Synthesis and absolute configuration of the 7-phenylhepta-4,6-diyne-1,2- diol isolated from Bidens pilosa

Article abstract of DOI:10.1055/s-0030-1260604

The title diynediol was synthesized in enantiopure (>98.4% ee) forms, with the cross coupling of phenylacetylene with either (R)- or (S)-5-benzyloxypent-1-yn-4-ol catalyzed by nickel(II) chloride-copper(I) iodide as the key step. Comparison of the spectro

Full text of DOI:10.1055/s-0030-1260604

PAPER
2131
Synthesis and Absolute Configuration of the 7-Phenylhepta-4,6-diyne-1,2-diol
Isolated from Bidens pilosa
C
onfiguration
h
of
a
4,6-Diy
anIsolated from
BideC
ns pilosa ui,a,b Yang Zou,a Yikang Wu,*a Po Gao*b
a
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China
E-mail: yikangwu@sioc.ac.cn
b
School of Chemistry and Materials, Heilongjiang University, Harbin 150080, P. R. of China
Received 29 March 2011; revised 24 April 2011
TLC. Therefore, the progress of the reaction was moni-
tored by H NMR analysis. It was observed that in order
to convert all the starting material 5 into the desired prod-
uct 6, additional amounts of phenylacetylene and catalyst
Abstract: The title diynediol was synthesized in enantiopure
(>98.4% ee) forms, with the cross coupling of phenylacetylene with
either (R)- or (S)-5-benzyloxypent-1-yn-4-ol catalyzed by nickel(II)
chloride–copper(I) iodide as the key step. Comparison of the spec-
1
troscopic data (especially the optical rotations) for the synthetic and must be introduced repeatedly at several hours intervals.
natural samples revealed that the natural diynediol is of S-configu-
When full conversion of (R)-5 into (R)-6 was finally
ration. The unexpected formation of a pyranone ring at the alkyne
achieved as shown by 1H NMR, we set out to cleave the
terminal when cleaving a benzyl protecting group with acetic anhy-
benzyl protecting group to obtain the target product diol
(R)-1. Because of the presence of the diyne unit, common-
ly employed methods such as catalytic hydrogenolysis or
treatment with lithium and naphthalene5 were not attempt-
ed. Instead, a mild, indirect procedure using acetic anhy-
dride and trimethylsilyl triflate6 was tried, which
smoothly transformed (R)-6 into the corresponding diace-
tate (R)-7. The acetyl groups were then hydrolyzed with
potassium carbonate in methanol to deliver the desired
target product diol (R)-1.
dride and trimethylsilyl triflate is also detailed; this approach illus-
trates a novel and mild entry to related pyranones.
Key words: alkynes, alcohols, natural products, coupling, epoxides
The title compound (1) is one of the components recently
isolated by Shi1 and co-workers from Bidens pilosa (fam-
ily Asteraceae), which has been used for a long time in tra-
ditional medicines to treat malaria, hypertension, and
hyperglycerolemia.2 Through extensive spectroscopic
analyses, the planar structure of this compound was estab-
lished with confidence. However, the limited amount of
isolated natural sample available did not1 allow determi-
nation of its absolute configuration. An enantioselective
synthesis thus appeared to be necessary to complete the
structural assignment. We therefore made the synthetic ef-
forts presented below, which finally led to establishment
of the absolute configuration of the natural product 1.
n-BuLi
BF3⋅OEt2
SiMe3
O
OBn
+
Me3Si
OH
(R)-4
H
THF, –78 °C
98%
OBn
(R)-3
2
n-Bu4NF
THF
90%
Ph
NiCl2, CuI
TMEDA
Ph
As the target structure contains only one stereogenic cen-
ter, in principle, synthesis of either enantiomer would re-
veal the absolute configuration of the natural product. For
this reason we arbitrarily chose to begin with the R-iso-
mer. The initial sequence is shown in Scheme 1. Starting
from the commercially available trimethylsilyl-protected
acetylene 2 and (R)-3, the expected ring-opened product
(R)-4 was obtained in 98% isolated yield under the condi-
tions previously3 reported. Removal of the trimethylsilyl
protecting group was then achieved by treatment with tet-
rabutylammonium fluoride (TBAF) in tetrahydrofuran to
free the terminal alkyne for the intended coupling.
OBn
OH
OBn
THF, r.t.
62%
OH
(R)-5
(R)-6
TMSOTf
Ac2O
100%
K2CO3
MeOH
Ph
Ph
OH
OAc
OAc
100%
OH
(R)-1
(R)-7
The cross coupling of (R)-53a with phenylacetylene was
Scheme 1
performed under the conditions developed by Lei4 and co-
1
workers (NiCl2·6H2O, CuI, TMEDA). The product 6 was The H and 13C NMR spectra of (R)-1 were in excellent
practically inseparable from the starting material 5 on agreement with those reported for the natural sample.
However, the optical rotation was of opposite sign, which
revealed that (R)-1 is the mirror image of the natural prod-
uct.
SYNTHESIS 2011, No. 13, pp 2131–2135
Advanced online publication: 26.05.2011
DOI: 10.1055/s-0030-1260604; Art ID: H34111SS
x
x.
x
x
.
2
0
1
1
© Georg Thieme Verlag Stuttgart · New York

2132
S. Cui et al.
PAPER
Following the sequence shown in Scheme 2, with the ep- mation of an entirely unexpected product that showed,
oxide (S)-3 as the source of the stereogenic center, the diol among others, two alkenylic CH singlets (d = 6.34 and
of the opposite configuration (S)-1 was then synthesized. 6.12 ppm) and three (rather than the expected two) uncou-
As expected, all spectroscopic data for (S)-1 were consis- pled CH3 groups (d = 2.25, 2.10, and 2.09 ppm) in the 1H
tent with those reported7 for the natural product 1 in the NMR spectrum. The IR spectrum was also confusing, pre-
literature.
senting a strong signal at 1659 cm–1 (accompanied by sig-
nals of moderate strength at 1622 and 1587 cm–1) in
addition to the expected ester carbonyl C=O stretching at
1745 cm–1. These data, along with five additional carbon
signals observed in the 13C NMR spectrum, made it rather
difficult to work out a complete structure for the unidenti-
fied product.
SiMe3
+
O
n-BuLi
OBn
BF3⋅OEt2
Me3Si
OH
(S)-4
H
THF, –78 °C
98%
OBn
(S)-3
or
2
n-Bu4NF
K2CO3
MeOH
93%
THF
83%
Ph
To simplify the structural assignment and also to find out
whether this unexpected reaction is common to other sim-
ilar alkynes, a simpler trimethylsilyl-protected alkynol
118 was then examined under the same acetic anhydride
and trimethylsilyl triflate6 conditions (Scheme 4). Again,
the 1H and 13C NMR spectra of the product bore a striking
resemblance to those of 10 (albeit simpler). This com-
pound was then hydrogenated over Pd/C to give a saturat-
ed ketone. The structure of the latter could be reliably
assigned as 13 with the aid of the coupling information
gained in the 2D NMR experiments. With this result in
hand, it was then relatively straightforward to assign the
structures of 12 and 10.
NiCl2, CuI
TMEDA
Ph
OBn
OH
OBn
THF, r.t.
71%
OH
(S)-5
(S)-6
TMSOTf
92%
Ac2O
K2CO3
MeOH
Ph
Ph
OH
OAc
OAc
65%
OH
(S)-7
(S)-1
Scheme 2
OAc
H2, Pd/C
MeOH
Me3Si
During the course of this synthesis, we also attempted to
remove the benzyl protecting group before the cross cou-
pling of the two alkynes units (Scheme 3), because the
diol 9 (with R = H) was expected to be of higher polarity
than 5 and consequently might be readily differentiated
from the coupling product diyne 6 on silica gel. We rea-
soned that, under these conditions, both monitoring the
progress of the cross coupling and isolation of the product
6 might be much easier.
O
61%
OH
11
TMSOTf
O
13
r.t., 4 h
71%
O
Ac2O
(cis/trans mixture)
OAc
O
12
Scheme 4
OAc
TMSOTf
R
OAc
A rationalization for the formation of 10 and 12 is given
in Scheme 5. It is known9 that, in the presence of a Lewis
acid, trimethylsilyl-protected alkynes may be readily con-
verted into the corresponding acetylated alkynes. There-
fore, in our case, an acetyl group is also very likely to be
installed onto the terminal alkyne. The methyl ketone can
then undergo an aldol reaction with another molecule of
acetic anhydride to form an acetoacetyl group. The ketone
carbonyl group at the propargylic position then enolizes to
form a thermodynamically more stable conjugated sys-
tem. The resulting enol hydroxy group is subsequently
acetylated by a third molecule of acetic anhydride , afford-
ing an enol acetate motif. Finally, intramolecular aldol
condensation (with the methyl at the terminal ketone at-
tacking the acetate carbonyl group followed by dehydra-
tion) closes the six-membered ring and delivers the
pyranone unit. It is noteworthy that, compared with the
conditions10 employed in the previous syntheses of pyra-
nones, the present approach is remarkably mild and might
Ac2O
8
lithium
naphthalene
R
OBn
Me3Si
OH
(R)-4
OH
TMSOTf
Ac2O
r.t., 4 h
OH
OAc
O
9
OAc
50%
R = TMS or H
O
10
Scheme 3
Unfortunately, all attempts to achieve the benzyl depro-
tection were unsuccessful. Under the Li/naphthalene5
conditions, no desired diol 9 could be detected. Use of
acetic anhydride and trimethylsilyl triflate6 led to the for-
Synthesis 2011, No. 13, 2131–2135 © Thieme Stuttgart · New York

PAPER
Configuration of a 4,6-Diyne-1,2-diol Isolated from Bidens pilosa
2133
stirred for 12 h and concentrated on a rotary evaporator. The resi-
due, which did not contain any starting material 5 as shown by 1H
NMR analysis, was purified by chromatography on silica gel
(EtOAc–PE, 1:4) to give (S)-6.
Yield: 49 mg (0.169 mmol, 71% from 5); yellowish oil; [a]D23 +23.4
(c 1.2, CHCl3).
thus also be applicable to the synthesis other related pyra-
nones.
O
O
O
SiMe3
O
HO
Ac2O
Ac2O
FTIR (film): 3429, 3063, 3033, 2911, 2861, 2245, 2168, 1593,
1490, 1453, 1442, 1361, 1203, 1103, 1027, 755, 890 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.50 (br d, J = 8.1 Hz, 2 H), 7.41–
7.30 (m, 8 H), 4.60 (s, 2 H), 4.09–3.98 (m, 1 H), 3.65 (A of an ABX,
dd, J = 9.5, 3.5 Hz, 1 H), 3.56 (B of an ABX, dd, J = 9.3, 6.3 Hz,
1 H), 2.65 (d, J = 6.5 Hz, 2 H), 2.61 (br s, 1 H).
TMSOTf
R
R
R
R
OH
O
O
O
O
Ac2O
O
O
O
13C NMR (100 MHz, CDCl3): d = 137.7, 132.5, 129.0, 128.4, 128.3,
127.8, 127.7, 121.7, 80.1, 75.3, 74.0, 73.4, 72.7, 68.8, 67.1, 24.6.
MS (ESI): m/z = 313.1 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C20H18O2Na: 313.1199;
H2O
R
R
R
found: 313.1204.
Scheme 5
(R)-1-(Benzyloxy)-7-phenylhepta-4,6-diyn-2-ol [(R)-6]
Obtained through cross coupling of phenylacetylene with (R)-5 us-
ing the procedure for the conversion of (S)-5 into (S)-6 described
In summary, through chiral building block based synthe-
ses, it has been shown that the 7-phenylhepta-4,6-diyne-
1,2-diol isolated from Bidens pilosa (family Asteraceae) above.
is of (S)-configuration.11 The cross coupling between the
phenylacetylene and alkyne 5 was found to be much slow-
er than self-coupling of the former. It was hence necessary
to use a rather large excess of phenylacetylene to drive the
desired cross coupling to completion. In the debenzylation
with acetic anhydride and trimethylsilyl triflate an unex-
pected condensation of additional acetyl groups onto the
alkyne terminal leading to formation of a pyranone was
observed. The mild conditions also appear to be applica-
ble to the synthesis of other related pyranones.
[a]D27 –22.0 (c 1.0, CHCl3). Other data were as those for (S)-6.
(S)-7-Phenylhepta-1,2-diacetyloxy-4,6-diyne [(S)-7]
A solution of Me3SiOTf (46 mL, 0.255 mmol) in Ac2O (1.0 mL) was
added to a solution of (S)-6 (37 mg, 0.127 mmol) in Ac2O (1.0 mL)
and stirred at –40 °C. The mixture was stirred at the same tempera-
ture for 30 min (TLC showed completion of the reaction), then sat.
aq NaHCO3 (2 mL) was added. The mixture was extracted with
Et2O (3 × 5 mL) and the combined organic layers were washed with
brine (10 mL) and dried over anhydrous MgSO4. Removal of sol-
vent by rotary evaporation left an oil, which was purified by chro-
matography on silica gel (EtOAc–PE, 1:4) to give diacetate (S)-7.
25
Yield: 33 mg (0.116 mmol, 92%); yellowish oil; [a]D +64.0 (c
All chemicals were reagent grade and used as purchased. Flash col-
umn chromatography was carried out on silica gel (300–400 mesh).
Petroleum ether (PE), where used, had a boiling range of 60–90 °C.
NMR spectra were recorded on a Varian Mercury 300 (300 MHz
for 1H) or a Bruker Avance NMR 400 (400 MHz for 1H) spectrom-
eter. IR spectra were measured on a Nicolet 380 infrared spectro-
photometer. ESI-MS data were acquired on a Shimadzu LCMS-
2010EV mass spectrometer, and HRMS data were obtained with a
Bruker APEXIII 7.0 Tesla FT-MS spectrometer. Optical rotations
were measured on a Jasco P-1030 polarimeter.
0.31, CHCl3).
FTIR (film): 2968, 2250 (very weak), 2170 (very weak), 1747,
1495, 1444, 1372, 1222, 1046, 758, 690 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.49–7.47 (br d, J = 6.8 Hz, 2 H),
7.36–7.29 (m, 3 H), 5.20–5.09 (m, 1 H), 4.37 (A of an ABX, dd,
J = 12.1, 3.8 Hz, 1 H), 4.23 (B of an ABX, J = 12.0, 5.9 Hz, 1 H),
2.77 (A of an ABX, dd, J = 17.5, 6.6 Hz, 1 H), 2.72 (B of an ABX,
dd, J = 17.5, 6.6 Hz, 1 H), 2.11 (s, 3 H), 2.09 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 170.5, 170.1, 132.6, 129.1, 128.4,
121.6, 77.9, 75.7, 73.8, 69.0, 67.6, 63.7, 22.1, 20.9, 20.7.
(S)-1-(Benzyloxy)-7-phenylhepta-4,6-diyn-2-ol [(S)-6]
MS (ESI): m/z = 307.1 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H16NaO4: 307.0941;
TMEDA (28 mL, 0.189 mmol) was added to a mixture of
NiCl2·6H2O (14 mg, 0.047 mmol) and CuI (9 mg, 0.047 mmol) in
THF (1 mL) and stirred at ambient temperature. After 5 min at the
same temperature, a solution of alkyne (S)-5 (45 mg, 0.237 mmol)
in THF (1.0 mL) was added, followed by phenylacetylene (neat,
130 mL, 1.183 mmol). The mixture was stirred at ambient tempera-
ture for 12 h. Then, to the reaction mixture were added NiCl2·6H2O
(14 mg, 0.047 mmol), CuI (9 mg, 0.047 mmol), TMEDA (28 mL,
0.189 mmol) and phenylacetylene (130 mL, 1.183 mmol). After
completion of the addition, stirring was continued for another 5 h
before an additional portion of phenylacetylene (130 mL, 1.183
mmol) was added. The mixture was stirred at ambient temperature
for 12 h (starting material 5 was still present in significant amounts
as shown by 1H NMR analysis). To the mixture were added
NiCl2·6H2O (14 mg, 0.047 mmol), CuI (9 mg, 0.047 mmol),
TMEDA (28 mL, 0.189 mmol) and phenylacetylene (130 mL, 1.183
mmol). Stirring was continued for 5 h then a final portion of phenyl-
acetylene (130 mL, 1.183 mmol) was added. The mixture was
found: 307.0947.
(R)-7-Phenylhepta-1,2-diacetyloxy-4,6-diyne [(R)-7]
Obtained from (R)-6 using the same procedure for conversion of
(S)-6 into (S)-7 described above.
[a]D24 –61.9 (c 0.35, CHCl3). Other data were as those for (S)-7.
(S)-7-Phenylhepta-4,6-diyne-1,2-diol [(S)-1]
A solution of (S)-7 (24 mg, 0.084 mmol) and K2CO3 (0.035 g, 0.253
mmol) in MeOH (1 mL) was stirred at ambient temperature for 30
min (TLC showed disappearance of 7), then sat. aq NH4Cl (2 mL)
was added. The mixture was extracted with Et2O (3 × 5 mL) and the
combined organic layers were washed with brine (10 mL) and dried
over anhydrous MgSO4. Removal of solvent by rotary evaporation
Synthesis 2011, No. 13, 2131–2135 © Thieme Stuttgart · New York

2134
S. Cui et al.
PAPER
left an oil, which was purified by chromatography on silica gel
(EtOAc–PE, 1:2) to give the known diacetate (S)-1.
Yield: 11 mg (0.055 mmol, 65%); yellowish oil; [a]D24 –7.1 (c 0.4,
acetone) {Lit.1 [a]D20 –7.0 (c 0.4, acetone)}; 98.4% ee measured by
HPLC (CHIRALPAK IC column; 0.46 × 25 cm; particle size 5 mm;
n-hexane–i-PrOH, 90:10; flow rate 0.7 mL/min; 214 nm).
MgSO4. Removal of solvent by rotary evaporation left an oil, which
was purified by chromatography on silica gel (EtOAc–PE, 3:2) to
give acetate 12.
Yield: 125 mg (0.50 mmol, 71%); unstable yellow oil.
FTIR (film): 2956, 2236, 1738, 1658, 1391, 1240, 935 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.33 (s, 1 H), 6.12 (s, 1 H), 4.11
(t, J = 6.0 Hz, 2 H), 2.51 (t, J = 6.7 Hz, 2 H), 2.27 (s, 3 H), 2.06 (s,
3 H), 1.81–1.75 (m, 2 H), 1.75–1.69 (m, 2 H).
13C NMR (100 MHz, CDCl3): d (1H-coupling established by 2D
HSQC) = 179.3 (q), 171.0 (q), 166.3 (q), 148.3 (q), 118.6 (coupled
to 1H at d = 6.33 ppm), 114.7 (coupled to 1H at d = 6.12 ppm), 98.0
(q), 73.3 (q), 63.6 (coupled to 1H at d = 4.11 ppm), 27.7 (coupled to
1H at d = 1.81–1.75 ppm), 24.3 (coupled to 1H at d = 1.75–
1.69 ppm), 20.9 (coupled to 1H at d = 2.06 ppm), 19.9 (coupled to
1H at d = 2.27 ppm), 19.0 (coupled to 1H at d = 2.51 ppm).
FTIR (film): 3360, 2926, 2248, 2163, 1490, 1442, 1092, 1026, 754,
689 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.49–7.47 (br d, J = 7.5 Hz, 2 H),
7.35–7.28 (m, 3 H), 4.00–3.90 (m, 1 H), 3.80 (A of an ABX, dd,
J = 11.2, 2.8 Hz, 1 H), 3.64 (B of an ABX, dd, J = 11.2, 6.4 Hz,
1 H), 2.65 (A of an ABX, dd, J = 17, 6.5 Hz, 1 H), 2.60 (B of an
ABX, dd, J = 17, 6.5 Hz, 1 H), 3.07–2.06 (v. br, 2 H, 2 × OH).
13C NMR (100 MHz, CDCl3): d = 132.5, 129.1, 128.4, 121.6, 79.8,
75.6, 73.8, 70.2, 67.4, 65.4, 24.6.
MS (ESI): m/z = 223.0 [M + Na]+.
MS (ESI): m/z = 271.1 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C13H12O2Na: 223.0730;
HRMS (ESI): m/z [M + Na]+ calcd for C14H16O4Na: 271.0941;
found: 223.0737.
found: 271.0948.
(R)-7-Phenylhepta-4,6-diyne-1,2-diol [(R)-1]
(R)-1 was obtained from (R)-7 using the same procedure for conver-
sion of (S)-7 into (S)-1 described above.
6-(6-Methyl-4-oxo-tetrahydro-2H-pyran-2-yl)hexyl Acetate
(13)
A mixture of 12 (40 mg, 0.16 mmol) and 10% Pd/C (40 mg) in
MeOH (2.5 mL) was stirred at ambient temperature under H2
(1 atm) for 6 h. The catalyst was filtered off and the filtrate was con-
centrated on a rotary evaporator to dryness. The residue was puri-
fied by chromatography on silica gel (EtOAc–PE, 1:6) to give 13.
26
[a]D +7.0 (c 0.4, acetone); 98.9% ee as measured by HPLC
(CHIRALPAK IC column; 0.46 × 25 cm; particle size 5 mm; n-hex-
ane–i-PrOH, 90:10; flow rate 0.7 mL/min; 214 nm). Other data
were as those for (S)-1.
Yield: 25 mg (0.10 mmol, 61%); yellowish oil.
FTIR (film): 2934, 2859, 1738, 1239, 1038 cm–1.
(R)- 1,2-Diacetyloxy-5-(6-methyl-4-oxo-4H-pyran-2-yl)pent-4-
yne (10)
1H NMR (300 MHz, CDCl3): d (coupling established by 2D COSY) =
4.05 (t, J = 6.6 Hz, 2 H, coupled to 1H at d = 1.72–1.61 ppm), 3.77–
3.67 (m, 1 H, coupled to the methyl at d = 1.33 ppm), 3.60–3.54 (m,
1 H, coupled to 1H at d = 1.72–1.61 and 1.55–1.46 ppm), 2.32 (br d,
J = 14 Hz, 2 H), 2.23 (br t, J = 11.4 Hz, 1 H), 2.22 (br t, J = 11.1 Hz,
2 H), 2.06 (s, 3 H), 1.72–1.61 (m, 3 H), 1.55–1.46 (m, 2 H), 1.36–
1.32 (m, 6 H), 1.33 (d, J = 6.3 Hz, 3 H).
A solution of Me3SiOTf (110 mL, 0.61 mmol) in Ac2O (1.0 mL) was
added to a solution of (R)-4 (50 mg, 0.19 mmol) in Ac2O (2.0 mL)
and stirred at –40 °C. The mixture was stirred at the same tempera-
ture for 4 h (TLC showed completion of the reaction), then sat. aq
NaHCO3 (2 mL) was added. The mixture was extracted with Et2O
(3 × 5 mL) and the combined organic layer was washed with brine
(10 mL) and dried over anhydrous MgSO4. Removal of the solvent
by rotary evaporation left an oil, which was purified by chromatog-
raphy on silica gel (EtOAc–PE, 2:1) to give diacetate 10.
13C NMR (100 MHz, CDCl3): d (1H-coupling established by 2D
HSQC) = 207.7 (q), 171.2 (q), 76.9 (coupled to 1H at d = 3.57 ppm),
1
1
22
73.2 (coupled to H at d = 3.71 ppm), 64.5 (coupled to H at d =
Yield: 28 mg (0.096 mmol, 50%); yellowish oil; [a]D –43.8 (c
1
4.05 ppm), 49.4 (coupled to H at d = 2.34 (d, 1 H) and 2.23 (t,
0.25, CHCl3).
1
1 H) ppm), 47.6 (coupled to H at d = 2.32 (d, 1 H) and 2.22 (t,
FTIR (film): 2245, 1746, 1659, 1622, 1587, 1435, 1392, 1374,
1223, 1047, 918, 867 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.35 (d, J = 1.9 Hz, 1 H), 6.12 (s,
1 H), 5.27–5.16 (m, 1 H), 4.35 (A of an ABX, dd, J = 12.1, 3.7 Hz,
1 H), 4.20 (B of an ABX, dd, J = 12.1, 4.4 Hz, 1 H), 2.82 (d, J = 6.0,
1 H), 2.11 (s, 1 H), 2.10 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 179.0, 170.4, 170.0, 166.3, 147.7,
119.3, 115.0, 92.2, 75.0, 68.6, 63.6, 21.9, 20.8, 20.7, 19.9.
MS (ESI): m/z = 315.2 [M + Na]+.
1
1 H) ppm), 36.3 (coupled to H at d = 1.70 and 1.54 ppm), 29.1
(coupled to 1H at d = 1.34 ppm), 28.5 (coupled to 1H at d =
1.65 ppm), 25.8 (coupled to 1H at d = 1.66 ppm), 25.2 (coupled to
1H at d = 1.36 ppm), 22.1 (coupled to 1H at d = 1.47 and 1.34 ppm),
21.0 (coupled to the doublet at d = 1.33 ppm).
MS (ESI): m/z = 279.1 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C14H24O4Na: 279.1567;
found: 279.1574.
HRMS (ESI): m/z [M + Na]+ calcd for C15H16O6Na: 315.0839;
found: 315.0848.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
6-(6-Methyl-4-oxo-4H-pyran-2-yl)hex-5-ynyl Acetate (12)
Me3SiOTf (650 mL, 2.82 mmol) was added to a solution of 11 (120
mg, 0.71 mmol) in Ac2O (4.0 mL) stirred at –40 °C under argon. Af-
ter completion of the addition, the bath was allowed to warm to
0 °C. The mixture was stirred at 0 °C for 2 h (TLC showed comple-
tion of the reaction), then sat. aq NaHCO3 (5 mL) was added to the
blood-red mixture. The mixture was extracted with Et2O
(3 × 10 mL) and the combined organic layers were washed with
H2O (20 mL) and brine (20 mL) before being dried over anhydrous
Acknowledgment
This work was supported by the National Basic Research Program
of China (the 973 Program, 2010CB833200), the National Natural
Science Foundation of China (21032002, 20921091, 20672129,
20621062, 20772143), and the Chinese Academy of Sciences
(KJCX2.YW.H08).
Synthesis 2011, No. 13, 2131–2135 © Thieme Stuttgart · New York

PAPER
Configuration of a 4,6-Diyne-1,2-diol Isolated from Bidens pilosa
2135
(6) Alzeer, J.; Vasella, A. Helv. Chim. Acta 1995, 78, 177.
(7) The propargylic CH2 group in the end product 1 was
reported to give rise to a signal at d = 2.63 (d, J = 6.6 Hz,
2 H) ppm (measured at 300 MHz) in the original isolation
paper (see ref. 1). In this work, it is assigned as d = 2.65 (dd,
J = 17, 6.5 Hz, 1 H), 2.60 (dd, J = 17, 6.5 Hz, 1 H) ppm,
because, in the 400 MHz spectrum, a doublet of rather low
intensity was clearly seen on each side of the rather intense
ones (which might be taken as a broadened doublet with a
splitting of ca. 6.5 Hz if the small doublets on both sides are
overlooked).
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