Catalytic enantioselective synthesis of optically active α-hydroxyl-β,γ-unsaturated acid esters as novel side chains of cerebrosides

Article abstract of DOI:10.1016/j.tetasy.2013.01.007

Six optically active α-hydroxyl-β,γ-unsaturated acid esters 1a to 1f were synthesised, and they are significant moieties of the cerebrosides. The chiral intermediate alkynol 4 prepared by catalytic asymmetric addition had 99% ee, and which was converted i

Full text of DOI:10.1016/j.tetasy.2013.01.007

Tetrahedron: Asymmetry 24 (2013) 173–177
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Catalytic enantioselective synthesis of optically active
a-hydroxyl-b,
c-unsaturated acid esters as novel side chains of cerebrosides
⇑
⇑
Lei Wang, Ruiquan Liu, Cong Lv, Junjun Ou, Feng Liu, Shangzhong Liu , Min Wang, Jiangchun Zhong
Department of Applied Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing 100193, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 November 2012
Accepted 10 January 2013
Six optically active
a
-hydroxyl-b,
c
-unsaturated acid esters 1a to 1f were synthesised, and they are signif-
icant moieties of the cerebrosides. The chiral intermediate alkynol 4 prepared by catalytic asymmetric
addition had 99% ee, and which was converted into the target compounds 1a to 1f with high enantio-
meric purity.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
auxiliary.7 (R,E)-2-Hydroxyoctadec-3-enoic acid has been synthes-
ised by the sharpless asymmetric epoxidation of (E)-2-octadecen-
Cerebroside, a molecule containing a ceramide fragment and
one or more sugar units, has been isolated from various marine
invertebrates, such as sea stars, soft corals, sponges, sea anemones
and ascidians. Several studies have shown that most cerebrosides
possess unique antifungal, antitumor, antiviral and immunomodu-
1-ol in the presence of L-(+)-diethyl tartarate as a chiral auxiliary,
followed by ring cleavage and oxidation.8 Lipase PS-catalysed ki-
netic resolution has been employed to obtain the desired com-
pounds after Mg(ClO4)2-mediated isomerisation of an epoxide.9
Racemic
a-hydroxyl-b,c-unsaturated carboxylic acid has been
latory activities.1 Chiral
a
-hydroxyl-b,c-unsaturated carboxylic
synthesised using the Jocic reaction for the treatment of trichloro-
acids are some of the main fragments of many cerebrosides, such
methyl carbinols.10
as sarcoehrenosides,2 chrysogesides3 and symbioramides4 (Fig. 1).
In our previous study, terminal alkynes were added asymmetri-
cally to aldehydes.11 In the present study, the same approach was
Optically active a-hydroxyl-b,c-unsaturated acid esters are ver-
satile building blocks in organic synthesis. Their existing functional
groups, including hydroxyls, double bonds and esters, can be easily
converted into other groups. Thus, they have great potential in
synthesising useful chiral molecules, especially the cerebrosides.
Several studies have focused on the unique structures of
chrysogesides A to E (Fig. 1) and their special biological activities.
used to develop a concise method to prepare
a-hydroxyl-b,
c-unsaturated acid esters (Scheme 1). The stereogenic centre was
obtained through the enantioselective addition of trimethylsilyl-
acetylene to acrolein followed by double-bond oxidation and a
reduction reaction to obtain the target structure. The methodology
developed is easy to conduct and effectively synthesises various
However, only a few studies have prepared optically active
hydroxyl-b, -unsaturated acid esters. Optically active -hydroxyl-
b, -unsaturated acid esters have been prepared using two main
a
-
a-hydroxyl-b,c-unsaturated acid esters with the desired configura-
tions and high enantiomeric purity.
c
a
c
strategies. The first involves building a stereogenic centre through
chemical reactions in the presence of a chiral auxiliary and the sec-
ond involves biocatalytic reactions in the presence of enzymes. (R)-
2-Hydroxy-3-enoic acid was first synthesised from the biocatalytic
reduction of the corresponding 2-oxo acids with Proteus vulgaris.5
2. Results and discussion
Six a-hydroxyl-b,c-unsaturated carboxylic esters 1a to 1f were
synthesised according to the pathway outlined in Scheme 1. The
chiral alkynol 3 was synthesised from the enantioselective alkyny-
lation of aldehyde 2 in the presence of a BINOL-Ti system as an
asymmetric catalyst to produce 82% yield and 93% ee.12 To readily
obtain a highly enantiomerically pure product, a reliable method
was established to increase the enantiomeric purity of the result-
ing alkynols as follows: alkynol 3 was esterified with 3,5-dinitro-
benzoyl chloride and recrystallised in hexane/dichloromethane
(12/1, v/v), which increased the ee value of 4 to 99%. Acetylenic
alcohol 5 was obtained by treating 4 with excess anhydrous potas-
sium carbonate in methanol at room temperature. The recrystalli-
sation and detrimethylsilylation of 4 were conducted with 60%
a
-Hydroxyl-b,
alytic enantioselective reduction of an
dehydrogenase.6
-Hydroxyl-b, -unsaturated esters have been
synthesised by reducing b, -unsaturated
c
-unsaturated acid has been synthesised by the cat-
a
-keto acid using lactate
a
c
c
a
-oxo esters using (ꢀ)-
8-phenylmenthol or (ꢀ)-trans-2-phenylcyclohexanol as a chiral
⇑
Corresponding authors. Tel./fax: +86 010 62731070 (S.L.); tel.: +86 010
62731356; fax: +86 010 62820325 (J.Z.).
E-mail addresses: shangzho@cau.edu.cn (S. Liu), dr_zhongjiangchun@yahoo.
com.cn (J. Zhong).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.01.007

174
L. Wang et al. / Tetrahedron: Asymmetry 24 (2013) 173–177
HO
HO
HO
HO
HO
HO
O
O
NH
O
O
NH
O
O
HO
HO
n
OH
OH
OH
OH
Chrysogeside A
Chrysogeside A n = 3, 4, 6
OH
O
HO
O
HN
OH
HO
HO
OH
O
NH
O
HO
OH
OH
Symbioramide A
Sarciehrenosides A
Figure 1. Cerebrosides with novel carboxylic acid side chains.
O2N
NO2
OH
OH
OHC
b
a
c
O
O
TMS
2
3
5
93% ee
99% ee
TMS
4
OH
OAc
OAc
d
f,g
h
e
COOMe
R
R
R
7
8
6
OAc
R
COOMe
a
c
e
b
: R = n-C10H21 : R = n-C11H23
d
: R = n-C12H25 : R = n-C13H27
f
: R = n-C14H29 : R = n-C15H31
1
Scheme 1. Reagents and conditions: (a) (i) Trimethylsilylacetylene, ZnEt2, toluene, 100 °C; (ii) (S)-BiNOL, titanium(IV) isopropoxide, Et2O, rt; (b) 3,5-dinitrobenzoyl chloride,
Et3N, CH2Cl2, 0 °C, rt, then recrystallisation from hexane/dichloromethane; (c) K2CO3, MeOH, rt; (d) HMPA, n-BuLi, BrR (R = n-C10H21, n-C11H23, n-C12H25, n-C13H27, n-C14H29, n-
C
15H31), THF, ꢀ78 °C, ꢀ30 °C, rt; (e) Ac2O, Et3N, CH2Cl2; (f) RuCl3ꢁ3H2O, NaIO4, CH3CN/CCl4/H2O (1:1:1.5), rt; (g) CH2N2, Et2O, rt; (h) (i) EtOSiMe2H, [Cp⁄Ru(MeCN)3]PF6, CH2Cl2,
0 °C; (ii) CuI, TBAF, THF, 0 °C, rt.
total yield.11b Compound 5 was subsequently reacted with an alkyl
bromide in the presence of excess n-BuLi and 6.0 equiv of hexam-
ethylphosphoramide (HMPA) in tetrahydrofuran (THF) at ꢀ78 °C to
generate the corresponding long-chain alkynol 6 with 51% to 60%
yield.13 The hydroxyl group of 6 was protected with acetic anhy-
dride to obtain 7 with 90% to 95% yield. We initially failed to oxi-
dise the double bond of 7 with RuCl3–NaIO4 in various solvent
systems, such as dichloromethane (DCM)/water, AcOEt/CH3CN/
H2O and CCl4/H2O.14 However, when the amount of oxidant was
decreased from 10 to 2.5 equiv and the reaction was conducted
at room temperature, compound 7 was smoothly oxidised to the
observed.15 An (EtO)3SiH was conducted catalytically with
[Cp⁄Ru(MeCN)3]PF6, which yielded the desired (E)-allylic ester
but with low yield (20%).16 When (EtO)3SiH was replaced with EtO-
SiMe2H and increasing quantities of the ruthenium catalyst, the
hydrosilylation intermediate was converted effectively. Finally,
desilylation was conducted in THF at ꢀ30 °C in the presence of
3.5 equiv tetra-n-butylammonium fluoride (TBAF) and 20 mol %
of CuI as a catalyst to produce (E)-allylic ester 1 in 70% to 80% yield.
3. Conclusion
desired molecules. Compound
7 in mixed solvents of CCl4/
In conclusion, we have developed a new catalytic asymmetric
CH3CN/H2O was treated sequentially with 2.5 equiv of sodium per-
iodate and 5 mol % of RuCl3ꢁ3H2O at 0–5 °C and esterified with
diazomethane to produce ester 8 with 30% to 55% yield. To convert
the alkynyl group into a trans-double bond, Red-Al was first
employed as a reducing agent. However, product 8 was not
addition method for synthesising enantiomerically enriched
a-hy-
droxyl-b, -unsaturated acid esters, which are the key side chains
c
of natural product cerebrosides. Six compounds 1a–1f were ob-
tained with high enantiomeric purity.

L. Wang et al. / Tetrahedron: Asymmetry 24 (2013) 173–177
175
alcohol/hexane = 2:98, v/v, flow rate: 1.0 mL/min, detection wave-
length 254 nm, retention time: tmajor = 6.54 min, tminor = 7.13 min.)
4. Experimental
4.1. General
4.4. (S)-Pent-1-en-4-yn-3-ol 5
All reactions were conducted under a dry nitrogen atmosphere.
Diethylzinc (1.5 M solution in toluene) was purchased from Acros.
Toluene and DCM were distilled after drying with calcium hydride
under nitrogen, and diethyl easer and THF were distilled after dry-
ing with lithium aluminium hydride. Unless otherwise stated, all
reagents were commercially available and used without purifica-
tion. Nuclear magnetic resonance (NMR) spectra were recorded
by a 300 MHz NMR instrument. Mass spectra were recorded on
an Agilent instrument using a time-of-flight mass spectrometer.
Enantiomeric excesses (ee) were determined by chiral high-perfor-
mance liquid chromatography (HPLC) analyses using Daicel chiral
columns (AD-H, Lux Cellulose-2). Optical rotations were deter-
mined on a Perkin Elmer 341 Polarimeter.
Potassium carbonate (60.0 g, 434 mmol) was added to a solu-
tion of (S)-1-(trimethylsilyl)pent-4-en-1-yn-3-yl 3,5-dinitrobenzo-
ate (36.0 g, 108 mmol) in 300 mL of methanol at room
temperature. The mixture was then stirred at room temperature
for 3.5 h, treated with 600 mL of cold aqueous saturated solution
of ammonium chloride and extracted with ether (200 mL ꢂ 3).
The organic layer was washed with brine, dried over anhydrous so-
dium sulfate and concentrated under atmospheric pressure. The
residue was distilled and 8.0 g of (S)-pent-1-en-4-yn-3-ol as a col-
ourless oil at 27–33 °C/20 mmHg was collected in 96% yield. 1H
NMR (300 MHz, CDCl3) d: 6.04–5.94 (m, 1H), 5.53–5.48 (dt, 1H,
J = 17, 1.4 Hz), 5.28–5.24 (dt, 1H, J = 10, 1.2 Hz), 4.92–4.87 (m,
1H), 2.59–2.58 (d, 1H, J = 2.2 Hz), 1.99–1.97 (m, 1H).
4.2. (S)-5-(Trimethylsilyl)pent-1-en-4-yn-3-ol 3
4.5. (S)-Pentadec-1-en-4-yn-3-ol 6a
Diethylzinc (16.0 mL, 24.0 mmol, 1.5 M in toluene) was added
(S)-1-Penten-4-yn-3-ol l (2.46 g, 2.5 mL, 30 mmol) and HMPA
(32.6 g, 31.8 mL, 180 mmol) were dissolved in 80 mL of THF and
cooled to ꢀ78 °C under a nitrogen atmosphere. n-BuLi (2.40 M in
hexanes, 26.25 mL, 63 mmol) was then added dropwise to the mix-
ture. The resulting heterogeneous solution was stirred for 3 h at
ꢀ30 °C. A solution of 1-bromodecane (6.7 g, 6.27 mL, 30.0 mmol)
in 10 mL of THF was then added dropwise to the solution, and
the reaction mixture was stirred for 48 h at room temperature.
After quenching with 40 mL of aqueous saturated ammonium
chloride, the reaction solution was extracted with ether
(50 mL ꢂ 3). The combined organic extracts were washed with
brine, dried over sodium sulfate, filtered and evaporated in vacuo.
The residue was then purified by flash chromatography (hexanes/
ether, 15:1, v/v) to produce 4.11 g of (S)-pent-1-en-4-yn-3-ol as a
dropwise to
a solution of trimethylsilylacetylene (3.31 mL,
24.0 mmol) in 12 mL of toluene at room temperature under a
nitrogen atmosphere. The mixture was then heated to 100 °C, kept
for 1 h and cooled to room temperature. A solution of acrolein
(0.4 mL, 6.0 mmol) was also added dropwise to the mixture. One
hour after the addition of 100 mL of diethyl ether, 1.8 mL of tita-
nium(IV) isopropoxide and 0.68 g of (S)-binaphthol were added
sequentially. The reaction mixture was then stirred for 18 h and
treated with 20 mL of aqueous saturated ammonium chloride.
The resulting mixture was extracted with ether (20 mL ꢂ 3). The
organic layer was washed with brine, dried over anhydrous sodium
sulfate and then concentrated and purified by flash column chro-
matography to produce 0.73 g of (S)-5-(trimethylsilyl)pent-1-en-
4-yn-3-ol as a colourless oil in 80% yield. ½a D20
¼ þ36:2 (c 1.30,
ꢃ
yellow oil in 60.5% yield. ½a D20
ꢃ
¼ þ261:8 (c 0.5, CH2Cl2). 1H NMR
CH2Cl2), 1H NMR (300 MHz, CDCl3) d: 6.02–5.91 (m, 1H), 5.50–
5.44 (dt, 1H, J = 17, 1.4 Hz), 5.25–5.21 (dt, 1H, J = 10, 1.2 Hz),
4.89–4.85 (m, 1H), 1.95–1.93 (d, 1H), 0.19 (s, 9H). HRMS (TOF):
calcd for C8H14NaOSi, m/z [M+Na]+: 177.0712, found: 177.0708.
HPLC: 93% ee. (Determined by chiral HPLC with column AD-H,
chromatographic condition: isopropyl alcohol/hexane = 2:98, v/v,
flow rate: 1.0 mL/min, detection wavelength 210 nm, retention
time: tmajor = 7.35 min, tminor = 7.67 min.)
(300 MHz, CDCl3) d: 6.03–5.92 (m, 1H), 5.47–5.41 (dt, 1H, J = 17,
1.4 Hz), 5.21–5.18 (dt, 1H, J = 10, 1.3 Hz), 4.87–4.85 (m, 1H),
2.26–2.20 (m, 2H), 1.80 (m, 1H), 1.56–1.47 (m, 2H), 1.32–1.26
(m, 14H), 0.88 (t, 3H, J = 6.5 Hz). HRMS (TOF): calcd for C15H25O,
[Mꢀ1]ꢀ: 221.1905 found: 221.1888.
4.6. (S)-Pentadec-1-en-4-yn-3-yl acetate 7a
Triethylamine (2.7 mL, 19.5 mmol) and acetic anhydride
(1.48 mL, 15.6 mmol) were added sequentially into a solution of
(S)-pent-1-en-4-yn-3-ol (2.9 g, 13 mmol) in 50 mL of DCM at 0 °C
under a nitrogen atmosphere. The mixture was then stirred for
4 h at room temperature and poured into 50 mL of cold water.
The aqueous layer was extracted with DCM (50 mL ꢂ 2), and the
combined organic phase was washed with 50 mL of brine, dried
over sodium sulfate and filtered. The solvent was then removed
by rotary evaporation to produce a crude product, which was puri-
fied by column chromatography (silica gel, hexane/EtOAc, 19/1 to
4.3. (S)-1-(Trimethylsilyl)pent-4-en-1-yn-3-yl 3,5-dinitrobenzo-
ate 4
Triethylamine (28.0 mL, 200 mmol) and 3,5-dinitrobenzoyl
chloride (37.3 g, 160 mmol) in 100 mL of DCM were added sequen-
tially into a solution of (S)-5-(trimethylsilyl)pent-1-en-4-yn-3-ol
(20.1 g, 135 mmol) in 200 mL of DCM at 0 °C under a nitrogen
atmosphere. The mixture was then stirred for 4 h at room temper-
ature and poured into 200 mL of cold water. The aqueous layer was
extracted with DCM (50 mL ꢂ 2) and the organic layers were com-
bined. After washing with 100 mL of brine, drying over anhydrous
sodium sulfate and filtering, the solution was concentrated and
purified by flash column chromatography to produce 36.9 g of
(S)-1-(trimethylsilyl)pent-4-en-1-yn-3-yl 3,5-dinitrobenzoate as a
white solid in 92% yield and 99% ee mp 99.5–100 °C,
9/1, v/v) to produce 6a as
a colourless oil in 95% yield.
½
a 2D0
ꢃ
¼ ꢀ53:4 (c 0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3) d: 5.95–
5.84 (m, 2H), 5.57–5.49 (m, 1H), 5.31–5.28 (m, 1H), 2.27–2.21
(m, 2H), 2.10 (s, 3H), 1.57–1.48 (m, 2H), 1.39–1.26 (m, 14H), 0.88
(t, 3H, J = 6.3 Hz). HRMS (TOF): calcd for C17H28NaO2, [M+Na]+:
287.1987, found, 287.2029.
½
a 2D0
ꢃ
¼ þ49:4 (c 1.30, CH2Cl2), 1H NMR (300 MHz, CDCl3) d: 9.25–
9.24 (m, 1H), 9.206–9.200 (m, 2H), 6.21–6.19 (m, 1H), 6.09–5.98
4.7. (R)-Methyl 2-acetoxytetradec-3-ynoate 8a
(m, 1H), 5.74–5.68 (dt, 1H, J = 16.8, 1 Hz), 5.49–5.45 (m, 1H), 0.21
(s, 9H). HRMS (TOF): calcd for
C
15H17N2O6, m/z [M+H]+:
To a solution of (S)-pentadec-1-en-4-yn-3-yl acetate (1.48 g,
5.6 mmol) and sodium periodate (4.8 g, 22.5 mmol) in tetrachloro-
methane (20 mL), acetonitrile (20 mL) and water (30 mL) was
349.0856, found: 349.0843. HPLC: 99% ee. (Determined by chiral
HPLC with column AD-H, chromatographic condition: isopropyl

176
L. Wang et al. / Tetrahedron: Asymmetry 24 (2013) 173–177
added RuCl3ꢁ3H2O (68.5 mg, 0.28 mmol). The resulting mixture
was then stirred vigorously for 8 h at room temperature. After
addition of 100 mL of water to the mixture, the aqueous phase
was extracted with DCM (50 mL ꢂ 2). The organic phase was dried
with sodium sulfate and evaporated under reduced pressure. The
crude mixture was then treated with CH2N2 for 2 h at room tem-
perature and evaporated under reduced pressure. The residue
was purified by flash chromatography (hexane/Et2O = 15/1, v/v)
to produce 0.51 g of (R)-methyl 2-acetoxytetradec-3-ynoate in
d: 170.15, 169.61, 138.25, 121.66, 73.31, 52.42, 32.28, 31.91,
29.68, 29.66, 29.63, 29.57, 29.41, 29.34, 29.11, 28.57, 22.67,
20.69, 14.08. HRMS (TOF): calcd for
344.280, found: 344.2856.
C
19H38NO4, [M+NH4]+:
4.11. Characterisation of (R,E)-methyl 2-acetoxyheptadec-3-
enoate 1d
Colourless oil, 80% yield, ½a D20
ꢃ
¼ þ37 (c 0.5, CH2Cl2). 1H NMR
30% yield. ½a 2D0
ꢃ
¼ þ63:2 (c 0.5, CH2Cl2). 1H NMR (300 MHz, CDCl3)
(300 MHz, CDCl3) d: 5.97–5.89 (m, 1H), 5.58–5.49 (m, 1H), 5.40–
5.38 (m, 1H), 3.75 (s, 3H), 2.15 (s, 3H), 2.11–2.04 (m, 2H), 1.41–
1.36 (m, 2H), 1.32–1.26 (m, 20H), 0.88 (t, 3H, J = 6.5 Hz). 13C NMR
(75 MHz, CDCl3) d: 170.14, 169.60, 138.25, 121.64, 73.31, 52.42,
32.28, 31.91, 29.67, 29.66, 29.64, 29.56, 29.41, 29.34, 29.10,
28.57, 22.67, 20.70, 14.09. HRMS (TOF): calcd for C20H40NO4,
[M+NH4]+: 358.2957, found: 358.3020.
d: 5.69–5.68 (m, 1H), 3.82 (s, 3H), 2.30–2.21 (m, 2H), 2.18 (s, 3H),
1.55–1.48 (m, 2H), 1.39–1.26 (m, 14H), 0.88 (t, 3H, J = 6.2 Hz).
HRMS (TOF): calcd for C17H32NO4, [M+NH4]+: 314.2331, found,
314.2369.
4.8. (R,E)-Methyl 2-acetoxytetradec-3-enoate 1a
Catalyst [Cp⁄Ru(MeCN)3]PF6 (15.4 mg, 0.03 mmol, 3 mol %) was
added to a solution of (R)-methyl 2-acetoxytetradec-3-ynoate
(312 mg, 1.0 mmol) and ethoxydimethylsilane (207.0 mg,
1.98 mmol) in 3 mL of DCM at 0 °C. The ice-bath was then removed
and the reaction mixture was stirred for 15 min at room tempera-
ture. After completion of the reaction, the reaction mixture was fil-
tered over a short plug of florisil and concentrated in vacuo. The
crude product was collected as yellow oil and used for the next
step of the experiment without further purification. A solution of
TBAF (1.0 M in THF, 3.0 mL, 3.0 mmol) was added dropwise at
4.12. Characterisation of (R,E)-methyl 2-acetoxyoctadec-3-
enoate 1e
Colourless oil, 69% yield, ½a D20
ꢃ
¼ þ64:5 (c 0.5, CH2Cl2). 1H NMR
(300 MHz, CDCl3) d: 5.97–5.92 (m, 1H), 5.57–5.50 (m, 1H), 5.40–
5.38 (m, 1H), 3.75 (s, 3H), 2.15 (s, 3H), 2.11–2.04 (m, 2H), 1.41–
1.36 (m, 2H), 1.32–1.26 (m, 22H), 0.88 (t, 3H, J = 6.4 Hz). 13C
NMR (75 MHz, CDCl3) d: 170.14, 169.60, 138.25, 121.65, 73.31,
52.42, 32.28, 31.91, 29.68, 29.67, 29.66, 29.64, 29.56, 29.41,
29.34, 29.10, 28.57, 22.67, 20.69, 14.09 HRMS (TOF): calcd for
0 °C to
a
solution of the crude product and CuI (38.0 mg,
C
21H42NO4, [M+NH4]+: 372.3114, found: 372.3170.
0.20 mmol, 20 mol %) in 5 mL of dry THF and stirred for 24 h at
the same temperature. The reaction was then quenched by the
addition of 5 mL of aqueous saturated ammonium chloride. The
resulting solution was extracted with diethyl ether (30 mL ꢂ 2).
The combined organic phase was dried over sodium sulfate and
the solvent was removed in vacuo. The residue was then purified
by flash chromatography (hexanes/Et2O = 20/1, v/v) to produce
4.13. Characterisation of (R,E)-methyl 2-acetoxynonadec-3-
enoate 1f
Colourless oil, 70% yield, ½a D20
ꢃ
¼ þ88:2 (c 0.5, CH2Cl2). 1H NMR
(300 MHz, CDCl3) d: 5.96–5.91 (m, 1H), 5.57–5.50 (m, 1H), 5.40–
5.38 (m, 1H), 3.75 (s, 3H), 2.14 (s, 3H), 2.11–2.04 (m, 2H), 1.41–
1.37 (m, 2H), 1.33–1.26 (m, 24H), 0.88 (t, 3H, J = 6.5 Hz). 13C
NMR (75 MHz, CDCl3) d: 170.12, 169.58, 138.22, 121.62, 73.30,
52.40, 32.26, 31.90, 29.67, 29.63, 29.55, 29.39, 29.33, 29.09,
28.54, 22.66, 20.67, 14.07. HRMS (TOF): calcd for C22H44NO4,
[M+NH4]+: 386.3270, found: 386.3332.
(R,E)-methyl 2-acetoxytetradec-3-enoate as
a colourless oil
(218.4 mg, 70%). ½a D20
ꢃ
¼ þ30 (c 0.5, CH2Cl2). 1H NMR (300 MHz,
CDCl3) d: 5.97–5.89 (m, 1H), 5.58–5.50 (m, 1H), 5.40–5.38 (m,
1H), 3.75 (s, 3H), 2.14 (s, 3H), 2.11–2.04 (m, 2H), 1.39–1.37 (m,
2H), 1.30–1.26 (m, 14H), 0.88 (t, 3H, J = 6.4 Hz). 13C NMR
(75 MHz, CDCl3) d: 170.15, 169.60, 138.25, 121.64, 73.31, 52.42,
32.27, 31.89, 29.58, 29.56, 29.40, 29.31, 29.09, 28.56, 22.66,
Acknowledgments
20.69, 14.08. HRMS (TOF): calcd for
316.2488, found: 316.2529.
C
17H34NO4, [M+NH4]+:
We thank the Twelfth Five-year Science and Technology Sup-
port Program (No. 2012BAK25B03), the National Natural Science
Foundation of China (NNSFC) (No. 20972186, 21172256 and
81102340) for their financial support.
The same procedure was used to prepare the target compounds
1b to 1f.
4.9. Characterisation of (R,E)-methyl 2-acetoxypentadec-3-eno-
ate 1b
References and notes
Colourless oil, 75% yield, ½a D20
ꢃ
¼ þ33:6 (c 0.5, CH2Cl2). 1H NMR
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