Chemistry Letters 2000
1199
Carbometallation of alkynes with vinylmetal species is a
useful method for the preparation of conjugated dienes.
However only a limited number of such reactions have been ex-
plored. Normant and co-workers reported the addition of
alkenyl cuprates to unsubstituted and heteroatom substituted
acetylenes.12 Klei and Teuben showed that the reaction of (1-
methylprop-1-enyl)titanocene with diphenylacetylene produced
the syn-adduct, which afforded the diene upon hydrolysis.13
Therefore we were interested in the reaction of the vinyltitani-
um(IV) species 4 with alkynes 8 (Scheme 2). Although the
treatment of 4 prepared from 2c with diphenylacetylene 8a
afforded the conjugated diene 9a as a mixture of the stereoiso-
mers14 in 38% yield (Table 2, Entry 1), aliphatic internal alkyne
was found to be unreactive towards the vinyltitanium species 4.
We found, however, that terminal alkynes 8b–d did react with 4
to form the E,E-dienes 9 in good overall yields with complete
regio- and stereo-selectivity.15 The formation of trans-car-
bon–carbon double bond is explained well by the syn-addition
of the vinyltitanium species 4.16 The regioselectivity of the
present reaction is of special interest. The reaction of or-
ganometallic reagents with terminal alkynes is usually compli-
cated by formation of the two possible regioisomers, and an or-
ganic group tends to add to the substituted side of triple
bond.12,17 The regioselectivity of the present reaction is defer-
ent from the conventional reactions; a vinyl group selectively
attacks at the terminus of alkyne.
species, the present study demonstrates potential utility of vinylti-
tanium compounds as reagents in organic synthesis. Further
study on their preparation and reaction is currently underway.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports, and
Culture, Japan (No. 11119214 and 11440213).
References and Notes
1
a) M. T. Reetz, “Organotitanium Reagents in Organic
Synthesis,” Springer-Verlag, Berlin (1986). b) C. Ferreri, G.
Palumbo, and R. Caputo, in “Comprehensive Organic
Synthesis,” ed. by B. M. Trost and I. Fleming, Pergamon,
Oxford (1991), Vol. 1, p. 139. c) M. T. Reetz, in “Or-
ganometallics in Synthesis,” ed. by M. Schlosser, Wiley,
Chichester (1994), p. 195.
2
3
4
5
M. T. Reetz, J. Westermann, R. Steinbach, B. Wenderoth, R.
Peter, R. Ostarek, and S. Maus, Chem. Ber., 118, 1421 (1985).
T. Takeda, I. Miura, Y. Horikawa, and T. Fujiwara,
Tetrahedron Lett., 36, 1495 (1995) and references cited therein.
B. Weidmann, C. D. Maycock, and D. Seebach, Helv. Chim.
Acta, 64, 1552 (1981).
H. Urabe, T. Hamada, and F. Sato, J. Am. Chem. Soc., 121,
2931 (1999).
6
7
H. Urabe and F. Sato, J. Am. Chem. Soc., 121, 1245 (1999).
O. Kitagawa, T. Suzuki, T. Inoue, and T. Taguchi, Tetrahedron
Lett., 39, 7357 (1998).
8
9
B. J. Hewitt, A. K. Holliday, and R. J. Puddephatt, J. Chem.
Soc., Dalton Trans., 1973, 801.
D. J. Cardin and R. J. Norton, J. Chem. Soc., Chem. Commun.,
1979, 513.
10 a) T. Takeda and T. Fujiwara, J. Synth. Org. Chem., Jpn., 56,
1048 (1998). b) T. Takeda and T. Fujiwara, Rev. Heteroatom
Chem., 21, 93 (1999).
11 T. Takeda, N. Nozaki, N. Saeki, and T. Fujiwara, Tetrahedron
Lett., 40, 5353 (1999).
12 J. F. Normant and A. Alexakis, Synthesis, 1981, 841.
13 E. Klei and J. H. Teuben, J. Organomet. Chem., 222, 79 (1981).
14 The ratio of two isomers was found to be variable in the differ-
ent runs, indicating the isomerization of the initial product dur-
ing work-up and isolation.
15 The typical experimental procedure is as follows: Magnesium
turnings (51 mg, 2.1 mmol; purchased from Nakarai Tesque
Inc. Kyoto, Japan), finely powdered molecular sieves 4 A (175
mg), and Cp2TiCl2 (436 mg, 1.75 mmol) were placed in a flask
and dried by heating with a heat gun under reduced pressure
(2–3 mmHg). During this procedure, care was taken not to sub-
lime Cp2TiCl2. After cooling, THF (3.5 mL) and P(OEt)3 (0.60
mL, 3.5 mmol) were added successively with stirring at room
temperature under argon. After 3 h, 2c (186 mg, 0.5 mmol) in
THF (1.5 mL) was added to the mixture at 0 °C, and stirring
was continued for 10 min. Then tert-butyl chloride (46 mg, 0.5
mmol) in THF (1 mL) was added and the reaction mixture was
stirred for 1 h. A THF (1 mL) solution of 8d (102 mg, 1 mmol)
was added and the mixture was stirred for 30 min at the same
temperature and then at 25 °C for 1.5 h. The reaction was
quenched by addition of 1 M NaOH (20 mL), and the resulting
insoluble materials were filtered off through Celite and washed
with ether (10 mL). The organic materials were extracted with
ether (3 × 20 mL), and the extract was dried (Na2SO4). After
removal of solvent, the residue was purified by PTLC (hexane)
to give 9d (90 mg, 58%).
16 When the reaction of 2a with (trimethylsilyl)acetylene 8c was
quenched with D2O, 5-benzyl-6,6-dimethyl-1-(trimethylsilyl)[1-
2H]hepta-1,3-diene was obtained in 55% yield (85% deuterium
incorporation), indicating the formation of the dienyltitanium
species 10.
17 a) E. Negishi, Pure Appl. Chem., 53, 2333 (1981). b) P. Knochel,
in “Comprehensive Organic Synthesis,” ed. by B. M. Trost and I.
Fleming, Pergamon, Oxford (1991), Vol. 4, p. 865. c) E. Negishi
and D. Y. Kondakov, Chem. Soc. Rev., 1996, 417.
Although more work will be required to elucidate the
relationship between the structure and reactivity of vinyltitanium