Metal free synthesis of homoallylic alcohols promoted by ultrasound

Article abstract of DOI:10.1016/j.ultsonch.2014.04.001

The use of ultrasound irradiation to promote the allylation of aldehydes containing different functionalities with potassium allyltrifluoroborates is described. The method features the use of a minimum amount of acetone as solvent, without any other catalyst or promoter. The products were obtained in high yields, short reaction times, at room temperature and without the need of further purification.

Full text of DOI:10.1016/j.ultsonch.2014.04.001

Ultrasonics Sonochemistry xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson
Short Communication
Metal free synthesis of homoallylic alcohols promoted by ultrasound
Jucleiton José R. Freitas a, Túlio R. Couto a, Italo H. Cavalcanti a, Juliano C.R. Freitas b, Roberta A. Oliveira a,
,
⇑
Paulo H. Menezes a,
⇑
a Departamento de Química Fundamental, Universidade Federal de Pernambuco, Recife, PE 50740-540, Brazil
b Centro de Educação e Saúde, Universidade Federal de Campina Grande, Olho D’agua da Bica, s/n, Cuité, PB 58175-000, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
The use of ultrasound irradiation to promote the allylation of aldehydes containing different functional-
ities with potassium allyltrifluoroborates is described. The method features the use of a minimum
amount of acetone as solvent, without any other catalyst or promoter. The products were obtained in
high yields, short reaction times, at room temperature and without the need of further purification.
Ó 2014 Elsevier B.V. All rights reserved.
Received 18 September 2013
Received in revised form 5 March 2014
Accepted 1 April 2014
Available online xxxx
Keywords:
Potassium organotrifluoroborates
Allylation
Green chemistry
1. Introduction
Herein, we wish to describe an environmentally benign reaction
for the synthesis of homoallylic alcohols based on the reaction of
The addition of an allylic organometallic reagent to
carbonyl compound is an important synthetic method, not only
to afford the formation of a new carbon–carbon bond and the
a
potassium allyltrifluoroborate and aldehydes containing different
functional groups promoted by ultrasound without the use of
any metal or additive.
introduction of two new functionalities, an alcohol and
a
double bond, but also because these can be used for further
transformations [1].
2. Materials and methods
Thus, the development and application of allylic organome-
tallic reagents have attracted attention with several approaches
already described based on the use of allylic organometallics [2]
or organometalloid [3] reagents, as well as electrochemical
based methods [4].
Some allylic organometallics present drawbacks such as the dif-
ficulty to handle due to its Lewis base character, which requires the
use of strictly anhydrous conditions and because of competing
Wurtz coupling reactions [5].
Thereby, the search for more efficient synthetic methods based
on the use of less expensive and easy to handle reagents have
attracted considerable interest from chemists. Moreover, the
development of methods focusing on environmentally benign
reactions has become particularly prominent [6]. In this context,
the use of ultrasound in organic synthesis has attracted consider-
able attention, not only because it can easily promote organic
transformations which normally requires drastic conditions, but
also because it can enhance the reaction rate and increase the yield
[7].
2.1. Materials
All solvents used were previously purified and dried in agree-
ment with the literature [8]. Compounds 1a–o and E-crotylboronic
acid pinacol ester were purchased from Aldrich Chemical Co. and
used as received. All other commercially available reagents and
solvents were used as received. Reactions were monitored by
thin-layer chromatography on 0.25 mm E. Merck silica gel 60
plates (F254) using UV light, vanillin and p-anisaldehyde as visual-
izing agents. All compounds were sufficiently pure for use in fur-
ther experiments, unless indicated otherwise.
2.2. Instrumentation
1H (300 MHz) NMR and 13C (75 MHz) NMR data were recorded
in CDCl3 or DMSO-d6. The chemical shifts are reported as delta (d)
units in parts per million (ppm) relative to the solvent residual
peak as the internal reference. 11B (128 MHz) and 19F (376 MHz)
NMR spectra were recorded in DMSO-d6. Spectra were calibrated
using BF3ꢀEt2O (0.0 ppm) as external reference in the case of 11B
NMR and chemical shifts were referenced to external CF3CO2H
⇑
Corresponding authors. Tel.: +55 81 2126 7473; fax: +55 81 2126 8442.
E-mail addresses: paulo.menezes@pq.cnpq.br, pmenezes@ufpe.br (P.H. Menezes).
http://dx.doi.org/10.1016/j.ultsonch.2014.04.001
1350-4177/Ó 2014 Elsevier B.V. All rights reserved.
Please cite this article in press as: J.J.R. Freitas et al., Metal free synthesis of homoallylic alcohols promoted by ultrasound, Ultrason. Sonochem. (2014),
http://dx.doi.org/10.1016/j.ultsonch.2014.04.001

2
Jucleiton José R. Freitas et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
(0.0 ppm) in the case of 19F NMR. Coupling constants (J) for all
spectra are reported in Hertz (Hz). The sonication was performed
in an 8890E-DTH ultrasonic cleaner (with a frequency of 47 kHz
and a nominal power 35 W; Cole Parmer Co.). The reaction flask
was located at the maximum energy area in the cleaner, the sur-
face of reactants was slightly lower than the level of the water.
The reaction temperature was controlled by water bath.
The data for all synthesized compounds match with the literature
[3a].
2.3.3.1. (3a) (E)-1-Phenylhexa-1,5-dien-3-ol. 1H NMR (300 MHz,
CDCl3) d 7.40–7.21 (m, 5H, HAryl), 6.61 (dd, J = 15.9, 1.2 Hz, 1H,
PhCH = CH), 6.24 (dd, J = 15.9, 6.3 Hz, 1H, PhCH = CH), 5.86 (ddt,
J = 17.1, 10.2, 6.9 Hz, 1H, CH = CH2), 5.22–5.14 (m, 2H, CH = CH2),
4.40–4.33 (m, 1H, CHOH), 2.50–2.33 (m, 2H, CHCH2), 1.78 (br s,
1H, OH); 13C NMR (75 MHz, CDCl3) d 136.5, 134.0, 131.5, 130.2,
128.5, 127.6, 126.4, 118.3, 71.6, 41.9.
2.3. Typical procedures
2.3.1. Synthesis of potassium allyltrifluoroborate, 2
2.3.3.2. (3b) 1-(Furan-2-yl)but-3-en-1-ol. 1H NMR (300 MHz, CDCl3)
d 7.38 (dd, J = 1.8, 0.9 Hz, 1H, HHet), 6.34 (dd, J = 2.1, 1.8 Hz, 1H,
HHet), 6.26 (dd, J = 2.1, 0.9 Hz, 1H, HHet), 5.81 (ddt, J = 17.1, 10.2,
6.9 Hz, 1H, CH = CH2), 5.23–5.13 (m, 2H, CH = CH2), 4.76 (dd,
J = 6.6, 6.3 Hz, 1H, CHOH), 2.66–2.60 (m, 2H, CHCH2), 2.05 (br s,
1H, OH); 13C NMR (75 MHz, CDCl3) d 155.9; 141.9; 133.6, 118.6,
110.1, 106.1, 66.9, 40.1.
To a solution of B(OMe)3 (8.15 mL, 7.59 g, 73.2 mmol) in THF
(40 mL) was added dropwise allylmagnesium chloride (30 mL,
60 mmol, 2.0 M in THF) at À78 °C. The mixture was stirred for
30 min. The ice bath was removed. The yellow solution with a
white precipitate was allowed to reach the room temperature over
a 1 h period. Then, it was cooled to 0 °C and KHF2 (23.4 g,
300 mmol) was added in one portion. This was followed by the
dropwise addition of H2O (30 mL). The ice bath was removed.
The mixture was stirred for 30 min and then concentrated under
high vacuum. The white solid was extracted with hot acetone
(4 Â 100 mL). The extracts were filtered through a Celite pad and
the filtrate was concentrated in vacuo to afford a white solid. The
solid was purified by dissolving in the minimum amount of hot
acetone, followed by cooling to room temperature and precipita-
tion with Et2O. The solution was allowed to stand for 20 min to
complete precipitation. The precipitate was collected and dried
under high vacuum to yield 3.37 g (38%) of the title compound as
a white solid powder, which can be stored at room temperature
without degradation. 1H NMR (300 MHz, DMSO-d6) d 5.85–5.74
(m, 1H, CH2@CH), 4.56 (d, J = 17.2 Hz, 1H, CH2@CH), 4.49 (d,
J = 9.6 Hz, 1H, CH2@CH), 0.92 (br s, 2H, CH2BF3K); 13C NMR
(75 MHz, DMSO-d6) d 142.9, 108.9; 11B NMR (128 MHz, DMSO-
2.3.3.3. (3c) 1-(2-Nitrophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.94 (dd, J = 8.1, 1.2 Hz, 1H, HAryl), 7.84 (dd, J = 8.1,
1.5 Hz, 1H, HAryl), 7.65 (td, J = 8.1, 1.2 Hz, 1H, HAryl), 7.43 (td,
J = 8.1, 1.2 Hz, 1H, HAryl), 5.97–5.83 (m, 1H, CH@CH2), 5.32 (dd,
J = 8.4, 3.6 Hz, 1H, CHOH), 5.25–5.18 (m, 2H, CH@CH2), 2.76–2.67
(m, 1H, CHCH2), 2.48–2.37 (m, 2H, CHCH2 and OH); 13C NMR
(75 MHz, CDCl3) d 147.7, 139.2, 133.9, 133.4, 128.1, 128.0, 124.3,
119.0, 68.3, 42.8.
2.3.3.4. (3d) 1-(3-Nitrophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 8.24 (t, J = 1.5 Hz, 1H, HAryl), 8.13 (ddd, J = 8.1, 2.1,
0,9 Hz, 1H, HAryl), 7.71 (d, J = 8.1 Hz, 1H, HAryl), 7.53 (t, J = 8.1 Hz,
1H, HAryl), 5.87–5.73 (m, 1H, CH@CH2), 5.22–5.16 (m, 2H, CH@CH2),
4.87 (dd, J = 8.1, 5.1 Hz, 1H, CHOH), 2.63–2.43 (m, 2H, CHCH2), 2.19
(br s, 1H, OH); 13C NMR (75 MHz, CDCl3) d 148.1, 145.9, 133.2,
131.9, 129.3, 122.4, 120.8, 119.6, 72.0, 43.9.
d6)
d
4.21 (q, J11B,19F = 61.3 Hz, BF3K); 19F NMR (376 MHz,
DMSO-d6) d À136.4 (J19F,11B = 61.3 Hz, BF3K). The NMR data are in
agreement with previously reported literature values [3a].
2.3.3.5. (3e) 1-(4-Nitrophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 8.21 (d, J = 8.7 Hz, 2H, HAryl), 7.54 (d, J = 8.7 Hz, 2H, HAryl),
5.86–5.72 (m, 1H, CH@CH2), 5.22–5.16 (m, 2H, CH@CH2), 4.87 (dd,
J = 7.8, 4.5 Hz, 1H, CHOH), 2.62–2.40 (m, 2H, CHCH2), 2.07 (br s, 1H,
OH); 13C NMR (75 MHz, CDCl3) d 151.1, 147.1, 133.1, 126.5, 123.5,
119.5, 72.1, 43.8.
2.3.2. Synthesis of potassium E-crotyltrifloroborate, 4
To a solution of E-crotylboronic acid pinacol ester (0.5 g,
2.75 mmol) in MeOH (12 mL) was added dropwise a 4.5 M solution
of KHF2 (2.0 mL) over a 30 min at 0 °C. The mixture was stirred for
additional 30 min at room temperature and concentrated under
high vacuum. The residual solids were extracted with 20% MeOH
in acetone (3 Â 10 mL). The combined extracts were concentrated
close to the saturation point and Et2O was added until no more
precipitation was observed. The solid was collected, washed with
Et2O (2 Â 10 mL), and dried under high vacuum to give 300 mg
(60%) of the title compound as a white powdered solid. 1H NMR
(300 MHz, DMSO-d6): d 5.43–5.36 (m, 1H, CH3–CH), 4.96–4.91
(m, 1H, CH@CH–CH2), 1.51 (d, J = 5.9 Hz, 3H, CH3–CH), 0.92 (br s,
2H, CH2BF3K); RMN 13C (75 MHz, DMSO-d6) d 135.0, 117.9, 18.2;
2.3.3.6. (3f) 1-(2-Methoxyphenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.34 (dd, J = 7.5, 1.8 Hz, 1H, HAryl), 7.25 (td, J = 7.5,
1.8 Hz, 1H, HAryl), 6.96 (td, J = 8.4, 1.2 Hz, 1H, HAryl), 6.88 (d,
J = 8.4 Hz, 1H, HAryl), 5.85 (ddt, J = 17.1, 10.2, 7.5 Hz, 1H, CH@CH2),
5.17–5.09 (m, 2H, CH = CH2), 4.96 (dd, J = 8.1, 5.1 Hz, 1H, CHOH),
3.84 (s, 3H, OMe), 2.64–2.44 (m, 2H, CHCH2), 2.41 (br s, 1H, OH);
13C NMR (75 MHz, CDCl3) d 156.2, 135.1, 131.7, 128.2, 126.7,
120.6, 117.4, 110.3, 69.5, 55.1, 41.8.
RMN 11B (128 MHz, DMSO-d6) d 6.21 (q, J11B 19F
= 61.4 Hz, BF3K);
,
2.3.3.7. (3g) 1-(3-Methoxyphenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.18 (dd, J = 8.1, 7.8 Hz, 1H, HAryl), 6.86–6.84 (m, 2H, HAryl),
6.74 (ddd, J = 8.1, 2.7, 1.2 Hz, 1H, HAryl), 5.73 (ddt, J = 17.1, 10.2,
7.5 Hz, 1H, CH@CH2), 5.12–5.04 (m, 2H, CH@CH2), 4.63 (dd,
J = 7.5, 5.4 Hz, 1H, CHOH), 3.73 (s, 3H, OMe), 2.46–2.39 (m, 2H,
CHCH2), 1.95 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3) d 159.5,
145.6, 134.4, 129.3, 118.2, 118.0, 112.8, 111.2, 73.1, 55.1, 43.6.
RMN 19F (376 MHz, DMSO-d6) d À136.4 (J19F,11B = 61.4 Hz, BF3K).
The NMR data are in agreement with previously reported literature
values [3i].
2.3.3. General procedure for the allylation of aldehydes (1a–o) with
potassium allyltrifluoroborate (2) promoted by ultrasound
To a solution of the appropriate aldehyde 1a–o (1.0 mmol) in
acetone (0.5 mL) was added potassium allyltrifluoroborate
2
2.3.3.8. (3h) 1-(4-Methoxyphenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.28 (d, J = 9.0 Hz, 2H, HAryl), 6.88 (d, J = 9.0 Hz, 2H, HAryl),
5.79 (ddt, J = 16.8, 9.9, 6.6 Hz, 1H, CH@CH2), 5.19–5.10 (m, 2H,
CH@CH2), 4.68 (t, J = 6.6 Hz, CHOH), 3.80 (s, 3H, OMe), 2.52–2.47
(m, 2H, CHCH2), 2.01 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3) d
158.9, 136.0, 134.6, 127.0, 118.2, 113.7, 72.9, 55.2, 43.7.
(177 mg, 1.20 mmol). The mixture was placed in an ultrasound
bath for the time indicated on Table 2 and then diluted with EtOAc
(5 mL) and washed with water (2 Â 15 mL). The organic layer was
dried over MgSO4 and the solvent was removed under reduced
pressure to yield 3a–q without the need of further purification.
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Jucleiton José R. Freitas et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
3
2.3.3.9. (3i) 1-(2-Fluorophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.41 (t, 1H, J = 7.6 Hz, HAryl), 7.22–7.15 (m, 1H, HAryl),
7.09 (t, J = 7.6 Hz, 1H, HAryl), 6.99–6.92 (m, 1H, HAryl), 5.83–5.69
(m, 1H, CH@CH2), 5.14–5.08 (m, 2H, CH@CH2), 5.00 (dd, 1H,
J = 7.6, 4.4 Hz, CHOH), 2.57–2.37 (m, 2H, CHCH2), 2.03 (br s, 1H,
OH); 13C NMR d (75 MHz, CDCl3) d 160.9, 134.0, 130.8, 128.8,
127.2, 124.2, 118.7, 115.3, 67.3, 42.6.
(t, J = 6.3 Hz, 6H, CH3CH2); 13C NMR (75 MHz, CDCl3) d 134.9,
118.0, 70.6, 41.9, 36.7, 31.8, 25.3, 22.6, 14.0.
2.3.4. General procedure for the crotylation of 1a with potassium (E)-
crotyltrifluoroborate, 4 promoted by ultrasound
The same procedure described above was used for the crotyla-
tion reaction. To a solution of 1a (132 mg, 1.0 mmol) in acetone
(0.5 mL) was added potassium (E)-crotyltrifluoroborate
4
2.3.3.10. (3j) 1-(4-Fluorophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.28–7.24 (m, 2H, HAryl), 6.97 (t, 2H, J = 8.4 Hz, HAryl),
5.79–5.65 (m, 1H, CH@CH2), 5.13–5.06 (m, 2H, CH@CH2), 4.66
(dd, 1H, J = 7.2, 5.7 Hz, CHOH), 2.45–2.40 (m, 2H, CHCH2), 1.82
(br s, 1H, OH); 13C NMR d (75 MHz, CDCl3) d 163.4, 139.6, 134.1,
127.4, 118.7, 115.3, 72.6, 43.9.
(194 mg, 1.20 mmol). The mixture was placed in an ultrasound
bath for the time indicated on Table 2 and then diluted with EtOAc
(5 mL) and washed with water (2 Â 15 mL). The organic layer was
dried over MgSO4 and the solvent was removed under reduced
pressure to yield 5 in 60% yield (112 mg). The NMR data obtained
for 3a are in agreement with previously reported literature values
[3h]. (5) (E)-4-Methyl-1-phenylhexa-1,5-dien-3-ol: anti isomer:
1H NMR (300 MHz, CDCl3): d 7.33–7.17 (m, 5H, HAryl), 6.55 (d,
J = 16.00 Hz, 1H, PhCH@CH), 6.16 (dd, J = 6.80 Hz, 16.00 Hz, 1H,
PhCH@CH), 5.78–5.70 (m, 1H, CH@CH2), 5.22–5.11 (m, 2H,
CH@CH2), 3.99 (t, J = 6.8 Hz, 1H, CHOH), 2.32–2.27 (m, 1H,
CH(CH3)), 1.57 (br, 1H, OH), 1.00 (d, J = 6.8 Hz, 3H CH(CH3). RMN
13C (75 MHz, CDCl3): d 140.1, 136.7, 131.7, 130.1, 128.5, 127.6,
126.5, 116.7, 76.6, 76.1, 53.4, 44.7, 16.0.
2.3.3.11. (3k) 1-(4-Chlorophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.27–7.19 (m, 4H, HAryl), 5.78–5.64 (m, 1H, CH@CH2),
5.13–5.05 (m, 2H, CH@CH2), 4.65 (dd, J = 7.5, 5.4 Hz, CHOH),
2.49–2.32 (m, 2H, CHCH2), 2.04 (br s, 1H, OH); 13C NMR (75 MHz,
CDCl3) d 142.2, 133.9, 131.1, 128.5, 127.2, 118.8, 72.5, 43.8.
2.3.3.12. (3l) 1-(4-Bromophenyl)but-3-en-1-ol. 1H NMR (300 MHz,
CDCl3) d 7.41 (d, J = 8.7 Hz, 2H, HAryl), 7.17 (d, J = 8.7 Hz, 2H, HAryl),
5.78–5.64 (m, 1H, CH@CH2), 5.13–5.06 (m, 2H, CH@CH2), 4.64 (dd,
J = 7.8, 5.4 Hz, CHOH), 2.49–2.32 (m, 2H, CHCH2), 2.00 (br s, 1H,
OH); 13C NMR (75 MHz, CDCl3) d 142.8, 133.9, 131.4, 127.5,
121.2, 118.9, 72.5, 43.8.
3. Results and discussion
In the course of developing the best reaction conditions, ultra-
sound promotion of allylation was first investigated in different
solvents. Thus, cinnamaldehyde, 1a (1 mmol) and potassium allyl-
trifluoroborate, 2 (1.2 mmol) were added to a flask followed by the
appropriate solvent (0.5 mL). The mixture was sonicated for
10 min and the progress of the reaction was monitored by TLC.
The results are presented in Table 1, and all reported yields in this
and other tables are isolated yields.
In all cases, using different solvents the corresponding 1,2-addi-
tion product was obtained exclusively, proving that the reaction is
regioselective. The best result was observed when acetonitrile was
used as solvent, however, due to environmental concerns and the
toxicity of this solvent it was discarded [9]. When dichloromethane
was used as solvent, the corresponding product was obtained in
81% yield (Table 1, entry 2).
The use of water as a (co)-solvent in the development of meth-
ods focusing on environmentally benign reaction media seems to
be the best option due to its simplicity and very low cost. When
a biphasic mixture of dichloromethane and water (1:1) was used
in the reaction, the yield decreased drastically (Table 1, entry 3).
When water was used solely as the reaction solvent, the
corresponding product was obtained in moderate yield (Table 1,
2.3.3.13.
(300 MHz, CDCl3) d 7.84–7.79 (m, 4H, HAryl), 7.48–7.45 (m, 3H,
Aryl), 5.82 (ddt, J = 17.1, 10.2, 7.5 Hz, 1H, CH@CH2), 5.20–5.12
(3m)
1-(Naphthalen-2-yl)but-3-en-1-ol. 1H
NMR
H
(m, 2H, CH@CH2), 4.88 (dd, J = 7.2, 5.1 Hz, 1H, CHOH), 2.56–2.61
(m, 2H, CHCH2), 2.08 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3) d
141.2, 134.3, 133.2, 133.0, 128.1, 127.9, 127.6, 126.0, 125.8,
124.2, 123.9, 118.4, 73.3, 43.6.
2.3.3.14. (3n) 1-Phenyl-but-3-en-1-ol. 1H NMR (300 MHz, CDCl3) d
7.36–7.25 (m, 5H, HAryl), 5.88–5.74 (m, 1H, CH@CH2), 5.19–5.12
(m, 2H, CH@CH2), 4.73 (dd, J = 7.5, 5.4 Hz, 1H, CHOH), 2.53–2.46
(m, 2H, CHCH2), 2.00 (br s, 1H, OH); 13C NMR d (75 MHz, CDCl3)
d 143.8, 134.4, 128.2, 127.3, 125.7, 118.0, 73.2, 43.6.
2.3.3.15. (3o) Non-1-en-4-ol. 1H NMR (300 MHz, CDCl3) d 5.90–5.77
(m, 1H, CH@CH2), 5.17–5.10 (m, 2H, CH@CH2), 3.69–3.50 (m, 1H,
CHOH), 2.35–2.26 (m, 2H, CHCH2), 2.19–2.08 (m, 2H, CHOH) 1.67
(br s, 1H, OH), 1.50–1.25 (m, 6H, CH3CH2CH2CH2), 0.88
Table 1
Effect of the solvent on the allylation of cinnamaldehyde 1a by potassium allyltrifluoroborate 2 at room temperature.
OH
solvent
BF3K
O
+
25oC, 10 min
1a
2
3a
Entry
Solvent
3a (%)
1
2
3
4
5
6
7
8
Acetonitrile
Dichloromethane
Dichloromethane/water (1:1)
Acetone/water (7:3)
Acetone/water (1:1)
Water
92
81
45
82
80
71
68
85
Ethanol
Acetone
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Jucleiton José R. Freitas et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
entry 4). Conversely, the use of a mixture of acetone and water in
different proportions did not increase the yield significantly
(Table 1, entries 5 and 6).
Finally, when ethanol and acetone were used as the reaction
solvent, the corresponding product was obtained in 68% and 85%
yield, respectively, indicating that the use of a polar non-protic sol-
vent could enhance the reaction yield (Table 1, entries 7 and 8).
The optimized reaction conditions, namely: potassium allyltri-
fluoroborate (1.2 mmol), aldehyde (1.0 mmol), acetone (0.5 mL);
were then applied in the allylation reaction of aldehydes
containing different functionalities (Table 2). The method tolerates
a wide range of functional groups and aliphatic, aromatic, and
heterocyclic aldehydes were efficiently allylated in moderate to
high yields. In the absence of ultrasound irradiation, conversion
of cinnamaldehyde 1a into the corresponding alcohol 3a was not
observed after 10 min under the optimized reaction conditions.
From Table 2, it can be seen that several aldehydes containing
electron-withdrawing and electron-donating groups were effi-
ciently allylated under the specified conditions. The allylation of
aldehydes containing electron-withdrawing groups gave the
Table 2
Allylation of various aldehydes 1 by potassium allyltrifluoroborate 2 promoted by ultrasound irradiation.
OH
acetone
BF3K
R
+
O
R
25oC
1
2
3
Product
Time (min.)
10
Yield (%)
85
R
O
1
2
OH
O
1a
3a
OH
5
60
95
O
O
1b
1c
O
3b
OH
3
4
15
O
NO2
NO2
3c
OH
15
96
O
NO2
NO2
1d
3d
5
6
15
30
95
95
OH
O
O2N
1e
O2N
3e
OH
O
OMe
1f
OMe
3f
OH
7
8
30
30
94
96
O
OMe
1g
OMe
MeO
3g
OH
O
MeO
1h
3h
Please cite this article in press as: J.J.R. Freitas et al., Metal free synthesis of homoallylic alcohols promoted by ultrasound, Ultrason. Sonochem. (2014),
http://dx.doi.org/10.1016/j.ultsonch.2014.04.001

Jucleiton José R. Freitas et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
5
Table 2 (continued)
Product
Time (min.)
30
Yield (%)
75
R
O
9
OH
O
F
1i
F
3i
10
11
30
15
75
96
OH
O
F
1j
F
3j
OH
O
Cl
1k
Cl
3k
OH
12
13
15
15
74
95
O
Br
1l
Br
3l
OH
O
1m
3m
OH
14
15
30
30
70
60
O
1n
3n
OH
O
1o
3o
OH
OH
BF3K
+
4
O
Acetone
30 min
5-anti
5-syn
1a
60 %
84:16
Scheme 1. Crotylation of cynnamaldehyde 1a by potassium (E)-crotyltrifluoroborate 4 promoted by ultrasound irradiation.
corresponding products in high yields (Table 2, entries 3–5, 9–12).
In addition, when 2-, 3- and 4-NO2 (Table 2, entries 3–5) were
used, similar yields were observed, indicating that the substituent
position has little influence in the reaction (Table 2, entries 1–3).
Aromatic aldehydes containing electron-donating groups
(Table 2, entries 6–8) also gave the respective homoallylic alcohols
in high yields, however, longer reaction times were required.
Moreover, b-naphtaldehyde (Table 2, entry 13), and benzaldehyde
(Table 2, entry 14) also were allylated in high yields.
[2,3], our method gave similar results using shorter reaction times
without the need of any catalyst under milder reaction conditions.
Finally, the regio- and diastereoselectivity of the reaction were
also studied. Thus, the addition of potassium E-crotyltrifluorobo-
rate, 4 to cinnamaldehyde 1a using the described conditions gave
exclusively the corresponding
(Scheme 1).
c-adduct 5 in a 84:16 ratio (anti:syn)
This result is close to the data described in the literature for the
allylation of cinnamaldehyde using organoboranes [3j].
When a heterocyclic aldehyde was used, the corresponding
addition product was obtained in moderate yield using the
described conditions (Table 2, entry 2). For an aliphatic aldehyde,
the ultrasound promoted allylation with moderate efficiency,
probably due to volatilization losses of the starting material during
the reaction (Table 2, entry 15).
4. Conclusion
In summary, we have demonstrated that ultrasound can effi-
ciently promote the allylation of aldehydes. The green method fea-
tures the use of a small amount of solvent, avoid the preparation of
unstable allyl organometallics and the products were obtained in
Although the available methods for the allylation of aldehydes
gave the corresponding products in good yields in some cases
Please cite this article in press as: J.J.R. Freitas et al., Metal free synthesis of homoallylic alcohols promoted by ultrasound, Ultrason. Sonochem. (2014),
http://dx.doi.org/10.1016/j.ultsonch.2014.04.001

6
Jucleiton José R. Freitas et al. / Ultrasonics Sonochemistry xxx (2014) xxx–xxx
Amberlyst A-15, Tetrahedron 69 (2013) 7006–7010;
short reaction times with moderate to high yields and purity at
room temperature. The methodology is simple, fast and efficient,
and is synthetically useful while it could be applied for the synthe-
sis of more complex compounds.
(b) J.C.R. Freitas, C.K. de Oliveira, E.C. Cunha, I. Malvestiti, S. Alves, R.L.
Longo, et al., Allylation of aldehydes with potassium allyltrifluoroborate
catalyzed by lanthanide-based metal-organic framework, Tetrahedron Lett.
54 (2013) 1558–1561;
(c) J.C.R. Freitas, T.R. Couto, A.a.S. Paulino, J.R. de freitas Filho, I. Malvestiti,
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by TeCl4 under mild conditions, Tetrahedron 68 (2012) 8645–8654;
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of functionalized aldehydes by potassium allyltrifluoroborate catalyzed by
18-crown-6 in aqueous media, Molecules 17 (2012) 14099–14110;
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catalyzed allylation of aldehydes with allylsilanes, Tetrahedron Lett. 50 (2009)
2967–2969;
(f) R.L. Guimarães, D.J.P. Lima, M.E.S.B. Barros, L.N. Cavalcanti, F. Hallwass, M.
Navarro, et al., Aqueous Barbier allylation of aldehydes mediated by tin,
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Acknowledgements
We gratefully acknowledge CNPq (484778/2011-0), FACEPE
(PRONEX APQ-0859-1.06/08), CAPES and inct-INAMI for financial
support. The authors are also thankful to CNPq for their
fellowships.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ultsonch.2014.
04.001.
(h) A. Thadani, R. Batey,
A mild protocol for allylation and highly
diastereoselective syn or anti crotylation of aldehydes in biphasic and
aqueous media utilizing potassium allyl-and crotyltrifluoroborates, Org. Lett.
(2002) 8–11;
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http://dx.doi.org/10.1016/j.ultsonch.2014.04.001