An efficient cis-reduction of alkyne to alkene in the presence of a vinyl iodide: Stereoselective synthesis of the C22-C31 fragment of leiodolide A

Article abstract of DOI:10.1016/j.tet.2012.12.008

Rapid and efficient reduction of alkyne bond in the presence of a vinyl iodide is established using freshly prepared Brown's P2-Ni as the catalyst, affording the semihydrogenated alkene products in good to excellent yields (73-91%). Based on this new method, a stereoselective synthesis of the key C22-C31 fragment of marine macrolide leiodolide A has been developed.

Full text of DOI:10.1016/j.tet.2012.12.008

Tetrahedron 69 (2013) 1553e1558
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An efficient cis-reduction of alkyne to alkene in the presence
of a vinyl iodide: stereoselective synthesis of the C22eC31 fragment
of leiodolide A
,
,
a
,
,b,
Xing Zhang a b, Jun Liu a , Xue Sun b, Yuguo Du a
*
*
a State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
b School of Chemistry and Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 August 2012
Received in revised form 27 November 2012
Accepted 4 December 2012
Available online 10 December 2012
Rapid and efficient reduction of alkyne bond in the presence of a vinyl iodide is established using freshly
prepared Brown’s P2-Ni as the catalyst, affording the semihydrogenated alkene products in good to
excellent yields (73e91%). Based on this new method, a stereoselective synthesis of the key C22eC31
fragment of marine macrolide leiodolide A has been developed.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Vinyl iodide
Alkyne
Cis-reduction
Leiodolides
Stereoselective synthesis
1. Introduction
Leiodolide A (Fig. 1) is a marine natural product originally iso-
lated from the deep-water marine sponge Leiodermatium by Fenical
Vinyl iodides, with well-defined geometry structures, have been
widely used as important building blocks in organic natural prod-
uct synthesis, owing to the valuable application of the transition-
metal catalyzed cross-coupling reactions, such as Heck, Sonoga-
shira, and SuzukieMiyaura reactions, et al.1,2 Efficient methods for
the preparation of stereodefined vinyl iodide structures, employing
as synthons in CeC bond formation, have been investigated
through introducing the iodide at the very end reaction sequence.3
Very few studies have been made regarding the stability and
compatibility of vinyl iodide in functional group modification and
transformation.4 It is generally believed that vinyl iodide could not
survive under most of the common reduction conditions, leading to
the corresponding olefin or saturated carbonecarbon bond, in-
stead. To our best knowledge, the only example of cis-reduction of
propargyl alcohol bearing a vinyl iodide was reported by Parker in
his synthesis of discodermolide.4a Herein we report the stereo-
selective synthesis of the C22eC31 fragment of leiodolide A
employing a diastereoselective Seebach alkylation and a Brown’s
P2-Ni catalyzed alkyne semihydrogenation in the presence of a vi-
nyl iodide.
and co-workers in 2006.5 Preliminary biological testing indicated
that leiodolide A exhibited significant cytotoxic activity in the NCI
60 tumor cell line assay, with enhanced activity against HL-60
leukemia and OVCAR-3 ovarian cancer cells. The promising bi-
ological activities as well as densely functionalized structures have
prompted some efforts toward leiodolide synthesis.6
To provide sufficient material for further biological studies, as
well as to assign the absolute configuration at C13, we initiated
a study toward the total synthesis of leiodolide A and its de-
rivatives. Due to the structural complexity of the leiodolide A, our
20
Me
30
HO
Me
13
15
O
17
OMe
28
O
9
HO
Me
22
N
O
1
O
OH
31
4
Me
19
OH
Me
18
* Corresponding authors. E-mail addresses: junliu@rcees.ac.cn, jeromeorg@ya-
hoo.com.cn (J. Liu), duyuguo@rcees.ac.cn (Y. Du).
Fig. 1. Proposed structure of leiodolide A.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.008

1554
X. Zhang et al. / Tetrahedron 69 (2013) 1553e1558
synthetic approach involves the synthesis of three distinct frag-
ments (C1eC10, C11eC17, and C22eC31) with strategic bond dis-
connections (Fig. 2). In this report, we describe a convenient
strategy for the stereoselective synthesis of fragment C22eC31 (3),
quaternary carbon was assigned as (S)-configuration based on lit-
erature precedent.7a
With the efficient access to vinyl iodide 8, we next examined the
semihydrogenation of triple bond under Lindlar reduction condi-
tion.11 However, the envisaged partial hydrogenation of the alkyne
8 in the presence of vinyl iodide, turned out to be more difficult
than we expected. Exposure of 8 to hydrogen gas in the presence of
Lindlar catalyst with or without quinoline only resulted in the re-
covery of most starting material and some decomposition of the
substrate due to hydrogenolysis of the vinyl iodide.
the a-hydroxy-a-methyl carboxylic acid side-chain, based on our
new methodology. Thus, precursor 3 could be achieved via a dia-
stereoselective alkylation of the Seebach’s dioxolanone7 4 with
a propargylic bromide 5 derived from propargyl alcohol. The key
transformation in this synthetic strategy was a semihydrogenation
of the C25eC26 internal acetylene.
20
Me
30
Seebach Alkylation
HO
*
Me
15
25
13
O
Me
O
O
11
OMe
17
28
O
HO
22
N
O
Me
9
O
I
O
OH
31
Me
1
7
tBu
3
4
Me
19
OH
Me
18
O
Me
Me
Br
O
I
O
tBu
5
4
R-Lactic acid
HO
Fig. 2. Retrosynthetic analysis of leiodolide A (1).
2. Results and discussion
To circumvent this problem, we chose the more easily available
alcohol as suitable model compound, and its semi-
7
a
The synthesis of the fragment C22eC31 of leiodolide A is out-
lined in Scheme 1. The diyne 68 was prepared in a moderate yield
by means of copper-mediated cross-coupling reaction between the
commercially available propargyl alcohol and propargyl bromide.9
Selective carboalumination of the terminal alkyne followed by
quenching with iodine afforded vinyl iodide 7 as a single isomer in
65% yield.10 The hydroxyl group of 7 was converted into the bro-
mide 5 with PPh3/CBr4 in dichloromethane. Subsequent treatment
of Seebach’s (R)-lactic acid-derived dioxolanone 4 with LDA at
ꢀ90 ꢁC followed by the addition of propargyl bromide 5 furnished
compound 8 in 85% yield and greater than 20:1 dr according to the
crude NMR.7 The absolute stereochemistry of the newly formed
hydrogenation was investigated under a variety of different re-
action conditions (Table 1).
Treatment of 7 with 1 atm of hydrogen gas in the presence of
Lindlar catalyst with a catalytic amount of quinoline in ethyl acetate
or methanol resulted in the recovery of starting material (entries 1
and 2). Attempts to semi-reduce the triple bond in the absence of
quinoline also failed and only returned alcohol 7 (entries 3 and 4).
Literature searching revealed that the reduction of propargyl al-
cohol to cis-allylic alcohol, in the presence of a vinyl iodide, could be
carried out at H2 atmosphere using Pd/CaCO3 in hexane.4a To our
depressing, hydrogenation under this condition, or at H2 pressures
as high as 4 atm, also resulted in the recovered starting material
H
Me
a
HO
HO
c
b
I
HO
Br
6
7
O
O
Me
Me
O
d
O
I
I
X
Me
Me
O
I
O
tBu
5
tBu
3
8
Scheme 1. Attempted synthesis of compound 3: (a) propargyl bromide, Et3N, CuI, DMF, Et2O, 54%; (b) ZrCp2Cl2, AlMe3, DCM, room temperature, then I2, Et2O, 0 ꢁC, 65%; (c) CBr4,
PPh3, DCM, 0 ꢁC, 89%; (d) 4, LDA, THF, ꢀ90 ꢁC, 10 min, then 5, ꢀ78 ꢁC, 2 h, 85%.

X. Zhang et al. / Tetrahedron 69 (2013) 1553e1558
1555
observed.14 Finally, the partial reduction of the alkyne 8 under
optimized conditions, in 3 min, accomplished the synthesis of the
target fragment C22eC31 3 in 79% yield (entry 8). In all cases
studied here, the cis-olefins were formed cleanly without any de-
tectable over-reduction products. The current results clearly dem-
onstrate the potential usage of this method to structurally related
natural product synthesis.
Table 1
Screening the semihydrogenation conditions of alkyne in the presence of vinyl
iodide
Me
Me
HO
HO
I
I
9
7
Entry Conditions
Product Yield (%)
3. Conclusion
1
2
3
4
5
Lindlar catalyst,b quinoline, ethyl acetate, H2 (1 atm), 5 h d
NDc
ND
ND
ND
ND
ND
ND
ND
42a
77a
Lindlar catalyst, quinoline, methanol, H2 (1 atm), 5 h
Lindlar catalyst, ethyl acetate, H2 (1 atm), 5 h
Lindlar catalyst, methanol, H2 (1 atm), 5 h
Pd/CaCO3, hexane, H2 (1 atm), 10 h
Pd/CaCO3, hexane, H2 (4 atm), 10 h
Zn,d MeOH/H2O, 30 ꢁC, 4 h
d
d
d
d
d
d
d
9
A practical method for the cis-reduction of alkyne to alkene has
been developed employing Brown’s P2-Ni as the catalyst. This new
approach allows the presence of vinyl iodide in the reduction
substrates. Based on this finding, a successful stereoselective syn-
thesis of the key C22eC31 fragment of the marine macrolide leio-
dolide A has been achieved in five steps from propargyl alcohol
with 21% overall yield. The completion of natural leiodolide A
synthesis is currently underway in our laboratory.
6
7
8
9
10
Zn, 1,2-dibromoethane, EtOH, reflux, 4 h
P2-Ni,e EtOH, H2 (1 atm), 10 h
P2-Ni,f EtOH, H2 (1 atm), 4 min
9
a
Isolated yield.
Approximately 5% Pd/CaCO3, poisoned with lead.
No desired product.
The Zn dust was activated by stirring it in a 0.1 M HCl solution for ca. 15 min.
Ni(OAc)2$4H2O (0.5 equiv), NaBH4 (0.5 equiv), and ethylenediamine (0.2 equiv)
b
c
4. Experimental section
4.1. General experimental
d
e
were used at room temperature.
f
Ni(OAc)2$4H2O (3.0 equiv), NaBH4 (3.0 equiv), and ethylenediamine (1.2 equiv)
All reactions were performed under a nitrogen atmosphere and
solvents were dried according to the established procedures ahead of
use. All reagents were purchased from commercial corporations.
Flash chromatography (FC) was performed using E Merck silica gel 60
(240e400 mesh). All reactions under standard conditions were
monitored by thin-layer chromatography (TLC) on gel F254 plates.
Optical rotations were recorded on a polarimeter. Infrared spectra
were recorded on a PerkineElmer 1000 series FTIR with wave num-
bers expressed in cmꢀ1 using samples prepared as thin films between
salt plates. HRMS were measured with mass spectrometer. 1H NMR
and 13C NMR were measured on 400 MHz spectrometers (NMR in
were used at room temperature.
(entries 5 and 6). We felt that the conventional methods using
poisoned heterogeneous Pd-catalysts may not work for this semi-
hydrogenation. So we turned our efforts to other metal catalysts,
such as activated zinc in methanol/H2O12a or Zn/BrCH2CH2Br sys-
tem,12b but failed to generate the desired products (entries 7 and 8).
After considerable experimentation, to our delight, the partial
reduction was finally achieved and afforded the clean cis-reductive
product in moderate yield (42%) with 0.5 equiv of Brown’s P2-Ni
catalyst,13 which is generated in situ by reduction of nickel ace-
tate with sodium borohydride in anhydrous ethanol. It is worth
noting that the loading amount of P2-Ni catalyst is critical to the
reaction. If the amount was less than 1.0 equiv, the yield could not
be improved significantly even at prolonged reaction time. By
adding over 2.5 equiv of catalyst, we observed the good yields
(72e77%) and shorten reaction time (2e10 min) during screening
the suitable reaction conditions. The reaction conditions were
eventually optimized and set to 3.0 equiv freshly prepared P2-Ni as
the catalyst, anhydrous ethanol as the solvent, and the reaction
could proceed at room temperature.
To investigate the reaction scope, we further expanded the
method to other substrates under the optimized conditions
(Table 2). As expected, TBS and Bz groups were compatible to the
reaction conditions, and partial hydrogenation of the protected
propargyl alcohols 10 and 12, in the presence of vinyl iodide, was
achieved with excellent selectivity and high yields (entries 2 and 3).
It was found that electron-donating substituent (TBS) at the hy-
droxyl group favored product formation, whereas an electron-
withdrawing group (Bz) hindered product formation and took
much longer reaction time. In addition, the terminal alkyne 14
could be reduced to the terminal alkene 15 in good yield (entry 4).
The disubstituted vinyl iodide 16 also provided the corresponding
alkene 17 in 81% yield (entry 5). It is interesting to note that, for the
1,4-diyne 18, terminal alkene intermediate 19 could be trapped
cleanly under our partial reduction conditions (entry 6), whereas,
1,4-diene 20 was generated with much longer reaction time (entry
7). Entries 6 and 7 also suggest the possibility of selectively
obtaining terminal alkene for partial reduction of diyne by using
Brown’s P2-Ni as the catalyst. To our delight, the reaction pro-
ceeded smoothly to afford the designed product even in a large
scale (entry 1, 7/9, 1.0 mmol) and no over-reduction product was
CDCl3 with TMS as an internal standard). Chemical shifts (
in parts per million relative to residual solvent (usually chloroform;
7.26 for 1H NMR or 77.23 for proton decoupled 13C NMR), and
d) are given
d
coupling constants (J) in hertz. Multiplicity is tabulated as s for sin-
glet, d for doublet, t for triplet, q for quadruplet, and m for multiplet,
whereby the prefix app is applied in cases where the true multiplicity
is unresolved, and br when the signal in question is broadened.
4.1.1. Hexa-2,5-diyn-1-ol (6). To a solution of propargyl alcohol
(50 mg, 0.893 mmol) in Et2O (0.6 mL) and DMF (0.2 mL) at room
temperature were added CuI (170 mg, 0.893 mmol) and Et3N
(90 mg, 0.893 mmol). After 5 min, a solution of propargyl bromide
(105 mg, 0.893 mmol) in Et2O (0.4 mL) was added, and the reaction
mixture was stirred vigorously for 3.5 h. Then the mixture was
treated with satd NH4Cl solution (0.5 mL). The crude reaction
mixture was filtered through a Celite pad and the organic layer was
removed under reduced pressure and extracted with Et2O
(3ꢂ20 ml). The combined organic layers were washed with aque-
ous brine, dried over Na2SO4, and concentrated under vacuum. The
crude was purified by FC (silica gel, hexanes/EtOAc 6:1) to give
known compound 6 as a light yellow oil (45 mg, 54%). 1H NMR
(400 MHz, CDCl3)
d
: 4.25 (t, J¼2.0, 2H), 3.21 (dd, J¼2.0, 4.8, 2H), 2.08
(t, J¼2.8, 1H), 1.95 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d 79.2, 79.1,
77.8, 69.1, 51.1, 9.6; IR (film, cmꢀ1): 3290, 2291, 2227, 2126.
4.1.2. (E)-6-Iodo-5-methylhex-5-en-2-yn-1-ol (7). To a solution of
bis(cyclopentadienyl)zirconium dichloride (565 mg, 1.934 mmol) in
dry DCM (7 mL) at 0 ꢁC was added AlMe3 (6.286 mmol, 6.5 equiv)
dropwise. After stirring for 45 min at room temperature, alkyne 6
(91 mg, 0.967 mmol) in DCM (1.5 ml) was added dropwise. The
reaction mixture was stirred at room temperature for 30 h and then
cooled to 0 ꢁC, followed by the addition of iodide (828 mg,

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X. Zhang et al. / Tetrahedron 69 (2013) 1553e1558
Table 2
Semihydrogenation of alkynes in the presence of vinyl iodide using P2-Ni catalyst
Entry
Substrate
Producta
Time (min)
Yield (%)b
Me
Me
HO
TBSO
BzO
HO
TBSO
BzO
I
1
4
77
I
7
9
Me
Me
I
2
3
2
5
91
I
10
11
Me
Me
73c
I
I
12
13
OH
OH
4
5
2
5
73
81
I
I
Me
15
Me
H
14
H
I
I
OH
OH
16
17
OH
OH
H
H
6
3
75
19
18
I
I
OH
OH
20
7
>15
83
18
I
I
I
O
O
O
Me
O
8
3
79
Me
Me
O
O
I
tBu
tBu
3
8
a
Unless otherwise noted, Ni(OAc)2$4H2O (3.0 equiv), NaBH4 (3.0 equiv), and ethylenediamine (1.2 equiv) were used at room temperature.
Isolated yield. Caution: most compounds above need handle with care for their low boiling point.
Starting material of 21% was recovered.
b
c

X. Zhang et al. / Tetrahedron 69 (2013) 1553e1558
1557
3.259 mmol) in dry Et2O. The resulting mixture was allowed to
general procedure as a colorless oil. 1H NMR (400 MHz, CDCl3)
d:
warm to room temperature and stirred for 1.5 h. The reaction was
quenched by the careful addition of satd Na2S2O3 solution, and the
resulting mixture was filtered through a Celite pad and the aqueous
layer was extracted with DCM (3ꢂ20 mL), and the combined or-
ganic phase was washed with brine, dried over Na2SO4, and con-
centrated under vacuum. The crude was purified by FC (silica gel,
hexanes/EtOAc 5:1) to give compound 7 as a colorless oil (148 mg,
5.95 (s, 1H), 5.75 (dt, J¼6.4, J¼11.2, 1H), 5.54 (dt, J¼7.6, J¼10.8, 1H),
4.21 (d, J¼6.4, 2H), 2.97 (d, J¼7.6, 2H), 1.84 (s, 3H); 13C NMR
(100 MHz, CDCl3) d 145.9, 130.8, 128.5, 75.9, 58.4, 37.1, 24.1; IR (film,
cmꢀ1): 3336, 2920, 2850, 1028, 766, 666; EI-HRMS calcd for
C7H11IO, 237.9855; found: 237.9860 ([M]þ).
4.2.2. tert-Butyl-(2Z,5E)-6-iodo-5-methylhexa-2,5-dienyloxy)dime-
thylsilane (11). Compound 11 was prepared in 91% yield after puri-
fication according to the general procedure as a light yellow oil. 1H
65%). 1H NMR (400 MHz, CDCl3)
d: 6.26 (s, 1H), 4.28 (s, 2H), 3.10 (d,
J¼1.6, 2H), 1.90 (s, 3H), 1.66 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d
141.7, 81.9, 81.6, 77.2, 51.3, 28.6, 23.8; IR (film, cmꢀ1): 2289, 2213,
NMR (400 MHz, CDCl3)
d
: 5.93 (s, 1H), 5.66 (dt, J¼6.0, J¼11.2, 1H),
1668, 1627, 1271, 1012; EI-HRMS calcd for C7H9IO, 235.9698; found:
5.42 (dt, J¼7.6, J¼11.2,1H), 4.22 (d, J¼6.0, 2H), 2.93 (d, J¼7.2, 2H),1.83
235.9701 ([M]þ).
(s, 3H), 0.90 (s, 9H), 0.07 (s, 6H); 13C NMR (100 MHz, CDCl3)
d
146.0,
132.0, 126.4, 75.7, 59.2, 37.3, 25.9, 24.1, 18.3, ꢀ5.2; IR (film, cmꢀ1):
2954, 2929, 2856, 1661, 1254, 1101, 776, 667; HRMS (EI) peaks and
HRMS (ESIþ) peaks due to [MþH]þ or [MþNa]þ were not detected.
4.1.3. (E)-6-Bromo-1-iodo-2-methylhex-1-en-4-yne (5). To a solu-
tion of 7 (39 mg, 0.165 mmol) and CBr4 (72 mg, 0.215 mmol) in dry
DCM (2 mL) at 0 ꢁC under N2 protection, was added PPh3 (65 mg,
0.248 mmol) portionwise. After 15 min, the solution was warmed to
room temperature and stirred for another 1 h. The solvent was
removed in vacuum and the crude was purified by FC (silica gel,
hexanes) to give compound 5 as a light yellow oil (43 mg, 89%). 1H
4.2.3. (2Z,5E)-6-Iodo-5-methylhexa-2,5-dienyl benzoate (13).
Compound 13 was prepared in 73% yield (recovered 20% SM)
after purification according to the general procedure as a pale
yellow oil. 1H NMR (400 MHz, CDCl3)
d: 8.05e8.03 (m, 2H),
NMR (400 MHz, CDCl3)
d
: 6.26 (s, 1H), 3.93 (t, J¼2.4, 2H), 3.12 (d,
7.58e7.52 (m, 1H), 7.46e7.42 (m, 2H), 6.00 (s, 1H), 5.83 (dt, J¼6.8,
J¼1.6, 2H),1.90 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 141.4, 83.4, 77.5,
J¼11.2, 1H), 5.42 (dt, J¼7.6, J¼10.8, 1H), 4.87 (d, J¼6.8, 2H), 3.07
77.2, 28.7, 23.8, 14.9; IR (film, cmꢀ1): 2233, 1632, 1208, 1130, 611,
(d, J¼7.6, 2H), 1.87 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 166.4,
565; EI-HRMS calcd for C7H8BrI, 297.8854; found: 297.8859 ([M]þ).
145.5, 133.0, 131.1, 130.1, 129.6, 128.4, 125.9, 76.2, 60.3, 37.3, 24.1;
IR (film, cmꢀ1): 2923, 1717, 1601, 1584, 1451, 768, 711; HRMS (EI)
peaks and HRMS (ESIþ) peaks due to [MþH]þ or [MþNa]þ were
not detected.
4.1.4. (2R,5S)-2-tert-Butyl-5-((E)-6-iodo-5-methylhex-5-en-2-ynyl)-
5-methyl-1,3-dioxolan-4-one (8). To a solution of diisopropylamine
(44 mg, 0.430 mmol) in THF (1 mL) at ꢀ60 ꢁC was added n-BuLi
(0.173 mL, 0.415 mmol, 2.4 M in hexanes) dropwise. The solution
was warmed to ꢀ10 ꢁC over 1 h and then recooled to ꢀ90 ꢁC. Next,
a solution of dioxolanone 4 (66 mg, 0.415 mmol) in THF (1 mL) was
added slowly down the walls of the flask for precooling. The re-
action mixture was stirred at ꢀ90 ꢁC for 10 min and then the
bromide 5 (40 mg, 0.134 mmol) was added dropwise. The reaction
mixture was warmed slowly to ꢀ10 ꢁC over 2 h and then quenched
with satd aqueous NH4Cl (1 mL). The aqueous layer was extracted
with EtOAc (3ꢂ20 mL), and the combined organic phase was
washed with brine, dried over Na2SO4, and concentrated under
4.2.4. (E)-1-Iodo-2-methylpenta-1,4-dien-3-ol (15). Compound 15
was prepared in 73% yield after purification according to the gen-
eral procedure as a pale yellow oil. 1H NMR (400 MHz, CDCl3)
d:
6.40 (s, 1H), 5.86e5.78 (m, 1H), 5.35e5.21 (m, 2H), 4.67 (d, J¼5.6,
1H), 1.81 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 148.1, 137.8, 116.5,
78.9, 78.2, 20.3; IR (film, cmꢀ1): 3398, 2955, 2918, 1462, 1377; EI-
HRMS calcd for C6H9IO, 223.9698; found: 223.9701 ([M]þ).
4.2.5. 2-Iodopenta-1,4-dien-3-ol (17). Compound 17 was prepared
in 81% yield after purification according to the general procedure as
vacuum. The crude was purified by FC (silica gel, hexanes/EtOAc
a colorless oil. 1H NMR (400 MHz, CDCl3)
d: 6.45e6.44 (m, 1H), 5.92
20
20:1) to give compound 8 as a pale yellow oil (42 mg, 85%). [
a
]
(d, J¼1.6, 1H), 5.84 (ddd, J¼5.2, J¼10.4, J¼15.6, 1H), 5.42 (dt, J¼1.2,
D
ꢀ10.2 (c 1.2, CHCl3); 1H NMR (400 MHz, CDCl3)
d: 6.25 (s, 1H), 5.37
17.2, 1H), 5.33 (dt, J¼1.2, 10.4, 1H), 4.37 (s, 1H), 1.56 (br s, 1H); 13C
(s, 1H), 3.03 (s, 2H), 2.70e2.57 (m, 2H), 1.89 (s, 3H), 1.48 (s, 3H),
NMR (100 MHz, CDCl3) d 137.5, 125.9, 117.5, 115.7, 78.5; IR (film,
0.96(s, 9H); 13C NMR (100 MHz, CDCl3)
d
174.5, 142.0, 109.5, 79.4,
cmꢀ1): 3405, 3081, 2924, 2854, 1640, 1631, 1082, 1038, 990, 910;
HRMS (EI) peaks and HRMS (ESIþ) peaks due to [MþH]þ or
[MþNa]þ were not detected.
79.0, 77.2, 77.1, 34.6, 28.7, 27.8, 23.7, 23.3, 23.1; IR (film, cmꢀ1):
2964, 2218, 1799, 1694, 1632, 1485, 1175, 1146, 1077, 983; EI-HRMS
calcd for C15H21IO3, 376.0535; found: 376.0540 ([M]þ).
4.2.6. (E)-8-Iodo-7-methylocta-1,7-dien-4-yn-3-ol (19). Compound
19 was prepared in 75% yield (recovered 25% SM) after purification
according to the general procedure as a colorless oil. 1H NMR
4.2. General experimental procedure for the partial
hydrogenation
(400 MHz, CDCl3)
d
: 6.25 (s, 1H), 5.97 (ddd, J¼5.2, 10.0, 15.2, 1H),
To a solution of nickel acetate tetrahydrate (72 mg, 0.289 mmol)
in EtOH (2 mL) was added a solution of sodium borohydride (11 mg,
0.289 mmol) in EtOH (0.5 mL) quickly. The solution was stirred for
5.44 (d, J¼17.2, 1H), 5.22 (d, J¼10.4, 1H), 4.89 (dd, J¼1.2, 3.6, 1H),
3.12 (s, 2H), 1.90 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 141.6, 137.2,
116.4, 82.5, 82.2, 77.2, 63.4, 28.6, 23.8; IR (film, cmꢀ1): 3359, 3065,
2914, 2878, 2247, 2210, 1643, 1416, 1378, 928; EI-HRMS calcd for
C9H11IO, 261.9855; found: 261.9858 ([M]þ).
30 min and then added ethylenediamine (7.5 mL, 0.115 mmol) fol-
lowed by addition of alkyne (0.096 mmol) dissolved in EtOH
(0.2 mL). The reaction mixture was stirred under 1 atm of hydrogen
for a few minutes (2e5 min) and then removed the hydrogen tube.
The reaction was monitored by TLC. Upon transformation of the
starting material, water was added. The mixture was extracted with
EtOAc, and the combined organic phase was washed with brine,
dried over Na2SO4, and concentrated under vacuum. The crude was
purified by FC (silica gel) to give the designed product.
4.2.7. (4Z,7E)-8-Iodo-7-methylocta-1,4,7-trien-3-ol (20). Compound
20 was prepared in 83% yield after purification according to the
general procedure as a colorless oil. 1H NMR (400 MHz, CDCl3)
d:
5.96 (s, 1H), 5.89 (ddd, J¼6.0, 10.4, 16.8, 1H), 5.58e5.49 (m, 2H), 5.26
(d, J¼17.6,1H), 5.14 (d, J¼10.4, 1H), 4.94e4.93 (m,1H), 3.00 (d, J¼6.0,
2H), 1.85 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 145.7, 139.2, 132.7,
128.1, 115.1, 76.1, 68.9, 37.3, 24.1; IR (film, cmꢀ1): 3364, 3066, 2964,
2878, 1642, 1619, 987, 926, 765, 669; EI-HRMS calcd for C9H13IO,
264.0011; found: 263.9898 ([M]þ).
4.2.1. (2Z,5E)-6-Iodo-5-methylhexa-2,5-dien-1-ol (9). Compound 9
was prepared in 77% yield after purification according to the

1558
X. Zhang et al. / Tetrahedron 69 (2013) 1553e1558
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dienyl)-5-methyl-1,3-dioxolan-4-one (3). Compound 3 was pre-
pared in 79% yield after purification according to the general
20
procedure as a pale yellow oil. [
(400 MHz, CDCl3)
a
]
ꢀ13.5 (c 0.4, CHCl3); 1H NMR
D
4. (a) Denton, R. W.; Parker, K. A. Org. Lett. 2009, 11, 2722e2723; (b) Arefolov, A.;
d
: 5.93 (s, 1H), 5.65e5.56 (m, 2H), 5.18 (s, 1H),
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ꢀ
Chem. Soc. 2005, 127, 5596e5603; (d) de Lemos, E.; Poree, F. H.; Bourin, A.;
0.94 (s, 9H); 13C NMR (100 MHz, CDCl3)
d
175.4, 145.8, 130.6,
Barbion, J.; Agouridas, E.; Lannou, M. I.; Commerc¸ on, A.; Betzer, J. F.; Pancrazi,
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124.2, 108.8, 79.9, 75.8, 37.0, 34.6, 34.2, 24.2, 23.3, 23.0; IR (film,
cmꢀ1): 2963, 1798, 1682, 1632, 1485, 1172, 1140, 1078, 983, 793,
768; EI-HRMS calcd for C15H23IO3, 378.0692; found: 378.0697
([M]þ).
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Acknowledgements
mild conditions, see: (c) Blay, G.; Fernandez, I.; Monje, B.; Montesinos-Magraner,
M.; Pedro, J. R. Tetrahedron 2011, 67, 881e890; (d) Battaglia, A.; Baldelli, E.; Barbaro,
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This work was supported by NNSF of China (Projects
2012CB822101, 21072217, 21202193, and 2012ZX09502001).
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Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.12.008.
€
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10. (a) Furstner, A.; Bouchez, L. C.; Funel, J. A.; Liepins, V.; Poree, F. H.; Gilmour, R.;
Beaufils, F.; Laurich, D.; Tamiya, M. Angew. Chem., Int. Ed. 2007, 46, 9265e9270;
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