Switch of selectivity in the synthesis of α-methylene-γ- lactones: Palladium-catalyzed intermolecular carboesterification of alkenes with alkynes

Article abstract of DOI:10.1002/anie.201109141

Three in one: A highly efficient and mild Pd^II-catalyzed carboesterification of alkenes with carboxylic alkyne derivatives proceeds through a domino-type alkyne-alkene coupling/C-O-bond formation (see scheme). The stereoselectivity is controlled by the choice of substrates and temperature. The reaction provides a convenient method for the construction of naturally occurring biologically active compounds with α-methylene-γ-lactone skeletons. Copyright

Full text of DOI:10.1002/anie.201109141

Angewandte
Chemie
DOI: 10.1002/anie.201109141
Synthetic Methods
Switch of Selectivity in the Synthesis of a-Methylene-g-Lactones:
Palladium-Catalyzed Intermolecular Carboesterification of Alkenes
with Alkynes**
Liangbin Huang, Qian Wang, Xiaohang Liu, and Huanfeng Jiang*
The development of transition-metal-mediated transforma-
tions for the construction of highly functional products in
a convenient and concise manner continues to attract broad
interest.[1] In particular, cross-coupling reactions of alkynes
and alkenes catalyzed by palladium complexes have been
studied extensively, because of the accessibility of reactants
and the diversity of products.[2–4] One of the major challenges
that remain in the nucleopalladation of alkynes is to improve
the stereo- and regioselectivities of the nucleopalladation to
struct g lactones through copper-catalyzed oxidative [3+2]
cycloaddition reactions between alkenes and anhydrides.[9] To
the best of our knowledge, only one report focuses on the
intramolecular [3+2] cycloaddition of alkenes with alkynes to
construct a fused ring system that contains an a-methylene-g-
lactone skeleton.[10] Moreover, the products have a Z-type
configuration. Herein, we present a novel palladium-cata-
lyzed intermolecular carboesterification of alkenes with
alkynoates to selectively construct (E)-a-methylene-g-lac-
tone. Interestingly, the stereoselectivities can be switched by
a simple modification, the carboesterification of alkenes with
alkynamides at room temperature (Scheme 2).
À
C C triple bonds. Three strategies are typically employed:
1) the concentration of the nucleophiles is increased;[5] 2) one
palladated isomer is dominant if it leads to the formation of
kinetically more stable structures, that is, aromatic rings;[6]
3) a directing group determines the selectivity.[7]
The a-methylene-g-lactone skeleton is an important
moiety in natural products and exhibits potential biological
activities. For example, andrographolide and some sesquiter-
pene lactones, which contain an a-methylene-g-lactone
moiety in the molecule, are used extensively in anti-inflam-
matory drugs, and have antipyretic, cytotoxic, antitumoral,
and often bactericidal properties (Scheme 1).[8] Very recently,
we reported an intermolecular carboesterification to con-
Scheme 2. Switch of stereoselectivity in Pd-catalyzed alkyne–alkene
coupling reaction. EWG=electron-withdrawing group.
Our initial investigations of Pd-catalyzed intermolecular
carboesterification reactions focused on the cyclization of
ethyl 3-phenylpropiolate 1a with styrene 2a. No reaction
occurred and 1a was recovered when 1a and 2a were treated
with 5 mol% PdCl2 and four equivalents of LiCl at 1008C
under 8 atm O2 in benzene/acetonitrile (v/v = 1:1). a-Methyl-
ene-g-lactone 3a was produced in low yield with two
equivalents of PIDA or DDQ as oxidants (Table 1, entries 2
and 4). The reaction at 408C with PIDA as oxidant gave the
product in 23% yield (Table 1, entry 3). To our delight,
product 3a was obtained in 92% yield when 1 atm O2 and two
equivalents of CuCl2·2H2O were used as co-oxidants[11]
(Table 1, entry 5). PdCl2 was the best catalyst (Table 1,
entries 5, 7, and 8), and a mixture of benzene and acetonitrile
(v/v = 1:1) was the best solvent for this reaction (see the
Supporting Information for details).[12] In addition, only
a trace amount of product was formed when the reaction
was performed under anhydrous conditions (Table 1, entry 6).
Further studies showed that one oxygen atom of the product
came from water [Eq. (1)].[13]
Scheme 1. Chemical structures of andrographolide (A) and sesquiter-
pene lactones (B and C).
[*] L. B. Huang, Q. Wang, X. H. Liu, Prof. Dr. H. F. Jiang
School of Chemistry and Chemical Engineering
South China University of Technology (China)
E-mail: jianghf@scut.edu.cn
Homepage: http://www2.scut.edu.cn/ce/lshxyjzx/links.html
[**] This work was supported by the National Natural Science
Foundation of China (21172076 and 20932002), the National Basic
Research Program of China (973 Program) (2011CB808600),
a doctoral fund from the Ministry of Education of China
(20090172110014), the Guangdong Natural Science Foundation
(10351064101000000), and the Fundamental Research Funds for
the Central Universities (2010ZP0003).
Subsequently, we explored the scope of the reaction
between various alkynoates and alkenes under the optimized
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201109141.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
Table 1: Impact of reaction parameters on the carboesterification of
alkenes.[a]
Entry
Catalyst
Oxidant
Additive
Yield [%][b]
1
2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Pd(OAc)2
[Pd(dba)2]
8 atm O2
PIDA
PIDA
DDQ
CuCl2·2H2O/1 atm O2
CuCl2/1 atm O2
CuCl2·2H2O/1 atm O2
CuCl2·2H2O/1 atm O2
LiCl
LiCl
LiCl
LiCl
–
–
–
–
n.o.
28
23
3[c]
4
18
5
95(92)
trace
83
6[d]
7
8
54
[a] Reaction conditions: Unless otherwise noted, all reactions were
performed with 1a (0.5 mmol), 2a (0.6 mmol) and Pd catalyst (5 mol%)
in 1 mL of benzene/acetonitrile (v/v=1:1) at 1008C for 12 h. [b] Deter-
mined by GC using dodecane as the internal standard. Data in
parentheses is the yield of isolated product. [c] 408C. [d] 1 mL of
anhydrous benzene/anhydrous acetonitrile (v/v=1:1). DDQ=2,3-
dichloro-5,6-dicyano-1,4-benzoquinone, n.o.=not obtained, PIDA=
phenyliodonium diacetate.
conditions. Propiolic acids and propiolic acid esters reacted
with styrene to afford carboesterification products 3a and 3b
in good yields (Scheme 3). Both styrene derivatives and
simple, electronically deficient alkenes afforded the desired
products in good to excellent yields (Scheme 3, 3a–k and 3r).
A series of para-substituted styrenes, including some with
electron-donating groups (R’ = OMe, Me, tBu) and some with
electron-withdrawing groups (R’ = F, CN, NO2), were con-
verted into the corresponding a-methylene-g-lactones in
excellent yields (Scheme 3, 3c–j).
This transformation was compatible with alkenes that
contain Cl- and Br-substituted aryl rings, which could undergo
a Heck-type reaction with themselves under Pd catalysis, but
in this case do not (Scheme 3, 3 f and 3g). The structure of 3 f
was confirmed by X-ray crystallographic analysis (see the
Supporting Information for details), and the configuration of
the a-methylene-g-lactone moiety is different from that of the
products of Pd-catalyzed intramolecular carboesterifications
of alkenes.[5,10] Other substituted styrenes were also good
substrates for this transformation and afforded the corre-
sponding products 3k–m in high yields. These results showed
that this new transformation was tolerant toward electronic
and steric effects of the aromatic ring. In contrast to 1,1-
diphenylethene, which was unreactive (Scheme 3, product
3n), sterically less hindered 1,1-disubstituted olefins gave
products 3o–3q in high yields. When ethyl but-2-ynoate was
employed as substrate, the desired product 3t was isolated in
82% yield (Scheme 3 3t). Unfortunately, internal olefins
failed to afford the desired products.
Scheme 3. Substrate scope of the carboesterification of alkenes with
alkynoates. The reactions were carried out at 1008C and 1 atm of O2
using alkynes (0.5 mmol), alkenes (0.6 mmol), PdCl2 (5 mol%),
CuCl2·2H2O (1 mmol), and 1 mL of benzene/acetonitrile (v/v=1:1) for
12 h.
To our delight, the bromopalladation of alkynoates under
similar reaction conditions in AcOH/Ac2O = 1:1 (v/v, see the
Supporting Information) as solvent and with CuBr2 as co-
oxidant could also initiate this domino-type reaction with
various alkenes to give a-bromo-a-methylene-g-lactones
(Scheme 4). Upon completion of the carboesterification of
alkenes and extraction with diethyl ether, crude products 3
were directly subjected to the palladium-catalyzed Sonoga-
shira coupling without additional purification. Similarly,
reactions with both electron-deficient alkenes and styrene
derivatives proceeded smoothly to give the products in
moderate to good yields. Electron-deficient olefins proved
to be the better substrates (4g, 4h).
To our surprise, the major products had a reversed
configuration when alkynamides were used as substrates
(Table 2; X-ray crystallographic analysis in the Supporting
Information). Inspired by these results, we decided to attempt
increasing the selectivity toward the (Z)-a-methylene-g-
lactone skeleton. When the temperature was decreased to
room temperature, a selectivity of Z/E = 97:3 could be
À
achieved (Table 2, entries 1–3). At least one N H bond was
necessary for this transformation to occur; disubstituted
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Scheme 4. Conversion of vinylbromides to multifunctional lactones.
The carboesterification reactions were carried out at 1008C under
1 atm of O2 with alkynoates (0.5 mmol), alkenes (0.6 mmol), Pd(OAc)2
(5 mol%), CuBr2 (1 mmol), and AcOH/Ac2O=1:1 (v/v, 1 mL) for 12 h.
The crude products were extracted with diethyl ether. Terminal alkynes
(0.6 mmol), [Pd(PPh3)2Cl2] (5 mol%), CuI (5 mol%), TEA (0.1 mL),
and DMF (1.5 mL) were added and the Sonogashira coupling was
carried out at 808C for 8 h. TEA=triethylamine.
Scheme 5. Carboesterification of alkenes with alkynamides: The reac-
tions were carried out under 1 atm of O2, with alkynes (0.5 mmol),
alkenes (0.6 mmol), PdCl2 (5 mol%), and CuCl2·2H2O (1 mmol) in
acetonitrile (0.5 mL) for 12 h.
and 6s (75%), respectively, were obtained. Interestingly,
when cyclopentene was used as the terminating coupling
reagent, product 6t (67%) was obtained. When the initial
coupling reagent was but-2-ynamide or oct-2-ynamide, the
corresponding (Z)-a-methylene-g-lactones were obtained in
high yields.
Table 2: Carboesterification of alkenes with alkynamides.[a]
Entry
R1
R2
T [8C]
Z/E
Yield [%][b]
It should be noted that the corresponding (E)-g-lactone
could not be obtained when the temperature was decreased to
808C [Eq. (2)].[4g] This result indicates that, in this case,
1
2
3
4
5
6
H
H
H
H
H
Me
H
H
H
Me
tBu
Me
100
50
RT
RT
RT
RT
91:9
95:5
97:3
97:3
98:2
–
73
89
93
89
78
–
[a] The reactions were carried out under 1 atm of O2, with alkynes
(0.5 mmol), alkenes (0.6 mmol), PdCl2 (5 mol%), and CuCl2·2H2O
(1 mmol) in acetonitrile (0.5 mL) for 12 h. [b] Yields of isolated products.
temperature plays a crucial role in the transformation. A
competitive reaction occurred when allyl chloride and allyl
acetate were used as the terminating coupling reagents. A
alkynyl carboxamides did not give the desired product
(Table 2, entry 6).[14]
À
tentative explanation for this phenomenon is that the C Pd
The scope of the reaction at room temperature was
further expanded to a range of alkynamides and alkenes
(Scheme 5). Styrene derivatives could be smoothly trans-
formed into the desired products in good yields. Ethyl
acrylate reacted efficiently to produce 6j in 89% yield,
whereas OH- or Br-substituted ethyl acrylate was converted
into the corresponding products in lower yields (53% and
61%, respectively). The reaction was compatible with OH
and Br substituents when substituted allyl acrylates were used
as the substrates. Acryl amide derivatives also worked well for
this transformation. When vinyl ketone and acrylonitrile were
used for this reaction, carboesterification products 6r (98%)
bond in the shown intermediate [Eq. (3)] could be quenched
3
À
by b-X elimination to afford product 7a, or by C(sp ) O bond
formation[16] to obtain 6x. In addition, (Z)-product 6a, which
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Experimental Section
General procedure for the palladium-catalyzed
carboesterification of alkenes with alkynoates:
Alkynoate (0.5 mmol), alkene (0.6 mmol), PdCl2
(5 mol%), CuCl2 (0.75 mmol), and CH3CN/ben-
zene = 1:1 (1 mL) were added to a Schlenk tube.
The tube was charged with O2 (1 atm), and the
mixture was stirred at 1008C (oil bath temper-
ature) for the desired reaction time. After the
reaction was finished, the mixture was cooled to
room temperature and quenched with aqueous
NaCl, and the crude product was extracted with
ethyl acetate. The organic extracts were concen-
trated in vacuum, and the resulting residue was
purified by column chromatography on silica gel
with light petroleum ether/ethyl acetate as eluent
to afford the desired product.
Scheme 6. Tentative mechanisms that explain the switched selectivity in Pd-catalyzed
alkyne–alkene coupling reactions.
Received: December 25, 2011
Revised: March 24, 2012
Published online: && &&, &&&&
was obtained at room temperature, could not be converted
Keywords: a-methylene-g-lactones · carboesterification ·
palladium · reductive elimination · synthetic methods
into the isomer with E configuration [Eq. (4)]. It seems that
the two configurations are obtained through two different
reaction pathways.
.
[1] a) G. Zeni, R. C. Larock, Chem. Rev. 2006, 106, 4644; b) G. Zeni,
R. C. Larock, Chem. Rev. 2004, 104, 2285; c) N. P. Patil, Y.
Yamamoto, Chem. Rev. 2008, 108, 3395; d) E. Negishi, C.
Coperet, S. Ma, S. Y. Liou, F. Liu, Chem. Rev. 1996, 96, 365.
[2] Examples for the PdII/0-catalyzed intramolecular alkyne and
alkene coupling reactions: a) Q. Zhang, X. Lu, J. Am. Chem.
Soc. 2000, 122, 7604; b) L. Zhao, X. Lu, Angew. Chem. 2002, 114,
4519; Angew. Chem. Int. Ed. 2002, 41, 4343; c) X. Xie, X. Lu, Y.
Liu, W. Xu, J. Org. Chem. 2001, 66, 6545; d) L. Zhao, X. Lu, W.
Xu, J. Org. Chem. 2005, 70, 4059; e) W. Xu, X. Lu, J. Org. Chem.
2006, 71, 3854; f) C. Aubert, O. Buisine, M. Malacria, Chem. Rev.
2002, 102, 813; g) T. A. Rodolfo, A. M. Harned, Org. Lett. 2009,
11, 3998.
A tentative mechanism for the switched selectivity in Pd-
catalyzed intermolecular carboesterification of alkenes to
synthesize a-methylene-g-lactones is proposed on the basis of
the above-mentioned results (Scheme 6). The left pathway is
initiated by trans-halopalladation of alkynoate and keto–enol
equilibria, subsequently, cis-oxypalladation gives intermedi-
ate I,[16] followed by the formation of II through the addition
of the enol to the PdII species. The reductive elimination to
[3] Examples for the PdII/IV-catalyzed intramolecular alkynes and
alkenes coupling reaction: a) L. L. Welbes, T. W. Lyons, K. A.
Cychosz, M. S. Sanford, J. Am. Chem. Soc. 2007, 129, 5836;
b) T. W. Lyons, M. S. Sanford, Tetrahedron 2009, 65, 3211; c) X.
Tong, M. Beller, M. K. Tse, J. Am. Chem. Soc. 2007, 129, 4906;
d) G. Yin, G. Liu, Angew. Chem. 2008, 120, 5522; Angew. Chem.
Int. Ed. 2008, 47, 5442; e) H. Liu, L. Wang, X. Tong, Tetrahedron
Lett. 2008, 49, 6924.
2
3
À
the C(sp ) C(sp ) bond and hydrolysis then afforded the (E)-
product. For the right pathway, PdII-catalyzed carboesterifi-
cation of alkenes with alkynamide was also initiated by the
halopalladation of alkynamide, giving vinylpalladium inter-
mediate III. Subsequently, III is captured by the alkene
through a Heck addition to produce intermediate IV. Isomer-
ization to form intermediate V[14] is followed by b-X
elimination if the alkenes were allyl choride and allyl acetate,
[4] Examples for the PdII/0-catalyzed intermolecular alkynes and
alkenes coupling reaction: a) P. Zhou, L. Huang, H. Jiang, A.
Wang, X. Li, J. Org. Chem. 2010, 75, 8279; b) P. Zhou, H. Jiang,
L. Huang, X. Li, Chem. Commun. 2011, 47, 1003; c) Y. Shen, H.
Jiang, Z. Chen, J. Org. Chem. 2010, 75, 1321; d) J. Huang, L.
Zhou, H. Jiang, Angew. Chem. 2006, 118, 1979; Angew. Chem.
Int. Ed. 2006, 45, 1945; e) S. V. Gagnier, R. C. Larock, J. Org.
Chem. 2000, 65, 1525; f) Q. Huang, R. C. Larock, Org. Lett. 2002,
4, 2505; g) J. Huang, Y. Dong, X. Wang, H. Luo, Chem.
Commun. 2010, 46, 1035.
[5] a) S. Ma, X. Lu, J. Org. Chem. 1991, 56, 5120; b) S. Ma, G. Zhu,
X. Lu, J. Org. Chem. 1993, 58, 3692; c) J. Ji, C. Zhang, X, Lu, J.
Org. Chem. 1995, 60, 1160; d) G. Zhu, X. Lu, Organometallics
1995, 14, 4899.
[6] a) C. Feng, T.-P. Loh, J. Am. Chem. Soc. 2010, 132, 17710; b) S.
Cacchi, G. Fabrizi, Chem. Rev. 2011, 111, 215; c) A. Arcadi, S.
Cacchi, S. D. Giuseppe, G. Fabrizi, F. Marinelli, Org. Lett. 2002,
4, 2409; d) G. Battistuzzi, S. Cacchi, G. Fabrizi, F. Marinelli,
3
[15]
À
or by C(sp ) O bond formation. The hydrolysis of inter-
mediate VI affords (Z)-lactones. Finally, the active PdII
species is regenerated by oxidation with CuII and O2.
In conclusion, we have developed a new and convenient
carboesterification method to construct a-methylene-g-lac-
tone rings. The selectivity can be switched by using either
alkynoates or alkynamides as substrates together with
alkenes, the temperature also plays an important role in this
transformation. Our ongoing studies involve broadening of
the scope of the carboesterification to the carboetherification
and the carboamination of alkenes. An investigation toward
potential applications, for example, in stereoselective syn-
thesis, is currently under way.
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
L. M. Parisi, Org. Lett. 2002, 4, 1355; e) F. Zhou, X. Han, X. Lu,
J. Org. Chem. 2011, 76, 1491.
g) C. C. Scarborough, S. S. Stahl, Org. Lett. 2006, 8, 3251; h) M.
Wasa, J. Yu, J. Am. Chem. Soc. 2008, 130, 14058.
[12] a) N. P. Grimster, G. Gauntlett, C. R. A. Godfrey, M. J. Gaunt,
Angew. Chem. 2005, 117, 3185; Angew. Chem. Int. Ed. 2005, 44,
3125; b) J. Li, H. Jiang, A. Feng, L. Jia, J. Org. Chem. 1999, 64,
5984; c) J. Li, S. Tang, Y. Xie, J. Org. Chem. 2005, 70, 477.
[13] The 13C NMR (CDCl3) data of the carbonyl group in the lactone
moiety 3a (see the Supporting Information): 165.894 ppm and
165.987 ppm (product [18O]-3a). See: Z. Wang, W. Zhang, L.
Gong, R. Tang, X. Yang, Y. Liu, J. H. Li, Angew. Chem. 2011,
123, 9130; Angew. Chem. Int. Ed. 2011, 50, 8968.
[7] H. Jiang, C. Qiao, W. Liu, Chem. Eur. J. 2010, 16, 10968.
[8] a) L. Chen, H. Zhu, R. Wang, K. Zhou, Y. Jing, F. Qiu, J. Nat.
Prod. 2008, 71, 825; b) C. Mang, S. Jakupovic, S. Schunk, H.
Ambrosi, O. Schwarz, J. Jakupovic, J. Comb. Chem. 2006, 8, 268;
c) A. J. Reynolds, A. J. Scott, C. I. Turner, M. S. Sherburn, J. Am.
Chem. Soc. 2003, 125, 12108; d) C. Han, F. J. Barrios, M. V.
Riofski, D. A. Colby, J. Org. Chem. 2009, 74, 7176; e) B. Siedle,
A. J. Garcia, R. Murillo, J. Schulte, V. Castro, P. Rungeler, C. A.
Klaas, F. B. Da, W. Kisiel, I. Merfort, J. Med. Chem. 2004, 47,
6042; f) D. A. Kummer, J. B. Brenneman, S. F. Martin, Org. Lett.
2005, 7, 4621.
[14] a) T. K. Hyster, T. Rovis, J. Am. Chem. Soc. 2010, 132, 10565;
b) C. B. Jacobsen, M. Nielsen, D. Worgull, T. Zweifel, E. Fisker,
K. A. Jorgensen, J. Am. Chem. Soc. 2011, 133, 7398; c) B. M.
Cochran, F. E. Michael, Org. Lett. 2008, 10, 5039.
[9] L. Huang, H. Jiang, C. Qi, X. Liu, J. Am. Chem. Soc. 2010, 132,
17652.
[10] Y. Li, K. J. Jardine, R. Tan, D. Song, V. M. Dong, Angew. Chem.
2009, 121, 9870; Angew. Chem. Int. Ed. 2009, 48, 9690.
[11] Examples of the use of molecular oxygen and MXn as oxidants:
a) M. J. Schultz, M. S. Sigman, J. Am. Chem. Soc. 2006, 128,
1460; b) K. B. Urkalan, M. S. Sigman, Angew. Chem. 2009, 121,
3192; Angew. Chem. Int. Ed. 2009, 48, 3146; c) Y. Zhang, M. S.
Sigman, J. Am. Chem. Soc. 2007, 129, 3076; d) A. M. Balija, K. J.
Stowers, M. J. Schultz, M. S. Sigman, Org. Lett. 2006, 8, 1121;
e) Y. Kawamura, Y. Kawano, T. Matsuda, Y. Ishitobi, T.
Hosokawa, J. Org. Chem. 2009, 74, 3048; f) K. Minami, Y.
Kawamura, K. Koga, T. Hosokawa, Org. Lett. 2005, 7, 5689;
[15] a) S. L. Marquard, J. F. Hartwig, Angew. Chem. 2011, 123, 7257;
Angew. Chem. Int. Ed. 2011, 50, 7119; b) P. Novꢀk, A. Correa,
G. D. Joan, R. Martin, Angew. Chem. 2011, 123, 12444; Angew.
Chem. Int. Ed. 2011, 50, 12236; c) H. Grennberg, J. E. Backvall,
Chem. Eur. J. 1998, 4, 1083.
[16] a) J. P. Wolfe, Eur. J. Org. Chem. 2007, 571; b) J. P. Wolfe, Synlett
2008, 2913; c) N. Momiyama, M. W. Kanan, D. R. Liu, J. Am.
Chem. Soc. 2007, 129, 2230; d) K. Yonehara, Y. Miyoshi, A.
Tsukajima, T. Akatsuka, M. Saito, Adv. Synth. Catal. 2011, 353,
1071.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Synthetic Methods
L. B. Huang, Q. Wang, X. H. Liu,
H. F. Jiang*
&&&& — &&&&
Switch of Selectivity in the Synthesis of a-
Methylene-g-Lactones: Palladium-
Catalyzed Intermolecular
Carboesterification of Alkenes with
Alkynes
Three in one: A highly efficient and mild
PdII-catalyzed carboesterification of
alkenes with carboxylic alkyne derivatives
proceeds through a domino-type alkyne–
controlled by the choice of substrates and
temperature. The reaction provides
a convenient method for the construction
of naturally occurring biologically active
compounds with a-methylene-g-lactone
skeletons.
À
alkene coupling/C O-bond formation
(see scheme). The stereoselectivity is
6
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!