Ruthenium-catalyzed propargylic alkylation of propargylic alcohols with ketones: Straightforward synthesis of γ-keto acetylenes [2]

Full text of DOI:10.1021/ja015670z

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

3394 J. Am. Chem. Soc., Vol. 123, No. 14, 2001
Communications to the Editor
Table 2. Propargylic Alkylation of 2a Catalyzed by 1a
Striking regioselectivity was observed when unsymmetrical
simple ketones were used as carbon-centered nucleophiles (eq
1). Thus, the propargylic alkylation occurred at the more
encumbered R-site of the ketones. The reaction at room temper-
ature improved the regioselectivity of the products. This highly
regioselective alkylation of the R-position of unsymmetrical
ketones is of potential use in organic synthesis.11,12
Reactions with other symmetrical dialkyl ketones, â-diketones,
and silyl enol ethers have been investigated. Typical results are
shown in Table 2. When the reactions of 2a with 3-pentanone,
cyclopentanone, and cyclohexanone were carried out at 60 °C
for 4 h, a mixture of two diastereomeric isomers was obtained in
71%, 52%, and 75% yields, respectively (Table 2; runs 1-3).
Treatment of 2a with 3 equiv of â-diketones and a silyl enol ether
in ClCH2CH2Cl at 60 °C for 4 h gave rise to the formation of the
corresponding propargylic alkylated products in good yields,
respectively (Table 2; runs 4-8).
a Isolated yield. b Reaction of 2a (0.60 mmol) with ketone (36 mL)
was carried out in the presence of 1a (0.03 mmol) and NH4BF4 (0.06
mmol) at 60 °C for 4 h. c Two diastereoisomers were formed with the
isomer ratio of 63:37. d Two diastereoisomers were formed with the
isomer ratio of 85:15. e Two diastereoisomers were formed with the
isomer ratio of 70:30. f Reaction of 2a (0.60 mmol) with 3 equiv of
nucleophile was carried out in the presence of 1a (0.03 mmol)
and NH4BF4 (0.06 mmol) in ClCH2CH2Cl at 60 °C for 4 h. g FcCH-
(OH)CtCH (Fc ) ferrocenyl) was used in place of 2a.
Reaction of 1a with 1 equiv of propargylic alcohols (2) in the
presence of NH4BF4 in tetrahydrofuran (THF) at room temperature
for 30 min afforded the allenylidene complexes [Cp*RuCl(µ2-
SMe)2RuCp*(CdCdCHAr)]BF4 (Ar ) Ph (4a), Ar ) o-CH3C6H4
(4b)) in moderate yields (eq 2).4 Heating of the allenylidene
proceeds via the nucleophilic attack of an enolate carbon on the
electrophilic Cγ atom in allenylidene intermediates13 like 4, but
the detailed reaction mechanism involved in this reaction still
remains unknown. Further investigations are currently in progress.
In summary, we have found novel ruthenium-catalyzed pro-
pargylic alkylation of propargylic alcohols with various ketones
under mild and neutral reaction conditions to afford the corre-
sponding propargylic alkylated products in high yields with
complete regioselectivities. This provides a versatile propargylic
alkylation method directly from propargylic alcohols with ketones
and ketone derivatives to afford the corresponding γ-keto
acetylenes, which are very useful synthetic intermediates because
of their regioselective convertibility to 1,4- and 1,5-diketones and,
subsequently, to cyclopentenones and cyclohexenones.
complexes (4a, 4b) in acetone at reflux temperature for 3 h led
to the formation of 3a and 3b in 28% and 32% yields,
respectively. Interestingly, when the reaction of 4b with acetone
was performed in the presence of 1 equiv of 2a, the yield of 3b
was improved to 47% together with the formation of 3a in 42%
yield. Furthermore, reaction of 2b with acetone in the presence
of 5 mol % of 4b at reflux temperature for 3 h afforded 3b in
99% yield. These results indicate that the propargylic alkylation
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Science, Sports, and
Culture of Japan. We thank Dr. Hidetake Seino at The University of
Tokyo for measuring HRMS spectra.
Supporting Information Available: Experimental procedures and
spectral data for all of the new compounds (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
(11) Highly regioselective alkylations at the more hindered R-site of
unsymmetrical ketones have been reported. (a) Saito S.; Ito, M.; Yamamoto,
H. J. Am. Chem. Soc. 1997, 119, 611. (b) Mahrwald, R.; Gu¨ndogan, B. J.
Am. Chem. Soc. 1998, 120, 413.
(12) Nicholas, K. M.; Mulvaney, M.; Bayer, M. J. Am. Chem. Soc. 1980,
102, 2508.
JA015670Z
(13) (a) Esteruelas, M. A.; Go´mez, A. V.; Lo´pez, A. M.; Modrego, J.; On˜ate,
E. Organometallics 1997, 16, 5826. (b) Cadierno, V.; Gamasa, M. P.; Gimeno,
J.; Pe´rez-Carren˜o, E.; Ienco, A. Organometallics 1998, 17, 5216. (c) Cadierno,
V.; Gamasa, M. P.; Gimeno, J. Eur. J. Inorg. Chem. 2001, 571.