Indium-catalyzed Barbier allylation reaction

Article abstract of DOI:10.1016/S0022-328X(03)00515-1

Barbier allylation reaction of carbonyl compounds with allyl bromide was investigated using a catalytic amount of indium (0), indium (I) or indium (III) salts in the presence of a reducer and chlorotrimethylsilane (TMSCl). The Mn/TMSCl couple turned out to be the most efficient system to regenerate active indium in the allylation reaction of various carbonyl compounds including α- and β-oxygenated aldehydes.

Full text of DOI:10.1016/S0022-328X(03)00515-1

Journal of Organometallic Chemistry 679 (2003) 79ꢁ83
/
www.elsevier.com/locate/jorganchem
Indium-catalyzed Barbier allylation reaction
Jacques Auge´ *, Nade`ge Lubin-Germain, Sylvain Marque, Latifa Seghrouchni
Unite´ CNRS-UCP-ESCOM 8123, 5 mail Gay-Lussac, Neuville-sur-Oise, 95031 Cergy-Pontoise, France
Received 30 May 2003; received in revised form 30 May 2003; accepted 3 June 2003
Abstract
Barbier allylation reaction of carbonyl compounds with allyl bromide was investigated using a catalytic amount of indium (0),
indium (I) or indium (III) salts in the presence of a reducer and chlorotrimethylsilane (TMSCl). The Mn/TMSCl couple turned out
to be the most efficient system to regenerate active indium in the allylation reaction of various carbonyl compounds including a- and
b-oxygenated aldehydes.
# 2003 Elsevier B.V. All rights reserved.
Keywords: Indium; Manganese; Catalysis; Allylation reaction; Homocoupling
1. Introduction
Indium-mediated reactions have elicited considerable
interest [1] in various reactions such allylation [2],
propargylation [3], alkynylation [4], Reformatsky [5]
reactions, cyclopropanations [6], reductions [7] and
oxidations [8]. Indium was generally used in a stoichio-
metric amount but in some cases, catalytic versions were
proposed [9]. We have recently investigated the use of
the Mn/TMSCl (chlorotrimethylsilane) system as a
possible regenerator of indium [10]. In this report, we
describe alternative systems for regenerating active
indium species along with the scope and limitations of
the Mn/TMSCl system in allylation of various carbonyl
compounds.
after 3 h remained low (Table 1, entry 2). Combined
with PbCl2 [12] or GeI2 (Table 1, entry 3) the reaction
was then effective. Mischmetall is also an efficient
reducer [13] and the combination of mischmetall with
TMSCl allowed to perform the reaction within 24 h
(Table 1, entry 4). Either with manganese or mischme-
tall in combination with TMSCl, a catalytical amount of
indium allowed to accelerate and increase the yield of
the reaction (compare entries 2 and 7, entries 4 and 8 in
Table 1). Aluminium, which was recently used as the
anode in an indium electrochemical process [15], turned
out to be less efficient as the reducer in the chemical
process using TMSCl (Table 1, entry 9). If an organo-
metallic species is involved in the mechanism, it could be
either an indium (III) sesquihalide [16] or an allylindium
(I) species [17]. The reactivity of such species could give
rise to an indium alkoxide which could undergo a
transmetallation to indium alkoxide by trimethylsilyl
chloride. The liberating indium trichloride could be
reduced by a mild reducer metal, such as manganese or
mischmetall. In that hypothesis, indium trichloride
should be an alternative catalyst. Surprisingly in that
2. Results and discussion
The allylation reaction of benzaldehyde as the model
was studied with different additives in the presence of
allyl bromide (Table 1).
Manganese in particular conditions is an efficient
metal in various reactions [11]. In THF, manganese has
to be activated by TMSCl to be reactive but the yield
* Corresponding author. Tel.: ꢀ
7067.
E-mail address: jacques.auge@chim.u-cergy.fr (J. Auge´).
/
33-13-425-7051; fax: ꢀ33-13-425-
/
0022-328X/03/$ - see front matter # 2003 Elsevier B.V. All rights reserved.
doi:10.1016/S0022-328X(03)00515-1

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J. Auge´ et al. / Journal of Organometallic Chemistry 679 (2003) 79ꢁ83
/
Table 1
Barbier allylation reaction of benzaldehyde with allyl bromide
Table 3
Allylation of a- and b-oxygenated aldehydes
Entry Conditions
Time (h)
Yield (%)
1
Mn stoich.
Mn/TMSCl
24
3
0
14
94
77
32
77
88
77
41
0
2
3
Mn/TMSCl/10%GeI2
Mischmetal stoich./TMSCl
In stoich.
8
4
24
3
5
6
In stoich./TMSCl
Mn/TMSCl/10%In
Mischmetal/TMSCl/10%In
Al/TMSCl/10%In
Fe/TMSCl/10%In
InCl stoich.
3
7
3
8
8
9
3
10
11
12
13
14
15
16
17
18
19
20
24
24
3
57
90
54
61
13
64
77
67
47
57
InCl stoich./TMSCl
Mn/TMSCl/10%InCl3
Mn/TMSCl/10%InBr3
Mn/TMSCl/10%In(OH)3
Mn/TMSCl/10%In2O3
Mn/TMSCl/10%InCl
Mn/TMSCl/10%InBr
Mn/TMSCl/10%InI
TDAE/TMSCl/10%In
the yield is only moderate, this experiment evidences the
regeneration of indium (0) by this powerful reducer.
The more favourable conditions to achieve indium-
catalyzed allylation reaction were obtained when a
catalytic amount of indium (0.1 equivalent) was used
with the Mn/TMSCl system. Even if we cannot exclude
the direct involvement of manganese activated by
indium in these conditions, the role of manganese could
be related to its reducing character allowing the
regeneration of an indium reactive species. This regen-
eration system was applied to the allylation of various
aldehydes and ketones (Table 2).
28
3
28
3
22
3
4
6
All reactions were performed in THF at room temperature except
the last one which was performed in DMF at 50 8C.
case, the yield in the homoallylic alcohol decreased
(Table 1, entry 13) owing to the formation of benzpi-
nacol as a side-product in these conditions. Indium (III)
bromide or indium (III) oxide as catalysts were more
efficient (Table 1, entries 14ꢁ16).
/
Other indium species, in particular indium (I) species
as catalysts were tested with success (Table 1, entries
The same conditions were also tested in the allylation
of a- and b-oxygenated aldehydes to evaluate the
diastereoselectivity of the reaction (Table 3).
17ꢁ19); we report also the first Barbier reaction with
/
Starting from cyclohexanecarboxaldehyde, the known
aldehyde 1 [21,22] was prepared according the following
sequence: addition of vinylmagnesium bromide [23],
benzylation (NaH, PhCH2Br, 82% yield), osmylation
(4% OsO4, NMO, 80% yield) and periodate cleavage
(NaIO4, 86% yield). The stereochemistry of the allyla-
tion product 3, arising from the a-oxygenated aldehyde
1, was determined from the data of the literature [22].
The main difference between the syn and anti products
is relative to the chemical shifts and coupling constants
of the H1 proton. The H1 proton of the anti isomer is
more deshielded and appeared as a triplet whereas the
H1 proton of the syn isomer appeared as a doublet of
doublet. The coupling constants J1,2 of the anti and syn
isomers have different values, 5.2 and 3.6 Hz respec-
tively. The selectivity of the indium-catalyzed allylation
reaction was in favour of the anti isomer, arising from a
non-chelation controlled transition state as observed in
the stoichiometric process [23]. The dominant effect
stoichiometric indium (I) chloride alone or with combi-
nation of TMSCl (Table 1, entries 11 and 12). In these
particular conditions an allylindium (I) species is pre-
cluded [18]. Another interesting experiment (Table 1,
entry 20) deals with the use of tetrakis dimethylamino
ethylene (TDAE) as an organic reducer [20]. The
reaction was performed in DMF at 50 8C. Although
Table 2
Indium-catalyzed allylation of carbonyl compounds
Entry
R1, R2
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
10
Ph, H
3
1.5
16
4
88
77
57
83
39
32
91
74
98
80
nC7H15, H
t Bu, H
C6H11, H
PhCHÄ
CH3CHÄ
/
CH, H
4
/CH, H
4
Ã
/
(CH2)5Ã
/
16
6
CH3(CH2)3, H
Ph, Ph
Ph, CH3
4
comes from a lowering CÃ/O antibonding orbital bring-
6
ing about an increased stabilisation of a Felkin-Anh
antiperiplanar nucleophilic addition of the organoin-
dium species to the aldehyde carbonyl [24].
Conditions: 0.1 eq. In, 5 eq. Mn and TMSCl, room temperature,
THF.

J. Auge´ et al. / Journal of Organometallic Chemistry 679 (2003) 79ꢁ
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83
81
dehyde is unstable in the air. Thus a flash chromato-
graphy allowing to isolate the coupling compounds of
benzaldehyde yielded to only 47% of diphenylacetalde-
hyde, along with 12% of desoxybenzoin and 20% of
benzophenone. We think that diphenylacetaldehyde
could be oxidized in the air into a carboxylic acid,
then into an a-peroxyacid which underwent a decarbox-
ylation leading to benzophenone. We then discovered
that the commercial sample of diphenylacetaldehyde we
purchased contained a small amount of benzophenone;
this proportion increases rapidly if no precaution is
taken. Use of stilbene epoxide as the substrate in the
conditions of the reductive coupling (In/TMSCl in THF)
led to diphenylacetaldehyde and trans stilbene in a small
amount; desoxybenzoin was not detected, which could
rule out the epoxide as the main intermediate in the
reductive coupling of benzaldehyde in THF. Contrary to
The b-oxygenated aldehyde 2 was also prepared from
cyclohexanecarboxaldehyde according a similar se-
quence: allylation (AllylBr, In/Mn/TMSCl, 83%), ben-
zylation (NaH, PhCH2Br, 87% yield), osmylation (4%
OsO4, NMO, 61% yield) and periodate cleavage (NaIO4,
86% yield). To elucidate the stereochemistry of the
allylation product 4 we have transformed it into 1,3-
diol acetonide 5 by hydrogenation followed by acetali-
sation and then analyzed the crude mixture according to
the method proposed by Rychnovsky et al. [25].
the reductive coupling with zincꢁcopper which involves
/
a transient epoxide [26], the indium coupling is mainly
processing via a pinacol-type intermediate, since benz-
pinacol in the presence of 0.7 molar amount of indium
and 2 molar amounts of TMSCl in THF led after 11 min
to diphenylacetaldehyde and desoxybenzoin in the 85:15
ratio. This rearrangement is slower in the absence of
indium affording 56% of diphenylacetaldehyde and 10%
of desoxybenzoin after 7 h; as far as we know, it is the
first time such a TMSCl-promoted rearrangement is
mentioned [27]. By contrast, when indium is activated
under ultrasound conditions in the absence of TMSCl
the coupling reaction of benzaldehyde gives benzpinacol
in aqueous solvents [29].
In this method the exploration of 13C-NMR spectrum
in the region ranging from 19 to 30 ppm gives an
evidence of the syn or anti configuration of the 1,3-diol
acetonides. Unfortunately the signals of 13C for the
cyclohexyl group are also visible in that region. Accord-
ing to the authors, the quaternary C-acetal 13C chemical
shift is also indicative of the change in conformation,
where typical syn- and anti-acetonides have 13C chemi-
cal shifts of 98.5 and 100.4 ppm, respectively. Since the
spectrum of our sample displayed two signals at 98.15
and 100.11 ppm, we have concluded that the major peak
at 100.11 ppm should correspond to the anti-acetonide
whereas the minor one at 98.15 ppm should correspond
to the syn-acetonide. Based upon these considerations,
3. Conclusion
1
we were then able to attribute the H and 13C chemical
Catalytic amounts of zero, mono or trivalent indium
were used in the Barbier allylation of carbonyl com-
pounds to afford the corresponding homoallylic alco-
hols. Indium was regenerated with a mild reducer, such
as manganese, in the presence of an oxophile such as
shifts of the syn and anti isomers of the allylation
compound 4 and to determine the syn:anti ratio (Table
3).
With aromatic aldehydes we have sometimes detected
pinacols. This observation prompted us to investigate
more precisely the indium-mediated pinacolisation of
benzaldehyde. Thus a solution of benzaldehyde and
TMSCl (2 molar amounts) dissolved in tetrahydrofuran
was added dropwise to indium (0.7 molar amount); the
mixture was stirred for 2 h at room temperature and
gave 97% of conversion: diphenylacetaldehyde and
desoxybenzoin were obtained in the ratio 88/12 as
evidenced by gas chromatography.
chlorotrimethylsilane in order to cleave the carbonꢁ
/
oxygen bond of the indium alcoolate arising from the
nucleophilic attack of an organoindium intermediate
upon the carbonyl function.
4. Experimental
4.1. General reaction conditions
All reactions were carried out under argon using
Schlenk techniques. Solvents were distilled prior to use:
THF from Na-benzophenone. Preparative flash column
chromatographies were carried out using SDS silicagel
It is worthy to note that any attempt to isolate the
products led to a loss of material since diphenylacetal-
60 (6ꢁ
/
35 m); solvent composition are quoted as v/v. 1H-
and 13C-NMR spectra were recorded on a Brucker

82
J. Auge´ et al. / Journal of Organometallic Chemistry 679 (2003) 79ꢁ
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83
1
Advance DPX 250 spectrometer (250 MHz for H and
62.5 MHz for 13C); chemical shifts were expressed in
parts per million downfield from tetramethylsilane.
13C-NMR (CDCl3, 62.5 MHz): d 14 (C-6), 18.2 (C-5),
18.6 (C-4), 19.8 (Me-acetal, syn), 24.3 and 24.6 (2Me-
acetal, anti), 25.6-38 (c-Hex), 42.6, 42.7, 43.6, 98.1 (C-
acetal, syn), 100.1 (C-acetal, anti).
4.2. General procedure for indium-catalyzed allylation of
aldehydes and ketones
4.3. Homocoupling of benzaldehyde
As a typical experiment, indium (23 mg, 0.2 mmol)
and manganese (550 mg, 10 mmol) were placed in a
Schlenk tube. The mixture was stirred under vacuum for
30 min. THF (12.5 ml) was then added under argon and
the mixture stirred vigorously; allyl bromide (432 ml, 5
mmol), benzaldehyde (203 ml, 2 mmol), TMSCl (1.27 ml,
10 mmol) were successively added under argon. The
mixture was allowed to react at room temperature for 3
h under a vigorous stirring; it turned progressively from
black to gray and then white. After 3 h, a saturated
solution of ammonium chloride (12 ml) was added and
the adduct extracted with ethyl acetate. The organic
layers were dried, filtered off and then evaporated to
afford after silicagel chromatography 1-phenyl-but-3-
en-1-ol in 88% yield.
Indium (804 mg, 7 mmol) was placed in a Schlenk
tube. The mixture was stirred under vacuum for 30 min.
THF (60 ml), benzaldehyde (1.06 g, 10 mmol) and
TMSCl (2.17 g, 20 mmol) were successively added. The
mixture was allowed to react at room temperature for 4
h under a vigorous stirring. After adding 20 ml of ethyl
acetate and 50 ml of water, the mixture was extracted
three times with 20 ml of ethyl acetate. The organic
layers were washed with 50 ml of a saturated solution of
sodium bicarbonate and dried over magnesium sul-
phate. After evaporation of the solvents, the residue
was chromatographed (cyclohexaneꢁethyl acetate, 95:5,
/
v/v) to give diphenylacetaldehyde 5 (461 mg, 47%),
desoxybenzoin 6 (118 mg, 12%) and benzophenone (182
mg, 20%).
4.2.1. 1-benzyloxy-1-cyclohexylpent-4-en-2-ol (3)
1H-NMR (CDCl3, 250 MHz): d 1ꢁ
/
1.9 (m, 11H, c-
References
Hex), 2ꢁ
/
2.4 (m, 3H, OH and H-3), 2.95 (dd, 0.33H, J
5.7, J1,2 3.6, H-1, syn), 3.06 (t, 0.67H, J1,2 5.2, H-1, anti),
3.6 (m, 0.33H, H-2, syn), 3.66 (ddd, 0.67H, J2,3 8.7, J1,2
5.2, J2,3? 3.9, H-2, anti), 4.31 (d, 0.33H, J 11.8, PhCH2,
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(2d, 1H, PhCH2, syn and anti), 4.91ꢁ5.06 (m, 2H, H-5
and H-5?), 5.63ꢁ5.83 (m, 1H, H-4), 7.1ꢁ7.3 (m, 5H).
13C-NMR (CDCl3, 62.5 MHz): dꢂ
25.7, 25.8, 25.9,
/
4.55
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26.0, 26.1, 26.3, 28.4, 28.5, 29.8 (syn), 30.1 (anti), 36.8
(anti), 39.3 (syn), 39.7 (anti), 39.9 (syn), 70.5 (C-2, syn),
70.7 (C-2, anti), 74.6 (PhCH2), 85.4 (C-1, syn), 86.5 (C-
1, anti), 116.9 (C-5, syn), 117. 5 (C-5, anti), 127.3, 127.4,
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/
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(PhCH2, anti), 79.7, 116.5 (C-6, syn), 117.2 (C-6, anti),
127.3, 127.7, 128.2 (PhCH), 134.9 (C-5), 138.8 (PhC).
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/
4.2.3. 1-cyclohexyl-1,3-O-isopropylidenehexane (5)
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2 (m, 26H), 3.2ꢁ
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83
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