First total synthesis of the brominated polyacetylenes (+)-diplyne a and D: Proof of absolute configuration

Article abstract of DOI:10.1016/j.tetasy.2004.11.010

The first total syntheses of the enantiomers of two novel brominated polyacetylenic natural products, diplynes A and D, are reported. The syntheses are based on Pd and Cu(I)-catalyzed coupling reactions. The stereocenter was derived from D-mannitol. The stereocenter in the naturally occurring (-)-diplyne A was established to have an (R)-configuration.

Full text of DOI:10.1016/j.tetasy.2004.11.010

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 3973–3977
First total synthesis of the brominated polyacetylenes (+)-diplyne
A and D: proof of absolute configuration
Benjamin W. Gung,* Craig Gibeau and Amanda Jones
Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA
Received 18 October 2004; accepted 1 November 2004
Abstract—The first total syntheses of the enantiomers of two novel brominated polyacetylenic natural products, diplynes A and D,
are reported. The syntheses are based on Pd and Cu(I)-catalyzed coupling reactions. The stereocenter was derived from D-mannitol.
The stereocenter in the naturally occurring (À)-diplyne A was established to have an (R)-configuration.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
R1
R2
OH
OH
Several fractions of moderate polarity from the crude
extract of the Philippine sponge Diplastrella sp. were
recently found to inhibit the activity of the HIV-1 integ-
rase.1 Five novel brominated polyacetylenic diols
diplynes A–E 1–5 were isolated via the inhibitory acti-
vity guided screen. This was the first report of metabo-
lites from the genus Diplastrella and the first
description of naturally occurring brominated poly-
acetylenic diols. Each member of this group of biologi-
cally active natural products possesses one stereogenic
center and diplyne A 1 was isolated as an optically active
white powder.1 However, the absolute configuration of
diplyne A was not determined due to the small quanti-
ties of each isolated compound.
1 R1 = Br; R2 = H
2 R1 = H; R2 = Br
Br
OH
OH
3
4
Br
Br
OH
OH
OH
OH
5
As part of our effort toward the total synthesis of poly-
acetylenic natural products,2–4 we became interested in
the synthesis of these brominated polyacetylenic diols.
Herein, we report the total synthesis of diplynes A and
D and the establishment of the C2 configuration in nat-
ural diplyne A as (R) (Fig. 1).
Figure 1. Polyacetylenic diols diplynes A–E 1–5 isolated from the
Philippine sponge Diplastrella sp. The absolute configuration at C2
was not determined in the original report. We have established the C2
stereogenic center in the natural (À)-diplyne A 1 to be (R) and the
stereocenter in the other members is tentatively assigned accordingly.
link the left hand piece to 1,9-decadiyne5 and a Cu(I) cat-
alyzed cross coupling reaction should connect the right
hand fragment to the center piece.6 The synthesis of dip-
lyne D 4 would follow a similar strategy with one extra
acetylene unit in the left-hand side of the molecule.
We envisioned a synthetic route (Fig. 2) that should rap-
idly provide diplyne A 1 based on our experience in the
synthesis of polyacetylenes.2–4 In this plan, the target
molecule is divided into three components: the left hand
piece is envisioned as arising from 1,2-dibromoethylene,
the right hand piece from D-mannitol, and the center piece
1,9-decadiyne. A Sonogashira coupling reaction should
2. Results and discussion
The synthesis of diplyne A 1 started with the commer-
cially available 1,9-decadiyne 6 (Scheme 1) and the
*
Corresponding author. E-mail: gungbw@muohio.edu
0957-4166/$ - see front matter ꢀ 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.11.010

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B. W. Gung et al. / Tetrahedron: Asymmetry 15 (2004) 3973–3977
Sonogashira coupling
a value of [a]D = +9.6 in the same solvent. The plus sign
corresponds to an (S)-configuration since the stereocen-
ter in the synthetic sample was derived from D-mannitol.
The absolute configuration in the synthetic diplyne A is
(S) even though D-mannitol has an (R)-configuration.
The Cahn–Ingold–Prelog priority of the substituents
has changed when D-mannitol was transformed into the
acetylenic diol derivative 7. Therefore, the naturally
occurring diplyne A should have an (R)-configuration.
Cu(I) catalyzed coupling
OH
Br
1
OH
1,2-dibromoethylene
D-mannitol
Br
OH
OH
With diplyne A 1 in hand, we turned our attention to
diplyne D 4. Using the same cross-coupling reaction
and starting with 1,7-octadiyne 11, the desired cross-
coupling product 12 was obtained in 43% yield along
with 16% of a symmetrical product 13, Scheme 2. Com-
pound 13 is the result of coupling at both ends of 1,7-
octadiyne.
4
Figure 2. Retrosynthetic analysis for diplynes A 1 and D 4.
coupling reaction proceeded smoothly with the right
hand fragment 7, which was prepared as previously
reported from our laboratory.3 Exactly 1equiv of bromo-
alkyne 7 was added dropwise to a mixture of 1,9-deca-
diyne 6, and the reagents in MeOH to minimize the
coupling of 7 to both terminals of 6.6 The desired cross
coupling product 8 was obtained in an unoptimized 44%
yield along with a small amount of unidentified by-prod-
ucts. The next step was a cross-coupling reaction
between the terminal alkyne 8 and 1,2-dibromoethylene
9. A few modified Sonogashira coupling conditions were
tried;7,8 however, the reagents that gave a satisfactory
yield were a combination of Pd(PPh3)4 and CuI in
Et3N. Four equivalents of a cis/trans mixture of 9 were
used in the reaction, which provided 63% yield of a
98:2 ratio of the enyne 10 in favor of the trans coupling
product. The terminal alkyne 8 reacts preferentially with
the trans isomer of 1,2-dibromoethylene, which is con-
sistent with a previous report that trans-1,2-dibromoeth-
ylene is more reactive than the corresponding cis-isomer
in the Pd-catalyzed cross-coupling reactions.9
The desired cross-coupling product 12 was brominated
with NBS in the presence of AgNO3 to yield bromo-
alkyne 14 in 94%.10 The palladium-catalyzed cross-cou-
pling reaction of 14 with triisopropylsilyl(TIPS)-
protected acetylene afforded in 65% the desired tetrayne
15 and in 20% of the homocoupling product of TIPS-
acetylene 16.11 Intended removal of the TIPS group
from 15 with HFÆpyridine complex resulted in the re-
moval of the acetonide to afford diol 17 in 92% yield.
There was no need to change reagents or conditions
since the diol protecting group needed to be removed
anyway and the remaining steps should not be affected
by the open hydroxy groups. The TIPS group was then
removed using tetrabutylammonium fluoride (TBAF) in
THF to produce the terminal diyne 18 in 97% yield. Diol
18 is a solid with a melting point of 77–79ꢁC. Although
it is a terminal diyne, compound 18 is remarkably stable
in light of previous reports of instability for terminal
diynes.12,13 The final step is the coupling reaction be-
tween 18 and a mixture of cis/trans 1,2-dibromoethylene
9 in the presence of Pd(PPh3)4 and CuI in Et3N. This
cross-coupling reaction provided (+)-diplyne D in 56%
yield with a specific rotation of [a]D = +7.2. No optical
activity was reported for natural diplyne D. Thus from
a common starting material, D-mannitol, the synthetic
samples of diplynes A and D have the same (+)-sign in
optical rotation. Since the structure of diplyne D is simi-
lar to diplyne A, it is reasonable to assume that the nat-
ural diplyne D also has an (R)-configuration.
The final step in the preparation of diplyne A 1 is the re-
moval of the acetonide protecting group, which was
accomplished using a catalytic amount of p-toluenesulf-
onic acid in MeOH to afford the synthetic sample of dipl-
yne A in 74% yield. The synthetic sample exhibits
essentially identical spectroscopic data as that reported
for the natural product except that the optical rotation
is opposite of the natural product. The natural diplyne
A
was reported to have a specific rotation of
[a]D = À8.7 in MeOH1 while the synthetic sample showed
O
Br
O
7
CuCl, EtNH2
MeOH, NH2OH
O
6
8
44%
O
Br
Br
9
(cis/trans mixture)
Br
Cat. TsOH,
O
Pd(PPh3)4
CuI, Et3N
63%
Diplyne A 1
MeOH
74%
O
10 ratio of trans/cis >98:2
Scheme 1.

B. W. Gung et al. / Tetrahedron: Asymmetry 15 (2004) 3973–3977
3975
O
O
+
Br
12 43%
O
O
7
O
CuCl, EtNH2
11
MeOH, NH2OH
O
2
O
13 16%
2
O
NBS, AgNO3
acetone
Br
O
12
94%
14
O
TIPS
TIPS
O
Pd(II), CuI, (i-Pr)2NH
15 65%
16 20%
O
+
TIPS
TIPS
OH
pyridine
THF, 0 C to rt
HF
TIPS
°
TBAF, THF
97%
15
92%
17
OH
Br
Br
9
OH
OH
(cis/trans mixture)
Diplyne D 4
18
Pd(PPh3)4
CuI, Et3N
56%
Scheme 2.
3. Conclusion
of NH2OHÆHCl (18mg, 0.25mmol), 5mL 70% aq
solution of EtNH2, CuI (25mg, 0.25mmol), and diyne
6 (682mg, 5.0mmol) in that order. The bromoalkyne 7
(1.02g, 5.0mmol) was added over a period of one and
a half hours to the reaction mixture via a syringe pump
keeping the temperature between 30–35ꢁC. After an
additional 30min a solution of 1.2g of KCN and 5g
of NH4Cl in 16mL of H2O was added under vigorous
stirring. The product was isolated by extraction with
Et2O (3 · 20mL) and the combined organic layers were
washed with saturated NH4Cl solution and dried over
MgSO4. The solvents were removed under reduced
pressure and the residue was purified over silica gel
(5% EtOAc/Hex) to afford 569mg (44%) of a light yel-
low oil.
We have completed an expedient first total synthesis of
the enantiomers of two novel brominated polyacetylenic
natural products (+)-diplynes A and D. The configura-
tion of the natural product (À)-diplyne A is established
to be of (R)-configuration since the synthetic sample,
which has an (S)-configuration, exhibits a (+) sign in
specific rotation.
4. Experimental
All reactions were carried out under an atmosphere of
nitrogen in oven-dried glassware. Reagents were pur-
chased from commercial sources and used without fur-
ther purification. Flash column chromatographic
separations were performed using silica gel 40–63lm.
Reactions were monitored with TLC and UV light.
NMR spectra (1H, 13C) were recorded on Bruker 200
and 300MHz spectrometers with CDCl3 or CD3OD as
the solvents. Melting points are not corrected.
1
[a]D = +38.4( c 1.63, CHCl3). UV (MeOH) 201nm. H
NMR (300MHz, CDCl3): d 1.36 (3H, s), 1.41 (4H, m),
1.48 (3H, s), 1.52 (4H, m), 1.94 (1H, t, J = 2.6Hz),
2.17 (2H, t, J = 13.7Hz), 2.28 (2H, dt, J = 6.8, 2.5Hz),
3.93 (1H, dd, J = 8.1, 6.1Hz), 4.14 (1H, dd, J = 8.0,
6.5Hz), 4.76 (1H, dd, J = 6.5, 5.2). 13C NMR
(75MHz, CDCl3): d 18.2, 19.1, 25.8, 26.0, 27.8, 28.0,
28.1 (2), 64.4, 65.7, 68.2, 69.6, 70.6, 72.7, 81.8, 84.3,
110.4. IR: m cmÀ1 3300 (sharp), 2256, 2217, 1458,
1235, 1065, 839. HRMS: calcd for C17H22O2 + Na,
281.1518, found M + Na, 281.1517.
4.1. 1,2-Isopropylidenetetradeca-3,5,13-triyne 8
To a 50mL round-bottom flask under an atmosphere of
N2 was added 5mL of MeOH, 0.22mL of an aq solution

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B. W. Gung et al. / Tetrahedron: Asymmetry 15 (2004) 3973–3977
4.2. (15E)-1,2-Isopropylidene-16-bromohexadeca-15-en-
3,5,13-triyne 10
compound 11 (1.0g, 9.42mmol) was added in one por-
tion. Next, a solution of compound 7 (1.92g, 9.42mmol)
in MeOH (2mL) was added over the course of 0.5h
using a syringe pump. The resulting mixture was stirred
for an additional 0.5h at room temperature. A solution
of KCN (1.76g) and NH4Cl (7.32g) in H2O (25mL) was
then added with vigorous stirring. The resulting mixture
was extracted three times with Et2O and the organic lay-
ers dried with MgSO4. The solution was filtered and the
solvent removed under reduced pressure. The crude mix-
ture was purified over a silica gel column to afford a pale
yellow oil (0.94g, 43%) and a second fraction (0.53g,
16%).
To a 50mL round-bottom flask under an atmosphere of
N2 was added 19mL of Et3N, triyne 8 (100mg,
0.387mmol), 1,2-dibromoethylene (0.127mL, 1.54
mmol), Pd(PPh3)4 (27mg, 0.023mmol), and CuI (9mg,
0.046mmol) in that order. The resulting mixture was
stirred overnight at room temperature. After 12h the
mixture was filtered through a plug of Florisil with ex-
cess hexanes. The filtrate was concentrated and the resi-
due was purified over silica gel (5% EtOAc/Hex) to
afford 10 (87.1mg, 62%) and its cis-isomer (1.6mg
1.1%) as light yellow oils.
1
Compound 12: [a]D = +34.7 (c 0.21, MeOH), H NMR
Compound 10 [a]D = +27.3 (c = 0.68, CHCl3). UV
(MeOH) 238nm. H NMR (300MHz, CDCl3): d 1.35
(300MHz, CDCl3): d 1.35 (3H, s), 1.46 (3H, s), 1.63
(4H, m), 1.93 (1H, t, J = 2.5Hz), 2.19 (2H, m), 2.30
(2H, m), 3.91 (1H, dd, J = 6.2, 8.0Hz), 4.12 (1H, dd,
J = 6.4, 7.9Hz), 4.73 (1H, t, J = 6.2Hz). 13C NMR
(75MHz, CDCl3): d 18.28, 19.19, 26.31, 26.51, 27.37,
27.74, 65.14, 66.23, 69.08, 70.11, 71.09, 73.41, 81.79,
84.19, 111.00. Compound 13: [a]D = +47.75 (c 0.49,
1
(3H, s), 1.37 (4H, m), 1.46 (3H, s), 1.51 (4H, m), 2.25
(4H, m), 3.91 (1H, dd, J = 7.8, 6.3Hz), 4.12 (1H, dd,
J = 7.8, 6.7Hz), 4.73 (1H, dd, J = 6.2, 5.3Hz), 6.15
(1H, dt, J = 14.0, 2.0Hz), 6.54 (1H, d, J = 14.0). 13C
NMR (75MHz, CDCl3): d 19.2, 19.4, 25.9, 26.1, 28.0,
28.1 (2), 28.2, 64.5, 65.9, 69.7, 70.6, 70.8, 72.9, 76.8,
81.9, 93.0, 117.0, 118.0. IR m cmÀ1 2256, 2216, 1458,
1235, 1064. HRMS: calcd for C19H23BrO2 + Na,
385.0779, found M + Na, 385.0751.
1
MeOH), H NMR (200MHz, CDCl3): d 1.35 (6H, s),
1.46 (6H, s), 1.62 (4H, m), 2.29 (4H, m), 3.92 (2H, dd,
J = 6.1, 8.1Hz), 4.13 (2H, dd, J = 6.4, 8.1Hz), 4.73
(1H, t, J = 6.3Hz). 13C NMR (50MHz, CDCl3): 19.18,
26.34, 27.39, 65.30, 66.24, 70.13, 71.05, 73.51, 81.56,
111.05.
1
cis-isomer: H NMR (300MHz, CDCl3): d 1.35 (3H, s),
1.37 (4H, m), 1.46 (3H, s), 1.51 (4H, m), 2.25 (4H, m),
3.91 (1H, dd, J = 7.8, 6.3Hz), 4.12 (1H, dd, J = 7.8,
6.7Hz), 4.73 (1H, dd, J = 6.2, 5.3Hz), 6.26 (1H, dt,
J = 6.6, 2.1Hz), 6.45 (1H, d, J = 7.4Hz).
4.5. 4-(10-Bromo-deca-1,3,9-triynyl)-2,2-dimethyl-
[1,3]dioxolane 14
To a suspension of NBS (812mg, 4.56mmol) and com-
pound 12 (897mg, 3.89mmol) in acetone (39mL) at
room temperature was added AgNO3 (66.1mg,
0.39mmol). The mixture was stirred at room tempera-
ture for 1h and was then diluted with H2O (75mL).
The aqueous layer was extracted three times with Et2O
and the combined organic layers were dried over
MgSO4, filtered, and the solvent removed under reduced
pressure. The crude mixture was purified over a silica gel
column to afford the desired product as a yellow oil
4.3. (+)-Diplyne A 1
A solution of 10 (51mg, 0.14mmol) and p-TsOH
(2.6mg, 0.014mmol) in MeOH (2.8mL) was stirred for
24h at room temperature. To the reaction mixture, solid
NaHCO3 (29mg, 0.28mmol) was added and the mixture
was stirred for 15min. The resulting solution was filtered
and MeOH was evaporated. The remaining residue was
purified over silica gel (50% EtOAc/Hex) to afford
32.6mg (74%) a white solid.
1
(1.08g, 94%). [a]D = +27.6 (c 2.98, MeOH), H NMR
(300MHz, CDCl3): d 1.35 (3H, s), 1.46 (3H, s), 1.61
(4H, m), 2.21 (2H, m), 2.28 (2H, m), 3.92 (1H, dd,
J = 6.2, 7.3Hz), 4.13 (1H, dd, J = 6.7, 7.8Hz), 4.73
(1H, t, J = 6.1Hz), 13C NMR (75MHz, CDCl3): 19.19,
19.56, 26.31, 26.51, 27.40, 27.59, 38.67, 65.20, 66.23,
70.12, 71.07, 73.46, 79.97, 81.71, 111.02. HRMS: Calcd
for C15H17BrO2 + Na, 331.0310, found M + Na:
331.0309.
[a]D = +9.6 (c 0.29, MeOH) (lit.1 [a]D = À8.7). UV
(MeOH) 238nm. Mp 95–96ꢁC. 1H NMR (500MHz,
MeOH): d 1.45 (4H, m), 1.55 (4H, m), 2.31 (4H, m),
3.56 (1H, dd, J = 11.2, 6.8Hz), 3.61 (1H, dd, J = 11.2,
5.0Hz), 4.36 (1H, dd, J = 6.0, 5.6Hz), 6.25 (1H, dt,
J = 14.0, 2.3Hz), 6.71 (1H, d, J = 14.0Hz). 13C NMR
(125MHz, MeOH): d 19.6, 19.9, 29.2, 29.3 (2), 29.4,
64.5, 65.6,67.1, 70.7, 75.8, 78.2, 81.7, 93.7, 117.9,
119.1. IR: m cmÀ1 3298 (broad), 2254, 2216, 1693,
1461, 1085, 922, 728. HRMS: calcd for C16H19BrO2 +
Na, 345.0466, found M + Na, 345.0487.
4.6. [12-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-dodeca-
1,3,9,11-tetraynyl]-triisopropyl-silane 15
To a solution of compound 14 (1.08g, 3.49mmol),
TIPS–acetylene (0.96g, 5.24mmol), Pd(PPh3)2Cl2
(0.25g, 0.35mmol), and CuI (67mg, 0.35mmol) in
THF (21mL) at room temperature was added diisoprop-
ylamine (1.0mL, 7.15mmol) with stirring. The reaction
was allowed to proceed for 2h before quenching with
saturated NH4Cl solution and diluting with Et2O. The
organic layer was washed one time with saturated NaCl,
4.4. 4-Deca-1,3,9-triynyl-2,2-dimethyl-[1,3]dioxolane 12
To a round bottom flask equipped with a stirring bar
under an atmosphere of nitrogen was added a solution
of NH2OHÆHCl (32.7mg, 0.47mmol) in H2O
(0.40mL), MeOH (9.5mL), a 70% aqueous solution of
EtNH2 (9.5mL), and CuCl (46.6mg, 0.47mmol). Then

B. W. Gung et al. / Tetrahedron: Asymmetry 15 (2004) 3973–3977
3977
dried over MgSO4, and filtered. The solvent was re-
moved under reduced pressure and the crude mixture
purified over a silica gel column to afford the major
product as an orange oil (936mg, 65%), and a second
fraction as a yellow solid (mp 64–66ꢁC, 249mg, 20%).
68.03, 69.66, 75.03, 76.99, 80.22. HRMS: Calcd for
C14H14O2 + Na, 237.0891, found M + Na: 237.0885.
4.9. (+)-Diplyne D 4
To a round bottom flask equipped with a stirring bar
under nitrogen was added triethylamine (3mL),
Pd(PPh3)4 (6.8mg, 0.006mmol), CuI (2.2mg,
0.012mmol), a mixture of cis and trans dibromoethylene
(73mg, 0.39mmol), and compound 18 (21mg). The
resulting solution was stirred at room temperature for
6.5h. The mixture was then diluted with CHCl3 (5mL)
and filtered through a pad of Florisil using CHCl3.
The solvents were removed under reduced pressure
and the crude mixture purified over a silica gel column
to afford the product as a pale yellow solid (mp 103–
105ꢁC, 16.7mg, 56%). [a]D = +7.2 (c 0.10, MeOH),
UV (MeOH): 290, 273, 258, 221nm. IR m cmÀ1 : 3055,
1
Compound 15: [a]D = +31.8 (c 0.19, CHCl3), H NMR
(300MHz, CDCl3): d 1.06 ( 21H, m), 1.35 (3H, s), 1.47
(3H, s), 1.63 (4H, m), 2.29 (4H, m), 3.92 (1H, dd,
J = 6.1, 8.1Hz), 4.13 (1H, dd, J = 6.4, 8.0Hz), 4.73
(1H, t, 6.2Hz). 13C NMR (75MHz, CDCl3): d 11.68,
18.94, 19.18 (2), 26.31, 26.50, 27.46 (2), 65.27, 66.23,
66.74, 70.11, 71.05, 73.50, 77.60, 78.24, 80.81, 81.58,
111.02. HRMS: Calcd for C26H38O2Si + Na, 433.2539,
found M + Na: 433.2545. Compound 16: 1H NMR
(500MHz, CDCl3): d 1.07 (42H, m). 13C NMR
(125MHz, CDCl3): d 11.32, 18.56, 81.59, 90.20.
1
4.7. 14-Triisopropylsilanyl-tetradeca-3,5,11,13-tetrayne-
1,2-diol 17
2987, 2927, 2341, 1266, 896, 739. H NMR (300MHz,
MeOH-d4): d 1.62 (4H, m), 2.34 (4H, m), 3.53 (1H,
dd, J = 6.6, 11.1Hz), 3.57 (1H, dd, J = 5.1, 11.1Hz),
4.33 (1H, dd, J = 5.3, 6.4Hz), 6.32 (1H, dt, J = 1.0,
14.0Hz), 7.00 (1H, d, J = 14.6Hz). 13C NMR
(125MHz, MeOH-d4): 19.22, 19.57, 28.27, 28.38,
64.51, 65.89, 65.99, 67.06, 70.59, 72.12, 76.07, 77.13,
81.11, 86.24, 117.74, 123.03. HRMS: Calcd for
C16H15BrO2 + Na, 341.0153, found M + Na: 341.0178.
To a solution of compound 15 (0.94g, 2.28mmol) in
THF (23mL) at 0ꢁC was added HFÆpyridine complex
(2.51mL). The resulting solution was warmed to room
temperature and stirred for an additional 18h. Then,
the mixture was diluted with Et2O and washed one time
with saturated NaHCO3 solution and one time with satu-
rated NaCl solution. The organic layer was then dried
over MgSO4, filtered, and the solvent removed under re-
duced pressure. The crude mixture was purified over a
silica gel column giving a yellow oil (777mg, 92%).
Acknowledgements
This research is supported in part by a grant from the
National Institutes of Health (GM60263) and the Beck-
man Foundation. Acknowledgment is also made to the
donors of the Petroleum Research Fund (PRF#36841-
AC4) administered by the American Chemical Society.
We thank Scott Bresler for preparing some of the start-
ing materials.
[a]D = +7.3 (c 0.36, MeOH), UV (MeOH): 217, 240, 253,
268nm. H NMR (300MHz, CDCl3): d 1.05 (21H, m),
1
1.63 (4H, m), 2.28 (4H, m), 3.65 (1H, dd, J = 6.5,
11.5Hz), 3.73 (1H, dd, J = 3.6, 11.5Hz), 4.46 (1H,
dd, 3.8, 6.4Hz). 13C NMR (75MHz, CDCl3): d 11.67,
18.94, 19.16 (2), 27.45, 27.47, 63.98, 65.09, 66.68,
66.74, 71.42, 73.77, 78.24, 80.83, 81.67, 90.28. HRMS:
Calcd for C23H34O2Si + Na: 393.2226, found M + Na:
393.2223.
References
1. Lerch, M. L.; Harper, M. K.; Faulkner, D. J. J. Nat. Prod.
2003, 66, 667–670.
4.8. Tetradeca-3,5,11,13-tetrayne-1,2-diol 18
2. Gung, B. W.; Kumi, G. J. Org. Chem. 2004, 69, 3488–
3492.
3. Gung, B. W.; Kumi, G. J. Org. Chem. 2003, 68, 5956–
5960.
4. Gung, B. W.; Dickson, H. Org. Lett. 2002, 4, 2517–2519.
5. Sonogashira, K. J. Organomet. Chem. 2002, 653, 46–49.
6. Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.;
Elsevier: New York, 1988; Vol. 34.
7. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 4467–4470.
8. Alami, M.; Linstrumelle, G. Tetrahedron Lett. 1991, 32,
6109–6112.
9. Andreini, B. P.; Benetti, M.; Carpita, A.; Rossi, R. Gazz.
Chim. Ital. 1988, 118, 469–474.
10. Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, R.
Angew. Chem., Int. Ed. Engl. 1984, 23, 727–729.
11. Wityak, J.; Chan, J. B. Synth. Commun. 1991, 21, 977–979.
12. Haley, M. M.; Bell, M. L.; English, J. J.; Johnson, C. A.;
Weakley, T. J. R. J. Am. Chem. Soc. 1997, 119, 2956–2957.
13. Heuft, M. A.; Collins, S. K.; Yap, G. P. A.; Fallis, A. G.
Org. Lett. 2001, 3, 2883–2886.
To a solution of compound 17 (150mg, 0.38mmol) in
THF (5mL) was added TBAF (1M, 0.58mL,
0.58mmol) and the resulting mixture was stirred for
1.5h at room temperature. Next, ice water (20mL) fol-
lowed by 1M HCl (2mL) was added and the aqueous
layer was extracted two times with Et2O. The combined
organic layers were then washed once with H2O, dried
over MgSO4, filtered, and the solvent removed under re-
duced pressure. The crude mixture was purified over a
silica gel column to afford a pale brown solid (mp 77–
79ꢁC, 79mg, 97%).
[a]D = +21.0 (c 0.20, CHCl3), IR m cmÀ1: 3276, 2937,
2871, 2299, 2223, 1454, 1279, 1082. 1H NMR
(300MHz, CDCl3): d 1.64(H4, m), 1.96 (1H, t,
J = 1.1Hz), 2.29 (4H, m), 3.67 (1H, dd, J = 6.1,
11.4Hz), 3.74 (1H, dd, J = 4.0, 11.4Hz), 4.48 (1H, dd,
J = 4.0, 6.1Hz). 13C NMR (50MHz, MeOH): d 18.06,
18.29, 27.31, 27.40, 63.51, 64.91, 65.08, 65.67, 66.05,