Palladium-catalyzed synthesis of butatrienes

Article abstract of DOI:10.1246/cl.2000.776

Palladium-catalyzed synthesis of functionalized butatrienes was achieved starting from 2-bromo-1-buten-3-yne derivatives and nucleophiles. The reaction proceeded under very mild conditions giving the products in moderate to good yields. The reactivity of the bromobutenyne substrates was highly dependent on substituents at 1-position. A subtle balance of nucleophilicity and basicity in the nucleophiles was also important for the success of the reactions.

Full text of DOI:10.1246/cl.2000.776

776
Chemistry Letters 2000
Palladium-Catalyzed Synthesis of Butatrienes
Masamichi Ogasawara, Hisashi Ikeda, Kazunori Ohtsuki, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received April 12, 2000; CL-000345)
Palladium-catalyzed synthesis of functionalized butatrienes
was achieved starting from 2-bromo-1-buten-3-yne derivatives
and nucleophiles. The reaction proceeded under very mild condi-
tions giving the products in moderate to good yields. The reac-
tivity of the bromobutenyne substrates was highly dependent on
substituents at 1-position. A subtle balance of nucleophilicity
and basicity in the nucleophiles was also important for the suc-
cess of the reactions.
Compounds with cumulated double bonds, such as allene or
ketene, are fairly reactive because of their strained structures,
thus, effective synthesis of these compounds is still challenging
in organic chemistry.1 Construction of three cumulated
carbon–carbon double bonds is a more difficult problem, and the
effective synthetic methods of butatrienes are still very few.1,2 In
addition, reported examples of transition metal-catalyzed synthe-
sis of butatrienes are limited to dimerization of terminal
acetylenes.3 We have recently established a new synthetic
method of functionalized allenes starting from 2-bromo-1,3-buta-
dienes (eq 1).4 The reaction is catalyzed by a π-allylpalladium
species, and the allenic product obtained by this method always
comes with a methylene unit between the allenyl moiety and the
Nu substituent due to the structural requirement of the substrate.
We started the project reported here with intention to utilize this
extra carbon for preparation of higher cumulenes: i.e., butatrienes
may be prepared by the analogous method starting from 2-
bromo-1-buten-3-yne (eq 2). Indeed, the reaction proceeded
effectively in certain cases to give the functionalized butatrienes
in moderate to good yield. In this report, we describe the new
synthetic method of butatrienes with its scope and limitation.
with nucleophile 2m under analogous reaction conditions
employed for the allene synthesis.4 It was found that the reaction
was efficiently catalyzed by a palladium–dpbp7 complex generat-
ed in situ from [PdCl(η3-C3H5)]2 and 1.05 equiv (to Pd) of dpbp.
Thus, a mixture of 1a (104.1 mg, 503 µmol), 2m (97.9 mg, 582
µmol), [PdCl(η3-C3H5)]2 (4.6 mg, 25.1 µmol/Pd, 5 mol% Pd),
and dpbp (13.2 mg, 25.3 µmol) in THF (5 mL) was stirred at 35
°C for 18 h. After removing the precipitated sodium salt by fil-
tration, the residue was purified by silica gel chromatography to
give 223 mg (45% yield) of 3am (entry 1 in Table 1). The
obtained butatriene 3am was a mixture of two geometrical iso-
mers and the E/Z isomeric ratio in 3am was determined to be
52/48 by 1H NMR.8,9
The R substituents in 1 played a very important role in con-
trolling the reactivity of the substrates. The substrates with aryl
groups gave 3 in moderate to good yield (entries 1–4), while no
butatrienyl products were isolated with benzyl or alkyl R groups
(entries 5 and 6). Comparison of the reactivity between 1a, 1c,
and 1d is interesting: introduction of an electron-withdrawing CF3
on the phenyl group increased the yield of the cumulene (entries 1
vs 3), while 3 was obtained in much lower yield with the more
electron-donating p-anisyl group (entry 4). This remote electronic
effect is quite unique to this reaction, i.e., formally, the electronic
characteristics of the R groups at 1-position control nucleophilic
attacks to the carbons at 4-position. Meanwhile steric characteris-
tics of the R substituents is less important. The bromoenyne 1b,
which is with a bulkier 1-naphthyl substituent, gave 3bm in 46%
yield (entry 2), which is almost identical to that for 3am.
However, introduction of a substituent to the terminal sp carbon
diminished the reactivity of the enyne. (Z)-PhCH=CBr-C≡C-
The substrates, (Z)-2-bromo-1-buten-3-ynes (1a–f), were
easily prepared in moderate yield by two-step reactions starting
from readily available 1,1-dibromoalkenes5 as shown in
Scheme 1. The first step, palladium-catalyzed cross-coupling
of the dibromoalkene with trimethylsilylethynylzinc chloride,
proceeded with high stereoselectivity giving the (Z)-product
exclusively.4,6 The trimethylsilyl protecting group was easily
removed with either catalytic amount of K2CO3 in methanol or
stoichiometric tetrabutylammonium fluoride in THF.
The obtained substrate 1a (R = Ph) was allowed to react
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
777
nC4H9, which was prepared from the corresponding dibro-
moalkene and 1-hexynylzinc chloride by the Pd-catalyzed cross-
coupling in 67% yield, was completely inert to the Pd-catalyzed
butatriene formation reaction with 2m.
References and Notes
1
"The Chemistry of Ketenes, Allenes, and Related Compounds," ed.
by S. Patai, Wiley, New York (1980).
a) H.-F. Chow, X.-P. Cao, and M.-K. Leung, J. Chem. Soc., Chem.
Commun., 2121 (1994), and references cited therein. b) H.-F. Chow,
X.-P. Cao, and M.-K. Leung, J. Chem. Soc., Perkin Trans. 1, 193
(1995). c) R. W. Saalfrank, A. Welch, and M. Haubner, Angew.
Chem., Int. Ed. Engl., 34, 2709 (1995).
2
3
a) Y. Wakatsuki, H. Yamazaki, N. Kumegawa, T. Satoh, and J. Y.
Satoh, J. Am. Chem. Soc., 113, 9604 (1991). b) Y. Wakatsuki, H.
Yamazaki, N. Kumegawa, and P. S. Johar, Bull. Chem. Soc. Jpn., 66,
987 (1993). c) Y. Wakatsuki, N. Koga, H. Yamazaki, and K.
Morokuma, J. Am. Chem. Soc., 116, 8105 (1994). d) C. S. Yi and N.
Liu, Organometallics, 15, 3968 (1996). e) Y. Suzuki, R. Hirotani, H.
Komatsu, and H. Yamazaki, Chem. Lett., 1299 (1999). f) T. Ohmura,
S. Yorozuya, Y. Yamamoto, and N. Miyaura, Organometallics, 19,
365 (2000).
4
5
M. Ogasawara, H. Ikeda, and T. Hayashi, Angew. Chem., Int. Ed.
Engl., 39, 1042 (2000).
a) F. Ramirez, N. B. Desai, and N. McKelvie, J. Am. Chem. Soc., 84,
1745 (1962). b) E. J. Corey and P. L. Fuchs, Tetrahedron Lett., 13,
3769 (1972).
6
Palladium-catalyzed selective substitutions of one of the two halides
from 1,1-dihalo-1-alkene have been reported. See, a) A. Minato, K.
Suzuki, and K. Tamao, J. Am. Chem. Soc., 109, 1257 (1987). b) J.
Uenishi, R. Kawahama, O. Yonemitsu, and J. Tsuji, J. Org. Chem.,
61, 5716 (1996). c) J. Uenishi, R. Kawahama, Y. Shiga, O.
Yonemitsu, and J. Tsuji, Tetrahedron Lett., 37, 6759 (1996).
a) dpbp = 2,2'-bis(diphenylphosphino)-1,1'-biphenyl. b) M.
Ogasawara, K. Yoshida, and T. Hayashi, Organometallics, 19, 1567
(2000), and references cited therein.
7
8
The assignment of the E- and Z-isomers was made by comparison of
The reaction is very sensitive to nucleophiles 2: while 1c
reacted with 2m to give 3cm in 73% yield, the closely related
nucleophile 2p was completely inert under the same reaction
condition and unreacted 1c was recovered from the reaction mix-
ture (entries 3 and 9). Because the nucleophilic center in 2m is
more hindered than that in 2p, the higher reactivity of 2m in the
reaction cannot be accounted for by the steric factors. The
unusual reactivity was double-checked by an independent experi-
ment. An equimolar mixture of 1c, 2m, and 2p was reacted for
22 h in THF at 35 °C in the presence of 5 mol% of the Pd–dpbp
catalyst, and 3cm was obtained with E/Z = 60/40 selectivity as a
sole butatriene product.10 The corresponding butatriene from 1c
and 2p was not detected at all by NMR and GC–MS analyses. In
the reactions with more basic nucleophiles, such as 2q or
Grignard reagents, dehydrobromination from 1 was a dominant
reaction giving conjugated diyne as main products (entry 10).
The reaction reported here can be regarded as a skeletal
rearrangement of the conjugated enynes to the butatriene frame-
works. Considering ca. 20 kcal/mol energy difference between
1,4-dimethylbutatriene and the corresponding enynes,3a the repre-
sented reaction is very unique and the difference of bond energy
between C–Br and C–Nu must be mainly contributory to the for-
mation of the butatrienes. Since the butatrienes obtained here
keep some energy in their skeletons, they must be reactive mole-
cules, and thus their application to further organic transforma-
tions will be an interesting subject.
1
5JHH values of the olefinic protons.9 3am: H NMR (CDCl3, 23 °C):
δ 1.67 (s, 3H of Z-isomer), 1.78 (s, 3H of E-isomer), 3.78 (s, 6H of Z-
5
isomer), 3.79 (s, 6H of E-isomer), 6.12 (d, J = 7.7 Hz, 1H of E-iso-
5
5
mer), 6.19 (d, J = 7.3 Hz, 1H of Z-isomer), 6.55 (d, J = 7.7 Hz, 1H
of E-isomer), 6.58 (d, 5J = 7.3 Hz, 1H of Z-isomer), 7.24–7.28 (m, 1H
of both isomers), 7.31–7.36 (m, 2H of both isomers), 7.41–7.44 (m,
2H of both isomers). 3bm: 1H NMR (CDCl3, 23 °C): δ 1.72 (s, 3H of
Z-isomer), 1.80 (s, 3H of E-isomer), 3.79 (s, 6H of Z-isomer), 3.80 (s,
6H of E-isomer), 6.19 (d, 5J = 7.8 Hz, 1H of E-isomer), 6.25 (d, 5J =
5
7.5 Hz, 1H of Z-isomer), 7.29 (d, J = 7.8 Hz, 1H of E-isomer), 7.32
(d, 5J = 7.5 Hz, 1H of Z-isomer), 7.45–7.58 (m, 3H of both isomers),
7.73–7.75 (m, 1H of both isomers), 7.78–7.81 (m, 1H of both iso-
mers), 7.85–7.87 (m, 1H of both isomers), 8.35–8.37 (m, 1H of both
isomers). 3cm: 1H NMR (CDCl3, 23 °C): δ 1.68 (s, 3H of Z-isomer),
5
1.77 (s, 3H of E-isomer), 3.79 (s, 6H of both isomers), 6.25 (d, J =
5
7.6 Hz, 1H of E-isomer), 6.33 (d, J = 7.3 Hz, 1H of Z-isomer), 6.57
5
5
(d, J = 7.6 Hz, 1H of E-isomer), 6.60 (d, J = 7.3 Hz, 1H of Z-iso-
mer), 7.50–7.54 (m, 2H of both isomers), 7.57–7.61 (m, 2H of both
isomers). 3dm: 1H NMR (CDCl3, 23 °C): δ 1.66 (s, 3H of Z-isomer),
1.76 (s, 3H of E-isomer), 3.78 (s, 6H of both isomers), 3.82 (s, 3H of
Z-isomer), 3.83 (s, 3H of E-isomer), 6.01 (d, 5J = 7.7 Hz, 1H of E-iso-
5
5
mer), 6.08 (d, J = 7.2 Hz, 1H of Z-isomer), 6.50 (d, J = 7.7 Hz, 1H
of E-isomer), 6.53 (d, 5J = 7.2 Hz, 1H of Z-isomer), 6.86–6.89 (m, 2H
of both isomers), 7.35–7.38 (m, 2H of both isomers). 3cn: H NMR
1
(CDCl3, 23 °C): δ 1.30 (t, J = 7.1 Hz, 3H of Z-isomer), 1.31 (t, J = 7.1
Hz, 3H of E-isomer), 1.60 (s, 3H of Z-isomer), 1.68 (s, 3H of E-iso-
mer), 2.25 (s, 3H of Z-isomer), 2.26 (s, 3H of E-isomer), 4.25–4.30
5
(m, 2H of both isomers), 6.30 (d, J = 7.7 Hz, 1H of E-isomer), 6.37
5
5
(d, J = 7.3 Hz, 1H of Z-isomer), 6.57 (d, J = 7.7 Hz, 1H of E-iso-
mer), 6.59 (d, 5J = 7.3 Hz, 1H of Z-isomer), 7.51–7.53 (m, 2H of both
isomers), 7.57–7.62 (m, 2H of both isomers).
9
a) Although it was claimed previously that the E-isomer should have
5
a larger JHH value than that of the corresponding Z-isomer,9b others
5
Judging from similarity between this reaction and the allene
synthesis,4 a probable intermediate of the Pd-catalyzed reaction is
a π-allenylpalladium species. Establishment of the intermediate
will be our next goal.
reported that JHH values of Z- and E-isomers of corresponding buta-
trienes were almost identical.9c We could detect the slight, but mean-
5
ingful differences between the JHH values of the two isomers of the
obtained butatrienes using high-resolution NMR technique (at 500
MHz with 0.076 Hz of digital resolution). b) R. Mantione, A. Alves,
P. P. Montijn, G. A. Wildschut, H. J. T. Bos, and L. Brandsma, Rec.
Trav. Chim. Pays-Bas, 89, 97 (1970). c) P. J. Bauer, O. Exner, R.
Ruzziconi, T. D. An, C. Tarchini, and M. Schlosser, Tetrahedron, 50,
1707 (1994).
This work was supported by "Research for the Future"
Program (the Japan Society for the Promotion of Science), a
Grant-in-Aid for Scientific Research (the Ministry of Education,
Science, Sports and Cullture, Japan), and Mitsubishi Chemical
Corporation Fund (to M. O.).
10 The yield of 3cm of this experiment is 34%, which is much lower
than that of Entry 1 in Table 1. This negative effect of 2p is unex-
pected and cannot be explained at this moment.