Indium-mediated allylation of carbonyl compounds in ionic liquids: Effect of salts in ionic liquids

Article abstract of DOI:10.3390/molecules23071696

The In-mediated allylation of carbonyl compounds can be performed in various types of solvents including ionic liquids. However, we have found that in [bmim][BF₄] (where bmim = 1-butyl-3-methylimidazolium), the In-mediated coupling of crotyl bromide with benzaldehyde gives a complex mixture, and some additives, such as halides and amines, are crucial for the successful conversion to the corresponding γ-adduct. Instead, the addition of alcohols or water promotes the formation of the α-adduct. An asymmetric induction with up to 62% enantiomeric excess (ee) was observed employing cinchonidine as an additive in a binary solvent consisting of an ionic liquid and dichloromethane.

Full text of DOI:10.3390/molecules23071696

molecules
Communication
Indium-Mediated Allylation of Carbonyl Compounds
in Ionic Liquids: Effect of Salts
in Ionic Liquids
Tsunehisa Hirashita * ID , Fusako Takahashi, Takayuki Noda, Yuji Takagi and Shuki Araki
Life Science and Applied Chemistry, Graduate School of Engineering, Nagoya Institute of Technology,
Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan; f.takahashi.144@nitech.jp (F.T.); t.noda.686@nitech.jp (T.N.);
y.takagi.570@nitech.jp (Y.T.); a510224@hotmail.co.jp (S.A.)
*
Correspondence: hirasita@nitech.ac.jp; Tel.: +81-527-355-626
Academic Editors: Akio Baba and Makoto Yasuda
ꢀ
ꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀ
ꢁꢂꢃꢄꢅꢆ
Received: 30 May 2018; Accepted: 10 July 2018; Published: 11 July 2018
Abstract: The In-mediated allylation of carbonyl compounds can be performed in various
types of solvents including ionic liquids. However, we have found that in [bmim][BF4]
(
where bmim = 1-butyl-3-methylimidazolium), the In-mediated coupling of crotyl bromide with
benzaldehyde gives a complex mixture, and some additives, such as halides and amines, are crucial
for the successful conversion to the corresponding -adduct. Instead, the addition of alcohols or water
promotes the formation of the -adduct. An asymmetric induction with up to 62% enantiomeric
γ
α
excess (ee) was observed employing cinchonidine as an additive in a binary solvent consisting of an
ionic liquid and dichloromethane.
Keywords: indium; allylation; ionic liquids; carbonyl compounds; homoallylic alcohols
1
. Introduction
Indium-mediated allylations of carbonyl compounds have been extensively studied during the
last two decades [1–4]. Allylindium reagents are prepared from metallic indium and allylic halides in
a broad range of solvents, including water, and can be used in the Barbier-type allylation of carbonyl
compounds. We previously reported the allylation of carbonyl compounds with catalytic amounts of
indium(III) trichloride and stoichiometric amounts of aluminum (0) in aqueous tetrahydrofuran [5].
This method provides an easy access to reactions of allylic indium reagents and employs reduced
quantities of the relatively expensive indium metal. However, this catalytic allylation proceeds slowly
and a couple of days are needed to complete the reaction. More recently, we reported a catalytic
variation in a binary solvent system constituted of water and an ionic liquid [6].
Ionic liquids have emerged as recyclable solvents in organic synthesis, and their electrochemical
properties have also received attention. The preparation of organometallic compounds in ionic
liquids has also been of interest. Grignard reagents, however, have not been prepared in ordinary
ionic liquids, and a chelating group such as an ether functionality is required in the ionic liquids to
stabilize the Grignard reagents [7,8]. The preparation of allylic indium reagents and their reactions
with aldehydes [ 12] or imines [13] in ionic liquids have been reported, where the corresponding
9–
homoallylic alcohols or homoallylic amines have been obtained in high yields. Noteworthy, the use of
ionic liquids possessing chelating units is not required for promoting allylation when allylic indium
reagents are involved. Herein, we report that, in contrast to previous results, there are limitations
in using ionic liquids for preparing allylic indium reagents, and special additives, including halides,
are required in the crotylation of aldehydes depending on the nature of the ionic liquid employed.
Molecules 2018, 23, 1696; doi:10.3390/molecules23071696
www.mdpi.com/journal/molecules

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2
. Results and Discussion
2
.1. Allylation
We began screening a wide range of ionic liquids to perform the Barbier-type In-mediated
allylation. Thus, when allyl bromide and benzaldehyde were mixed with indium powder in
bmim][BF ] (where bmim = 1-butyl-3-methylimidazolium), the corresponding homoallylic alcohol
[
4
1
was obtained in good yield and in a shorter time (5 h) than that previously reported [10] (entry 1,
Table 1). The reactions in [bpy][BF ] (where bpy = N-butylpyridinium) and [bmim][(CN) N]
4
2
also gave
The reaction in [bmim][Cl], which was performed under conventional heating as [bmim][Cl] is not
liquid at room temperature, gave in low yield (entry 5). The allylation in [bmim][NTf ] (where
1 in high yields (entries 2 and 3), while the yield decreased in [bmim][OTf] (entry 4).
1
2
NTf = bis(trifluoromethanesulfonyl)amide) did not proceed (entry 6).
2
Table 1. Indium-mediated allylation in ionic liquid. a
Yield of 1 (%) b
Entry
Ionic Liquid
1
2
3
4
5
6
[bmim][BF4]
[bpy][BF4]
95
82
88
69
41
0
[bmim][(CN) N]
2
[bmim][OTf]
[bmim][Cl]
[bmim][NTf2]
c
a
All reactions were carried out with allyl bromide (1.6 mmol), benzaldehyde (1.0 mmol) and indium (1.0 mmol) in
b
ionic liquid (1.0 mL) at room temperature for 5 h; NMR yields determined using 1,3,5-trimethoxybenzene as the
internal standard; c Reaction carried out at 73 C.
◦
We next focused on the allylation involving a reductive transmetalation of a π-allylpalladium(II)
with In(I), in which a variety of solvents can be used [14]. Among the ionic liquids employed, as above
bmim][BF ] gave the best yield (entry 1, Table 2). The reactions in [bpy][BF ] and [bmim][OTf]
[
4
4
proceeded in moderate yields (entries 2 and 3), while [bmim][(CN) N] was not suitable for the
2
allylation (entry 4).
Table 2. Pd-catalyzed indium-mediated allylation in ionic liquid a.
Yield of 1 (%) b
Entry
Ionic Liquid
1
2
3
4
[bmim][BF4]
[bpy][BF4]
[bmim][OTf]
75
61
50
16
[bmim][(CN) N]
2
a
All reactions were carried out with allyl acetate (1.0 mmol), benzaldehyde (0.50 mmol) and indium(I) iodide
1.0 mmol), and Pd(PPh
(0.025 mmol) in ionic liquid (1.0 mL) at room temperature for 24 h; b NMR yields
determined using 1,3,5-trimethoxybenzene as the internal standard.
(
3 4
)
2
.2. Crotylation
We then turned our attention to the crotylation of benzaldehyde. The conversions in
bmim][(CN) N] and [bmim][OTf] proceeded well affording homoallylic alcohol in good yields
[
2
2

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(
entries 1 and 2, Table 3). Instead, [bmim][BF ], which had proved advantageous in the above reactions
4
(
Tables 1 and 2), gave a complicated mixture when used for the coupling of crotyl bromide and
1
benzaldehyde. The H-NMR spectrum of the crude mixture is shown in Figure 1a. As the crotylation
in [bmim][BF ] had previously been successful [10], the above result suggests that there are problems
4
associated with the source of the ionic liquid employed. We anticipated that the difference may be
caused by some type of impurity present in the ionic liquid, such as [bmim][X] the precursor of
[
bmim][BF ], which presumably plays an essential role in the allylation of aldehydes as it does in the
4
allylation of imines [13].
Table 3. Crotylation of benzaldehyde in ionic liquid a.
Yield of 2 (%) b
Entry
Ionic Liquid
Time (h)
c
1
2
3
[bmim][(CN) N]
[bmim][OTf]
[bmim][BF4]
0.5
1
1
80 (58:42)
67 (55:45)
2
c
Complex mixture
a
All reactions were carried out at a 0.5 mmol scale of benzaldehyde at room temperature in ionic liquid (1 mL);
Determined by H-NMR using 1,3,5-trimethoxybenzene as the internal standard; Syn:anti.
b
1
c
(
a) In the absence of [bmim][Cl]
(b) In the presence of [bmim][Cl]
Figure 1. Crotylation of benzaldehyde in [bmim][BF ] in the absence (a) or presence (b) of [bmim][Cl].
4
We then tested whether the [bmim][Cl] residue in [bmim][BF ] affected the crotylation.
4
When crotyl bromide and benzaldehyde were stirred with indium powder in [bmim][BF ] containing a
4
small amount of [bmim][Cl], homoallylic alcohol 2 was formed cleanly as depicted in Figure 1b (entry 1,
Table 4). In place of [bmim][Cl], LiCl was next examined to clarify the role of halides. The addition of a
stoichiometric amount of LiCl also improved the yield, giving 2 in high yield (entry 2). The reactions
with either a catalytic or excess amount of LiCl gave lower yields (entries 3 and 4). To get further
insights into the role of LiCl in the mechanism of the reaction, we carried out a set of Grignard-type
reactions; thus, a mixture of crotyl bromide and indium in [bmim][BF ] was stirred at room temperature
4
for 0.5 h in the presence or absence of LiCl prior to the addition of benzaldehyde. Without LiCl, the
reaction did not give homoallylic alcohol
Scheme 1).
2. Instead, the reaction with LiCl afforded 2 in 97% yield
(

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Scheme 1. Effects of LiCl on the crotylation of benzaldehyde.
During the reaction of crotyl bromide with indium in [bmim][BF ] in the absence of LiCl,
4
the consumption of indium powder was sluggish and an unidentified solid was deposited [15].
These results demonstrate that LiCl stabilizes both the crotylindium reagent and the resulting indium
homoallylic alkoxide and prevents from unexpected reactions leading to a decreased yield of
The addition of catalytic amounts (10 mol %) of [bmim][Cl], [bmim][Br], or LiBr was sufficient
for a clean formation of (entries 5–7), which probably relates to the tendency of these halides to
2.
2
dissociate and their solubility in the media. We next set out to examine other organic/inorganic salts
in the crotylation. The addition of triphenylphosphine gave a good yield (entry 8). While a primary
alkylamine worked as a promoter to some extent, tertiary amines were less efficient (entries 9 and 10).
Pyridine and cinchonidine [16] proved to be good promoters (entries 11 and 12) [17]. Some alcohols,
except phenol, promoted the crotylation. However, linear homoallylic alcohol
the major product (entries 13–15). The addition of water also gave a mixture of
3
was formed as
2
and (entry 16),
3
indicating that an oxonia[3,3]-sigmatropic rearrangement occurs under these conditions [18].
Table 4. Crotylation of benzaldehyde in the presence of additives a.
NMR Yield (%) (syn:anti) b
Entry
Additive (mol %)
Time (h)
1
2
3
4
5
6
7
8
9
[bmim][Cl] (114)
LiCl (100)
1
1
1
1
5
5
1
2
3
18
6
6
6
6
3
6
2: 90 (54:46)
2: 92 (59:41)
2: 8 (66:34) d
2: 58 (57:43)
2: 65 (58:42)
2: 80 (63:37)
2: 62 (63:37)
2: 78 (56:44)
2: 48 (58:42)
trace
c
LiCl (10)
LiCl (200)
[bmim][Cl] (10)
[bmim][Br] (10)
LiBr (10)
PPh (100)
3
1-Butylamine (100)
e
10
11
12
13
14
15
16
TMEDA (100)
Pyridine (100)
Cinchonidine (100)
1-Hexanol (100)
Phenol (100)
Diethyl L-tartrate (100)
2: 75 (57:43)
2: 82 (54:46)
d
d,f
2: 26 (73:27) , 3: 41 (47:53)
0
d
d,f
d,f
2: 19 (75:25) , 3: 33 (55:45)
2: 45 (74:26) , 3: 42 (48:52)
d
H O (100)
2
a
4
All reactions were carried out at a 0.5 mmol scale of benzaldehyde at room temperature in [bmim][BF ]
1 mL); 1,3,5-Trimethoxybenzene was used as the internal standard; With 1.0 mmol scale; d Isolated yield;
b
c
(
e
f
Tetramethylethylenediamine; E:Z.

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2
.3. Intramolecular Auxiliary
As pyridine proved to function as a good promoter, we next employed 2- and
-pyridinecarboxaldehydes instead of benzaldehyde as substrates of the crotylation reaction in the
3
absence of additives in order to assess the influence of intramolecular interactions between the pyridyl
and carbonyl groups (Scheme 2). Although both aldehydes gave the corresponding homoallylic
alcohols
4 and 5, 2-pyridinecarboxaldehyde gave a higher yield of the corresponding product than
the reaction performed with the 3-pyridinyl isomer. This result suggests that the ring nitrogen atom
adjacent to the carbonyl group not only stabilizes the crotylindium reagent and derivatives thereof in
[
bmim][BF ] but also helps the rapid transformation by intramolecular chelation [19,20].
4
Scheme 2. Effects of intramolecular chelating units.
2
.4. Chiral Auxiliary
The importance of intra- and intermolecular chelating groups to promote a clean crotylation
prompted us to examine an asymmetric version of the present reaction. We anticipated that an
asymmetric induction would function well with a judicious choice of chiral additives due to their
critical role in promoting the allylation in [bmim][BF ]. As the use of cinchonidine had been reported by
4
Loh and co-workers as a suitable chiral auxiliary for the asymmetric addition of allylindium reagents
to aldehydes [21], we set to investigate the effect of cinchonidine on the allylation of benzaldehyde
in [bmim][BF ] under similar conditions to those reported by Loh. After stirring a mixture of allyl
4
bromide and cinchonidine with indium in [bmim][BF ] for 3 h at room temperature, benzaldehyde
4
was added. The reaction in [bmim][BF ] gave a lower yield than that performed without additive
4
(
entry 1, Table 1), and a neglectable ee was observed (entry 1, Table 5). We then examined the reaction
at low temperature, where the ionic liquid needed to be diluted with an organic solvent due to its
high viscosity, and thus, CH Cl was chosen due to its weakly coordinating character. The reaction
2
2
in the binary solvent gave a good yield at room temperature with a moderate ee (entry 2), while at
◦ ◦
78 C both the yield and ee remarkably decreased (entry 3). At 40 C, a somewhat higher ee was
−
observed (entry 4). Because cinchonidine is poorly soluble in [bmim][BF ], its benzyl ammonium
4
salt was next employed in the reaction (entry 5). This salt completely dissolved and the reaction
quickly proceeded, albeit the ee significantly decreased. The reaction in [bpy][BF ] showed a similar
4
tendency to that found in [bmim][BF ]; the ee value decreased at low temperature (entries 6 and 7).
4
The reaction in a mixture of [bmim][OTf] and CH Cl also perceived an improvement both in yield
2
2
and ee, while the opposite phenomena to that found in [bmim][BF ] was observed at low temperature,
4
and the ee increased as a result of lowering the temperature (entries 8–11).
Table 5. Asymmetric indium-mediated allylation of benzaldehyde using cinchonidine a.
◦
Ee (%) b
Entry
Solvent Solvent 1/Solvent 2
Temp. ( C)
Time (h)
Yield (%)
1
2
3
4
[bmim][BF4]
rt
rt
15
15
15
15
50
90
41
51
2
33
2
[bmim][BF ]/CH Cl
4
2
2
2
2
[bmim][BF ]/CH Cl
−78
4
2
[bmim][BF ]/CH Cl
40
20
4
2

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Table 5. Cont.
◦
Ee (%) b
Entry
Solvent Solvent 1/Solvent 2
Temp. ( C)
Time (h)
Yield (%)
5 c
6
7
8
9
[bmim][BF ]/CH Cl
2
rt
rt
1
81
71
76
81
98
23
34
6
28
3
4
2
[bpy][BF ]/CH Cl
15
65
15
1
15
15
4
2
2
2
[bpy][BF ]/CH Cl
−60
4
2
[bmim][OTf]
rt
0
[bmim][OTf]/CH Cl
rt
51
62
61
2
2
2
2
1
1
0
1
[bmim][OTf]/CH Cl
−20
2
[bmim][OTf]/CH Cl
−78
2
a
Benzaldehyde (0.25 mmol), allyl bromide (320 mol %), indium (200 mol %), and cinchonidine (200 mol %) were
used; b Determined by HPLC; c N-Benzylcinchonidium bromide was used instead of cinchonidine.
3
. Materials and Methods
3
.1. Analysis
1H-NMR spectra were recorded on a Varian Mercury spectrometer (300 MHz). Please see the
H-NMR of compounds in Supplementary Materials. The optical purities of the products were
1
1–5
measured by HPLC (Daicel Chiralcel OD-H column). 1-Phenyl-3-buten-1-ol: hexane/i-PrOH = 98:2,
−
1
flow rate 1.0 mL min , tR = 17.5 min (R)-enantiomer, tR = 20.9 min (S)-enantiomer [22].
2
−
-Methyl-1-phenylbut-3-en-1-ol: hexanes/i-PrOH = 99:1, 0.5 mL min , t (S,S; anti) = 29.9 min,
R
1
t (S,R; syn) = 32.2 min, t (R,R; anti) = 34.2 min, t (R,S; syn) = 35.5 min [23].
R
R
R
Ionic liquids and indium metal were purchased from commercial sources and used as received.
N-Benzylcinchonidium bromide was prepared according to the literature [24]. Allylic bromides and
aldehydes were distilled just before use. All reactions were carried out under argon.
3
.2. General Procedure for the Allylation of Benzaldehyde in Ionic Liquids
A mixture of allyl bromide (138 L, 1.6 mmol), benzaldehyde (102
115 mg, 1.0 mmol) was stirred in ionic liquid (1.0 mL) at room temperature for 5 h. Water was added
to the reaction mixture and the product was extracted with diethyl ether. The extracts were purified by
µ
µL, 1.0 mmol), and indium
(
short column chromatography on silica gel. The yield of 1-phenyl-3-buten-1-ol (
H NMR analysis using 1,3,5-trimethylbenzene as the internal standard.
1
) was determined by
1
3
.3. General Procedure for the Pd-Catalyzed Allylation of Benzaldehyde in Ionic Liquids
A mixture of allyl acetate (108 L, 1.0 mmol), benzaldehyde (51 L, 0.5 mmol), indium(I) iodide
424 mg, 1.0 mmol), and Pd(PPh ) (29 mg, 0.025 mmol) was stirred in ionic liquid (1.0 mL) at room
µ
µ
(
3
4
temperature for 24 h. Dilute hydrochloric acid (1 M) was added to the reaction mixture and the
product was extracted with diethyl ether. The organic layer was washed with saturated NaHCO3,
water, and brine, and dried over Na SO . The yield of 1-phenyl-3-buten-1-ol (1) was determined by
2
4
1
H NMR analysis using 1,3,5-trimethylbenzene as the internal standard.
3
.4. General Procedure for the Crotylation of Benzaldehyde in Ionic Liquids
A mixture of crotyl bromide (81 L, 0.8 mmol), benzaldehyde (51
58 mg, 0.50 mmol) was stirred in ionic liquid (1.0 mL) at room temperature for 1 h. Dilute hydrochloric
acid (1 M) was added to the reaction mixture and the product was extracted with diethyl
µ
µL, 0.50 mmol), and indium
(
ether. The organic layer was washed with saturated NaHCO , water, and brine, and dried over
3
1
Na SO . The yield of
2
was determined by H-NMR analysis using 1,3,5-trimethylbenzene as the
2
4
internal standard.
3
.5. Crotylation of Benzaldehyde in the Presence of Additives
A mixture of crotyl bromide (81 L, 0.80 mmol), benzaldehyde (58
58 mg, 0.50 mmol), and additive was stirred in [bmim][BF ] (1.0 mL) at room temperature for 1 h.
µ
µL, 0.50 mmol), indium
(
4

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Dilute hydrochloric acid (1 M) was added to the reaction mixture and the product was extracted with
diethyl ether. The organic layer was washed with saturated NaHCO , water, and brine, and dried
3
1
over Na SO . The yield of
2
was determined by H NMR analysis using 1,3,5-trimethylbenzene as the
2
4
internal standard.
3.6. General Procedure for the Asymmetric Indium-Mediated Allylation of Benzaldehyde Using Cinchonidine
The reaction in entry 10 is described as a representative typical procedure. A mixture of allyl
bromide (69
µL, 0.8 mmol), indium (58 mg, 0.50 mmol), and cinchonidine (147 mg, 0.50 mmol) was
stirred in [bmim][OTf] (1.0 mL) at room temperature for 3 h. To the resulting mixture a solution
of benzaldehyde (25
µ
L, 0.25 mmol) in CH Cl (1 mL) was added and the mixture was stirred at
2
2
◦
−
78 C for another 15 h. The mixture was quenched with dilute hydrochloric acid (1 M, 2 mL) and
the product extracted with diethyl ether. The organic layer was washed with saturated NaHCO ,
3
water, and brine, and dried over Na SO . The solvent was removed under reduced pressure to give a
2
4
1
slightly yellow oil. The yield of 1-phenyl-3-buten-1-ol (
,3,5-trimethylbenzene as the internal standard (34%), and the ee for (R)-
analysis (61%).
1
) was determined by H-NMR analysis using
1
1
was determined by HPLC
3
.7. Product Characterization
1
1
-Phenyl-3-buten-1-ol (1) [22]. H-NMR (300 MHz, CDCl ): δ 2.05 (brs, 1H), 2.47–2.57 (m, 2H), 4.72–4.77
3
(q, J = 7.5 Hz, 1H), 5.12–5.20 (m, 2H), 5.75–5.89 (m, 1H), 7.25–7.37 (m, 5H).
1
2
3
7
-Methyl-1-phenyl-3-buten-1-ol (
2
) [25]. H-NMR (300 MHz, CDCl ) syn isomer:
δ
1.01 (d, J = 6.6 Hz,
3
H), 1.93 (brs, 1H), 2.45–2.62 (m, 1H), 4.62 (d, J = 4.8 Hz, 1H), 5.04–5.08 (m, 2H), 5.71–5.88 (m, 1H),
.26–7.337 (m, 5H); anti isomer:
δ
0.87 (d, J = 6.9 Hz, 3H), 1.93 (bs, 1H), 4.36 (d, J = 5.2 Hz, 1H), 5.17–5.24
(m, 1H).
1
1-Phenyl-3-penten-1-ol (
3
) [18]. H-NMR (300 MHz, CDCl ) (E)- isomer:
δ
1.61 (dd, J = 6.8, 0.8 Hz,
3
3H), 2.00 (s, 1H), 2.34–2.63 (m, 2H), 4.66–4.75 (m, 1H), 5.38–5.47 (m, 1H), 5.55–5.68 (m, 1H), 7.26–7.39
(m, 5H); (Z)- isomer: δ 1.69 (dd, J = 6.2 Hz, 0.9 Hz, 3H), 2.06 (s, 1H).
1
2
-Methyl-1-(2-pyridinyl)-3-buten-1-ol (
4
) [20]. H-NMR (300 MHz, CDCl ) syn isomer:
δ 0.91
3
(
(
d, J = 6.9 Hz, 3H), 2.57–2.73 (m, 1H), 4.12 (t, J = 6.3 Hz, 1H), 4.71 (t, J = 4.8 Hz, 1H), 5.00–5.10
m, 2H), 5.86–5.99 (m, 1H), 7.18–7.26 (m, 2H), 7.67 (t, J = 7.8 Hz, 1H), 8.55 (d, J = 4.8 Hz, 1H); anti isomer:
δ 1.08 (d, J = 6.9 Hz, 3H), 4.64 (t, J = 4.8 Hz, 1H), 5.69–5.81 (m, 1H).
1
2-Methyl-1-(3-pyridinyl)-3-buten-1-ol (
5) [26].
H-NMR (300 MHz, CDCl ) syn isomer: δ 0.91
3
(
(
(
d, J = 6.9 Hz, 3H), 2.48 (sext, J = 7.5 Hz, 1H), 4.43 (d, J = 7.5 Hz, 1H), 5.03–5.11 (m, 1H), 5.18–5.23
m, 1H), 5.70–5.85 (m, 1H), 7.27–7.30 (m, 1H), 7.65–7.71 (m, 1H), 8.53 (brs, 2H); anti isomer:
d, J = 6.6 Hz, 3H), 2.60 (sext, J = 6.6 Hz, 1H), 4.67 (d, J = 5.4 Hz, 1H).
δ 1.02
4
. Conclusions
The choice of ionic liquid is important to achieve a clean In-mediated allylation and crotylation
of carbonyl compounds. From a screening of ionic liquids, [bmim][BF ] was found to be the most
4
promising solvent for both the In-promoted couplings of allyl bromide to carbonyl compounds and
the Pd-catalyzed In(I)-mediated version. Instead, when crotyl bromide is employed, the use of pure
[
bmim][BF ] has detrimental effects, and the addition of appropriate halide salts or amines is crucial
4
for a successful crotylation leading to the
bmim][BF ] favor the formation of the -adduct isomer. Furthermore, cinchonidine functions as a
chiral promoter in the coupling of allyl bromide and benzaldehyde in [bmim][BF ]/CH Cl , affording
γ-adduct. Instead, the addition of alcohols and water in
[
α
4
4
2
2
the corresponding homoallylic alcohol with up to 62% ee.

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1
Supplementary Materials: The following are available online. H-NMR of compounds 1–5.
Author Contributions: T.H. and S.A. conceived and designed the experiments; F.T., T.N., and Y.T. performed the
experiments and analyzed the data; T.H. wrote the paper.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflicts of interest.
References and Notes
1
2
3
4
5
6
.
.
.
.
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Sample Availability: Not available.
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