Strictly "pair"-selective and economical synthesis of conjugated diynes via Pd-catalyzed reaction of terminal alkynes with 1,1-dichloroethylene, elimination with LDA, and subsequent transformations

Article abstract of DOI:10.1021/op034029+

Various unsymmetrically substituted conjugated diynes can be synthesized in a completely "pair"-selective manner via Pd-catalyzed reaction of terminal alkynes with 1,1-dichloroethylene in the presence of Pd(PPh₃)₄ followed by elimina

Full text of DOI:10.1021/op034029+

Organic Process Research & Development 2003, 7, 412−417
Strictly “ Pair” -Selective and Economical Synthesis of Conjugated Diynes via
Pd-Catalyzed Reaction of Terminal Alkynes with 1,1-Dichloroethylene,
Elimination with LDA, and Subsequent Transformations
Mingxing Qian and Ei-ichi Negishi*
Herbert C. Brown Laboratories of Chemistry, Purdue UniVersity, West Lafayette, Indiana 47907-2084, U.S.A.
Abstract:
applicable in a selective and satisfactory manner. The
authors’ group developed a strictly “pair”-selective route to
conjugated diynes via Pd-catalyzed alkynylation of ICHd
CHCl5 and ICHdCHBr,5b which has been shown to be
widely applicable, selective, and generally satisfactory6 (eq
2, Scheme 1). As selective and widely satisfactory as the
alkynyl-alkenyl coupling protocol5,6 is, the current costs of
1,2-dihaloethylenes are relatively high. With the goal of
developing a more economical route to conjugated diynes,
our attention was drawn to the Pd-catalyzed Sonogashira
alkynylation7 of inexpensive 1,1-dichloroethylene8 (eq 3,
Scheme 2). To the best of our knowledge, however, the
synthesis of conjugated diynes via 2-chloro-1-en-3-ynes (1)
prepared by this route has not been demonstrated in the
literature.9
Various unsymmetrically substituted conjugated diynes can be
synthesized in a completely “pair”-selective manner via Pd-
catalyzed reaction of terminal alkynes with 1,1-dichloroethylene
in the presence of Pd(PPh3)4 followed by elimination with 2
equiv of lithium diisopropylamide (LDA), zincation with ZnBr2
or ZnCl2, and Pd-catalyzed cross-coupling with aryl and alkenyl
iodides and bromides. The desired unsymmetrically substituted
conjugated diynes have been obtained in >80% yields except
in two cases where an alkenylzinc reagent generated in situ from
(E)-3-iodo-2-propenol was used. The use of 1,1-dichloroethylene
renders this method more economical than those involving 1,2-
dihaloethylenes previously reported.
Introduction
Conjugated diynes are frequently encountered part struc-
tures of natural products1 and compounds of material
chemical interest.2 These compounds, in the past, have been
most widely synthesized by the Cadiot-Chodkiewicz reac-
tion3 (eq 1, Scheme 1). More recently, various procedures
for Pd-catalyzed alkynyl-alkynyl coupling4 have been
reported as alternative routes. Although these alkynyl-
alkynyl coupling reactions are satisfactory in many cases,
they also suffer from cross-homo scrambling leading to the
formation of two homodiynes and low product yields in many
other cases. None of them has been shown to be widely
Results and Discussion
1. Preparation of 2-Chloro-1-en-3-ynes by the Pd-
Catalyzed Alkynylation of 1,1-Dichloethylene. Compari-
son of the Sonogashira and Negishi Protocols. In view
of the favorable results of the synthesis of 2-chloro-1-en-3-
ynes previously reported,8 n-HexCtCH, PhCtCH, and
Me3SiCtCH were chosen as three representative terminal
alkynes and converted into the corresponding 2-chloro-1-
en-3-ynes 1a-1c by their reaction with 5 molar equiv of
1,1-dichloroethylene according to the literature procedure.8
The desired compounds were obtained in 66%, 82%, and
69% yields by GLC, respectively. These yield figures are
somewhat lower than those reported, but the reported results
were reproduced more or less as described. The main
byproducts were the dialkynylation products. On the other
hand, the Negishi alkynylation protocol10 with the use of
alkynylzinc derivatives led to extensive formation of the
* Corresponding author. Telephone: 765-494-5301. Fax: 765-492-0239.
E-mail: negishi@purdue.edu.
(1) (a) For a recent example, see: Negishi, E.; Alimardanov, A.; Xu, C. Org.
Lett. 2000, 2, 65. (b) For recent reviews of natural products containing
conjugated diynes, see: Faulkner, D. J. Nat. Prod. Rep. 2001, 18, 1; 2002,
19, 1.
(2) For various applications of conjugated diynes in this area, see: (a) Tieke,
B.; Wegner, G.; Naegele, D.; Ringsdorf, H. Angew. Chem. 1976, 88, 805.
(b) Batchelder, D. N.; Evans, S. D.; Freeman, T. L.; Ha¨ussling, L.; Ringsdorf,
H.; Wolf, H. J. Am. Chem. Soc. 1994, 116, 1050. (c) Kim, T.; Crooks, R.
M. Tetrahedron Lett. 1994, 35, 9501. (d) Peek, B. M.; Callahan, J. H.;
Namboodiri, K.; Singh, A.; Gaber, B. P. Macromolecules 1994, 27, 292.
(e) Chang, J. Y.; Yeon, J. R.; Shin, Y. S.; Han, M. J.; Hong, S. K. Chem.
Mater. 2000, 12, 1076. (f) Lee, C. J.; Lee, S. J.; Chang, J. Y. Tetrahedron
Lett. 2002, 43, 3863.
(3) (a) Cadiot, P.; Chodkiewicz, W. In Chemistry of Acetylenes; Viehe, H. G.,
Ed.; Marcel Dekker: New York, 1969; p 597. (b) Brandsma, L.; Vasilevski,
S. F.; Verkruijsse, H. D. Application of Transition Metal Catalysts in
Organic Synthesis; Springer-Verlag: Berlin, 1999; p 49.
(5) (a) Negishi, E.; Okukado, N.; Lovich, S. F.; Luo, F. J. Org. Chem. 1984,
49, 2629. (b) Negishi, E.; Hata, M.; Xu, C. Org. Lett. 2000, 2, 3687.
(6) For a related paper, see: Kende, A. S.; Smith, C. A. J. Org. Chem. 1988,
53, 2655.
(7) (a) For a recent review, see: Sonogashira, K. In Handbook of Organopal-
ladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-Inter-
science: New York, 2002; p 493. (b) For a seminal paper, see: Sonogashira,
K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 16, 4467.
(8) Ratovelomanana, V.; Hammoud, A.; Linstrumelle, G. Tetrahedron Lett.
1987, 28, 1649.
(4) (a) King, A. O. Ph.D. Dissertation, Syracuse University, 1979, 45. (b)
Wityak, J.; Chan, J. B. Synth. Commun. 1991, 21, 977. (c) Hoye, T. R.;
Hanson, P. R. Tetrahedron Lett. 1993, 34, 5043. (d) Alzeer, J.; Vasella, A.
HelV. Chim. Acta. 1995, 78, 177. (e) Amatore, C. A.; Blart, E.; Geneˆt, J.
P.; Jutand, A.; Lemaire-Audoire, S.; Savignac, M. J. Org. Chem. 1995, 60,
6829. (f) Alami, M.; Ferri, F. Tetrahedron Lett. 1996, 37, 2763. (g)
Nishihara, Y.; Ikegashira, K.; Mori, A.; Hiyama, T. Tetrahedron Lett. 1998,
39, 4075.
(9) For a much different conversion of 1,1-dibromo-1-alkenes into mixtures of
unsymmetrical and symmetrical conjugated diynes, see: Shen, W.; Thomas,
S. A. Org. Lett. 2000, 2, 2857.
(10) (a) For a recent review, see: Negishi, E.; Xu, C. In Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; Wiley-
Interscience: New York, 2002; p 531. (b) For a seminal paper, see: King,
A. O.; Okukado, N.; Negishi, E. J. Chem. Soc., Chem. Commun. 1977,
683.
412
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10.1021/op034029+ CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/04/2003

Scheme 1
Scheme 2a,b
a By GLC. bFormation of 1% of 2 accounts for 2% of the starting alkyne.
dialkynylation products along with relatively low yields of
the desired products. The best results were obtained by using
then at -30 °C for another 30 min followed by addition of
dry ZnBr2 or ZnCl2 (-30 to 0 °C, 30 min) produced the
corresponding 1,3-diynylzinc derivatives 3a-3c in nearly
quantitative yields, as judged by the nearly quantitative
formation of 1-deuterio-1,3-diynes upon deuteriolysis with
D2O. (Scheme 3). 1,3-Diynes, in principle, can be converted
to a wide variety of unsymmetrically or symmetrically
disubstituted conjugated diynes by a variety of known
reactions. In this work, however, we opted for the preparation
of unsymmetrically disubstituted conjugated diynes by Pd-
catalyzed alkynylation of aryl and alkenyl halides with
alkynylzincs.10
As summarized in Table 1, all of the reactions carried
out with two aryl and five alkenyl iodides and bromides in
the presence of 5 mol % of Pd(PPh3)4 in THF at 23 °C
proceeded cleanly to produce the desired 1,3-diynes in over
80% isolated yields except in the reactions of (E)-3-iodo-
2-propenol, where the product yields were 67% and 71%.
As might be readily expected, there was no sign of the
formation of conjugated homodiynes throughout this study.
11
Pd(tBu3P)2 as a catalyst, as shown in eq 4, Scheme 2.
Clearly, the high intrinsic reactivity of organozincs must
be detrimental to this reaction. Since the corresponding
Pd-catalyzed alkynylation of 2-substituted 1,1-dichloro-1-
alkenes12 has been shown to proceed well and better under
Negishi conditions10 than under Sonogashira conditions,7 it
is advisable to experimentally determine the optimal protocol
for a given transformation of this type.
2. Conversion of 2-Chloro-1-en-3-ynes to Conjugated
Diynes via Elimination with LDA and Pd-Catalyzed
Alkynylation Using the Negishi Protocol. Treatment of
2-chloro-1-en-3-ynes (1a-1c) with 2.0 equiv of LDA
(lithium diisoproylamide) in THF at -78 °C for 30 min and
(11) For the use of Pd(tBu3P)2 in the Pd- or Ni-catalyzed C•C cross coupling,
see: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387. (b)
Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1999, 38, 2411. (c) Littke,
A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020. (d) Dai, C.;
Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719. (e) Littke, A. F.; Schwarz,
L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 6343
(12) Negishi, E.; Qian, M.; Zeng, F.; Anastasia, L.; Babinski, D. Manuscript in
preparation.
Vol. 7, No. 3, 2003 / Organic Process Research & Development
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413

Scheme 3
Table 1. Strictly “Pair”-Selective Synthesis of Unsymmetrically Disubstituted Conjugated Diynes via Pd-Catalyzed Cross
Coupling and â-Elimination
a All stereodefined products are >98-99% E by 13C and 1H NMR spectroscopy except for 3vii which is 91% E.
The reaction of 1-octyne with 5 equiv of (E)-1,2-
dichloroethylene in benzene in the presence of 5 mol % each
of Pd(PPh3)4 and CuI as well as n-BuNH2 (1.5 equiv)
produced (E)-1-chloro-1-decen-3-yne in 78% yield by GLC
along with the dialkynylation product (11%), as previously
reported.13 Sequential treatment of the chloroenyne obtained
previously with n-BuLi (2.0 equiv), dry ZnBr2 (1.1 equiv),
PhI (1 equiv), and 5 mol % of Pd(PPh3)4 in THF gave
1-phenyl-1,3-decadiyne in 89% yield by GLC. Similarly, the
corresponding cross-coupling reaction with methyl (E)-3-
bromo-2-methyl-2-propenoate gave the expected cross-
coupling product in 91% yield by GLC, while that with
1-iodo-1-octyne produced 7,9,11-octadecatriyne in 72% yield
by GLC. These results are roughly comparable to those
observed with 1,1-dichloroethylene. However, 1,2-dichloro-
ethylene appears to be significantly more expensive than 1,1-
dichloroethylene (their prices per 100 g in a recent Aldrich
catalog are $151.80 and $17.50, respectively).
In summary, the two-step synthesis of conjugated diynes
reported herein promises to be not only clean, selective,
(13) Ratovelomanana, V.; Linstrumelle, G. Tetrahedron Lett. 1981, 22, 315.
414
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Vol. 7, No. 3, 2003 / Organic Process Research & Development

widely applicable, and generally satisfactory but also the
most economical among all known methods.
mg, 1.0 mmol) in THF (4 mL) was added n-BuLi (0.4 mL
of 2.5 M hexane solution, 1.0 mmol) at -78 °C. The reaction
mixture was stirred at -78 °C for 30 min, treated with a
solution of anhydrous ZnBr2 (223 mg, 1.0 mmol) in THF (1
mL), and warmed to 0 °C over 30 min. 1,1-Dichloroethylene
(485 mg, 5.0 mmol) and Pd(tBu3P)2 (26 mg, 0.05 mmol)
was added to the reaction mixture at 0 °C, which was then
stirred at 23 °C for 6 h. Analysis of an aliquot of the reaction
mixture by GLC indicated the formation of the title
compound in 33% yield along with the dialkynylation
product formed in 22% yield.
A second reaction used Pd(PPh3)2Cl2 (35 mg, 0.05 mmol)
as catalyst. The reaction mixture was stirred at 50 °C for 4
h. Analysis of an aliquot of the reaction mixture by GLC
indicated the formation of the dialkynylation product in 35%
yield.
Experimental Section
General Methods. All reactions were run under Ar
atmosphere. Reactions were monitored by GLC analysis of
reaction aliquots. GLC analysis was performed on an HP6890
gas chromatograph by using an HP-5 capillary column (30
m × 0.32 mm, 0.5 µm film). GLC yields were determined
by using mesitylene as the internal standard. Column
chromatography was carried out on 230-400 mesh silica
1
gel. H and 13C NMR spectra were recorded on a Varian
Inova-300 spectrometer. Isomeric purity of the compounds
reported herein was determined by 1H and 13C NMR
spectroscopy. THF is distilled from sodium/benzophenone.
ZnBr2 was flame-dried at <1 mmHg.
Pd-Catalyzed Alkynylation of 1,1-Dichloroethylene
under the Sonogashira Conditions. (a) 2-Chloro-1-decen-
3-yne.8 Representative Procedure. The following experi-
ments were carried out according to the literature procedure.8
To a solution of Pd(PPh3)4 (1.44 g, 1.25 mmol) in benzene
(40 mL) was added 1,1-dichloroethylene (12.1 g, 125 mmol),
and the reaction mixture was stirred at 23 °C for 15 min. To
this were added a mixture of 1-octyne (2.76 g, 25 mmol)
and n-BuNH2 (2.74 g, 37.5 mmol) and then copper iodide
(0.24 g, 1.25 mmol). The reaction mixture was stirred for 5
h, and an aliquot was analyzed by GLC with mesitylene as
an internal standard. Analysis indicated the formation of the
title compound in 66% yield along with the dialkynylation
product in 5% yield. Then, the reaction mixture was
hydrolyzed with aqueous ammonium chloride, extracted with
Et2O, dried over MgSO4, filtered, and concentrated. Distil-
lation gave 2.56 g (60%) of the title compound as a colorless
Conversion of 2-Chloro-1-en-3-ynes to Conjugated
Unsymmetrically Substituted Diynes Wia Elimination with
LDA and Pd-Catalyzed Negishi Coupling. (i) 1-Phenyl-
1,3-decadiyne.5b Representative Procedure. To a solution
of N,N-diisopropylamine (223 mg, 2.2 mmol) in 4 mL of
THF was added n-BuLi (0.88 mL of 2.5 M solution in
hexane, 2.2 mmol) at 0 °C in a flame-dried flask under Ar
atmosphere. After 30 min, 2-chloro-1-decen-3-yne (187 mg,
1.1 mmol) in 1 mL of THF was added to the LDA solution
prepared previously by cannula at -78 °C. The reaction
mixture was stirred first at -78 °C for 30 min and then at
-30 °C for 30 min, treated with a solution of anhydrous
ZnBr2 (270 mg, 1.2 mmol) in THF (1 mL), and warmed to
0 °C over 30 min. Iodobenzene (204 mg, 1.0 mmol) and
Pd(PPh3)4 (58 mg, 0.05 mmol) were added to the reaction
mixture at 0 °C, which was then stirred at 23 °C for 3 h.
The reaction mixture was diluted with Et2O, washed with
aqueous NH4Cl and then with aqueous NaHCO3, dried over
MgSO4, filtered, and concentrated. Chromatography on silica
gel (hexane) gave 193 mg (92%) of the title compound as a
colorless oil: 1H NMR (CDCl3) 0.95 (t, J ) 6.6 Hz, 3 H),
1.3-1.65 (m, 8 H), 2.41 (t, J ) 7.0 Hz, 2 H), 7.3-7.5 (m,
5 H) ppm; 13C NMR (CDCl3) 14.35, 19.89, 22.84, 28.56,
28.88, 31.62, 65.42, 74.80, 74.98, 85.15, 122.45, 128.63
(2 C), 129.07, 132.77 (2 C) ppm.
(ii) (E)-7-Octadecen-9,11-diyne.5b The title compound
was prepared from 2-chloro-1-decen-3-yne (187 mg, 1.1
mmol) and (E)-1-iodo-1-octene (238 mg, 1.0 mmol). Puri-
fication by column chromatography (silica gel, hexane)
afforded 215 mg (88%) of the title compound as a colorless
oil: 1H NMR (CDCl3) 0.9-0.95 (m, 6 H), 1.3-1.6 (m, 16
H), 2.16 (q, J ) 7.0 Hz, 2 H), 2.35 (t, J ) 6.7 Hz, 2 H),
5.55 (d, J ) 15.9 Hz, 1 H), 6.3-6.4 (m, 1 H) ppm; 13C
NMR (CDCl3) 14.28, 14.29, 19.79, 22.79, 22.84, 28.57,
28.80 (2 C), 29.02, 31.58, 31.89, 33.49, 65.51, 73.15, 74.23,
83.82, 108.92, 148.38 ppm.
1
liquid: bp 78-80 °C (5 mmHg); H NMR (CDCl3) 0.93
(t, J ) 6.6 Hz, 3 H), 1.3-1.6 (m, 8 H), 2.38 (t, J ) 7.0 Hz,
2 H), 5.55 (s, 1 H), 5.58 (s, 1 H) ppm; 13C NMR (CDCl3)
14.24, 19.45, 22.75, 28.36, 28.79, 31.52, 77.81, 93.03,
120.51, 121.03 ppm.
(b) 2-Chloro-4-phenyl-1-buten-3-yne.8 The title com-
pound was prepared from phenylacetylene (2.55 g, 25 mmol)
and 1,1-dichloroethylene (12.1 g, 125 mmol). Distillation
afforded 3.25 g (80%) of the title compound as a yellow
1
liquid: yield by GLC, 82%; bp 95-97 °C (5 mmHg); H
NMR (CDCl3) 5.73 (d, J ) 1.0 Hz, 1 H), 5.80 (d, J ) 1.0
Hz, 1 H), 7.35-7.5 (m, 5 H) ppm; 13C NMR (CDCl3) 85.95,
90.87, 120.73, 121.86, 122.21, 128.74 (2 C), 129.58, 132.10
(2 C) ppm.
(c) 2-Chloro-4-trimethylsilyl-1-buten-3-yne.8 The title
compound was prepared from trimethylsilylacetylene (2.46
g, 25 mmol) and 1,1-dichloroethylene (12.1 g, 125 mmol).
Distillation afforded 2.46 g (62%) of the title compound as
a colorless liquid: GLC in 69% yield along with the
dialkynylation product in 4% yield; bp 57-59 °C (20
(iii) (E)-2-Tridecen-4,6-diyn-1-ol.14 To a solution of N,N-
diisopropylamine (223 mg, 2.2 mmol) in 4 mL of THF was
added n-BuLi (0.88 mL of 2.5 M solution in hexane, 2.2
mmol) at 0 °C in a flame-dried flask under Ar atmosphere.
1
mmHg); H NMR (CDCl3) 0.24 (s, 9 H), 5.64 (d, J ) 1.1
Hz, 1 H), 5.72 (d, J ) 1.1 Hz, 1 H) ppm; 13C NMR (CDCl3)
-0.29 (3 C), 96.78, 100.44, 120.45, 122.55 ppm.
Pd-Catalyzed Alkynylation of 1,1-Dichloroethylene
under the Negishi Conditions. 2-Chloro-1-decen-3-yne.
Representative Procedure. To a solution of 1-octyne (110
(14) For the synthesis of the Z isomer only, see: Zeni, G.; Menezes, P. H.; Moro,
A. V.; Braga, A. L.; Silveira, C. C.; Stefani, H. A. Synlett 2001, 1473.
Vol. 7, No. 3, 2003 / Organic Process Research & Development
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415

After 30 min, 2-chloro-1-decen-3-yne (187 mg, 1.1 mmol)
in 1 mL of THF was added to the LDA solution prepared
previously by cannula at -78 °C. The reaction mixture was
stirred first at -78 °C for 30 min and then at -30 °C for 30
min. Anhydrous ZnBr2 (270 mg, 1.2 mmol) in THF (1 mL)
was added to the reaction mixture at -30 °C and warmed
to 0 °C over 30 min. A solution of (E)-3-iodo-2-propen-1-
ol (184 mg, 1.0 mmol) in 2 mL of THF was treated with
Et2Zn (74 mg, 0.6 mmol) at 0 °C under Ar atmosphere. After
30 min, the reaction mixture was transferred by cannula,
and 3 mL of DMF were added by syringe. The mixture was
treated with Pd(PPh3)4 (58 mg, 0.05 mmol) into the first flask
at 0 °C, which was then stirred at 60 °C for 6 h. The reaction
mixture was diluted with Et2O, washed with aqueous NH4-
Cl and then with aqueous NaHCO3, dried over MgSO4,
filtered, and concentrated. Purification by column chroma-
tography (silica gel, hexane/EtOAc ) 80/20, v/v) afforded
127 mg (67%) of the title compound as a yellow oil: 1H
NMR (CDCl3) 0.93 (t, J ) 7.4 Hz, 3 H), 1.3-1.6 (m, 9 H),
2.36 (t, J ) 6.7 Hz, 2 H), 4.28 (d, J ) 3.5 Hz, 2 H), 5.85 (d,
J ) 16.0 Hz, 1 H), 6.35-6.45 (m, 1 H) ppm; 13C NMR
(CDCl3) 14.29, 19.81, 22.76, 28.46, 28.79, 31.54, 63.65,
65.25, 73.13, 75.34, 85.00, 109.56, 144.85 ppm. HRMS:
calculated for C13H18O, 190.1358; found, 190.1363.
(iv) Methyl (E)-2-Methyl-2-tridecen-4,6-diynoate.5b The
title compound was prepared from 2-chloro-1-decen-3-yne
(187 mg, 1.1 mmol) and methyl (E)-3-bromo-2-methyl-2-
propenoate (179 mg, 1.0 mmol). Purification by column
chromatography (silica gel, hexane/EtOAc ) 95/5, v/v)
afforded 209 mg (90%) of the title compound as a colorless
oil: 1H NMR (CDCl3) 0.93 (t, J ) 6.4 Hz, 3 H), 1.3-1.6
(m, 8 H), 2.13 (s, 3 H), 2.41 (t, J ) 6.9 Hz, 2 H), 3.80 (s,
3 H), 6.66 (s, 1 H) ppm; 13C NMR (CDCl3) 14.24, 15.86,
19.99, 22.74, 28.33, 28.79, 31.50, 52.38, 65.16, 71.30, 86.39,
89.41, 119.03, 141.97, 167.41 ppm.
(v) (E)-1-Trimethylsilyl-3-tetradecen-1,5,7-triyne. The
title compound was prepared from 2-chloro-1-decen-3-yne
(187 mg, 1.1 mmol) and (E)-1-bromo-4-trimethylsilyl-1-
buten-3-yne (203 mg, 1.0 mmol). Purification by column
chromatography (silica gel, hexane) afforded 218 mg (85%)
of the title compound as a colorless oil: 1H NMR (CDCl3)
0.23 (s, 9 H), 0.93 (t, J ) 6.6 Hz, 3 H), 1.3-1.6 (m, 8 H),
2.38 (t, J ) 6.9 Hz, 2 H), 6.07 (d, J ) 16.2 Hz, 1 H), 6.14
(d, J ) 16.2 Hz, 1 H) ppm; 13C NMR (CDCl3) -0.03 (3 C),
14.29, 19.95, 22.76, 28.39, 28.79, 31.53, 65.28, 73.23, 80.25,
87.86, 102.13, 103.09, 121.17, 123.52 ppm. HRMS: calcu-
lated for C17H24Si, 256.1647; found, 256.1647.
(vi) 1-Phenyl-4-(2-thienyl)-1,3-butadiyne.15 The title
compound was prepared from 2-chloro-4-phenyl-1-buten-3-
yne (179 mg, 1.1 mmol) and 2-iodothiophene (210 mg, 1.0
mmol). Purification by column chromatography (silica gel,
hexane) afforded 171 mg (82%) of the title compound as a
yellow oil: 1H NMR (CDCl3) 7.0-7.6(m, 8 H) ppm; 13C
NMR (CDCl3) 74.18, 75.00, 78.42, 84.00, 121.96, 122.36,
127.55, 128.83 (2 C), 129.09, 129.68, 132.80 (2 C), 134.65
ppm.
(vii) (E)-7-Phenyl-2-hepten-4,6-diyn-1-ol.16 To a solution
of N,N-diisopropylamine (223 mg, 2.2 mmol) in 3 mL of
THF was added n-BuLi (0.88 mL of 2.5 M solution in
hexane, 2.2 mmol) at 0 °C in a flame-dried flask under Ar
atmosphere. After 30 min, 2-chloro-4-phenyl-1-buten-3-yne
(179 mg, 1.1 mmol) in 1 mL of THF was added to the LDA
solution prepared previously by cannula at -78 °C. The
reaction mixture was stirred first at -78 °C for 30 min and
then at -30 °C for 30 min. Anhydrous ZnBr2 (270 mg, 1.2
mmol) in THF (1 mL) was added to the reaction mixture at
-30 °C, which warmed to 0 °C over 30 min. A solution of
(E)-3-iodo-2-propen-1-ol (184 mg, 1.0 mmol) in 2 mL of
THF was treated with Et2Zn (74 mg, 0.6 mmol) at 0 °C under
Ar atmosphere. After 30 min, the reaction mixture was
transferred by cannula, and 3 mL of DMF were added by
syringe. The mixture was treated with Pd(PPh3)4 (58 mg,
0.05 mmol) into the first flask at 0 °C, which was then stirred
at 60 °C for 6 h. The reaction mixture was diluted with Et2O,
washed with aqueous NH4Cl and then with aqueous NaH-
CO3, dried over MgSO4, filtered, and concentrated. Purifica-
tion by column chromatography (silica gel, hexane/EtOAc
) 80/20, v/v) afforded 129 mg (71%) of the title compound
as a yellow oil: 1H NMR (CDCl3) 1.51 (s, 1 H), 4.31 (s, 2
H), 5.94 (d, J ) 14.0 Hz, 1 H), 6.4-6.5 (m, 1 H), 7.3-7.5
(m, 5 H) ppm; 13C NMR (CDCl3) 62.96, 74.16, 74.77, 80.11,
81.59, 109.17, 122.03, 128.68 (2 C), 129.45, 132.73 (2 C),
145.75 ppm.
(viii) Methyl (E)-2-Methyl-7-phenyl-2-hepten-4,6-di-
ynoate. The title compound was prepared from 2-chloro-4-
phenyl-1-buten-3-yne (179 mg, 1.1 mmol) and methyl (E)-
3-bromo-2-methyl-2-propenoate (179 mg, 1.0 mmol). Puri-
fication by column chromatography (silica gel, hexane/
EtOAc ) 95/5, v/v) afforded 208 mg (93%) of the title
1
compound as a yellow oil: H NMR (CDCl3) 2.18 (s, 3 H),
3.82 (s, 3 H), 6.75 (s, 1 H), 7.35-7.5 (m, 5 H) ppm; 13C
NMR (CDCl3) 16.09, 52.49, 73.84, 78.10, 85.57, 85.69,
118.62, 121.64, 128.77 (2 C), 129.86, 132.79 (2 C), 142.63,
167.25 ppm. HRMS: calculated for C15H12O2, 224.0837;
found, 224.0838.
(ix) (E)-1-Bromo-6-phenyl-1-hexen-3,5-diyne. The title
compound was prepared from 2-chloro-4-phenyl-1-buten-3-
yne (163 mg, 1.0 mmol) and (E)-1-iodo-2-bromoethylene
(350 mg, 1.5 mmol). Purification by column chromatography
(silica gel, hexane) afforded 205 mg (89%) of the title
compound as a yellow oil: 1H NMR (CDCl3) 6.38 (d, J )
14.2 Hz, 1 H), 6.17 (d, J ) 14.2 Hz, 1 H), 7.3-7.55 (m, 5
H) ppm; 13C NMR (CDCl3) 73.92, 76.48, 78.13, 83.12,
116.93, 121.73, 122.66, 128.76 (2 C), 129.53, 132.80 (2 C)
ppm. HRMS: calculated for C12H7Br, 229.9731; found,
229.9725.
(x) (E)-1-Trimethylsilyl-8-phenyl-3-octen-1,5,7-triyne.
The title compound was prepared from 2-chloro-4-phenyl-
1-buten-3-yne (179 mg, 1.1 mmol) and (E)-1-bromo-4-
trimethylsilyl-1-buten-3-yne (203 mg, 1.0 mmol). Purification
by column chromatography (silica gel, hexane) afforded 216
mg (87%) of the title compound as a yellow oil: 1H NMR
(CDCl3) 0.25 (s, 9 H), 6.17 (d, J ) 16.0 Hz, 1 H), 6.23 (d,
(15) Ziegler, C. B., Jr.; Harris, S. M.; Baldwin, J. E. J. Org. Chem. 1987, 52,
443.
(16) Jones, S. E. R. H.; Safe, S.; Thaller, V. J. Chem. Soc. C 1967, 1038.
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J ) 16.0 Hz, 1 H), 7.3-7.55 (m, 5 H) ppm; 13C NMR
(CDCl3) -0.01 (3 C), 74.04, 79.66, 80.05, 84.29, 103.06,
120.79, 121.81, 124.17, 128.73 (2 C), 129.69, 132.78 (2 C)
ppm. HRMS: calculated for C17H16Si, 248.1021; found,
248.1021.
compound found in 11% yield. The reaction mixture was
hydrolyzed with aqueous ammonium chloride, extracted with
Et2O, dried over MgSO4, filtered, and concentrated. Distil-
lation gave the title compound 2.56 g (75%) as a colorless
liquid: bp 83-85 °C (5 mmHg); 1H NMR (CDCl3) 0.92 (t,
J ) 6.4 Hz, 3 H), 1.3-1.6 (m, 8 H), 2.3-2.35 (m, 2 H),
5.9-5.95 (m, 1 H), 6.47 (d, J ) 13.6 Hz, 1 H) ppm; 13C
NMR (CDCl3) 14.19, 19.60, 22.78, 28.74, 28.81, 31.58,
75.91, 93.55, 114.54, 122.82 ppm.
(xi) Methyl (E)-2-Methyl-7-trimethylsilyl-2-hepten-4,6-
diynioate. The title compound was prepared from 2-chloro-
4-trimethylsilyl-1-buten-3-yne (174 mg, 1.1 mmol) and
methyl (E)-3-bromo-2-methyl-2-propenoate (179 mg, 1.0
mmol). Purification by column chromatography (silica gel,
hexane) afforded 202 mg (92%) of the title compound as a
Conversion of (E)-1-Chloro-1-decen-3-yne to Conju-
gated Diynes Wia Elimination with n-BuLi and Pd-
Catalyzed Negishi Coupling. (a) 1-Phenyl-1,3-decadiyne
(3i).5b Representative Procedure. To a solution of (E)-1-
chloro-1-decen-3-yne (187 mg, 1.1 mmol) in 1 mL of THF
(4 mL) was added n-BuLi (0.88 mL of 2.5 M hexane
solution, 2.2 mmol) at -78 °C. The reaction mixture was
stirred first at -78 °C for 30 min and then at -30 °C for 30
min, treated with a solution of anhydrous ZnBr2 (270 mg,
1.2 mmol) in THF (1 mL), and warmed to 0 °C over 30
min. Iodobenzene (204 mg, 1.0 mol) and Pd(PPh3)4 (58 mg,
0.05 mmol) were added to the reaction mixture at 0 °C, which
was then stirred at 23 °C for 3 h, and an aliquot was analyzed
by GLC with mesitylene as an internal standard. Analysis
indicated the formation of the title compound in 89% yield.
(b) Methyl (E)-2-Tridecen-4,6-diynoate (3iv).5b The title
compound was prepared from (E)-1-chloro-1-decen-3-yne
(187 mg, 1.1 mmol) and methyl (E)-3-bromo-2-methyl-2-
propenoate (179 mg, 1.0 mmol): yield 91% by GLC.
(c) 7,9,11-Octadecatriyne. The title compound was
prepared from (E)-1-chloro-1-decen-3-yne (187 mg, 1.1
mmol) and 1-iodo-1-octyne (236 mg, 1.0 mmol): yield, 148
mg (61%, 72% by GLC); 1H NMR (CDCl3) 0.91 (t, J ) 6.4
Hz, 6 H), 1.3-1.6 (m, 16 H), 2.30 (t, J ) 6.9 Hz, 4 H)
ppm; 13C NMR (CDCl3) 14.27, 19.65, 22.76, 28.34, 28.77,
31.51, 60.64, 65.96, 79.59 ppm. HRMS: calculated for
C18H26, 242.2035; found, 242.2028.
1
colorless oil: H NMR (CDCl3) 0.26 (s, 9 H), 2.14 (s, 3 H),
3.80 (s, 3 H), 6.65 (s, 1 H) ppm; 13C NMR (CDCl3) -0.32
(3 C), 15.99, 52.43, 73.07, 85.61, 87.48, 95.09, 118.19,
143.31, 167.08 ppm. HRMS: calculated for C12H16O2Si,
220.0920; found, 220.0924.
(xii) (E)-1-Bromo-6-trimethylsilyl-1-hexen-3,5-diyne.
The title compound was prepared from 2-chloro-4-trimeth-
ylsilyl-1-buten-3-yne (159 mg, 1.0 mmol) and (E)-1-iodo-
2-bromoethylene (350 mg, 1.5 mmol). Purification by column
chromatography (silica gel, hexane) afforded 188 mg (83%)
of the title compound as a colorless oil: 1H NMR (CDCl3)
0.25 (s, 9 H), 6.30 (d, J ) 14.0 Hz, 1 H), 6.93 (d, J ) 14.0
Hz, 1 H) ppm; 13C NMR (CDCl3) -0.25 (3 C), 73.23, 76.58,
87.60, 92.62, 116.59, 123.26 ppm. HRMS: calculated for
C9H11BrSi, 225.9813; found, 225.9812.
(xiii) (E)-1-Trimethylsilyl-8-trimethylsilyl-3-octen-1,5,7-
triyne. The title compound was prepared from 2-chloro-4-
trimethylsilyl-1-buten-3-yne (174 mg, 1.1 mmol) and (E)-
1-bromo-4-trimethylsilyl-1-buten-3-yne (203 mg, 1.0 mmol).
Purification by column chromatography (silica gel, hexane)
afforded 210 mg (86%) of the title compound as a colorless
oil: 1H NMR (CDCl3) 0.23 (s, 9 H), 0.25 (s, 9 H), 6.07 (d,
J ) 16.0 Hz, 1 H), 6.19 (d, J ) 16.0 Hz, 1 H) ppm; 13C
NMR (CDCl3) -0.20 (3 C), -0.03 (3 C), 75.12, 79.82,
87.88, 93.56, 102.89, 103.13, 120.42, 124.81 ppm. HRMS:
calculated for C14H20Si2, 244.1104; found, 244.1109.
(E)-1-Chloro-1-decen-3-yne.13 Copper iodide (190 mg,
1 mmol) was added to a solution of (E)-1,2-dichloroethylene
(9.69 g, 100 mmol), 1-octyne (2.20 g, 20 mmol), n-BuNH2
(2.19 g, 30 mmol), and Pd(PPh3)4 (1.16 g, 1 mmol) in
benzene (40 mL) at 23 °C. The reaction mixture was stirred
for 5 h, and an aliquot was analyzed by GLC with mesitylene
as an internal standard. Analysis indicated the formation of
the title compound in 78% yield along with the dialkynylation
Received for review February 17, 2003.
Acknowledgment
The authors thank the National Science Foundation (CHE-
0080795) and Purdue University for support of this research.
OP034029+
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