Chloroprene as a source of fine chemicals: Palladium-catalyzed synthesis of terminal allenes

Article abstract of DOI:10.1021/ol016320k

(Equation presented) Several functionalized terminal allenes were prepared in moderate to excellent yield by a palladium-catalyzed reaction of chloroprene (2-chloro-1,3-butadiene) with soft nucleophiles.

Full text of DOI:10.1021/ol016320k

ORGANIC
LETTERS
2001
Vol. 3, No. 16
2615-2617
Chloroprene as a Source of Fine
Chemicals: Palladium-Catalyzed
Synthesis of Terminal Allenes
Masamichi Ogasawara, Hisashi Ikeda, Takashi Nagano, and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo,
Kyoto 606-8502, Japan
thayashi@kuchem.kyoto-u.ac.jp
Received June 21, 2001
ABSTRACT
Several functionalized terminal allenes were prepared in moderate to excellent yield by a palladium-catalyzed reaction of chloroprene (2-
chloro-1,3-butadiene) with soft nucleophiles.
Chloroprene (2-chloro-1,3-butadiene) is one of the few
conjugate dienes that are mass-produced and utilized on an
industrial scale. Although it is an economically very attractive
resource, most of its use is for polymerization, producing
chloroprene rubber. Its application to organic synthesis as a
source of a C4-unit is limited to Diels-Alder reactions1 and
reactions of its Grignard reagent.2 Utilization of chloroprene
for synthesis of fine chemicals, accordingly, is an interesting
subject in synthetic organic chemistry.
inert to the reaction (eq 2; vide infra). However, the parent
chlorodiene (chloroprene, 1) was found to be reactive toward
the palladium-catalyzed reaction, giving a terminal allene
as a product (Figure 1).
We have recently established a novel synthetic method
for preparing a variety of functionalized allenes (eq 1).3 The
Figure 1. Substrates for functionalized terminal allenes.
Alternatively, analogous terminal allenes were prepared
by the Pd-catalyzed reaction of allenylmethyl esters4 which
were prepared by multistep reactions.5 The nonsubstituted
2-bromo-1,3-diene is another candidate for a substrate to
prepare the terminal allenes, but it polymerizes easily and is
relatively difficult to handle.6 Chloroprene has advantages
over these compounds because of its easy access, low-cost
availability, and easier handling.
substrates used for the reaction are (Z)-1-substituted-2-bromo-
1,3-butadienes, and the corresponding chlorodienes are nearly
(1) For recent examples, see: (a) Davis, H. M. L.; Stafford, D. G.; Doan,
B. D.; Houser, J. H. J. Am. Chem. Soc. 1998, 120, 3326. (b) Sarakinos, G.;
Corey, E. J. Org. Lett. 1999, 1, 1741.
(2) Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A.,
Ed.; John Wiley & Sons: Chichester, 1995; Vol. 2, pp 812-813, and
references therein.
(4) (a) Djahanbini, D.; Cazes, B.; Gore´, J. Tetrahedron Lett. 1984, 25,
203. (b) Djahanbini, D.; Cazes, B.; Gore´, J. Tetrahedron 1987, 43, 3441.
(c) Cazes, B.; Djahanbini, D.; Gore´, J.; Gene´t, J.-P.; Gaudin, J.-M. Synthesis
1988, 983.
(3) (a) Ogasawara, M.; Ikeda, H.; Hayashi, T. Angew. Chem., Int. Ed.
2000, 39, 1042. (b) Ogasawara, M.; Ikeda, H.; Nagano, T.; Hayashi, T. J.
Am. Chem. Soc. 2001, 123, 2089.
(5) (a) Djahanbini, D.; Cazes, B.; Gore´, J. Tetrahedron 1984, 40, 3645.
(b) Cowie, J. S.; Landor, P. D.; Landor, S. R. J. Chem. Soc., Perkin Trans.
1 1973, 720.
10.1021/ol016320k CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/14/2001

Among a numerous reports on the reactions of allenes,7
those of terminal allenes have a unique position in organic
synthesis.8 In the terminal allenes, the two cumulated double
bonds are effectively discriminated from each other by the
steric factors, which brings about high regioselectivity. The
reaction described in this report provides a simple and single-
step route to these useful synthons starting from inexpensive
and readily available materials.
Scheme 1
Our initial studies were focused on the development of
reaction conditions including reaction temperature, palladium
precursor, and phosphine ligand for the reaction of 1 and
sodium salt of MeCH(COOMe)2 (2a) producing a terminal
allene CH2dCdCHCH2CMe(COOMe)2 (3a). It was found
that the reaction is efficiently catalyzed by 5 mol % of a
palladium complex generated in situ by mixing Pd2(dba)3‚
CHCl3 with DPEphos9 (1.1 equiv to Pd) in the presence of
a large excess of chloroprene (ca. 5 equiv to 2a). Thus, a
mixture of 1 (ca. 3.0 g, ca. 30 mmol),10 2a (850 mg, 5.82
mmol), NaOMe (345 mg, 6.39 mmol), Pd2(dba)3‚CHCl3 (161
mg, 156 µmol), and DPEphos (170 mg, 316 µmol) in THF
(10 mL) was heated at 70 °C (bath temperature). The reaction
was complete within 3 h, and 1.08 g (94% yield based on
2a) of 3a was isolated as a colorless liquid by vacuum
distillation. A catalyst generated from Pd2(dba)3‚CHCl3 and
dpbp,11 which is a bisphosphine ligand used for allene
preparation from the bromodiene,3b showed the lower
catalytic acitivity and gave only 78% of 3a under similar
reaction conditions.
ized, it is likely to be a mixture of the residual catalyst and
the chloroprene polymer/oligomer.
A variety of functionalized terminal allenes are prepared
in this way. Table 1 shows the results obtained with several
types of “soft” nucleophiles such as 2-substituted or unsub-
stituted malonates (entries 1-6), acetoacetate (entry 7), and
As a palladium catalyst precursor, [PdCl(π-allyl)]2 can be
used as well, although the allene product 3a is contaminated
with the allylated nucleophile (CH2dCHCH2CMe(COOMe)2),
which is formed by the catalyst during nucleophilic attack
of malonate on the π-allylpalladium, generating a palladium-
(0) species (Scheme 1).
Table 1. Palladium-Catalyzed Synthesis of Terminal Allenesa
The use of a large excess of chloroprene (1/2a ) ca. 5/1
mol/mol) is essential for a high yield of the allene prepara-
tion. With 2 equiv of 1, conversion of 2a into 3a was
incomplete in 24 h (GC analysis). The necessity of excess
chloroprene 1 is ascribed to competing polymerization of 1.
After removal of the generated NaCl (by filtration) and 3a
(by vacuum distillation), a nonvolatile gummy material was
left in the vessel. Although the material was not character-
(6) (a) Carothers, W. H.; Collins, A. M.; Kirby, J. E. J. Am. Chem. Soc.
1933, 55, 786. (b) Carothers, W. H.; Kirby, J. E.; Collins, A. M. J. Am.
Chem. Soc. 1933, 55, 789.
(7) For recent reviews, see: (a) Hashmi, A. S. K. Angew Chem., Int.
Ed. 2000, 39, 3590. (b) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan,
F. A. Chem. ReV. 2000, 100, 3067.
(8) For selected recent examples, see: (a) Yang, F.-Y.; Cheng, C.-H. J.
Am. Chem. Soc. 2001, 123, 761. (b) Ma, S.; Zhao, S. Org. Lett. 2000, 2,
2495. (c) Rutjes, F. P. J. T.; Tjen, K. C. M.; Wolf, L. B.; Karstens, W. F.
J.; Schoemaker, H. E.; Hiemstra, H. Org. Lett. 1999, 1, 717. (d) Sudo, T.;
Asao, N.; Gevorgyan, V.; Yamamoto, Y. J. Org. Chem. 1999, 64, 2494.
(e) Meguro, M.; Yamamoto, Y. J. Org. Chem. 1999, 64, 694. (f) Trost, B.
M.; Pinkerton, A. B. J. Am. Chem. Soc. 1999, 121, 10842. (g) Trost, B.
M.; Pinkerton, A. B. J. Am. Chem. Soc. 1999, 121, 4068. (h) Hideura, D.;
Urabe, H.; Sato, F. Chem. Commun. 1998, 271. (i) Xiao, W.-J.; Yasapollo,
G.; Alper, H. J. Org. Chem. 1998, 63, 2609. (j) Larock, R. C.; He, Y.;
Leong, W. W.; Han, X.; Refvik, M. D.; Zenner, J. M. J. Org. Chem. 1998,
63, 2154.
entry NuH
baseb
temp/°Cc time/h yield/%d
1
2a NaOMe (1.1)
2a NaOMe (1.1)
70
70
3
18
24
3
94 (3a )
78 (3a )
57f (3b)
67 (3b′)
91 (3b′)
89 (3c)
76 (3d )
50 (3e)
35 (3f)h
2e
3
2b NaOMe (1.0)
2b NaOMe (2.5)
3b NaOMe (1.1)
2c NaH (1.1)
2d NaH (1.1)
2e KH (1.1)
70
4g
5
6
100
70
70
70
100
50
20
12
18
20
5
7
8g
9
2f
LHMDS (2.0) + ZnCl2 (1.0)
a With 5 mol % of the palladium catalyst generated from Pd2(dba)3‚CHCl3
and DPEphos (1.1 equiv) in the presence of 5 equiv of 1 unless otherwise
noted. b Equivalence to NuH 2 in parentheses. c Bath temperature. d Yield
relative to the amount of used NuH 2 after isolation by distillation or silica
gel chromatography. e With dpbp instead of DPEphos. f Doubly reacted
product 3b′ was isolated in 13% yield (based on 2b). g In a pressure-resistant
reactor. h 50% of 2f was recovered.
(9) DPEphos ) bis[2-(diphenylphosphino)phenyl]ether. See: Kranen-
burg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J.; van Leeuwen, P. W. N.
M.; Goubitz, K.; Fraanje, J. Organometallics 1995, 14, 3081.
2616
Org. Lett., Vol. 3, No. 16, 2001

can be ascribed to slow oxidative addition of 4 to the
palladium(0) species. It was reported that the palladium-
catalyzed cross-coupling reaction of 1,1-dichloro-2-substituted-
ethylenes with Grignard reagents proceeded highly selec-
tively at the position trans to the 2-substituents.15 The
remarkable trans-selectivity in the cross-coupling reaction
was explained as a steric effect of the 2-substituent which
inhibits the reaction at the vicinal cis-chloride. The two
palladium-catalyzed reactions, the allene synthesis and the
regioselective cross-coupling, proceed through the catalytic
cycles involving oxidative addition of the olefinic C-Cl bond
to a Pd(0). The low reactivity of 4 to the allene synthesis
should be ascribed to steric effects of the phenyl substituent
at 1-position. The phenyl group in 4 interferes with oxidative
addition at the vicinal cis-chloride. Because there is no
substituent at the vicinal cis position to the chloride in 1, it
exhibits high reactivity toward the palladium-catalyzed allene
synthesis reaction (Scheme 3).
Scheme 2
amide (entry 8). Generally, reactions proceeded very cleanly
and the products were easily isolated in pure form in good
to excellent yields by vacuum distillation or column chro-
matography after usual workup.
As shown in Scheme 2, when a mixture of unsubstituted
malonate 2b and a stoichiometric amount (to 2b) of base
(NaOMe) as nucleophile was used, the product was obtained
as a mixture of mono-allene 3b (57%) and bis-allene 3b′
(13% based on 2b), which were separated by silica gel
chromatography (Table 1, entry 4). The same result was
obtained with a prepurified isolated sodium salt Na[CH-
(COOMe)2]. Because the sodium salt of initially formed 3b
is more reactive than that of 2b, the mono-allene 3b could
not be prepared selectively under the conditions employed
for this study. Interestingly, the bis-allene 3b′ was obtained
as a sole allenic product in 67% yield using more than 2
equiv (to 2b) of NaOMe, although the higher temperature
(100 °C in a pressure-resistant reactor) was required to
complete the reaction (entry 4).
Scheme 3
The present method can be applied to synthesis of an
unusual R-amino acid. The reaction of 1 with a chelated zinc
enolate of 2f 12 in the presence of the Pd/DPEphos catalyst
gave the allene CH2dCdCHCH2CH(NHBoc)(COOtBu) (3f)
in 35% yield (Table 1, entry 9). Deprotection will afford a
naturally occurring amino acid allenylalanine,13 which is one
of the simplest routes to this amino acid.4c,14
Chloroprene 1 and 1-substituted-2-bromo-1,3-dienes are
reactive substrates for the palladium-catalyzed allene syn-
thesis, while 1-substituted-chloroprenes, such as (Z)-2-chloro-
1-phenyl-1,3-butadiene (4), were found to be nearly inert to
the reaction (eq 2 and Scheme 3). The low reactivity of 4
In conclusion, we have demonstrated that chloroprene 1
is an excellent source of a variety of functionalized terminal
allenes. The allene synthesis is effectively catalyzed by the
palladium species generated in situ from Pd2(dba)3‚CHCl3
and DPEphos. The nature of chloroprene, especially its low
cost, and the usefulness of the products will make the present
reaction attractive for further applications.
Acknowledgment. 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, Japan), and the Kurata Foundation
(to M.O.). We thank Denki Kagaku Kogyo Co. Ltd. for a
generous gift of chloroprene.
(10) Chloroprene, which we have used, contained ca. 10 mol % of toluene
and was used for the present studies without further purification.
(11) dpbp ) 2,2′-bis(diphenylphosphino)-1,1′-biphenyl. See: Ogasawara,
M.; Yoshida, K.; Hayashi, T. Organometallics 2000, 19, 1567, and
references therein.
(12) (a) Kazmaier, U.; Zumpe, F. L. Angew. Chem., Int. Ed. 1999, 38,
1468. (b) Kazmaier, U.; Zumpe, F. L. Angew. Chem., Int. Ed. 2000, 39,
802.
(13) (a) Chilton, W. S.; Tsou, G.; Kirk, L.; Benedict, R. G. Tetrahedron
Lett. 1968, 6283. (b) Hatanaka, S.-I.; Nimura, Y.; Takishima, K.; Sugiyama,
J. Phytochemistry 1998, 49, 573, and references therein.
(14) (a) Black, D. K.; Landor, S. R. J. Chem. Soc. C 1968, 283. (b)
Baldwin, J. E.; Adlington, R. M.; Basak, A. J. Chem. Soc., Chem. Commun.
1984, 1284.
Supporting Information Available: Detailed experi-
mental procedures and compound characterization data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL016320K
(15) Minato, A.; Suzuki, K.; Tamao, K. J. Am. Chem. Soc. 1987, 109,
1257.
Org. Lett., Vol. 3, No. 16, 2001
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