Alkynylzirconation of alkynes and application to one-pot bisalkynylation of alkynes

Article abstract of DOI:10.1021/jo026037e

Stereocontrolled alkynylzirconation of unactivated alkynes was achieved by the reaction of an alkyne with Cp₂ZrEt₂ and alkynyl halide in this order. After hydrolysis of the alkynylzirconation product, trisubstituted enyne derivatives were obtained in good yields. Functionalized enynes were also prepared by the reaction of the alkynylzirconation products with a variety of electrophiles. Subsequent addition of the second alkynyl halide to the alkynylzirconation products provided an in situ protocol for bisalkynylation of alkynes into (Z)-enediynes in good yields.

Full text of DOI:10.1021/jo026037e

Alk yn ylzir con a tion of Alk yn es a n d Ap p lica tion to On e-P ot
Bisa lk yn yla tion of Alk yn es
Yuanhong Liu, Zhenqi Zhong, Kiyohiko Nakajima,† and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University and
CREST, Science and Technology Corporation (J ST), Sapporo 060-0811, J apan, and Department of
Chemistry, Aichi University of Education, Igaya, Kariya 448-8542, J apan
tamotsu@cat.hokudai.ac.jp
Received J une 10, 2002
Stereocontrolled alkynylzirconation of unactivated alkynes was achieved by the reaction of an alkyne
with Cp2ZrEt2 and alkynyl halide in this order. After hydrolysis of the alkynylzirconation product,
trisubstituted enyne derivatives were obtained in good yields. Functionalized enynes were also
prepared by the reaction of the alkynylzirconation products with a variety of electrophiles.
Subsequent addition of the second alkynyl halide to the alkynylzirconation products provided an
in situ protocol for bisalkynylation of alkynes into (Z)-enediynes in good yields.
In tr od u ction
Stereoselective carbometalation of alkynes is an at-
tractive method for the preparation of stereodefined
alkenylmetal compounds.1 This method has been suc-
cessfully applied for the synthesis of stereodefined di-,
tri-, or tetrasubstituted olefins. Especially, functionalized
carbometalation, such as acyl-,2 alkenyl-,3 and allylmeta-
lation,4 and metalloesterification5 of alkynes led to the
convenient formation of functionalized alkenes. However,
as for alkynylmetalation of alkynes (eq 1), only palladium
or nickel-catalyzed alkynylstannylation of alkynes has
been reported.6 This alkynylstannylation of alkynes is
useful for terminal or relatively electron-deficient alkynes.
There is no report, to our best knowledge, of alkynyl-
metalation of internal unactivated alkynes. In 1992, it
was reported that the zirconocene-cation complex,
[Zr(C5Me5) 2Me{B(4-C6H4F)4}], catalyzed the dimerization
reaction of terminal alkynes.7 The intermediate was
isolated in the case of t-Bu-substituted terminal alkyne
and it was shown that the intermediate was an alkyn-
ylzirconation product. From the viewpoint of organic
synthesis, however, we had to wait for development of a
more general method for the alkynylmetalation of unac-
tivated internal alkynes.
* Address correspondence to this author at Hokkaido University.
Fax: +81-11-706-3274.
† Aichi University of Education.
(1) For reviews on carbometalation of alkynes, see (a) Knochel, P.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, UK, 1991; Vol. 4, pp 865-911. (b) Negishi,
E. Acc. Chem. Res. 1987, 20, 65-72. (c) Normant, J . F.; Alexakis, A.
Synthesis 1981, 841-870. (d) Marek, I.; Normant, J . F. In Metal-
catalyzed Cross-coupling Reactions; Diederich, F., Stang, P. J ., Eds.;
Wileyvch, Weinheim, Germany, 1998; pp 271-337. (e) Lipshutz, B.
H.; Sengupta, S. Org. React. 1992, 41, 135-631.
(2) For acyl-metalation of alkynes, see: (a) Hoberg, H.; Schaefer,
D.; Burkhart, G.; Kru¨ger, C.; Romao, M. J . J . Organomet. Chem. 1984,
266, 203 and references therein. (b) Hoberg, H.; Apotecher, B. J .
Organomet. Chem. 1984, 270, C15. (c) DeShong, P.; Sidler, D. R.;
Rybczynski, P. J .; Slough, G. A.; Rheingold, A. L. J . Am. Chem. Soc.
1988, 110, 2575. (d) DeShong, P.; Sidler, D. R. J . Org. Chem. 1988,
53, 4892. (e) Takai, K.; Kataoka, Y.; Yoshizumi, K.; Oguchi, Y.; Utimoto,
K. Chem. Lett. 1991, 1479-1482.
(3) For alkenyl-metalation of alkynes, see the following. For Cu: (a)
Negishi, E. Acc. Chem. Res. 1987, 20, 65-72. (b) Normant, J . F.;
Cahiez, G.; Bourgain, M.; Chuit, C.; Villieras, J . Bull. Soc. Chim. Fr.
1974, 1656-1666. (c) Alexakis, A.; Normant, J . F. Tetrahedron Lett.
1982, 23, 5151-5154. (d) Furber, M.; Taylor, R. J . K.; Burford, S. C.
Tetrahedron Lett. 1985, 26, 3285-3288. (e) Furber, M.; Taylor, R. J .
K.; Burford, S. C. J . Chem. Soc., Perkin Trans. 1 1986, 1809-1815.
For Al: (f) Wilke, G.; Muller, H. Chem. Ber. 1956, 89, 444-447. (g)
Eisch, J . J .; Kaska. W. C. J . Am. Chem. Soc. 1966, 88, 2213-2220. (h)
Zweifel, G.; Snow, J . T.; Whitney, C. C. J . Am. Chem. Soc. 1968, 90,
7139-7141. For Mg: (i) Richey, H. G., J r.; Von Rein, F. W. J .
Organomet. Chem. 1969, 20, P32-35. For Zr: (j) Takahashi, T.;
Kondakov, D. Y.; Xi, Z.; Suzuki, N. J . Am. Chem. Soc. 1995, 117, 5871-
5872.
On the other hand, we have investigated the zirconium
approach for functionalization of unactivated alkynes via
the formation of zirconacycles. Here we found the alkyn-
ylzirconation could be achieved using the combination of
unactivated internal alkynes, alkynyl halides, and Cp2-
ZrEt2. In this paper we report the novel alkynylzircona-
tion of internal alkynes (eq 2). We also demonstrate here
(4) For allyl-metalation of alkynes, see the following. For Mg: (a)
Richey, H. G.; Von Rein, F. W. Tetrahedron Lett. 1971, 3777. (b) Eisch,
J . J .; Merkley, J . H.; Galle, J . E. J . Org. Chem. 1979, 44, 587. For Zn:
(c) Courtois, G.; Miginiac, L. J . Organomet. Chem. 1974, 69, 1. (d)
Bernardou, F.; Miginiac, L. J . Organomet. Chem. 1977, 125, 23. (e)
Negishi, E.; Miller, J . A. J . Am. Chem. Soc., 1983, 105, 6761-6763.
For Al: (f) Miller, J . A.; Negishi, E. Tetrahedron Lett. 1984, 25, 5863.
For Zr: (g) Suzuki, N.; Kondakov, D. Y.; Kageyama, M.; Kotora, M.;
Hara, R.; Takahashi, T. Tetrahedron 1995, 51, 4519-4540. (h) Taka-
hashi, T.; Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron Lett. 1994,
35, 5685. (i) Yamanoi, S.; Imai, T.; Matsumoto, T.; Suzuki, K.
Tetrahedron Lett. 1997, 38, 3031-3034. For Sn: (j) Shirakawa, E.;
Yamasaki, K.; Yoshida, H.; Hiyama, T. J . Am. Chem. Soc. 1999, 121,
10221-10222.
(5) Takahashi, T.; Xi, C.; Ura, Y.; Nakajima, K. J . Am. Chem. Soc.
2000, 122, 3228-3229.
(6) Shirakawa, E.; Yoshida, H.; Kurahashi, T.; Nakao, Y.; Hiyama,
T. J . Am. Chem. Soc. 1998, 120, 2975-2976.
(7) Horton, A. D. J . Chem. Soc., Chem. Commun. 1992, 185-187.
10.1021/jo026037e CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/25/2002
J . Org. Chem. 2002, 67, 7451-7456
7451

Liu et al.
the further reactions of alkynylzirconation products for
the stereoselective synthesis of conjugated enediynes.
alkynyl halides to give enynes 3a -g in 42-75% yields
after hydrolysis. It was notable that aryl-substituted
alkynyl halides usually afforded better results than alkyl-
substituted halides. These results are summarized in
Table 1.
Reactions of 2 with various electrophiles are shown in
Scheme 1 and Table 1.8 The alkynylzirconium product
2a reacted with allyl chloride or benzyl chloride in the
presence of a catalytic amount of CuCl to give the
corresponding products 7 and 8 in 87% and 76% NMR
yields, respectively. In the case of coupling with benzoyl
chloride, a stoichiometric amount of CuCl (1 equiv) was
used to obtain 9 in a good yield (72% isolated yield). The
reaction of 2a with p-trifluoromethyliodobenzene in the
presence of 5 mol % of Pd(PPh3)4 and 1 equiv of CuCl
gave the cross-coupling product 10 in 85% NMR yield.
The structure of 10 was characterized by X-ray study to
verify its stereochemistry.
Resu lts a n d Discu ssion
Alk yn ylzir con a tion of In ter n a l Alk yn es via Zir -
con a cycles. Treatment of internal alkynes 1 such as
diphenylacetylene, di(p-tolyl)acetylene, and di(2-thienyl)-
acetylene with Cp2ZrEt2 and alkynyl chloride (or bro-
mide) in this order afforded alkynylzirconation products
2a -d in high yields as shown in eq 3. When diphenyl-
acetylene was used as an internal alkyne and 1-phenyl-
ethynyl chloride was used as an alkynyl halide, alkyn-
ylzirconation product 2a was formed in 80% NMR yield.
Mech a n ism of Alk yn ylzir con a tion . We have re-
cently reported allylzirconation,4g,h vinylzirconation,3j and
esterzirconation reactions5 via zirconacyclopentenes. On
the basis of the results obtained here, it is reasonable to
propose that the alkynylzirconation reactions also pro-
ceed in a similar way. The mechanism is shown in
Scheme 2. It involves (i) the formation of zirconacyclo-
pentene 12 by the reaction of an alkyne with Cp2ZrEt2,9
(ii) replacement of ethylene by alkynyl halide through
â,â′-C-C bond cleavage of 12 to form a zirconacyclopen-
tadiene 13 with a halogen X at the â-position, which
might be in equilibrium with the regioisomer 14, and (iii)
â-halogen elimination of 13 to afford 2, which upon
hydrolysis gives enyne 3.
On e-P ot P r oced u r e for th e Syn th esis of En e-
d iyn es: cis-En ed iyn es. Alkynylzirconation described
above could be used for an efficient synthesis of (Z)-
enediynes in one pot from internal alkynes. Recently,
enediyne derivatives have attracted much attention since
they exist in bioactive compounds such as antitumor
agents,10 and as a substrate of the Masamune-Bergman
reaction.11 Although a variety of enediynes has been
synthesized, for example, by Pd-catalyzed cross coupling
of vinyl halides with terminal acetylenes,12 by elimination
of a silanol from R-silyl alcohols13 or by conversion of 1,5-
diynes into cis-enediynes after dehydration of prop-2-ynyl
alcohols,14 by reductive elimination,15 by acid or base-
induced elimination of alcohols, etc.,16 one-pot synthesis
of Z-enediynes from alkynes is very attractive. We
The 1H NMR spectrum of 2a in C6D6/THF (2:1) solution
showed a singlet peak at 6.3 ppm assigned to Cp protons.
Its 13C NMR spectrum revealed one singlet at 112.84 ppm
assigned to Cp ligands. Other characteristic signals
appeared at 89.75, 95.60, and 202.05 ppm which were
assignable to the two carbons of the CtC and one carbon
of the Zr-C(sp2) moiety, respectively. The chemical shift
of the two alkynyl carbons in the sp carbon region
indicated that the alkynyl substituent in 2a has no
interaction with the zirconium center. When di(p-tolyl)-
acetylene and di(2-thienyl)acetylene were used, the cor-
responding alkynylzirconation products 2c and 2d were
formed in 81% and 79% yields, respectively, with 1-phen-
ylethynyl chloride. In their 13C NMR spectra, signals
assigned to two carbons of the CtC appeared in a similar
region (89.37 and 95.84 ppm for 2c; 87.77 and 91.24 ppm
for 2d ). It is interesting to note that addition of 1 equiv
of MgBr2 to the solution of 2a with 1 h of stirring at room
temperature led to the halogen-exchange reaction of 2a .
As a result, the brominated analogue of 2a was obtained
as a mixture with 2a in a ratio of 2.3:1. This result
indicated that in order to obtain a clean chlorozirconium
product of 2, EtMgCl has to be used instead of EtMgBr
to prepare Cp2ZrEt2 from Cp2ZrCl2, although it did not
influence further reactions of 2 with electrophiles at all.
Hydrolysis of 2a afforded 1,3,4-triphenylbut-3E-en-1-
yne 3a in 75% isolated yield with high stereoselectivity
(isomerical purity >98%). Iodination of 2a with 1 equiv
of iodine gave iodinated product 4 in 74% yield. Bromi-
nation of 2a was cleanly achieved by the reaction with
NBS (88%). However, the use of NCS resulted in the
formation of a mixture of the desired chlorinated com-
pound 6 and hydrolysis product 3a in the ratio of 1:1.7
after hydrolysis. Alkynes bearing phenyl, 2-thienyl,
or alkyl substituents undergo alkynylzirconation with
(8) (a) Takahashi, T.; Kotora, M.; Xi, Z. J . Chem. Soc., Chem.
Commun. 1995, 1503-1504. (b) Takahashi, T.; Xi, Z.; Kotora, M.; Xi,
C.; Nakajima, K. Tetrahedron Lett. 1996, 37, 7521-7524. (c) Taka-
hashi, T.; Hara, R.; Nishihara, Y.; Kotora, M. J . Am. Chem. Soc. 1996,
118, 5154-5155. (d) Hara, R.; NIshihara, Y.; Landre, P. D.; Takahashi,
T. Tetrahedron Lett. 1997, 38, 447-450.
(9) Takahashi, T.; Suzuki, N.; Kageyama, M.; Nitto, Y.; Saburi, M.;
Negishi, E. Chem. Lett. 1991, 1579-1582.
(10) Wender, P. A.; Zercher, C. K.; Beckham, S.; Haubold, E.-M. J .
Org. Chem. 1993, 58, 5867.
(11) Lockhart, T. P.; Bergman, R. G. J . Am. Chem. Soc. 1981, 103,
4091.
(12) (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467-4470. (b) Sonogashira, K. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: New York,
1991; Vol 3, pp 521-549.
(13) Petasis, N. A.; Teets, K. A. Tetrahedron Lett. 1993, 34, 805.
(14) Yoshimatsu, M.; Yamada, H.; Shimizu, H.; Kataoka, T. J . Chem.
Soc., Chem. Commun. 1994, 2107-2108.
(15) Myers, A. G.; Dragovich, P. S. J . Am. Chem. Soc. 1992, 114,
5859-5860.
7452 J . Org. Chem., Vol. 67, No. 21, 2002

Alkynylzirconation of Alkyne
TABLE 1. Alk yn ylzir con a tion of Alk yn es: F or m a tion of F u n ction a lized En yn e Der iva tives
a
b
Except of hydrolysis, the reaction conditions shown here are the reactions of alkynylzirconation products with electrophiles. NMR
yields; isolated yields are given in parentheses. c EtMgCl was used to prepare Cp2ZrEt2. Combined yield. A mixture of chloro and hydrolysis
products was obtained in the ratio of 1:1.7. 10 mol % of CuCl was used. e 1 equiv of CuCl was used. f 5 mol % of Pd(PPh3)4 and 1 equiv
d
of CuCl were added.
SCHEME 1
expected that zirconium product 2 could react with the
second alkynyl halide to give cis-enediynes in one pot
(Scheme 1, product 11).
In the same way as described above for the formation
of 2, an alkyne was treated with Cp2ZrEt2 and the first
alkynyl halide in this order. To achieve (Z)-enediyne
formation cleanly, 1.0 equiv of the first alkynyl halide
was used. After addition of the second alkynyl halide
(1.25 equiv) and a catalytic amount of CuCl (0.1 equiv),
the mixture was stirred at 50°C for an additional 6 h.
The 1,3,4,6-tetrasubstituted en-1,5-diyne 11 was formed
in moderate to good yields. In all cases, only (Z)-
J . Org. Chem, Vol. 67, No. 21, 2002 7453

Liu et al.
SCHEME 2
TABLE 2. On e-P ot P r ep a r a tion of (Z)-En ed iyn es fr om
enediynes were obtained. For example, the reaction of
diphenylacetylene with phenylethynyl halide using Cp2-
ZrEt2 afforded 1,3,4,6-tetraphenyl-3-hexen-1,5-diyne 11a
in 63% isolated yield with exclusively cis configuration.
(Z)-Di(2-thienyl) and dialkyl enediynes were also ob-
tained (entries 2, 3, and 4). When two different alkynyl
halides were used, the unsymmetrical (Z)-enediyne 11f
was formed in 72% yield.
Un a ctiva ted In ter n a l Alk yn esa
Cis-Tr a n s Isom er iza tion of En ed iyn es: P r ep a r a -
t ion of tr a n s-E n ed iyn es. It was known that cis-
enediynes isomerize to trans under heating or irradia-
tion.17 (Z)-Enediynes obtained here also could be converted
into trans isomers in organic solvents. For example, in a
warm (50°C) THF solution of 11a , a ca. 2.3:1 mixture of
cis/trans isomers was obtained after 24 h. The trans
isomer of 11a crystallized from hexane/acetone (5/1)
solution. Thus pure trans-11a could be obtained. Simi-
larly, pure trans-11c was also prepared.
As described above, the alkynylzirconation reaction we
report here can provide various kinds of enyne deriva-
tives by the reaction of electrophiles. In particular, this
method provides a convenient route to a one-pot proce-
dure for bisalkynylation of internal alkynes.
Exp er im en ta l Section
All reactions were carried out with standard Schlenk
techniques under nitrogen. THF was distilled over sodium/
benzophenone. All commercial reagents were used without
further purification. Flash chromatography was performed
with Merck silica gel 60 (40-60 µm). Alkynyl halide was
prepared by the reaction of alkynyllithium with NCS or NBS.
1H and 13C NMR spectra were recorded in CDCl3 (containing
1% TMS) solutions at 400 and 100 MHz, respectively. All
melting points were determined by a micro melting point
apparatus and are uncorrected. IR spectra were measured with
a FT-IR spectrometer. Single-crystal X-ray diffraction data
were collected in Enraf-Nonius CAD4 diffractometers with
molybdenum or copper cathodes.
a
b
Alkynylzirconation products were prepared in situ. Isolated
yields. Reactions were carried out at 50 °C for 3-9 h in the
presence of 10 mol % CuCl.
(16) (a) Yoshimatsu, M.; Yamada, H.; Shimizu, H.; Kataoka, T. J .
Chem. Soc., Chem. Commun. 1994, 2107-2108. (b) Audrain, H.;
Skrydstrup, T.; Ulibarri, G.; Grierson, D. S. Synlett 1993, 20-22. (c)
Shibuya, M.; Sakai, Y.; Naoe, Y. Tetrahedron Lett. 1995, 36, 897-898.
(d) Iida, K.; Hirama, M. J . Am. Chem. Soc. 1995, 117, 8875-8876.
(17) It has been reported that enediynes undergo cis-trans isomer-
ization under heating or irradiation. (a) Vollhardt, K. P. C.; Winn. L.
S. Tetrahedron Lett. 1985, 26, 709-712. (b) Ko¨nig, B.; Schofield, E.;
Bubenitschek, P.; J ones, P. G. J . Org. Chem. 1994, 59, 7142-7143. (c)
Martin, R. E.; Bartek, J .; Diederich, F.; Tykwinski, R. R.; Meister, E.
C.; Hilger, A.; Lu¨thi, H. P. J . Chem. Soc., Perkin Trans. 1998, 233. (d)
Shimizu, T.; Miyasaka, D.; Kamigata, N. Org. Lett. 2000, 2, 1923-
1925. (e) Diederich, F. Chem. Commun. 2001, 219-227.
A Typ ica l P r oced u r e for th e Alk yn ylzir con a tion of
Alk yn es. 1,3,4-Tr ip h en yl-4-[bis(η5-cyclop en ta d ien yl)ch lo-
r ozir con iu m ]bu t-3Z-en -1-yn e (2a ). To a solution of Cp2ZrCl2
(0.36 g, 1.25 mmol) in THF (5 mL) was added EtMgCl (1.0 M
THF solution, 2.5 mmol) at -78°C and the mixture was stirred
for 1 h at the same temperature. Diphenylacetylene (0.18 g, 1
mmol) was added and the mixture was warmed to 0 °C. After
the mixture was stirred for 1 h, phenylethynyl chloride (0.17
g, 1.0 mmol) was added and stirring was continued at room
temperature for 3 h or at 50°C for 1 h. Alkynylzirconation
product 2a was cleanly formed in 80% NMR yield. 1H NMR
7454 J . Org. Chem., Vol. 67, No. 21, 2002

Alkynylzirconation of Alkyne
(C6D6/THF: 2/1, Me4Si): δ 6.28 (s, 10H), 6.81-6.92 (m, 5H),
6.93-7.05 (m, 5H), 7.31-7.55 (m, 5H). 13C NMR (C6D6/THF,
Me4Si): δ 89.75, 95.60, 112.84, 124.57, 126.32, 127.76, 127.94,
128.16, 128.30, 128.39, 128.60, 128.98, 129.06, 129.28, 131.60,
141.40, 202.11. HRMS calcd for C32H25ClZr 534.0692, found
534.0698.
91.16, 124.76, 127.20, 127.60, 128.00 (2C), 128.34, 128.99,
129.21, 135.05, 136.36, 138.30. IR (neat): 3024, 2922, 2181,
1599, 1495, 760, 696 cm-1. Anal. Calcd for C22H24: C, 91.61;
H, 8.39. Found: C, 91.28, H, 8.47.
1,2-Dip h en yloct-1E-en -3-yn e (3d ): 47% (isolated); pale
yellow oil. 1H NMR (CDCl3, Me4Si): δ 0.93 (t, J ) 7.26 Hz,
3H), 1.41-1.50 (m, 2H), 1.53-1.60 (m, 2H), 2.38 (t, J ) 7.05
Hz, 2H), 6.95 (s, 1H), 7.02-7.05 (m, 2H), 7.11-7.16 (m, 3H),
7.23-7.29 (m, 3H), 7.32-7.36 (m, 2H). 13C NMR (CDCl3, Me4-
Si) δ 13.65, 19.26, 22.04, 30.86, 83.29, 91.08, 124.76, 127.21,
127.62, 128.01, 128.36, 128.99, 129.21, 135.08, 136.36, 138.29.
1-(p -Tolyl)-3,4-d ip h en yl-4-[b is(η5-cyclop en t a d ien yl)-
ch lor ozir con iu m ]bu t-3Z-en -1-yn e (2b). NMR yield: 83%.
1H NMR (C6D6/THF: 2/1, Me4Si): δ 2.09 (s, 3H), 6.27 (s, 10H),
6.84-6.85 (m, 2H), 6.86-6.99 (m, 8H), 7.37-7.42 (m, 4H). 13
C
NMR (C6D6/THF, Me4Si) δ 21.27, 89.94, 94.96, 112.79, 121.59,
126.33, 127.80, 128.35, 128.63, 128.80, 129.01, 129.30, 129.80,
IR (neat): 3019, 2276, 1599, 1496, 1442, 918, 756, 698 cm-1
HRMS calcd for C20H20 260.1565, found 260.1566.
.
131.56, 131.92, 138.46, 141.45, 201.62. HRMS calcd for C33H27
ClZr 548.0848, found 548.0829.
-
1-(p-Tolyl)-3,4-d i(2-th ien yl)bu t-3E-en -1-yn e (3e): 42%
1
1-P h en yl-3,4-di(p-tolyl)-4-[bis(η5-cyclopen tadien yl)ch lo-
r ozir con iu m ]bu t-3Z-en -1-yn e (2c). NMR yield: 81%. 1H
NMR (C6D6/THF: 2/1, Me4Si): δ 2.03 (s, 3H), 2.12 (s, 3H), 6.30
(s, 10H), 6.81-6.92 (m, 5H), 7.17-7.21 (m, 4H), 7.35 (d, J )
8.3 Hz, 2H), 7.53 (d, J ) 8.3 Hz, 2H). 13C NMR (C6D6/THF,
Me4Si): δ 20.93, 21.20, 89.37, 95.84, 112.49, 124.73, 128.35,
128.53, 128.84, 129.04, 129.53, 129.68, 131.59, 131.84, 132.24,
135.65, 136.42, 138.72, 201.85. HRMS calcd for C34H29ClZr
562.1005, found 562.1013.
(isolated); yellow oil. H NMR (CDCl3, Me4Si): δ 2.35 (s, 3H),
6.92-6.94 (m, 1H), 7.06-7.08 (m, 2H), 7.12 (d, J ) 8.06 Hz,
2H), 7.18 (d, J ) 5.00 Hz, 1H), 7.21 (dd, J ) 3.5, and 0.91 Hz,
1H), 7.26 (d, J ) 8.06 Hz, 1H), 7.35 (d, J ) 8.07 Hz, 2H), 7.43
(d, J ) 5.08 Hz, 1H). 13C NMR (CDCl3, Me4Si) δ 21.53, 90.70,
90.80, 114.46, 120.02, 126.53, 127.22, 127.30, 127.83, 128.01,
129.06, 130.20, 131.41, 131.58, 138.44, 139.15. IR (Nujol):
3096, 2191, 1601, 1508, 1228, 700 cm-1. Anal. Calcd for
C
19H14S2: C, 74.47; H, 4.60; S, 20.93. Found: C, 74.28; H, 4.81;
S, 20.73.
1-P h en yl-3-eth ylh ex-3E-en -1-yn e (3f): 58% (isolated);
1-P h en yl-3,4-d i(2-th ien yl)-4-[bis(η5-cyclop en ta d ien yl)-
ch lor ozir con iu m ]bu t-3Z-en -1-yn e (2d ). NMR yield: 79%.
1H NMR (C6D6/THF: 2/1, Me4Si): δ 6.16 (s, 10H), 6.54 (d, J )
3.5 Hz, 1H), 6.76 (dd, J ) 5.0, 3.8 Hz, 1H), 6.99 (dd, J ) 5.0,
3.6 Hz, 1H), 7.16-7.23 (m, 5H), 7.45 (dd, J ) 3.6, 1.0 Hz, 1H),
7.57-7.60 (m, 2H). 13C NMR (C6D6/THF, Me4Si): δ 87.77,
91.24, 109.88, 121.98, 123.74, 123.97, 124.13, 124.89, 126.34,
126.68, 126.78, 127.14, 127.89, 129.09, 129.69, 141.42, 189.99.
HRMS calcd for C28H21ClS2Zr 545.9820, found 545.9818.
F or m a tion of a Br om in a ted Alk yn ylzir con a tion P r od -
u ct by Ha logen -Exch a n ge Rea ction . To a solution of 2a
described above was added 1 mmol of MgBr2. The mixture was
stirred at room temperature for 1 h. The brominated product
was formed in the ratio of 1:2.3 to 2a . When Cp2ZrEt2 derived
from EtMgBr and alkynyl chloride were used to prepare
compound 2, formation of a mixture of chloro- and bromozir-
conocene complexes with the same ratio was observed. 1,3,4-
Tr ip h en yl-4-[bis(η5-cyclop en ta d ien yl)br om ozir con iu m ]-
bu t-3Z-en -1-yn e: 1H NMR (C6D6/THF: 2/1, Me4Si): δ 6.30
(s, 10H), 6.80-7.10 (m, 5H), 7.10-7.58 (m, 10H). 13C NMR
(C6D6/THF, Me4Si) δ 89.45, 95.30, 112.36, 124.49, 126.48,
127.17, 127.65, 127.69, 128.44, 128.75, 128.96, 129.48, 129.74,
131.18, 131.82, 141.49, 202.30.
1,3,4-Tr ip h en ylbu t-3E-en -1-yn e (3a ). Quenching the re-
action mixture of 2a with 3 N HCl afforded 3a , which was
purified by chromatography on silica (hexane) and afforded
the product in 75% yield: white solid, mp 63-65 °C. 1H NMR
(CDCl3, Me4Si): δ 7.07-7.09 (m, 2H), 7.11 (s, 1H), 7.12-7.17
(m, 3H), 7.26-7.33 (m, 6H), 7.42-7.45 (m, 2H), 7.46-7.48 (m,
2H). 13C NMR (CDCl3, Me4Si): δ 89.79, 92.22, 123.30, 124.20,
127.60, 127.84, 128.09, 128.16, 128.26, 128.51, 129.04, 129.34,
131.56, 136.05, 136.42, 137.71. IR (Nujol): 3020, 2305, 1595,
1490, 1442, 920, 756, 719 cm-1. Anal. Calcd for C22H16: C,
94.25; H, 5.75. Found: C, 94.22; H, 5.73.
pale yellow oil. 1H NMR (CDCl3, Me4Si): δ 1.02 (t, J ) 7.52
Hz, 3H), 1.15 (t, J ) 7.52 Hz, 3H), 2.15 (q, J ) 7.52 Hz, 2H),
2.23 (q, J ) 7.52 Hz, 2H), 5.93 (t, J ) 7.48 Hz, 1H), 7.25-7.32
(m, 3H), 7.41-7.44 (m, 2H). 13C NMR (CDCl3, Me4Si): δ 13.33,
13.93, 21.57, 23.93, 86.76, 91.47, 123.86, 124.09, 127.65,
128.21, 131.43, 139.36. IR (Nujol): 2995, 2168, 1599, 758, 712
cm-1. HRMS calcd for C14H16 184.1263, found 184.1252.
1-P h en yl-3-bu tyloct-3E-en -1-yn e (3g): 52% (isolated);
pale yellow oil. 1H NMR (CDCl3, Me4Si): δ 0.91-0.96 (m, 6H),
1.33-1.42 (m, 6H), 1.52-1.60 (m, 2H), 2.14-2.24 (m, 4H), 5.96
(t, J ) 7.56 Hz, 1H), 7.25-7.32 (m, 3H), 7.41-7.43 (m, 2H).
13C NMR (CDCl3, Me4Si): δ 13.97, 14.05, 22.33, 22.40, 28.04,
30.39, 30.71, 31.50, 86.48, 91.90, 123.06, 123.91, 127.61,
128.20, 131.42, 138.56. IR (Nujol): 2950, 2202, 1599, 758, 690
cm-1. HRMS calcd for C18H24 240.1877, found 240.1892.
Rea ction of Vin ylzir con ocen e P r od u ct 2 w ith Elec-
tr op h iles. To a solution of vinylzirconocene 2 in THF were
added electrophiles such as allyl chloride, benzyl bromide,
p-trifluoromethyliodobenzene, and acyl chloride in the pres-
ence of a catalytic amount of Pd(PPh3)4 and/or CuCl. In the
cases of I2, NBS, and NCS, direct halogenation occurred
without CuCl. The reaction mixture was stirred for an ad-
ditional 3-6 h at 50°C, quenched with 3 N HCl, and extracted
with hexane. Combined organic extracts were washed with
aqueous NaHCO3 and water, dried over MgSO4, and concen-
trated in a vacuum. Column chromatography on silica gel
afforded the corresponding products.
4-Iod o-1-(p-tolyl)-3,4-d ip h en ylbu t-3Z-en -1-yn e (4): 55%
1
(isolated); brown oil. H NMR (CDCl3, Me4Si): δ 2.36 (s, 3H),
7.10-7.16 (m, 8H), 7.18-7.25 (m, 4H), 7.46 (d, J ) 7.9 Hz,
2H). 13C NMR (CDCl3, Me4Si): δ 21.58, 94.79, 95.11, 108.16,
119.87, 127.46, 127.93, 128.03, 129.12, 129.50, 129.96, 131.55,
133.08, 137.64, 138.97, 143.00. IR (Nujol): 3050, 2199, 1597,
1494, 928, 702 cm-1. Anal. Calcd for C23H17I: C, 65.73; H, 4.08;
I, 30.19. Found: C, 65.54; H, 4.19; I, 30.44.
1-p-Tolyl-3,4-d ip h en ylbu t-3E-en -1-yn e (3b): 66% (iso-
1
lated); white needles, mp 91-92°C. H NMR (CDCl3, Me4Si):
δ 2.34 (s, 3H), 7.07-7.09 (m, 2H), 7.11 (s, 2H), 7.13-7.15 (m,
4H), 7.29-7.33 (m, 3H), 7.36 (m, 2H), 7.41-7.44 (m, 2H). 13C
NMR (CDCl3, Me4Si): δ 21.51, 90.04, 91.60, 120.22, 124.37,
127.52, 127.80, 128.08, 128.50, 129.05, 129.07, 129.33, 131.46,
136.08, 136.15, 137.83, 138.31. IR (Nujol): 3020, 2193, 1595,
1508, 1442, 814, 700 cm-1. Anal. Calcd for C23H18: C, 93.84;
H, 6.16. Found: C, 93.79; H, 6.15.
4-Br om o-1-(p-tolyl)-3,4-diph en ylbu t-3Z-en -1-yn e (5): 79%
1
(isolated). H NMR (CDCl3, Me4Si): δ 2.38 (s, 3H), 7.16-7.20
(m, 8H), 7.24-7.27 (m, 4H), 7.46 (d, J ) 7.9 Hz, 2H). 13C NMR
(CDCl3, Me4Si): δ 21.56, 90.78, 96.29, 119.92, 126.41, 127.57,
127.98, 128.05, 128.48, 129.11, 129.35, 129.49, 130.10, 131.58,
137.75, 138.91, 139.45. IR (Nujol): 3085, 2189, 1597, 1442, 898,
708 cm-1. Anal. Calcd for C23H17Br: C, 74.00; H, 4.59; Br,
21.41. Found: C, 73.89; H, 4.65; Br, 21.30.
1,2-Dip h en yld ec-1E-en -3-yn e (3c): 42% (isolated); yellow
oil. 1H NMR (CDCl3, Me4Si): δ 0.89 (t, J ) 6.95 Hz, 3H), 1.27-
1.35 (m, 4H), 1.39-1.44 (m, 2H), 1.46-1.61 (m, 2H), 2.37 (t, J
) 7.10 Hz, 2H), 6.95 (s, 1H), 7.01-7.04 (m, 2H), 7.12-7.13
(m, 3H), 7.25-7.28 (m, 3H), 7.32-7.37 (m, 2H). 13C NMR
(CDCl3, Me4Si) δ 14.07, 19.57, 22.56, 28.63, 28.73, 31.34, 83.32,
4-Ch lor o-1-(p-tolyl)-3,4-diph en ylbu t-3Z-en -1-yn e (6): 49%
(combined yield with hydrolysis product). 1H NMR (CDCl3,
Me4Si): δ 2.36 (s, 3H), 7.16-7.20 (m, 8H), 7.24-7.27 (m, 4H),
7.41-7.43 (m, 2H). 13C NMR (CDCl3, Me4Si): δ 21.51, 88.72,
J . Org. Chem, Vol. 67, No. 21, 2002 7455

Liu et al.
97.13, 119.93, 122.96, 127.63, 127.97, 128.12, 128.64, 129.09,
129.60, 129.81, 131.60, 137.37, 137.45, 137.66, 138.85. IR
(Nujol): 3026, 2189, 1595, 1442, 1188, 814, 700 cm-1. HRMS
calcd for C23H17Cl 328.1019, found 328.1017.
1,3,4,6-Tetr aph en ylh exa-3E-en -1,5-diyn e (11a′): 60% (iso-
lated). Its NMR spectra were consistent with the published
data.17d
3,4-Di(2-t h ie n yl)-1,6-d i(p -t olyl)h e x-3Z-e n -1,5-d iyn e
(11b): 45% (isolated); yellow solid, mp 95-96°C. 1H NMR
(CDCl3, Me4Si): δ 2.35 (s, 6H), 6.96-6.98 (m, 2H), 7.11-7.13
(m, 4H), 7.19-7.22 (m, 2H), 7.31-7.32 (m, 2H), 7.43-7.45 (m,
4H). 13C NMR (CDCl3, Me4Si): δ 21.55, 90.13, 97.37, 120.04,
121.83, 126.91, 127.87, 129.14, 129.24, 131.49, 138.87, 139.25.
IR (Nujol): 2201, 1604, 1508, 814, 707 cm-1. Anal. Calcd for
1,3,4-Tr ip h en ylh ep t -3E-3,6-d ien -1-yn e (7): 75% (iso-
1
lated); white solid, mp 97-99°C. H NMR (CDCl3, Me4Si): δ
3.73 (d, J ) 6.60 Hz, 2H), 5.05 (dd, J ) 10.08 and 1.40 Hz,
2H), 5.86-5.95 (m, 1H), 7.07-7.20 (m, 10H), 7.31-7.33 (m,
3H), 7.47-7.50 (m, 2H). 13C NMR (CDCl3, Me4Si): δ 42.65,
90.27, 94.35, 116.34, 121.65, 123.64, 126.77, 127.02, 127.73,
127.92, 128.13, 128.32, 129.20, 129.85, 131.47, 134.97, 138.77,
140.66, 147.07. IR (Nujol): 3020, 2278, 1632, 1595, 916, 689
cm-1. Anal. Calcd for C25H20: C, 93.71; H, 6.29. Found: C,
93.88; H, 6.19.
C
28H20S2: C, 79.96; H, 4.79; S, 15.25. Found: C, 79.94; H, 4.84;
S, 15.39.
3,4-Dieth yl-1,6-d ip h en ylh ex-3Z-en -1,5-d iyn e (11c): 61%
(isolated); white oil. 1H NMR (CDCl3, Me4Si): δ 1.20 (t, J )
7.52 Hz, 6H), 2.60 (q, J ) 7.52 Hz, 4H), 7.26-7.36 (m, 6H),
7.45-7.48 (m, 4H). 13C NMR (CDCl3, Me4Si): δ 13.35, 25.32,
90.76, 94.30, 123.81, 128.02, 128.28, 130.22, 131.49. IR (Nu-
jol): 2963, 2201, 1599, 758, 692 cm-1. HRMS calcd for C22H20
284.1574, found 284.1565.
1,3,4,5-Tetr a p h en ylp en t-3E-1-yn e (8): 62% (isolated);
white needles, mp 106-107°C. 1H NMR (CDCl3, Me4Si): δ 4.32
(s, 2H), 6.93-6.95 (m, 2H), 7.06-7.08 (m, 4H), 7.11-7.15 (m,
4H), 7.20-7.25 (m, 4H), 7.29-7.32 (m, 4H), 7.44-7.45 (m, 2H).
13C NMR (CDCl3, Me4Si): δ 43.99, 90.83, 93.78, 122.08, 123.55,
126.08, 126.80, 126.95, 127.70, 127.83, 128.14, 128.30, 128.84,
129.33, 129.91, 131.51, 138.74, 139.19, 140.43, 148.16. IR
(Nujol): 3080, 2310, 1597, 1487, 914, 754, 698 cm-1. Anal.
Calcd for C29H22: C, 94.01; H, 5.99. Found: C, 94.13; H, 5.93.
3,4-Dip h en yl-4-p h en ylca r bon yl-1-(p-tolyl)bu t-3Z-en -1-
3,4-Dieth yl-1,6-d ip h en ylh ex-3E-en -1,5-d iyn e (11c′). This
isomer was obtained by isomerization: 39% (isolated); white
1
oil. H NMR (CDCl3, Me4Si): δ 1.22 (t, J ) 7.52 Hz, 6H), 2.60
(q, J ) 7.52 Hz, 4H), 7.30-7.35 (m, 6H), 7.45-7.48 (m, 4H).
13C NMR (CDCl3, Me4Si): δ 13.11, 28.43, 88.67, 98.77, 123.56,
128.15, 128.33, 130.25, 131.37. IR (Nujol): 2932, 2461, 1595,
1441, 756, 690 cm-1. Anal. Calcd for C22H20: C, 92.91; H, 7.09.
Found C, 92.87; H, 7.21.
1
yn e (9): 72% (isolated); white solid, mp 134-136°C. H NMR
(CDCl3, Me4Si): δ 2.34 (s, 3H), 7.10 (d, J ) 7.9 Hz, 2H), 7.14-
7.20 (m, 3H), 7.22-7.24 (m, 2H), 7.26-7.34 (m, 3H), 7.35-
7.41 (m, 3H), 7.45-7.47 (m, 2H), 7.76-7.78 (m, 2H), 7.86 (d,
J ) 7.8 Hz, 2H). 13C NMR (CDCl3, Me4Si): δ 21.55, 89.07,
96.58, 119.82, 125.29, 128.18, 128.19, 128.28, 128.37, 128.46,
128.82, 129.08, 129.09, 129.59, 131.50, 133.10, 136.92, 137.43,
138.22, 138.94, 145.47, 197.95. IR (Nujol): 3082, 2200, 1661,
1597, 1269, 818, 696 cm-1. Anal. Calcd for C30H22O: C, 90.42;
H, 5.56. Found: C, 90.47; H, 5.65.
3,4-Dibu tyl-1,6-d ip h en ylh ex-3Z-en -1,5-d iyn e (11d ): 41%
1
(isolated); pale yellow oil. H NMR (CDCl3, Me4Si): δ 0.96 (t,
J ) 7.30 Hz, 6H), 1.37-1.46 (m, 4H), 1.58-1.66 (m, 4H), 2.35
(t, J ) 7.56 Hz, 4H), 7.24-7.32 (m, 6H), 7.47-7.50 (m, 4H).
13C NMR (CDCl3, Me4Si): δ 14.02, 22.43, 30.89, 31.71, 91.04,
94.03, 123.79, 127.96, 128.24, 129.37, 131.46. IR (Nujol): 2932,
1599, 1450, 760, 696 cm-1. Anal. Calcd for C26H28: C, 91.71;
H, 8.29. Found: C, 91.76; H, 8.41.
3,4-Dip h en yl-4-(p -t r iflu or om et h ylp h en yl)-1-(p -t olyl)-
bu t-3Z-en -1-yn e (10): 71% (isolated); white solid, mp 153-
156°C. 1H NMR (CDCl3, Me4Si): δ 2.32 (s, 3H), 6.97-7.00 (m,
2H), 7.05-7.10 (m, 4H), 7.11-7.24 (m, 6H), 7.33-7.35 (m, 2H),
7.61 (d, J ) 8.3 Hz, 2H), 7.67 (d, J ) 8.4 Hz, 2H). 13C NMR
(CDCl3, Me4Si): δ 21.50, 91.07, 94.22, 120.07, 123.12, 124.54,
124.58, 124.62, 124.65, 127.35, 127.51, 127.97, 129.07, 129.89,
130.84, 131.04, 131.25, 138.55, 139.10, 140.68, 146.49, 146.66.
IR (Nujol): 3028, 2193, 1612, 1323, 698 cm-1. Anal. Calcd for
3,4-Dip h en yl-1,6-d it r im et h ylsilylh ex-3Z-en -1,5-d iyn e
(11e): 56% (isolated); white solid, mp 159-160°C. 1H NMR
(CDCl3, Me4Si): δ 0.15 (s, 18H), 7.02-7.14 (m, 10H). 13C NMR
(CDCl3, Me4Si): δ 0.03, 102.43, 106.04, 127.75, 127.92, 129.66,
129.84, 137.15. IR (Nujol): 2959, 2131, 1599, 1444, 842 cm-1
.
Anal. Calcd for C24H28Si2: C, 77.55; H, 7.57. Found: C, 77.85;
H, 7.40.
C
30H21F3: C, 82.17; H, 4.83; F, 13.00. Found: C, 82.19; H, 4.95;
F, 12.86.
A Typ ica l P r oced u r e for th e P r ep a r a tion of En ed iyn es
1,3,4-Tr ip h en yl-6-t r im et h ylsilylh ex-3Z-en -1,5-d iyn e
(11f): 72% (isolated); white solid, mp 130-131°C. 1H NMR
(CDCl3, Me4Si): δ 0.26 (s, 9H), 7.17-7.20 (m, 6H), 7.22-7.27
(m, 4H), 7.33-7.34 (m, 3H), 7.52-7.54 (m, 2H). 13C NMR
(CDCl3, Me4Si): δ 0.02, 91.55, 96.71, 102.30, 106.24, 123.28,
127.75, 127.83, 127.95, 128.02, 128.26, 128.50, 128.96, 129.63,
129.72, 130.14, 131.73, 137.12, 137.35. IR (Nujol): 2959, 2187,
1595, 1442, 842, 696 cm-1. Anal. Calcd for C27H24Si: C, 86.12;
H, 6.42. Found: C, 86.11; H,6.31.
a n d Isom er iza tion of cis-11a to tr a n s-11a . To a solution
of alkynylzirconation product 2a described above were added
phenylethynyl bromide (0.22 g, 1.25 mmol) and CuCl (0.01 g,
0.1 mmol) then the mixture was stirred at 50°C for 3 h. The
reaction mixture was quenched with 3 N HCl and extracted
with ethyl acetate. The extract was washed with brine and
water and dried over MgSO4. The solvent was evaporated in
vacuo and the residue was purified by chromatography on
silica (covered with aluminum foil to avoid the light) to
afforded cis-11a in 63% yield. When the cis isomer was kept
in hexane/acetone (5:1) solution for several days, the cis-trans
isomerization occurred and trans-11a (11a ′) was crystallized
from the solution in 60% yield.
Su p p or tin g In for m a tion Ava ila ble: Tables of crystal-
lographic data, atomic coordinates, thermal parameters, and
bond lengths and angles for 10 as well as spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1,3,4,6-Tetr a p h en ylh ex-3Z-en -1,5-d iyn e (11a ): 63% (iso-
lated). Its NMR spectra were consistent with the published
data.17d
J O026037E
7456 J . Org. Chem., Vol. 67, No. 21, 2002