A divergent synthesis of triyne natural products and glycosylated analogues using a carbenoid rearrangement

Article abstract of DOI:10.1055/s-2005-918428

Using a carbenoid rearrangement to introduce the conjugated acetylenic framework, a series of triynols has been synthesized in five steps from 1,4-butynediol. Several of the triyne alcohols are known natural products and others are glycosylated analogues.

Full text of DOI:10.1055/s-2005-918428

FEATURE ARTICLE
3167
A Divergent Synthesis of Triyne Natural Products and Glycosylated
Analogues Using a Carbenoid Rearrangement
Synthesis of
T
ri
h
yne
N
atural
a
Products
a
n
n
d Glycosylat
h
ed Analogues Luu, Wei Shi, Todd L. Lowary,* Rik R. Tykwinski*
Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
Fax +1(780)4928231 ; E-mail: rik.tykwinski@ualberta.ca; E-mail: tlowary@ualberta.ca
Received 23 July 2005
Numerous polyynes found in nature feature a propargylic
alcohol group at one terminus of the molecule
(Scheme 1). In the case of triynes with this motif, e.g. 1,
retrosynthetic analysis suggested that the six-carbon
Abstract: Using a carbenoid rearrangement to introduce the conju-
gated acetylenic framework, a series of triynols has been synthe-
sized in five steps from 1,4-butynediol. Several of the triyne
alcohols are known natural products and others are glycosylated an-
alogues. This route avoids the use of terminal diynes as precursors, triyne segment could be constructed via a Fritsch–Butten-
burg–Wiechell (FBW) rearrangement12 of a suitably func-
which can be unstable and/or difficult to prepare. It is therefore pro-
tionalized dibromoolefin 2.13 This precursor, in turn,
would be readily available in three steps from aldehyde 3,
via acetylide addition, oxidation, and dibromoolefination.
The divergent nature of this approach would result from
cedurally attractive in comparison to more traditional routes such as
the Cadiot–Chodkiewicz and Sonogashira coupling reactions.
Key words: polyacetylenes, polyynes, carbohydrates, Fritsch–But-
tenberg–Wiechell reaction, carbenoids, natural products
the ability to vary the pendent group R as a function of the
metal acetylide used in the initial reaction with 3. Finally,
aldehyde 3 would be available in two steps (monoprotec-
tion and oxidation) from a commercially available feed-
Introduction
Natural products bearing a conjugated polyyne1 frame-
work have been isolated from plants, fungi, bacteria,
sponges, and even an insect.2–4 In fact, they are surprising-
ly common natural products, despite the fact that these
compounds can demonstrate significant instability as a re-
sult of their often fragile sp-hybridized carbon core. When
sufficient quantities of the natural product are available,
studies of biological and physiological function have re-
vealed a broad scope of activities such as larvicidal,5 anti-
microbial,6 anti-viral (HIV),7 and cytotoxicity toward a
range of cell lines.8 Due to their inherently unstable na-
ture, however, polyynes are often difficult to isolate from
natural sources, particularly in the case of longer deriva-
tives such as triynes, tetraynes, and pentaynes. Over the
past 50 years, there have been a number of strategies used
for the synthesis of polyyne-based natural products.2b,g,9,10
The most common method by far is the copper-catalyzed
oxidative coupling procedure developed by Cadiot and
Chodkiewicz, as well as the palladium-catalyzed variants
of their original protocol that have been subsequently de-
veloped.11 There are, however, a number of challenges as-
sociated with the implementation of this strategy,
including the significant instability of one or both of the
precursors and the formation of troublesome byproducts
due to competition from oxidative homocoupling reac-
tions. There is thus a need for the development of alterna-
tive synthetic methods, in particular, those that allow for
the versatile and expedient synthesis of these molecules
using readily available starting materials.
stock, 1,4-butynediol.
Br
Br
OPG
R
OPG
R
2
1
OH
H
OPG
HO
O
3
Scheme 1 Retrosynthesis showing divergent approach to conjuga-
ted triynols from butynediol (PG = protecting group).
We report herein the synthesis of a series of conjugated
triynols starting with the inexpensive precursor 1,4-bu-
tynediol. The key step in this procedure exploits alkyne
migration in a carbenoid FBW rearrangement to construct
the triyne core. We then demonstrate the versatility of this
route through the synthesis of four naturally occurring
triynes. The ability to elaborate these triynols into other
potentially bio-active derivatives is demonstrated through
the formation of six acetylenic saccharide derivatives.14
Methodology and Model Systems
The initial route to explore triyne formation employed the
TBDMS-protected alcohol 4 (Scheme 2), the synthesis of
which has been reported by Diederich.15 Reaction of lithi-
ated trimethylsilylacetylene with 4 in THF gave the alco-
hol 5, which was readily oxidized to ketone 6 with MnO2.
The next step in the synthesis, however, proved problem-
atic, and all attempts to convert 6 to the dibromoolefin 7
SYNTHESIS 2005, No. 18, pp 3167–3178
x
x.
x
x
.
2
0
0
5
Advanced online publication: 25.10.2005
DOI: 10.1055/s-2005-918428; Art ID: M04805SS
© Georg Thieme Verlag Stuttgart · New York

3168
T. Luu et al.
FEATURE ARTICLE
met with limited success. Typical Corey–Fuchs dibro- tion of the alcohol, as has been previously reported by
moolefination conditions,16 when applied to 6, were met Mattes and Benezra.17 Further complicating the formation
primarily with frustration, and modifications of this stan- and use of 7 was its kinetic instability. The pure com-
dard protocol did little to improve the outcome of the re- pound decomposed over a period of days, even when
actions. Yields were consistently low with a maximum stored at low temperature, necessitating additional purifi-
17% yield. The formation of numerous byproducts was cation. Analysis of the decomposed material suggested
observed in all cases, including propargyl bromide deriv- that removal of the TMS group was slowly occurring
ative 8, the result of desilylation and subsequent bromina-
Biographical Sketches
Thanh Luu (upper right) was born in macromolecules. In the fall of 2002, of Prof. Rik Tykwinski on synthetic
Saigon, Vietnam in 1971. He re- he entered the graduate program in methodology and characterization of
ceived a BSc in Chemistry from the Chemistry at the University of Alber- polyynes for use in natural products
University of Alberta in 2002. Dur- ta to continue research on the topic of and materials chemistry.
ing his final undergraduate year he polyynes. He is currently working on
explored the chemistry of acetylenic his PhD thesis under the supervision
Wei Shi (lower right) was born in University of Science and Technolo- new analogues of doxorubicin as po-
Anhui, China, in 1971. He studied gy where he earned a MSc degree in tential topoisomerase inhibitors un-
chemistry at the Shanghai Jiao Tong 2000. He is currently working on his der the supervision of Prof. Todd L.
University where he obtained a BSc PhD thesis at the University of Alber- Lowary.
degree in 1993 and at the East China ta on the synthesis and evaluation of
Todd Lowary (upper left) was born 1995), and then with Dr. Morten the Department of Chemistry and a
in 1966 in Canton, IL. He received Meldal at the Carlsberg Laboratory member of the Alberta Ingenuity
his BA in Chemistry from the Uni- in Copenhagen, Denmark (1995– Centre for Carbohydrate Science.
versity of Montana in 1988 and ob- 1996). In 1996, he took a position in Research in the Lowary group is fo-
tained his PhD in Organic Chemistry The Department of Chemistry at The cused on the areas of synthetic carbo-
under the supervision of Prof. Ole Ohio State University as an Assistant hydrate chemistry, conformational
Hindsgaul at the University of Alber- Professor and in 2002 was promoted analysis of furanose-containing oli-
ta in 1993. He carried out postdoctor- to Associate Professor. In 2003, he gosaccharides, and the identification
al research with Prof. David Bundle returned to the University of Alberta of novel anti-tuberculosis agents and
at the University of Alberta (1993– where he is an Associate Professor in topoisomerase inhibitors.
Rik R. Tykwinski (lower left) was salts, receiving his PhD in 1994.
Chemistry. He is currently preoccu-
born in 1965 in Marshall, MN. He He was awarded an Office of Naval pied with the development of syn-
completed his BSc degree in 1987 at Research Postdoctoral Fellowship thetic methods for assembling
the University of Minnesota, Duluth, and moved to ETH Zürich (1994– oligo(enynes) and polyynes, charac-
where he also developed his interest 1997) to work with Prof. François terization of their electronic proper-
in organic chemistry working as an Diederich on the chemistry of func- ties, applications of conjugated
undergraduate researcher with Prof. tionalized tetraethynylethenes and systems to nonlinear optics, and
Ron Caple. With Prof. Peter J. Stang their material properties. He joined mountain biking.
at the University of Utah, he explored the faculty at the University Alberta
the chemistry of alkynyl iodonium in 1997, where he is now Professor of
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Triyne Natural Products and Glycosylated Analogues
3169
when 7 was stored either as a neat oil or in solutions of,
for example, hexanes.
OH
a
4
OTBDMS
TIPS
Similar results were arrived at when TIPS was used in
place of the TMS group as a protecting group to pre-
vent the premature desilylation (Scheme 3). Addition
of i-Pr3SiC≡CLi to aldehyde 4 gave 9 in good yield, fol-
lowing workup and column chromatography.15
9 82%
X
b
d
OTBDMS
TIPS
10 X = O 91%
c
O
OH
a
b
11 X = CBr2 77%
H
OTBDMS
OTBDMS
Br
Br
H
TMS
c
OTBDMS
4
5 69%
TIPS
OTBDMS
Br
TIPS
O
12 61%
13
X
OTBDMS
Scheme 3 Reagents and conditions: a) i-Pr3SiC≡CLi, THF, –78 °C;
b) BaMnO4, CH2Cl2, r.t.; c) CBr4, PPh3, CH2Cl2, r.t.; d) BuLi, hex-
anes, –78 °C.
TMS
TMS
6 59%
7 X = OTBDMS 17%
8 X = Br 7%
Scheme 2 Reagents and conditions: a) Me3SiC≡CLi, THF, –78 °C;
dard conditions, the reaction was devoid of the trouble-
some byproducts that accompanied the formation of 7 and
11. Use of Et3N, which had improved the yield of 11, had
no effect on the yield of 18. Other attempts to optimize the
formation of 18 included the use of zinc as the reductant
in place of PPh3.19 Monitoring the reaction using 1H NMR
spectroscopy, however, showed less than 10% conversion
in this reaction based on integration of the propargylic
methylene protons. The FBW rearrangement of 18 effec-
tively formed 19 in 41% yield as a relatively stable oil.
While yields of 19 were slightly lower than that of 12, the
reactions were free of the monoprotonated olefin byprod-
uct that had plagued the formation of the latter. Global
protiodesilylation with TBAF gave the terminal triyne 20.
While this product could be identified and characterized
in solution via IR spectroscopy, it was insufficiently sta-
ble to be isolated. The highly unstable 20 was the first nat-
ural C7 polyyne to be identified and was isolated from the
fungus Ramaria flava by Jones and coworkers.20
b) MnO2, CH2Cl2, r.t.; c) CBr4, PPh3, CH2Cl2, Et3N, –78 °C.
Using BaMnO4, alcohol 9 was cleanly oxidized to the ke-
tone 10 in 91% yield. Ultimately, it was determined that
the dibromoolefination reported by McIntosh et al. using
one equivalent of Et3N gave the best results in the forma-
tion of 11.18 Using this protocol, reducing the reaction
time to 3 min, and workup with aqueous NaHCO3 gave 11
in yields as high as 77%. This reaction was, however, re-
markably irreproducible, and lower yields were more
common than higher yields due to the loss of the TBDMS
protecting group during the reaction. Nonetheless, pure 11
was considerably more stable under ambient conditions
than its analogue 7. With 11 in hand, conversion to triyne
12 was effected via reaction with BuLi at –78 °C. It is
worth noting that while the isolated yield of 12 was rea-
sonable in some cases (up to 61%), its formation was al-
ways accompanied by that of 13, a byproduct formed by
reaction of the intermediate carbenoid of the FBW reac-
tion with water in the medium.13a Frustratingly, all proce-
dures that have been previously effective in preventing
this side reaction were in this case unsuccessful. As a re-
sult of the difficulties encountered in the formation of pre-
cursor 11, the consistent presence of byproduct 13, and
the similar retention times of 12 and 13 on common chro-
matographic supports that made separation difficult and
time-consuming, a third protection scheme was explored.
OR
b
c
O
H
TBDPS
HO
R = H
15 58%
a
14 R = TBDPS 84%
X
OH
d
TBDPS
e
TIPS
17 X = O 91%
18 X = CBr2 45%
TBDPS
TIPS
The more resilient nature of TBDPS ethers suggested this
as a reasonable option for solving the problems encoun-
tered with the TBDMS ether as a protecting group. In a se-
quence of steps analogous to that used in the formation of
4, reaction of 1,4-butynediol with TBDPSCl in the pres-
ence of DMAP gave the mono-protected product 14
(Scheme 4), which was then cleanly oxidized to aldehyde
15 with BaMnO4 in 58% yield (84% yield based on recov-
ered starting material). Reaction of 15 with i-Pr3SiC≡CLi
in THF gave alcohol 16, which was then oxidized to ke-
tone 17 using BaMnO4. While conversion of ketone 17 to
dibromoolefin 18 proceeded in moderate yield under stan-
16 84%
OR
f
R'
19 R = TBDPS; R' = TIPS 41%
20 R = R' = H
g
Scheme 4 Reagents and conditions: a) TBDPSCl, THF, Et3N,
DMAP, r.t.; b) BaMnO4, CH2Cl2, r.t.; c) i-Pr3SiC≡CLi, THF, –78 °C;
d) BaMnO4, CH2Cl2, r.t.; e) CBr4, PPh3, CH2Cl2, Et3N, 0 °C; f) BuLi,
hexanes, –78 °C; g) TBAF, THF, –20 °C.
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

3170
T. Luu et al.
FEATURE ARTICLE
from the flowering perennial Dahlia pinnata.24 The for-
mation of these triynes was initiated with the reaction of
Synthesis of Naturally Occurring Triynols
With ready access to a protecting group scheme that the PhC≡CLi with 15 in THF, which efficiently generated
would tolerate the chemical transformations requisite for alcohol 28 in 85% yield as a light yellow oil. The typical
the FBW approach, the divergent nature of this synthetic sequence of oxidation with BaMnO4 to ketone 29 and di-
scheme was explored. Jones and coworkers isolated the bromoolefination to 30 was then accomplished with rea-
triynol 21 from the neutral fractions of cultures of the sonable yields in both steps. It was found that while the
sheathed (or two-toned) woodtuft (Kuehneromyces muta- mild oxidant BaMnO4 alone was effective for a small-
bilis), a very commonly encountered toadstool, as well as scale conversion of 28 to 29 (< 2 g), on a larger scale the
from three other fungal sources (Scheme 4).20 The triyne reaction would fail to go to completion, regardless of the
framework of 21 could be assembled in a manner similar amount of BaMnO4 employed. Thus, MnO2 was utilized
to that used for 20.21 Reaction of 15 with LiC≡CCH3 gave to force the reaction to completion in these cases. Car-
alcohol 22 as a colorless oil in quantitative yield. This al- benoid FBW rearrangement effected on 30 with BuLi
cohol was oxidized to the ketone 23 with BaMnO4, and gave the triyne 31 in 90% yield as an oil. Liberation of the
then converted directly to the dibromoolefin 24. A penul- alcohol moiety with TBAF gave 26, which could then be
timate carbenoid rearrangement afforded the triyne frame- easily acylated to give 27.25
work of 25, from which the product 21 could be accessed
through desilylation with TBAF at room temperature.
It is interesting to compare the biological activity of
polyynes. Towers and coworkers have studied the activity
The kinetic instability of triynes resulting from the pres- of numerous polyynes from the aster family (Asteraceae)
ence of a terminal alkyne moiety is highlighted by com- as larvicidal agents against the mosquito Aedes aegypti,
parison of the behavior of 20 and 21. Whereas triynol 20 including compound 26 and the structurally related natu-
was far too unstable to be isolated in neat form, the pres- ral products phenylheptatriyne (PHT, 32) and diyne 33
ence of a terminal methyl group in 21 allowed for standard (Figure 1).26 Whereas PHT and enediynol 33 show sub-
chromatographic purification on silica, affording a crys- stantial larvicidal activity, the triynol 26 was found to be
talline solid with a melting point of 92 °C.
inactive. Furthermore, this activity was clearly linked to a
polyyne chromophore present within the molecules, while
ruling out any mechanism based on metabolic action(s) of
the polyyne.
The triynol 26 and triyne acetate 27 (Scheme 6) were first
isolated by Bohlmann and coworkers from several species
of the genus Bidens, including B. pilosus and B. leucan-
thus,22,23 and later in trace amounts by Lam and coworkers
X
OH
b
a
TBDPS
15
H3C
TBDPS
H3C
23 X = O 80%
c
22 100%
24 X = CBr2 25%
OR
e
d
H3C
25 R = TBDPS 39%
21 R = H 75%
Scheme 5 Synthesis of polyyne natural product 21. Reagents and conditions: a) CH3C≡CLi, LiBr, THF, –78 °C; b) BaMnO4, CH2Cl2, r.t.;
c) CBr4, PPh3, CH2Cl2, 0 °C; d) BuLi, hexanes, –78 °C; e) TBAF, THF, r.t.
X
OH
b
a
15
TBDPS
c
Ph
29 X = O 89%
TBDPS
Ph
28 85%
30 X = CBr2 53%
O
OR
e
O
d
f
Ph
Ph
CH3
31 R = TBDPS 90%
26 R = H 96%
27 81%
Scheme 6 Synthesis of polyyne natural products 26 and 27. Reagents and conditions: a) PhC≡CLi, THF, –78 °C; b) BaMnO4, CH2Cl2, r.t.;
c) PPh3, CBr4, Et3N, CH2Cl2, 0 °C; d) BuLi, hexanes, –78 to 10 °C; e) TBAF, THF, r.t.; f) Ac2O, DMAP, Et3N, CH2Cl2, r.t.
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Triyne Natural Products and Glycosylated Analogues
3171
cosylating agent: glycosyl acetates, glycosyl halides, and
glycosyl imidates.
CH3
OH
33
32 (PHT)
We first explored the use of glycosyl acetates 37, 38, and
39. Thus, reaction of each donor with 26 and BF3·OEt2,32
yielded the corresponding glycosides 40, 41, or 42 in
yields ranging from 61–78% (Scheme 7). The use of do-
nors with an acetoxy group at C-2 ensured good selectiv-
ity for the 1,2-trans-glycoside via the initial formation of
a dioxolenium ion intermediate. In addition to the glyco-
side product, in all reactions we also isolated significant
(ca. 20%) quantities of the acetylated triynol 27. The for-
mation of the acetylated acceptor species in glycosylation
reactions is well precedented when acetylated donors are
used.33
Figure 1
Synthesis of Polyyne Glycosides
A number of polyyne glycosides have been isolated from
natural sources and have been shown to possess a host of
different biological activities including the inhibition of
nitric oxide production,27 antibacterial activity,28 the mod-
ulation of blood glucose levels,29 as well as the inhibition
of histamine release.27 This latter function has led to the
exploration of these compounds as anti-allergic agents.30
Despite the range of biological processes influenced by
these glycoconjugates, their synthesis has not been widely
investigated. Indeed, to the best of our knowledge, only a
single paper has described the synthesis of such species.
In 2004, Gung and Fox described the synthesis of biden-
syneosides A2 and C,31 which are glucosides of enediyne
alcohols that have been isolated from Bidens parviflora.
There are no reports of the synthesis of triynol glycosides.
We next studied the synthesis of these glycosides using
glycosyl bromide donors, by reacting 26 with 43 in the
presence of silver triflate and collidine in dichlo-
romethane (Figure 2).34 However, the rate of the reaction
was very slow and after several days the reaction gave
only low yields (<20%) of the desired product, 40. Al-
though we are unsure as to why this reaction was so slug-
gish, it is possible the preferential complexation of the
silver promoter to the alkyne moieties reduces the rate of
glycosylation. In principal this could be circumvented by
using a large excess of silver triflate; however, for cost
reasons, we do not view this as a viable solution. We then
explored the reaction of 26 with trichloroacetimidate 44 in
dichloromethane in the presence of BF3·OEt2.35 In this
case, glycosylation led to a number of products (by TLC)
from which 40 could be isolated in only low yield. Gly-
cosyl trichloroacetimidates are among the most useful
glycoslyating agents and the reasons for why they perform
poorly here are unknown. Therefore, based on these re-
sults, it appears that the glycosyl acetates are the best of
Given the lack of syntheses of glycosylated triyne alco-
hols, we were interested in exploring methods for their
preparation. As targets, we selected three such species, in
which phenyltriynol 26 was conjugated to glucopyranose,
galactopyranose, or mannopyranose to give 34–36, re-
spectively.
In theory, coupling triynol 26 to different sugar moieties
could be achieved through the use of a number of different
glycosylation protocols. We chose to investigate three
standard methods, each employing a different class of gly-
RO
RO
RO
AcO
O
O
a
AcO
O
OAc
AcO
Ph
AcO
37
RO
40 R = Ac 61%
34 X = H 69%
b
AcO
AcO
RO
OAc
O
OR
O
a
O
OAc
RO
Ph
AcO
RO
41 R = Ac 74%
35 X = H 64%
38
b
OAc
O
OR
O
RO
RO
RO
AcO
AcO
AcO
a
O
OAc
Ph
39
42 R = Ac 78%
36 X = H 77%
b
Scheme 7 Synthesis of glycosylated triynols 34, 35, and 36. Reagents and conditions: a) 26, BF3·OEt2, 4 Å MS, CH2Cl2, r.t.; b) K2CO3,
MeOH, –78 °C to r.t.
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

3172
T. Luu et al.
FEATURE ARTICLE
or Na2SO4 were used as the drying agent after aqueous workup.
Evaporation and concentration in vacuo was done at water-aspirator
pressure. All reactions were performed in standard, dry glassware
under an inert atmosphere of Ar. Column chromatography: silica
gel-60 (230–400 mesh) from General Intermediates of Canada.
TLC: aluminum sheets covered with silica gel-60 F254 from Mach-
erey-Nagel; visualization by UV light or KMnO4 stain. Mp: Gallen-
kamp apparatus; uncorrected. IR spectra: Nicolet Magna-IR 750
(neat) or Nic-Plan IR Microscope (solids). 1H and 13C NMR: Varian
Gemini-300, 400, or 500 instruments, at r.t. in CDCl3, CD3CN, or
CD3OD; solvent peaks (7.24, 1.93, 4.78, and 3.30 ppm, respective-
ly, for 1H NMR and 77.0, 1.8, and 49.0 ppm, respectively, for 13C
NMR) as reference. MS (EI): Kratos MS50 instrument. MS (ESI):
PerSeptive Biosystem Mariner instrument. For mass spectral analy-
ses, low-resolution data are provided in cases when M+ is not the
base peak; otherwise, only high-resolution data are provided. Opti-
cal rotation (°·mL/g·dm): Perkin-Elmer 241. Elemental analyses
were effected by Spectral Services at the University of Alberta. In
cases where crude reaction mixtures were passed through a plug of
silica gel and celite, the following procedure was employed: to a
fritted funnel, a mixture of silica and hexanes was added, which was
then covered by celite; a sample solution was introduced and
flushed with the solvent (as indicated below); progress of separation
was monitored by means of TLC.
AcO
AcO
AcO
AcO
AcO
O
O
AcO
AcO
Br
AcO
O
NH
CCl3
43
44
Figure 2
these three donor types for the synthesis of triynol glyco-
sides.
Deprotection of the acetate esters from the products of the
glycosylation reactions was more difficult than anticipat-
ed. The use of KOMe (generated from K2CO3 in MeOH)
at room temperature provided chromatographically pure
compounds 34, 35, and 36 in somewhat modest yields (ca.
70%) compared to those usually obtained for deacylation
reactions. In addition, following purification by chroma-
tography, NMR spectroscopy in CDCl3 revealed that
these supposedly pure compounds were contaminated
with inseparable impurities, the structures of which could
not be determined. We considered that these deprotected
glycosides might form partial aggregates in CDCl3, which
could account for the apparent impurities. To test this hy-
pothesis, a few drops of benzene-d6 were added to a solu-
tion of 34 in CDCl3 and the NMR spectra were recorded
again. No significant differences were seen thus suggest-
ing that aggregation in CDCl3 does not occur. We then ex-
plored acidic conditions (1 M HCl in MeOH) for cleavage
of the acetate esters. However, under these conditions sig-
nificant degradation of the products was observed given
their sensitivity to acidic reaction medium. Eventually, we
found that deacetylation could be achieved under basic
conditions by initiating the reaction at –78 °C, and allow-
ing the reaction mixture to warm to room temperature.
Under these conditions the purity of the products was
good, although the yields were still modest.
6-(tert-Butyldimethylsilanyloxy)-1-trimethylsilanylhexa-1,4-
diyn-3-ol (5)
To Me3SiC≡CH (341 mg, 3.47 mmol) in THF (14 mL) at –78 °C
was added BuLi (2.4 M, hexanes; 1.4 mL, 3.4 mmol). After stirring
for 1 h at –78 °C, aldehyde 4 (0.561 g, 2.81 mmol) was added in one
portion and the reaction was warmed to r.t. Et2O (14 mL) and sat.
aq NH4Cl (14 mL) were added. The organic phase was separated,
washed with sat. aq NH4Cl (2 × 14 mL), sat. aq NaCl (2 × 14 mL),
and dried over MgSO4. Solvent removal and purification by column
chromatography (CH2Cl2) afforded 5.
Yield: 572 mg (69%); light yellow oil; Rf 0.4 (CH2Cl2).
IR (cast, CDCl3): 3395, 2958, 2179, 1363 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.12 (d, J = 7 Hz, 1 H), 4.37 (s, 1
H), 4.36 (s, 1 H), 2.16 (d, J = 7 Hz, 1 H), 0.95 (s, 9 H), 0.18 (s, 9 H),
0.13 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 101.7, 89.5, 83.2, 81.9, 52.6,
51.7, 25.8, 18.3, –0.3, –5.0.
MS (EI, 70 eV): m/z (%) = 239.1 (8) [M – t-Bu]+, 147.1 (100).
HRMS (EI): m/z calcd for C11H19O2Si2 [M – t-Bu]+: 239.0924;
Conclusions
found: 239.0923.
In summary, we have established a protecting group se-
quence that allows for the divergent formation of dibro-
moolefins in four steps starting from 1,4-butynediol.
These dibromoolefins are suitable precursors for effecting
a Fritsch–Buttenberg–Wiechell rearrangement that af-
Anal. Calcd for C15H28O2Si2: C, 60.75; H, 9.52. Found: C, 60.60; H,
9.46.
6-(tert-Butyldimethylsilanyloxy)-1-trimethylsilanylhexa-1,4-
diyn-3-one (6)
fords triynol products. While yields under this protocol To 5 (442 mg, 1.49 mmol) in anhyd CH2Cl2 (7 mL) at r.t. was added
MnO2 (1.55 g, 17.8 mmol) in one portion. After stirring for 8 h at
are at times modest, the use of highly unstable precursors
r.t., the mixture was filtered through a plug of celite and silica gel
(CH2Cl2) affording 6.
that have been necessary in previous syntheses is conve-
niently avoided. This general route has been used to as-
semble four known natural products and several silyl-
protected derivatives. An optimized procedure was then
developed to provide three glycosylated triynols that are
interesting analogues to naturally occurring polyyne gly-
cosides.
Yield: 257 mg (59%); yellow oil; Rf 0.6 (hexanes–CH2Cl2, 1:2).
IR (cast, CHCl3): 2958, 2930, 2858, 2229, 2147, 1634 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.47 (s, 2 H), 0.89 (s, 9 H), 0.23
(s, 9 H), 0.13 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 160.0, 102.2, 99.5, 91.5, 84.8,
51.6, 25.7, 18.2, –0.99, –5.22.
Reagents were purchased as reagent grade from commercial suppli-
ers and were used without further purification. Et2O and THF were
distilled from Na/benzophenone ketyl, and hexanes and CH2Cl2
were distilled from CaH2 immediately prior to use. Anhyd MgSO4
MS (EI, 70 eV): m/z (%) = 294.1 (1) [M+], 237.1 (95) [M – t-Bu]+,
209.1 (100) [M – t-Bu – Me2]+.
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Triyne Natural Products and Glycosylated Analogues
3173
HRMS (EI): m/z calcd for C11H17O2Si2 [M – t-Bu]+: 237.0767;
6-(tert-Butyldimethylsilanyloxy)-3-(dibromomethylidene)-1-
found: 237.0767.
triisopropylsilanylhexa-1,4-diyne (11)
To CBr4 (648 mg, 1.95 mmol) in CH2Cl2 (8 mL) at 0 °C was added
PPh3 (1.02 g, 3.90 mmol). The mixture was stirred for 30 min and
Et3N (0.1 mL) was added. The mixture was transferred to a soln of
10 (369 mg, 0.974 mmol) in CH2Cl2 (1 mL) at 0 °C and stirred for
3 min. The mixture was poured into sat. aq NaHCO3 (13 mL). The
organic phase was separated, washed with sat. aq NH4Cl (2 × 30
mL), sat. aq NaCl (2 × 30 mL), and dried over MgSO4. The mixture
was reduced to 10 mL and hexanes (10 mL) was added. The crude
mixture was filtered through silica and purified by column chroma-
tography (hexanes–CH2Cl2, 2:1) affording 11.
Anal. Calcd for C15H26O2Si2: C, 61.17; H, 8.90. Found: C, 61.03; H,
8.84.
6-(tert-Butyldimethylsilanyloxy)-3-(dibromomethylidene)-1-
trimethylsilanylhexa-1,4-diyne (7) and 6-Bromo-3-(dibromo-
methylidene)-1-trimethylsilanylhexa-1,4-diyne (8)
To CBr4 (512 mg, 1.54 mmol) in CH2Cl2 (3 mL) at 0 °C was added
PPh3 (809 mg, 3.08 mmol) and the mixture was stirred for 30 min.
The mixture was added to 6 (227 mg, 0.772 mmol) in CH2Cl2 (3
mL) at 0 °C and stirred for 3 h. The mixture was filtered through
celite and purified by column chromatography (petroleum ether, bp
35–60 °C) affording 7 and 8.
Yield: 402 mg (77%); colorless oil; Rf 0.7 (hexanes–CH2Cl2, 2:1).
IR (cast, CHCl3): 2944, 2892, 2865, 2223, 2156, 1463 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.44 (s, 2 H), 1.08 (s, 21 H), 0.89
7
(s, 9 H), 0.12 (s, 6 H).
Yield: 57.5 mg (17%); light yellow oil; Rf 0.2 (hexanes).
IR (cast, CHCl3): 2957, 2929, 2857, 2159 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.43 (s, 2 H), 0.89 (s, 9 H), 0.20
(s, 9 H), 0.13 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 113.9, 108.9, 102.5, 100.1, 94.7,
81.1, 52.2, 25.8, 18.2, –0.52, –5.08.
13C NMR (100 MHz, CDCl3): d = 114.2, 108.7, 101.9, 99.5, 94.5,
81.3, 52.2, 25.7, 18.6, 18.2, 11.1, –5.1.
MS (EI, 70 eV): m/z (%) = 534.1 (11) [M+], 173.1 (100).
HRMS (EI): m/z calcd for C22H38O79Br81BrSi2 [M+]: 534.0808;
found: 534.0815.
MS (EI, 70 eV): m/z (%) = 450.0 (2) [M+], 145.0 (100) [M – Br2 –
Anal. Calcd for C22H38OBr2Si2: C, 49.43; H, 7.17. Found: C, 49.43;
H, 7.49.
TBDMSCH2O]+.
HRMS (EI): m/z calcd for C16H26OSi281Br79Br [M+]: 449.9869;
found: 449.9854.
7-(tert-Butyldimethylsilanyloxy)-1-triisopropylsilanyl-1,3,5-
heptatriyne (12) and 5-(tert-Butyldimethylsilanyloxy)-1-bromo-
2-triisopropylsilanyl-3-yn-1-pentene (13)
To 11 (402 mg, 0.751 mmol) in anhyd hexanes (6 mL) at –78 °C
was added dropwise BuLi (2.5 M, hexanes; 0.6 mL, 1.5 mmol). The
reaction was stirred at –78 °C for 5 min and then warmed to 10 °C
for 30 min. Et2O (10 mL) and sat. aq NH4Cl (6 mL) were added. The
organic phase was separated, washed with sat. aq NaCl (2 × 6 mL),
and dried over MgSO4. Solvent removal and purification by column
chromatography (hexanes) afforded 12 and 13.
8
Yield: 20 mg (7%); light yellow oil; Rf 0.4 (hexanes).
IR (cast, CHCl3): 2959, 2150, 1250 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.05 (s, 2 H), 0.23 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 113.4, 111.0, 103.1, 99.7, 90.6,
82.5, 14.1, –0.53.
MS (EI, 70 eV): m/z (%) = 399.8 (46) [M+], 101.0 (100).
HRMS (EI): m/z calcd for C10H11Si79Br81Br2 [M+]: 399.8139;
found: 399.8138.
HRMS (EI): m/z calcd for C10H11Si79Br281Br: 397.8160; found:
12
Yield: 172 mg (61%); colorless oil; Rf 0.5 (hexanes–CH2Cl2, 6:1).
IR (cast, CHCl3): 2945, 2865, 2194, 2164, 2078, 1463 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.37 (s, 2 H), 1.06 (s, 21 H), 0.88
(s, 9 H), 0.10 (s, 6 H).
397.8159.
13C NMR (100 MHz, CDCl3, APT): d = 89.6, 84.9, 69.8, 63.5, 60.3,
52.1, 25.8, 18.5, 11.3, –5.2; two coincident signals not observed.
6-(tert-Butyldimethylsilanyloxy)-1-triisopropylsilanylhexa-1,4-
diyn-3-ol (9)
To i-Pr3SiC≡CH (565 mg, 3.10 mmol) in THF (10 mL) at –78 °C
was added BuLi (2.5 M, hexanes; 1.25 mL, 3.1 mmol). After stir-
ring for 2 h at –78 °C, aldehyde 4 (514 mg, 2.58 mmol) was added
in one portion and the reaction was warmed to r.t. overnight. Et2O
(10 mL) and sat. aq NH4Cl (10 mL) were added. The organic phase
was separated, washed with sat. aq NH4Cl (2 × 10 mL), sat. aq NaCl
(2 × 10 mL), and dried over MgSO4. Solvent removal and purifica-
tion by column chromatography (CH2Cl2) afforded 9. Spectral data
were consistent with the literature.15b
MS (EI, 70 eV): m/z (%) = 374.2 (7) [M+], 287.2 (100) [M – t-Bu –
Me2]+.
HRMS (EI): m/z calcd for C22H38OSi2 [M+]: 374.2461; found:
374.2465.
13
Undefined stereochemistry; Rf 0.4 (hexanes–CH2Cl2, 6:1).
IR (cast, CHCl3): 2942, 2891, 2865, 2154 cm–1.
Yield: 805 mg (82%).
1H NMR (400 MHz, CDCl3): d = 6.88 (s, 1 H), 4.391 (s, 1 H), 4.390
(s, 1 H), 1.10 (s, 21 H), 0.90 (s, 9 H), 0.11 (s, 6 H).
6-(tert-Butyldimethylsilanyloxy)-1-triisopropylsilanylhexa-1,4-
diyn-3-one (10)
To 9 (576 mg, 1.52 mmol) in anhyd CH2Cl2 (30 mL) was added
BaMnO4 (1.31 g, 5.12 mmol) in one portion. After stirring over-
night at r.t., the mixture was filtered through a plug (celite and silica
gel, CH2Cl2) affording 10. Spectral data were consistent with the lit-
erature.15b
13C NMR (100 MHz, CDCl3, APT): d = 123.1, 112.1, 100.9, 99.0,
88.4, 80.8, 52.0, 25.8, 18.5, 18.2, 11.1, –5.1.
MS (EI, 70 eV): m/z (%) = 485.2/483.2 (1) [M+], 147.1 (100).
4-(tert-Butyldiphenylsilanyloxy)-2-butyn-1-ol (14)
To 1,4-butynediol (15 g, 174 mmol) in THF (100 mL) at r.t. were
added TBDPSCl (8.46 g, 30.8 mmol), Et3N (5 mL), and DMAP
(100 mg, 0.819 mmol). After stirring overnight, the mixture was
washed with H2O (100 mL). The organic phase was separated,
Yield: 523 mg (91%).
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

3174
T. Luu et al.
FEATURE ARTICLE
washed with sat. aq NH4Cl (2 × 100 mL), sat. aq NaCl (2 × 100
mL), and dried over MgSO4. Solvent removal and purification by
column chromatography (CH2Cl2) afforded 14 (starting material
1,4-butynediol was also recovered).
ica gel (CH2Cl2) affording 17 (523 mg, 91%) as a yellow oil, which
was used in the next step without further purification.
Rf 0.5 (hexanes–CH2Cl2, 1:1).
To CBr4 (660 mg, 1.99 mmol) in CH2Cl2 (10 mL) at 0 °C was added
PPh3 (1.05 g, 4.00 mmol). The mixture was stirred for 30 min and
Et3N (0.1 mL) was added. The mixture then was added to 17 (501
mg, 0.998 mmol) in CH2Cl2 (1 mL) at –20 °C and stirred for 10 min.
Et2O (20 mL) and sat. aq NH4Cl (20 mL) were added. The organic
phase was separated, washed with sat. aq NH4Cl (2 × 30 mL), sat.
aq NaCl (2 × 30 mL), and dried over MgSO4. The mixture was re-
duced to 10 mL and hexanes (10 mL) was added. The mixture was
filtered through silica and purified by column chromatography
(hexanes–CH2Cl2, 2:1) affording 18.
Yield: 8.38 g (84%); colorless oil; Rf 0.3 (CH2Cl2).
IR (cast, CHCl3): 3344, 3070, 2957, 2857, 1589 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.71–7.68 (m, 4 H), 7.44–7.36 (m,
6 H), 4.35 (t, J = 2.0 Hz, 2 H), 4.18 (t, J = 2.0 Hz, 2 H), 1.33 (br s,
1 H), 1.04 (s, 9 H).
13C NMR (500 MHz, CDCl3): d = 135.7, 133.1, 129.8, 127.7, 84.3,
83.4, 52.6, 51.2, 26.7, 19.1.
MS (EI, 70 eV): m/z (%) = 267.1 (41) [M – t-Bu]+, 199.2 (100).
HRMS (EI): m/z calcd for C16H15O2Si [M – t-Bu]+: 267.0841;
found: 267.0835.
Yield: 293 mg (45%); colorless oil; Rf 0.7 (hexanes–CH2Cl2, 2:1).
IR (cast, CH2Cl2): 3071, 2942, 2864, 2224, 2156, 1589, 1471 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.72–7.67 (m, 4 H), 7.44–7.34 (m,
4-(tert-Butyldiphenylsilanyloxy)-2-butyn-1-al (15)
6 H), 4.43 (s, 2 H), 1.09 (s, 21 H), 1.04 (s, 9 H).
To 14 (866 mg, 2.67 mmol) in CH2Cl2 (100 mL) at r.t. was added
BaMnO4 (2.05 g, 8.01 mmol). After stirring overnight, the mixture
was filtered through a plug (celite, CH2Cl2). Solvent removal and
purification by column chromatography (CH2Cl2) afforded 15.
13C NMR (125 MHz, CDCl3): d = 135.6, 132.9, 129.8, 127.8, 114.2,
108.8, 102.0, 99.5, 94.2, 81.5, 53.2, 26.7, 19.2, 18.6, 11.2.
MS (EI, 70 eV): m/z (%) = 601.0 (100) [M – t-Bu]+.
Yield: 498 mg (58%, 84% based on recovered starting material);
colorless oil; Rf 0.7 (CH2Cl2).
IR (cast, CHCl3): 3071, 2958, 2858, 2262, 2188, 1674 cm–1.
1H NMR (500 MHz, CDCl3): d = 9.14 (s, 1 H), 7.69–7.66 (m, 4 H),
7.46–7.37 (m, 6 H), 4.47 (s, 2 H), 1.06 (s, 9 H).
HRMS (EI): m/z calcd for C28H33OSi279Br81Br [M – t-Bu]+:
601.0416; found: 601.0417.
Anal. Calcd for C32H42OBr2Si2: C, 58.35; H, 6.43. Found: C, 58.12;
H, 6.24.
7-(tert-Butyldiphenylsilanyloxy)-1-triisopropylsilanyl-1,3,5-
heptatriyne (19)
13C NMR (100 MHz, CDCl3): d = 176.4, 135.6, 132.3, 130.1, 127.9,
94.4, 84.5, 52.4, 26.6, 19.1.
To 18 (228 mg, 0.345 mmol) in anhyd hexanes (15 mL) at –78 °C
was added dropwise BuLi (2.5 M, hexanes; 0.17 mL, 0.42 mmol).
The reaction was warmed to 10 °C. Et2O (15 mL) and sat. aq NH4Cl
(15 mL) were added. The organic phase was separated, washed with
sat. aq NaCl (2 × 15 mL), and dried over MgSO4. Solvent removal
and purification by column chromatography (hexanes–CH2Cl2, 4:1)
afforded 19.
MS (EI, 70 eV): m/z (%) = 322.1 (1) [M+], 265.1 (100) [M – t-Bu]+.
HRMS (EI): m/z calcd for C20H22O2Si [M+]: 322.1389; found:
322.1384.
6-(tert-Butyldiphenylsilanyloxy)-1-triisopropylsilanylhexa-1,4-
diyn-3-ol (16)
To i-Pr3SiC≡CH (621 mg, 3.41 mmol) in THF (65 mL) at –78 °C
was added BuLi (1.6 M, hexanes; 2.3 mL, 3.7 mmol). After stirring
for 2 h at –78 °C, aldehyde 15 (1.00 g, 3.10 mmol) was added in one
portion and the reaction was warmed to r.t. overnight. Et2O (65 mL)
and sat. aq NH4Cl (65 mL) were added. The organic phase was sep-
arated, washed with sat. aq NH4Cl (2 × 65 mL), sat. aq NaCl (2 × 65
mL), and dried over MgSO4. Solvent removal and purification by
column chromatography (hexanes–CH2Cl2, 2:1) afforded 16.
Yield: 71.0 mg (41%); colorless oil; Rf 0.6 (hexanes–CH2Cl2, 4:1).
IR (cast, CHCl3): 3071, 2943, 2864, 2164, 2078, 1463, 1369 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.69–7.64 (m, 4 H), 7.45–7.36 (m,
6 H), 4.35 (s, 2 H), 1.07 (s, 21 H), 1.04 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 135.6, 132.6, 130.0, 127.8, 89.6,
85.0, 76.3, 70.0, 63.6, 60.4, 53.1, 26.7, 19.2, 18.6, 11.3.
MS (EI, 70 eV): m/z (%) = 498.3 (4) [M+], 441.2 (24) [M – t-Bu]+,
199.1 (100).
Yield: 1.31 g (84%); colorless oil; Rf 0.2 (hexanes–CH2Cl2, 2:1).
IR (cast, CHCl3): 3405, 3071, 2942, 2180, 1589 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.70–7.68 (m, 4 H), 7.44–7.3 (m,
6 H), 5.05 (br d, J = 4.0 Hz, 1 H), 4.353 (d, J = 1.0 Hz, 1 H), 4.350
(d, J = 1.0 Hz, 1 H), 1.95 (br s, 1 H), 1.07 (s, 21 H), 1.05 (s, 9 H).
HRMS (EI): m/z calcd for C32H42OSi2 [M+]: 498.2774; found:
498.2776.
2,4,6-Heptatriyn-1-ol (20)
To 19 (60.3 mg, 0.121 mmol) in wet THF (2 mL) at –20 °C was add-
ed TBAF (1.0 M, THF; 0.2 mL, 0.2 mmol). The reaction was stirred
and warmed to r.t. until TLC analysis showed that desilylation had
taken place. Et2O (10 mL) and sat. aq NH4Cl (5 mL) were added.
The organic phase was separated, washed with sat. aq NaCl (2 × 5
mL), and dried over MgSO4. The product was insufficiently stable
to isolate and attempted purification by column chromatography
(hexanes–EtOAc, 4:1) led to decomposition.
13C NMR (100 MHz, CDCl3): d = 135.65, 135.67, 133.0, 133.0,
129.8, 127.7, 103.8, 85.9, 82.7, 82.3, 52.64, 52.58, 26.7, 19.1, 18.4,
11.1; two coincident signals not observed.
HRMS (ES, MeOH–toluene, 3:1): m/z calcd for C31H44O2Si2Na [M
+ Na]+: 527.2772; found: 527.2770.
Anal. Calcd for C31H44O2Si2: C, 73.75; H, 8.78. Found: C, 73.48; H,
8.95.
Rf 0.5 (hexanes–EtOAc, 4:1).
IR (cast, CHCl3): 3350, 3286, 2960, 2179 cm–1.
6-(tert-Butyldiphenylsilanyloxy)-3-(dibromomethylidene)-1-
triisopropylsilanylhexa-1,4-diyne (18)
To 16 (576 mg, 1.14 mmol) in CH2Cl2 (30 mL) at r.t. was added
BaMnO4 (1.31 g, 5.11 mmol) in one portion. After stirring over-
night at r.t. the mixture was filtered through a plug of celite and sil-
1-(tert-Butyldiphenylsilanyloxy)hepta-2,5-diyn-4-ol (22)
To excess propyne, condensed in THF (300 mL) at –78 °C, was
added BuLi (1.6 M, hexanes; 5.3 mL, 8.5 mmol) and LiBr (0.5 g, 6
mmol). After stirring for 2 h at –20 °C, aldehyde 15 (1.82 g, 5.65
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Triyne Natural Products and Glycosylated Analogues
3175
mmol) was added in one portion and the reaction was warmed to r.t.
overnight. Et2O (100 mL) and sat. aq NH4Cl (100 mL) were added.
The organic phase was separated, washed with sat. aq NH4Cl
(2 × 100 mL), sat. aq NaCl (2 × 100 mL), and dried over MgSO4.
Solvent removal and purification by column chromatography (hex-
anes–CH2Cl2, 1:4) afforded 22.
13C NMR (100 MHz, CDCl3): d = 135.6, 132.6, 130.0, 127.8, 76.6,
74.9, 70.3, 64.8, 63.8, 58.9, 53.1, 26.7, 19.2, 4.5.
MS (EI, 70 eV): m/z (%) = 356.2 (1) [M+], 299.1 (96) [M – t-Bu]+,
269.1 (100).
HRMS (EI): m/z calcd for C24H24OSi [M+]: 356.1596; found:
356.1594.
Yield: 2.04 g (100%); light yellow oil; Rf 0.4 (hexanes–CH2Cl2,
1:4).
IR (cast, CHCl3): 3396, 3071, 2958, 2893, 2258, 2226, 1472 cm–1.
Anal. Calcd for C24H24OSi: C, 80.85; H, 6.78. Found: C, 80.28; H,
7.01.
1H NMR (400 MHz, CDCl3): d = 7.72–7.68 (m, 4 H), 7.45–7.35 (6,
m, 6 H), 4.99 (br s, 1 H), 4.353 (s, 1 H), 4.351 (s, 1 H), 1.91 (br s, 1
H), 1.84 (s, 3 H) 1.04 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 135.70, 135.69, 133.05, 133.04,
129.8, 127.7, 82.7, 82.6, 81.2, 76.4, 52.6, 52.3, 26.7, 19.1, 3.6; two
coincident signals not observed.
2,4,6-Octatriyn-1-ol (21)
To 25 (108 mg, 0.302 mmol) in wet THF (15 mL) was added TBAF
(0.6 mL, 1.0 M in THF, 0.6 mmol). The reaction was stirred at r.t.
until TLC analysis showed that desilylation had taken place. Et2O
(15 mL) and sat. aq NH4Cl (15 mL) were added. The organic phase
was separated, washed with sat. aq NaCl (2 × 15 mL), and dried
over MgSO4. Solvent removal and purification by column chroma-
tography (CH2Cl2) afforded 21.
HRMS (ES, MeOH–toluene, 3:1): m/z calcd for C23H26O2SiNa [M
+ Na]+: 385.1594; found: 385.1595.
Yield: 26.9 mg (75%); magenta crystals; mp 89–92 °C (Lit.21b 93
°C); Rf 0.3 (CH2Cl2).
IR (cast, CHCl3): 3243, 2912, 2849, 2220, 1432 cm–1.
1-(tert-Butyldiphenylsilanyloxy)-4-(dibromomethylidene)hep-
ta-2,5-diyne (24)
To 22 (746 mg, 2.06 mmol) in anhyd CH2Cl2 (15 mL) was added
BaMnO4 (1.05 g, 4.10 mmol) in one portion. After stirring over-
night at r.t., the mixture was filtered through a plug (celite and silica
gel, CH2Cl2) affording 23 (589 mg, 80%) as a yellow oil, which was
used in the next step without further purification.
1H NMR (400 MHz, CDCl3): d = 4.32 (d, J = 6.4, 2 H), 1.96 (s, 3
H), 1.55 (t, J = 6.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 74.4, 71.1, 64.6, 64.4, 58.3, 51.6,
4.5; one signal not observed.
HRMS (EI, 70 eV): m/z calcd for C8H6O [M+]: 118.0419; found:
118.0420.
Rf 0.7 (hexanes–CH2Cl2, 1:5).
To CBr4 (826 mg, 2.45 mmol) in CH2Cl2 (16 mL) at 0 °C was added
PPh3 (1.30 g, 4.96 mmol). The mixture was stirred for 30 min. The
mixture was added to 23 (589 mg, 1.63 mmol) in CH2Cl2 (1 mL) at
0 °C and stirred for 3 min. Then the mixture was poured into
NaHCO3 (13 mL). The organic phase was separated, washed with
sat. aq NH4Cl (2 × 15 mL), sat. aq NaCl (2 × 15 mL), and dried over
MgSO4. The mixture was reduced to 10 mL and hexanes (10 mL)
was added. The mixture was filtered through silica and purified by
column chromatography (hexanes–CH2Cl2, 2:1) affording 24.
1-(tert-Butyldiphenylsilanyloxy)-6-phenylhexa-2,5-diyn-4-ol
(28)
To phenylacetylene (558 mg, 5.46 mmol) in THF (100 mL) at –78
°C was added BuLi (2.5 M, hexanes; 2.2 mL, 5.4 mmol). After stir-
ring for 1 h at –78 °C, aldehyde 15 (1.46 g, 4.52 mmol) was added
in one portion and the reaction was warmed to r.t. Et2O (100 mL)
and sat. aq NH4Cl (100 mL) were added. The organic phase was
separated, washed with sat. aq NH4Cl (2 × 100 mL), sat. aq NaCl
(2 × 100 mL), and dried over MgSO4. Solvent removal and purifi-
cation by column chromatography (CH2Cl2) afforded 28.
Yield: 210 mg (25%); colorless oil; Rf 0.7 (hexanes–CH2Cl2, 1:1).
IR (cast, CHCl3): 3070, 2958, 2245, 2225, 1589 cm–1.
Yield: 1.63 g (85%); light yellow oil; Rf 0.4 (CH2Cl2).
IR (cast, CHCl3): 3383, 3070, 3050, 2930, 2231, 1589 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.74–7.69 (m, 4 H), 7.46–7.35 (m,
6 H), 4.44 (s, 2 H), 1.98 (s, 3 H), 1.06 (s, 9 H).
13C NMR (125 MHz, CDCl3): d = 135.6, 132.9, 129.8, 127.7, 114.1,
1H NMR (500 MHz, CDCl3): d = 7.72–7.70 (m, 4 H), 7.44–7.30 (m,
11 H), 5.24 (d, J = 7.7 Hz, 1 H), 4.385 (s, 1 H), 4.382 (s, 1 H), 2.00
(d, J = 7.7 Hz, 1 H), 1.00 (s, 9 H).
13C NMR (125 MHz, CDCl3): d = 135.79, 135.78, 133.13, 133.12,
131.9, 129.90, 129.89, 128.9, 128.4, 127.8, 122.0, 85.9, 84.4, 83.3,
82.3, 52.7, 52.6, 26.7, 19.2; one coincident signal not observed.
MS (EI, 70 eV): m/z (%) = 367.1 (96) [M – t-Bu]+, 199.1 (100).
HRMS (EI): m/z calcd for C24H19O2Si [M – t-Bu]+: 367.1155;
106.6, 93.8, 93.7, 81.9, 76.8, 53.2, 26.7, 19.2, 4.8.
MS (EI, 70 eV): m/z (%) = 458.9 (81) [M – t-Bu]+, 428.9 (100).
HRMS (EI): m/z calcd for C20H15OSi79Br81Br [M – t-Bu]+:
458.9239; found: 458.9253.
Anal. Calcd for C24H24OBr2Si: C, 55.83; H, 4.69. Found: C, 55.59;
H, 4.76.
1-(tert-Butyldiphenylsilanyloxy)-2,4,6-octatriyne (25)
found: 367.1146.
To 24 (259 mg, 0.502 mmol) in anhyd hexanes (15 mL) at –78 °C
BuLi (2.5 M, hexanes; 0.24 mL, 0.60 mmol) was added dropwise.
The reaction was stirred at –78 °C for 5 min and then warmed to 10
°C for 30 min. Et2O (15 mL) and sat. aq NH4Cl (15 mL) were added.
The organic phase was separated, washed with sat. aq NaCl (2 × 15
mL), and dried over MgSO4. Solvent removal and purification by
column chromatography (hexanes) afforded 25.
Anal. Calcd for C28H28O2Si: C, 79.20; H, 6.65. Found: C, 79.37; H,
6.41.
1-(tert-Butyldiphenylsilanyloxy)-6-phenylhexa-2,5-diyn-4-one
(29)
To 28 (519 mg, 1.22 mmol) in anhyd CH2Cl2 (27 mL) at r.t. was
added BaMnO4 (940 mg, 3.67 mmol) in one portion. After stirring
for 8 h at r.t., the mixture was filtered through a plug of celite and
silica gel (CH2Cl2) affording 29.
Yield: 69.0 mg (39%); colorless oil; Rf 0.3 (hexanes–CH2Cl2, 3:1).
IR (cast, CHCl3): 3070, 2958, 2892, 2223, 1472 cm–1.
Yield: 459 mg (89%); yellow oil; Rf 0.4 (hexanes–CH2Cl2, 1:1).
IR (cast, CHCl3): 3070, 2958, 2893, 2196, 1596, cm–1.
1H NMR (400 MHz, CDCl3): d = 7.70–7.67 (m, 4 H), 7.46–7.37 (m,
6 H), 4.36 (s, 2 H), 1.96 (s, 3 H), 1.06 (s, 9 H).
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3176
T. Luu et al.
FEATURE ARTICLE
1H NMR (500 MHz, CDCl3): d = 7.71–7.69 (m, 4 H), 7.59–7.57 (m,
TLC analysis showed that desilylation had taken place. Et2O (5 mL)
and sat. aq NH4Cl (5 mL) were added. The organic phase was sep-
arated, washed with sat. aq NaCl (2 × 5 mL), and dried over
MgSO4. Solvent removal and purification by column chromatogra-
phy (hexanes–EtOAc, 4:1) afforded 26. Compound 26 was previ-
ously reported to be a solid,22 but in our hands, all attempts at
crystallization have been unsuccessful.
2 H), 7.49–7.37 (m, 9 H), 4.50 (s, 2 H), 1.06 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 160.5, 135.7, 133.4, 132.4, 131.3,
130.1, 128.8, 127.9, 119.5, 91.8, 91.2, 89.1, 85.1, 52.6, 26.7, 19.3.
MS (EI, 70 eV): m/z (%) = 422.2 (2) [M+], 365.1 (100) [M – t-Bu]+.
HRMS (EI): m/z calcd for C28H26O2Si [M+]: 422.1702; found:
422.1698.
Yield: 31 mg (96%); light yellow oil; Rf 0.3 (hexanes–EtOAc, 4:1).
IR (cast, CHCl3): 3307, 3064, 2928, 2856, 2190, 1490 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.50 (d, J = 7.5 Hz, 2 H), 7.38 (t,
J = 7.5 Hz, 1 H), 7.31 (t, J = 7.5 Hz, 2 H), 4.40 (s, 2 H), 1.60 (s, 1
Anal. Calcd for C28H26O2Si: C, 79.58; H, 6.20. Found: C. 79.28; H,
6.26.
1-(tert-Butyldiphenylsilanyloxy)-4-(dibromomethylidene)-6-
phenylhexa-2,5-diyne (30)
H).
To CBr4 (1.51 g, 4.55 mmol) in CH2Cl2 at 0 °C was added PPh3
(2.30 g, 8.78 mmol). The mixture was stirred for 30 min. Et3N (0.4
mL) was added to the mixture at 0 °C. The mixture was transferred
to 29 (1.26 g, 2.97 mmol) in CH2Cl2 (5 mL) at 0 °C and stirred for
5 min. The reaction was poured over NaHCO3 (50 mL). The organic
phase was separated, washed with sat. aq NH4Cl (2 × 50 mL), sat.
aq NaCl (2 × 50 mL), and dried over MgSO4. The mixture was re-
duced to 10 mL and hexanes (10 mL) was added. The mixture was
filtered through celite and purified by column chromatography
(hexanes–CH2Cl2, 1:1) affording 30.
13C NMR (125 MHz, CDCl3): d = 133.1, 129.9, 128.6, 120.8, 77.9,
77.3, 77.1, 71.0, 65.8, 63.5, 51.7.
MS (EI, 70 eV): m/z (%) = 180.1 (95) [M+], 126.0 (100)
[PhC≡CC≡CH]+.
HRMS (EI): m/z calcd for C13H8O [M+]: 180.0575; found:
180.0574.
7-Phenylhepta-2,4,6-triynylacetate (27)
To 26 (158 mg, 0.877 mmol) in CH2Cl2 (10 mL) was added Ac2O
(108 mg, 1.06 mmol), DMAP (50 mg, 0.41 mmol), and Et3N (0.1
mL). The reaction was stirred at r.t. for 5 h until TLC analysis
showed that acetylation had taken place. Et2O (10 mL) and sat. aq
NH4Cl (10 mL) were added. The organic phase was separated,
washed with sat. aq NaCl (2 × 10 mL), and dried over MgSO4. Sol-
vent removal and purification by column chromatography (hex-
anes–EtOAc, 4:1) afforded 27.
Yield: 158 mg (81%); white solid,22 decomposed immediately un-
der ambient condition; Rf 0.5 (hexanes–EtOAc, 4:1).
IR (cast, CHCl3): 3056, 2929, 2192, 1749, 1220 cm–1.
1H NMR (300 MHz, CD3CN): d = 7.69 (d, J = 7.5 Hz, 2 H), 7.60 (t,
J = 7.5 Hz, 1 H), 7.51 (t, J = 7.5 Hz, 2 H), 4.88 (s, 2 H), 2.16 (s, 3
H).
13C NMR (100 MHz, CD3CN): d = 170.8, 134.0, 131.5, 129.8,
120.9, 78.5, 76.3, 74.0, 70.7, 66.2, 63.8, 53.0, 20.7.
Yield: 905 mg (53%, 57% based on recovered starting material); a
light yellow oil; Rf 0.8 (hexanes–CH2Cl2, 1:1).
IR (cast, CHCl3): 3070, 2998, 2958, 2216, 2192, 1471 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.73–7.70 (m, 4 H), 7.51–7.47 (m,
2 H), 7.43–7.30 (m, 9 H), 4.47 (s, 2 H), 1.06 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 135.6, 132.9, 131.6, 129.9, 129.2,
128.4, 127.8, 122.1, 113.9, 107.9, 95.7, 94.4, 86.1, 81.5, 53.2, 26.7,
19.2.
MS (EI, 70 eV): m/z (%) = 520.9 (27) [M – t-Bu]+, 491.0 (100).
HRMS (EI): m/z calcd for C25H17OSi79Br81Br [M – t-Bu]+:
520.9395; found: 520.9385.
Anal. Calcd for C29H26OBr2Si: C, 60.22; H, 4.53. Found: C, 59.63;
H, 4.39.
1-(tert-Butyldiphenylsilanyloxy)-7-phenyl-2,4,6-heptatriyne
(31)
HRMS (ES, MeOH–toluene, 3:1): m/z calcd for C15H10O2Na [M +
Na]+: 245.0573; found: 245.0571.
To 30 (548 mg, 0.948 mmol) in anhyd hexanes (32 mL) at –78 °C
was added dropwise BuLi (2.4 M, hexanes; 0.8 mL, 2 mmol). The
reaction was warmed to 10 °C. Et2O (32 mL) and sat. aq NH4Cl (32
mL) were added. The organic phase was separated, washed with sat.
aq NaCl (2 × 30 mL), and dried over MgSO4. Solvent removal and
purification by column chromatography (hexanes–CH2Cl2, 1:1) af-
forded 31 (1H NMR of the purified product showed ca. 5% of an im-
purity that could not be separated chromatographically).
7-Phenylhepta-2,4,6-triynyl 2,3,4,6-Tetra-O-acetyl-b-D-gluco-
pyranoside (40)
To 26 (30 mg, 0.17 mmol) in CH2Cl2 (2 mL) at r.t. was added
1,2,3,4,6-penta-O-acetyl-b-D-glucopyranose (130 mg, 0.33 mmol)
and crushed activated 4 Å molecular sieves (20 mg). After stirring
for 30 min at r.t., the mixture was cooled to –30 °C. BF3·OEt2 (64
mL, 0.50 mmol) was added slowly and the reaction was warmed to
r.t. over 24 h. K2CO3 (135 mg), H2O (2.5 mL), a sat. aq soln of
NaHCO3 (2.5 mL), and CH2Cl2 (15 mL) were then added. The or-
ganic phase was separated, washed with a sat. aq soln of NaCl (15
mL), and dried over Na2SO4. Solvent removal and purification by
column chromatography (hexanes–EtOAc, 2:1) afforded 40.
Yield: 356 mg (90%); yellow oil; Rf 0.6 (hexanes–CH2Cl2, 1:1).
IR (cast, CHCl3): 3071, 2958, 2857, 2191, 1472 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.70–7.67 (m, 4 H), 7.52–7.50 (m,
2 H), 7.46–7.29 (m, 9 H), 4.39 (s, 2 H), 1.06 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 135.6, 133.0, 132.6, 130.0, 129.7,
128.5, 127.8, 120.9, 78.4, 76.97, 74.3, 70.1, 66.3, 62.9, 53.2, 26.4,
19.2.
MS (EI, 70 eV): m/z (%) = 418.1 (2) [M+], 361.1 (23) [M – t-Bu]+,
199.1 (100).
HRMS (EI): m/z calcd for C29H26OSi [M+]: 418.1753; found:
418.1753.
Yield: 52 mg (61%); yellow oil; Rf 0.3 (hexanes–EtOAc, 2:1); [a]D
–32.9 (c 1.6, CH2Cl2).
IR (cast, CH2Cl2): 2190, 1752 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.52–7.32 (m, 5 H, Ar), 5.27 (dd,
J2,3 = 9.5 Hz, J3,4 = 9.5 Hz, 1 H, H-3), 5.11 (dd, J3,4 = 9.5 Hz,
J4,5 = 9.5 Hz, 1 H, H-4), 5.02 (dd, J2,3 = 9.5 Hz, J1,2 = 7.9 Hz, 1 H,
H-2), 4.76 (d, J1,2 = 7.9 Hz, 1 H, H-1), 4.51 (d, J = 17.2 Hz, 1 H,
propargyl CHH), 4.47 (d, J = 17.2 Hz, 1 H, propargyl CHH), 4.28
(dd, J6,6¢ = 12.4 Hz, J5,6 = 4.7 Hz, 1 H, H-6), 4.15 (dd, J6,6¢ = 12.4
Hz, J5,6¢ = 2.4 Hz, 1 H, H-6¢), 3.75 (ddd, J4,5 = 9.5 Hz, J5,6 = 4.7 Hz,
7-Phenyl-2,4,6-heptatriyn-1-ol (26)
To 31 (77 mg, 0.18 mmol) in wet THF (5 mL) was added TBAF (1.0
M, THF; 0.4 mL, 0.4 mmol). The reaction was stirred at r.t. until
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Triyne Natural Products and Glycosylated Analogues
3177
J
5,6¢ = 2.4 Hz, 1 H, H-5), 2.11 [s, 3 H, C(O)CH3], 2.09 [s, 3 H, 7-Phenylhepta-2,4,6-triynyl b-D-Glucopyranoside (34)
C(O)CH3], 2.04 [s, 3 H, C(O)CH3], 2.02 [s, 3 H, C(O)CH3].
To a soln of 40 (13.0 mg, 0.0255 mmol) in MeOH (2 mL) at –78 °C
was added K2CO3 (1.4 mg, 0.01 mmol). The soln was allowed to
warm to r.t. over 18 h and then concentrated. Purification by column
chromatography (CH2Cl2–MeOH, 10:1) afforded 34.
13C NMR (125 MHz, CDCl3): d = 170.6, 170.2, 169.4, 169.3, 133.1
(2 C), 129.9, 128.5 (2 C), 120.6, 98.5, 77.6, 74.4, 73.9, 72.7, 72.2,
72.1, 71.0, 68.2, 65.5, 63.7, 61.4, 56.7, 20.7 (2 C), 20.6 (2 C).
Yield: 6.0 mg (69%); white solid; Rf 0.2 (CH2Cl2–MeOH, 10:1);
[a]D –112.2 (c 0.4, MeOH).
IR (cast, CH2Cl2): 3374, 2190 cm–1.
HRMS (ES, MeOH–toluene, 3:1): m/z calcd for C27H26O10Na [M +
Na]+: 533.1418; found: 533.1425.
7-Phenylhepta-2,4,6-triynyl 2,3,4,6-O-Tetraacetyl-b-D-galacto-
pyranoside (41)
1H NMR (600 MHz, CD3OD): d = 7.56–7.37 (m, 5 H, Ar), 4.57 (s,
2 H, propargyl CH2), 4.42 (d, J1,2 = 7.8 Hz, 1 H, H-1), 4.15 (dd,
Alcohol 26 (30 mg, 0.17 mmol) was glycosylated with 1,2,3,4,6-
penta-O-acetyl-b-D-galactopyranose (130 mg, 0.33 mmol) in
CH2Cl2 (2 mL) at r.t. in the presence of crushed activated 4 Å mo-
lecular sieves (20 mg) and BF3·OEt2 (64 mL, 0.50 mmol) as de-
scribed for the synthesis of 40. Purification by column
chromatography (hexanes–EtOAc, 2:1) afforded 41.
J6,6¢ = 11.9 Hz, J5,6¢ = 5.5 Hz, 1 H, H-6¢), 3.88 (dd, J6,6¢ = 11.9 Hz,
J5,6 = 2.0 Hz, 1 H, H-6), 3.37 (dd, J3,4 = 9.0 Hz, J4,5 = 9.0 Hz, 1 H,
H-4), 3.25–3.29 (m, 2 H, H-3, H-5), 3.20 (dd, J2,3 = 9.3 Hz,
J1,2 = 7.8 Hz, 1 H, H-2).
13C NMR (125 MHz, CDCl3): d = 134.0 (2 C), 131.3, 129.8 (2 C),
121.7, 102.6, 78.1(9), 78.1(6), 78.0, 77.4, 74.9, 74.3, 71.6, 71.5,
66.5, 63.4, 62.8, 57.1.
HRMS (ES, MeOH): m/z calcd for C19H18O6Na [M + Na]+:
365.0996; found: 365.0996.
Yield: 63 mg (74%); yellow oil; Rf 0.3 (hexanes–EtOAc, 2:1); [a]D
–27.1 (c 3.0, CH2Cl2).
IR (cast, CH2Cl2): 2191, 1750 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.51–7.32 (m, 5 H), 5.40 (dd,
J3,4 = 3.4 Hz, J4,5 = 1.0 Hz, 1 H, H-4), 5.22 (dd, J2,3 = 10.4 Hz,
J1,2 = 7.9 Hz, 1 H, H-2), 5.06 (dd, J2,3 = 10.4 Hz, J3,4 = 3.4 Hz, 1 H,
H-3), 4.70 (d, J1,2 = 7.9 Hz, 1 H, H-1), 4.52 (d, J = 17.1 Hz, 1 H,
propargyl CHH), 4.48 (d, J = 17.1 Hz, 1 H, propargyl CHH), 4.18
(dd, J6,6¢ = 11.4 Hz, J5,6 = 6.6 Hz, 1 H, H-6), 4.15 (dd, J6,6¢ = 11.4
Hz, J5,6¢ = 6.6 Hz, 1 H, H-6¢), 3.95 (ddd, J5,6 = 6.6 Hz, J5,6¢ = 6.6 Hz,
J4,5 = 1.0 Hz, 1 H, H-5), 2.15 [s, 3 H, C(O)CH3], 2.10 [s, 3 H,
C(O)CH3], 2.07 [s, 3 H, C(O)CH3], 1.99 [s, 3 H, C(O)CH3].
7-Phenylhepta-2,4,6-triynyl b-D-Galactopyranoside (35)
To a soln of 41 (12.3 mg, 0.0241 mmol) in MeOH (2 mL) at –78 °C
was added K2CO3 (1.7 mg, 0.01 mmol). The soln was allowed to
warm to r.t. over 18 h and then concentrated. Purification by column
chromatography (CH2Cl2–MeOH, 10:1) afforded 35.
Yield: 5.3 mg (64%); white solid; Rf 0.2 (CH2Cl2–MeOH, 10:1);
[a]D –71.3 (c 0.3, MeOH).
IR (microscope, CH2Cl2): 3368, 2191 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.55–7.36 (m, 5 H, Ar), 4.57 (s, 2
H, propargyl CH2), 4.38 (d J1,2 = 7.4 Hz, 1 H, H-1), 3.82 (dd,
J3,4 = 3.3 Hz, J4,5 = 1.0 Hz, 1 H, H-4), 4.15 (dd, J6,6¢ = 11.4 Hz,
13C NMR (125 MHz, CDCl3): d = 170.4, 170.2, 170.0, 169.5, 133.1
(2 C), 129.9, 128.5 (2 C), 120.6, 99.1, 77.6, 74.5, 73.9, 72.1, 71.0,
70.8, 68.5, 67.0, 65.6, 63.6, 61.3, 56.7, 20.8, 20.7, 20.6, 20.5.
HRMS (ES, MeOH–toluene, 3:1): m/z calcd for C27H26O10Na [M +
J6,6¢ = 11.4 Hz, 1 H, H-6¢), 3.77 (dd, J6,6¢ = 11.4 Hz, J5,6 = 7.0 Hz, 1
Na]+: 533.1418; found: 533.1419.
H, H-6), 3.51–3.55 (m, 2 H, H-2, H-5), 3.48 (dd, J2,3 = 9.7 Hz,
J3,4 = 3.3 Hz, 1 H, H-3).
7-Phenylhepta-2,4,6-triynyl 2,3,4,6-O-Tetraacetyl-a-D-manno-
pyranoside (42)
13C NMR (125 MHz, CDCl3): d = 134.0 (2 C), 131.2, 129.8 (2 C),
121.7, 103.2, 78.1, 77.6, 77.0, 74.9, 74.3, 72.3, 71.4, 70.3, 66.6,
63.3, 62.6, 57.0.
HRMS (ES, MeOH): m/z calcd for C19H18O6Na [M + Na]+:
365.0996; found: 365.0996.
Alcohol 26 (30 mg, 0.17 mmol) was glycosylated with 1,2,3,4,6-
penta-O-acetyl-a-D-mannopyranose (130 mg, 0.33 mmol) in
CH2Cl2 (2 mL) at r.t. in the presence of crushed activated 4 Å mo-
lecular sieves (20 mg) and BF3·OEt2 (64 mL, 0.50 mmol) as de-
scribed for the synthesis of 40. Purification by column
chromatography (hexanes–EtOAc, 2:1) afforded 42.
7-Phenylhepta-2,4,6-triynyl a-D-Mannopyranoside (36)
To a soln of 42 (34.0 mg, 0.0666 mmol) in MeOH (3 mL) at –78 °C
was added K2CO3 (6.0 mg, 0.04 mmol). The soln was allowed to
warm to r.t. over 18 h and then concentrated. Purification by column
chromatography (CH2Cl2–MeOH, 10:1) afforded 36.
Yield: 66 mg (78%); yellow oil; Rf 0.2 (hexanes–EtOAc, 2:1); [a]D
+57.6 (c 3.6, CH2Cl2).
IR (cast, CHCl3): 2191, 1751 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.51–7.55 (m, 2 H, Ar), 7.37–7.42
(m, 1 H, Ar), 7.31–7.36 (m, 2 H, Ar, 5.27–5.35 (m, 3 H, H-2, H-3,
H-4), 5.00 (d, J1,2 = 1.8 Hz, 1 H), 4.45 (d, J = 17.2 Hz, 1 H, propar-
gyl CHH), 4.41 (d, J = 17.2 Hz, 1 H, propargyl CHH), 4.31 (dd,
Yield: 17.5 mg (77%); white solid; Rf 0.2 (CH2Cl2–MeOH, 10:1);
[a]D +75.4 (c 0.5, MeOH).
IR (cast, MeOH): 3364, 2191 cm–1.
1H NMR (600 MHz, CDCl3): d = 7.53–7.57 (m, 2 H, Ar), 7.42–7.46
(m, 1 H, Ar), 7.37–7.40 (m, 2 H, Ar, 4.92 (d, J1,2 = 1.7 Hz, 1 H, H-
1), 4.45 (d, J = 17.2 Hz, 1 H, propargyl CHH), 4.41 (d, J = 17.2 Hz,
1 H, propargyl CHH), 3.84 (dd, J6,6¢ = 11.8 Hz, J5,6 = 2.4 Hz, 1 H,
H-6), 3.81 (dd, J2,3 = 3.2 Hz, J1,2 = 1.7 Hz, 1 H, H-2), 3.70 (dd,
J
J
6,6¢ = 12.3 Hz, J5,6 = 5.3 Hz, 1 H, H-6), 4.12 (dd, J6,6¢ = 12.3 Hz,
5,6¢ = 2.5 Hz, 1 H, H-6¢), 4.00-4.05 (m, 1 H, H-5), 2.17 [s, 3 H,
C(O)CH3], 2.12 [s, 3 H, C(O)CH3], 2.05 [s, 3 H, C(O)CH3], 1.99 [s,
3 H, C(O)CH3].
13C NMR (125 MHz, CDCl3), d = 170.6, 169.9, 169.8, 169.7, 133.1
(2 C), 129.9, 128.5 (2 C), 120.6, 96.9, 77.6, 74.2, 74.0, 72.2, 69.3,
69.2, 68.9, 66.0, 65.5, 63.8, 62.3, 55.9, 20.8, 20.7(3), 20.6(8),
20.6(4).
J
6,6¢ = 11.8 Hz, J5,6¢ = 6.0 Hz, 1 H, H-6¢), 3.59–3.68 (m, 2 H, H-3, H-
4), 3.50 (ddd, J4,5 = 8.9 Hz, J5,6¢ = 6.0 Hz, J5,6 = 2.4 Hz, 1 H, H-5).
13C NMR (125 MHz, CDCl3): d = 134.0 (2 C), 131.3, 129.8 (2 C),
121.7, 100.6, 78.2, 77.4, 75.3, 74.2, 72.4, 71.9, 71.3, 68.4, 66.4,
63.4, 62.8, 55.5.
HRMS (ES, MeOH–toluene, 3:1): m/z calcd for C27H26O10Na [M +
Na]+: 533.1418; found: 533.1419.
HRMS (ES, MeOH): m/z calcd for C19H18O6Na [M + Na]+:
365.0996; found: 365.0996.
Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York

3178
T. Luu et al.
FEATURE ARTICLE
(12) For reviews, see: (a) Stang, P. J. Chem. Rev. 1978, 78, 383.
(b) Knorr, R. Chem. Rev. 2004, 104, 3795.
(13) (a) Eisler, S.; Chahal, N.; McDonald, R.; Tykwinski, R. R.
Chem. Eur. J. 2003, 9, 2452. (b) Shi Shun, A. L. K.;
Chernick, E. T.; Eisler, S.; Tykwinski, R. R. J. Org. Chem.
2003, 68, 1339. (c) Shi Shun, A. L. K.; Tykwinski, R. R. J.
Org. Chem. 2003, 68, 6810.
Acknowledgment
This work was supported by the Natural Sciences and Engineering
Research Council of Canada (NSERC), the Alberta Ingenuity Cen-
tre for Carbohydrate Science and the University of Alberta. WS is
the recipient of a Studentship from the Alberta Ingenuity Fund.
(14) For an excellent summary of natural and synthetic
acetylenosaccharides, see: Vasella, A. In Acetylene
Chemistry – Chemistry, Biology, and Materials Science;
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Synthesis 2005, No. 18, 3167–3178 © Thieme Stuttgart · New York