Cationic Pd(II)-catalyzed enantioselective cyclization of aroylmethyl 2-alkynoates initiated by carbopalladation of alkynes with arylboronic acids

Article abstract of DOI:10.1021/ol0711772

A cationic palladium(II)-catalyzed enantioselective intramolecular addition of vinylpalladium species to ketones initiated by the carbopalladation of alkynoates under mild conditions without a Pd(II)/Pd(0) redox system was developed with high yield and en

Full text of DOI:10.1021/ol0711772

ORGANIC
LETTERS
2007
Vol. 9, No. 15
2947-2950
Cationic Pd(II)-Catalyzed
Enantioselective Cyclization of
Aroylmethyl 2-Alkynoates Initiated by
Carbopalladation of Alkynes with
Arylboronic Acids
Juan Song,† Qi Shen,*,† Fan Xu,† and Xiyan Lu*,†,‡
Department of Chemistry and Chemical Engineering, Suzhou UniVersity,
Suzhou, China, and State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai, 200032, China
xylu@mail.sioc.ac.cn
Received May 23, 2007
ABSTRACT
A cationic palladium(II)-catalyzed enantioselective intramolecular addition of vinylpalladium species to ketones initiated by the carbopalladation
of alkynoates under mild conditions without a Pd(II)/Pd(0) redox system was developed with high yield and enantioselectivity. This cascade
reaction provides an efficient method for the construction of optically active hydroxylactones.
Suffering from the less nucleophilic properties of the
organopalladium species, the addition of carbon-palladium
bond toward carbon-heteroatom multiple bonds has received
scant attention compared with the numerous reports on the
insertion of carbon-carbon multiple bonds.1 Although, some
reactions catalyzed by Rh,2 Ni,3 and others have been
reported in this area, there were only a few examples on the
addition of the organopalladium species to carbon-hetero-
atom multiple bonds.4-7 Even so, most of them were
catalyzed by Pd(0) species which involved a Pd(II)/Pd(0)
redox system.4,5
In our earlier work, we reported a Pd(II)-catalyzed addition
of a carbon-palladium species initiated by the acetoxypal-
(3) (a) Huang, Y.-C.; Majumdqr, K. K.; Cheng, C.-H. J. Org. Chem.
2002, 67, 1682. (b) Sato, Y.; Saito, N.; Mori, M. J. Am. Chem. Soc. 2000,
122, 2371. (c) Sato, Y.; Takimoto, M.; Hayashi, K.; Katsuhara, T.; Takagi,
K.; Mori, M. J. Am. Chem. Soc. 1994, 116, 9771. (d) Shibata, K.; Kimura,
M.; Shimizu, M.; Tamaru, Y. Org. Lett. 2001, 3, 2181.
(4) For recent papers on the nucleophilic attack by palladium species,
see: (a) Yamamoto, Y.; Nakamura, I. Top. Organomet. Chem. 2005, 14,
211 and references therein. (b) Fernandes, R. A.; Yamamoto, Y. J. Org.
Chem. 2004, 69, 735. (c) Solin, N.; Kjellgren, J.; Szabo´, K. J. J. Am. Chem.
Soc. 2004, 126, 7026. (d) Solin, N.; Wallner, O. A.; Szabo´, K. J. Org. Lett.
2005, 7, 689. (e) Sebelius, S.; Szabo´, K. J. Eur. J. Org. Chem. 2005, 12,
2539.
(5) (a) Zhou, C.; Larock, R. C. J. Am. Chem. Soc. 2004, 126. 2302. (b)
Zhou, C.; Larock, R. C. J. Org. Chem. 2006, 71, 3551. (c) Suzuki, K.;
Arao, T.; Ishii, S.; Maeda, Y.; Kondo, K.; Aoyama, T. Tetrahedron Lett.
2006, 47, 5789. (d) Hopkins, C. D.; Guan, L.; Malinakova, H. C. J. Org.
Chem. 2005, 70, 6848.
(6) (a) Zhao, B.; Lu, X. Tetrahedron Lett. 2006, 47, 6765. (b) Zhao, B.;
Lu, X. Org. Lett. 2006, 8, 5987.
† Suzhou University.
‡ Shanghai Institute of Organic Chemistry.
(1) For general reviews on palladium chemistry, see: (a) Tsuji, J., Ed.
Palladium in Organic Synthesis; Springer: New York, 2005. (b) Negishi,
E., Ed. Handbook of Organopalladium Chemistry for Organic Synthesis;
Wiley-Interscience: New York, 2002.
(2) (a) Fagnou, K.; Lartens, M. Chem. ReV. 2003, 103, 169. (b) Miura,
T.; Shimada, M.; Murakami, M. Synlett 2005, 667. (c) Shintani, R.;
Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc.
2005, 127, 54. (d) Shintani, R.; Inoue, M.; Hayashi, T. Angew. Chem., Int.
Ed. 2006, 45, 3353. (e) Toullec, P. Y.; Jagt, R. B. C.; de Vries, J. G.; Feringa,
B. L.; Minnaard, A. J. Org. Lett. 2006, 8, 2715. (f) Ueura, K.; Miyamura,
S.; Satoh, T.; Miura, M. J. Organomet. Chem. 2006, 691, 2821. (g) Miura,
T.; Murakami, M. Chem. Commun. 2007, 217.
10.1021/ol0711772 CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/20/2007

ladation of alkynes to a carbonyl group.8 In the course of
the reaction, vinylpalladium intermediates were generated
by the acetoxypalladation of alkynes. The presence of the
acetoxy group in the olefinic bond made the formed vinyl-
palladium species relatively more nucleophilic, and the
nucleophilic addition to the carbonyl group became possible
(Scheme 1). The question arises if this addition reaction is
Table 1. Cationic Pd(II)-Catalyzed Cyclization of Aroylmethyl
2-Alkynoatesa
yield
(%)b
Scheme 1. Addition of 2-Acetoxyvinylpalladium Species to
entry
1
R1
R2
Ar
2
the Ketone Group
1c
2d
3e
4
5
6
7
8
9
10
11
12
13
14
15
16
17
1a CH3
1a CH3
1a CH3
1a CH3
1a CH3
1a CH3
1a CH3
1a CH3
1a CH3
1a CH3
1b n-C3H7
1c n-C7H15 Ph
1d Ph
1e CH3
1f CH3
1g CH3
1h CH3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2aa
2aa
2aa
2aa
39
30
89
92
90
94
96
85
88
81
79
84
82
90
89
76
4-MeOC6H4 2ab
4-MeC6H4
4-FC6H4
3-NO2C6H4 2ae
3-MeOC6H4 2af
2-naphthyl
Ph
Ph
Ph
2ac
2ad
still possible when the reaction is initiated by carbopallada-
tion of an alkyne.
2ag
2ba
2ca
2da
2ea
2fa
Organoboronic acids have been well-used in transition-
metal-catalyzed carbon-carbon bond-forming reactions.9 The
carbopalladation of alkynes triggered by the addition of
arylboronic acids is a promising way to generate vinylpal-
ladium intermediates.10 On the other hand, we have reported
the addition of arylboronic acids to nitriles6 and the intramo-
lecular addition to ketones7 catalyzed by cationic Pd com-
plexes recently. It occurred to us that the cationic Pd catalyst
may favor the addition of the vinylpalladium species to
carbon-heteroatom bonds. Compared to the neutral Pd(II)
species, there are two advantages for cationic Pd(II) species:
Ph
4-MeOC6H4 Ph
4-ClC6H4
4-BrC6H4
CH3
Ph
Ph
Ph
2ga
2ha
a Reaction conditions: Substrate (0.2 mmol), arylboronic acid (0.3 mmol)
[(dppp)Pd(H2O)2](OTf)2 (0.006 mmol) in dioxane/H2O (2 mL/0.2 mL) at
70 °C. b Isolated yield. c Catalyzed by Pd(OAc)2/dppp. d Catalyzed by
[(bpy)Pd(OH)]2(OTf)2; 3aa was obtained also in 33% yield. e Catalyzed
by [(dppe)Pd(H2O)2](OTf)2; 3aa was obtained also in 21% yield.
11,12
vacant coordination sites and stronger Lewis acidity.
6,13b
Herein, we wish to describe an unprecedented asymmetric
cascade reaction which consists of the intermolecular car-
bopalladation of the alkynoates using arylboronic acids and
subsequent intramolecular addition of vinylpalladium inter-
mediates to the ketone group catalyzed by cationic Pd(II)
complexes.
Our initial studies started by employing benzoylmethyl
2-butynoate as a model substrate in combination with
PhB(OH)2 to examine the reaction activity in the pres-
ence of different Pd(II) catalyst. When the neutral catalyst
Pd(OAc)2/dppp was employed, the protonolysis product 3aa
was obtained in 41% yield (Table 1, entry 1). Using [(dppp)-
Pd(H2O)2](OTf)213a as the catalyst, the reaction afforded 2aa
in 89% yield (Table 1, entry 4). However, the transformation
was sluggish when the reaction was catalyzed by the two
other cationic Pd catalysts [(bpy)Pd(OH)]2(OTf)2
and
[(dppe)Pd(H2O)2](OTf)213c (Table 1, entries 2 and 3). These
results indicated that the acetoxy group is crucial in the
addition of vinylpalladium species to ketones under neutral
Pd(II) catalyst conditions. Meanwhile, the higher Lewis
acidity of the cationic Pd(II) species might be the another
reason for the success of the reaction.
A series of R-alkylidene-â-hydroxy-γ-lactones were ob-
tained in good to excellent yields (Table 1, entries 4-17)
when a variety of arylboronic acids and aroylmethyl
2-alkynoates were employed. However, ortho-substituted
arylboronic acid gave no cyclization product probably
because of the steric hindrance. The stereochemistry of the
exocyclic double bond in products 2 was assigned as (E)-
configuration on the basis of the lower field chemical shift
Scheme 2. Chiral Bidentate Phosphorus Ligands Screened in the Asymmetric Cyclization of Aroylmethyl 2-Alkynoates
2948
Org. Lett., Vol. 9, No. 15, 2007

Subsquently, the asymmetric version of this cascade
cyclization was studied. Unexpectedly, [(R)-(binap)Pd(H2O)2]-
(OTf)2 which was effective in cationic palladium-catalyzed
intramolecular addition of arylboronic acid to ketones7
showed low reactivity in the present reaction in dioxane
(25% yield). Although the yield was improved to 71% in
CH3NO2, low enantioselectivity (34% ee) was still observed.
Some other chiral bidentate phosphorus ligands16 also gave
negative results (Scheme 2). Fortunately, enlightened by the
structure of dppp, (S,S)-BDPP16d was tested, and good yields
with moderate to excellent ee values were obtained (Table
2). It is important to note here that to simplify the
experimental manipulation, Pd(CF3COO)2/(S,S)-BDPP was
used directly in the reaction to generate cationic palladium-
(II) species in situ.17
Table 2. Asymmetric Cyclization of Aroylmethyl 2-Alkynoates
under the Catalysis of Pd(CF3COO)2/(S, S)-BDPPa
The possible mechanism is proposed as shown in Scheme
3.18 First, arylpalladium species A is formed by transmeta-
Scheme 3. Proposed Mechanism of the Asymmetric
Cyclization of Aroylmethyl 2-Alkynoates under the Catalysis of
Cationic Palladium(II) Initiated by Carbopalladation
lation of the cationic Pd(II) species with arylboronic acids.
Regioselective insertion of 1 to A affords vinylpalladium
intermediate B (carbopalladation). High Lewis acidity of the
(9) (a) Brown, H. C. Organic Syntheses Via Boranes; Wiley-Inter-
science: New York, 1975. (b) Matteson, D. S. Stereodirected Synthesis
with Organoboranes; Springer-Verlag: Berlin, 1995. (c) Suzuki, A.
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a Reaction conditions: Substrate (0.2 mmol), arylboronic acid (0.5 mmol),
Pd(CF3COO)2 (0.006 mmol), (S, S)-BDPP (0.0066 mmol) in CH2ClCH2Cl/
H2O (2 mL/ 0.2 mL) at 70 °C. b Isolated yield. c The ee values were
determined by chiral HPLC. The sign of optical rotation was indicated in
parentheses (for details see Supporting Information).
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Yamamoto, A. J. Organomet. Chem. 1995, 500, 337. (b) Coates, G. W.
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2005, 14, 279 and references therein.
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2003, 42, 2768. (b) Nishikata, T.; Yamamoto, Y.; Miyaura, N. Organo-
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1
of the methyl or alkyl group for the E isomer in H NMR
spectra14 and compared with the data in the literature.15
Again, the structure of 2af was confirmed by X-ray crystal-
lography.
(7) Liu, G.; Lu, X. J. Am. Chem. Soc. 2006, 128, 16504.
(8) Zhao, L.; Lu, X. Angew. Chem. Int. Ed. 2002, 41, 4343.
Org. Lett., Vol. 9, No. 15, 2007
2949

Pd center in cationic species B may activate the carbonyl
group by coordination to the unshared electron pairs on the
oxygen atom, facilitating the formation of the intermediate
C.11e It is also proposed that this coordinated intermediate
B is helpful to the enantioface discrimination of ketones
resulting in high ee values.19 A competitive reaction is the
protonolysis of the vinyl palladium species producing
byproduct 3. After the addition of the Csp2 carbon to the
activated carbonyl group in B generates C, the product 2 is
formed by protonolysis of the palladium alkoxide intermedi-
ate C with regeneration of the palladium species to make
the catalytic cycle possible. Of course, another pathway to
form intermediate C by the insertion of carbonyl group
coordinated to palladium via the π-electrons to carbon-
palladium bond in B could not be excluded.
In summary, we have developed a cationic palladium(II)-
catalyzed enantioselective addition of vinylpalladium species
to ketones initiated by carbopalladation of the alkynes
without a Pd(II)/Pd(0) redox system. This cascade reaction
provided an efficient way for the construction of optically
active hydroxylactones.
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Acknowledgment. We thank the Department of Chem-
istry and Chemical Engineering, Suzhou University, the
National Natural Science Foundation of China (Grant
20423001), and Chinese Academy of Sciences for financial
support.
Supporting Information Available: Experimental pro-
cedures and characterization data of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL0711772
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Org. Lett., Vol. 9, No. 15, 2007