Synthesis of naturally occurring acetylenes via an alkylidene carbenoid rearrangement

Article abstract of DOI:10.1021/jo034734g

Naturally occurring mosquito larvicidal acetylenes 1 and 2, and analogues 3 and 4, each containing either a 1,3-butadiynyl or a 1,3,5-hexatriynyl moiety, are synthesized via a Fritsch - Buttenberg - Wiechell rearrangement. The alkylidene carbenoid interme

Full text of DOI:10.1021/jo034734g

Syn th esis of Na tu r a lly Occu r r in g
Acetylen es via a n Alk ylid en e Ca r ben oid
Rea r r a n gem en t
Annabelle L. K. Shi Shun and Rik R. Tykwinski*
Department of Chemistry, University of Alberta,
Edmonton, AB, T6G 2G2 Canada
rik.tykwinski@ualberta.ca
Received May 29, 2003
F IGURE 1.
cal studies conducted on compound 1 revealed it to be
highly phototoxic toward Aedes atropalpus larvae and
Aedes aegypti larvae, with LC50 values of 0.100 and 0.079
ppm, respectively. Compound 1 was also phototoxic to
blackfly larvae and adult nematodes.7b 1-Phenylhepta-
1,3,5-triyne (2) has been isolated from diverse plant
species, such as Bidens pilosa L. (Asteraceae),9 and
several members of the Coreopsis family.8b Triyne 2 has
been extensively studied and displays insecticidal activity
(LC50 204 ng/cm2) on first instar larvae of the fall
armyworm Spodoptera frugiperda Smith., phototoxicity
toward Aedes aegypti larvae, antimicrobial activity, ovi-
cidal activity, and nematicidal activity.7b,c,10 Diene-diyne
3, atractylodin, has previously been isolated from the
rhizomes of various Atractylodes species,11 and is photo-
toxic and antibiotic against Escherichia coli, Saccharo-
myces cerevisiae, and Candida albicans,11c but it has not
yet been tested for mosquito larvicidal activity. Ene-diyne
4, 2-hept-1-ene-3,5-diynylfuran, is a novel synthetic
compound that has been synthesized in view of its
potential as a mosquito larvicidal agent due to its
structural analogy to compound 1.
Abstr a ct: Naturally occurring mosquito larvicidal acety-
lenes 1 and 2, and analogues 3 and 4, each containing either
a 1,3-butadiynyl or a 1,3,5-hexatriynyl moiety, are synthe-
sized via a Fritsch-Buttenberg-Wiechell rearrangement.
The alkylidene carbenoid intermediate results from lithium-
halogen exchange of a suitable dibromoolefin precursor, and
the rearrangement is accomplished under mild conditions.
Synthesis of the dibromoolefin precursors to acetylenes 1-4
is easily achieved in three steps from commercially available
carboxylic acids or aldehydes, making this procedure a viable
alternative to conventional methods for the synthesis of
naturally occurring acetylenes.
Mosquito larvicidal agents are important in the fight
to eradicate mosquito-borne diseases such as the West
Nile Virus, malaria, and dengue fever.1 The allure of
naturally occurring toxins for this purpose is attributable
to their biodegradability and the fact that they generally
leave no long-lived residues.2 Naturally occurring acety-
lenes3 have been isolated from a wide variety of plant
species,3 cultures of higher fungi,3a-c,4 and marine sponges,5
and have proven to be important biologically active
compounds due to their antibacterial, antimicrobial,
antifungal, and pesticidal properties.2,6 The natural
products 1 and 2 illustrate the potency of certain acety-
lenes, and both are extremely phototoxic toward mosquito
larvae.7 Ene-triyne 1 was first isolated by Bohlmann et
al. from various Chrysanthemum plant species.8 Biologi-
We now report the synthesis of acetylenes 1-412-14 via
a modification of the Fritsch-Buttenberg-Wiechell rear-
(7) (a) Arnason, J . T.; Philoge`ne, B. J . R.; Berg, C.; MacEachern,
A.; Kaminski, J .; Leitch, L. C.; Morand, P.; Lam, J . Phytochemistry
1986, 25, 1609-1611. (b) Wat, C.-K.; Prasad, S. K.; Graham, E. A.;
Partington, S.; Arnason, T.; Towers, G. H. N.; Lam, J . Biochem. Syst.
Ecol. 1981, 9, 59-62. (c) Arnason, T.; Swain, T.; Wat, C.-K.; Graham,
E. A.; Partington, S.; Towers, G. H. N. Biochem. Syst. Ecol. 1981, 9,
63-68.
(1) (a) Busvine, J . R. Disease Transmission by Insects - Its Discovery
and 90 Years of Effort to Prevent It; Springer-Verlag: Berlin, Germany,
1993. (b) Baqar, S.; Hayes, C. G.; Murphy, J . R.; Watts, D. M. Am. J .
Trop. Med. Hyg. 1993, 48, 757-762.
(8) (a) Bohlmann, F.; von Kap-Herr, W.; Fangha¨nel, L.; Arndt, C.
Chem. Ber. 1965, 98, 1411-1415. (b) Bohlmann, F.; Burkhardt, H.;
Zdero, C. Naturally Occurring Acetylenes; Academic Press: New York,
1973. (c) Bohlmann, F.; Fangha¨nel, L.; Kleine, K.-M.; Kramer, H.-D.;
Mo¨nch, H.; Schuber, J . Chem. Ber. 1965, 98, 2596-2604.
(9) (a) Wat, C.-K.; Biswas, R. K.; Graham, E. A.; Bohm, L.; Towers,
G. H. N.; Waygood, E. R. J . Nat. Prod. 1979, 42, 103-111. (b) Alvarez,
L.; Marquina, S.; Villarreal, M. L.; Alonso, D.; Aranda, E.; Delgado,
G. Planta Med. 1996, 62, 355-357.
(2) (a) Towers, G. H. N.; Wat, C. K.; Lambert, J . D. H.; Arnason, J .
T. Canadian Patent 1173743, 1984. (b) Biologically Active Natural
Products - Potential Use in Agriculture; Cutler, H. G., Ed.; ACS Symp.
Ser. No. 380; American Chemical Society: Washington, DC, 1988.
(3) (a) J ones, E. R. H. Proc. Chem. Soc., London 1960, 199-210. (b)
So¨rensen, N. A. Proc. Chem. Soc., London 1961, 98-110. (c) Bohlmann,
F.; Bornowski, H.; Arndt, C. Fortsch. Chem. Forsch. 1962, 4, 138-
272. (d) Bu’Lock, J . D. Prog. Org. Chem. 1964, 6, 86-134. (e)
Bohlmann, F. Fortsch. Chem. Forsch. 1966, 6, 65-100. (f) Bohlmann,
F. In Chemistry of Acetylenes; Viehe, H. G., Ed.; Marcel Dekker: New
York, 1969; Chapter 14, pp 977-986.
(4) Gardner, J . N.; J ones, E. R. H.; Leeming, P. R.; Stephenson, J .
S. J . Chem. Soc. 1960, 691-697.
(5) (a) Dai, J .-R.; Hallock, Y. F.; Cardellina, J . H., II; Gray, G. N.;
Boyd, M. R. J . Nat. Prod. 1996, 59, 860-865. (b) Faulkner, D. J . Nat.
Prod. Rep. 2000, 17, 7-55. (c) Faulkner, D. J . Nat. Prod. Rep. 2002,
19, 1-48. (d) Nakao, Y.; Uehara, T.; Matunaga, S.; Fusetani, N.; van
Soest, R. W. M. J . Nat. Prod. 2002, 65, 922-924.
(10) (a) Nakajima, S.; Kawazu, K. Agric. Biol. Chem. 1980, 44,
1529-1533. (b) Kawazu, K.; Nishii, Y.; Nakajima, S. Agric. Biol. Chem.
1980, 44, 903-906.
(11) (a) Yosioka, I.; Hikino, H.; Sasaki, Y. Chem. Pharm. Bull. 1960,
8, 949-951. (b) Yosioka, I.; Hikino, H.; Sasaki, Y. Chem. Pharm. Bull.
1960, 8, 952-956. (c) Wat, C.-K.; J ohns, T.; Towers, G. H. N. J .
Ethnopharm. 1980, 2, 279-290. (d) Ding, H.-Y.; Wu, Y.-C.; Lin, H.-C.
J . Chin. Chem. Soc. (Taipei) 2000, 47, 561-566. (e) Resch, M.;
Heilmann, J .; Steigel, A.; Bauer, R. Planta Med. 2001, 67, 437-442.
(12) The ene-triyne 1 has previously been synthesized by Bohlmann
et al. using a Wittig reaction, ref 8a.
(13) 1-Phenylhepta-1,3,5-triyne (2) has previously been synthesized
by Cadiot-Chodkiewicz coupling and elimination protocols: (a) Meier,
J .; Chodkiewicz, W.; Cadiot, P.; Willemart, A. C. R. Hebd. Se´ances
Acad. Sci. 1957, 245, 1634-1636. (b) Mavrov, M. V.; Kucherov, V. F.
Bull. Acad. Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1966, 833-836.
(c) Shim, S. C.; Lee, T. S. Bull. Korean Chem. Soc. 1986, 7, 357-362.
(6) Chemistry and Biology of Naturally-Occurring Acetylenes and
Related Compounds (NOARC); Lam, J ., Breteler, H., Arnason, T.,
Hansen, L., Eds.; Bioactive Molecules, Vol. 7; Elsevier: New York,
1988.
10.1021/jo034734g CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/31/2003
6810
J . Org. Chem. 2003, 68, 6810-6813

SCHEME 1a
SCHEME 2a
a
Reagents and conditions: (a) Me3Si(CtC)nSiMe3, AlCl3, CH2Cl2,
0 °C. (b) PPh3 (2 equiv), CBr4, CH2Cl2, rt. (c) n-BuLi, hexanes,
-78 to -40 °C. (d) K2CO3, MeOH/THF. (e) n-BuLi, THF, -78 °C,
then Mel, -78 °C to rt.
a
Reagents and conditions: (a) Me3Si(CtC)nMe, AlCl3, CH2Cl2,
0 °C. (b) PPh3 (2 equiv), CBr4, CH2Cl2, rt. (c) n-BuLi, hexanes,
-78 to -40 °C.
rangement15 recently developed by our group.16 The
synthesis of the dibromoolefin precursors is easily achieved
in three procedurally facile steps from commercially
available carboxylic acids or aldehydes, rendering this
route a viable alternative to previous methods for acety-
lenic natural product synthesis.12-14
SCHEME 3a
Ene-triyne 1 was synthesized as shown in Scheme 1.
Friedel-Crafts acylation of 3-(2-furyl)acryloyl chloride
with 1,4-bis(trimethylsilyl)-1,3-butadiyne gave ketone 5,
and dibromoolefination produced compound 6. Subjecting
dibromoolefin 6 to n-BuLi at -78 °C in hexanes gave ene-
triyne 7 in an excellent 82% yield. Protiodesilylation of
7 with K2CO3 afforded the corresponding terminal ene-
triyne, which was then converted to the lithium acetylide.
Methylation with methyl iodide gave the target ene-
triyne 1 (11% overall yield).17
Likewise, the diyne analogue of compound 1, 2-hept-
1-ene-3,5-diynylfuran (4), was synthesized via a similar
sequence of Friedel-Crafts acylation to provide ketone
8, dibromoolefination to 9, and rearrangement to 10.
Protiodesilylation of 10, lithiation of the corresponding
terminal ene-diyne, and subsequent methylation fur-
nished 4 in 11% overall yield.
Clearly, the weakest step in the above scheme involves
methylation of the unstable terminal alkyne to afford
either 1 or 4, so a more effective synthetic pathway for
targets 1 and 4 was explored (Scheme 2). Friedel-Crafts
acylation with trimethylsilylpenta-1,3-diyne18 gave the
ketone 11 directly from 3-(2-furyl)acryloyl chloride. Di-
bromoolefination provided 12, and rearrangement pro-
duced the desired product, ene-triyne 1, in 84% yield.
This amounted to an overall yield of 21%, a 2-fold
increase relative to the previous synthetic scheme for
compound 1.
a
Reagents and conditions: (a) Me3SiCtCMe, AlCl3, CH2Cl2,
0 °C. (b) PPh3 (2 equiv), CBr4, CH2Cl2, rt. (c) n-BuLi, hexanes,
-78 to -40 °C.
Similarly, ene-diyne 4 was synthesized via a sequence
of Friedel-Crafts acylation with trimethylsilylpropyne
to produce ketone 13, dibromoolefination to give 14, and
carbenoid rearrangement of 14 to afford the desired
product 4 in 59% yield. Thus, the overall yield of 13% is
slightly higher than that for the previous synthetic route
and consists of one less step. Somewhat surprising is the
fact that dibromoolefins 9 and 14 are less stable than
their diyne counterparts 6 and 12, which ultimately
lowers the overall yield of 4 in both cases.
1-Phenylhepta-1,3,5-triyne (2) was synthesized (Scheme
3) starting from a Friedel-Crafts acylation reaction of
phenylpropiolyl chloride with trimethylsilylpropyne, giv-
ing ketone 15 in 56% yield.19 Dibromoolefination yielded
compound 16 (67%), and subjecting 16 to n-BuLi pro-
duced 1-phenylhepta-1,3,5-triyne (2) in 18% overall yield.
The synthesis of atractylodin (3) is outlined in Scheme
4. The lithium acetylide 17 was generated from 1,1-
dibromo-1,3-pentadiene20 and reacted with 2-furan-
acrolein to give alcohol 18 (54% yield over two steps).
Oxidation of 18 to ketone 19, followed by dibromoole-
fination, yielded compound 20 (58%). Finally, rearrange-
ment of dibromoolefin 20 gave atractylodin 3 in 13%
overall yield.
(14) Atractylodin (3) has been synthesized by oxidative coupling,
but no yield was reported: Yosioka, I.; Hikino, H.; Sasaki, Y. Chem.
Pharm. Bull. 1960, 8, 957-959.
(15) (a) Fritsch, P. Liebigs Ann. Chem. 1894, 279, 319-323. (b)
Buttenberg, W. P. Liebigs Ann. Chem. 1894, 279, 324-337. (c) Wiechell,
H. Liebigs Ann. Chem. 1894, 279, 337-344.
(16) (a) Eisler, S.; Tykwinski, R. R. J . Am. Chem. Soc. 2000, 122,
10736-10737. (b) Chernick, E. T.; Eisler, S.; Tykwinski, R. R.
Tetrahedron Lett. 2001, 42, 8575-8578. (c) Shi Shun, A. L. K.;
Chernick, E. T.; Eisler, S.; Tykwinski, R. R. J . Org. Chem. 2003, 68,
1339-1347. (d) Eisler, S.; Chahal, N.; McDonald, R.; Tykwinski, R. R.
Chem. Eur. J . 2003, 9, 2542-2550.
(17) Transformation of the terminal triyne into its methylated
derivative 1 required that THF be used as solvent. Use of diethyl ether
was unsuccessful, consistent with that observed by Holmes and J ones
in a similar methylation reaction, see: Holmes, A. B.; J ones, E. G.
Tetrahedron Lett. 1980, 21, 3111-3112.
(18) Solladie´, G.; Colobert, F.; Kala¨ı, C. Tetrahedron Lett. 2000, 41,
4197-4200.
(19) Rule, G. N.; Detty, M. R.; Kaeding, J . E.; Sinicropi, J . A. J . Org.
Chem. 1995, 60, 1665-1673.
(20) Bestmann, H. J .; Frey, H. Liebigs Ann. Chem. 1980, 2061-
2071.
J . Org. Chem, Vol. 68, No. 17, 2003 6811

SCHEME 4a
room temperature, quenched with saturated aqueous NH4Cl,
and extracted with ether. After removal of the solvent under
reduced pressure, the resulting product was purified by flash
column chromatography (SiO2, hexanes) to give triyne 1 (34.4
mg, 35%) as a white solid that darkens to a yellow color: mp
63-66 °C; Rf 0.30 (hexanes); UV-vis (THF) λmax (ꢀ) 272 (14 600),
274 (14 600), 287 (29 100), 325 (19 100), 340 (29 900), 365
(29 000) nm; IR (CH2Cl2 cast) 3119, 3013, 2913, 2219, 2199, 2166,
1612, 1479, 1261 cm-1 1H NMR (400 MHz, CDCl3) δ 7.38 (d,
;
J ) 1.3 Hz, 1H), 6.84 (d, J ) 15.9 Hz, 1H), 6.40 (m, 2H), 6.04
(dd, J ) 15.9, 0.4 Hz, 1H), 1.99 (s, 3H); 13C NMR (100 MHz,
APT, CDCl3) δ 151.7, 143.8, 132.3, 112.2, 111.7, 103.9, 78.9, 77.7,
75.1, 68.5, 65.0, 59.2, 4.7; EI HRMS m/z calcd for C13H8O (M+)
180.0575, found 180.0574. Spectral data were consistent with
those reported in ref 8a.
2-Non -1-en -3,5,7-tr iyn ylfu r a n (1). Dibromoolefin 12 (0.139
g, 0.407 mmol) was reacted with n-BuLi (0.20 mL, 2.5 M in
hexanes, 0.49 mmol) as per the general procedure to give triyne
1 (61.9 mg, 84%) as a white solid that turns progressively yellow.
Spectral data were consistent with those for the triyne 1
obtained from the previous procedure.
1-P h en ylh ep ta -1,3,5-tr iyn e (2). Dibromoolefin 16 (0.131 g,
0.404 mmol) was reacted with n-BuLi (0.19 mL, 2.5 M in
hexanes, 0.49 mmol) as per the general procedure to give triyne
2 (31.9 mg, 48%) as a white solid: mp 58 °C; Rf 0.40 (hexanes);
UV-vis (THF) λmax (ꢀ) 241 (61 600), 252 (172 000), 276 (10 100),
292 (19 600), 311 (26 700), 333 (19 700) nm; IR (CH2Cl2 cast)
2220, 1593, 1490, 1441 cm-1; EI HRMS m/z calcd for C13H8 (M+)
164.0626, found 164.0624. Anal. Calcd for C13H8: C, 95.09; H,
4.91. Found C, 94.69; H, 4.64. Spectral data were consistent with
literature values.9b,10a,22
a
Reagents and conditions: (a) n-BuLi, THF, -78 °C to rt. (b)
THF, -78 °C to rt. (c) MnO2, CH2Cl2, rt. (d) PPh3 (2 equiv), CBr4,
CH2Cl2, rt. (e) n-BuLi, hexanes, -78 to -40 °C.
In conclusion, the applicability of an alkylidene car-
benoid rearrangement toward the synthesis of naturally
occurring acetylenes and their analogues has been dem-
onstrated by the total synthesis of acetylenes 1-4. The
usefulness of this method is emphasized by the fact that
the dibromoolefin precursors of this reaction can be easily
realized from commercially available carboxylic acids and
aldehydes. This feature eliminates the need for unstable
acetylenic precursors commonly required for other routes.
Exp er im en ta l Section
Gen er a l. Reagents were purchased reagent grade from
commercial suppliers and used without further purification. THF
was distilled from sodium/benzophenone ketyl, and hexanes
were distilled from CaH2 immediately prior to use. Anhydrous
MgSO4 was used as the drying agent after aqueous workup.
Evaporation and concentration in vacuo was done at H2O-
aspirator pressure. All reactions were performed in standard,
dry glassware under an inert atmosphere of N2. For mass
spectral analyses, low-resolution data are provided in cases when
M+ is not the base peak; otherwise, only high-resolution data
are provided.
Gen er a l P r oced u r e for Diyn e/Tr iyn e F or m a tion . Unless
otherwise noted, the following procedure was followed. To the
appropriate dibromoolefin (0.368 mmol) in dry hexanes (10 mL)
at -78 °C was added dropwise over 10 min 1.1-1.2 equiv of
n-BuLi (0.15 mL, 2.5 M in hexanes, 0.38 mmol). The mixture
was warmed to approximately -40 °C for 30 min, re-cooled to
-78 °C, and quenched with a saturated aqueous solution of
NH4Cl. Et2O was added (∼50 mL), and the organic layer was
separated, washed with brine, and dried over magnesium
sulfate. Solvent removal in vacuo and passing the residue
through a short plug of silica gel with the solvent system detailed
for each product afforded the desired diyne/triyne. If necessary,
additional purification could be achieved via flash column
chromatography.21
2-Non -1-en -3,5,7-tr iyn ylfu r a n (1). To a solution of triyne
7 (0.132 g, 0.554 mmol) in a 1:1 mixture of methanol (5 mL)
and THF (5 mL) at room temperature was added K2CO3 (5 mg).
After the reaction mixture was stirred for 1 h, saturated aqueous
NH4Cl (10 mL) was added and the solution was extracted with
ether (20 mL). Evaporation of the solvent in vacuo yielded a
white solid that was used directly in the next step. To a solution
of the deprotected triyne in THF (10 mL) at -78 °C was added
n-BuLi (0.22 mL, 2.5 M in hexanes, 0.55 mmol). After the
reaction mixture was stirred for 1 h, methyl iodide (0.70 mL,
1.6 g, 11 mmol) was added, and the reaction was warmed to
Atr a ctylod in (3). Dibromoolefin 20 (0.145 g, 0.424 mmol) was
reacted with n-BuLi (0.20 mL, 2.5 M in hexanes, 0.51 mmol) as
per the general procedure and purified by column chromatog-
raphy (pentane) to give diyne 3 (55.9 mg, 72%) as a white solid
that turns progressively pale yellow: mp 50-52 °C; Rf 0.18
(hexanes); UV-vis (THF) λmax (ꢀ) 260 (11 500), 273 (12 600), 339
(32 700) nm; IR (CDCl3 cast) 3113, 2182, 2124, 1616, 1477, 1442
cm-1 1H NMR (400 MHz, CDCl3) δ 7.37 (m, 1H), 6.77 (d, J )
;
15.9 Hz, 1H), 6.40 (dd, J ) 3.4, 1.8 Hz, 1H), 6.35 (m, 1H), 6.31
(m, 1H), 6.09 (d, J ) 15.9 Hz, 1H), 5.58 (m, 1H), 1.82 (dd, J )
6.9, 1.8 Hz, 3H); 13C NMR (100 MHz, APT, CDCl3) δ 151.9, 143.6,
143.5, 130.7, 112.1, 111.0, 110.0, 104.9, 81.9, 80.2, 77.2, 72.5,
18.9; EI HRMS m/z calcd for C13H10O (M+) 182.0732, found
182.0732. 1H and 13C NMR spectral data were consistent with
literature values.14,23
2-Hep t-1-en e-3,5-d iyn ylfu r a n (4). To a solution of diyne 10
(0.108 g, 0.505 mmol) in a 1:1 mixture of methanol (5 mL) and
THF (5 mL) at room temperature was added K2CO3 (5 mg). After
the reaction mixture was stirred for 1 h, saturated aqueous
NH4Cl (10 mL) was added and the solution was then extracted
with ether (20 mL). Evaporation of the solvent in vacuo yielded
a white solid that was used directly in the next step. To a
solution of the deprotected diyne in THF (10 mL) at -78 °C was
added n-BuLi (0.20 mL, 2.5 M in hexanes, 0.51 mmol). After
the reaction mixture was stirred for 1 h, methyl iodide (0.64 mL,
1.45 g, 10 mmol) was added, and the reaction was warmed to
room temperature, quenched with saturated aqueous NH4Cl,
and extracted with ether. After removal of the solvent under
reduced pressure, the resulting product was purified by flash
column chromatography (SiO2, hexanes) to give diyne 4 (31.2
mg, 40%) as a yellow oil: Rf 0.25 (hexanes); IR (CHCl3 cast) 3117,
1
3046, 2912, 2841, 2230, 2138, 1618, 1480, 1262 cm-1; H NMR
(400 MHz, CDCl3) δ 7.36 (d, J ) 1.8 Hz, 1H), 6.77 (d, J ) 16.0
Hz, 1H), 6.40 (dd, J ) 3.4, 1.8 Hz, 1H), 6.34 (d, J ) 3.4 Hz, 1H),
6.04 (d, J ) 16.0 Hz, 1H), 1.99 (s, 3H); 13C NMR (100 MHz, APT,
CDCl3) δ 151.9, 143.3, 130.7, 112.0, 110.7, 105.0, 81.3, 77.4, 73.8,
64.6, 4.7; EI HRMS m/z calcd for C11H8O (M+) 156.0575, found
156.0575.
(21) Empirical evidence suggests that lithium-halogen exchange
is more rapid than quenching of the n-BuLi by adventitious water.
Any water present in the reaction medium therefore results in in situ
protonation of the carbenoid intermediate. This extensively complicates
purification because of similar retention times on common chromato-
graphic supports, thus reiterating the need for strictly anhydrous
reagents and reaction conditions.
(22) (a) Shim, S. C.; Lee, T. S. Chem. Lett. 1986, 1075-1078. (b)
Chang, M. H.; Wang, G. J .; Kuo, Y. H.; Lee, C. K. J . Chin. Chem. Soc.
2000, 47, 1131-1136.
(23) Nishikawa, Y.; Yasuda, I.; Watanabe, Y.; Seto, T. Yakugaku
Zasshi 1976, 96, 1322-1326.
6812 J . Org. Chem., Vol. 68, No. 17, 2003

1
2-Hep t-1-en e-3,5-d iyn ylfu r a n (4). Dibromoolefin 14 (0.129
g, 0.409 mmol) was reacted with n-BuLi (0.20 mL, 2.5 M in
hexanes, 0.49 mmol) as per the general procedure to give diyne
4 (37.4 mg, 59%) as a yellow oil. Spectral data were consistent
with those for the diyne 4 obtained from the previous procedure.
[8-(2-F u r yl)-oct-7-en -1,3,5-tr iyn yl]tr im eth ylsila n e (7). Di-
bromoolefin 6 (60.0 mg, 0.151 mmol) was reacted with n-BuLi
(0.07 mL, 2.5 M in hexanes, 0.18 mmol) as per the general
procedure to give triyne 7 (29.5 mg, 82%) as an orange oil: Rf
0.31 (hexanes); IR (CHCl3 cast) 2959, 2160, 2074, 2070, 1612,
1479, 1251 cm-1; H NMR (400 MHz, CDCl3) δ 7.37 (d, J ) 1.8
Hz, 1H), 6.80 (d, J ) 16.0 Hz, 1H), 6.41 (dd, J ) 3.4, 1.8 Hz,
1H), 6.37 (d, J ) 3.4 Hz, 1H), 6.04 (d, J ) 16.0 Hz, 1H), 0.20 (s,
9H); 13C NMR (100 MHz, APT, CDCl3) δ 151.7, 143.6, 131.6,
112.1, 111.4, 104.2, 91.7, 88.0, 77.1, 76.5, -0.4; EI HRMS m/z
calcd for C13H14OSi (M+) 214.0814, found 214.0814.
Ack n ow led gm en t. We gratefully acknowledge the
University of Alberta and the Natural Sciences and
Engineering Research Council of Canada (NSERC) for
financial support.
1
1479, 1251 cm-1; H NMR (400 MHz, CDCl3) δ 7.39 (d, J ) 1.6
Hz, 1H), 6.87 (d, J ) 15.9 Hz, 1H), 6.41 (m, 2H), 6.05 (d, J )
15.9 Hz, 1H), 0.23 (s, 9H); 13C NMR (100 MHz, APT, CDCl3) δ
151.6, 144.0, 132.8, 112.3, 112.0, 103.5, 89.6, 88.1, 77.3, 76.8,
67.9, 61.8, -0.5; EI HRMS m/z calcd for C15H14OSi (M+)
238.0814, found 238.0814.
[6-(2-F u r yl)-h ex-5-en e-1,3-d iyn yl]t r im et h ylsila n e (10).
Dibromoolefin 9 (0.912 g, 2.44 mmol) was reacted with n-BuLi
(1.17 mL, 2.5 M in hexanes, 2.92 mmol) as per the general
procedure to give diyne 10 (0.366 g, 70%) as a yellow oil: Rf 0.3
(hexanes); IR (CHCl3 cast) 2959, 2925, 2188, 2101, 2095, 1616,
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal and spectroscopic details for precursor alcohols, ketones,
and dibromoolefins, and H and 13C NMR spectra for precursor
1
alcohols, ketones, dibromoolefins, and di- and triyne products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O034734G
J . Org. Chem, Vol. 68, No. 17, 2003 6813