J. Am. Chem. Soc. 2001, 123, 3393-3394
3393
Table 1. Propargylic Alkylation of Propargylic Alcohols (2) with
Acetone Catalyzed by [Cp*RuCl(µ2-SMe)2RuCp*Cl] (1a)a
Ruthenium-Catalyzed Propargylic Alkylation of
Propargylic Alcohols with Ketones: Straightforward
Synthesis of γ-Keto Acetylenes
Yoshiaki Nishibayashi,† Issei Wakiji,‡ Youichi Ishii,‡
Sakae Uemura,*,† and Masanobu Hidai*,§
run
1
R
yield, %b run
R
yield, %b
2a Ph
3a, 78 (85)c
7
8
9
2f p-MeOC6H4 3f, 56
2g p-FC6H4
2h p-ClC6H4
Department of Energy and Hydrocarbon Chemistry
Kyoto UniVersity, Kyoto 606-8501, Japan
Department of Chemistry and Biotechnology
The UniVersity of Tokyo, Tokyo 113-8656, Japan
Department of Materials Science and Technology
Science UniVersity of Tokyo, Chiba 278-8510, Japan
2d 2a Ph
3a, (64)c
3g, 75
3h, 67
3i, 83
3j, 88
3
4
5
6
2b o-MeOC6H4 3b, 72
2c o-MeC6H4 3c, 74
2d m-MeC6H4 3d, 74
2e p-MeC6H4 3e, 82
10 2i 1-naphthyl
11 2j 2-naphthyl
12 2k Ph2CdCH- 3k, 55e
a All the reactions of 2 (0.60 mmol) were carried out in the presence
of 1a (0.03 mmol) and NH4BF4 (0.06 mmol) in acetone (36 mL) at
reflux temperature for 4 h. b Isolated yield. c GLC yield. d Reaction was
carried out at room temperature for 8 h. e 10 mol % of 1a was used.
ReceiVed February 14, 2001
The allylic substitution reaction of allylic alcohol derivatives
with nucleophiles catalyzed by transition-metal complexes is one
of the most successful and reliable methods in organic synthesis.1
The reaction proceeds via (η-allyl)metal species to afford a wide
variety of allylated products with high chemo-, regio-, and
stereoselectivities.1 In sharp contrast, much less attention has been
paid to the propargylic substitution reaction of propargylic alcohol
derivatives with nucleophiles.2 The Nicholas reaction is known
to be an effective tool for such transformation but has some
drawbacks: a stoichiometric amount of Co2(CO)8 is required, and
several steps are necessary to obtain propargylic products from
propargylic alcohols via cationic propargyl complexes [(propargyl)-
Co2(CO)6]+.3 We have recently disclosed the ruthenium-catalyzed
propargylic substitution reactions of propargylic alcohols with
various heteroatom-centered nucleophiles such as alcohol, amide,
amine, thiol, and diphenylphosphine oxide to afford the corre-
sponding propargylic products in high yields with complete
regioselectivities.4 Interestingly, the reactions are catalyzed by
thiolate-bridged diruthenium complexes5 such as [Cp*RuCl(µ2-
SR)2RuCp*Cl] (Cp* ) η5-C5Me5; R ) Me (1a), Et, nPr, iPr (1b))
and [Cp*RuCl(µ2-SiPr)2RuCp*(OH2)]OTf (1c; OTf ) OSO2CF3).4
We have now extended this chemistry to a more valuable carbon-
carbon bond formation reaction by using carbon-centered nu-
cleophiles. Surprisingly, not only â-diketones such as acetyl-
acetone but also simple dialkyl ketones such as acetone have been
found to work effectively as nucleophiles, giving the correspond-
ing propargylic alkylated products in high yields with complete
regioselectivities. Preliminary results on this propargylic alkylation
are described here.
temperature for 4 h afforded 4-phenyl-5-hexyn-2-one (3a) in 78%
isolated (85% GLC) yield (Table 1; run 1).7,8 Neither allenic
byproducts nor other regioisomers of 3a were observed by GLC
1
and H NMR. The carbon-carbon bond formation exclusively
occurred at the propargylic carbon of 2a. The reaction proceeded
even at room temperature, but 8 h was required to produce 3a in
64% GLC yield (Table 1; run 2). Substantial isotope effect (kH/
kD ) 2) was observed when the reaction was carried out at 40
°C.9 This result indicates that the C-H bond breaking at the
R-position of acetone is involved in the rate-determining step. It
is noteworthy that the propargylic alkylation of 2a with acetone
proceeds smoothly under extremely mild and neutral reaction
conditions. This is in sharp contrast to the allylic alkylation
catalyzed by a variety of transition-metal complexes where a
stoichiometric amount of base is required to activate carbon-
centered nucleophiles.10
Reactions of various propargylic alcohols with acetone have
been carried out in the presence of 1a and NH4BF4. Propargylic
substitution reactions of 1-aryl- and 1-alkenyl-substituted pro-
pargylic alcohols (2b-k) with acetone at reflux temperature for
4 h proceeded smoothly to afford the corresponding propargylic
alkylated products (3b-k) in moderate to high yields (Table 1;
runs 3-12). When (R)-1-phenyl-2-propyn-1-ol was treated with
acetone at room temperature for 12 h, racemic 3a was formed in
69% isolated yield. Reaction of 1,1-diaryl-substituted propargylic
alcohols such as Ph2C(OH)CtCH did not proceed even after a
prolonged reaction time (72 h).
Treatment of 1-phenyl-2-propyn-1-ol (2a) in acetone in the
(6) Preparation of 1a is as follows. To a suspension of [Cp*RuCl2]2 (8.3
g, 14 mmol) in THF (150 mL) was added MeSSiMe3 (4.2 g, 35 mmol), and
the mixture was stirred at room temperature for 24 h. A brown solid
precipitated was filtered off, washed with n-hexane, and recrystallized from
presence of 1a6 (5 mol %) and NH4BF4 (10 mol %) at reflux
† Kyoto University.
‡ The University of Tokyo.
CH2Cl2-n-hexane to give brown crystals of 1a (6.4 g, 10 mmol, 71%); H
1
§ Science University of Tokyo.
NMR δ 1.62 (s, 30H, C5Me5), 2.51 (s, 6H, SMe3).
(1) For recent reviews, see: (a) Tsuji, J. Palladium Reagents and Catalysts;
John Wiley & Sons: New York, 1995. (b) Trost, B. M.; Van Vranken, D. L.
Chem. ReV. 1996, 96, 395. (c) Trost, B. M.; Lee, C. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; Wiley-VCH: New York, 2000; Chapter 8E.
(2) (a) Macdonald, T. L.; Reagan, D. R. J. Org. Chem. 1980, 45, 4740. (b)
Imada, Y.; Yuasa, M.; Nakamura, I.; Murahashi, S.-I. J. Org. Chem. 1994,
59, 2282. (c) Mahrwald, R.; Quint, S. Tetrahedron 2000, 56, 7463.
(3) (a) Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207 and references
therein. (b) Caffyn, A. J. M.; Nicholas, K. M. In ComprehensiVe Organo-
metallic Chemistry II; Abel, E. W., Stone, G. A.; Wilkinson, G., Eds.;
Pergamon: New York, 1995; Vol. 12, Chapter 7.1.
(7) A typical experimental procedure for the reaction of 2a with acetone
catalyzed by 1a is described below. In a 50 mL flask were placed 1a (0.03
mmol) and NH4BF4 (0.06 mmol) under N2. Anhydrous acetone (36 mL) was
added, and then the mixture was magnetically stirred at room temperature.
After addition of 2a (0.60 mmol), the reaction flask was kept at reflux
temperature for 4 h. The reaction mixture was treated with brine (150 mL)
and extracted with diethyl ether (20 mL × 3). The ether layer was dried over
anhydrous MgSO4. For isolation, the extract was concentrated under reduced
pressure by an aspirator, and then the residue was purified by TLC (SiO2)
with EtOAc-n-hexane (1/9) to give 3a as a yellow solid (0.47 mmol, 78%
yield).
(4) Nishibayashi, Y.; Wakiji, I.; Hidai, M. J. Am. Chem. Soc. 2000, 122,
11019.
(8) Other di- and monoruthenium complexes except for 1b and 1c were
ineffective for the propargylic alkylation. See Supporting Information for
experimental details.
(5) The thiolate-bridged diruthenium complexes (1a-c) have been found
to provide unique bimetallic reaction sites for activation and transformation
of various terminal alkynes, see: Nishibayashi, Y.; Yamanashi, M.; Wakiji,
I.; Hidai, M. Angew. Chem., Int. Ed. Engl. 2000, 39, 2909 and references
therein.
(9) See Supporting Information for experimental details.
(10) (a) Trost, B. M.; Schroeder, G. M. J. Am. Chem. Soc. 1999, 121, 6759.
(b) Braun, M.; Laicher, F.; Meier, T. Angew. Chem., Int. Ed. Engl. 2000, 39,
3494.
10.1021/ja015670z CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/17/2001