Palladium(II)-catalyzed enyne coupling reaction initiated by acetoxypalladation of alkynes and quenched by protonolysis of the carbon-palladium bond

Article abstract of DOI:10.1021/jo050121n

Divalent palladium-catalyzed inter- and intramolecular enyne coupling reactions initiated by acetoxypalladation of alkynes were developed. The reaction involves the acetoxypalladation of the alkyne, followed by the insertion of the alkene and the protonolysis of the carbon-palladium bond. The protonolysis of the carbon-palladium bond in the presence of bidentate nitrogen containing ligands is the key step in completing the Pd(II) catalytic cycle. The nitrogen-containing ligands, like halides, served to favor the protonolysis of the carbon-palladium bond over the β-H elimination in the Pd(II)-mediated reactions. The intermolecular coupling reactions provide an efficient method for synthesizing γ,δ-unsaturated carbonyls. The intramolecular coupling reactions offer a method to construct a variety of synthetically important carbo- and heterocycles. The asymmetric version of such a cyclization was developed with moderate enantioselectivity when employing pymox (pyridyl monooxazoline) as the ligand.

Full text of DOI:10.1021/jo050121n

Palladium(II)-Catalyzed Enyne Coupling Reaction Initiated by
Acetoxypalladation of Alkynes and Quenched by Protonolysis of
the Carbon-Palladium Bond
Ligang Zhao, Xiyan Lu,* and Wei Xu
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 January 20, 2005
Divalent palladium-catalyzed inter- and intramolecular enyne coupling reactions initiated by
acetoxypalladation of alkynes were developed. The reaction involves the acetoxypalladation of the
alkyne, followed by the insertion of the alkene and the protonolysis of the carbon-palladium bond.
The protonolysis of the carbon-palladium bond in the presence of bidentate nitrogen containing
ligands is the key step in completing the Pd(II) catalytic cycle. The nitrogen-containing ligands,
like halides, served to favor the protonolysis of the carbon-palladium bond over the â-H elimination
in the Pd(II)-mediated reactions. The intermolecular coupling reactions provide an efficient method
for synthesizing γ,δ-unsaturated carbonyls. The intramolecular coupling reactions offer a method
to construct a variety of synthetically important carbo- and heterocycles. The asymmetric version
of such a cyclization was developed with moderate enantioselectivity when employing pymox (pyridyl
monooxazoline) as the ligand.
Introduction
hydride species (usually generated from Pd(0) species)
to alkynes3 and the oxidative addition of Pd(0) onto
vinylhalides or triflates.4 These two pathways all require
Pd(0) species as the catalyst.
We are interested in the method of assembling the
γ-lactone ring by intramolecular enyne coupling: R-alky-
lidene-γ-butyrolactones could be constructed conveniently
from the easily available acyclic allylic 2-alkynoate
precursors.5 However, zerovalent palladium-catalyzed
cyclization of unsaturated allylic esters has not been
studied, probably due to the possible allylic carbon-
In recent years, enyne coupling has been achieved with
a wide range of transition-metal complexes either in a
catalytic or in a stoichiometric manner, which represents
a versatile approach to a variety of products by a simple
manipulation.1 In palladium chemistry, formation of
carbon-carbon bonds via vinylpalladium intermediates
offers a useful tool for constructing some synthetically
important polyfunctionalized molecules with high ef-
ficiency.2 In general, vinylpalladium intermediates mainly
come from two pathways: the addition of palladium
(3) (a) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1996, 118, 6305.
(b) Goeke, A.; Sawamura, M.; Kuwano, R.; Ito, Y. Angew. Chem., Int.
Ed. Engl. 1996, 35, 662. (c) Trost, B. M.; Romero, D. L.; Rise, F. J.
Am. Chem. Soc. 1994, 116, 4268. (d) Trost, B. M.; Czeskis, B. A.
Tetrahedron lett. 1994, 35, 211. (e) Trost, B. M.; Phan, L. T. Tetrahe-
dron Lett. 1993, 34, 4735. (f) Trost, B. M.; Pedregal, C. J. Am. Chem.
Soc. 1992, 114, 7292. (g) Trost, B. M.; Lee, D. C.; Rise, F. Tetrahedron
lett. 1989, 30, 651.
(4) (a) Negishi, E.-I.; Cope´ret, C.; Ma, S.; Liou, S.-Y.; Liu, F. Chem.
Rev. 1996, 96, 365. (b) de Meijere, A.; Meyer, F. E. Angew. Chem., Int.
Ed. Engl. 1994, 33, 2379. (c) Bra¨se, S.; de Meijere, A. Palladium-
catalyzed Coupling of Organyl Halids to alkenes-The Heck Reaction.
In Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: Weinheim, Germany, 1998; pp 99-164.
(1) For reviews, see: (a) Aubert, C.; Buisine, O.; Malacria, M. Chem.
Rev. 2002, 102, 813. (b) Trost, B. M.; Toste, F. D.; Pinkerton, A. B.
Chem. Rev. 2001, 101, 2067. (c) Fletcher, A. J.; Christie, S. D. R. J.
Chem. Soc., Perkin Trans. 1 2000, 1657. (d) Trost, B. M.; Krishce, M.
J. Synlett 1998, 1. (e) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan,
R. Chem. Rev. 1996, 96, 635. (f) Trost, B. M. Acc. Chem. Res. 1990, 23,
34.
(2) (a) Negishi, E. Handbook of Organopalladium Chemistry for
Organic Synthesis; John Wiley & Sons: New York, 2002. (b) Tsuji, J.
Palladium Reagents and Catalysts; John Wiley: Chichester, UK, 1995.
(c) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. In
Principles and Applications of Organotransition Metal Chemistry;
University Science Books: Mill Valley, CA, 1987.
10.1021/jo050121n CCC: $30.25 © 2005 American Chemical Society
Published on Web 04/15/2005
J. Org. Chem. 2005, 70, 4059-4063
4059

Zhao et al.
SCHEME 1
SCHEME 2
oxygen bond cleavage by the Pd(0) catalyst.6 In the
literature where a divalent palladium complex is the
catalytically active species, zerovalent palladium is gen-
erally formed during the reaction and then reoxidized to
complete the catalytic cycle.7 In our synthetic application
studies directed to a number of bioactive γ-lactone
SCHEME 3
natural products,
a Pd(II)-catalyzed cyclization of
4′-X-2′-butenyl 2-alkynoates (X ) leaving groups) or
4′-oxo-2′-butenyl 2-alkynoates has been developed for the
synthesis of γ-butyrolactones, using halide ions as the
nucleophile to attack the Pd(II)-coordinated alkynes as
the initial step and â-heteroatom elimination (when X )
leaving group) or protonolysis (when 4′-oxo substrates
were used) as the final step.8 However, there exist
problems in the method of developing the catalytic
asymmetric version of these reactions. A major problem
lies in the inevitable disturbance of the excess of requisite
halide ions to the coordination of chiral ligands with
palladium species. To solve this problem, we developed
the first example of asymmetric synthesis of γ-butyro-
lactones under Pd(II) catalysis in the presence of chiral
nitrogen ligands using acetoxypalladation as the first
step and â-deacetoxypalladation as the final step.9 The
problem arouse whether or not the acetoxypalladation
initiated reaction can take place with protonolysis as the
quenching step. Herein we wish to report our recent
results.10
Intramolecular Enyne Coupling Reaction. With
the three-component coupling of nonterminal alkynes,
acrolein or MVK, and acetic acid to form γ,δ-unsaturated
carbonyls in hand, we wish to extend this catalytic
system to the intramolecular version. In our previous
work, we established an efficient method for synthesizing
R-alkylidene-γ-butyrolactone derivatives using halopal-
ladation-intramolecular olefin insertion-protonolysis as
the key step.5,8c In this reaction, the 4′-oxoallylic alkynoate
(5) cyclized under the catalysis of Pd(II) to give the alde-
hydic γ-lactone derivative (6) with high yield (Scheme
2).8c Unfortunately, when 4′-oxoallylic alkynoate (5)
(0.5 mmol) was treated with Pd(OAc)2 (0.025 mmol) and
bpy (0.030 mmol) in acetic acid, no cyclization products
can be isolated after heating for 24 h at 80 °C (Scheme
2). Compound 7 was the simple hydroacetoxylation
product and compound 8 may result from the ester
exchange of HOAc and the starting material. The slower
rate for the insertion of the disubstituted alkenes in the
intramolecular reaction and the easy protonolysis of the
vinylpalladium species formed from acetoxypalladation
of alkynoates before the insertion of the olefinic double
bond might be the reason for the failure of this reaction
(Scheme 2).
Results and Discussion
Intermolecular Enyne Coupling Reaction. A di-
valent palladium-catalyzed coupling reaction of electron-
deficient alkynes and acrolein or MVK (methyl vinyl
ketone) was developed (Scheme 1).10,11 The reaction
provides an efficient method to synthesize γ,δ-unsatur-
ated carbonyls and involves a Pd(II)-catalyzed tandem
reaction initiated by acetoxypalladation of alkynes and
regeneration of Pd(II) species via protonolysis of the
C-Pd bond in the presence of nitrogen-containing ligands,
which are crucial to this reaction.9b
On comparing the intermediate structures of the
halopalladation and the acetoxypalladation of 4′-oxoal-
lylic alkynoates, the electronic effect of the acetoxy group
may allow the vinylic carbon-palladium bond to be easily
protonized (Scheme 3).
The tethered atom is another factor that is needs to
be considered because the electronic effect of the carbonyl
group also influences the reactivity of the vinylpalladium
intermediate to some extent. As an example, Pd(II)-
catalyzed construction of R-alkylidene-γ-butyrolactams
from N-allylic alkynamides has been developed in our
group.12 Compound 9 was treated with the present
catalytic system; fortunately, cyclization product 10 was
isolated even though with a low yield (Scheme 4). This
result clearly shows that the difference in the electronic
effect of the carbonyl group of the ester and the amide
can also influence the reactivity of the vinylpalladium
intermediate.
(5) (a) Lu, X.; Ma, S. New Age of Divalent Palladium Catalysis. In
Transition Metal Catalyzed Reaction; Murahashi, S.-I., Davies, S. G.,
Eds.; Blackwell Science: Oxford, UK, 1999; Chapter 6, p 133.. (b) Lu,
X.; Zhu, G.; Wang, Z. Synlett 1998, 115.
(6) Yamamoto, A. Organotransion Metal Chemistry, Wiley: New
York, 1986; p 233.
(7) Tsuji, J. Palladium Reagents and Catalysis: Innovations in
Organic Synthesis: John Wiley: Chichester, UK, 1995; p 19.
(8) (a) Ma, S.; Lu, X. J. Chem. Soc., Chem. Commun. 1990, 733.
(b) Ma, S.; Lu, X. J. Org. Chem. 1991, 56, 5120. (c) Wang, Z.; Lu, X.
Tetrahedron Lett. 1997, 38, 5213.
(9) (a) Zhang, Q.; Lu, X. J. Am. Chem. Soc. 2000, 122, 7604.
(b) Zhang, Q.; Lu, X.; Han, X. J. Org. Chem. 2001, 66, 7676.
(10) For a preliminary communication of intermolecular coupling
reaction initiated by acetoxypalladation, see: Zhao, L.; Lu, X. Org. Lett.
2002, 4, 3903.
(11) Fora similar process initiated by halopalladation, see: Wang,
Z.; Lu, X. J. Chem. Soc., Chem. Commun. 1996, 535.
From the results obtained above, it occurs to us that
the electronic nature of the alkyne part of the substrate
(12) (a) Xie, X.; Lu, X. J. Org. Chem. 2001, 66, 6545. (b) Jiang, H.;
Ma, S.; Zhu, G.; Lu, X. Tetrahedron 1996, 52, 10945.
4060 J. Org. Chem., Vol. 70, No. 10, 2005

Palladium(II)-Catalyzed Enyne Coupling Reaction
TABLE 1. Pd(II)-Catalyzed Intramolecular Enyne
Coupling Reactionsa
SCHEME 4
may have an important influence to the competition
between the protonolysis step and the olefin insertion
step. Fortunately, on switching from the electron-
deficient alkynes to the electron-rich alkynes, most of the
substrates can proceed smoothly to afford desirable
cyclization products in the present catalytic system. The
scope and generality of the present reaction was studied
as shown in Table 1. The reaction of carbon, oxygen,
nitrogen-tethered enyne substrates proceeded smoothly
and five- or six-membered carbo- or heterocycles products
were obtained in moderate to good yields.
In some of our reported reactions, only substrates with
(Z)-olefin are efficient in cyclization;9 however, in the
present system, most of the (E)-enyne substrates can also
proceed smoothly to afford the cyclization products.13
Terminal alkyne is still not feasible in the present system
(entry 1).9,10 Alkyl-substituted enynes (entries 3 and 4)
usually need shorter reaction time and afford better
results compared to aryl-substituted enynes (entry 5).
Phenyl vinyl ketone is not reactive in intermolecular
reactions; however, compound 15b can easily undergo
cyclization (entry 10). Using this reaction, the tetra-
hydropyrrole and hexahydrobenzofuran skeleton can be
constructed conveniently in a single step with moderate
yields (entries 11 and 12). Enynes usually afforded five-
membered-ring products in the present catalytic system.
However, the five (12f)- and six (12g)-membered ring
product was found when using 11f as substrate (entry
6). The presence of two symmetric oxygen atoms in the
molecule (11) may be the cause of the different regio-
selectivity of the cyclization. Furthermore, employing an
electron-withdrawing group in substrate 21 gave only six-
membered-ring product 22 in 76% yield. Substrate 23
afforded six-membered-ring 24 with high regioselectivity
(Scheme 5). The stereochemistry of the exocyclic double
bond was deduced by NOESY spectra as the (Z) form on
the cyclization product 12b. The stereochemistry of the
fused ring in compound 20 was proved also by NOESY
spectra as cis in compound 20.
To test the effect of changing the length of the tethered
atoms, a 1,7-enyne 25 was tried. While no cyclization
product was observed, the reaction can only give the
hydroacetoxylation product 26 in 76% yield (Scheme 6).
Proposed Mechanism for the Coupling Reaction.
The mechanism for the intramolecular cyclization is
believed to be analogous to that of the halopalladation
initiated enyne coupling reactions (Scheme 7).8c,11 This
will involve insertion of the pendant olefin into the vinyl-
palladium intermediate formed by trans-acetoxypalla-
dation of the carbon-carbon triple bond, followed by the
protonolysis of the carbon-palladium bond to regenerate
a Reaction conditions: A mixture of enyne substrate (0.5 mmol),
Pd(OAc)2 (0.025 mmol), and bpy (0.05 mmol) in HOAc (7.5 mL)
and 1,4-dioxane (7.5 mL) was heated at the temperature and the
time indicated. b Isolated yield. c Disordered reaction. d HOAc
(4 mL) was used as the solvent.
(13) It was found that (Z)-enyne substrates were not stable in acidic
medium forming a mixture of (E)- and (Z)-4′-oxoallylic alkynyl ethers.
Thus, (E)-enyne substrates were used in this work except for compound
19 (Table 1, entry 12).
J. Org. Chem, Vol. 70, No. 10, 2005 4061

Zhao et al.
TABLE 2. Pd(II)-Catalyzed Reactions of
Phenylmercuric Acetate with Acrolein or MVKa
SCHEME 5
SCHEME 6
entry
R
bpy, mol %
t, °C
yield,b %
28:29c
1
H
0
10
25
0
10
25
25
70
70
70
50
50
50
70
6
48
78
7
47
47
76
86:14
15:85
<3:97
>97:3
27:73
15:85
<3:97
2
H
3
H
4
Me
Me
Me
H
5
6
7d
SCHEME 7
a Reaction conditions: PhHgOAc (1 mmol), acrolein or MVK
(5 mmol), Pd(OAc)2 (0.05 mol), and HOAc (4 mL) were heated at
the indicated temperature. b Isolated total yield of 28 and 29. c The
ratio of 28 and 29 was determined by 1H NMR (300 MHz) spectra.
d Using 1,10-phenanthroline as ligand.
SCHEME 8
the catalytic Pd(II) species, giving cyclization products,
respectively. Here, the nitrogen-containing ligand was
crucial to the reaction. It not only played the same role
as the halide ions to inhibit the â-hydride elimination
but also stabilized the vinylpalladium intermediate and
promoted the intramolecular olefinic insertion into the
vinyl-palladium bond.9
The stereospecific (Z)-configuration of the exocyclic
double bond in the cyclization products supports the
mechanism of the trans-acetoxypalladation of alkynes.
This point is different from the halopalladation of alkynes
where cis-halopalladation is manifested especially in the
case of low concentration of halides ions.8b,14
Role of Nitrogen-Containing Ligands. In our pre-
vious paper on Pd(II)-catalyzed reactions initiated by
halopalladation of an alkyne, we found that halide ion
plays an important role in inhibiting the â-hydride
elimination and promoting the â-heteroatom elimination
or protonolysis of the carbon palladium bond to make the
regeneration of the Pd(II) species possible.15 In our recent
study of Pd(II)-catalyzed reactions initiated by acetoxy-
palladation and quenched by â-heteratom elimination,
it was found that nitrogen-containing ligands are crucial
for the success of the cyclization of enyne esters.9 In this
work, we found that the bpy ligand is also important
here. To study the role of bpy in the above catalytic
system, we investigated a catalytic process incorporating
Pd(II)-mediated transmetalation. The reaction of phenyl-
mercuric acetate with acrolein or MVK in the presence
of 5 mol % of Pd(OAc)2 in HOAc was conducted by
different loading of bpy as shown in Table 2. With the
increase of the amount of bpy, the total yield of the
product increased obviously and the protonolysis product
29 was dominant compared to â-hydride elimination
product 28. Employment of 1,10-phenanthroline as the
ligand gave a similar result to that of bpy. The results
strongly supported the fact that these nitrogen-contain-
ing ligands play a crucial role in inhibiting the â-H
elimination of intermediate (I) and promoting the proton-
(14) (a) Maitlis, P. M. The Organic Chemistry of Palladium; Aca-
demic Press: New, York, 1971; Vol. 1, p 79. (b) Maitlis, P. M. Acc.
Chem. Res. 1976, 9, 93-99. (c) Larock, R. C.; Riefling, B. Tetrahedron
Lett. 1976, 17, 4661. (d) Kaneda, K.; Uchiyama, T.; Fujiwarka, Y.;
Teranishi, S. J. Org. Chem. 1979, 44, 55. (e) Lambert, C.; Utimoto K.;
Nazaki, H. Tetrahedron Lett. 1984, 25, 5323. (f) Yanagihara, N.;
Lambert, C.; Iritani, K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc.
1986, 108, 2753. (g) Arcardi, A.; Burini, A.; Cacchi, S.; Delmastro, M.;
Marinelli, F.; Pietroni, B. R. J. Org. Chem. 1992, 57, 976. (h) Kosugim,
M.; Sakavya, T.; Ogawa, S.; Migita, T. Bull. Chem. Soc. Jpn. 1993,
66, 3058. (i) Ba¨ckvall, J.-E.; Nilsson, Y. I. M.; Andersson, P. G.; Gatti,
R. G. P.; Wu, J. Tetrahedron Lett. 1994, 35, 5713. (j) Ba¨ckvall, J.-E.;
Nilsson, Y. I. M.; Gatti, R. G. P. Organometallics 1995, 14, 4242.
(15) In the Pd(II)-catalyzed coupling reactions, the halide ion can
prohibit the â-H elimination of a carbon-palladium bond, giving
preferentially the protonolysis or â-heteroatom elimination product,
see: (a) Wang, Z.; Zhang, Z.; Lu, X. Organometallics 2000, 19, 775.
(b) Zhang, Z.; Lu, X.; Xu, Z.; Zhang, Q.; Han, X. Organometallics 2001,
20, 3724.
4062 J. Org. Chem., Vol. 70, No. 10, 2005

Palladium(II)-Catalyzed Enyne Coupling Reaction
TABLE 3. Asymmrtric Cyclization of 11d Employing
Oxazoline Ligandsa
of alkynes, in which the carbon-palladium bond was
quenched by protonolysis in the presence of nitrogen-
containing ligands. This is a reaction using Pd(II) catalyst
without the use of additional additives or redox systems.
While the intermolecular coupling reactions provide an
efficient method to synthesize γ,δ-unsaturated carbonyls,
the intramolecular version offers a method to construct
a variety of synthetically important carbo- and hetero-
cycles.
entry
ligand (mol %)
T, °C
yield,b %
ee % of 12dc
1
2
3
4
5
6
7
8
(S)-32a (20)
(S)-32b (20)
(S)-32c (10)
(S)-32c (20)
(S)-32d (20)
(S)-32e (20)
(S)-33 (10)
(S)-34 (20)
60
60
80
60
60
60
80
60
72
30
32
65
29
50
32
37
66
66
53
77
75
29
40
29
Experimental Section
Typical Procedure for the Intramolecular Enyne
Coupling Reaction. To a solution of Pd(OAc)2 (5.6 mg,
0.025 mmol) and 2,2′-bipyridine (7.8 mg, 0.05 mmol) in a
mixture of HOAc (7.5 mL) and 1,4-dioxane (7.5 mL) at 80 °C
was added 11d (111 mg, 0.5 mmol) with stirring. After the
reaction was complete as monitored by TLC, the reaction
mixture was neutralized with saturated NaHCO3 and ex-
tracted with Et2O. The combined ether solution was washed
with saturated NaCl, dried (Na2SO4), and concentrated. The
residue was purified by flash chromatography (EtOAc:petro-
leum ether ) 1:4) to give the coupling product 12d in 96%
yield: oil; 1H NMR (300 MHz, CDCl3) δ 9.79 (s, 1H), 4.29
(d, J ) 13.2 Hz, 1H), 4.14 (d, J ) 13.2 Hz, 1H), 3.87 (dd, J )
9.2 Hz, J ) 5.4 Hz, 1H), 3.74 (d, J ) 9.2 Hz, 1H), 3.25
(m, 1H), 2.79 (dd, J ) 18.3 Hz, J ) 10.0 Hz, 1H), 2.60 (d, J )
18.3 Hz, 1H), 2.23 (t, J ) 7.2 Hz, 2H), 2.15 (s, 3H), 1.41-1.26
(m, 10H), 0.87 (t, J ) 6.5 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 200.7, 168.4, 141.2, 128.7, 73.9, 68.3, 47.5, 35.5, 31.7, 31.2,
29.2, 29.0, 26.4, 22.6, 20.6, 14.0; IR (neat) ν 2930, 2858, 1757,
1723, 1693, 1371, 1207, 1142, 929 cm-1; MS (EI) m/z 241, 223
(M+ - OAc), 181, 43 (100); HRMS calcd for C14H22O2
[M+ - HOAc] 222.1620, found 222.1612.
a The reaction was carried out under the following conditions:
11d (0.5 mmol), Pd(OAc)2 (0.025 mmol), and chiral ligand in HOAc/
1,4-dioxane (7.5 mL/7.5 mL), 24 h. b Isolated yield. c Determined
by chiral GC with ChiralDexG-TA column.
olysis of the carbon-palladium bond making the catalytic
cycles possible.
Asymmetric Version of the Cyclization. With these
results in hand, further effort to develope an aymmmetric
version of this reaction was made, using the homochiral
nitrogen-containing ligands (Scheme 8).16 Unfortunately,
when we used the C2-symmetric bisoxazoline ligands 30
and 31, the present reaction turned to a disordered
reaction. Using pymox (pyridyl monooxazoline) as ligand,
the cyclization proceeded more efficiently and led to
moderated yield and enantioselectivity (entries 1-5,
Table 3). Employment of isopropyl-substituted pyridyl
monooxazoline gave the highest enantioselectivity (77%
ee) (Table 3, entry 4). Two other enyne substrates of 15b
also afforded a similar yield (64%) and ee value (77%).17
The intramolecular coupling reaction of other substrates was
carried out with a similar procedure. For the detailed proce-
dure and characterization data of the new compounds, see the
Supporting Information.
Acknowledgment. We thank the Major State Basic
Research Program (Grant G20000077502-A). We also
thank the National Natural Sciences Foundation of
China and Chinese Academy of Sciences for financial
support.
Conclusion
In summary, we developed a novel Pd(II)-catalyzed
enyne coupling reaction initiated by acetoxypalladation
Supporting Information Available: Experimental pro-
cedures for all the substrates, copies of 1H NMR and 13C NMR
spectra for compounds 12b-g, 14a,b, 16a, 18, 20, 22, 24, and
26, and NOESY spectra for compounds 12b and 20. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(16) For recent contributions to enantioselective enyne cyclizations,
see: (a) Hatano, M.; Mikami, K. J. Am. Chem. Soc. 2003, 125, 4704.
(b) Chakrapani, H.; Liu, C.; Widenhoefer, R. A. Org. Lett. 2003, 5, 157.
(c) Lei, A.; Waldkirch, J. P.; He, M.; Zhang, X. Angew. Chem., Int. Ed.
2002, 41, 4526. (d) Cao, P.; Zhang, X. Angew. Chem., Int. Ed. 2000,
39, 4104.
(17) The enantioselectivity of compound 10b was determined by
chiral HPLC, using chiralcel OJ column (λ ) 214 nm).
JO050121N
J. Org. Chem, Vol. 70, No. 10, 2005 4063