SCHEME 3. Generation of Benzylzirconocene Intermediate 9
SCHEME 4. Transformations of Vinyl Bromide
Derivatives to Acetylene Derivatives
12a proceeded to give Dane’s diene 13a in 75% yield. In
enyne metathesis chemistry, a fluorine substituent on the
aromatic ring afforded fluorine analogue 13b in 52% yield
(Scheme 4).
In conclusion, we have demonstrated the efficient
generation and carbon-carbon bond formation of o-
alkenyl- or alkynylbenzylzirconocene intermediates with
allylic halide derivatives under CuCl-catalyzed condi-
tions. The enyne metathesis of the allylation product
derived from the o-alknylbenzylzirconocene intermediates
with Grubbs catalyst afforded Dane’s diene with high
efficiency, which is a key intermediate for the estrone
synthesis.
SCHEME 5. Enyne Metathesisa
Experimental Section
Typical Procedure for Allylations of o-Vinylbenzylzir-
conocene Intermediate. To a solution of Cp2ZrCl2 (153 mg,
0.525 mmol) in THF (5 mL) was added n-BuLi (1.6 M solution
in n-hexane, 0.66 mL, 1.05 mmol) at -78 °C, and the mixture
was stirred for 1 h. To this solution was added a solution of 1a
(112 mg, 0.5 mmol) in THF (2 mL), and the mixture was
gradually warmed to room temperature and stirred for 3 h. To
this reaction mixture was added a solution of allyl bromide (65
µL, 0.75 mmol) in THF (1 mL) and CuCl (5 mg, 0.05 mmol), and
then the mixture was refluxed for 5 h. After the mixture was
cooled to room temperature, 1 M HCl (aq) was added, and the
mixture was extracted with ether. The combined organic layer
was washed with brine and dried over anhydrous MgSO4, and
the filtrate was concentrated to dryness under reduced pressure.
The residue was purified by flash chromatography (n-hexane),
and further purification was carried out by MPLC (n-hexane)
to give 4a (70 mg, 88%).
1-(3-Butenyl)-2-vinylbenzene (4a). Colorless oil. IR (liquid
film): 2937, 1641, 1484, 991, 911, 772, 753. 1H NMR (CDCl3,
300 MHz): δ 7.53-7.49 (1H, m), 7.26-7.15 (3H, m), 7.02 (1H,
dd, J ) 17.3, 10.8 Hz), 5.90 (1H, dddd, J ) 17.0, 10.3, 6.7, 6.4
Hz), 5.68 (1H, dd, J ) 17.3, 1.5 Hz), 5.33 (1H, dd, J ) 10.8, 1.5
Hz), 5.12-4.99 (2H, m), 2.83-2.77 (2H, m), 2.39-2.31 (2H, m).
13C NMR (CDCl3, 75.5 MHz): δ 139.0, 137.8, 136.2, 134.3, 129.3,
127.5, 126.1, 125.6, 115.3, 114.7, 35.2, 32.9. EI-MS (m/z): 158
(M+). Anal. Calcd for C12H14: C, 91.08; H, 8.92. Found: C, 91.06;
H, 8.79.
a Reagents and conditions: (a) TBAF, THF, rt; (b) second-
generation Grubbs catalyst, CH2Cl2, rt.
it is possible to introduce a propargyl or allenyl group to
the benzylic position by the choice of the reaction.
Recent advances of the ring-closing metathesis (RCM)
provide a powerful tool for the synthesis of cyclic com-
pounds with a wide range of ring sizes. The present CuCl-
catalyzed allylation of 5b provides ene-yne compound 7b.
As a synthetic application of the present allylation
product 7b, RCM of ene-yne derivative 7b, which is
expected to give a conjugated diene compound known as
Dane’s diene 13a,10 an important intermediate for the
synthesis of estrone,11 was examined. The preparation
of the intermediate 13a was efficiently carried out by an
intramolecular enyne metathesis12 using Grubbs cata-
lyst13 (Scheme 4).
Typical Procedure for Synthesis of (3-Butynyl)-Deriva-
tives. To a solution of diisopropylamine (140 µL, 1.0 mmol) in
THF (5 mL) was added n-BuLi (1.6 M solution in n-hexane, 0.63
mL, 1.0 mmol) at 0 °C, and the mixture was stirred for 0.5 h at
Although the direct enyne metathesis of 7b or 7c did
not proceed even under reflux conditions, intramolecular
enyne metathesis (second-generation Grubbs catalyst
(5 mol %), CH2Cl2, rt) of desilylated acetylene derivatives
(12) For recent reviews on enyne metathesis, see: (a) Diver, S. T.;
Giessert, A. J. Chem. Rev. 2004, 104, 1317. (b) Poulsen, C, S.; Madsen,
R. Synthesis 2003, 1. (c) Mori, M. Top. Organomet. Chem. 1998, 1, 133.
For reviews on olefin metathesis, see: (d) Schrock, R. R.; Hoveyda, A.
H. Angew. Chem., Int. Ed. 2003, 42, 4592. (e) Connon, S. J.; Blechert,
S. Angew. Chem., Int. Ed. 2003, 42, 1900. (f) Fu¨rstner, A. Angew.
Chem., Int. Ed. 2000, 39, 3013. (g) Armstrong, S. K. J. Chem. Soc.,
Perkin Trans. 1 1998, 371. (h) Grubbs, R. H.; Chang, S. Tetrahedron
1998, 54, 4413. For recent examples on intramolecular enyne metath-
esis, see: (i) Hansen, E. C.; Lee, D. Org. Lett. 2004, 6, 2035. (j)
Brenneman, J. B.; Martin, S. F. Org. Lett. 2004, 6, 1329. (k) Hansen,
E. C.; Lee, D. J. Am. Chem. Soc. 2003, 125, 9582. (l) Kitamura, T.;
Mori, M. Org. Lett. 2001, 3, 1161. (m) Mori, M.; Kitamura, T.;
Sakakibara, N.; Sato, Y. Org. Lett. 2000, 2, 543. (n) Stragies, R.;
Voigtmann, U.; Blechert, S. Tetrahedron Lett. 2000, 41, 5465.
(13) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953.
(9) Reaction of vinyl chloride derivative 4d with sodium amide (4
equiv, THF-HMPA) or LDA (2 equiv, THF) gave a trace or a small
amount of the desired ene-yne product 10.
(10) (a) Dane, E.; Eder, K. Liebigs Ann. Chem. 1939, 539, 207. (b)
Dane, E.; Schmitt, J. Liebigs Ann. Chem. 1938, 536, 196. (c) Dane, E.;
Schmitt, J. Liebigs Ann. Chem. 1939, 537, 246.
(11) For recent examples on total synthesis of estrone using Dane’s
diene, see: (a) Hu, Q. Y.; Rege, P. D.; Corey, E. J. J. Am. Chem. Soc.
2004, 126, 5984. (b) Tsogoeva, S. B.; Durner, G.; Bolte, M.; Gobel, M.
Eur. J. Org. Chem. 2003, 1661. (c) Tanaka, K.; Nakashima, H.;
Taniguchi, T.; Ogasawara, K. Org. Lett. 2000, 2, 1915.
758 J. Org. Chem., Vol. 70, No. 2, 2005