Synthesis of a vinylchlorine-containing 1,3-diol from a marine cyanophyte

Article abstract of DOI:10.1016/j.tet.2014.04.090

Using epoxy chiral building blocks readily derived from d-gluconolactone as the source of the stereogenic centers, both (6R,8R)- and (6R,8S)-isomers of (E)-1-chlorotridec-1-ene-6,8-diol were synthesized. The vinylchloro unit was installed onto the substrate carbon chain in an approximately 9:1 (E)/(Z) ratio via a condensation of CrCl₂/CHCl₃ with a terminal aldehyde. A tosylation protocol featuring addition of H₂O was also developed for a highly polar tetraol. The synthetic products allowed for re-acquisition of the NMR spectra of better quality and revealed some delicate yet unignorable discrepancies in the ¹³C NMR for the natural isomer obtained by synthesis and that isolated some 30 years ago from the marine cyanophyte. The puzzling discrepancies were eventually shown to be caused by deuteration of the hydroxyl groups.

Full text of DOI:10.1016/j.tet.2014.04.090

Accepted Manuscript
Synthesis of a vinylchlorine-containing 1,3-diol from a marine cyanophyte
Xiao-Long Wang , Yang-Yang Yang , Hui-Jun Chen , Yikang Wu , Dong-Sheng Ma
PII:
S0040-4020(14)00624-3
10.1016/j.tet.2014.04.090
TET 25540
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 April 2014
Revised Date: 14 April 2014
Accepted Date: 17 April 2014
Please cite this article as: Wang X-L, Yang Y-Y, Chen H-J, Wu Y, Ma D-S, Synthesis of a vinylchlorine-
containing 1,3-diol from a marine cyanophyte, Tetrahedron (2014), doi: 10.1016/j.tet.2014.04.090.
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Synthesis of a vinylchlorine-containing 1,3-
diol from a marine cyanophyte
Leave this area blank for abstract info.
Xiao-Long Wanga,b, Yang-Yang Yangb, Hui-Jun Chenb, Yikang Wub, and Dong-Sheng Maa
aSchool of Chemistry and Materials, Heilongjiang University, China; bState Key Laboratory of Bioorganic and
Natural Products Chemistry, Shanghai Institute of Organic Chemistry

1
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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of a vinylchlorine-containing 1,3-diol from a marine cyanophyte
Xiao-Long Wanga,b , Yang-Yang Yangb, Hui-Jun Chenb, Yikang Wub, and Dong-Sheng Maa,*
a School of Chemistry and Materials, Heilongjiang University, Harbin 150080, China
b State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling
Road, Shanghai 200032, China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Using expoxy chiral building blocks readily derived from D-gluconolactone as the source of the
stereogenic centers, both (6R,8R)- and (6R,8S)- isomers of (E)-1-chlorotridec-1-ene-6,8-diol
were synthesized. The vinylchloro unit was installed onto the substrate carbon chain in an
approximately 9:1 (E)/(Z) ratio via a condensation of CrCl2/CHCl3 with an terminal aldehyde. A
tosylation protocol featuring addition of H2O was also developed for a highly polar tetraol. The
synthetic products allowed for re-acquisition of the NMR spectra of better quality and revealed
some delicate yet unignorable discrepancies in the 13C NMR for the natural isomer obtained by
synthesis and that isolated some 30 years ago from the marine cyanophyte. The puzzling
discrepancies were eventually shown to be caused by deuteration of the hydroxyl groups.
Available online
Keywords:
natural products
metathesis
epoxides
2009 Elsevier Ltd. All rights reserved
.
diols
aldehydes
In connection with our studies4 on synthesis of 1,3-diol motif-
containing natural products5 using the epoxy chiral building
blocks6 readily accessible from the inexpensive D-
gluconolactone as the source of the stereogenic centers, we also
completed a synthesis of 1, which allowed for collection of
spectral data of better quality (thanks to the modern instruments
compared with those three decades ago) and revealed some
unexpected discrepancies that may puzzle many investigators
who need the data for comparison yet have no access to any
authentic sample of 1. Here below are the details of this
endeavor.
1. Introduction
Marine cyanobacteria are known to be prolific producers of
bioactive secondary metabolites.1 Among the numerous
structurally interesting compounds generated by cyanobacteria,
those that contain a vinylchlorine moiety (Figure 1, 1-5[2])
comprise a unique class. One of them, (–)-(E)-(6R,8S)-1-
chlorotridec-1-ene-6,8-diol (1) was disclosed2a in 1978, with its
first synthesis3 briefly communicated in 1998.
OH OH
Cl
Cl
8
6
1
2. Results and Discussion
2
1
The initial route to 1 we examined is shown in Scheme 1. The
starting enantiopure epoxy building block 6 was treated with
nBuLi in the presence of CuI as reported4h in our previous work
to afford the known diol 7. Protection7 of the hydroxyl groups
with PMBCl using NaH as the base furnished the corresponding
diPMB ether 8 in 90% isolated yield.
NHAc
O
O
HN
O
Cl
OMe
CO2Me
Cl
O
Removal8 of the acetonide protecting group in 8 was then
realized via exposure to MeOH at ambient temperature in the
presence of PPTS. The resulting vicinal diol 9 was treated with
Ph3P/I2/imidazole9 at 80 °C gave the desired vinyl species 10 in
97% yield. It is noteworthy that the reactants concentration
appeared to play a critical role in this reaction. With a fixed
3
Cl
4
Cl
SO3H
O Cl
Cl
Cl
Cl
Cl
Cl
5
reactant ratio (cf. the experimental section),
a substrate
Figure 1. The structures for some of the known vinylchlorine-containing
concentration of > 0.2 M seemed to be essential to secure a
marine natural products produced by cyanobacteria.
———
Corresponding author. Tel.: +86-(0)21-54925115; fax: +86-(0)21-64166128; e-mail: yikangwu@sioc.ac.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
successful conversion, while at concentrations < 0.1 M the
The coupling of iodide 12 with dichloride 13 under the Zn
dust/CuCN/LiCl/TMSCl11 conditions did not occur as expected.
The only product that could be identified was the alkane derived
from 12 via de-iodination, although a model reaction using allyl
chloride (i.e., without the vinyl chlorine in the molecule) instead
of 13 did generate the corresponding coupling product as a 1:1
inseparable mixture with the deiodination product.
intermediate iodoalcohol (with primary hydroxyl group in 9
being replaced by an iodine atom) was almost always the major
product.
O
O
O
O
O
b
a
O
3
OH
H
OPMB
OH
OH
(ref. 4h)
As the Cu-mediated coupling did not seem to be feasible, we
next turned to a CM (cross metathesis) based approach. As
shown in Scheme 2, the alkene 10 was treated with homoallyl
alcohol 14 in the presence of Grubbs II catalyst (16) to afford 15.
Because the self-coupling of the homoallyl alcohol occurred very
rapidly, repeated further addition of 14 was essential for the
formation of the desired 15. The solvent also made a difference
here. Initially, the coupling was carried out in CH2Cl2 in the
presence of catalyst 16 as in most literature CM cases. However,
the desired 15 was obtained in only ca. 21% yield. Use of Et2O12
to replace CH2Cl2 as the reaction solvent led to significantly
improved yields. Thus, under otherwise the same conditions, the
15 was obtained in 51% yield. Attempt to use Hoveyda-Grubbs II
catalyst (16’) instead of 16 under comparable conditions resulted
in 15 in only 10% yield.
5
OPMB
O
6
7
8
PMBO
OPMB
PMBO
HO
OPMB
c
d
HO
9
10
I
e
f
PMBO
OPMB
OPMB
OPMB
HO
OH OH
11
Cl
Cl
Cl
13
8
6
1
12
g
1
Scheme 1. Reagents and conditions. a) nBuLi, CuI, THF, –78 °C 3 h, 96%; b)
PMBCl, NaH, DMF, nBu4NI, RT, 5 h, 90%; c) PPTS, MeOH, RT, 12 h, 85%
for 9 along with 15% recovered 8, d) Ph3P, imidazole, I2, THF, 80 °C, 1 h,
97%; e) (i) BH3, THF, 0 °C, 3 h, (ii) NaOH, H2O2, RT, 2 h, 60% from 10; f)
Ph3P, imidazole, I2, THF, RT, 2 h, 100%; g) Zn dust, CuCN, TMSCl, LiCl,
DMF. THF = tetrahydrofuran. PMBCl = p-methoxybenzyl chloride. DMF =
N,N’-dimethylformamide. PPTS = Pyridium p-toluenesulfonate. TMS =
Trimethylsilyl.
Saturation of the C-C double bond in 15 by atmospheric
hydrogenation over the commercially available Skeletal Ni (from
Aldrich) gave 17 as a colorless oil; the often inseparable traces of
dark impurities related to the CM catalyst were also readily
removed at this stage. The resulting alcohol was oxidized into the
corresponding aldehyde 18 with Dess-Martin13 periodinane,
which on treatment with CrCl2/CHCl3/THF14 furnished vinyl
chloride 19 in 63% yield with a 92:8 (E)/(Z) ratio. Finally, the
PMB protecting group were cleaved smoothly with CAN to
afford end product 1.
Installation of the (E)-vinylchlorine unit was first planned to
use a coupling reaction of a suitable carbanion species with the
known allyl chloride 13, because that the desired (E)-
configuration might be secured from the beginning. To this end,
the terminal alkene was converted into the primary alcohol 11 via
Table 1. Comparison of the 13C NMR for the natural and
synthetic 1 .
Natural 1a
133.4 (C-2)
116.9 (C-1)
69.0 (C-8)
68.6 (C-6)
42.4 (C-7)
37.4 (C-9)
36.6 (C-5)
31.8 (C-11)
30.7 (C-3)
25.4 (C-10)
25.1 (C-4)
22.6 (C-12)
14.0 (C-13)
Synth 1b
133.6
117.2
69.6
Synth 1c
134.3
116.6
68.0
Synth 1d
133.7
117.1
69.3
a
standard hydroboration. The hydroxyl group was then
transformed into an iodide in high yield by exposure to
Ph3P/I2/imidazole10 at ambient temperature.
PMBO
OPMB
MesN
Cl
NMes
Ph
OH
69.1
67.7
68.8
Ru
6
8
42.4
44.0
42.3
a
PMBO
PMBO
Cl
10
37.5
37.9
37.4
PCy3
15
16
36.8
37.2
36.6
OH
MesN
Cl
NMes
14
31.8
31.8
31.9
PMBO
OPMB
OH
Ru
30.8
30.5
30.8
Cl
b
25.4
25.3
25.5
O
17
25.1
25.0
25.1
c
16'
22.6
22.4
22.7
PMBO
OPMB
d
14.0
13.4
14.0
CHO
aData taken from ref 2a along with the assignments, recorded at 25 MHz
18
b
OPMB
OPMB
without specifying the solvent. This work, measured at 125 MHz in CDCl3.
cThis work, measured at 125 MHz in d6-acetone. dThis work, measured at 125
HO
8
OH
6
Cl
e
MHz in CDCl3-CD3OD (0.6 mL/0.01 mL)
1
(E)/(Z) = 92:8
The 1H and 13C NMR for 1 were then acquired in CDCl3. The
data were generally compatible with those reported for the
natural 1. However, delicate yet unignorable discrepancies
occurred at the C-6 and C-8 (δ 69.0 and 68.6 vs 69.6 and 69.1
ppm, respectively), the two oxygenated carbon atoms (Table 1).
The original report2a did not specify the solvent for the 13C NMR,
but the 1H NMR was recorded in CDCl3 and d6-acetone,
23
Nat. 1 [ ]D
12.2 (c 3.3, MeOH)
23
Synth. 1 [ ]D
Synth. 1 [ ]D
11.2 (c 1.0, MeOH) (ref. 3)
10.8 (c 1.0, MeOH) (this work)
28
Cl
19
Scheme 2. Reagents and conditions. a) 16 (10 mol%), Et2O, RT, 2 h, 51%; b)
H2 (1 atm), Skeletal Ni, RT, 1 h, 49% overall from 10; c) Dess-Martin
periodinane, NaHCO3, CH2Cl2 RT, 2 h, 85% along with 10% of recovered 17;
d) CrCl2, CHCl3, THF, 65 °C, 4 h, 63%; e) CAN, MeCN-H2O (10:1, v/v), RT,
1 h, 89%. CAN = cerium ammonium nitrate.

3
respectively. Therefore, we next recorded the 13C NMR in d6-
acetone.
advantage of the epoxidation process compared with formation
of an oxetane or a THP ring.
ACCEPTED MANUSCRIPT
Somewhat to our surprise, the 13C NMR in d6-acetone (Table 1,
The primary hydroxyl group in the resulting tetraol 20 was
then selectively tosylated to afford tosylate 21. Because of the
poor solubility of 20 in CH2Cl2, the most commonly employed
solvent for tosylation, was not applicable here. Addition of
MeCN did not result in any discernible improvements. THF,
which was employed in one of our previous studies16 to solve a
similar problem, could fairly dissolve the added the tetraol
20.and thus made it possible to execution of the tosylation under
the pTsCl/Et3N/DMAP/ nBu2SnO17 conditions. However, the
desired product 21 (71%) was unavoidably accompanied by the
undesired di-tosylated product (29%), which was observed even
well before the starting 20 was substantially consumed.
column 3 from the left) turned out to be even more incompatible
with that for the natural 1 than that recorded in CDCl3. As the
previous synthesis did not provide any NMR information, the
spectroscopic data reported for the isolated natural 1 were the
only available ones that can be used for comparison. Given the
simple structure of 1, especially with a previous synthesis already
published in the literature, there was really no reason to doubt
about the correctness of the assigned structure. However, the
identity of our sample was just as unequivocal; we were stuck in
the middle of nowhere.
Then we recalled that in
a
previous4g case, similar
discrepancies in the 13C NMR were proven to be caused by
deuteration of the hydroxyl groups. In the present case, the
discrepancies also occurred at those oxygenated carbon atoms
and chemical shifts for the involved carbon atoms of the
synthetic sample were also larger in value than those reported for
the natural ones. Could the present discrepancies also stem from
deuteration of the hydroxyl groups? Although there were no
traces of clues for the possibility of deuteration of the natural 1 in
the original[2a] report, under the given circumstances we really did
not have any other choices but looking into the deuteration of the
hydroxyl groups.
O
OH
OH
OTs
OH
a
b
HO
HO
O
OH
OH
OH
OH
20
21
7
HO
OH
d
c
HO
OH
O
H
22
23
The synthetic 1 was dissolved in CD3OD. And a 13C NMR
was recorded. However, the data were apparently incompatible
with those for the natural 1. The solvent (CD3OD) in the NMR
sample solution was then removed by rotary evaporation. The
residue was re-dissolved in CD3OD and stirred overnight. The
process was repeated three times before the residue was
eventually dissolved in CDCl3 to acquire another 13C NMR.
e
OH OH
HO
25
OBn
HO
24
f
OBn
HO
OH OH
HO
OH
Entirely to our surprise, the 13C NMR of the “deuterated” 1 in
CDCl3 turned out to be exactly the same as the one without the
deuteration treatment. Because of the structural similarity
between the previous[4g] diol and compound 1 here (both are 1,3-
diols with the hydroxyl groups located in the middle of an alkyl
chain), it appears impossible to explain why deuteration of the
hydroxyl groups in 1 would not cause any changes in the 13C
NMR. This forced us to consider that the deuterium might be lost
in the CDCl3. Indeed, a brief estimation suggested that only a
fraction of 1 mg of H2O in the CDCl3 may suffice for washing
out the deuterium in diol 1 in the NMR sample solution. To
exclude this possibility, we re-recorded the 13C NMR of the
deuterated 1 in CDCl3 in the presence of a very small amount of
CD3OD (which nevertheless was still in large molar excess with
respect to the dissolved 1 and thus ensured its deuteration). To
our gratification, the data acquired under such conditions (Table
1, the first column from the right) were indeed in full consistence
with those reported for the natural 1 and thus provided the
ultimate answer to the otherwise “mysterious” discrepancies15 in
the 13C NMR.
g
8
6
O
HO
OH
OH
CHO
27
27'
h
Cl
OH OH
1
8
6
26
1
Scheme 3. Reagents and conditions. a) HS(CH2)3SH, BF3-Et2O, CH2Cl2, RT,
1 h, 96%; b) pTsCl, Et3N, DMAP, THF, H2O, nBu2SnO, RT, 3 h, 87%; c)
K2CO3, MeOH, RT, 20 min; d) KSeCN MeOH-H2O, 65 °C, 22 h, 83%
overall from 21; e) 16 (10 mol%), CH2Cl2, PhOH, RT, 2 h, 41% (or 35% if
with Et2O as the solvent instead of CH2Cl2) along with recovered 23 (29%); f)
H2 (1 atm), Pd-C, EtOH, RT, 22 h, 87% from 25; g) NaIO4, MeOH-H2O (1:1,
v/v), RT, 40 min; h) CrCl2, CHCl3, THF, 65 °C, 4 h, see the text.
In light of the experience from a previous over-tosylation
case,18 we reasoned that the undesired di-tosylate(s) might be a
consequence of the better solubility of the primary product 21
compared with that of tetraol 20. However, all conventional
solvents compatible with tosylation all failed to effect better
solvation. Addition of H2O (which normally should be depleted)
to the THF solution of 20 was then tried. Interestingly, the
presence of traces of water indeed improved the solubility of 20
and significantly suppressed formation of the over-tosylation.
However, the reaction stopped well before full consumption of
the starting 20, because of full consumption of the p-TsCl by
hydrolysis. Increasing the added p-TsCl to 1.5 mol. equiv. (with
respect to 20) provided the desired mono tosylate 21 in 87%
yield, along with 7% of di-tosylates and 6% of recovered 20.
While working on the data discrepancies, efforts were also
made in exploring another route to 1, which did not involve
protection of the 1,3-diol functionality. As shown in Scheme 3,
the acetonide protecting group in the aforementioned diol 7 was
removed by treatment with propan-1,3-dithiol in the presence of
BF3-Et2O. To convert the terminal diol into a vinyl group in the
presence of the unmasked 1,3-diol functionality, the strategy
employed in Scheme 1 was apparently not applicable. Therefore,
an alternative via the corresponding epoxide 22 was devised,
which demanded selective activation of the primary hydroxyl
group and subsequent epoxidation exploiting the kinetic

4
Tetrahedron
ACCEPTED MANUSCRIPT
The functions of nBu2SnO and DMAP were also briefly
The terminal vic-diol in the resulting tetraol 26 was then
examined in the THF-H2O system. In the absence of either
species the reaction proceeded apparently much slower
(incomplete even after several days), while the di-tosylate
formation was evidently facilitated without nBu2SnO.
oxidatively cleaved with NaIO4 to cleanly afford the intermediate
aldehyde 27. However, subsequent reaction with CrCl2/CHCl3
failed to give any desired 1, presumably because of the strong
interference of cyclic hemiacetal formation.
Conversion of the mono tosylate 21 to furnish epoxide 22 by
treatment with K2CO3/MeOH proceeded without event. However,
the resulting epoxide was rather unstable, which began to
decompose even during work-up/chromatographic purification
and decomposed largely after standing at ambient temperature
overnight); subsequent reaction with KSeCN in tBuOH-H2O at
reflux according to the literature19 failed to give any acceptable
results because of extensive formation of side products.
For the purpose of direct comparison, we also synthesized the
cis diol 37 as shown in Scheme 4, which was similar to that in
Schemes 2-3, except that at the final step of this route, use of the
inexpensive and readily available CrCl3 as a precursor of the air-
sensitive CrCl2 was examined. To this end, we first tried to
employ the French protocol20 with Zn/NaI as the reducing agent.
However, although the outcomes in the literature were very
encouraging, this method failed to give acceptable results in our
case; the product was always accompanied by undesired iodine-
containing side product(s). It thus seemed that the presence of
NaI in the reaction system should be avoided. Use of LiAlH4 in
THF21 was then examined (with CHCl3 to replace the CHI3). To
our gratification, this reaction led to the desired vinyl
intermediate 36 smoothly, which on removal of the PMB
protecting groups with CAN gave the end product 37 in 83%
yield. The 13C NMR for 37 is indeed significantly different from
that for 1 (for quick comparison, cf. Table S1, Supplementary
information)
Then, we next tried to combine the two reactions into a “one-
flask” conversion using MeOH-H2O as the solvent (required for
the first step). Under such modified conditions, the desired
alkene 23 formed in good yields (65%). Even better results (80%
overall from 21) were later obtained by portionwise additions of
the reaction mixture of newly formed epoxide 22 to a solution of
KSeCN in MeOH-H2O and minimizing the reaction (heating)
time.
A CM reaction between 23 and the known 24 was performed
in the presence of catalyst 16 and phenol (to suppress the rather
facile allylol re-arrangement4h of 23 to the corresponding ethyl
ketone). The product 25 was rather difficult to purify because of
contamination of the dark catalyst-related species. Fortunately,
colored species could be readily removed after exposure of the
mixture to H2/Pd-C, the conditions for the simultaneous removal
of the benzyl protecting group and the saturation of the C-C
double bond.
3. Conclusion
Using expoxy chiral building blocks readily derived from
inexpensive D-gluconolactone as the source of the stereogenic
centers, both (6R,8R)-(E)-1-chlorotridec-1-ene-6,8-diol (a natural
product isolated from marine cyanophytes some 30 years ago)
and its (6R,8S) isomer were synthesized. The vinylchloro unit
was installed onto the substrate carbon chain in an approximately
9:1 (E)/(Z) ratio via a condensation of CrCl2/CHCl3 with an
terminal aldehyde, using either commercially available CrCl2 or
that formed in situ from CrCl3 and a reducing agent. Different
approaches for extending the carbon chain from the epoxy
building blocks were also explored. An abnormal tosylation of a
highly polar tetraol was developed featuring use of THF as the
reaction solvent in the presence of small amounts of added water
to suppress the unwanted over tosylation. The synthetic samples
allowed for re-acquisition of the NMR spectra and thus revealed
some delicate yet unignorable discrepancies in the 13C NMR for
the natural isomer obtained by synthesis and that isolated some
30 years ago from the marine cyanophyte. Although in retrospect
probably the hidden discrepancies (caused by the lack of an
explicit description of the NMR solvent employed for the natural
1) were already noticed by the previous investigators back in the
late 1990’s when they published the first synthesis of 1 (with
only optical rotation without any NMR data), the mysterious
smaller shifts of the C-6 and C-8 reported for the natural sample
were finally reproduced in this work by deuteration (or partial
deuteration) of the hydroxyl groups.
O
O
O
b
O
O
a
O
3
OH
OH
H
OPMB
OH
5
OPMB
O
29
28
30
PMBO
HO
OPMB
PMBO
OPMB
d
c
HO
32
31
e
PMBO
OPMB
PMBO
OPMB
OH
f
OH
g
34
33
(E)/(Z) = 92:8
PMBO
8
OPMB
6
PMBO
OPMB
h
Cl
1
4. Experimental
CHO
36
35
4.1. General.
OH OH
i
Cl
8
6
The NMR spectra were recorded on a Bruker Avance NMR
spectrometer operating at 400 MHz for 1H unless otherwise
stated. IR spectra were measured on a Nicolet 380 Infrared
spectrophotometer. ESI-MS data were acquired on a Shimadzu
LCMS-2010EV mass spectrometer. ESI-HRMS data were
obtained with a Bruker APEXIII 7.0 Tesla FT-MS spectrometer.
EI-MS were recorded on an Agilent Technologies 5973N
37
1
[ ]D27 +1.6 (c 0.33, MeOH)
Scheme 4. Reagents and conditions. a) cf. ref. 4h, 98%; b) PMBCl, NaH,
DMF, nBu4NI, RT, 5 h, 63%, or La(OTf)3, PMBOC(=NH)CCl3, DMF, RT,
12 h, 64%; c) PPTS, MeOH, RT, 12 h, 83% for 31 along with 17% recovered
30, d) Ph3P, imidazole, I2, THF, 80 °C, 1 h, 100%; e) 16 (10 mol%), Et2O, RT,
2 h; f) H2 (1 atm), skeletal Ni, RT, 1 h, 50% from 32; g) Dess-Martin
periodinane, NaHCO3, CH2Cl2 RT, 2 h, 93% along with 7% of recovered 34;
h) (i) CrCl3, LiAlH4, THF, 0 °C, (ii) CHCl3, THF, 65 °C, 3 h, 73%; i) CAN,
MeCN-H2O (10:1, v/v), RT, 1 h, 83%.
spectrometer. EI-HRMS were acquired using
a
Waters
Micromass GCT Premier instrument. Optical rotations were
measured on a Jasco P-1030 polarimeter. Melting points were

5
uncorrected (measured on a hot stage melting point apparatus
ESI-HRMS calcd for C26H38O6Na ([M+Na]+): 469.2561; found:
469.2557.
ACCEPTED MANUSCRIPT
equipped with a microscope). Dry THF was obtained by
distillation over Na/Ph2CO under argon prior to use. Dry toluene
and CH2Cl2 were acquired via drying over activated 4Å MS
(molecular sieves). All reagents were of reagent grade and used
as purchased. Column chromatography was performed on silica
gel (300-400 mesh) under slightly positive pressure. PE
(chromatography solvent) stands for petroleum ether (b.p. 60-90
°C).
4.4. Conversion of diol 9 into alkene 10.
A mixture of diol 9 (217 mg, 0.487 mmol), Ph3P (511 mg,
1.948 mmol), imidazole (256 mg, 3.895 mmol) and I2 (493 mg,
1.948 mmol) in THF (1.5 mL) was stirred in a 60-80 °C bath for
1 h with precaution to exclude direct light. After cooling to
ambient temperature, the mixture was diluted with Et2O (10 mL),
washed in turn with aq. sat. Na2S2O3 (2 mL) and water (2 mL)
before being dried over anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chromatography (15:1
PE/EtOAc) on silica gel afforded alkene 10 as a colorless oil
(195 mg, 0.472 mmol, 97% from 9). [α]D28 –74.4 (c 1.0, CHCl3);
1H NMR (400 MHz, CDCl3): δ = 7.22 (d, J = 8.7 Hz, 2H), 7.17
(d, J = 8.5 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.7 Hz,
2H), 5.75 (ddd, J = 17.7, 14.4, 7.5, 1H), 5.23 (d, J = 17.2 Hz,
1H), 5.19 (d, J = 10.2 Hz, 1H), 4.50 (d, J = 11.1 Hz, 1H), 4.42 (d,
J = 11.1 Hz, 1H), 4.23 (d, J = 11.2 Hz, 1H), 4.17 (d, J = 11.3 Hz,
1H), 3.99 (td, J = 8.3, 4.0 Hz, 1H), 3.742 (s, 3H), 3.737 (s, 3H),
3.68-3.60 (m, 1H), 1.76-1.60 (m, 2H), 1.59-1.41 (m, 2H), 1.39-
1.20 (m, 6H), 0.88 (t, J = 6.5 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 159.01, 158.97, 139.2, 131.1, 130.7, 129.4,
129.2,116.3, 113.62, 113.59, 76.7, 75.0, 70.7, 69.7, 55.08, 55.07,
41.3, 34.1, 32.0, 24.5, 22.5, 14.0 ppm; FT-IR (film): 2931, 2859,
1613, 1586, 1513, 1465, 1301, 1247, 1172, 1068, 1036, 924, 820
cm–1. ESI-MS m/z 435.6 ([M+Na]+). ESI-HRMS calcd for
C26H38O6Na ([M+Na]+): 435.2506; found: 435.2486.
4.2. PMB protection of diol 7 to afford 8.
NaH (60% suspension in mineral oil, 159 mg, 3.98 mmol) was
added in portions to a solution of diol 7 (196 mg, 0.80 mmol) and
nBu4NI (29 mg, 0.08 mmol) in dry DMF (1.6 mL) stirred under
N2 (balloon) in an ice-water bath. After completion of the
addition, the bath was removed. The mixture was stirred at
ambient temperature for 1 h. Then with cooling (ice-water bath),
PMBCl (0.49 mL, 3.59 mmol)) was added slowly. Stirring was
continued at ambient temperature for 5 h. Crushed ice was added
to the reaction system, followed by Et2O (30 mL) and water (5
mL). The phases were separated. The organic layer was washed
with brine and dried over anhydrous Na2SO4. Removal of the
solvent by rotary evaporation and column chromatography (10:1
PE/EtOAc) on silica gel gave 8 as a colorless oil (348 mg, 0.720
28
1
mmol, 90% from 7). [α]D –57.9 (c 1.0, CHCl3). H NMR (400
MHz, CDCl3): δ = 7.23 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 8.5 Hz,
2H), 6.85 (d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.9 Hz, 2H), 4.67 (d, J
= 11.0 Hz, 1H), 4.46 (d, J = 11.0 Hz, 1H), 4.38 (d, J = 10.9 Hz,
1H), 4.19 (d, J = 11.1 Hz, 1H), 4.13 (dt, J = 3.8, 7.1 Hz, 1H),
3.98 (dd, J = 7.8, 6.6 Hz, 1H), 3.88(t, J = 7.7 Hz, 1H), 3.85-3.81
(m, 1H), 3.77 (s, 6H), 3.63-3.55 (m, 1H), 1.70-1.46 (m, 4H ),
1.44 (s, 3H ), 1.35 (s, 3H), 1.34-1.22 (m, 6H), 0.89 (t, J = 7.0 Hz,
3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.1, 159.0, 131.0,
130.9, 129.33, 129.26, 113.71, 113.68, 108.9, 78.8, 75.1, 75.0,
73.0, 70.1, 65.4, 55.20, 55.18, 37.1, 33.7, 32.0, 26.4, 25.2, 24.5,
22.6, 14.0 ppm; FT-IR (film): 2932, 2861, 1613, 1514, 1464,
1379, 1301,1248, 1173, 1069, 1036, 820 cm–1. ESI-MS m/z 509.7
([M+Na]+). ESI-HRMS calcd for C29H42O6Na ([M+Na]+):
509.2874; found: 509.2869.
4.5. Hydroboration of alkene 10 to afford alcohol 11.
BH3 (0.2 M solution in THF, 3.38 mL, 6.735 mmol) was
added via a syringe to a solution of alkene 10 (150 mg, 0.364
mmol) in dry THF (14 mL) stirred under N2 (balloon) in an ice-
water bath. After completion of the addition, the cooling bath
was removed. The mixture was stirred at ambient temperature for
3.5 h. With cooling (ice-water bath), EtOH (2 mL) was added
slowly to decompose the excess BH3, followed by aq. NaOH (3
M, 2 mL) and H2O2 (2 mL, added very slowly). The mixture was
stirred at ambient temperature for 2 h. White precipitates formed.
The mixture was diluted with EtOAc (20 mL), washed with
water (3 mL). The aq. layer was back extracted with EtOAc (10
mL). The combined organic layers were washed with brine and
dried over anhydrous Na2SO4. Removal of the solvent by rotary
evaporation and column chromatography (3:1 PE/EtOAc) on
silica gel furnished alcohol 11 as a colorless oil (93 mg, 0.218
mmol, 60% from 10) along with a side product with one of the
two PMB group removed (14 mg, 0.045 mmol, 12 % from 10).
Data for 11: [α]D –42.6 (c 1.0, CHCl3); H NMR (400 MHz,
CDCl3): δ = 7.217 (d, J = 8.6 Hz, 2H), 7.204 (d, J = 8.6 Hz, 2 H),
6.85 (d, J = 8.5 Hz, 4H), 4.464 (d, J = 11.0 Hz, 1H), 4.456 (d, J =
11.0 Hz, 1H), 4.32 (d, J = 10.9 Hz, 1H), 4.25 (d, J = 11.0 Hz,
1H), 3.83-3.72 (m, 2H), 3.761 (s, 3H), 3.756 (s, 3H), 3.70-3.62
(m, 1H), 3.61-3.52 (m, 1H), 2.71-2.40 (br s, 1H, OH),1.91-1.80
(m, 1H), 1.80-1.45 (m, 5H), 1.40-1.27 (m, 6H), 0.89 (t, J = 6.3
Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.13, 159.06,
130.8, 130.5, 129.39, 129.35, 113.72, 113.68, 75.4, 74.6, 70.8,
70.3, 59.8, 55.1, 39.6, 36.2, 33.8, 32.0, 24.4, 22.5, 14.0 ppm; FT-
IR (film): 3441, 2930, 2857, 1613, 1586, 1514, 1465, 1354,
1302, 1248, 1173, 1035, 820 cm–1. ESI-MS m/z 453.8 ([M+Na]+).
ESI-HRMS calcd for C26H38O5Na ([M+Na]+): 453.2612; found:
453.2606.
4.3. Hydrolysis of the acetonide in 8 to afford diol 9.
A solution of acetonide 8 (163 mg, 0.335 mmol) and PPTS
(169 mg, 0.671 mmol) in MeOH (6.7 mL) was stirred at ambient
temperature overnight. The solvent was removed on a rotary
evaporator. The residue was dissolved in EtOAc (30 mL) and
washed with water (5 mL). The phases were separated. The
aqueous layer was back extracted with EtOAc (2×10 mL). The
combined organic layers were washed with brine and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (1:1 PE/EtOAc) on silica gel gave
diol 9 as a colorless oil (126 mgꢀ0.285mmol, 85% from 8)
along with recovered starting 8 (24 mg, 0.050 mmol, 15%). Data
for 9: [α]D27 –57.7 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ
= 7.22 (d, J = 8.7 Hz, 2H), 7.20 (d, J = 8.7 Hz, 2H), 6.862 (d, J =
8.5 Hz, 2H), 6.857 (d, J = 8.4 Hz, 2H), 4.51 (d, J = 11.3 Hz, 1H),
4.48 (d, J = 12.3 Hz, 1H), 4.38 (d, J = 11.3 Hz, 1H), 4.23 (d, J =
11.1 Hz, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 3.76-3.71 (m, 1H), 3.70-
3.59 (m, 3H), 3.58-3.50 (m, 1H), 2.56-2.19 (br s, 2H, OH), 1.78-
1.58 (m, 3H ), 1.58-1.47 (m, 1H ), 1.40-1.27 (m, 6H), 0.90 (t, J =
6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ = 159.3, 159.2,
130.4, 130.3, 129.52, 129.46, 113.86, 113.83, 78.0, 75.9, 73.2,
72.2, 70.2, 63.4, 55.2, 36.3, 33.5, 32.0, 24.4, 22.6, 14.0 ppm; FT-
IR (film): 3442, 2931, 2859, 1612, 1586, 1514, 1465, 1302,
1248, 1173, 1073, 1035, 820 cm–1. ESI-MS m/z 469.7 ([M+Na]+).
27
1
4.6. Conversion of alcohol 11 into iodide 12.
I2 (39 mg, 0.154mmol) was added to a solution of 11 (33 mg,
0.077 mmol), Ph3P (41 mg, 0.154 mmol) and imidazole (21 mg,

6
Tetrahedron
ACCEPTED MANUSCRIPT
0.308 mmol) in THF (0.4 mL) stirred in an ice-water bath with
131.07, 129.32, 129.30, 113.7, 75.53, 75.47, 70.6, 70.4, 62.8,
precaution to exclude light. Then, stirring was continued for 2 h
before being diluted with Et2O (10 mL), washed with aq. sat.
NaS2SO3 (1 mL) and water (2 mL) and dried over anhydrous
Na2SO4. Removal of the solvent by rotary evaporation and
column chromatography (10:1 PE/EtOAc) on silica gel afforded
iodide 12 as a colorless oil (39 mg, 0.077 mmol, 100% from
11).[α]D27 –30.0 (c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3): δ =
7.25 (d, J = 9.0 Hz, 2H), 7.22 (d, J = 9.0 Hz, 2H), 6.858 (d, J =
8.4 Hz, 2H), 6.853 (d, J = 8.5 Hz, 2H), 4.45 (d, J = 11.1 Hz, 1H),
4.44 (d, J = 11.0 Hz, 1H), 4.33 (d, J = 10.9 Hz, 1H), 4.27 (d, J =
10.6 Hz, 1H), 3.77 (s, 6H), 3.70-3.63 (m, 1H), 3.58-3.51 (m, 1H),
3.27-3.16 (m, 2H), 2.12-2.02 (m, 2H), 1.74-1.67 (m, 1H), 1.64-
1.45 (m, 3H), 1.37-1.23 (m, 6H), 0.89 (t, J = 6.8 Hz, 3H) ppm;
13C NMR (125 MHz, CDCl3): δ = 159.2, 159.1, 130.9, 130.6,
129.4, 113.8, 113.7, 75.9, 75.3, 71.2, 70.3, 55.2, 39.6, 39.2, 33.9,
32.0, 24.5, 22.6, 14.0, 2.2 ppm; FT-IR (film): 2930, 2857, 1612,
55.2, 40.1, 34.0, 33.9, 32.9, 32.1, 24.6, 22.6, 21.1, 14.0 ppm; FT-
IR (film): 3431, 2931, 2859, 2363, 1612, 1586, 1513, 1464,
1354, 1301, 1248, 1173, 1064, 1036, 820 cm–1. ESI-MS m/z
481.8 ([M+Na]+). ESI-HRMS calcd for C28H42O5Na ([M+Na]+):
481.2925; found: 481.2935.
4.8. Oxidation of alcohol 17 to afford aldehyde 18.
Dess-Martin periodinane (185 mg, 0.436 mmol) was added to
a mixture of alcohol 17 (100 mgꢀ0.218 mmol) and NaHCO3
(183 mgꢀ2.18 mmol) in dry CH2Cl2 (4.3 mL) stirred in an ice-
water bath. After completion of the addition, the bath was
removed. Stirring was continued at ambient temperature for 2 h.
Aq. sat. Na2S2O3 (1 mL) was added, followe by EtOAc (20 mL)
and water (3 mL). The phases were separated. The organic layer
was washed with brine and dried over anhydrous Na2SO4.
Removal of the solvent by rotary evaporation and column
chromatography (5:1 PE/EtOAc) on silica gel gave aldehyde 18
as a colorless oil (85 mg, 0.185mmol, 85%), along with
recovered starting 17 (10 mg, 0.022 mmol, 10 %). Data for 18:
1586, 1513, 1464, 1355, 1301, 1248, 1172, 1064, 1036, 820 cm–
1
.
ESI-MS m/z 563.6 ([M+Na]+). ESI-HRMS calcd for
C26H37O4INa ([M+Na]+): 563.1629; found: 563.1627.
[α]D28 –62.0 (c 1.0, CHCl3); H NMR (500 MHz, CDCl3): δ =
1
4.7. Synthesis of 17 via cross metathesis between 10 and 14
9.74 (s, 1H), 7.22 (d, J = 8.9 Hz, 4H), 6.85 (d, J = 8.4 Hz, 4H),
4.45 (d, J = 11.1 Hz, 1H), 4.43 (d, J = 11.3 Hz, 1H), 4.33 (d, J =
13.2 Hz, 1H), 4.25 (d, J = 10.8 Hz, 1H), 3.78 (s, 6H), 3.65-3.55
(m, 2H), 2.41 (t, J = 7.1 Hz, 2H), 1.73-1.52 (m, 8H), 1.38-1.27
(m, 6H), 0.89 (t, J = 6.0Hz, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ = 202.5, 159.1, 159.07, 131.1, 130.9, 129.4, 129.3,
113.75, 113.73, 75.5, 75.1, 70.7, 70.5, 55.2, 43.9, 39.9, 34.0,
33.5, 32.1, 24.5, 22.6, 17.5, 14.0 ppm; FT-IR (film): 2930, 2857,
followed by hydrogenation.
A solution of 3-buten-1-ol (14, 0.15 mL, 1.663 mmol) in dry
Et2O (1 mL) was added slowly over 1 h (with the aid of a syringe
pump) to a mixture of alkene 10 (137 mg, 0.333 mmol) and
catalyst 16 (42 mg, 0.05 mmol) in dry Et2O (2 mL) stirred at
ambient temperature under N2 (balloon). After completion of the
addition, the mixture was stirred at the same temperature for 3 h
before another portion of 14 (0.15 mL, 1.663 mmol) was added.
Stirring was continued at the same temperature overnight. The
flask was then open to air with stirring continued for 5 h to
oxidize the catalyst. The mixture was then concentrated on a
rotary evaporator. The residue was chromatographed (2:1
PE/EtOAc) on silica gel to give 15 (79 mg, 0.17mmol, 51% from
10) as a dark oil (due to contamination of traces of the catalyst-
related impurities), from which the following data were acquired:
[α]D27 –64.7 (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ = 7.21
(d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.5 Hz, 2 H), 6.84 (d, J = 8.5 Hz,
2H), 6.83 (d, J = 8.5 Hz, 2H), 5.68-5.54 (m, 1H ), 5.54-5.41 (m,
1H), 4.45 (d, J = 11.6 Hz, 1H), 4.43 (d, J = 11.1 Hz, 1H), 4.22 (d,
J = 11.0 Hz, 1H), 4.17 (d, J = 11.3 Hz, 1H), 3.96 (dt, J = 3.5, 8.9
Hz, 1H), 3.761 (s, 3H), 3.755 (s, 3H), 3.62 (t, J = 6.4 Hz, 3H),
2.41-2.22 (m, 2H), 1.94-1.79 (br s, 1H, OH), 1.75-1.58 (m, 2H ),
1.58-1.41 (m, 2H), 1.37-1.19 (m, 6H), 0.88 (t, J = 6.3 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ = 159.12, 159.09, 134.0,
131.2, 130.9, 129.5, 129.4, 129.1, 113.8, 113.7, 76.3, 75.2, 70.8,
69.7, 62.0, 55.27, 55.25, 41.6, 35.7, 34.2, 32.1, 24.6, 22.7, 14.1
ppm; FT-IR (film): 3412, 2931, 2859, 1612, 1586, 1513, 1465,
1301, 1248, 1173, 1036, 970, 820 cm–1. ESI-MS m/z 479.7
([M+Na]+). ESI-HRMS calcd for C28H40O5Na ([M+Na]+):
479.2768; found: 479.2775.
1725, 1611, 1513, 1466, 1301, 1248, 1172, 1067, 1035, 820 cm–
1
.
ESI-MS m/z 479.6 ([M+Na]+). ESI-HRMS calcd for
C28H40O5Na ([M+Na]+): 479.2768; found: 479.2764.
4.9. Conversion of aldehyde 18 into chroroalkene 19.
A solution of aldehyde 18 (61 mg, 0.131 mmol) and CHCl3
(26 µL, 0.263 mmol) in dry THF (1.0 mL) was added via a
syringe to a mixture of CrCl2 (160 mg, 1.31 mmol) in dry THF
(1.5 mL) placed in a screw-capped (with a septum) test tube
stirred at ambient temperature under argon (balloon). The
resulting dark-red mixture was heated at 65 °C for 4 h. After
cooling to ambient temperature, the mixture was diluted with
Et2O (10 mL), washed in turn with water (1 mL), aq. sat.
NaHCO3, water and brine before being dried over anhydrous
Na2SO4. Removal of the solvent by rotary evaporation and
column chromatography (17:1 PE/EtOAc) on silica gel gave 19
as a colorless oil (a 92:8 inseparable (E)/(Z) mixture, 40 mg,
0.083mmol, 65% from 18). [α]D25 –47.3 (c 1.0, CHCl3); 1H NMR
(400 MHz, CDCl3): δ = 7.22 (d, J = 8.5 Hz, 2H), 7.21 (d, J = 8.5
Hz, 2H), 6.86 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 6.02
(dt, J = 7.0, 1.3 Hz, 0.08H), 5.92 (d, J = 13.3 Hz, 0.92H), 5.88
(dt, J = 13.4, 6.6 Hz, 0.92H), 5.73 (q, J = 14.5, 7.2 Hz, 0.08H ),
4.45 (d, J = 11.0 Hz, 1H), 4.42 (d, J = 11.0 Hz, 1H), 4.27 (d, J =
11.0 Hz, 1H), 4.25 (d, J = 11.1 Hz, 1H), 3.78 (s, 3H), 3.77 (s,
3H), 3.64-3.55 (m, 2H), 2.03 (q, J = 13.9, 7.1 Hz, 2H), 1.65-1.39
(m, 8H), 1.38-1.26 (m, 6H), 0.89 (t, J = 6.9 Hz, 3H) ppm; 13C
NMR (100 MHz, CDCl3): δ = 159.14, 159.12, 133.8, 131.2,
131.1, 129.37, 129.35, 117.0, 113.8, 75.6, 75.3, 70.7, 70.5, 55.3,
40.1, 34.1, 33.5, 32.1, 31.2, 24.6, 24.2, 22.7, 14.1 ppm; FT-IR
(film): 2931, 2858, 2063, 1613, 1586, 1514, 1464, 1442, 1353,
1302, 1248, 1172, 1070, 1037, 936, 821, 754 cm–1. ESI-MS m/z
511.7 ([M+Na]+). ESI-HRMS calcd for C26H37O4INa ([M+Na]+):
511.2586; found: 511.2599.
A mixture of the 15 obtained as the above (combined from
two parallel runs, 121 mg, 0.265 mmol) and skeletal Ni (30 mg)
in MeOH (1.5 mL) was stirred under atmospheric H2 for 1 h. The
catalyst was removed by filtration. The conbined filtrate and
EtOAc washings were concentrated on a rotary evaporator. The
residue was chromatographed (2:1 PE/EtOAc) on silica gel to
furnish 17 as a colorless oil (115 mg, 0.26mmol, 49% overall
from 10). Data for 17: [α]D26 –65.8 (c 1.0, CHCl3); 1H NMR (500
MHz, CDCl3): δ = 7.22 (d, J = 8.1 Hz, 4H), 6.85 (d, J = 8.5 Hz,
4H), 4.47 (d, J = 8.1 Hz, 1H), 4.44 (d, J = 8.1 Hz, 1H), 4.27 (d, J
= 8.3 Hz, 1H), 4.25 (d, J = 8.4 Hz, 1H), 3.77 (s, 6H), 3.63-3.56
(m, 4H), 1.65-1.46 (m, 8H), 1.44-1.24 (m, 8H), 0.89 (t, J = 6.6
Hz, 3H); 13C NMR (125 MHz, CDCl3): δ = 159.0, 131.13,
4.10. Removal of the PMB protecting groups in 19 to afford 1.

7
A mixture of 19 (49 mg, 0.10mmol) and CAN (137 mg,
0.25mmol) in MeCN-H2O (10:1, v/v, 1.65 mL) was stirred at
ambient temperature for 1 h. The mixture was diluted with
CH2Cl2 (5 mL), washed with aq. sat. NaHCO3 and brine before
being dried over anhydrous Na2SO4. Removal of the solvent by
rotary evaporation and column chromatography (4:1 PE/EtOAc)
on silica gel gave 1 as a white powder (22 mg, 0.089 mmol, 89%
= 8.2 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 4.20-4.15 (m, 2H),
ACCEPTED MANUSCRIPT
3.98-3.84 (m, 2H), 3.78-3.71 (m, 1H), 3.42-3.36 (br s, 3H, OH),
2.44 (s, 3H), 1.63 (t, J = 6.0 Hz, 2H), 1.54-1.22 (m, 8H), 0.88 (t,
J = 6.6 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 145.1,
132.3, 130.0, 128.0, 72.5, 71.6, 69.1, 68.8, 38.7, 37.6, 31.7, 25.3,
22.5, 21.6, 14.0 ppm; FT-IR (film of a conc. solution in CH2Cl2):
3399, 2929, 2859, 1598, 1456, 1356, 1190, 1175, 1096, 1065,
974, 814, 668, 555cm–1. ESI-MS m/z 383.3 ([M+Na]+). ESI-
HRMS calcd for C17H28O6SNa ([M+Na]+): 383.1499; found:
383.1502.
from 19). M.p. 49-51 °C. [α]D –10.8 (c 1.0, MeOH), [α]D28 = –
28
11.2 (c = 0.33, MeOH); 1H NMR (500 MHz, CDCl3): δ = 5.95 (d,
J = 13.0 Hz, 1H), 5.91 (dt, J = 13.1, 6.9 Hz, 1H), 3.99-3.91 (2H,
m), 2.10 (q, J = 14.1, 7.6 Hz, 2H), 1.96-1.72 (br s, 2H, OH),
1.94-1.82 (m, 2H), 1.64-1.25 (m, 12H), 0.90 (t, J = 7.0 Hz, 3H)
ppm; 1H NMR (400 MHz, d6-acetone): δ = 6.12 (dt J = 13.2, 1.0
Hz, 1H), 5.94 (dt, J=13.2, 7.2 Hz, 1H), 3.90-3.81 (m, 2H), 3.66
(d, J=5.1 Hz, 1H), 3.60 (d, J = 5.1 Hz, 1H), 2.15-2.06 (m, 2H),
1.52-1.23 (m, 14H), 0.88 (t, J = 6.8 Hz, 3H) ppm; 1H NMR (500
MHz, CD3OD): δ = 6.06 (d, J = 13.2 Hz, 1H), 5.91 (dt, J = 13.2,
7.3 Hz, 1H), 3.84-3.74 (m, 2H), 2.15-2.02 (m, 2H), 1.51-1.13 (m,
14H), 0.91 (t, J = 6.5 Hz, 3H) ppm; 1H NMR (500 MHz, CDCl3-
CD3OD (6:0.1, v/v)): δ = 5.96 (d, J = 13.5 Hz, 1H), 5.89 (dt, J =
13.2, 6.9 Hz, 0.8H), 3.86-3.95 (2H, m), 2.09 (q, J = 14.4 , 7.0 Hz,
2H), 1.99-1.87 (br s, 2H, OH), 1.28-1.60 (m, 16H), 0.90 (t, J =
7.0 Hz, 3H) ppm; 13C NMR (125 MHz, CD3OD): δ = 135.1,
118.1, 69.3, 69.0, 45.6, 39.2, 38.4, 33.1, 31.7, 26.5, 26.2, 23.2,
14.4 ppm; for 13C NMR in CDCl3, d6-acetone or CDCl3-CD3OD
(6/0.1, v/v), see Table 1; FT-IR (film of a conc. solution in
CH2Cl2): 3341, 2919, 2857, 1710, 1631, 1459, 1070, 935, 827
cm–1. ESI-MS m/z 271.4 ([M+Na]+). ESI-HRMS calcd for
C13H25ClO2Na ([M+Na]+): 271.1435; found: 271.1430.
4.13. Conversion of tosylate 21 into alkene 23 via epoxide 22.
K2CO3 (137 mg, 0.99 mmol) was added to a solution of 21
(236 mg, 0.660 mmol) in MeOH (1.2 mL) stirred in an ice-water
bath. After stirring at the same temperature for 30 min, the
mixture was cooled to –78 °C (bath). Solids were filtered through
Celite (washing with dry-ice cooled MeOH, 3 mL). The
combined filtrate and washings (cooled in a –78 °C bath before
the addition to KSeCN to avoid decomposition of the unstable
intermediate epoxide) were added (in ca. 0.5 mL portions
through a pipette over 3 h) to a solution of KSeCN(380 mg, 2.64
mmol) in MeOH (1.0 mL) and H2O (0.22 mL) stirred at refluxing
temperature. The resulting mixture was refluxed for 3h before
being cooled to ambient temperature. The solids were filtered
through Celite (washing with CH2Cl2). The combined filtrate and
washings were concentrated on a rotary evaporator. The residue
was dissolved in CH2Cl2, washed with water, and dried over
anhydrous Na2SO4. Removal of the solvent by rotary evaporation
and column chromatography (2:1 PE/EtOAc) on silica gel gave
the known alkene 23 as a colorless oil (94 mg, 0.55 mmol, 83%
from 21), with all data in full consistence with those[4h] in the
literature. (The 1H and 13C NMR are alsoprovided in the
Supporting Information).
4.11. Removal of the acetonide group in 7 to afford tetraol 20.
A solution of 7 (730 mg, 2.967 mmol), HS(CH2)2SH (0.75
mL, 7.418 mmol) and BF3·OEt2 (28 µL, 0.223 mmol) in CH2Cl2
(15 mL) was stirred at ambient temperature for 2 h. The mixture
was concentrated on a rotary evaporator. The residue was
chromatographed (1:6 MeOH/CH2Cl2) on silica gel to give tetraol
20 as a white powder (588 mg, 2.85 mmol, 96% from 7). M.p.
4.14. Cross metathesis between 23 and 24 and subsequent
hydrogenation leading to 26.
A mixture of 23 (20 mg, 0.116 mmol), 24 (111 mg, 0.58
mmol), PhOH (5.0 mg, 0.058 mmol), and catalyst 16 (10 mg,
0.012 mmol) in dry CH2Cl2 (2.5 mL) was heated at reflux under
argon (balloon) for 3 h. The mixture was then concentrated on a
rotary evaporator. The residue was chromatographed (1:1
PE/EtOAc) on silica gel to give 25 as a dark-brown oil (due to
contamination by traces of the catalyst-related impurities, 16 mg,
0.048 mmol, 41% from 23), together with recovered 23 (5.0 mg,
0.029 mmol, 25%). (The dark impurity made it impossible to
measure [α]). 1H NMR (500 MHz, CDCl3): δ = 7.38-7.27(m, 4H),
5.75-5.66 (m, 1H), 5.66-5.60 (m, 1H), 4.54(s, 2H), 4.39 (q, J =
10.6, 4.8 Hz, 1H), 3.91-3.83 (m, 2H), 3.52-3.46 (m, 1H), 3.40-
3.33 (m, 1H), 2.82-2.50 (br s, 3H, OH), 2.29-2.17(m, 2H), 1.65
(q, J = 10.5, 5.3 Hz, 2H), 1.55-1.36 (m, 3H), 1.36-1.22 (m, 6H),
0.89 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ =
137.93, 137.91, 135.93, 135.84, 128.49, 127.83, 127.78, 126.75,
126.59, 73.95, 73.91, 73.4, 70.47, 70.39, 69.90, 69.88, 69.21,
69.18, 42.68, 42.54, 37.60, 37.58, 36.24, 36.21, 31.9, 25.3, 22.6,
14.0 ppm; FT-IR (film): 3382, 2929, 2858, 1454, 1363, 1094,
1028, 971, 736 698 cm–1. ESI-MS m/z 359.1 ([M+Na]+). ESI-
HRMS calcd for C20H32O4Na ([M+Na]+): 359.2193; found:
359.2200.
24
54-56 °C. [α]D –22.6 (c 1.0, CHCl3). 1H NMR (500 MHz,
CD3OD): δ = 3.87-3.77 (m, 2H), 3.71 (dd, J = 11.3, 3.7 Hz, 1H),
3.57 (dd, J = 11.2, 6.5 Hz, 1H), 3.48 (dt, J = 4.0, 6.3 Hz, 1H),
1.67 (ddd, J = 14.7, 9.8, 2.3 Hz, 1H), 1.54 (ddd, J = 14.1, 9.6, 2.2
Hz, 1H), 1.51-1.43 (m, 3H), 1.41-1.24 (m, 5H), 0.92 (t, J = 6.7
Hz, 3H ) ppm; 13C NMR (125 MHz, CD3OD): δ = 76.4, 70.6,
69.2, 64.5, 41.1, 39.2, 33.1, 26.5, 23.7, 14.4 ppm; FT-IR (film of
a conc. solution in CH2Cl2): 3283, 2954, 2921, 2852, 1675, 1465,
1379, 1202, 1131, 1062, 1030, 908, 875, 669, 650 cm–1. EI-MS
m/z (%) 207 (M+ + 1, 3.0), 157 (8.0), 145 (20.2), 127 (21.0), 117
(65.7), 109 (97.2), 101 (31,4), 99 (30.9), 83 (71.0), 55 (100). EI-
HRMS calcd for C9H17O2 (M+ – CH2OH and H2O): 157.1231;
found: 157.1229.
4.12. Tosylation of tetraol 20 to afford monotosylate 21.
nBu2SnO (18mg, 0.071mmol) was added to a solution of
tetraol 20 (146 mg, 0.709 mmol) in THF (6.5 mL) and H2O (0.7
mL), followed by DMAP (9 mg, 0.071 mmol) and Et3N (0.15
mL, 1.06 mmol). The mixture was stirred at ambient temperature
for 15 min. pTsCl (202 mg, 1.06 mmol) was added. The mixture
was stirred at the same temperature for another 5 h. The solids
were filtered off (washing with EtOAc). The combined filtrate
and washings were concentrated on a rotary evaporator. The
residue was chromatographed (1:2 PE/EtOAc) on silica gel to
furnish the desired mono tosylate 21 as a white powder (222 mg,
0.62mmol, 87% from 20), along with an undesired ditosylate (26
A mixture of the above obtained 25 (14 mg, 0.042mmol) and
10% Pd-C (5 mg) in EtOH (1 mL) was stirred at ambient
temperature under atmospheric H2 for 22 h. The solids were
filtered off. The filtrate and washings were concentrated by
rotary evaporation. The residue was chromatographed (1:5
CH2Cl2/MeOH) on silica gel to furnish tetraol 26 (9 mg, 0.037
mmol, 87% from 25) as a white wax. [α]D24 –8.4 (c 1.0, CH3OH).
22
mg, 0.05 mmol, 7% from 20). Data for 21: M.p. 58-60 °C. [α]D
+1.8 (c 1.0, CH3OH). 1H NMR (400 MHz, CDCl3) δ = 7.80 (d, J

8
Tetrahedron
1H NMR (500 MHz, CD3OD): δ = 3.86-3.77 (m, 2H), 3.62-3.54
ESI-HRMS calcd for C26H38O6Na ([M+Na]+): 435.2506; found:
ACCEPTED MANUSCRIPT
(m, 1H), 3.52-3.39 (m, 2H), 1.71-1.20 (m, 16H), 0.92 (t, J = 6.7
Hz, 3H) ppm; 13C NMR (125 MHz, CD3OD): δ = 73.23, 73.21,
69.3, 69.20, 69.17, 67.38, 67.36, 45.57, 45.54, 39.20, 39.18,
34.42, 34.38, 33.1, 26.5, 23.7, 22.8, 14.4 ppm; FT-IR (film of a
conc. solution in CH2Cl2): 3315, 2931, 2857, 1459, 1409, 1376,
1351, 1176, 1064, 1030, 901, 831, 737 cm–1. EI-MS m/z (%) 199
(6.7, (M+ – CH2OH and H2O), 185 (2.1), 181 (3.3), 115 (58.2),
109 (34.6), 97 (38.5), 55 (100). EI-HRMS calcd for C12H23O2
(M+ – CH2OH and H2O): 199.1698; found: 199.1702.
435.2519.
4.18. Synthesis of 34 via cross metathesis between 32 and 14
followed by hydrogenation.
The same procedure described above for coupling of 10 with
14 followed by hydrogenation to afford 17 was employed (with
32 to replace 10). Data for 34 (a colorless oil, 250 mg, 0.54
mmol, 50% for two steps from 32): [α]D24 +6.9 (c 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 7.23 (d, J = 8.7 Hz, 4H), 6.85 (d, J
= 8.1 Hz, 4H), 4.47-4.34 (m, 4H), 3.79 (s, 6H), 3.59 (t, J = 6.1
Hz, 2H), 3.49-3.39 (m, 2H), 2.01-1.88 (m, 1H), 1.76-1.19 (m,
16H), 0.88 (t, J = 6.6 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ = 159.06, 159.03, 131.0, 130.9, 129.4, 113.7, 75.6,
75.5, 70.2, 70.1, 62.8, 55.23, 55.22, 38.6, 34.0, 33.8, 32.8, 32.0,
24.8, 22.6, 21.4, 14.0 ppm; FT-IR (film): 3460, 2932, 2859,
1734, 1612, 1586, 1513, 1464, 1364, 1302, 1248, 1173, 1061,
1036, 820 cm–1. ESI-MS m/z 481.5 ([M+Na]+). ESI-HRMS calcd
for C28H42O5Na ([M+Na]+): 481.2925; found: 481.2934.
4.15. PMB protection of diol 29 to afford 30.
The same procedure given above for conversion of 7 into 8
was employed (with 29 to place of 7). Data for 30 (a colorless
27
1
oil, 1.490 g, 63% from 29): [α]D +3.4 (c 1.0, CHCl3); H NMR
(500 MHz, CDCl3): δ = 7.24 (d, J = 9.1 Hz, 2H), 7.21 (d, J = 9.2
Hz, 2H), 6.89 (d, J = 9.0 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 4.59
(d, J = 11.1 Hz, 1H), 4.49 (d, J = 11.2 Hz, 1H), 4.41 (s, 2H), 4.12
(dt, J = 4.6, 6.9 Hz, 1H), 4.01 (dd, J = 8.4, 6.7Hz, 1H), 3.86 (t, J
= 7.4 Hz, 1H), 3.79 (s, 6H), 3.60-3.65 (m, 1H), 3.51 (quint, J =
6.0 Hz, 1H), 1.85 (dt, J = 14.7, 6.8 Hz, 1H), 1.65-1.59 (m, 1H ),
1.50-1.44 (m, 2H ), 1.43 (s, 3H ), 1.35 (s, 3H), 1.31-1.17 (m, 6H),
0.88 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ =
159.2, 131.0, 130.6, 129.5, 129.3, 113.69, 113.67, 109.0, 78.6,
75.6, 75.5, 72.2, 70.2, 66.0, 55.24, 55.21, 36.3, 33.9, 32.0, 26.5,
25.3, 24.8, 22.6, 14.0 ppm; FT-IR (film): 2933, 2860, 1612,
1514, 1464, 1370, 1301, 1248, 1173, 1069, 1036, 821 cm–1. ESI-
MS m/z 509.7 ([M+Na]+). ESI-HRMS calcd for C29H42O6Na
([M+Na]+): 509.2874; found: 509.2884.
4.19. Oxidation of alcohol 34 to afford aldehyde 35.
The same procedure described above for oxidation of 17 to
give 18 was employed (with 34 to replace 17). Data for 35 (a
colorless oil, 85 mg, 0.19 mmol, 93% from 34): [α]D +13.7 (c
27
1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 9.70 (t, J = 1.9 Hz,
1H), 7.22 (d, J = 7.6 Hz, 4H), 6.85 (d, J = 8.6 Hz, 4H), 4.48-4.33
(m, 4H), 3.80 (s, 6H), 3.51-3.38 (m, 2H), 2.34 (t, J = 7.4 Hz, 2H),
1.99-1.89 (m, 1H), 1.80-1.17 (m, 13H), 0.89 (t, J = 6.8 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3): δ = 202.6, 159.18, 159.15,
131.0, 130.9, 129.5, 113.78, 113.76, 75.5, 75.2, 70.28, 70.22,
55.3, 43.8, 38.5, 34.0, 33.4, 32.0, 24.9, 22.7, 17.9, 14.1 ppm; FT-
IR (film): 2932, 2859, 1725, 1612, 1513, 1464, 1301, 1248,
1173, 1064, 1036, 821 cm–1. ESI-MS m/z 479.6 ([M+Na]+). ESI-
HRMS calcd for C28H40O5Na ([M+Na]+): 479.2768; found:
479.2779.
4.16. Hydrolysis of the acetonide in 30 to afford diol 31.
The same procedure described above for the conversion of 8
to 9 was employed (with 30 to replace 8). Data for 31 (a colorless
oil, 709 mg, 1.59 mmol, 83% from 30): [α]D +59.2 (c 1.0,
23
1
CHCl3). H NMR (500 MHz, CDCl3): δ = 7.23 (d, J = 8.1 Hz,
2H), 7.22 (d, J = 9.0 Hz, 2H), 6.84 (d, J = 8.3 Hz, 4H), 4.50 (d, J
= 10.9 Hz, 1H), 4.48 (d, J = 10.7 Hz, 1H), 4.38 (d, J = 12.4 Hz,
1H), 4.36 (d, J = 10.4 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 3.74
(dd, J =10.1, 2.4Hz, 1H), 3.71-3.56 (m, 4H), 1.93-1.86 (m, 1H),
1.85-1.79 (m, 1H), 1.64-1.49 (m, 2H), 1.37-1.24 (m, 6H), 0.90 (t,
J = 6.8 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ = 159.3,
130.2, 130.0, 129.6, 129.5, 113.85, 113.83, 77.3, 75.2, 72.3, 71.3,
70.5, 63.9, 55.2, 34.0, 33.3, 31.9, 24.5, 22.6, 14.0 ppm; FT-IR
(film): 3478, 2931, 2858, 1849, 1612, 1514, 1464, 1301, 1248,
1173, 1073, 1035, 821 cm–1. ESI-MS m/z 469.5 ([M+Na]+). ESI-
HRMS calcd for C26H38O6Na ([M+Na]+): 469.2561; found:
469.2568.
4.20. Conversion of 35 into 36.
A solution of LiAlH4 (1.0 M, in THF, 0.27 mL, 0.27 mmol)
was added dropwise to a solution of CrCl3 (166 mg, 1.05 mmol)
in dry THF (0.5 mL) stirred in an ice-water bath under argon
(balloon). The initially purple solution turned light green, with a
lot of gas bubbles evolved. After completion of the addition, the
cooling bath was removed. The mixture was heated to reflux
(still under argon), while a solution of aldehyde 35 (48 mg, 0.105
mmol) and CHCl3 (21ꢀL, 0.21 mmol) in dry THF (1.5 mL) was
introduced. The solution turned dark-red. The mixture was then
heated with stirring for 3 h. The heating bath was removed. The
reaction was quenched by addition of water. The reaction mixture
was diluted with EtOAc (10 mL), washed water (3 mL), aq. sat.
NaHCO3 and brine before being dried over anhydrous Na2SO4.
Removal of the solvent by rotary evaporation and column
chromatography (10:1 PE/EtOAc) on silica gel gave 36 as a
colorless oil (a 92:8 inseparable (E)/(Z) mixture, 37 mg, 0.077
mmol, 73% from 35). [α]D26 +13.5 (c 1.0, CHCl3). 1H NMR (500
MHz, CDCl3): δ = 7.22(d, J = 8.3 Hz, 4H), 6.85 (d, J = 7.7 Hz,
4H), 6.01(d, J = 6.4 Hz, 0.08H), 5.90 (d, J = 13.0 Hz, 0.92H),
5.85 (dt, J = 13.2, 7.4 Hz, 0.92H), 5.71 (q, J = 14.3, 7.3 Hz,
0.08H), 4.48-4.33 (m, 4H), 3.80 (s, 6H), 3.49-3.38 (m, 2H), 2.07-
1.87 (m, 2H), 1.57-1.40 (m, 6H ), 1.40-1.18 (m, 8H), 0.89 (t, J =
6.8 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ = 159.13,
159.10, 133.8, 131.0, 130.9, 129.5, 129.4, 116.9, 113.74, 113.72,
75.5, 75.3, 70.3, 70.2, 55.3, 38.6, 34.0, 33.4, 32.0, 30.9, 24.9,
24.6, 22.7, 14.1 ppm; FT-IR (film): 2932, 2858, 1612, 1586,
1513, 1464, 1441, 1301, 1247, 1172, 1067, 1037, 935, 820cm–1.
4.17. Conversion of diol 31 into alkene 32.
The same procedure described above for conversion of 9 to 10
was employed (with 31 to replace 9). Data for 32 (a colorless oil,
576 mg, 1.40 mmol, 100% from 31): [α]D21 –23.7 (c 1.0, CHCl3).
1H NMR (500 MHz, CDCl3): δ = 7.23 (d, J = 8.6 Hz, 2H), 7.20
(d, J = 8.8 Hz, 2 H), 6.86 (d, J = 9.2 Hz, 2H), 6.84 (d, J = 9.1 Hz,
2H), 5.71 (ddd, J = 18.2, 10.2, 8.0 Hz, 1H ), 5.22 (dd, J = 10.3,
2.0 Hz, 1H), 5.15 (dd, J = 17.1, 1.0 Hz, 1H), 4.50 (d, J = 11.0 Hz,
1H), 4.41 (d, J = 10.9 Hz, 1H), 4.34 (d, J = 10.9 Hz, 1H), 4.26 (d,
J = 11.7 Hz, 1H), 3.88 (q, J = 14.5, 7.3 Hz, 1H), 3.79 (s, 6H),
3.45 (dq, J = 6.8, 5.5 Hz, 1H), 2.01 (quint, J = 6.7 Hz, 1H), 1.62-
1.54 (m, 1H), 1.54-1.41 (m, 2H), 1.38-1.17 (m, 6H), 0.87 (t, J =
7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 159.0, 138.9,
131.1, 130.7, 129.4, 129.3, 117.5, 113.68, 113.65, 77.5, 75.4,
70.1, 69.6, 55.22, 55.19, 40.13, 33.8, 31.9, 24.7, 22.6, 14.0 ppm;
FT-IR (film): 2931, 2858, 1736, 1612, 1513, 1465, 1301, 1247,
1172, 1074, 1036, 926, 820 cm–1. ESI-MS m/z 435.4 ([M+Na]+).

9
ESI-MS m/z 511.6 ([M+Na]+). ESI-HRMS calcd for
cf. (c) Mereyala, H. B.; Goud, P. M.; Gadikota, R. R.; Reddy, K.
R.; J. Carbohydr. Chem. 2000, 19, 1211-1212; (d) Banda, G.;
ACCEPTED MANUSCRIPT
C26H37O4INa ([M+Na]+): 511.2586; found: 511.2589.
Chakravarthy, I. E. Tetrahedron: Asymmetry 2006, 17, 1684-1687;
(e) Yadav, J. S.; Das, S.; Mishra, A. K. Tetrahedron: Asymmetry.
2010, 21, 2443-2447.
4.21. Removal of the PMB protecting groups in 36 to afford 37.
10. (a) Garegg, P. J.; Samuelsson, B. J. Chem. Soc., Perkin Trans. 1
1980, 2866-2869;( b) Classon, B.; Garegg, P. J.; Samuelsson, B.
Can. J. Chem. 1981, 59, 339-343; (c) Garegg, P. J.; Johansson, R.;
Orthega, C.; Samuelsson, B. J. Chem. Soc., Perkin Trans. 1 1982,
681-683.
The same procedure described above for the conversion of 19
to 1 was employed (with 36 to replace 19) Data for 37 (a
27
colorless oil, 4.0 mg, 0.02 mmol, 83% from 36) [α]D +1.6 (c
1
0.33, CH3OH). H NMR (500 MHz, CDCl3): δ = 5.96 (d, J =
13.0 Hz, 1H), 5.89 (dt, J = 13.2, 6.7 Hz, 1H), 3.92-3.81 (2H, m),
2.55-2.14 (br s, 2H, OH), 2.13-2.02 (m, 2H), 1.64–1.51 (m, 2H),
1.51-1.37 (m, 6H), 1.36-1.27 (m, 6H), 0.90 (t, J = 6.9 Hz, 3H)
ppm; 13C NMR (125 MHz, CDCl3): δ = 133.6, 117.1, 73.4, 72.7,
42.9, 38.4, 37.4, 31.8, 30.8, 25.0, 24.7, 22.6, 14.0 ppm; FT-IR
11. Lemen. G. S.; Wolfe, J. P. Org. Lett. 2010, 12, 2322-2325.
12. For a previous example using Et2O as CM reaction solvent, see:
Abbas, M.; Leitgeb, A.; Slugovc, C. Synlett 2013, 24, 1193-1196.
13. (a) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4145;
(b) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277-
7278; (c) Ireland, R. E.; Liu, L.-B. J. Org. Chem. 1993, 58, 2899-
2899; (d) Stevenson, P. J.; Treacy, A. B.; Nieuwenhuyzen, M. J.
Chem. Soc., Perkin Trans. 2 1997, 589-591.
(film): 3336, 2931, 2858, 2097, 1846, 1779, 1458, 1090, 847 cm–
1
.
ESI-MS m/z 271.3 ([M+Na]+). ESI-HRMS calcd for
C13H25ClO2Na ([M+Na]+): 271.1435; found: 271.1432.
14. Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986, 108,
7408-7410.
15. In retrospect, the previous investigators probably were also
puzzled by the data discrepancies and hence opted not to include
the NMR data when publishing the first synthesis of 1 (the ref 3
above); their 13C NMR data in CDCl3 were in full consistence with
ours in CDCl3, see: Powell, N. A. “Studies towards tandem “one-
way” Bergman radical cyclizations of aromatic enediynes and
synthesis of anti-1,3-diols by the cationic coupling of nucleophiles
with 4-acetoxy-1,3-dioxanes”, PhD dessertation, 1998, University
of California, Irvine, CA, USA; (CAN 131:184915).
Acknowledgments.
This work was supported by the National Basic Research
Program of China (the 973 Program, 2010CB833200), the
National Natural Science Foundation of China (21372248,
21172247, 21032002) and the Chinese Academy of Sciences.
16. Zhen, Z.-B.; Gao, J.; Wu, Y.-K. J. Org. Chem. 2008, 73, 7310-
7316.
Supplementary data
17. (a) Martinelli, M. J.; Nayyar, N. K.; Moher, E. D.; Dhokte, U. P.;
Pawlak, J.; M.; Vaidyanathan, R. Org. Lett. 1999, 1, 447-450; (b)
Martinelli, M. J.; Vaidyanathan, R.; Pawlak, J. M.; Nayyar, N. K.;
Dhokte, U. P.; Doecke, C. W.; Zollars, L. M. H.; Moher, E. D.;
Van Khau, V.; Kosmrlj, B. J. Am. Chem. Soc. 2002, 124, 3578-
3585; (c) Martinelli, M. J.; Vaidyanathan, R.; Van Khau, V.
Tetrahedron Lett. 2000, 41, 3773-3776.
18. Wu, Y.-K.; Ahlberg, P. J. Org. Chem. 1994, 59, 5076-5077.
19. (a) J. M. Behan, R. A. W. Johnstone, M. J. Wright, J. Chem. Soc.,
Perkin Trans. 1 1975, 1216-1217; (b) K. Matsuo, K. Ohtsuki,
T.Yoshikawa, K. Shishido, K. Yokotani-Tomita, M. Shindo,
Tetrahedron 2010, 66, 8407-8419; (c) the ref. 4g above.
20. Augé, J.; Boulerie, V.; Gil, R.; Lubin-Germain, N.; Picard, J.;
Uziel, J. Synth. Comm. 2003, 33, 3733-3739.
1
Copies of the H and 13C NMR spectra, FT-IR spectra for all
new compounds
References and Notes
1. Burja, A. M.; Banaigs, B.; Abou-Mansour, E.; Burgess, J. G.;
Wright, P. C. Tetrahedron 2001, 57, 9347-9377
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(compound 4)
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3103-3106.
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