Propargylation of aldehydes using potassium allenyltrifluoroborate

Article abstract of DOI:10.1055/s-0034-1379163

The commercially available resin Amberlyst A-31 was efficiently used to promote the propargylation of aldehydes using potassium allenyltrifluoroborate. The method is simple and fast, and the products were obtained in short reaction times in high yields and purity at room temperature in a regio- and chemoselective manner.

Full text of DOI:10.1055/s-0034-1379163

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2015, 47, 0071–0078
paper
71
T. R. Couto et al.
Paper
Synthesis
Propargylation of Aldehydes Using Potassium Allenyltrifluoroborate
Propargylation of Aldehydes
Túlio R. Coutoa
Jucleiton J. R. Freitasa
Juliano C. R. Freitasb
Italo H. Cavalcantia
Paulo H. Menezesa
Roberta A. Oliveira*a
BF3K
OH
R
O
R
Amberlyst A-31 (200% m/m)
CH2Cl2, 25 °C, 1.5 to 7 h
19 examples
72–95%
R = aryl, heteroaryl, alkyl
a Departamento de Química Fundamental, Universidade Federal
de Pernambuco, 50740-540 Recife-PE, Brazil
roberta.ayres@pq.cnpq.br
b Unidade de Educação e Saúde, Universidade Federal de Campina
Grande, 58175-000 Cuité-PB, Brazil
Received: 28.05.2014
Accepted after revision: 26.08.2014
Published online: 25.09.2014
The use of less reactive compounds such as allenylsil-
anes and allenylstannanes requires Lewis acid as additives.
Although the utility of allenylstannanes is further indicated
by the commercial availability of some of them, the toxicity
of these compounds makes them inappropriate for use in
pharmaceutical synthesis.12 Moreover, the removal of tribu-
tyltin residues from reaction mixtures is also a major issue.
The use of organoboranes is limited to their compatibil-
ity to functional groups and sensitivity to air and moisture.
Conversely, boronic acids are known for their difficulty to
purify and the uncertainty in the stoichiometry.13 This
problem can be circumvented by converting these into their
corresponding boronate esters,14 which is a more stable al-
ternative, but lacks atom economy. In addition, this class of
compounds has low hydrolytic stability, which is depen-
dent on the kind of alcohol used for its preparation.15
The use of potassium organotrifluoroborates seems to
be the best option due to their stability, which also allows
the complete characterization of these salts by heteronuclei
NMR analysis,16 and exact mass measurements.17 Addition-
ally, a marked increase in atom economy,18 stability, and the
apparent low toxicity19 of organotrifluoroborate salts make
them more appealing.
Recently, we have described the use of the commercially
available resin Amberlyst-15 as an efficient promoter for
the allylation of aldehydes using potassium allyltrifluorobo-
rate.20 Herein, we describe the synthesis of homopropargyl-
ic alcohols from the reaction of potassium allenyltrifluo-
roborate and aldehydes containing different functional
groups. To our knowledge, this is the first method for prop-
argylation of aldehydes based on the use of potassium or-
ganotrifluoroborates.
In the course of developing an optimal set of reaction
conditions, the amount of resin and the type of solvent
were first examined to promote the reaction. Thus, 4-nitro-
benzaldehyde (1a; 1 mmol) and potassium allenyltrifluo-
DOI: 10.1055/s-0034-1379163; Art ID: ss-2014-m0329-op
Abstract The commercially available resin Amberlyst A-31 was effi-
ciently used to promote the propargylation of aldehydes using potassi-
um allenyltrifluoroborate. The method is simple and fast, and the prod-
ucts were obtained in short reaction times in high yields and purity at
room temperature in a regio- and chemoselective manner.
Key words propargylation, potassium organotrifluoroborates, Am-
berlyst A-31
The propargylation of carbonyl compounds is an im-
portant reaction in organic synthesis.1 Usually, it involves
the use of an appropriate propargyl or allenyl organometal-
lic compound or the direct propargylic substitution of
propargyl alcohols or their derivatives with nucleophiles.2
The reactions involving the direct addition of an allenyl
or propargyl organometallic reagent to a carbonyl com-
pound usually proceed through an SE2-type mechanism.3
On the other hand, some reactions are based on the in situ
formation of the propargyl or allenyl organometallic spe-
cies, which can interconvert, followed by the subsequent
addition to the appropriate carbonyl compound. In this
case, the regioselectivity of the reaction is usually governed
by the rate of isomerization, stability, and the nucleophilic-
ity of propargyl or allenyl species involved in the reaction.3
The development of propargyl nucleophiles that are
able to form new C–C bonds under mild conditions in a very
regioselective manner is a subject of great interest and a va-
riety of propargyl or allenyl organometallics derived from
zinc,4 titanium,5 aluminum,6 lithium,7 and magnesium,8
were developed for this purpose. In addition, different sili-
con,9 tin,10 and boron derivatives11 were successfully em-
ployed in this reaction.
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72
T. R. Couto et al.
Paper
Synthesis
roborate (2; 1.7 mmol) were treated at room temperature
using Amberlyst A-15 and the progress of the reaction was
monitored by TLC. The results are presented in Table 1.
Table 2 Comparative Efficiency of Various Resins in the Addition of Po-
tassium Allenyltrifluoroborate to 4-Nitrobenzaldehydea
BF3K
OH
Table 1 Effect of Amberlyst A-15 on the Allylation of 4-Nitrobenzalde-
2
hyde by Potassium Allenyltrifluoroboratea
O
resin (200% m/m)
CH2Cl2, 25 °C
O2N
O2N
BF3K
OH
1a
3a
2
O
Entry
Resin (200% m/m)
Time (h)
3a (%)b
Amberlyst A-15
CH2Cl2, 25 °C
O2N
O2N
1
none
24.0
3.0
3.0
3.0
3.0
1.5
3.0
3.0
3.0
3.0
19
90
99
–
1a
3a
2
Amberlyst A-15
Amberlyst A-16
Amberlyst A-21
Amberlyst A-26
Amberlyst A-31
Amberlyst A-35
Amberlyst A-36
Amberlyst A-40
Amberlyst A-41
Entry Amberlyst A-15 (% m/m)
Solvent
Time (h)
3a (%)b
3
4
1
2
3
4
5
6
100
100
100
200
200
200
EtOH
H2O
16.5
16.5
16.5
5.0
33
6
5
–
6
99
99
76
93
85
CH2Cl2
EtOH
H2O
21
20
5
7
8
5.0
9
CH2Cl2
3.0
90
10
a Reaction conditions: reactions were performed with 1a (1 mmol) and 2
(1.7 mmol) in solvent (5 mL) at 25 °C for the time indicated.
b The conversion was determined by GC with respect to 1a.
a Reaction conditions: reactions were performed with 1a (1 mmol) and 2
(1.7 mmol) using the appropriate resin in CH2Cl2 (5 mL) at 25 °C for the
time indicated.
b The conversion was determined by GC with respect to 1a.
When a 100% m/m amount of Amberlyst A-15 was used,
the corresponding low conversions were observed. When
water was used as the reaction solvent, the corresponding
product 3a was obtained in low yield after 16.5 hours (Table
1, entry 2). This result can probably be explained by the low
solubility of aldehyde 1a in water. A similar behavior was
observed when dichloromethane was used as the reaction
solvent (Table 1, entry 3) where the formation of 3a was ob-
served to only 21%, probably due to the low solubility of po-
tassium allenyltrifluoroborate 2 in dichloromethane. When
ethanol was used as the reaction solvent, lower conversion
to 3a was observed together with the acid-catalyzed ketal-
ization product of the aldehyde (Table 1, entry 1).
terestingly, when the basic resins Amberlyst A-21 and A-26,
were used, the corresponding propargylation product 3a
was not observed in either case (Table 2, entries 4 and 5).
The effect of the amount of resin to promote the reac-
tion was also investigated. The load of Amberlyst A-31 was
varied from 50 to 400% m/m (Table 3). It was observed that
the reaction yield changed appreciably when the amount of
the resin varied from 50 to 200% m/m (Table 3, entries 1–3)
after 1.5 hours. However, higher amounts did not change
the reaction yield considerably (Table 3, entry 4).
Table 3 Allylation of 4-Nitrobenzaldehyde by Potassium Allenyltrifluo-
roborate Using Different Amounts of Amberlyst A-31a
A dramatic effect was observed when the amount of the
promoter was increased to 200% m/m. In this case, a higher
conversion of the aldehyde 1a into the product 3a was ob-
served when dichloromethane was used as the reaction sol-
vent (Table 1, entry 6).
Next, we examined a variety of commercially available
resins to promote the propargylation of 4-nitrobenzalde-
hyde (1a; 1.0 equiv) by potassium allenyltrifluoroborate (2;
1.7 equiv) using dichloromethane as the reaction solvent at
room temperature (Table 2).
In the absence of a promoter, the corresponding product
3a was obtained in low yield after 24 hours (Table 2, entry
1). When acidic resins were used, higher conversions of 1a
into the corresponding product 3a were observed (Table 2,
entries 2, 3, 6–10). The best result was obtained when Am-
berlyst A-31 was used as the promoter (Table 2, entry 6). In-
BF3K
OH
2
O
Amberlyst A-31
CH2Cl2, 25 °C, 1.5 h O2N
O2N
1a
3a
Entry
Amberlyst A-31 (% m/m)
3a (%)b
1
2
3
4
50
0
100
200
400
7
99
91
a Reaction conditions: reactions were performed with 1a (1 mmol) and 2
(1.7 mmol) using Amberlyst A-31 (200% m/m) in CH2Cl2 (5 mL) at 25 °C for
1.5 h.
b The conversion was determined by GC with respect to 1a.
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The optimized reaction conditions, namely: potassium
allenyltrifluoroborate 2 (1.7 mmol), aldehyde (1 mmol) and
Amberlyst A-31 (200% m/m) in dichloromethane (5 mL),
were then applied in the propargylation reaction of alde-
hydes containing a wide range of functional groups. Thus,
aliphatic, aromatic, α,β-unsaturated, and heterocyclic alde-
hydes were efficiently propargylated in high yields (Table
4).
Table 4 Propargylation of Aldehydes with Potassium Allenyltrifluoroboratea
BF3K
OH
2
R
O
R
Amberlyst A-31
CH2Cl2, 25 °C
1
3
Entry
1
Aldehyde 1
Product 3
Time (h)
1.5
Yield (%)b
95
OH
OH
O
1a
3a
O2N
O2N
O2N
O2N
O
2
3
1b
1c
3b
3c
3.0
2.5
87
95
NO2
NO2 OH
O
OH
O
4
5
6
1d
1e
1f
3d
3e
3f
5.0
5.0
2.5
78
87
88
F
F
OH
O
Cl
Br
Cl
Br
OH
O
OH
O
7
8
9
1g
1h
1i
3g
3h
3i
3.0
2.0
2.5
79
93
94
MeO
MeO
MeO
MeO
OH
O
OMe
OMe
OH
O
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T. R. Couto et al.
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Synthesis
Table 4 (continued)
Entry
Aldehyde 1
Product 3
Time (h)
7.0
Yield (%)b
72
OH
O
10
1j
3j
OH
O
11
12
1k
1l
3k
3l
2.5
3.0
95
73
OH
O
O
O
OH
O
13
14
1m
1n
3m
3n
7.0
3.0
90
80
OH
O
OH
Br
Br
O
15
16
1o
1p
3o
3p
2.5
2.0
82
85
OMe
OMe
OH
O
MeO2C
MeO2C
OH
OH
O
17
18
19
1q
1r
1s
3q
3r
3s
5.0
2.0
2.0
70
92
94
HO
HO
OMe
OMe
O
NC
NC
OH
O
O
O
a Reaction conditions: reactions were performed with the appropriate aldehyde 1 (1 mmol) and 2 (1.7 mmol) using Amberlyst A-31 (200% m/m) in CH2Cl2 (5 mL)
at 25 °C for the time indicated.
b Isolated yields.
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T. R. Couto et al.
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1H NMR and 13C NMR data were recorded in CDCl3 or DMSO-d6. The
chemical shifts are reported as delta (δ) units in parts per million
(ppm) relative to the solvent residual peak as the internal reference.
11B (128 MHz) NMR spectra were recorded in D2O and 19F (376 MHz)
in DMSO-d6. Spectra were calibrated using Et2O·BF3 (0.0 ppm) as ex-
ternal reference in the case of 11B NMR and chemical shifts were ref-
erenced to external CF3CO2H (0.0 ppm) in the case of 19F NMR spectra.
Coupling constants (J) for all spectra are reported in hertz (Hz). Reac-
tions were monitored by TLC on 0.25 mm E. Merck silica gel 60 plates
(F254) using UV light, vanillin, and p-anisaldehyde as visualizing
agents.
The effect of substituents on the aromatic ring has little
influence in the yield. The propargylation of aldehydes con-
taining electron-withdrawing groups gave the correspond-
ing products in high yields (Table 4, entries 1–6). Electron-
rich aldehydes, β-naphthaldehyde, benzaldehyde, and a
heterocyclic aldehyde led to the homopropargylic alcohols
also in high yields (Table 4, entries 7–12).
The reaction is regioselective while only the 1,2-addi-
tion product was observed when an α,β-unsaturated alde-
hyde was used (Table 4, entry 13). For aliphatic aldehydes,
the propargylation method also exhibited high efficiency
(Table 4, entry 14). The chemoselectivity of the method was
evaluated using different functionalized aldehydes. In all
cases, the corresponding products were selectively ob-
tained in good yields (Table 4, entries 15–19).
The preparation of potassium allenyltrifluoroborate (2) is described
in the Supporting Information.
Propargylation of Aldehydes 1 with Potassium Allenyltrifluorobo-
rate (2) Using Amberlyst A-31; General Procedure
To a solution of the appropriate aldehyde 1 (1.0 mmol) in CH2Cl2 (5
mL) was added Amberlyst A-31 (200% m/m) followed by potassium
allenyltrifluoroborate (2; 248 mg, 1.70 mmol). The mixture was
stirred for the time indicated in Table 4 and then diluted with CH2Cl2
(5 mL) and washed with H2O (2 × 15 mL). The aqueous layer was ex-
tracted with CH2Cl2 (2 × 5 mL). The combined organic layers were
dried (MgSO4), filtered, and the solvent was removed under reduced
pressure to yield 3 without the need for further purification.
The recoverability and recyclability of the resin were
also investigated. Thus, after each run, the catalyst was sep-
arated from the reaction mixture, washed with dichloro-
methane, and reused. It was found that the resin could be
recovered and reused in further propargylation reactions,
however, the conversion of 4-nitrobenzaldehyde 1a into the
propargylation product 3a significantly decreased after the
third run (Table 5).
1-(4-Nitrophenyl)but-3-yn-1-ol (3a)
Table 5 Amberlyst A-31 (200% m/m) Recycling after Successive Runsa
Yield: 183 mg (95%); white solid; mp 116–118 °C.
1H NMR (400 Hz, CDCl3): δ = 8.23 (d, J = 8.4 Hz, 2 Harom), 7.59 (d, J = 8.4
Hz, 2 Harom), 5.00 (dd, J = 7.2, 6.0 Hz, 1 H, OCHCH2), 2.72 (ddd, J = 16.8,
6.0, 2.8 Hz, 1 H, OCHCH2), 2.63 (ddd, J = 16.8, 7.2, 2.8 Hz, 1 H,
OCHCH2), 2.11 (t, J = 2.8 Hz, 1 H, C≡CH), 1.88 (br s, 1 H, OH).
13C NMR (100 Hz, CDCl3): δ = 149.4, 147.6, 126.6, 123.7, 79.3, 72.0,
71.3, 29.5.
BF3K
OH
2
O
Amberlyst A-31
CH2Cl2, 25 °C, 1.5 h O2N
O2N
1a
3a
The spectra were in accordance with the previously reported data.21
Run
Time (h)
3a (%)b
1-(3-Nitrophenyl)but-3-yn-1-ol (3b)
1
2
3
4
5
1.5
3.0
3.0
3.0
3.0
99
87
70
9
Yield: 168 mg (87%); yellow oil.
1H NMR (400 Hz, CDCl3): δ = 8.22 (t, J = 2.0, 1 Harom), 8.09 (ddd, J = 8.0,
2.0, 0.8 Hz, 1 Harom), 7.69–7.67 (m, 1 Harom), 7.48 (t, J = 7.6 Hz, 1 Harom),
4.93 (dd, J = 7.2, 5.6 Hz, 1 H, OCHCH2), 2.64–2.60 (m, 2 H, OCHCH2),
2.08 (br s, 1 H, OH), 2.04 (t, J = 2.8 Hz, 1 H, C≡CH).
13C NMR (100 Hz, CDCl3): δ = 148.3, 144.4, 131.9, 129.4, 122.9, 120.9,
79.4, 72.0, 71.2, 29.5.
0
a Reaction conditions: reactions were performed with 1a (1 mmol) and 2
(1.7 mmol) using Amberlyst A-31 (200% m/m) in CH2Cl2 (5 mL) at 25 °C for
the time indicated.
The spectra were in accordance with the previously reported data.21
b The conversion was determined by GC with respect to 1a.
1-(2-Nitrophenyl)but-3-yn-1-ol (3c)
Yield: 183 mg (95%); yellow oil.
1H NMR (400 Hz, CDCl3): δ = 7.90 (dd, J = 8.0, 1.2 Hz, 1 Harom), 7.82 (dd,
J = 8.0, 1.2 Hz, 1 Harom), 7.61 (t, J = 8.0 Hz, 1 Harom), 7.40 (t, J = 8.0 Hz, 1
In summary, we have shown that the resin Amberlyst A-
31 is an efficient promoter for the propargylation of alde-
hydes using potassium allenyltrifluoroborate. The method
features the use of a commercially available resin, and the
products were obtained in short reaction times in high
yield and purity at room temperature. The method is sim-
ple, fast and efficient and could be applied for the synthesis
of more complex compounds.
H
arom), 5.41 (dd, J = 7.6, 4.8 Hz, 1 H, OCHCH2), 2.86 (ddd, J = 16.4, 4.8,
2.8 Hz, 1 H, OCHCH2), 2.62 (ddd, J = 16.4, 7.6, 2.8 Hz, 1 H, OCHCH2),
2.04 (t, J = 2.8 Hz, 1 H, C≡CH).
13C NMR (100 Hz, CDCl3): δ = 147.8, 137.7, 133.5, 128.6, 128.2, 124.5,
79.7, 71.8, 67.4, 28.5.
The spectra were in accordance with the previously reported data.22
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T. R. Couto et al.
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1-(4-Fluorophenyl)but-3-yn-1-ol (3d)
The spectra were in accordance with the previously reported data.22
Yield: 129 mg (78%); yellow oil.
1-Phenyl-3-butyn-1-ol (3j)
1H NMR (400 Hz, CDCl3): δ = 7.32–7.28 (m, 2 Harom), 7.00–6.96 (m, 2
Yield: 106 mg (72%); colorless oil.
H
arom), 4.80 (t, J = 6.4 Hz, 1 H, OCHCH2), 2.56 (dd, J = 6.4, 2.8 Hz, 2 H,
1H NMR (400 MHz, CDCl3): δ = 7.34–7.24 (m, 5 Harom), 4.82 (t, J = 6.4
Hz, 1 H, OCHCH2), 2.60–2.57 (m, 2 H, OCHCH2), 2.10 (br s, 1 H, OH),
2.01 (t, J = 2.8 Hz, 1 H, C≡CH).
OCHCH2), 2.01 (t, J = 2.8 Hz, 1 H, C≡CH).
13C NMR (100 Hz, CDCl3): δ = 163.6, 138.1, 127.5, 115.4, 80.3, 71.7,
71.2, 29.6.
13C NMR (100 MHz, CDCl3): δ = 142.5, 128.4, 127.9, 125.7, 80.7, 72.0,
The spectra were in accordance with the previously reported data.21
70.7, 29.1.
1-(4-Chlorophenyl)but-3-yn-1-ol (3e)
The spectra were in accordance with the previously reported data.21
Yield: 158 mg (87%); yellow oil.
1-(Naphth-2-yl)but-3-yn-1-ol (3k)
1H NMR (300 Hz, CDCl3): δ = 7.27 (br s, 4 Harom), 4.79 (dd, J = 7.2, 6.0
Hz, 1 H, OCHCH2), 2.57–2.54 (m, 2 H, OCHCH2), 2.08 (br s, 1 H, OH),
2.01 (t, J = 2.8 Hz, 1 H, C≡CH).
Yield: 188 mg (95%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.79–7.75 (m, 4 Harom), 7.44–7.40 (m, 2
13C NMR (75 Hz, CDCl3): δ = 140.8, 133.7, 128.6, 127.2, 80.1, 71.6,
H
arom), 7.29 (s, 1 Harom), 4.98 (t, J = 6.0 Hz, 1 H, OCHCH2), 2.68–2.66 (m,
2 H, OCHCH2), 2.41 (br s, 1 H, OH), 2.01 (t, J = 2.8 Hz, 1 H, C≡CH).
71.3, 29.5.
13C NMR (100 MHz, CDCl3): δ = 139.8, 133.13, 133.09, 128.3, 128.0,
The spectra were in accordance with the previously reported data.21
127.7, 126.2, 126.0, 124.6, 123.7, 80.6, 72.4, 71.1, 29.4.
1-(4-Bromophenyl)but-3-yn-1-ol (3f)
The spectra were in accordance with the previously reported data.21
Yield: 200 mg (88%); yellow oil.
1-(2-Furyl)but-3-yn-1-ol (3l)
1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 8.4 Hz, 2 Harom), 7.21 (d, J =
8.4 Hz, 2 Harom), 4.78 (dd, J = 6.8, 5.6 Hz, 1 H, OCHCH2), 2.56–2.53 (m, 2
H, OCHCH2), 2.01 (t, J = 2.4 Hz, 1 H, C≡CH).
13C NMR (100 MHz, CDCl3): δ = 141.4, 131.6, 127.5, 121.8, 80.1, 71.6,
71.4, 29.4.
Yield: 101 mg (73%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.32 (t, J = 1.2 Hz, 1 Hhet), 6.28 (d, J = 1.2
Hz, 2 Hhet), 4.82 (t, J = 6.0 Hz, 1 H, OCHCH2), 2.71 (dd, J = 6.0, 2.4 Hz, 2
H, OCHCH2), 2.26 (s, 1 H, OH), 2.01 (t, J = 2.4 Hz, 1 H, C≡CH).
13C NMR (75 MHz, CDCl3): δ = 154.6, 142.3, 110.2, 106.6, 79.8, 71.1,
The spectra were in accordance with the previously reported data.22
66.1, 26.1.
1-(4-Methoxyphenyl)but-3-yn-1-ol (3g)
The spectra were in accordance with the previously reported data.21
Yield: 140 mg (79%); yellow oil.
(E)-1-Phenylhex-1-en-5-yn-3-ol (3m)
1H NMR (400 Hz, CDCl3): δ = 7.25 (d, J = 8.4 Hz, 2 Harom), 6.91 (d, J = 8.4
Hz, 2 Harom), 4.77 (t, J = 6.4 Hz, 1 H, OCHCH2), 3.74 (s, 3 H, OCH3), 2.58–
2.55 (m, 2 H, OCHCH2), 2.00 (t, J = 2.8 Hz, 1 H, C≡CH).
13C NMR (100 Hz, CDCl3): δ = 159.3, 134.6, 127.0, 113.8, 80.8, 72.0,
70.9, 55.3, 29.4.
Yield: 156 mg (90%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.33 (d, J = 7.6 Hz, 2 Harom), 7.25 (t, J =
7.6 Hz, 1 Harom), 7.20–7.16 (m, 2 Harom), 6.60 (d, J = 16.0 Hz, 1 H,
CH=CH), 6.21 (dd, J = 16.0, 6.4 Hz, 1 H, CH=CH), 4.43–4.39 (m, 1 H,
OCHCH2), 2.61 (ddd, J = 16.8, 5.6, 2.8 Hz, 1 H, OCHCH2), 2.55 (ddd, J =
16.8, 6.0, 2.4 Hz, 1 H, OCHCH2), 2.02 (t, J = 2.8 Hz, 1 H, C≡CH), 1.89 (br
s, 1 H, OH).
13C NMR (100 MHz, CDCl3): δ = 136.3, 131.4, 129.9, 128.6, 127.9,
126.6, 80.2, 71.1, 70.7, 27.7.
The spectra were in accordance with the previously reported data.21
The spectra were in accordance with the previously reported data.21
1-(3-Methoxyphenyl)but-3-yn-1-ol (3h)
Yield: 165 mg (93%); yellow oil.
1H NMR (400 Hz, CDCl3): δ = 7.23–7.18 (m, 1 Harom), 6.90–6.88 (m, 2
H
arom), 6.79–6.76 (m, 1 Harom), 4.79 (t, J = 6.4 Hz, 1 H, OCHCH2), 3.75 (s,
3 H, OCH3), 2.58–2.56 (m, 2 H, OCHCH2), 2.01 (t, J = 2.8 Hz, 1 H, C≡CH).
13C NMR (100 Hz, CDCl3): δ = 160.0, 144.4, 129.8, 118.3, 113.7, 111.5,
80.9, 72.5, 71.3, 55.5, 29.7.
Dec-1-yn-4-ol (3n)
Yield: 125 mg (80%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 3.80–3.72 (m, 1 H, OCHCH2), 2.43 (ddd,
J = 16.4, 4.8, 3.2 Hz, 1 H, OCHCH2C≡CH), 2.33 (ddd, J = 16.4, 6.4, 3.2 Hz,
1 H, OCHCH2C≡CH), 2.06 (t, J = 3.2 Hz, 1 H, C≡CH), 1.97 (br s, 1 H, OH),
1.59–1,51 (m, 2 H, CH2), 1.37–1.24 (m, 8 H, 4 × CH2), 0.89 (t, J = 6.4 Hz,
3 H, CH3).
13C NMR (75 MHz, CDCl3): δ = 80.9, 70.7, 69.9, 36.2, 31.7, 29.2, 27.3,
25.5, 22.6, 14.0.
The spectra were in accordance with the previously reported data.21
1-(2-Methoxyphenyl)but-3-yn-1-ol (3i)
Yield: 167 mg (94%); colorless oil.
1H NMR (400 MHz, CDCl3): δ = 7.34 (dd, J = 7.6, 1.6 Hz, 1 Harom), 7.23–
7.18 (m, 1 Harom), 6.91 (dd, J = 8.0, 7.2 Hz, 1 Harom), 6.82 (d, J = 8.0 Hz, 1
H
arom), 5.01 (dd, J = 7.6, 4.8 Hz, 1 H, OCHCH2), 3.79 (s, 3 H, OCH3), 2.70
The spectra were in accordance with the previously reported data.23
(ddd, J = 16.8, 4.8, 2,8 Hz, 1 H, OCHCH2), 2.57 (ddd, J = 16.8, 7.6, 2.8 Hz,
1 H, OCHCH2), 1.98 (t, J = 2.8 Hz, 1 H, C≡CH).
13C NMR (100 MHz, CDCl3): δ = 156.5, 130.6, 129.1, 127.1, 121.0,
1-(5-Bromo-2-methoxyphenyl)but-3-yn-1-ol (3o)
Yield: 211 mg (82%); yellow oil.
110.7, 81.6, 70.7, 69.3, 55.6, 27.7.
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77
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Synthesis
1H NMR (400 MHz, CDCl3): δ = 7.48 (d, J = 2.4 Hz, 2 Harom), 7.28 (dd, J =
8.4, 2.4 Hz, 1 Harom), 6.67 (d, J = 8.8 Hz, 1 Harom), 4.98 (dd, J = 7.6, 4.8
Hz, 1 H, OCHCH2), 3.75 (s, 3 H, CH3), 2.67 (ddd, J = 16.8, 7.2, 2.8 Hz, 1
H, OCHCH2), 2.48 (ddd, J = 16.8, 7.6, 2.4 Hz, 1 H, OCHCH2), 2.00 (t, J =
2.8 Hz, 1 H, C≡CH).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379163. Included are additional
experimental procedures and 1H, 13C, 19F, and 11B NMR for all synthe-
sized compounds.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
13C NMR (100 MHz, CDCl3): δ = 155.1, 132.5, 131.25, 129.6, 113.2,
112.0, 80.7, 70.9, 67.7, 55.5, 27.4.
The spectra were in accordance with the previously reported data.24
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1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.8 Hz, 2 Harom), 7.39 (d, J =
8.8 Hz, 2 Harom), 4.86 (t, J = 6.0 Hz, 1 Harom), 3.84 (s, 3 H, CH3), 2.61
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4-(1-Hydroxybut-3-ynyl)-2-methoxyphenol (3q)
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8.0 Hz, 1 Harom), 6.85 (dd, J = 8.4, 1.6 Hz, 1 Harom), 4.81 (t, J = 6.4 Hz, 1 H,
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4-(1-Hydroxybut-3-yn-yl)benzonitrile (3r)
Yield: 160 mg (92%); white solid; mp 120–122 °C.
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8.4 Hz, 2 Harom), 4.86 (t, J = 6.0 Hz, 1 H, OCHCH2), 2.63–2.51 (m, 2 H,
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1-[4-(1-Hydroxybut-3-yn-1-yl)phenyl]ethanone (3s)
Yield: 179 mg (94%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.88 (d, J = 11.2 Hz, 2 Harom), 7.43 (d, J =
11.2 Hz, 2 Harom), 4.87 (dd, J = 8.8, 8.4 Hz, 1 H, OCHCH2), 2.61–2.57 (m,
2 H, OCHCH2), 2.53 (s, 3 H, CH3), 2.47 (br s, 1 H, OH), 2.09 (t, J = 3.0 Hz,
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13C NMR (75 MHz, CDCl3): δ = 197.8, 147.6, 136.7, 128.6, 125.9, 79.9,
71.6, 71.5, 29.4, 26.7.
HRMS (ESI, MeOH–H2O): m/z calcd for C12H12O2 [M – H]+: 187.0765;
found: 187.0748.
Acknowledgment
The authors gratefully acknowledge CNPq (478947/2013-5 and
482299/2013-4), FACEPE (PRONEX APQ-0859-1.06/08), CAPES, and
inct-INAMI for financial support. The authors are also thankful to
CNPq for their fellowships.
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