Asymmetric total synthesis of all four isomers of 6-acetoxy-5- hexadecanolide: The major component of mosquito oviposition attractant pheromones

Article abstract of DOI:10.1016/j.tetasy.2014.03.006

An asymmetric total synthesis of (5S,6R)-(+)-erythro-6-acetoxy-5- hexadecanolide 1a has been accomplished from readily available hex-5-yn-1-ol via Shi's asymmetric epoxidation as the key step, in eight steps with an overall yield of 33.5%. In addition, the stereoselective synthesis of all four isomers of 6-acetoxy-5-hexadecanolide 1a-1d were obtained via Sharpless asymmetric dihydroxylation and Mitsunobu reaction as the key steps with overall yields of 16.5-21.2%, respectively.

Full text of DOI:10.1016/j.tetasy.2014.03.006

Tetrahedron: Asymmetry 25 (2014) 610–616
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric total synthesis of all four isomers
of 6-acetoxy-5-hexadecanolide: the major component
of mosquito oviposition attractant pheromones
⇑
Hong-Bo Dong, Ming-Yan Yang, Xiao-Teng Zhang, Ming-An Wang
Department of Applied Chemistry, China Agricultural University, 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:
An asymmetric total synthesis of (5S,6R)-(+)-erythro-6-acetoxy-5-hexadecanolide 1a has been accom-
plished from readily available hex-5-yn-1-ol via Shi’s asymmetric epoxidation as the key step, in eight
steps with an overall yield of 33.5%. In addition, the stereoselective synthesis of all four isomers of
6-acetoxy-5-hexadecanolide 1a–1d were obtained via Sharpless asymmetric dihydroxylation and
Mitsunobu reaction as the key steps with overall yields of 16.5–21.2%, respectively.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 18 January 2014
Accepted 3 March 2014
Available online 2 April 2014
1. Introduction
asymmetric total synthetic approach of this pheromone with high
overall yield is still required.
The mosquito oviposition attractant pheromones were first
isolated by Laurence and Pickett from apical droplets formed on
the egg of the mosquito Culex pipens fatigans in 1979,1 which is
distributed worldwide and can be a vector for filarial disease and
malaria as well as having the ability to transmit the West Nile virus
in hot climates.2 The absolute configuration of the only natural
active pheromone isomer was identified as (ꢀ)-(5R,6S)-6-acetoxy-
5-hexadecanolide 1b (Fig. 1).1b Recently, the crystal and solution
structures of an odorant-binding protein from the southern house
mosquito complexed with the oviposition pheromone 1b
(CquiOBP1ꢁ1b complex, 3OGN in the protein data bank) have been
reported, which showed that CquiOBP binds 1b in an unprece-
dented fashion using both a small central cavity for the lactone
head group and a long hydrophobic channel for its tail.3 Due to
its biological importance and application in the control of harmful
insects,4,5 the asymmetric synthesis of this pheromone has at-
tracted great attention. The first synthesis of compounds 1a and
1b was reported in 1982.6 Since then, numerous stereoselective
syntheses of natural (ꢀ)-erythro-6-acetoxy-5-hexadecanolide 1b
and unnatural isomers 1a, (+)- and (ꢀ)-threo-6-acetoxy-5-hexade-
canolides 1c and 1d have been reported,7 with d-gluconolactone,7a
Shi’s asymmetric epoxidations8 and Sharpless asymmetric
dihydroxylations9 are efficient methods to introduce two stereo-
genic centers at the same time, which have provided several new
protocols for obtaining chiral compounds in an environmentally
friendly manner. The application of Sharpless AE or AD reactions
in the synthesis of this pheromone has been reported using 1-tridecen-
3-ol, 2-tridecen-1-ol, 1,2-cyclohexanediol, and d-valerolactone as
starting materials.7l,10 Herein we report the asymmetric total
synthesis of (5S,6R)-(+)-erythro-6-acetoxy-5-hexadecanolide 1a
via Shi’s asymmetric epoxidation of (E)-olefin alcohol 7 and the
stereoselective synthesis of 6-acetoxy-5-hexadecanolides 1a–1d
via Sharpless asymmetric dihydroxylation of (E)-olefin acid 8 as
the key steps using very efficient synthetic routes with high overall
yields.
OAc
C10H21 (R)
OAc
O
(S)
O
O
(R)
O
(S)
C10H21
1a
1b
(+)-(5S,6R)-6-acetoxy-5-hexadecanolide
(-)-(5R,6S)-6-acetoxy-5-hexadecanolide
(2R,3S)-1,2-epoxy-4-penten-3-ol,7d
L
-(+)-tartaric acid,7e (R)-2,
3-cyclohexylideneglyceraldehyde,7h
D
-ribose,7k and so on being
OAc
OAc
used as chiral sources. However, a more efficient and inexpensive
O
(S)
O
O
(R)
O
(S)
(R)
C10H21
C10H21
(+)-(5R,6R)-6-acetoxy-5-hexadecanolide 1d
Figure 1. Structures of compounds 1a, 1b, 1c, and 1d.
(-)-(5S,6S)-6-acetoxy-5-hexadecanolide 1c
⇑
Corresponding author. Tel.: +86 106 273 4093.
E-mail address: wangma@cau.edu.cn (M.-A. Wang).
http://dx.doi.org/10.1016/j.tetasy.2014.03.006
0957-4166/Ó 2014 Elsevier Ltd. All rights reserved.

H.-B. Dong et al. / Tetrahedron: Asymmetry 25 (2014) 610–616
611
To the best of our knowledge, although these two methods have
found application in a number of syntheses,11 this would be the
first use of these methods to asymmetrically synthesize four
isomers of 6-acetoxy-5-hexadecanolide 1a–1d by key intermediate
(E)-olefin alcohol 7 and (E)-olefin acid 8; these strategies could be
used to synthesize various lactones with the desired configurations
acid in CH3OH to yield compound 6.12 Reduction of the alkyne 6 by
LiAlH4 in diglyme at 160 °C directly furnished the (E)-olefin alcohol
7 in 83% yield.13
With the key intermediate 7 in hand, it was oxidized with
pyridinium dichromate (PDC) in dimethylformamide (DMF) under
an argon atmosphere to give the desired trans-acid 8 in 58% yield.14
Epoxidation of compound 8 in CH2Cl2–water solvent system with
peracetic acid in the presence of Na2CO3 yielded rac-9, which auto-
matically cyclized to afford a racemic mixture (5R,6R) and (5S,6S)
rac-10 in the presence of catalytic quantity of camphorsulfonic
acid.15 In an effort to promote the application of the above proce-
dure, we next sought to exploit the Shi’s asymmetric epoxidation
procedure for the enantioselective conversion of key intermediate
acid 8 to compound 14a. We attempted to use the Shi’s asymmet-
ric epoxidation procedure16 for the enantioselective conversion of
carboxylic acid 8 into lactone 14a via epoxide 13, which was the
key reaction to introduce the two stereogenic centers into the mol-
ecule. The cyclization of 13 into lactone 14a was attempted under
typical basic asymmetric epoxidation conditions (pH = 10).17,18 The
application of Shi’s epoxidation conditions and then warming the
mixture to react at ambient temperature only gave the correspond-
ing carboxylic acid salts of 13, which could not be cyclized to chiral
lactone 14a in situ.
and side chains with
enantiomeric purity.
a-hydroxy or a-acyloxy groups with high
2. Results and discussion
The retro-synthetic analysis of 6-acetoxy-5-hexadecanolide
isomers by Shi’s asymmetric epoxidation and Sharpless
1
asymmetric dihydroxylation is shown in Scheme 1. Compound
(+)-(5R,6S)-6-acetoxy-5-hexadecanolide 1a was envisaged from
the intramolecular cyclization of epoxy carboxyl acid compound
13a, wherein the terminal carboxyl acid attacks the epoxide from
the other side of epoxy group to afford a six-membered lactone.
Compound 13a was easily obtained from the intermediate of Shi’s
asymmetric epoxidation and oxidation of the terminal olefin alco-
hol 7. Compound 7 could be prepared from LiAlH4 reduction of 6,
which was made from the commercially available hex-5-yn-1-ol
2 and 1-bromodecane 3 in very simple steps including THP protec-
tion, a coupling reaction, and methanolysis of the THP ether. The
four isomers of 1 were easily obtained from 14a to 14d, which
could be directly prepared from two vicinal diols 16a and 16b or
by configuration inversion via a Mitsunobu reaction. The vicinal
diols 16a and 16b were readily synthesized by Sharpless dihydr-
oxylation and oxidation of 7.
As shown in Scheme 2, our synthetic strategy started from
commercially available hex-5-yn-1-ol 2. The hydroxy group of
hex-5-yn-1-ol was protected as a THP ether to give compound 4.
Treatment of 4 with 1-iododecane (readily furnished from 1-bro-
modecane 3 and NaI in refluxing acetone) in the presence of n-BuLi
and hexamethylphosphoramide (HMPA) afforded a coupled prod-
uct 5. Accordingly, compound 5 was treated with p-toluenesulfonic
We next carried out Shi’s asymmetric epoxidation with olefin
alcohol 7 to obtain epoxide compound 12 in 88% yield and with
high enantioselectivity {½a D25
ꢂ
= +26.7 (c 0.52, CHCl3)} under rapid
and mild conditions (Fig. 2),10b,19 followed by oxidation of the ter-
minal alcohol with NaIO4 in the presence of RuCl3 to afford the key
intermediate (5R,6R)-acid 13. Next, cyclization of (5R,6R)-acid 13
occurred in the presence of a catalytic amount of (+)-camphorsul-
fonic acid to yield (5S,6R)-lactone 14a with 95.9% ee; the ee
value was determined by chiral HPLC (Chiralpak AD column) of
the p-nitrobenzoate derivative. Finally, the total synthesis of
(+)-(5S,6R)-6-acetoxy-5-hexadecanolide 1a was achieved by
acetylation of (5S,6R)-lactone 14a using Ac2O under the catalysis
of DMAP in 89% yield.
OAc
O
O
*
C10H21
*
1
OH
OH
OH
O
(S)
O
O
(R)
O
(S)
(R)
C10H21
O
(S)
O
C10H21
(R)
C10H21
14c
14a
14d
Mitsunobu reaction
OH
OH
O
(S)
O
O
(R)
O
(R)
O
H
(S)
C10H21
C10H21
OH
O
(R) (R)
C10H21
H
14a
14b
13a
OH
Shi's asymmetric
epoxidation
*
OC2H5
*
C10H21
OH
O
16a/b
OH
OH
C10H21
Sharpless asymmetric
dihydroxyation
7
OH
+
C10H21
C10H21Br
6
2
3
Scheme 1. Retrosynthetic analysis of 1 via Shi’s epoxidation and Sharpless dihydroxylation.

612
H.-B. Dong et al. / Tetrahedron: Asymmetry 25 (2014) 610–616
b
a
O
C10H21
O
OH
O
O
2
4
5
c
d
OH
C10H21
OH
C10H21
6
7
OR
OH
O
O
O
g
f
C10H21
C10H21
OH
OH
C10H21
O
e
i
8
O
rac-9
rac-10 R = H
7
h
rac-11 R = PNB
O
H
OR
OH
j
O
g
H
O
O
C10H21
H
C10H21
C10H21
H
12
O
14a
R = H
13
k
1a R = Ac
Scheme 2. Preparation of 1a. Reagents and conditions: (a) 3,4-dihydro-2H-pyran, CSA, CH2Cl2, rt, 4 h; (b) n-BuLi, 1-iododecane, THF/HMPA, ꢀ78 to 0 °C, overnight; (c) PTSA,
CH3OH, rt, 2 h; (d) LiAlH4, THF/diglyme, 160 °C, 13 h; (e) PDC, DMF, rt, overnight; (f) CH3COOOH, Na2CO3, CH2Cl2/H2O, 1 h; (g) CSA, CH2Cl2, rt, 8 h; (h) PNBC, DMAP, CH2Cl2, rt,
4 h; (i) oxone,
D-fructose-derived catalyst 18, buffer, CH3CN/H2O, 0 °C, 3 h; (j) NaIO4, RuCl3ꢁH2O, CCl4/H2O, rt, 1 h; (k) Ac2O, DMAP, CH2Cl2, rt, 4 h.
ketal directs orientation
of the E-alkene
O
O
O
H
O
O
O
R
O
OH
H
18
O
O
O
O
O
bottom face of dioxirane
blocked by ketal
R = C10H21
O
Figure 2. Shi’ model and the structure of catalyst 18.
OH
C10H21
8
O
O
a
OC2H5
C
10H21
15
b
c
OH OH
H
H
OC2H5
(S) (S)
OC2H5
H
C10H21
(R) (R)
C10H21
H
OH OH
O
O
16b
16a
d
d
OAc
OH
OH
OAc
O
O
O
(R)
O
O
(S)
O
O
(S)
O
(R)
g
C
10H21
C10H21 (R)
C10H21 (S)
g
(R)
C10H21 (S)
14c
1d
14d
1c
e
e
OR
OR
O
(S)
O
O
(R)
O
(R)
C10H21
(S)
C10H21
11a R = PNB
14a R = H
11b R = PNB
14b R = H
f
f
g
g
1a
R = Ac
1b
R = Ac
Scheme 3. Preparation of 1a–1d. Reagents and conditions: (a) H2SO4, CH3CH2OH, 78 °C, 5 h; (b) AD-mix-b, methanesulfonamide, t-BuOH/H2O, 0 °C, 60 h; (c) AD-mix-a,
methanesulfonamide, t-BuOH/H2O, 0 °C, 60 h; (d) (i) NaOH, H2O, CH3CH2OH, 60 °C, 2 h; (ii) CH2Cl2, TsOH, rt, 2.5 h; (e) Ph3P, DEAD, PNBA, THF, rt, 4 h; (f) K2CO3, CH3OH, rt,
10 min; (g) Ac2O, DMAP, CH2Cl2, rt, 4 h.

H.-B. Dong et al. / Tetrahedron: Asymmetry 25 (2014) 610–616
613
This synthetic sequence is simple, inexpensive, and is environ-
mentally friendly; however we could only obtain the inactive
(5S,6R)-isomer 1a. In order to obtain the active (5R,6S)-isomer
and the other two threo isomers, we decided to use Sharpless
asymmetric dihydroxylation to prepare the four isomers of erythro-
and threo-6-acetoxy-5-hexadecanolide 1a–1d. Our synthetic strat-
egy for the four isomers of 6-acetoxy-5-hexadecanolide from the
acid 8 is shown in Scheme 3.
isopropanol (90:10), flow rate: 1.0 mL/min, UV detection wave-
length: 254 nm.
4.2. 2-(Hex-5-ynyloxy)tetrahydro-2H-pyran 4
To a cold (0 °C) mixture of hex-5-yn-1-ol 2 (1.91 g, 19.5 mmol),
and 3,4-dihydro-2H-pyran (1.96 mL, 21.5 mmol,) in dry CH2Cl2
(25 mL) was added camphorsulfonic acid (5 mg, CSA). The reaction
mixture was warmed to room temperature and stirred for 4 h. The
reaction was then quenched with saturated aqueous NaHCO3, and
extracted with CH2Cl2. The combined organic layers were dried
over MgSO4, and concentrated to give pure 1-hex-5-ynyloxy-tetra-
hydropyran 7 3.47 g as a colorless oil, 98% yield. 1H NMR (300 MHz,
CDCl3) d: 4.58 (t, J = 3.5 Hz, 1H), 3.85–3.72 (m, 2H), 3.52–3.37
(m, 2H), 2.25–2.20 (m, 2H), 1.95 (t, J = 2.6 Hz, 1H), 1.74–1.49
(m, 10H), which were identical with that in the literature.22
The key intermediate (E)-olefin ester 15 was easily obtained
from acid 8 in 84% yield. The following Sharpless asymmetric
dihydroxylation reactions gave two vicinal diols 16a and 16b
respectively, which were hydrolyzed by NaOH and then cyclized
in the presence of TsOH to afford (5S,6S)-lactone 14c and
(5R,6R)-lactone 14d without any change of stereogenic centers.20,21
Next, 14c and 14d were acetylated with acetic anhydride and
DMAP in CH2Cl2 at room temperature to produce unnatural prod-
ucts threo-(5R,6R)- and threo-(5S,6S)-6-acetoxy-5-hexadecanolide
1c and 1d in 82% and 88% yields. Compounds 14c and 14d were
transferred and inverted the C-6 configuration using typical
Mitsunobu reaction conditions to afford the p-nitrobenzoates of
(5S,6R)-lactone 11a and (5R,6S)-lactone 11b in 83% and 90% yields,
with high enantioselectivities in 97.9% and 98.7% ee [the ee values
were determined by chiral HPLC (Chiralpak AD column)], respec-
tively.22,23 Hydrolysis of esters 11a and 11b with K2CO3 in MeOH
yielded (5S,6R)-lactone 14a and (5R,6S)-lactone 14b in good yields.
The reaction of (5S,6R)-lactone 14a and (5R,6S)-lactone 14b with
acetic anhydride and DMAP in CH2Cl2 at room temperature pro-
duced the corresponding natural products erythro-(5S,6R)- and
erythro-(5R,6S)-6-acetoxy-5-hexadecanolides 1a and 1b in 90%
and 96% yields, respectively. All of the products were characterized
by their 1H NMR, 13C NMR, high resolution mass spectra and
specific rotation values, and these data were consistent with those
reported in the literature.
4.3. Hexadec-5-yn-1-ol 6
To
a solution of 2-(hex-5-ynyloxy)tetrahydro-2H-pyran 4
(1.82 g, 10 mmol) in THF (50 mL) was added n-BuLi (2.5 M in
hexane, 6 mL, 15 mmol) at ꢀ78 °C and then allowed to warm to
ꢀ20 °C. After 2 h of stirring, the mixture was cooled to ꢀ78 °C
and hexamethylphosphoric triamide (HMPA, 20 mL) was added.
The resulting mixture was transferred into a solution of 1-iodode-
cane (3.48 g, 13 mmol, readily furnished from 1-bromodecane 3
and NaI in refluxing acetone) in THF (25 mL) at ꢀ78 °C via a can-
nula, and then warmed to room temperature and stirred overnight.
The reaction was quenched with saturated NH4Cl at 0 °C, and the
mixture was extracted with Et2O. The ether layer was washed with
saturated NaHCO3 and brine, dried over Na2SO4, and concentrated.
The residue was purified by silica gel column chromatography
(50:1 V/V petroleum ether/EtOAc) to give a colorless oil 5.
Compound 5 was dissolved in MeOH (25 mL) at room tempera-
ture and p-toluenesulfonic acid (150 mg, PTSA) was added. The
solution was stirred at room temperature for 2 h, the reaction
was quenched with NaHCO3, filtered, and MeOH was removed
under reduced pressure. Water (25 mL) was added to this residue,
extracted with ethyl acetate, and the organic phase was washed
with brine. The solution was dried over anhydrous Na2SO4, filtered,
and the solvent was removed under vacuum. Purification by flash
column chromatography (silica gel column, gradient elution with
10–20% EtOAc/petroleum ether) afforded compound 6 (1.74 g) as
a colorless oil in 73% yield. 1H NMR (CDCl3) d: 3.63 (t, J = 6.3 Hz,
2H), 2.19–2.08 (m, 4H), 1.84 (s, 1H), 1.67–1.32 (m, 6H), 1.32–
1.24 (m, 14H), 0.85 (t, J = 6.7 Hz, 3H); 13C NMR (CDCl3) d 80.64,
79.65, 62.34, 31.84, 31.80, 29.52, 29.49, 29.26, 29.09, 28.83,
25.33, 22.61, 18.67, 18.47, 14.01. HR-MS (ESI): calcd for
[C16H31O]+, 239.2369; found, 239.2370.
3. Conclusion
In conclusion, we have developed a concise and convergent ap-
proach for the total synthesis of (+)-(5S,6R)-6-acetoxy-5-hexade-
canolide 1a in 33.5% overall yield with Shi’s asymmetric
epoxidation as the key step. The stereoselective synthesis of
(+)-(5S,6R)-6-acetoxy-5- hexadecanolide 1a, (ꢀ)-(5R,6S)-6-acetoxy-
5-hexadecanolide 1b, (+)-(5R,6R)-6-acetoxy-5-hexadecanolide 1c,
and (ꢀ)-(5S,6S)-6-acetoxy-5-hexadecanolide 1d were successfully
achieved in 16.5%, 18.0%, 21.2%, and 22.1% overall yields by utiliz-
ing Sharpless asymmetric dihydroxylation and Mitsunobu reac-
tions as the key steps. The two synthetic sequences presented
are simple, inexpensive, and amenable for the synthesis of a num-
ber of lactones with the side chain having
groups with high enantiomeric purity.
a-hydroxy or a-acyloxy
4. Experimental
4.1. General
4.4. (E)-Pentadec-4-en-1-ol 7
A mixture of THF (6 mL), diglyme (54 mL), and LiAlH4 (1.52 g,
40 mmol) was stirred and heated to 130 °C at which point a low
boiling fraction was distilled off using a Dean-Stark trap. A solution
of alkynol 6 (2.38 g, 10 mmol) in diglyme (10 mL) was slowly
added to the above stirred mixture at 0 °C. The temperature was
then raised and kept at 160 °C for 13 h. The reaction mixture was
cooled and slowly quenched with ice-water. The resulting slurry
was filtered through a pad of Celite and the remaining solid was
washed extensively with CH2Cl2. The combined CH2Cl2 solution
was worked up. The residue was purified by silica gel flash
chromatography and eluted with AcOEt–hexane (1:5) to afford
Melting points were measured on a Yanagimoto apparatus and
are uncorrected. 1H NMR (300 MHz), and 13C NMR (75 MHz) spec-
tra were recorded on Bruker DPX 300 NMR Spectrometer with
CDCl3 as solvent and tetramethylsilane as internal standard. HR-
MS were obtained on Bruker Apex II mass spectrometer using
nitrobenzoyl alcohol and sodium chloride as matrix. The optical
rotations were measured on a Perkin–Elmer 241MC instrument.
HPLC analyses were performed on an Agilent LC 1100 instrument
equipped with a chiral Chiralpak AD column, eluent: hexane/

614
H.-B. Dong et al. / Tetrahedron: Asymmetry 25 (2014) 610–616
(E)-pentadec-4-en-1-ol 7 (2.0 g) as a white solid in 83%. Mp
21.8–22.0 °C 1H NMR (CDCl3) d: 5.42–5.37 (m, 2H), 3.64 (br s,
2H), 2.04–1.93 (m, 4H), 1.62–1.52 (m, 2H), 1.46–1.25 (m, 19H),
0.87 (t, J = 6.7 Hz, 3H); 13C NMR (CDCl3) d: 130.84, 129.72, 62.73,
32.54, 32.24, 32.17, 31.87, 29.59, 29.48, 29.30, 29.15, 25.68,
22.63, 14.03. HR-MS (ESI): calcd for [C16H33O]+, 241.2526; found,
241.2528.
31.96, 31.80, 31.69, 29.49, 29.45, 29.35, 29.21, 25.92, 22.56,
22.25, 13.97. HR-MS (ESI): calcd for [C16H32O2Na]+, 279.2295;
found, 279.2290.
4.8. (5S,6R)-6-Hydroxy-5-hexadecanolide 14a
A mixture of compound 12 (0.256 g, 1 mmol), NaIO4 (1.5 g,
7 mmol), H2O (20 mL) and CCl4 (15 mL) was stirred for 5 min. Next,
RuCl3ꢁH2O (5 mg) was added, the black slurry was stirred for 1 h at
ambient temperature. The mixture was diluted with water (20 mL)
and extracted with CH2Cl2. The organic phase was combined and
worked up. The residue was purified by silica gel column chroma-
tography and eluted with AcOEt–petroleum ether (1:3) to afford
compound 13 0.225 g in 83% yield as a white solid.
4.5. (E)-Hexadec-5-enoic acid 8
A mixture of (E)-pentadec-4-en-1-ol 7 (1.2 g, 5 mmol), PDC
(7.0 g, 18.7 mmol), and DMF (20 mL) was stirred at ambient
temperature overnight. The brown mixture was then poured into
H2O (100 mL) and extracted with Et2O. The combined organic
extracts were dried, concentrated, and purified by flash chroma-
tography (AcOEt/hexane = 1:5 v/v) to afford (E)-hexadec-5-enoic
acid 8 0.73 g in 58% yield as a colorless oil. 1H NMR (CDCl3):
11.20 (br, 1H), 5.46–5.31 (m, 2H), 2.34 (t, J = 7.5 Hz, 2H), 2.07–
1.93 (m, 4H), 1.74–1.64 (m, 2H), 1.26 (br, 16H), 0.87 (t, J = 6.6 Hz,
3H); 13C NMR (CDCl3): 180.05, 131.91, 128.61, 33.32, 32.54,
31.91, 31.80, 29.63, 29.53, 29.51, 29.33, 29.18, 24.45, 22.67,
14.08. HR-MS (ESI): calcd for [C16H30O2Na]+, 277.2138; found,
277.2138.
Compound 13 was dissolved in CH2Cl2 (15 mL) at room temper-
ature and CSA (5 mg) was added. The mixture was stirred at room
temperature for 8 h, washed with saturated NaHCO3 and brine,
dried over MgSO4, filtered, and the solvent removed under vacuum.
The residue was purified by silica gel flash chromatography and
eluted with AcOEt–petroleum ether (1:3) to afford a white solid,
which was recrystallized in hexane to give compound 14a
0.195 g in 72% yield for two steps. Mp 67.0–67.5 °C. ½a D25
ꢂ
= +12.0
(c 0.42, CHCl3) {lit.7m
½
a 2D5 = +12.7 (c 0.74, CHCl3)}. 1H NMR (CDCl3)
ꢂ
d: 4.28–4.22 (m, 1H), 3.81 (br, 1H), 2.60–2.42 (m, 2H), 2.21 (br, 1H),
1.98–1.73 (m, 4H), 1.53–1.42 (m, 3H), 1.26 (br, 16H), 0.88
(t, J = 6.7 Hz, 3H); 13C NMR (CDCl3) d: 171.69, 83.41, 72.30, 31.81,
31.73, 29.71, 29.50, 29.47, 29.44, 29.22, 25.78, 22.58, 21.18,
18.26, 14.00. HR-MS (ESI): calcd for [C16H30O3Na]+, 293.2087;
found, 293.2086. Compound 14a was reacted with p-nitrobenzoyl
chloride to form p-nitrobenzoate derivative 11a; the ee value
was determined to be 95.9% with the retention time of
19.580 min in the HPLC profile.
4.6. (5S,6R)- and (5R,6S)-6-hydroxy-5-hexadecanolide rac-10
To a solution of acid 8 (0.28 g, 1.1 mmol) in CH2Cl2 (10 mL) was
added a peracetic acid solution (2.1 mL = 3 ꢃ 0.7 mL) and anhy-
drous Na2CO3 (0.72 g = 3 ꢃ 0.24 g) in three portions. The reaction
mixture was stirred for 1.5 h at room temperature. After the reac-
tion was finished as detected by TLC, the mixture was diluted with
saturated Na2S2O3 (10 mL) and extracted with CH2Cl2 (3 ꢃ 10 mL).
The combined organic phases were washed with brine (3 ꢃ 10 mL),
dried over anhydrous Na2SO4, and concentrated in vacuo to give a
white solid compound rac-9. Compound rac-9 was dissolved in
CH2Cl2 (20 mL) at room temperature and CSA (5 mg) was added.
The mixture was stirred at ambient temperature overnight. After
the reaction was finished, the organic phase was washed with 5%
Na2CO3 solution and brine, dried over anhydrous Na2SO4, and con-
centrated in vacuo. Flash chromatography on silica gel (3:1 V/V
petroleum ether/EtOAc) afforded a white solid rac-10 0.22 g in
74% yield. Mp 67.0–67.8 °C. 1H NMR (CDCl3) d: 4.28–4.22
(m, 1H), 3.82 (br, 1H), 2.60–2.42 (m, 2H), 2.08 (br, 1H), 1.89–1.75
(m, 4H), 1.53–1.26 (m, 18H), 0.88 (t, J = 6.7 Hz, 3H). It was identical
to that in the literature.5
4.9. (5S,6R)-6-Acetoxy-5-hexadecanolide 1a
A mixture of 14a (0.31 g, 1.15 mmol), Ac2O (0.33 mL, 3.5 mmol)
and 4-(dimethylamino)pyridine (DMAP) (0.42 g, 3.4 mmol) in dry
CH2Cl2 (10 mL) was stirred at room temperature for 4 h. Next,
the mixture was quenched with NaHCO3 solution and extracted
with CH2Cl2. The combined extracts were dried over MgSO4,
filtered, the solvent removed, and purified by silica gel column
chromatography (petroleum ether/AcOEt 6:1) to give 1a 0.32 g in
89% yield as a colorless oil. ½a D25
ꢂ
= +38.0 (c 0.60, CHCl3) {lit.7m
½
a 2D5 = +36.4 (c 1.2, CHCl3)}. 1H NMR (CDCl3) d: 5.01–4.95 (m, 1H),
ꢂ
4.35 (ddd, J = = 3.3, 4.5, 13.1 Hz, 1H), 2.65–2.50 (m, 1H), 2.48–
2.41 (m, 1H), 2.09 (s, 3H), 1.96–1.89 (m, 3H), 1.70–1.61 (m, 3H),
1.26 (br, 16H), 0.88 (t, J = 6.7 Hz, 3H). 13C NMR (CDCl3) d: 170.62,
170.15, 80.27, 74.02, 31.65, 29.38, 29.36, 29.32, 29.30, 29.20,
29.16, 29.06, 25.02, 23.20, 22.43, 20.74, 18.01, 13.85. HR-MS
(ESI): calcd for [C18H32O4Na]+, 335.2193; found, 335.2196.
4.7. 4-((2R,3R)-3-Decyloxiran-2-yl)butan-1-ol 12
To a 100 mL three-necked flask were added a buffer [0.05 M
Na2B4O7ꢁ10H2O in 4 ꢃ 10ꢀ4 M aqueous Na2(EDTA)] (20 mL), aceto-
nitrile (30 mL), (E)-pentadec-4-en-1-ol 7 (0.48 g, 2 mmol), tetrabu-
tylammonium hydrogen sulfate (0.075 g, 0.02 mmol), and ketone
18 (0.167 g, 0.67 mmol). The reaction mixture was cooled with
an ice-water bath. A solution of oxone (1.7 g, 2.76 mmol) in aque-
ous Na2(EDTA) (4 ꢃ 10ꢀ4 M 13 mL) and a solution of K2CO3 (1.6 g,
11.6 mmol) in water (13 mL) were added dropwise through two
separate addition funnels over a period of 3 h. The epoxidation
reaction mixture was then allowed to warm up to room tempera-
ture and extracted with EtOAc (3 ꢃ 30 mL), worked up, purified by
silica gel flash chromatography, and eluted with petroleum ether/
EtOAc = 5:1 to give a white solid 4-((2R,3R)-3-decyloxiran-2-yl)bu-
4.10. (E)-Ethyl hexadec-5-enoate 15
(E)-Hexadec-5-enoic acid 8 (1.1 g, 0.44 mmol) was dissolved in
ethanol (60 mL) and 0.2 mL of concentrated H2SO4 were added.
After 5 h at reflux, the solvent was evaporated and the residue
was purified by silica gel column chromatography (100:1 V/V
petroleum ether/EtOAc) to give 15 (1.0 g, 84%) as a colorless oil.
1H NMR (CDCl3) d: 5.37–5.24 (m, 2H), 4.04 (q, J = 7.1 Hz, 2H),
2.21 (t, J = 7.5 Hz, 2H), 1.97–1.86 (m, 4H), 1.66–1.55 (m, 2H), 1.17
(br, 20H), 0.81 (t, J = 6.5 Hz, 3H); 13C NMR d: 173.55, 131.56,
128.77, 59.99, 33.54, 32.49, 31.84, 29.56, 29.48, 29.45, 29.27,
29.10, 24.71, 22.60, 14.14, 13.98. HR-MS (ESI): calcd for
[C18H35O2]+, 283.2632; found, 283.2635.
tan-1-ol 12 0.45 g in 88% yield. Mp 36.8–37.4 °C. ½a D25
ꢂ
= +26.7
(c 0.52, CHCl3); 1H NMR (CDCl3) d: 3.61 (t, J = 6.1 Hz, 2H), 2.75
(s, 1H), 2.68 (t, J = 4.5 Hz, 2H), 1.62–1.26 (m, 24H), 0.88
(t, J = 6.5 Hz, 3H). 13C NMR (CDCl3) d: 62.20, 58.83, 58.72, 32.27,

H.-B. Dong et al. / Tetrahedron: Asymmetry 25 (2014) 610–616
615
4.11. (5R,6R)-6-Hydroxy-5-hexadecanolide 14d
4.15. (5R,6S)-6-Hydroxy-5-hexadecanolide 4-nitrobenzoate 11b
Compound 15 (0.846 g, 3 mmol) was added to a cold (0 °C)
solution of AD-mix-b (1.5 g/mmol, 4.5 g) and MeSO2NH2 (0.31 g,
3.2 mmol) in tert-butyl alcohol and water (1:1, 60 mL). The
mixture was stirred at 0 °C for 60 h, then quenched by Na2S2O3
and extracted with EtOAc. The solvents were removed under
reduced pressure to give crude product 16b.
Under a nitrogen atmosphere, 25 mL of dry THF were added
into a 50 mL round-bottomed flask. It was then cooled to 0 °C, after
which triphenylphosphine (1.05 g, 4 mmol) and DEAD (0.59 g,
4 mmol) were added, followed by compound 14d (0.27 g, 1 mmol)
and p-nitrobenzoic acid (0.20 g, 1.2 mmol). The mixture was stir-
red at room temperature for 4 h. The solvent was removed under
reduced pressure and the residue was purified by chromatography
on silica gel (10:1–5:1 (v/v) petroleum ether/EtOAc) to afford
377 mg (90% yield) of (5R,6S)-6-hydroxy-5-hexadecanolide
Compound 16b was dissolved in methanol (10 mL) and aqueous
NaOH (3 M, 10 mL). After being stirred at 60 °C for 2 h, the mixture
was cooled to 0 °C, acidified with 3 M HCl, and extracted with ethyl
acetate. The solvents were removed under reduced pressure and
the residue was dissolved in 50 mL of CH2Cl2. Next, 30 mg of
p-toluenesulfonic acid were added, and the mixture was stirred
at ambient temperature overnight. Work-up was carried out and
followed by column chromatography (silica gel, petroleum ether/
EtOAc, 3:1) to give a white solid, which was recrystallized from
hexane to give compound 14d 0.65 g, 80% yield. Mp 69.5–71.0 °C,
p-nitrobenzoate compound 11b as a light yellow oil. ½a D25
ꢂ
= +10.8
(c 0.44, CHCl3). 1H NMR (CDCl3) d: 8.32–8.28 (m, 2H), 8.24–8.19
(m, 2H), 5.31–5.25 (m, 1H), 4.54–4.48 (m, 1H), 2.60–2.47 (m,
2H), 2.03–1.98 (m, 2H), 1.89–1.71 (m, 4H), 1.32–1.23 (m, 16H),
0.86 (t, J = 6.7 Hz, 3H). 13C NMR (CDCl3) d: 170.53, 164.04,
150.63, 135.22, 130.77, 123.54, 80.33, 76.01, 31.78, 29.50, 29.44,
29.41, 29.33, 29.30, 29.27, 29.19, 25.28, 23.55, 22.57, 18.23,
14.00. HR-MS (ESI): calcd for [C23H34NO6]+ 420.2381; found,
420.2378. The ee value of compound 11b was determined to be
97.9% with a retention time of 21.185 min in the HPLC profile.
½
a 2D5
ꢂ
= ꢀ10.5 (c 1.2, CHCl3) {lit.7n
½
aꢂD
= ꢀ10.2 (c 0.87, CHCl3)}. 1H
NMR (CDCl3) d: 4.22–4.16 (m, 1H), 3.58–3.54 (m, 1H), 2.64–2.39
(m, 3H), 1.96–1.71 (m, 4H), 1.56–1.26 (m, 18H), 0.88
(t, J = 6.6 Hz, 3H); 13C NMR (CDCl3) d: 171.38, 83.13, 73.24, 32.58,
31.80, 29.57, 29.49, 29.47, 29.45, 29.21, 25.36, 24.07, 22.57,
18.35, 13.99. HR-MS (ESI): calcd for [C16H30O3Na]+, 293.2087;
found, 293.2088.
4.16. (5S,6R)-6-Hydroxy-5-hexadecanolide p-nitrobenzoate 11a
The procedure was the same as compound 11b in Section 4.15
from compound 14c to afford a light yellow oil 11a in 83% yield.
½
a 2D5
ꢂ
= ꢀ11.2 (c 0.23, CHCl3). 1H NMR (CDCl3) d: 8.32–8.28 (m,
4.12. (5S,6S)-6-Hydroxy-5-hexadecanolide 14c
2H), 8.25–8.20 (m, 2H), 5.32–5.26 (m, 1H), 4.56–4.50 (m, 1H),
2.67–2.48 (m, 2H), 2.06–1.99 (m, 2H), 1.91–1.73 (m, 4H), 1.41–
1.23 (m, 16H), 0.85 (t, J = 6.7 Hz, 3H); 13C NMR (CDCl3) d: 170.52,
164.02, 150.61, 135.21, 130.75, 123.52, 80.31, 75.99, 31.77, 29.49,
29.42, 29.40, 29.32, 29.29, 29.25, 29.18, 25.26, 23.52, 22.55,
18.22, 13.99. HRMS (ESI): calcd for [C23H34NO6]+ 420.2381; found,
420.2378. The ee value of compound 11a was determined to be
98.7% with the retention time 19.895 min in the HPLC profile.
Dihydroxylation of compound 15 with AD-mix-
out in the same procedure as for compound 14d to obtain a white
a was carried
solid 14c in 87% yield. Mp 69.0–70.0 °C, ½a D25
ꢂ
= +9.8 (c 0.73, CHCl3).
{lit.7n
½
a D
= +11.5 (c 0.74, CHCl3)}. 1H NMR (CDCl3) d: 4.22–4.15 (m,
ꢂ
1H), 3.58–3.55 (m, 1H), 2.61–2.45 (m, 2H), 2.21 (d, J = 5.9 Hz, 1H),
1.96–1.84 (m, 4H), 1.56–1.26 (m, 18H), 0.88 (t, J = 6.7 Hz, 3H); 13C
NMR (CDCl3) d: 171.36, 83.13, 73.26, 32.59, 31.80, 29.58, 29.50,
29.48, 29.46, 29.22, 25.37, 24.08, 22.57, 18.36, 14.00. HR-MS
(ESI): calcd for [C16H30O3Na]+, 293.2087; found, 293.2085.
4.17. (5R,6S)-6-Hydroxy-5-hexadecanolide 14b
At first, 15 mL of CH3OH, K2CO3 (0.35 g, 2.5 mmol) and com-
pound 11b (0.21 g, 0.5 mmol) were added to a 50 mL round-
bottomed flask. The mixture was stirred for 10 min at room
temperature and then filtered. The solvent was removed under
reduced pressure, and the residue was purified by chromatography
on silica gel (4:1 (v/v) hexanes/EtOAc) to afford 0.23 g of (5R,6S)-
6-hydroxy-5-hexadecanolide 14b in 87% yield as a white solid.
4.13. (5R,6R)-6-Acetoxy-5-hexadecanolide 1c
The procedure was the same as for compound 1a in Section 4.9
from compound 14c to obtain a light yellow oil compound 1c in
92% yield. ½a 2D5
ꢂ
= +14.6 (c 0.12, CHCl3). {lit.7m
½
a 2D5
= +13.7 (c 0.6,
ꢂ
CHCl3)}. 1H NMR (CDCl3) d: 4.99 (ddd, J = 3.7, 5.6, 8.0 Hz, 1H),
4.39–4.33 (m, 1H), 2.66–2.41 (m, 2H), 2.10 (s, 3H), 1.99–1.82
(m, 3H), 1.70–1.61 (m, 3H), 1.25 (br s, 16H), 0.88 (t, J = 6.7 Hz,
3H). 13C NMR (CDCl3) d: 170.70, 170.49, 79.66, 73.78, 31.78,
29.82, 29.52, 29.44, 29.42, 29.33, 29.27, 29.19, 25.22, 24.00,
22.55, 20.83, 18.28, 13.98. HR-MS (ESI): calcd for [C18H33O4]+,
313.2373; found, 313.2368.
Mp 67.4–68.0 °C, ½a D25
ꢂ
= ꢀ12.5 (c 0.75, CHCl3) {lit.7g
½
a 2D5
ꢂ
= ꢀ12.7
(c 1.0, CHCl3)}. 1H NMR (CDCl3) d: 4.28–4.22 (m, 1H), 3.81 (br,
1H), 2.66–2.57 (m, 1H), 2.51–2.39 (m, 1H), 2.03 (d, J = 4.2 Hz,
1H), 2.00–1.75 (m, 4H), 1.51–1.42 (m, 3H), 1.26 (br, 15H), 0.88 (t,
J = 6.7 Hz, 3H); 13C NMR (CDCl3) d: 171.71, 83.43, 72.36, 31.85,
31.72, 29.74, 29.54, 29.50, 29.48, 29.27, 25.82, 22.63, 21.18,
18.30, 14.05. HR-MS (ESI): calcd for [C16H30O3Na]+, 293.2087;
found, 293.2089.
4.14. (5S,6S)-6-Acetoxy-5-hexadecanolide 1d
The procedure was the same as for compound 1c in Section 4.13
from compound 14d to obtain a light yellow oil compound 1d in
4.18. (5S,6R)-6-Hydroxy-5-hexadecanolide 14a
88% yield. ½a 2D5
ꢂ
= ꢀ13.7 (c 0.10, CHCl3). {lit.7m
½
a 2D5
ꢂ
= ꢀ11.5 (c 0.7,
The procedure was the same as for compound 14b in Sec-
tion 4.17 from compound 18a to obtain a white solid 14a in 90%
CHCl3)}. 1H NMR (CDCl3) d: 5.01–4.95 (m, 1H), 4.39–4.33 (m, 1H),
2.60–2.45 (m, 2H), 2.09 (s, 3H), 1.94–1.81 (m, 3H), 1.70–1.61
(m, 3H), 1.25 (br s, 16H), 0.88 (t, J = 6.7 Hz, 3H). 13C NMR (CDCl3)
d: 170.71, 170.49, 79.66, 73.78, 31.78, 29.82, 29.51, 29.44, 29.42,
29.33, 29.27, 29.19, 25.21, 24.00, 22.55, 20.83, 18.28, 13.98.
HR-MS (ESI): calcd for [C18H33O4]+, 313.2373; found, 313.2369.
yield. Mp 68.0–68.2 °C, ½a D25
ꢂ
= +11.6 (c 0.24, CHCl3). 1H NMR
(CDCl3) d: 4.28–4.22 (m, 1H), 3.82 (br, 1H), 2.60–2.42 (m, 2H),
2.17 (br, 1H), 1.98–1.75 (m, 4H), 1.53–1.42 (m, 3H), 1.26 (br,
15H), 0.88 (t, J = 6.7 Hz, 3H), which were identical with that in
Section 4.8.

616
H.-B. Dong et al. / Tetrahedron: Asymmetry 25 (2014) 610–616
3. Mao, Y.; Xu, X.; Xu, W.; Ishida, Y.; Leal, W. S.; Ames, J. B.; Clardy, J. Proc. Natl.
Acad. Sci. U.S.A. 2010, 107, 19102–19107.
4.19. (5R,6S)-6-Acetoxy-5-hexadecanolide 1b
4. (a) Syed, Z.; Leal, W. S. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 18803–18808; (b)
Mboera, L. E. G.; Mdira, K. Y.; Salum, F. M.; Takken, W.; Pickett, J. A. J. Mol.
Model. 2013, 19, 1301–1309.
5. Olagbemiro, T. O.; Birkett, M. A.; Mordue, A. J.; Pickett, J. A. J. Agric. Food Chem.
1999, 47, 3411–3415.
A mixture of 14b (95 mg, 0.35 mmol), Ac2O (0.1 mL, 1.1 mmol),
and 4-(dimethylamino)pyridine (140 mg, 1.1 mmol) in dry CH2Cl2
(5 mL) was stirred at room temperature for 4 h, then the mixture
was quenched with a NaHCO3 solution and extracted with CH2Cl2.
The combined extracts were dried over MgSO4, filtered, and the
solvent removed. The residue was purified by silica gel column
chromatography and deleted with hexane/AcOEt (6:1) to give 1b
6. Fuganti, C.; Grasselli, P.; Servi, S. J. J. Chem. Soc., Chem. Commun. 1982, 1285–
1286.
7. (a) Saibal, D.; Anand, K. M.; Ashish, K.; Ahamad, A. K. A. G.; Jhillu, S. Y.
Carbohydr. Res. 2012, 358, 7–11; (b) Park, Y. J.; Tae, J. S. Synthesis 2010, 21,
3627–3630; (c) Singh, S.; Guiry, P. J. Eur. J. Org. Chem. 2009, 1896–1901; (d)
Quinn, K. J.; Curto, J. M.; McGrath, K. P.; Biddick, N. A. Tetrahedron Lett. 2009, 50,
7121–7123; (e) Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2007, 18,
2479–2483; (f) Sabitha, G.; Swapna, R.; Reddy, E. V.; Yadav, J. S. Synthesis 2006,
24, 4242–4246; (g) Ikishima, H.; Sekiguchi, Y.; Ichikawa, Y.; Kotsuki, H.
Tetrahedron 2006, 62, 311–316; (h) Dhotare, B.; Goswami, D.; Chattopadhyay,
A. Tetrahedron Lett. 2005, 46, 6219–6221; (i) Sun, B.; Peng, L.; Chen, X.; Li, Y.
Tetrahedron: Asymmetry 2005, 16, 1305–1307; (j) Gao, X.; Hall, D. G. J. Am.
Chem. Soc. 2003, 125, 9308–9309; (k) Gallos, J. K.; Mihelakis, D. S.; Dellios, C. C.;
Pozarentzi, M. E. Heterocycles 2000, 53, 703–707; (l) Couladouros, E. A.; Mihou,
A. P. Tetrahedron Lett. 1999, 40, 4861–4862; (m) Lohray, B. B.; Venkateswarlu, S.
Tetrahedron: Asymmetry 1997, 8, 633–638; (n) Christine, G. P.; Yves, L. M.;
Depezay, J. C. Tetrahedron 1995, 51, 1663–1674.
8. Wong, O. A.; Shi, Y. Chem. Rev. 2008, 108, 3958–3987.
9. Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483–
2547.
10. (a) Mori, K.; Otsuka, T. Tetrahedron 1983, 39, 3267–3269; (b) Lin, G. Q.; Xu, H. J.;
Wu, B. C.; Guo, G. Z.; Zhou, W. S. Tetrahedron Lett. 1985, 26, 1233–1236; (c)
Wang, Z. M.; Qian, X. H.; Zhou, W. S. Tetrahedron 1990, 46, 1191–1198; (d)
Odinokov, V. N.; Akhmetova, V. R.; Khasanov, Kh. D.; Abduvakhabov, A. A.;
Tolstikov, G. A. Zhurnal Organicheskoi Khimii 1991, 27, 1459–1463.
11. Shi, Y. Acc. Chem. Res. 2004, 37, 488–496.
98 mg in 90% yield as a light yellow oil. ½a D25
= ꢀ37.4 (c 0.65, CHCl3)
ꢂ
{lit.7g
½
a 2D5
ꢂ
= ꢀ36.8 (c 1.55, CHCl3)}. 1H NMR (CDCl3) d: 5.01–4.95
(m, 1H), 4.36 (ddd, J = 3.3, 6.3, 9.3 Hz, 1H), 2.63–2.41 (m, 2H),
2.07 (s, 3H), 1.99–1.83 (m, 3H), 1.71–1.61 (m, 3H), 1.25 (br, 16H),
0.87 (t, J = 6.6 Hz, 3H); 13C NMR (CDCl3) d: 170.62, 170.18, 80.30,
74.07, 31.69, 29.42, 29.39, 29.35, 29.33, 29.24, 29.19, 29.09,
25.06, 23.26, 22.46, 20.78, 18.05, 13.89. HR-MS (ESI): calcd for
[C16H30O3Na]+, 335.2193; found, 335.2191.
4.20. (5S,6R)-6-Acetoxy-5-hexadecanolide 1a
The procedure was the same as for compound 1b in Section 4.19
from compound 14a to obtain a light yellow oil 1a (105 mg) in 96%
yield as a colorless oil. ½a D25
ꢂ
= +36.8 (c 0.60, CHCl3). 1H NMR
(300 MHz) d: 5.01–4.95 (m, 1H), 4.36 (ddd, J = 3.2, 6.4, 9.3 Hz,
1H), 2.59–2.39 (m, 2H), 2.08 (s, 3H), 1.97–1.89 (m, 3H), 1.68–
1.61 (m, 3H), 1.26 (br, 16H), 0.87 (t, J = 6.7 Hz, 3H), which were
identical with that in Section 4.9.
12. Kai, K.; Kasamatsu, K.; Hayashi, H. Tetrahedron Lett. 2012, 53, 5441–5444.
13. Moune, S.; Niel, G.; Busquet, M.; Eggleston, I.; Jouin, P. J. Org. Chem. 1997, 62,
3332–3339.
14. Siliva, A.; Sverko, E.; Arts, M. T.; Capretta, A. Tetrahedron Lett. 2011, 52, 787–
788.
15. Dong, H. B.; Yang, M. Y.; Jiang, J. Z.; Wang, M. A. J. Asian Nat. Prod. Res. 2013, 15,
880–884.
16. Wang, Z. X.; Tu, Y.; Frohn, M.; Zhang, J. R.; Shi, Y. J. Am. Chem. Soc. 1997, 119,
11224–11235.
17. Ager, J. D.; Anderson, K.; Oblinger, E.; Shi, Y.; VanderRoest, J. Org. Process. Res.
Dev. 2007, 11, 44–51.
18. Emmanuvel, L.; Sudalai, A. Tetrahedron Lett. 2008, 49, 5736–5738.
19. Zhou, W. S.; Cheng, J.; Lin, G. Q. Huaxue Xuebao 1988, 46, 274–280.
20. Santosh, C. S.; Subhash, C. S.; Ehud, K. J. Org. Chem. 1999, 64, 7067–7073.
21. Ahmed, M. M.; Cui, H.; O’Doherty, G. A. J. Org. Chem. 2006, 71, 6686–6689.
22. Hughes, D. L.; Reamer, R. A.; Bergan, J. J.; Grabowski, E. J. J. J. Am. Chem. Soc.
1988, 110, 6487.
Acknowledgements
This project was co-founded by the National Key Technologies
R&D Program (No. 2011BAE06B04), Natural Science Foundation
of China (No. 21172254), and National Hi-Tech R&D Program of
China (2011AA10A202).
References
1. (a) Laurence, B. R.; Pickett, J. A. J. Chem. Soc., Chem. Commun. 1982, 59–60; (b)
Laurence, B. R.; Mori, K.; Otsuka, T.; Pickett, J. A.; Wadhams, L. J. J. Chem. Ecol.
1985, 11, 643–648.
2. Anderson, J. F.; Andreadis, T. G.; Vossbrinck, C. R.; Tirrell, S.; Wakem, E. M.;
French, R. A.; Garmendia, A. E.; Van Kruiningen, H. J. Science 1999, 286, 2331–
2333.
23. Ye, L. W.; Wang, Y. Z.; Donald, A. H.; Zhang, L. M. J. Am. Chem. Soc. 2012, 134,
31–34.