Palladium-catalyzed preparation of vinylallenes from 2-bromo-1,3,5-trienes via an alkylidene-π-allylpalladium-mediated formal SN2″ pathway

Article abstract of DOI:10.1021/ol062309e

A novel Pd-catalyzed reaction to prepare conjugated vinylallenes from 2-bromo-1,3,5-triene and a soft nucleophile via a formal S_N2′ pathway was developed. The reaction proceeds via alkylidene-π-allylpalladium and allenyl-π-allylpalladium interm

Full text of DOI:10.1021/ol062309e

ORGANIC
LETTERS
2006
Vol. 8, No. 23
5409-5412
Palladium-Catalyzed Preparation of
Vinylallenes from 2-Bromo-1,3,5-trienes
via an
Alkylidene-π-allylpalladium-Mediated
Formal SN2′′ Pathway
Masamichi Ogasawara,* Liyan Fan, Yonghui Ge, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences,
Hokkaido UniVersity and SORST, Japan Science and Technology Agency (JST),
Kita-ku, Sapporo 001-0021, Japan
ogasawar@cat.hokudai.ac.jp
Received September 19, 2006
ABSTRACT
A novel Pd-catalyzed reaction to prepare conjugated vinylallenes from 2-bromo-1,3,5-triene and a soft nucleophile via a formal SN2′′ pathway
was developed. The reaction proceeds via alkylidene- -allylpalladium and allenyl- -allylpalladium intermediates, and a dynamic process involving
π
π
the two palladium intermediates played important roles in determining the selectivity of the Pd-catalyzed reaction. The reaction was extended
to an asymmetric counterpart, and an axially chiral vinylallene was obtained with up to 81% ee.
In many palladium-catalyzed reactions, π-allylpalladium
species have been recognized as key intermediates of the
catalytic cycles, and their dynamic behavior via a π-σ-π
process plays an important role in determining the stereo-
selectivity of the reactions (eq 1).1
cally enriched axially chiral allenes were obtained with up
to 89% ee (eq 2).2b,c,e Negishi and co-workers revealed that
analogous 2-bromo-1,3-dienes were also used as unique
substrates in Pd-catalyzed E/Z-selective preparation of
conjugated dienes.3
Recently, we developed a palladium-catalyzed reaction to
prepare functionalized allenes from 2-bromo-1,3-dienes.2 The
Pd-catalyzed reaction was extended into an asymmetric
counterpart using a Pd/(R)-binap catalyst, and enantiomeri-
(2) (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. (c) Ogasawara, M.; Ueyama, K.; Nagano,
T.; Mizuhata, Y.; Hayashi, T. Org. Lett. 2003, 5, 217. (d) Ogasawara, M.;
Ge, Y.; Uetake, K.; Fan, L.; Takahashi, T. J. Org. Chem. 2005, 70, 3871.
(e) Ogasawara, M.; Nagano, T.; Hayashi, T. J. Org. Chem. 2005, 70, 5764.
(f) Ogasawara, M.; Ge, Y.; Uetake, K.; Takahashi, T. Org. Lett. 2005, 7,
5697.
(1) (a) Negishi, E., Ed. Handbook of Organopalladium Chemistry for
Organic Synthesis; John Wiley and Sons: New York, 2002; p 1663. (b)
Tsuji, J. Palladium Reagents and Catalysts: New PerspectiVes for the 21st
Century; John Wiley and Sons: Chichester, 2004; p 431.
10.1021/ol062309e CCC: $33.50
© 2006 American Chemical Society
Published on Web 10/19/2006

An alkylidene-π-allylpalladium species (A) is suggested
as a possible intermediate4 in protocols of preparing both
allenes and conjugated dienes, and apparently, the dynamic
behavior of such a Pd intermediate controls the stereoselec-
tivity of the two Pd-catalyzed reactions.2b,3a Asymmetric
dynamic kinetic resolution of racemic allenylmethyl esters
reported by Imada et al.4i,k and by Trost et al.4j was also
proposed to proceed via analogous alkylidene-π-allylpalla-
dium intermediates. The two terminal carbons of an η3-allyl
moiety in A (Scheme 1) are electronically diverse: one is
Scheme 2
t
triene 1a, which was with a Bu group at the C(1) position
of the trienyl skeleton, with a pronucleophile 2m in the
presence of NaH and a palladium catalyst (2 mol %), which
was generated in situ from [PdCl(π-allyl)]2 and dpbp9 at 23
°C, gave a conjugated vinylallene 3am in 96% yield as a
sole allenic product (Table 1, entry 1). Analogous vinylal-
lenes 3an and 3ao were also obtained cleanly in 80 and 96%
yields, respectively, by the reactions of 1a with either 2n or
2o (entries 2 and 3). Products from 1b and 1c, which were
with sterically less bulky alkyl substituents at the C(1)
position, were obtained as mixtures of vinylallenes 3 and
nonconjugated allylallenes 4 (two diastereomers). The 3/4
selectivity decreased as the R substituents in 1 became
smaller (entries 1, 4, and 9; entries 2 and 7). On the other
hand, formation of the allylallenes 4 was suppressed by the
use of the less-reactive (slow-reacting) pronucleophile 2n
in place of 2m (entries 4 and 7).
A plausible mechanism of the Pd-catalyzed reactions is
shown in Scheme 3. An initially formed alkylidene-π-
allylpalladium species 5 is in equilibrium with a σ-(allenyl-
methyl)palladium intermediate 6, whose structure is similar
to that of the type-C species (see Scheme 1), and coordination
of the vinyl pendent in 6 to the Pd center forms an allenyl-
π-allylpalladium species 7. The nucleophile highly selectively
attacks the unsubstituted π-allyl terminal in 71,8,10 to afford
3. The isomerization of 5 to 7 becomes slower when the R
group is sterically more compact because the steric interac-
tion between the R group and the PdII(P-P) moiety in 5 is
less operative. Thus, a part of 5 reacts with the nucleophile
prior to the isomerization to 7 giving 4. On the other hand,
formation of 4 is suppressed in a reaction with a less-reactive
Scheme 1
sp- and the other is sp2-hybridized. Thus, η1-σ-coordination
at either carbon might produce σ-(1,3-dien-2-yl)palladium
(B) or σ-(allenylmethyl)palladium (C), respectively. Green
et al. demonstrated that palladium species analogous to A
and B were prepared either from 2-chloro-1,3-butadienes or
from 4-chloro-1,2-butadienes; however, Pd species such as
C were not observed.5,6
Here we wish to report a novel Pd-catalyzed reaction that
yields conjugated vinylallenes from 2-bromo-1,3,5-trienes via
a formal SN2′′ pathway, in which a dynamic process
involving both alkylidene-π-allylpalladium (A) and σ-(alle-
nylmethyl)palladium (C) plays important roles in determining
the selectivity of the reaction.
Although the σ-(allenylmethyl)palladium species C has
been neither detected nor isolated, its existence as a transient
intermediate was proposed in several reactions.3a,4b,c,g,h,7
Accordingly, a palladium-catalyzed reaction of an 1-alkyl-
2-bromo-1,3,5-hexatriene 1 with a soft nucleophile 2 was
explored for a possible formal SN2′′ reaction (Scheme 2,
Table 1).8 As we expected, treatment of a 2-bromo-1,3,5-
Table 1. Palladium-Catalyzed Reactions of 2-Bromo-1,3,5-trienes 1 with Soft Nucleophiles 2a
entry
bromotriene 1
NuH 2
base
Pd precursor
P-P
temp/°C
yield of 3 + 4/%b
3/4c
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
2m
2n
2o
2m
2
2m
2n
2n
2m
2m
NaH
KH
KH
NaH
NaH
NaH
KH
KH
NaH
NaH
[PdCl(π-allyl)]2
[PdCl(π-allyl)]2
[PdCl(π-allyl)]2
[PdCl(π-allyl)]2
Pd(dba)2
Pd(dba)2
[PdCl(π-allyl)]2
Pd(dba)2
dpbp
dpbp
dpbp
dpbp
dpbp
dppp
dpbp
dppp
dpbp
dppp
23
23
23
23
50
50
23
50
23
50
96 (3am)
80 (3an)
96 (3ao)
98 (3bm + 4bm)
73 (3bm + 4bm)
76 (3bm + 4bm)
98 (3bn + 4bn)
77 (3bn + 4bn)
80 (3cm + 4 cm)
98 (3cm + 4cm)
>99:ndd
>99:ndd
>99:ndd
77:23
87:13
91:9
91:9
96:4
69:31
84:16
[PdCl(π-allyl)]2
Pd(dba)2
10
a
The reactions were carried out in THF in the presence of a Pd catalyst (2 mol %) generated from an appropriate palladium precursor and a bisphosphine
ligand. b Isolated yield. c Determined by H NMR. d Allylallene products were not detected by H NMR.
1
1
5410
Org. Lett., Vol. 8, No. 23, 2006

allenes were obtained in reasonable yields at higher tem-
perature (50 °C) without loss of selectivity. Under the
optimized conditions, 3bm was obtained in 91% selectivity
(entry 6). The catalyst generated from Pd(dba)2 and dppp
was also applied to the reactions of 1b with 2n (entry 8)
and of 1c with 2m (entry 10), and the vinylallenes 3bn and
3cm were obtained in much better selectivity.
Scheme 3
Although the bromotriene substrates 1 are achiral, the
vinylallene products 3 are axially chiral. Accordingly, the
present reaction could be extended into an asymmetric
counterpart by using a chirally modified palladium catalyst.
It should be mentioned that examples of transition-metal-
catalyzed asymmetric synthesis of axially chiral allenes are
still very rare.2b,c,e,4i-k,11-13 The asymmetric extension of the
process was explored for a reaction of 1a with 2n, and the
results are summarized in Table 2. A Pd catalyst generated
nucleophile because the lifetime of the palladium intermedi-
ates becomes longer and 5 has enough time to isomerize to
7.
The analyses of the Pd-catalyzed reaction shown in
Scheme 3 implied that the vinylallene 3 might be formed
more preferentially with an appropriate Pd catalyst which
reacts more slowly with the nucleophiles. A variety of Pd
precursors and phosphine ligands were examined in the
reaction of 1b with 2m, and the 3bm/4bm ratio in the
Table 2. Palladium-Catalyzed Asymmetric Synthesis of
Vinylallene 3an from Bromotriene 1a and Pronucleophile 2na
1
products was monitored by H NMR. It was found that Pd
catalysts generated from Pd(dba)2 improved the 3bm/4bm
ratio, and the use of dppp as an ancillary ligand further
improved the selectivity (Table 1, entries 4-6). Yields of
the allenic products were lower (∼30%) for the reactions
catalyzed by Pd(dba)2/P-P at 23 °C because of lower
catalytic activity of the palladium species. However, the
entry
L*
solvent
base
temp/°C yield/%b % eec
1
2
3
4
5
6
binap
THF
THF
EtOH CsOtBu
EtOH CsOtBu
EtOH CsOtBu
EtOH NaOtBu
CsOtBu
CsOtBu
23
23
23
40
70
40
60
35
48
66
25
56
67
70
75
77
77
81d
(3) (a) Zeng, X.; Hu, Q.; Qian, M.; Negishi, E. J. Am. Chem. Soc. 2003,
125, 13636. (b) Zeng, X.; Qian, M.; Hu, Q.; Negishi, E. Angew. Chem.,
Int. Ed. 2004, 43, 2259.
segphos
segphos
segphos
segphos
segphos
(4) For examples of Pd-catalyzed reactions involving alkylidene-π-
allylpalladium intermediates, see: (a) Kleijn, H.; Westmijze, H.; Meijer,
J.; Vermeer, P. Recl. TraV. Chim. Pays-Bas 1983, 102, 378. (b) Djahanbini,
D.; Cazes, B.; Gore, J. Tetrahedron Lett. 1984, 25, 203. (c) Djahanbini,
D.; Cazes, B.; Gore, J. Tetrahedron 1985, 41, 867. (d) Djahanbini, D.; Cazes,
B.; Gore, J. Tetrahedron 1987, 43, 3441. (e) Trost, B. M.; Tour, J. M. J.
Org. Chem. 1989, 54, 484. (f) Nokami, J.; Maihara, A.; Tsuji, J. Tetrahedron
Lett. 1990, 31, 5629. (g) Piotti, M. E.; Alper, H. J. Org. Chem. 1994, 59,
1956. (h) Imada, Y.; Vasapollo, G.; Alper, H. J. Org. Chem. 1996, 61,
7982. (i) Imada, Y.; Ueno, K.; Kutsuwa, K.; Murahashi, S. Chem. Lett.
2002, 140. (j) Trost, B. M.; Fandrick, D. R.; Dinh, D. C. J. Am. Chem.
Soc. 2005, 127, 14186. (k) Imada, Y.; Nishida, M.; Kutsuwa, K.; Murahashi,
S.; Naota, T. Org. Lett. 2005, 7, 5837.
(5) Benyunes, S. A.; Brandt, L.; Fries, A.; Green, M.; Mahon, M. F.;
Papworth, T. M. T. J. Chem. Soc., Dalton Trans. 1993, 3785.
(6) Theoretical studies on closely related systems suggested that a
σ-(allenylmethyl)palladium species is less stable than an alkylidene-π-
allylpalladium and an σ-(1,3-dien-2-yl)palladium. See: Bigot, B.; Delbecq,
F. New J. Chem. 1990, 14, 659.
a The reactions were carried out with a Pd catalyst generated from
Pd(dba)2 and a chiral ligand L*. b Isolated yield by silica gel chromatography.
c Determined by HPLC analysis with a chiral stationary phase column
(Daicel Chiralpak AS-H). d [R]27.5 ) -26 (c 0.99, CHCl3).
D
from Pd(dba)2 and (R)-binap afforded the vinylallene (-)-
(R)-3an14 with 67% ee in 60% yield in THF at 23 °C in the
(11) (a) de Graaf, W.; Boersma, J.; van Koten, G.; Elsevier, C. J. J.
Organomet. Chem. 1989, 378, 115. (b) Matsumoto, Y.; Naito, M.; Uozumi,
Y.; Hayashi, T. J. Chem. Soc., Chem. Commun. 1993, 1468. (c) Tillack,
A.; Michalik, D.; Koy, C.; Michalik, M. Tetrahedron Lett. 1999, 40, 6567.
(d) Tillack, A.; Koy, C.; Michalik, D.; Fischer, C. J. Organomet. Chem.
2000, 603, 116. (e) Han, J. W.; Tokunaga, N.; Hayashi, T. J. Am. Chem.
Soc. 2001, 123, 12915. (f) Hayashi, T.; Tokunaga, N.; Inoue, K. Org. Lett.
2004, 6, 305.
(12) For transition-metal-catalyzed kinetic resolutions of racemic chiral
allenes, see: (a) Noguchi, Y.; Takiyama, H.; Katsuki, T. Synlett 1998, 543.
(b) Sweeney, Z. K.; Salsman, J. L.; Andersen, R. A.; Bergman, R. G. Angew.
Chem., Int. Ed. 2000, 39, 2339.
(7) For an analogous example of nickel species, see: Karlstro¨m, A. S.
E.; Itami, K.; Ba¨ckvall, J.-E. J. Org. Chem. 1999, 64, 1745.
(8) For Pd-catalyzed formal SN2′′ substitutions, see: (a) Trost, B. M.;
Hung, M.-H. J. Am. Chem. Soc. 1984, 106, 6837. (b) Trost, B. M.; Urch,
C. J.; Hung, M.-H. Tetrahedron Lett. 1986, 27, 4949. (c) Andersson, P. G.;
Ba¨ckvall, J.-E. J. Org. Chem. 1991, 56, 5349. (d) Nilsson, Y. I. M.;
Andersson, P. G.; Ba¨ckvall, J.-E. J. Am. Chem. Soc. 1993, 115, 6609. (e)
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M.; Bunt, R. C. J. Am. Chem. Soc. 1998, 120, 70.
(9) dpbp ) 2,2′-bis(diphenylphosphino)-1,1′-biphenyl. See: Ogasawara,
M.; Yoshida, K.; Hayahshi, T. Organometallics 2000, 19, 1567 and
references therein.
(10) (a) Åkermark, B.; Hansson, S.; Krakenberger, B.; Vitagliano, A.;
Zetterberg, K. Organometallics 1984, 3, 679. (b) Keinan, e.; Saha, M. J.
Chem. Soc., Chem. Commun. 1984, 648. (c) Frost, C. G.; Howarth, J.;
Williams, J. M. Tetrahedron: Asymmetry 1992, 3, 1089.
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Hoffmann-Ro¨der, A.; Krause, N. Angew. Chem., Int. Ed. 2002, 41, 2933.
(b) Ohno, H.; Nagaoka, Y.; Tomioka, K. In Modern Allene Chemistry;
Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, 2004; p 141.
(14) The absolute configuration of 3an was deduced by the Lowe-
Brewster rule. See: (a) Lowe, G. Chem. Commun. 1965, 411. (b) Brewster,
J. H. Top. Stereochem. 1967, 2, 1.
Org. Lett., Vol. 8, No. 23, 2006
5411

presence of CsOtBu (entry 1). The Pd/(R)-segphos15 catalyst
showed a better enantioselectivity than the (R)-binap ana-
logue (entries 2-5). It was found that the use of a more
polar solvent (EtOH) and slightly higher temperature (at 40
°C) improved the enantioselectivity (entries 3 and 4).
However, a reaction at 70 °C decreased the chemical yield
of 3an (entry 5). Under the optimized conditions with
NaOtBu as base, (R)-3an was obtained in the highest
enantioselectivity with 81% ee (entry 6).16
Scheme 4
A comparison between the two asymmetric processes
of producing axially chiral allenes, one with the bromodienes
(eq 2)2b,c,e and the other with the bromotrienes 1 (Table 2),
is illustrated in Scheme 4. In the reaction of a bromodiene
substrate, the configuration of an axially chiral allene is
determined at a nucleophilic attack of Nu- to an alkylidene-
π-allylpalladium intermediate (Scheme 4, left). In the reac-
tion of the bromotriene substrate 1, however, the local allenic
configuration is already determined prior to the nucleo-
philic attack of Nu- to an allenyl-π-allylpalladium inter-
mediate.
In summary, we have developed a novel Pd-catalyzed
reaction to prepare conjugated vinylallenes from 2-bromo-
1,3,5-triene and a soft nucleophile. The reaction proceeds
via a formal SN2′′ pathway, and a dynamic process of Pd
intermediates determines the selectivity of the Pd-catalyzed
reaction. The reaction was extended to an asymmetric
counterpart, and an axially chiral vinylallene was obtained
with up to 81% ee.
Acknowledgment. This work was partly supported by a
Grant-in-Aid for Scientific Research from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
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.
(15) Saito, T.; Yokozawa, T.; Ishizaki, T.; Moroi, T.; Sayo, N.; Miura,
T.; Kumobayashi, H. AdV. Synth. Catal. 2001, 343, 264.
(16) For an example of preparing enantiomerically enriched vinylallenes,
see: Molander, G. A.; Sommers, E. M.; Baker, S. R. J. Org. Chem. 2006,
71, 1563.
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