using
commercial tetrallyltin and 2-methoxybenzaldehyde in K2HPO4 solution, which after 6 hours afforded
the homoallylic alcohol in 70% yield. Theses results indicate that the organotin formation in K2HPO4
solution was very slow, what could explain the need for such long reaction times.
However, the CDCl3 extraction could leave behind water soluble allyltin species in the aqueous
1
media; therefore the reaction was also performed in D2O. First of all, the H-NMR spectrum of a
commercial sample of tetrallyltin was obtained in D2O, but it has low solubility, almost generating two
phases what did not allowed a clear assignment of the H-Sn coupling constant. The 119Sn spectrum was
then obtained and a signal at –44 ppm was observed, which could be used to determine the presence of
tetrallyltin. When the reaction of allyl bromide and tin was performed with K2HPO4 in D2O, the metal
is partially or totally consumed depending on the reaction time, generating a grey suspension whose
1H-NMR spectrum was hard to analyze due to quite broad signals. The 119Sn-NMR spectrum was not
conclusive, since no tetrallyltin was observed and only a broad signal at –530ppm was observed, a
chemical shift characteristic of inorganic tin salts. After extraction with CDCl3 containing cyclohexane
as an internal standard, 70% of tetrallyltin was recovered, suggesting that this is the main species
generated under these conditions. Considering the difficulties to analyze the reaction in D2O and the
lack of 119Sn-NMR data in D2O for the allyltin species, we continued the NMR studies in CDCl3.
The reaction performed in water was also monitored by 1H-NMR, after extraction with CDCl3, and
formation of organotin was observed only after 30 minutes of vigorous stirring. The species initially
observed had chemical shift of 1.9ppm and 2JH-Sn = 63 Hz, in agreement with data for tetrallyltin. The
samples monitored after longer reaction times showed the formation of other species at 2.4ppm (2JH-Sn
= 68 Hz) and 2.8ppm (2JH-Sn = 77 Hz), as shown in Figure 2. A change in the pH of the solution was
also observed during the progress of the reaction from 6 to approximately 1, after 30 minutes.
1
To our knowledge, the only H-NMR data available for allyltin(IV) bromides in the literature are
assigned to diallyltin dibromide [26]. However, in our experiments we observed tetrallyltin and two
other organotin compounds.
1
Naruta et. al describe the H- and 119Sn-NMR spectra of allyltin (IV) chlorides prepared by the
Kocheshkov redistribution reaction involving tetrallyltin and SnCl4 [30]. Based upon the chemical
shifts and coupling constants of allyltin (IV) chlorides, [30, 31] the doublets at 2.4ppm (2JH-Sn = 68 Hz)
and 2.8ppm (2JH-Sn = 77 Hz) were assigned to the triallyltin bromide and diallyltin dibromide species,
respectively. Another experiment was performed in order to corroborate these assignments. It is known
that the addition of HX or X2 can be used to break the tin–carbon bonds yielding an alkane as by-
product. [30] Therefore, HBr (50% in water) was added dropwise to tetrallyltin in deuterated
1
chloroform and monitored by H-NMR. The same species obtained previously were observed at
2.4ppm, 2.8ppm and 3.2ppm (2JH-Sn = 105.6 Hz), respectively, as presented in Figure 3.

Molecules 2007, 12
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1
Figure 3. Partial H-NMR spectra in CDCl3 of the reaction of tetrallyltin with HBr(aq).
(a) tetrallyltin; (b) first addition; (c) second addition, d) third addition. Assignments:
tetrallyltin (II); triallyltin bromide (III); diallyltin dibromide (IV), propene (V) and
allyltin tribromide (VI).
(IV)
(VI)
(V)
d)
c)
(III)
b)
a)
(II)
After the characterization of allyltin(IV) bromide species in CDCl3, the reaction of allyl bromide
and tin was performed in aqueous solutions of HCl and HNO3 (Figure 4). In these cases, significant
formation of tetrallyltin and triallyltin bromide was observed after five minutes and most of the allyl
bromide was consumed within 30 minutes and practically only one species giving a signal at 2.4ppm
remained present, namely triallyltin bromide. The same compound was observed in the reactions
performed in water, HCl and HNO3 aqueous solution, but the formation of this species was faster in
acidic media than in pure water.

Molecules 2007, 12
Figure 4. Partial 1H-NMR spectra in CDCl3 of the reaction of allyl bromide and metallic
2099
tin in HNO3 solution. a) 5 minutes; b) 15 minutes; c) 30 minutes. Assignments: allyl
bromide (I), tetrallyltin (II); triallyltin bromide (III).
(III)
c)
b)
a)
(I)
(III)
(II)
The reactivity of tetrallyltin and triallyltin bromide was probed by adding to the CDCl3 solution
1
small amounts of benzaldehyde followed by immediate H-NMR analysis as presented in Figure 5. It
is clear that triallyltin bromide was consumed first suggesting that it is more reactive than tetrallyltin.
The formation of organotin(IV) halide species is probably the rate-determining step; therefore, the
increase of the rate for the organometallic formation would decrease the allylation reaction times.
Since HX can cleave Sn-C bonds, the carbonyl addition step should also be faster than the organotin
decomposition in order to explain the observed high yields for the allylation reaction.
Conclusions
In summary, systematic studies of the aqueous Barbier allylations of hydroxy- and methoxy-
substituted benzaldehydes mediated by tin were reported. The reactions exhibited good to excellent
yields when mediated by tin in basic and in acidic medium, without the need to protect OH groups.
Even though, the reaction yields were good to excellent in the majority of the aldehydes, the excess of
halide and tin could be reduced only in the acid conditions, which also had the advantage of the shorter

Molecules 2007, 12
2100
reaction times. Considering the short reaction time, the ratio 1:1.2:1 aldehyde, halide and tin for
several methoxy- and hydroxybenzaldehydes and even for some aliphatic aldehydes, the acid
conditions seem quite promising for preparative purposes. For the aliphatic aldehydes, the yields are
moderate to excellent and reaction times ranging from 30 to 60 minutes. To our knowledge, the present
reaction times are the shortest obtained for the tin-mediated Barbier allylations. In addition, the
reactions were carried out under mild and convenient conditions, and no additive (except the HCl
solution), no inert atmosphere was needed.
1
Figure 5: Partial H-NMR spectra in CDCl3 of the reaction of benzaldehyde and the
tetrallyltin and triallyltin bromide mixture. a) Before addition of the aldehyde; b) first
addition of benzaldehyde; c) second addition. Assignments: tetrallyltin (II); triallyltin
bromide (III) and alcohol homoallylic (VII).
(VII)
c)
b)
(III)
(II)
anisole
a)
Regarding the mechanism of the Barbier reaction mediated by tin, the experiments using radical
initiators and inhibitors suggested that it should not involve a single electron transfer (SET), but more
likely it should involve an organotin intermediate. The NMR studies suggest that the organotin formed
depend upon the pH, where in basic conditions the major species observed was the tetrallyltin even
after 24h reactions. On the other hand, under acidic conditions more than one species was observed,
and their reactivity seems quite different. Furthermore, the decrease of the reaction times is due to the
use of acid solution that acts as a catalyst for the allyltin(IV) bromide formation. As for the selectivity,

Molecules 2007, 12
2101
the γ-product is obtained exclusively in crotylation, and the syn isomer is formed preferentially within
a few minutes. An increase of the reaction time for 2-methoxybenzaldehyde led to a decrease of the
syn/anti selectivity due to an equilibration process.
Experimental
General
All solvents and reagents were commercially available and used without further purification. Tin
powder 325 mesh (99.8%) from Acros Organics was used. ¹H-NMR (300 MHz), ¹³C-NMR (75 MHz)
and 119Sn (111.8 MHz) spectra were recorded on a VARIAN UNITY PLUS-300 instrument. Chemical
shifts (δ) are reported in parts per million (ppm) relative to tetramethylsilane (TMS) as an internal
1
standard to H and 13C spectra and coupling constants (J) are given in hertz (Hz). Neat SnCl4 at –
148ppm used as 119Sn NMR standard. All products were known and their physical and spectroscopic
data were compared with those of authentic samples.
General procedure for the Barbier reaction mediated by tin under basic conditions
Allyl halide (1.0 mmol), tin (0.5 mmol) and catalyst (0.06 mmol, when indicated) were added to
aldehyde (0.2 mmol) water or saturated solution of K2HPO4 (2 mL) at 30ºC. After 24 hours under
vigorous stirring, the mixture was acidified with 2 mol L–1 HCl and extracted with CHCl3 (or CDCl3)
(1 mL) containing cyclohexane (0.05 mmol) as internal quantitative standard. The extracts were
analyzed directly by ¹H-NMR.
General procedure for the Barbier reaction mediated by tin under acidic conditions
Aldehyde (0.5 mmol), allyl or crotyl bromide (0.6 mmol) and tin (0.5 mmol) in HCl (2.0 mL, 0.25
mol L-1) were stirred at 30ºC for the indicated time and then extracted with CHCl3 (or CDCl3) (1 mL)
containing cyclohexane (or anisole) as internal quantitative reference. The extracts were analyzed
directly by ¹H-NMR.
Procedure for the organotin intermediate formation
Tin powder (2.0 mmol) and allyl bromide (4.0 mmol) in saturated K2HPO4 solution (4 mL) were
vigorous stirred at 30ºC. Samples of the reaction mixture (1 mL) were extracted with CDCl3
1
(containing anisole as internal standard) in different time intervals and monitored by H- and 119Sn-
NMR.

Molecules 2007, 12
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Reaction between 2-methoxybenzaldehyde and tetrallyltin
2-Methoxybenzaldehyde (0.3 mmol) and tetrallyltin (0.15 mmol) were added to saturated K2HPO4
solution (2.0 mL) and vigorously stirred at 30ºC. After 6 h the reaction mixture was extracted with
CDCl3 (containing anisole as internal standard) and analyzed by 1H-NMR.
Measurement of the reduction potential and electron affinity calculations
The reduction potential measurements were obtained by cyclic voltammetry, using vitreous carbon
as the working electrode, Pt as auxiliary electrode and Ag/AgCl (3 mol L-1 KCl) as reference electrode
and CH3CN as solvent. The electron affinities were calculated as the energy difference between the
radical-anion and the neutral molecule, both at the neutral geometry, with the AM1 method.
Acknowledgements
This work was supported by CNPq, CAPES and FACEPE. Special thanks are due to Professor
Ricardo L. Longo for his help on the electron affinity calculations.
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Sample Availability: Samples of all the compounds are available from authors.
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