J. Am. Chem. Soc. 1999, 121, 8657-8658
8657
tive catalytic allylation of both carbon and nitrogen nucleophiles
at the more-substituted allylic termini. In our further investigation
of the reactivity of several ruthenium complexes toward sulfur-
containing compounds,12 we found the first example of the
transition-metal complex-catalyzed addition of organic disulfides
to alkenes.13 Therefore, the ruthenium complex seems to be one
of the most promising catalysts for the transformation of sulfur-
containing compounds. After many trials, we finally found the
first ruthenium-catalyzed allylation of both aliphatic and aromatic
thiols with various allylic reagents, including allylic alcohols,
under extremely mild reaction conditions. We report here the
development of this new ruthenium-catalyzed reaction which
enables a simple and general synthesis of allylic sulfides.
Treatment of aliphatic and aromatic thiols, represented by
pentanethiol (2a) and benzenethiol (2b), with allyl methyl
carbonate (1a) in the presence of 5 mol % Cp*RuCl(cod) in CH3-
CN at room temperature for 1 h under an argon atmosphere gave
the corresponding allylic sulfides, allyl pentyl sulfide (3a) and
allyl phenyl sulfide (3b), in high yields, respectively (eq 1).
First Ruthenium-Catalyzed Allylation of Thiols
Enables the General Synthesis of Allylic Sulfides
Teruyuki Kondo, Yasuhiro Morisaki, Shin-ya Uenoyama,
Kenji Wada, and Take-aki Mitsudo*
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering, Kyoto UniVersity
Sakyo-ku, Kyoto 606-8501, Japan
ReceiVed May 24, 1999
The transition-metal complex-catalyzed substitution reaction
of allylic alcohol derivatives with nucleophilic reagents is now a
well-established methodology in organic synthesis and is widely
used to construct complex organic molecules.1,2 However, even
though a wide range of nucleophiles, such as carbon, nitrogen,
and oxygen nucleophiles, and transition-metal catalysts, especially
those involving palladium,2 have been studied,3 a general method
for synthesizing allylic sulfides by the transition-metal complex-
catalyzed allylation of sulfur nucleophiles has not yet been
reported, since, in catalytic reactions, sulfur-containing compounds
have long been known to act as catalyst poisons because of their
strong coordinating properties.4 Recent progress in the transition-
metal complex-catalyzed synthesis of allylic sulfides without
poisoning of the catalyst has included (1) rearrangement of
O-allylphosphoro- or phosphonothionates,5 (2) conversion of
O-allyl or S-allyl dithiocarbonates with liberation of carbon oxide
sulfide (COS),6 and (3) allylic substitution by silylated thiols,7
heterocyclic sulfur nucleophiles,8 sodium thiophenoxides,9,10c and
aromatic thiols,10 However, some of these reactions have a serious
drawback with regard to substrate preparation. In addition, the
catalyst systems reported so far are strictly limited to palladium
catalysts,5-10 and in the simple allylic substitution with thiols,
only aromatic and heteroaromatic thiols can be used.10
First, the catalytic activity of several ruthenium complexes was
examined in the reaction of 1a with 2a. The results are
summarized in Table 1. Among the catalysts examined, Cp*RuCl-
(cod) and CpRuCl(cod) showed high catalytic activity. Other di-
and zerovalent ruthenium complexes, such as CpRuCl(PPh3)2, (p-
cymene)RuCl2(PPh3), RuCl2(PPh3)3, Ru(cod)(η6-C8H10), and Ru3-
(CO)12, were totally ineffective. Almost no reaction occurred with
Pd(PPh3)4, RhCl(PPh3)3, or IrCl(CO)(PPh3)2 catalysts, and the
present reaction is characteristic of ruthenium catalysts. The use
of an appropriate solvent is also critically important for a
successful reaction. Among the solvents examined, CH3CN gave
the best result, which strongly suggests that CH3CN acts as a
suitable ligand to an active ruthenium intermediate as well as a
solvent to prevent catalyst poisoning by thiols.
Various allylic compounds, such as allyl ethyl carbonate (1b),
allyl trifluoroacetate (1c), and allyl acetate (1d), can be used in
the present allylation reaction of pentanethiol (2a) to give allyl
pentyl sulfide (3a) in high yield (eq 2). On the other hand, the
yield of 3a decreased to 38% with allyl phenyl ether (1e).
Furthermore, under the present reaction conditions, it is difficult
to cleave the allylic carbon-sulfur bond with the ruthenium
catalyst,14 as shown in the reaction of allyl phenyl sulfide (3b)
with 2a. Note that allyl alcohol itself (1f), which is considered to
be a poor substrate for the formation of π-allyl transition-metal
complexes, gave 3a in high yield (88%). The direct use of allyl
alcohols as an effective allylating reagent is an important theme
in transition-metal complex-catalyzed allylation reactions and is
highly economical in terms of atoms used.15
On the other hand, we recently reported that ruthenium
complexes, such as Ru(cod)(η6-C8H10)11a (cod ) 1,5-cycloocta-
diene, η6-C8H10 ) 1,3,5-cyclooctatriene) and Cp*RuCl(cod)11b
(Cp* ) pentamethylcyclopentadienyl), facilitate the highly selec-
(1) Harrington, P. J. Transition Metals in Total Synthesis; John Wiley &
Sons: New York, 1990; p 25.
(2) For a review of palladium-catalyzed allylic alkylation, see: (a) Trost,
B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96, 395. (b) Tsuji, J. Palladium
Reagents and Catalysts; John Wiley & Sons: New York, 1995; p 290. (c)
Harrington, P. J. In ComprehensiVe Organometallic Chemistry II; Abel, E.
W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, U.K., 1995;
Vol. 12, p 797.
(3) (a) Fe: Enders, D.; Jandeleit, B.; Raabe, G. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1949; Angew. Chem. 1994, 106, 2033. (b) Co: Bhatia, B.;
Reddy, M. M.; Iqbal, J. Tetrahedron Lett. 1993, 34, 6301. (c) Ni: Bricout,
H.; Carpentier, J.-F.; Mortreux, A. J. Chem. Soc., Chem. Commun. 1995, 1863.
(d) Rh: Evans, P. A.; Nelson, J. D. J. Am. Chem. Soc. 1998, 120, 5581. (e)
Ir: Takeuchi, R.; Kashio, M. J. Am. Chem. Soc. 1998, 120, 8647. (f) Pt:
Brown, J. M.; MacIntyre, J. E. J. Chem. Soc., Perkin Trans. 2 1985, 961. (g)
Mo: Trost, B. M.; Hachiya, I. J. Am. Chem. Soc. 1998, 120, 1104. (h) W:
Lloyd-Jones, G. C.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1995, 34, 462;
Angew. Chem. 1995, 107, 534 and pertinent references therein.
(4) (a) Hegedus, L. L.; McCabe, R. W. Catalyst Poisoning; Marcel
Dekker: New York, 1984. (b) Hutton, A. T. In ComprehensiVe Coordination
Chemistry; Wilkinson, G., Gillard, R. D., McCleverty, J. A., Eds.; Perga-
mon: Oxford, U.K., 1984; Vol. 5, p 1151.
(5) (a) Yamada, Y.; Mukai, K.; Yoshioka, H.; Tamaru, Y.; Yoshida, Z.
Tetrahedron Lett. 1979, 5015. (b) Tamaru, Y.; Yoshida, Z.; Yamada, Y.;
Mukai, K.; Yoshioka, H. J. Org. Chem. 1983, 48, 1293.
(6) (a) Auburn, P. R.; Whelan, J.; Bosnich, B. J. Chem. Soc., Chem.
Commun. 1986, 146. (b) Lu, X.; Ni, Z. Synthesis 1987, 66.
(7) Trost, B. M.; Scanlan, T. S. Tetrahedron Lett. 1986, 27, 4141.
(8) (a) Moreno-Man˜as, M.; Pleixats, R.; Villarroya, M. Tetrahedron 1993,
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(9) Kang, S.-K.; Park, D.-C.; Jeon, J.-H.; Rho, H.-S.; Yu, C.-M. Tetrahedron
Lett. 1994, 35, 2357.
The allylation of several aliphatic and heteroaromatic thiols
(2c-j) with allyl methyl carbonate (1a) also proceeded smoothly
(11) (a) Zhang, S.-W.; Mitsudo, T.; Kondo, T.; Watanabe, Y. J. Organomet.
Chem. 1993, 450, 197. (b) Kondo, T.; Ono, H.; Satake, N.; Mitsudo, T.;
Watanabe, Y. Organometallics 1995, 14, 1945.
(12) (a) Fujita, K.; Ikeda, M.; Kondo, T.; Mitsudo, T. Chem. Lett. 1997,
57. (b) Fujita, K.; Ikeda, M.; Nakano, Y.; Kondo, T.; Mitsudo, T. J. Chem.
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(13) Kondo, T.; Uenoyama, S.; Fujita, K.; Mitsudo, T. J. Am. Chem. Soc.
1999, 121, 482.
(10) (a) Goux, C.; Lhoste, P.; Sinou, D. Tetrahedron Lett. 1992, 33, 8099.
(b) Goux, C.; Lhoste, P.; Sinou, D. Tetrahedron 1994, 50, 10321. (c) Geneˆt,
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10.1021/ja991704f CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/03/1999