Water enables direct use of allyl alcohol for Tsuji-Trost reaction without activators

Article abstract of DOI:10.1021/ol048207a

(Chemical Equation Presented) An aqueous biphasic reaction system enables the direct use of allyl alcohol in the Tsuji-Trost reaction without the help of any activating reagents for allyl alcohol. The reaction conditions are neutral to basic, allowing the use of amines as the nucleophile. Theoretical calculations have elucidated the importance of hydration of the hydroxy group for the smooth generation of π-allylpalladium species.

Full text of DOI:10.1021/ol048207a

ORGANIC
LETTERS
2004
Vol. 6, No. 22
4085-4088
Water Enables Direct Use of Allyl
Alcohol for Tsuji
Activators
−Trost Reaction without
Hidenori Kinoshita,† Hiroshi Shinokubo,*,‡,§ and Koichiro Oshima*,†
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Kyoto 606-8502, Japan, and Department of Material Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Kyoto 615-8510, Japan
hshino@kuchem.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received September 5, 2004
ABSTRACT
An aqueous biphasic reaction system enables the direct use of allyl alcohol in the Tsuji
reagents for allyl alcohol. The reaction conditions are neutral to basic, allowing the use of amines as the nucleophile. Theoretical calculations
have elucidated the importance of hydration of the hydroxy group for the smooth generation of -allylpalladium species.
−Trost reaction without the help of any activating
π
The Tsuji-Trost reaction using a π-allylpalladium interme-
diate has served as a pivotal reaction in a number of syntheses
of natural and unnatural compounds. The reaction often
employs Pd(0) complexes and activated allyl alcohol deriva-
tives, in particular, allylic halides, acetates, and carbonates.
Much attention has been paid to the direct use of allyl
alcohols for the allyl source. However, the precedent
protocols require stoichiometric or catalytic activators for
allyl alcohols such as acids, Lewis acids, Et3B, and CO2,
due to inherent low leaving aptitude of the hydroxy group.1
However, acidic activators cannot be compatible with basic
nucleophiles such as amines. Recently, particular ligands
have been reported to enable such conversion without the
aid of activators.2 Here we wish to disclose another solu-
tion: the direct use of allyl alcohol for the Tsuji-Trost
reaction at room temperature is achieved in an aqueous
system without any activator. Although there have been a
number of reports on the Tsuji-Trost reaction with allylic
acetates or carbonates in aqueous media,3 none of them
accomplished the direct use of allyl alcohol without activa-
tors.4 The reaction conditions are neutral to basic, allowing
the use of amines as the nucleophile.
We attempted the Tsuji-Trost reaction in water with allyl
alcohol as an allyl source. We selected 2-methylcyclohexane-
1,3-dione (1a) as a nucleophile and conducted the reaction
with the catalyst combination of [PdCl(η3-C3H5)]2 and tppts
in water. In an ethyl acetate-water biphasic system, the
allylated product 2a was obtained in 44% yield as a sole
product (Scheme 1). While the allylation reaction was
† Department of Engineering.
Scheme 1
‡ Department of Science.
§ PRESTO, Japan Science Technology Agency (JST).
(1) (a) Lu, X.; Jiang, X.; Tao, X. J. Organomet. Chem. 1988, 344, 109.
(b) Satoh, I.; Ikeda, M.; Miura, M.; Nomura, M. J. Org. Chem. 1997, 62,
4877. (c) Tamaru, Y.; Horino, Y.; Araki, M.; Tanaka, S.; Kimura, M.
Tetrahedron Lett. 2000, 41, 5705. (d) Stary, J.; Stara, I. G.; Kocovsky, P.
Tetrahedron 1993, 34, 179. (e) Lumin, S.; Falck, J. R.; Capdevila, J.; Karara,
A. Tetrahedron Lett. 1992, 33, 2091. (f) Sakamoto, M.; Shimizu, I.;
Yamamoto, A. Bull. Chem. Soc. Jpn. 1996, 69, 1065. (g) Patil, N. T.;
Yamamoto, Y. Tetrahedron Lett. 2004, 45, 3101.
(2) (a) Ozawa, F.; Okamoto, H.; Kawagishi, S.; Yamamoto, S.; Minami,
T.; Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 10968.(b) Kayaki, Y.; Koda,
T.; Ikariya, T. J. Org. Chem. 2004, 69, 2595.
10.1021/ol048207a CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/05/2004

Scheme 2
Table 1. Tsuji-Trost Reaction with Allyl Alcohol in Aqueous
Biphasic Systema
yield (entries 1 and 2). Ethyl acetoacetate (1c) afforded
monoallylated product as a sole product (entry 3). Cyclic
diketones 1d and 1e afforded the desired products in good
yields in the presence of catalytic Na2CO3 (entries 4-7).
The reaction system also accomplishes conversion of amines
to the corresponding allyl- or diallylamines (entries 7-11).
Aniline (1f) underwent selective monoallylation in the
absence of Na2CO3. No trace of diallylaniline was detected,
while the addition of Na2CO3 provided it.
Crotyl alcohol (4a) and its regioisomer 4b, 1-buten-3-ol,
yielded a mixture of isomeric amines 5a and 5b in the same
ratio, suggesting that the reaction proceeds via the π-allyl
intermediate (Scheme 2). The reaction of diols 4c and 4d
with dibenzylamine selectively afforded monoaminated
products 5c and 5d in 75% and 62%, respectively. None of
diaminated products were detected in the crude reaction
mixture. Because cinnamyl alcohol (4e) was completely
recovered under the reaction conditions, a very hydrophobic
substrate seems not reactive in this system. The selective
monoamination of diols 4c and 4d may be explained as
follows. While diols 4c and 4d are hydrophilic enough to
have reactivity, increased hydrophobicity of the products 5c
and 5d after the initial amination retards the second amina-
tion.
We confirmed that allylpalladium species can be readily
formed from allyl alcohol in water at room temperature.
Treatment of allyl alcohol with a stoichiometric amount of
a water-soluble palladium complex, prepared from Pd(OAc)2
and a trisodium salt of tris(m-sulfonatophenyl)phosphine
(tppts), provided a π-allylpalladium species on the basis of
a Reaction conditions: [PdCl(η3-C3H5)]2 (4.6 mg, 0.0125 mmol), tppts
(62.5 mg, 0.11 mmol), water (5 mL), AcOEt (5 mL), allyl alcohol (0.08
mL, 1.2 mmol), and nucleophile (0.05 mL, 0.5 mmol). b Aniline (2.2 mmol)
and allyl alcohol (1.0 mmol) were employed.
sluggish in water alone, no reaction proceeded in ethyl acetate
under otherwise identical reaction conditions. Addition of a
catalytic amount of sodium carbonate improved the yield of
2a to 92%.
Table 1 summarizes the results of allylation of various
nucleophiles with allyl alcohol. Acetylacetone (1b) under-
went monoallylation in the absence of Na2CO3, while the
addition of the base provided diallylated product in good
(3) (a) Safi, M.; Sinou, D. Tetrahedron Lett. 1991, 32, 2025. (b) Geneˆt,
J. P.; Blart, E.; Savignac, M. Synlett 1992, 715. (c) Blart, E.; Geneˆt, J. P.;
Safi, M.; Savignac, M.; Sinou, D. Tetrahedron 1994, 50, 505. (d) Kobayashi,
S.; Lam, W. W.-L.; Manabe, K. Tetrahedron Lett. 2000, 41, 6115. (e) Danjo,
H.; Tanaka, D.; Hayashi, T.; Uozumi, Y. Tetrahedron 1999, 55 14341, (f)
Uozumi, Y.; Shibatomi, K. J. Am. Chem. Soc. 2001, 123, 2919. (g)
Bergbreiter, D. E.; Liu, Y.-S. Tetrahedron Lett. 1997, 38, 7843.
(4) Recently, Kobayashi has reported allylation in aqueous media with
a carboxylic acid as an activator. Manabe, K.; Kobayashi, S. Org. Lett.
2003, 5, 3241.
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Org. Lett., Vol. 6, No. 22, 2004

Scheme 3
1H NMR and 31P NMR analyses in D2O (Scheme 3). The
NMR spectra of the reaction mixture were almost identical
with the solution of [PdCl(η3-allyl)]2 in D2O.5
Initially, we speculated that carbon dioxide from sodium
carbonate might act as the activator, since Yamamoto et al.
have already reported a formation of π-allylpalladium from
allyl alcohol under a pressure of CO2 (30 atm) via a half-
carbonate ester.1f However, the fact that the reaction also
proceeds in the absence of sodium carbonate clearly rules
out this possibility. Involvement of allyl acetate via trans-
esterification with AcOEt is not probable because the reaction
occurred in an Et2O-water biphasic system.6 At this time,
we propose the reaction mechanism in which water activates
allyl alcohol via hydration of the hydroxy group and
stabilizes the resulting hydroxide ion by strong solvation with
water, as outlined in Scheme 4. In organic solvents, elimina-
Scheme 4
tion of naked hydroxide is a very unfavorable process. In
water, however, the hydroxide ion can leave with hydrating
water molecules and the negative charge can be delocalized
in the water cluster.
To elucidate the effect of water, we have conducted
theoretical calculations.7 The geometry of palladium com-
plexes PC and the transition state TS was optimized with
the B3LYP functional. The 6-31G* basis set was employed
except for Pd, with which LANL2DZ+ECP were used
(denoted as BS1). During optimization, solvent effects were
taken into account by means of the Onsager method.8 At
the optimized geometries, energies were calculated with the
PCM method at the B3LYP/BS1 level.9
Figure 1. Calculated structures, Mulliken charges (italics), and
activation energies.
one water hydration, whereas Ea ) 26.8 kcal/mol for two
water hydration). Electron population analyses (Mulliken
charge) indicate that negative charge delocalizes in the
solvating waters in TS, and an increased degree of hydration
results in decreasing each charge on oxygen atoms (Figure
1). In the real system, a greater number of water molecules
The calculated activation energy with the PCM method
was very high (Ea ) 60.7 kcal/mol).10 We then included
hydrating waters coordinating to the hydroxy group. Addition
of hydrating waters changed the structure of transition state
depending on the number of waters during reoptimization.
Introduction of hydrating waters significantly lowered the
activation energy, and increasing the number of waters
resulted in decrease of the activation energy (Ea ) 36.0 for
(7) For theoretical calculations involving π-allylpalladium, see: (a)
Delbecq, F.; Lapouge, C. Organometallics 2000, 19, 2716. (b) Branchadell,
V.; Moreno-Manas, M.; Pleixats, R. Organometallics 2002, 21, 2407. (c)
Solin, N.; Szabo´, K. J. Organometallics 2001, 20, 5464. (d) Szabo´, K. J.
Chem. Eur. J. 1997, 3, 592. (e) Szabo´, K. J. Chem. Eur. J. 2000, 6, 4413.
(f) Solin, N.; Narayan, S.; Szabo´, K. J. J. Org. Chem. 2001, 66, 1686. (g)
Szabo´, K. J.; Hupe, E.; Larsson, A. L. E. Organometallics 1997, 16, 3779.
(h) Szabo´,K. J. Organometallics 1996, 15, 1128. (i) Szabo´, K. J. J. Am.
Chem. Soc. 1996, 118. 7818. (j) Sakaki, S.; Takeuchi, K.; Sugimoto, M.;
Kurosawa, H. Organometallics 1997, 16, 2995. (k) Sakaki, S.; Satoh, H.;
Shono, H.; Ujino, Y. Organometallics 1996, 15, 1713. (l) Biswas, B.;
Sugimoto, M.; Sakaki, S. Organometallics 1999, 18, 4015. (m) Branchadell,
V.; Moreno-Man˜as, M.; Pajuelo, F.; Pleixats, R. Organometallics 1999,
18, 4934; (n) Hagelin, H.; Åkermark, B.; Norrby, P.-O. Chem. Eur. J. 1999,
5, 902; (m) Dedieu, A. Chem. ReV. 2000, 100, 543.
(5) See the Supporting Information.
(6) The reaction of acetylacetone (1b) with allyl alcohol in an Et2O-
water biphasic system provided 3b in 53% yield under otherwise identical
conditions as entry 2 in Table 1.
Org. Lett., Vol. 6, No. 22, 2004
4087

should be involved in solvation, lowering the activation
energy more effectively.
ate. Further research to expand the scope and improve the
efficiency is currently underway in our laboratory.
In conclusion, we have found that aqueous reaction media
enable the direct use of allyl alcohol as the allyl source for
the Tsuji-Trost reaction without the help of any activating
reagents. Theoretical calculations have elucidated the im-
portance of hydration of the hydroxy group in allyl alcohol
for the smooth generation of the π-allylpalladium intermedi-
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research (No. 14703026) from the
Ministry of Education, Culture, Sports, Science, and Tech-
nology, Japan. H.K. acknowledges the Research Fellowships
of the JSPS for Young Scientists.
Supporting Information Available: General procedures,
1H and 31P NMR spectra of allylpalladium intermediates in
D2O, and the Cartesian coordinates. This material is available
free of charge via the Internet at http://pubs.acs.org.
(8) Optimization with the PCM method failed to converge.
(9) Cossi, M.; Scalmani, G.; Rega, N.; Barone, V. J. Chem. Phys. 2002,
117, 43.
(10) π-Allylpalladium (AP) is stabilized in water by 18.4 kcal/mol from
its optimized structure in a vacuum (B3LYP/BS1), whereas the Pd(0)-
olefin complex (PC) is destabilized by 14.3 kcal/mol. This can be one of
the driving forces.
OL048207A
4088
Org. Lett., Vol. 6, No. 22, 2004