One-Pot Preparation of (E)-α,β-Unsaturated Aldehydes by a Julia-Kocienski Reaction of 2,2-Dimethoxyethyl PT Sulfone Followed by Acid Hydrolysis

Article abstract of DOI:10.1021/acs.joc.1c00479

(E)-α,β-Unsaturated aldehydes were synthesized by the Julia-Kocienski reaction of 2,2-dimethoxyethyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfone 3 with various aldehydes, followed by acid hydrolysis. The reaction could be carried out in one pot, and various (E)-α,β-unsaturated aldehydes were obtained in a short time and with high yields.

Full text of DOI:10.1021/acs.joc.1c00479

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One-Pot Preparation of (E)‑α,β-Unsaturated Aldehydes by a Julia−
Kocienski Reaction of 2,2-Dimethoxyethyl PT Sulfone Followed by
Acid Hydrolysis
Kaori Ando,* Haruka Watanabe, and Xiaoxian Zhu
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ABSTRACT: (E)-α,β-Unsaturated aldehydes were synthesized by the Julia−
Kocienski reaction of 2,2-dimethoxyethyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfone 3
with various aldehydes, followed by acid hydrolysis. The reaction could be carried
out in one pot, and various (E)-α,β-unsaturated aldehydes were obtained in a short
time and with high yields.
α,β-Unsaturated aldehydes are useful synthetic intermediates,
often used in the syntheses of bioactive compounds and used
as substrates for new reactions.1,2 The preparations of α,β-
unsaturated aldehydes are generally carried out by two-carbon
homologation of aldehydes. For such transformation, the
Wittig or the Horner−Wadsworth−Emmons reaction is
commonly used to synthesize α,β-unsaturated esters, which
are reduced to allyl alcohols and then oxidized to α,β-
unsaturated aldehydes (reaction (a) in Scheme 1).3 More
imine preparation is not always easy, and the other methods
also suffer from the high cost of either reagents or catalysts.
The α-acetal reagents 2b are much more practical to give
mainly (Z)-α,β-unsaturated acetals, which are hydrolyzed with
concomitant isomerization to give (E)-α,β-unsaturated alde-
hydes (c). Unfortunately, acyclic acetal reagents’ preparation is
not straightforward,4a,5a,b and acid-catalyzed hydrolysis of
cyclic acetals generally require more time and stricter
conditions than acyclic acetals.5d,e Also, the separation of the
product alkenes from the byproduct, Ph3PO, is not always
easy. During our study on the stereoselective Julia−Kocienski
reaction,9,10 we prepared dimethyl acetal reagent 3. Here, we
would like to report the results of the Julia−Kocienski reaction
of 3 with a variety of aldehydes followed by acid hydrolysis.
After the treatment of 5-mercapto-1-phenyl-1H-tetrazole
with t-BuOK in DMF, 2-bromo-1,1-dimethoxyethane was
added to give sulfide 4 in 95% yield (Scheme 2). The oxidation
of 4 was carried out with 35% H2O2 and 0.1 equiv of
ammonium molybdate to give 3 in 98% yield.
Scheme 1. Preparation of α,β-Unsaturated Aldehydes
The reaction of 3 with 2-naphthaldehyde 5a was first
examined (Table 1). Since the Julia−Kocienski reaction is
generally more efficient under Barbier conditions, 3 was
treated with a base in the presence of 5a. A DME solution of 3
and 5a was treated with NaHMDS (1.3 equiv) at −55 °C, the
resulting mixture was allowed to warm to 0 °C over 1 h, and
the acetal 6a was obtained in 79% yield with E/Z = 64:36
direct methods have also been developed for this multistep
procedure using formylmethyl reagents such as 2a,4 acetal
reagents such as 2b,5 imine type reagents,6 the Peterson
reaction using silyl imine reagents,7 and others.8 The reagent
2a suffers from either dienal formation or low reactivity,5a and
generally moderate to low yields were obtained (b). These
difficulties can be circumvented with imine reagents. However,
Received: February 26, 2021
Published: April 19, 2021
https://doi.org/10.1021/acs.joc.1c00479
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 6969−6973
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Note
Scheme 2. Preparation of 2,2-Dimethoxyethyl PT Sulfone 3
Scheme 3. Reaction of 3 with Various Aromatic Aldehydes 5
a
Table 1. Reaction of Sulfone 3 with 2-Naphthaldehyde 5a
a
b
5. 0 mmol of 5 was used. 1.5 equiv of 3 and 10 equiv of HCl were
b
entry
base (equiv)
solvent
conditions
yield %
E/Z
used.
1
2
3
4
5
6
NaHMDS (1.3)
LiHMDS (1.3)
KHMDS (1.3)
NaHMDS (1.7)
DME
DME
DME
DME
THF
THF
−55 to 0 °C
−55 to 0 °C
−55 to 0 °C
−55 to 0 °C
rt, 1 h
6a 79
6a 72
6a 58
6a 52
6a 85
1a 94
64:36
92:8
82:18
54:46
63:37
>99:1
moderate 68% yield under the standard conditions (1.2 equiv
of 3 and 20 equiv of HCl), the yield was improved to 88% by
using 1.5 equiv of 3 and 10 equiv of HCl. Thus, the reaction of
3 with various aromatic aldehydes followed by acid hydrolysis
gave 1 in good yields with E/Z > 99:1.
When the same reaction conditions were applied to the
reaction with n-decanal 5j, 73% yield of 1j was obtained (entry
1 in Table 2). Although reducing t-BuOK to 1.5 equiv did not
c
d
t-BuOK (3.0)
t-BuOK (3.0)
c
e
f
rt, 1 h, HCl
a
b
0.30 mmol of 5a was used. Determined by 1H NMR using
PhCO2Me as an internal standard. 1.2 equiv of 3. 10% (E)-1a was
obtained. The reaction mixture was treated with 6 M HCl (aq) and
AcOEt for 0.5 h. Isolated yield.
c
d
e
f
Table 2. Reaction of 3 with n-Decanal 5j
(entry 1). The yield was determined by 1H NMR using methyl
benzoate as an internal standard. Compound 6a was isolated
by flash chromatography in 73% yield with E/Z = 61:39 along
with the aldehyde (E)-1a in 5% yield. When isolated 6a was
treated with aqueous hydrochloric acid in AcOEt, not only
hydrolysis but also Z-to-E isomerization occurred to give the
aldehyde (E)-1a in a quantitative yield. Using either LiHMDS
or KHMDS as a base gave 6a higher E-selectivity but slightly
lower yield than using NaHMDS (entries 2 and 3). Since
hydrolysis of 6a gives (E)-1a highly selectively, the stereo-
selectivity of the olefination reaction is not essential. Since
increasing the quantity of NaHMDS gave a lower yield, more
suitable conditions for the Julia−Kocienski reaction of 3 were
further studied. When a THF solution of 3 and 5a was treated
with 3 equiv of t-BuOK at room temperature11 for 1 h and the
reaction was quenched with aq NH4Cl, 6a was obtained in
85% yield with E/Z = 63:37 along with the aldehyde (E)-1a in
10% yield (entry 5). Sequential one-pot preparation of (E)-1a
is also possible by the Julia−Kocienski reaction of 3 and 5a for
1 h using t-BuOK in THF followed by the treatment with aq
HCl in EtOAc for 0.5 h. This procedure is more convenient
and economical, and α,β-unsaturated aldehyde 1a was isolated
in 94% yield by a 1.5 h reaction time (entry 6). Note that the
yield was 76% without the addition of EtOAc.
entry
x equiv
conditions
1j (%)
3 (%)
5j (%)
1
2
3
4
5
3.0
1.5
3.0
2.0
1.5
rt, 1 h
rt, 1 h
−40 to 0 °C
−40 to 0 °C
−40 to 0 °C
73
50
72
85
89
0
58
0
21
31
5
27
5
5
4
improve the yield, the yield was improved by reducing t-BuOK
and lowering the reaction temperature. Two equivalents of t-
BuOK was added to 3 at −40 °C, and the resulting mixture
was warmed to 0 °C over 1 h to give 1j in 85% yield (entry 4).
The yield was further improved to 89% by reducing t-BuOK to
1.5 equiv (entry 5).
The Julia−Kocienski reaction of 3 with various aliphatic
aldehydes followed by hydrolysis was carried out using method
B (entry 4 or 5 in Table 2) (Scheme 4). The reaction of 3-
phenylpropanal 5k proceeded smoothly to give (E)-1k in 86%,
while α-branched aldehyde 5l gave a moderate 77% yield
under the standard conditions. The yield was improved to 82%
by using 1.5 equiv of 3. Similarly, 1m was obtained in 80%
yield from 5m. When the same procedure was applied for
citronellal 5n, surprisingly, 1n was not obtained at all, and 5n
and 3 did not remain. It seems that a cyclization reaction of 1n
occurred during acid hydrolysis. Without acid hydrolysis, the
corresponding acetal 6n was obtained in 86% yield (E/Z =
60:40), and 9% aldehyde 5n was recovered. Fortunately, 1n
was obtained in 89% with E/Z = 98:2 by the hydrolysis using 5
equiv of HCl at 0 °C. It has been reported that the Wittig
The Julia−Kocienski reaction of 3 with various aromatic
aldehydes followed by subsequent hydrolysis using method A
(entry 6 in Table 1) was carried out (Scheme 3).
Benzaldehyde 5b and p-bromo- and p-fluorobenzaldehyde
5c−5d having electron-withdrawing groups gave 1b−1d in
88−92% yields. The reaction with 5d was also carried out at 5
mmol, and 1d was obtained in 86% yield. The reaction with
5e−5h having electron-donating groups gave 1e−1h in 75−
94% yield. Although the reaction with furfural 5h gave a
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Note
concentrated. Column chromatography (silica gel, hexane/AcOEt
2:1) provided 3 (6.932 g, 98% yield) as a colorless solid: mp 64.0−
65.0 °C (recrystallized from hexane/AcOEt (3:1)); 1H NMR
(CDCl3, 400 MHz) δ 7.58−7.68 (m, 5H), 4.93 (t, 1H, J = 5.5
Hz), 3.82 (d, 2H, J = 5.5 Hz), 3.29 (s, 6H); 13C{1H} NMR (CDCl3,
100 MHz) δ 153.9, 132.9, 131.6, 129.6, 125.7, 98.5, 58.1, 54.2;
HRMS (Fab) m/z [M + Na]+ calcd for C11H14N4O4SNa+ 321.0628,
found 321.0639.
Scheme 4. Reaction of 3 with Various Aliphatic Aldehydes 5
[Typical Experimental Procedure: Method A] (E)-3-(2-
Naphthalenyl)-2-propenal (1a, Entry 6 in Table 1). To a
solution of 3 (0.107 g, 0.36 mmol) and 2-naphtaldehyde 5a (0.047 g,
0.30 mmol) in THF (1.5 mL) under argon was added t-BuOK (0.101
g, 0.90 mmol) at 0 °C, and the mixture was stirring at room
temperature for 1 h. AcOEt (1.5 mL) and 6 M HCl (1 mL) were
added to the reaction mixture at 0 °C, and the mixture was stirred for
30 min at room temperature. The mixture was extracted twice with
AcOEt (10 and 5 mL), and the combined extracts were washed with 2
M NaOH (5 mL), NH4Cl (3 mL), and brine, dried (MgSO4), and
concentrated. Column chromatography (hexane/AcOEt (10:1))
provided (E)-1a (0.051 g, 94%) as a colorless solid: mp 124.0−
125.5 °C8e (recrystallized from hexane/CH2Cl2 (1:5)); 1H NMR
(CDCl3, 400 MHz) δ 9.74 (d, 1H, J = 7.8 Hz), 7.95 (s,1H), 7.81−
7.90 (m, 3H), 7.65 (dd, 1H, J = 1.6, 8.4 Hz), 7.60 (d, 1H, J = 15.6
Hz), 7.50−7.58 (m, 2H), 6.81 (dd, 1H, J = 7.4, 15.6 Hz).8e
(E)-Cinnamaldehyde (1b): Scheme 3, Method A, using 5b (0.030
mL, 0.30 mmol), 88% yield (0.035 g) as a colorless oil by column
chromatography (hexane/AcOEt (8:1)); 1H NMR (CDCl3, 400
MHz) δ 9.71 (d, 1H, J = 7.6 Hz), 7.55−7.60 (m, 2H), 7.49 (d, 1H, J
= 16.0 Hz), 7.42−7.47 (m, 3H), 6.73 (dd, 1H, J = 7.6, 16.0 Hz).13
(E)-3-(4-Bromophenyl)-2-propenal (1c): Scheme 3, Method A,
using 5c (0.056 g, 0.30 mmol), 92% yield (0.058 g) as colorless
needles by column chromatography (hexane/AcOEt (10:1)); mp
a
b
c
1.5 equiv of t-BuOK was used. 1.5 equiv of 3 was used. Hydrolysis
d
was performed using 5 equiv of HCl at 0 °C. The reaction was
e
performed at −20 °C for 1 h. Hydrolysis was performed using 10
equiv of HCl at 0 °C.
reaction of 5n and Ph3PCHCHO yields 1n in only 44%,12
demonstrating the superiority of this method. The reactions of
α,β-unsaturated aldehydes 5o and 5p were carried out at −20
°C to give (E)-alkenes 1o and 1p in 89 and 75% yields.
In summary, one-pot olefination of various aldehydes with
our new reagent, 2,2-dimethoxyethyl 1-phenyl-1H-tetrazol-5-yl
(PT) sulfone 3, and acid hydrolysis of the resulting acetals gave
(E)-α,β-unsaturated aldehydes in good yield with a short
reaction time and a simple operation.
1
80.8−81.8 °C (recrystallized from hexane/CH2Cl2 (3:1)); H NMR
(CDCl3, 400 MHz) δ 9.71 (d, 1H, J = 7.8 Hz), 7.58 (d, 2H, J = 8.2
Hz), 7.40−7.48 (m, 3H), 6.71 (dd, 1H, J = 7.8, 16.0 Hz).8e
(E)-3-(4-Fluorophenyl)-2-propenal (1d, Scheme 3, Method
A). To a solution of 3 (1.790 g, 6.00 mmol) and 4-
fluorobenzaldehyde 5d (0.537 mL, 5.00 mmol) in THF (20 mL)
under argon was added t-BuOK (1.68 g, 15.0 mmol) at 0 °C, and the
mixture was stirring at room temperature for 1 h. AcOEt (20.0 mL)
and 6 M HCl (16.7 mL) were added to the reaction mixture at 0 °C,
and the mixture was stirred for 30 min at room temperature. The
mixture was extracted twice with AcOEt (25 and 15 mL), and the
combined extracts were washed with 2 M NaOH (20 mL), NH4Cl (6
mL), and brine, dried (MgSO4), and concentrated. Column
chromatography (hexane/AcOEt (10:1)) provided (E)-1a (0.645 g,
86%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 9.69 (d, 1H, J
= 7.6 Hz), 7.55−7.60 (m, 2H), 7.45 (d, 1H, J = 16.0 Hz), 7.11−7.17
(m, 2H), 6.65 (dd, 1H, J = 7.6, 16.0 Hz).14
(E)-3-(4-Methoxyphenyl)-2-propenal (1e): Scheme 3, Method
A, using 5e (0.036 mL, 0.30 mmol), 75% yield (0.037 g) as colorless
plates by column chromatography (hexane/AcOEt (4:1)); mp 57.5−
58.0 °C (recrystallized from hexane/CH2Cl2 (1:1)); 1H NMR
(CDCl3, 400 MHz) δ 9.65 (d, 1H, J = 7.8 Hz), 7.52 (d, 2H, J =
8.7 Hz), 7.42 (d, 1H, J = 15.9 Hz), 6.94 (d, 2H, J = 8.7 Hz), 6.61 (dd,
1H, J = 7.8, 15.9 Hz), 3.86 (s, 3H).8c
(E)-3-(2-Methoxyphenyl)-2-propenal (1f): Scheme 3, Method
A, using 5f (0.036 mL, 0.30 mmol), 94% yield (0.046 g) as a colorless
oil by column chromatography (hexane/AcOEt (8:1)); 1H NMR
(CDCl3, 400 MHz) δ 9.69 (d, 1H, J = 7.8 Hz), 7.84 (d, 1H, J = 16.0
Hz), 7.56 (d, 1H, J = 7.8 Hz), 7.42 (dd, 1H, J = 7.3, 8.2 Hz), 7.00 (dd,
1H, J = 7.3, 7.8 Hz), 6.95 (d, 1H, J = 8.2 Hz), 6.80 (dd, 1H, J = 7.8,
16.0 Hz), 3.92 (s, 3H).3e
(E)-3-(2,4-Dimethoxyphenyl)-2-propenal (1g): Scheme 3,
Method A, using 5g (0.050 g, 0.30 mmol), 82% yield (0.047 g) as
a colorless solid by column chromatography (hexane/AcOEt (4:1));
mp 97.0−98.5 °C (recrystallized from hexane/CH2Cl2 (4:1)), 1H
NMR (CDCl3, 400 MHz) δ 9.63 (d, 1H, J = 7.8 Hz), 7.74 (d, 1H, J =
16.0 Hz), 7.50 (d, 1H, J = 8.7 Hz), 6.71 (dd, 1H, J = 7.8, 16.0 Hz),
EXPERIMENTAL SECTION
■
Commercially available reagents were used without purification.
Tetrahydrofuran (THF) and dimethoxyethane (DME) were dried
using 4 Å molecular sieves. Analytical thin-layer chromatography
(TLC) was performed on Merck TLC plates (no. 5715) precoated
with silica gel 60 F254. Column chromatography was carried out
1
using Kanto silica gel 60N (spherical, neutral, 63−210 μm). The H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded
on a JNM-ECS-400 spectrometer (JEOL) in CDCl3. Tetramethylsi-
lane (0.0 ppm) and CDCl3 (77.0 ppm) were used as an internal
standard for 1H NMR and 13C NMR, respectively. H NMR data are
1
reported as follows: chemical shift, multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, dd = doublet of doublets, m =
multiplet), integration, and coupling constants (Hz). High-resolution
mass spectra were recorded on a JMS-MStation 700 mass
spectrometer (double convergence).
Preparation of 2,2-Dimethoxyethyl 1-Phenyl-1H-tetrazol-5-
yl Sulfone (3). A solution of 5-mercapto-1-phenyl-1H-tetrazole
(4.455 g, 25.0 mmol) in DMF (25 mL) under Ar was treated with t-
BuOK (3.086 g, 27.5 mmol) for 10 min at 0 °C, and 2-bromo-1,1-
dimethoxyethane (3.08 mL, 26.3 mmol) was added. The resulting
mixture was heated at 80 °C using an oil bath for 6 h. The reaction
was quenched with NH4Cl (aq), and the mixture was extracted twice
with AcOEt (30 mL × 2). The combined extracts were washed with
H2O (30 mL × 2) and brine, dried (MgSO4), and concentrated.
Column chromatography (silica gel; hexane/AcOEt (2:1)) provided
the sulfide 4 (6.310 g, 95% yield) as a colorless solid: 1H NMR
(CDCl3, 400 MHz) δ 7.52−7.61 (m, 5H), 4.72 (t, 1H, J = 5.5 Hz),
3.60 (d, 2H, J = 5.5 Hz), 3.43 (s, 6H); 13C{1H} NMR (CDCl3, 100
MHz) δ 154.0, 133.4, 130.0, 129.7, 123.7, 102.1, 54.3, 35.1. The
obtained 4 was treated with (NH4)6Mo7O24·H2O (2.925 g, 2.37
mmol) and 34.5% H2O2 (18.2 mL, 207 mmol) in EtOH (20 mL).
After the resulting mixture was stirred at rt for 3 h, aq Na2SO3 was
added slowly at 0 °C. The mixture (pH = 4) was neutralized with
NaHCO3 and extracted twice with AcOEt (20 mL × 2). The
combined extracts were washed with brine, dried with MgSO4, and
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Note
6.55 (dd, 1H, J = 2.3, 8.7 Hz), 6.47 (d, 1H, J = 2.3 Hz), 3.90 (s, 3H),
3.86 (s, 3H).3c
9.2, 15.6 Hz), 6.36−6.24 (m, 2H), 6.08 (dd, 1H, J = 8.2, 15.6 Hz),
2.24−2.19 (m, 2H), 1.53−1.43 (m, 2H), 1.33−1.27 (m, 12H), 0.88
(t, 1H, J = 6.6 Hz).15
(E)-3-(3,4,5-Trimethoxyphenyl)-2-propenal (1h). Scheme 3,
Method A, using 5h (0.059 g, 0.30 mmol), 81% yield (0.054 g) as
colorless needles by column chromatography (hexane/AcOEt (3:1));
mp 110.0−111.0 (recrystallized from hexane/CH2Cl2 (1:1)); 1H
NMR (CDCl3, 400 MHz) δ 9.69 (d, 1H, J = 7.8 Hz), 7.40 (d, 1H, J =
15.6 Hz), 6.80 (s, 2H), 6.65 (dd, 1H, J = 7.8, 15.6 Hz), 3.91 (s, 9H).5e
(E)-3-(2-Furanyl)-2-propenal (1i): Scheme 3, Method A, using 5i
(0.025 mL, 0.30 mmol), 88% yield (0.032 g) as a colorless solid by
column chromatography (hexane/AcOEt (5:1)); mp 49.8−50.2 °C
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00479.
■
sı
1H NMR spectra of 4, 3, and 1a−1p nd 13C NMR
spectra of 3, 4, and 1m (PDF)
1
(recrystallized from hexane/AcOEt (2:1)); H NMR (CDCl3, 400
MHz) δ 9.63 (d, 1H, J = 7.8 Hz), 7.57 (d, 1H, J = 1.8 Hz), 7.22 (d,
1H, J = 15.6 Hz), 6.77 (d, 1H, J = 3.6 Hz), 6.59 (dd, 1H, J = 7.8, 15.6
Hz), 6.54 (dd, 1H, J = 1.8, 3.6 Hz).14
AUTHOR INFORMATION
Corresponding Author
■
[Typical Experimental Procedure: Method B] (E)-2-Dodece-
nal (1j, Entry 5 in Table 2). To a solution of 3 (0.107 g, 0.36 mmol)
and n-decanal 5j (0.056 mL, 0.30 mmol) in THF (1.5 mL) under
argon was added t-BuOK (0.050 g, 0.45 mmol) at −40 °C, and 5 min
later, the mixture was allowed to warm to 0 °C over 1 h. AcOEt (1.5
mL) and 6 M HCl (1 mL) were added to the reaction mixture at 0
°C, and the mixture was stirred for 30 min at room temperature. The
mixture was extracted twice with AcOEt (10 and 5 mL), and the
combined extracts were washed with 2 M NaOH (5 mL), NH4Cl (3
mL), and brine, dried (MgSO4), and concentrated. Column
chromatography (hexane/AcOEt (30:1)) provided (E)-1j (0.049 g,
89%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 9.51 (d, 1H, J
= 8.2 Hz), 6.86 (dt, 1H, J = 16.0, 6.9 Hz), 6.12 (ddt, 1H, J = 8.2, 16.0,
1.4 Hz), 2.30−2.37 (m, 2H), 1.47−1.55 (m, 2H), 1.21−1.38 (m,
12H), 0.88 (t, 3H, J = 6.9 Hz).15
Kaori Ando − Department of Chemistry and Biomolecular
Science, Faculty of Engineering, Gifu University, Gifu 501-
1193, Japan; orcid.org/0000-0001-5345-2754;
Email: ando@gifu-u.ac.jp
Authors
Haruka Watanabe − Department of Chemistry and
Biomolecular Science, Faculty of Engineering, Gifu
University, Gifu 501-1193, Japan
Xiaoxian Zhu − Department of Chemistry and Biomolecular
Science, Faculty of Engineering, Gifu University, Gifu 501-
1193, Japan
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00479
(E)-5-Phenyl-2-pentenal (1k): Scheme 4, Method B, using 5k
(0.040 mL, 0.30 mmol), 86% yield (0.041 g) as a colorless oil by
column chromatography (hexane/AcOEt (8:1)); H NMR (CDCl3,
1
Notes
The authors declare no competing financial interest.
400 MHz) δ 9.49 (d, 1H, J = 7.8 Hz), 7.31 (t, 2H, J = 7.3 Hz), 7.17−
7.25 (m, 3H), 6.86 (dt, 1H, J = 15.6, 6.7 Hz), 6.14 (dd, 1H, J = 7.8,
15.6 Hz), 2.84 (t, 2H, J = 7.6 Hz), 2.64−2.71 (m, 2H).4c
ACKNOWLEDGMENTS
This research was partially supported by the JSPS KAKENHI
grant (17K05781).
■
(E)-3-Cyclohexyl-2-propenal (1l): Scheme 4, Method B, using 3
(0.134 g, 0.45 mmol) and 5l (0.036 mL, 0.30 mmol), 82% yield
(0.034 g) as a colorless oil by column chromatography (hexane/
1
AcOEt (20:1)); H NMR (CDCl3, 400 MHz) δ 9.50 (d, 1H, J = 7.8
REFERENCES
■
Hz), 6.78 (dd, 1H, J = 6.4, 15.6 Hz), 6.07 (ddd, 1H, J = 1.4, 7.8, 15.6
Hz), 2.23−2.33 (m, 1H), 1.75−1.86 (m, 4H), 1.67−1.75 (m, 1H),
1.13−1.40 (m, 5H).3a
(1) For a review, see: Wang, Z. Advances in the Asymmetric Total
Synthesis of Natural Products Using Chiral Secondary Amine
Catalyzed Reaction of nnn-Unsaturated Aldehydes. Molecules 2019,
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(E)-4-Ethyl-2-octenal (1m): Scheme 4, Method B, using 5m
(0.047 mL, 0.30 mmol), 80% yield (0.037 g) as a pale yellow oil by
column chromatography (hexane/AcOEt (20:1)); 1H NMR (CDCl3,
400 MHz) δ 9.52 (d, 1H, J = 7.8 Hz), 6.62 (dd, 1H, J = 9.2, 15.6 Hz),
6.09 (dd, 1H, J = 7.8, 15.6 Hz), 2.16−2.26 (m, 1H), 1.20−1.60 (m,
8H), 0.89 (t, 3H, J = 7.3 Hz), 0.88 (t, 3H, J = 7.3 Hz); 13C{1H} NMR
(CDCl3, 100 MHz) δ 194.2, 163.3, 132.9, 44.7, 33.6, 29.3, 27.1, 22.7,
13.9, 11.6; HRMS (DART) m/z [M + H]+ calcd for C10H19O+
155.1430, found 155.1429.
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using 5n (0.054 mL, 0.30 mmol), 87% yield (0.047 g) as a colorless
1
oil by column chromatography (hexane/AcOEt (20:1)); H NMR
(CDCl3, 400 MHz) δ 9.51 (d, 1H, J = 7.8 Hz), 6.83 (dt, 1H, J = 15.6,
7.8 Hz), 6.12 (dd, 1H, J = 7.8, 15.6 Hz), 5.05−5.11 (m, 1H), 2.31−
2.41 (m, 1H), 2.14−2.23 (m, 1H), 1.92−2.09 (m, 2H), 1.67−1.76
(m, 1H), 1.69 (s, 3H), 1.60 (s, 3H), 1.33−1.43 (m, 1H), 1.19−1.29
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(2E,4E)-5-Phenyl-2,4-pentadienal (1o): Scheme 4, Method B,
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oil by column chromatography (hexane/AcOEt (5:1)); 1H NMR
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7.34−7.41 (m, 3H), 7.27 (ddd, 1H, J = 2.7, 7.3, 15.1 Hz), 6.96−7.06
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(2E,4E)-2,4-Tetradecadienal (1p): Scheme 4, Method B, using
(E)-1j (0.055 g, 0.30 mmol), 75% yield (0.047 g) as a pale yellow oil
by column chromatography (hexane/AcOEt (20:1)); 1H NMR
(CDCl3, 400 MHz) δ 9.54 (d, 1H, J = 8.2 Hz), 7.08 (dd, 2H, J =
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