Pd(II)-catalyzed dehydrogenative olefination of vinylic C-H bonds with allylic esters: General and selective access to linear 1,3-butadienes

Article abstract of DOI:10.1021/ol300442w

This work demonstrates a general and efficient method to prepare conjugated dienes by Pd(II)-catalyzed direct olefination of unactivated alkenes with allylic esters and acrylates via vinylic C-H activation. Various aryl and heteroaryl alkenes as well as a

Full text of DOI:10.1021/ol300442w

ORGANIC
LETTERS
2012
Vol. 14, No. 7
1838–1841
Pd(II)-Catalyzed Dehydrogenative
Olefination of Vinylic CÀH Bonds with
Allylic Esters: General and Selective
Access to Linear 1,3-Butadienes
Yuexia Zhang, Zili Cui, Zejiang Li, and Zhong-Quan Liu*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou
Gansu 730000, P. R. China
liuzhq@lzu.edu.cn
Received February 22, 2012
ABSTRACT
This work demonstrates a general and efficient method to prepare conjugated dienes by Pd(II)-catalyzed direct olefination of unactivated alkenes
with allylic esters and acrylates via vinylic CÀH activation. Various aryl and heteroaryl alkenes as well as aliphatic alkenes all give the desired
linear 1,3-butadienes with retention of the traditional leaving groups such as OAc and other carboxylic acid ester groups.
Conjugated dienes and polyenes represent a large class
ofimportant natural products and pharmaceutically active
compounds such as vitamin A, lissoclinolide, carotenes,
bombykol, scyphotatin, viridenomycin, etc.1 Methods
for the preparation of these molecules can be divided into
two general categories.1d One is the carbonyl olefination
reactions2 represented by the Wittig reaction3 and its vari-
ants such as the HornerÀWadsworthÀEmmons reaction,4
StillÀGennari modification,5 Julia olefination,6 and the
Peterson reaction.7 The second strategy is the alkenylation
via CÀC cross-coupling reactions such as Stille cross-
coupling,8 Heck alkenylation,9 and Negishi coupling.10
Recently, several interesting direct methods via oxidative
cross-coupling of alkenes with acrylates and styrenes have
been developed by Ishii,11Loh,12 Yu,13 and Glorius14 et al.
(7) Peterson, D. J. J. Org. Chem. 1968, 33, 780.
(8) Stille, J. K. Angew. Chem., Int. Ed. 1986, 25, 508.
(9) For selected reviews of FujiwaraÀMoritani oxidative Heck reac-
tions, see: (a) Moritani, I.; Fujiwara, Y. Synthesis 1973, 524. (b) Heck,
R. F. Org. React. 1982, 27, 345. (c) Dyker, G. Angew. Chem., Int. Ed.
1999, 38, 1698. (d) Fujiwara, Y.; Jia, C. Pure Appl. Chem. 2001, 73, 319.
(e) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34, 633. (f)
Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (g)
Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077. (h) Chen,
X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009,
48, 5094. (i) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (j)
Satoh, T.; Miura, M. Synthesis 2010, 3395. (k) Le Bras, J.; Muzart, J.
Chem. Rev. 2011, 111, 1170.
(10) (a) Negishi, E. Handbook of Organopalladium Chemistry for
Organic Synthesis; Wiley-Interscience: New York, 2002; Vol. 2, Part III,
pp 213À1119. (b) Negishi, E. Bull. Chem. Soc. Jpn. 2007, 80, 233.
(11) Hatamoto, Y.; Sakaguchi, S.; Ishii, Y. Org. Lett. 2004, 6, 4623.
(12) (a) Xu, Y.-H.; Lu, J.; Loh, T.-P. J. Am. Soc. Chem. 2009, 131,
1372. (b) Xu, Y.-H.; Wang, W.-J.; Wen, Z.-K.; Hartley, J. J.; Loh, T.-P.
Tetrahedron Lett. 2010, 51, 3504. (c) Xu, Y.-H.; Chok, Y. K.; Loh, T.-P.
Chem. Sci. 2011, 2, 1822.
(1) (a) Eiter, K. Fortschr. Chem. Org. Naturst. 1970, 28, 204. (b)
Nicolaou, K. C.; Daines, R. A.; Ogawa, Y.; Chakraborty, T. K. J. Am.
Soc. Chem. 1988, 110, 4696. (c) Cereghetti, D. M.; Carreira, E. M.
Synthesis 2006, 914. (d) Negishi, E.-i.; Huang, Z.; Wang, G.; Mohan, S.;
Wang, C.; Hattori, H. Acc. Chem. Res. 2008, 41, 1474. (e) Negishi, E.-i.;
Wang, G. Science of Synthesis; Rawal, V., Kozmin, S., Eds.; Thieme:
Stuttgart, 2009; Vol 46, pp 239À352. (f) Negishi, E.-i.; Wang, G. Science of
Synthesis; Jacobsen, E. N., de Meijere, A., Eds.; Thieme: Stuttgart, 2010;
Vol. 47, pp 909À1016. (g) Wang, G.; Mohan, S.; Negishi, E.-i. Proc. Natl.
Acad. Sci. U.S.A. 2011, 108, 11344. (h) Negishi, E.-i. Angew. Chem., Int.
Ed. 2011, 50, 6738.
(2) (a) Evans, D. A.; Nelson, J. V.; Taber, T. R. Top. Stereochem.
1982, 13, 1. (b) Mukaiyama, T. Org. React. 1982, 28, 203.
(3) (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863. (b)
Dong, D. J.; Li, H. H.; Tian, S. K. J. Am. Soc. Chem. 2010, 132, 5018.
(4) (a) Horner, L.; Hoffmann, H.; Wippel, H. G.; Klahre, G. Chem.
Ber. 1959, 92, 2499. (b) Wadsworth, W. S.; Emmons, W. D., Jr. J. Am.
Soc. Chem. 1961, 83, 1733.
(13) Yu, H.; Jin, W.; Sun, C.; Chen, J.; Du, W.; He, S.; Yu, Z. Angew.
Chem., Int. Ed. 2010, 49, 5792.
(5) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
(6) Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 14, 4833.
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2011, 17, 7167.
r
10.1021/ol300442w
Published on Web 03/19/2012
2012 American Chemical Society

Table 1. Modification of the Typical Reaction Conditionsa
Scheme 1. Direct Oxidative Olefination of Vinylic CÀH Bonds
yield
entry
catalyst
oxidant
solvent (v/v)
DMSO
(%)b
1
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
trace
trace
7
2
DMSO/HOAc (1:1)
5% DMSO/DMF
5% DMSO/THF
3
4
18
5
5% DMSO/ClCH2CH2Cl 34
5% DMSO/ClCH2CH2Cl 22
5% DMSO/ClCH2CH2Cl trace
5% DMSO/ClCH2CH2Cl 11
5% DMSO/ClCH2CH2Cl 18
5% DMSO/ClCH2CH2Cl 16
5% DMSO/ClCH2CH2Cl trace
6
7
Pd(TFA)2
8
Pd(PCy3)2Cl2 AgOAc
9
Pd(acac)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
AgOAc
Ag2CO3
Ag2O
10
11
12
Cu(OAc)2 5% DMSO/ClCH2CH2Cl trace
13c Pd(OAc)2
14d Pd(OAc)2
15f Pd(OAc)2
AgOAc
AgOAc
AgOAc
5% DMSO/ClCH2CH2Cl 50
5% DMSO/ClCH2CH2Cl 81e
5% DMSO/ClCH2CH2Cl 41
a Reaction conditions: styrene (0.5 mmol), allyl acetate (1.5 mmol),
oxidant (2 equiv), catalyst (10 mol %), 110 °C, 15 h, unless otherwise
noted. b Isolated yields of the E/E and Z/E isomers. c Pd(OAc)2 (15 mol %).
d Pd(OAc)2 (15mol%), AgOAc(2.5equiv). e Conversion of styrene is 75%;
Isolated yield based on conversion of styrene. f Pd(OAc)2 (15 mol %),
AgOAc (2.5 equiv), 80 °C.
(Scheme 1). Although these systems provide very efficient
and direct strategies for the construction of conjugated
alkenes by olefination of alkenes via vinylic CÀH bond
activation, most of them suffer from a limited substrate
scope and acidic conditions. For example, only vinyl car-
boxylates and acrylates are tolerated in Ishii’s system.11
Alkenes without R-substituents give no products in
Loh’s.12 The R-oxoketene dithioacetals13 and specific al-
kenes with directing or activating groups14 are the only
effective substrates in the latter two procedures, respec-
tively. In addition, acetic acid was used as solvent in
some cases, which would not tolerate certain functional
groups.11,12 Therefore, more efficient and general proto-
cols to prepare butadienes by direct oxidative vinylic CÀH
cross-coupling reactions would be highly desirable. Here-
in, we report a general and efficient strategy for conjugated
diene synthesis by Pd(II)-catalyzed direct oxidative olefi-
nation of various unactivated alkenes with allyl esters and
acrylates under nearly neutral conditions (Scheme 1). In
addition, a variety of phenyl, naphthalenyl, furyl, thienyl,
and alkyl alkenes could be selectively olefinated by allyl
esters and acrylates to form the corresponding 1,3-buta-
dienes in moderate to good yields.
esters are rarely achieved.16As anticipated from the mech-
anism for the oxidative Heck-type reaction, the β-H
elimination may be promoted by an electron-rich arene to
stabilize the positively charged benzylic carbon in the four-
membered transition state. Otherwise, an allylation would
occur by β-OAc elimination.9 Inspired by our previous
work in the oxidative olefination of arenes with allyl
esters,17 we began to wonder about the possibility of direct
oxidative Heck cross-coupling of alkenes with allyl esters.
Fortunately, we successfully accomplished the first exam-
ple of Pd(OAc)2-catalyzed direct olefination of various
unactivated alkenes with allylic esters, which would pro-
vide an efficient and general approach to 1,3-butadienes
and their derivatives.
Initially, we chose styrene and allylic acetate as the
model substrates to optimize suitable conditions for this
reaction (Table 1). It was found that the solvent, catalysts,
and oxidants critically affect the reaction efficiency. Sol-
vents such as DMSO, DMSO/HOAc (v/v = 1:1), 5%
DMSO/DMF (v/v), and 5% DMSO/THF were not effec-
tive (entries 1À4). The desired products were isolated in a
yield of 34% by using a mixed solvent of 5% DMSO/
ClCH2CH2Cl (v/v) (entry 5). The yield decreased with
increasing or decreasing the amount of DMSO (see Sup-
porting Information). The solvent effect indicates that a
Allylic estershavebeenwidelyused asallylation reagents
in organic synthesis.15However, Pd-catalyzed Heck-type
coupling reactions of boronic acids and halides with allyl
(15) For selected reviews, see: (a) Trost, B. M. Acc. Chem. Res. 1980,
13, 385. (b) Tsuji, J. Pure Appl. Chem. 1999, 71, 1539. (c) Marshall, J. A.
Chem. Rev. 2000, 100, 3163. (d) Schobert, R.; Gordon, G. J. Curr. Org.
Chem. 2002, 6, 1181. (e) Trost, B. M.; Crawley, M. L. Chem. Rev. 2003,
103, 2921. (f) Pan, D.; Jiao, N. Synlett 2010, 1577.
(16) (a) Pan, D.; Chen, A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.;
Liu, Q.; Zhang, L.; Jiao, N. Angew. Chem., Int. Ed. 2008, 47, 4729. (b) Su,
Y.; Jiao, N. Org. Lett. 2009, 11, 2980. (c) Pan, D.; Yu, M.; Chen, W.;
Jiao, N. Chem.;Asian J. 2010, 5, 1090.
(17) (a) Shang, X.; Xiong, Y.; Zhang, Y.; Zhang, L.; Liu, Z.-Q.
Synlett 2012, 259. (b) Zhang, Y.; Li., Z.; Liu, Z.-Q. Org. Lett. 2012, 14,
226. (c) Li., Z.; Zhang, Y.; Liu, Z.-Q. Org. Lett. 2012, 14, 74.
Org. Lett., Vol. 14, No. 7, 2012
1839

Table 2. Olefination of Various Alkenes with Allylic Acetates and Acrylatesa
a Reaction conditions: alkene (0.5 mmol, 1 equiv), allyl esters or acrylates (1.5 mmol, 3 equiv), AgOAc (2.5 equiv), Pd(OAc)2 (15 mol %), 5% DMSO/
ClCH2CH2Cl (v/v), 110 °C, unless otherwise noted. b Reaction time, indicated by TLC. c Isolated yields of the E/E and Z/E isomers. d Ratio of E/E and
Z/E isomers determined by 1H NMR. e The reaction was performed at 70 °C. f The reaction was performed at 60 °C.
specified volume of DMSO plays an important role in
this reaction. As the catalyst, Pd(OAc)2 was more efficient
than PdCl2, Pd(O2CCF3)2, PdCl2(Cy3P)2, and Pd(acac)2
(entries 6À9). The oxidant AgOAc was better than others
such as Ag2CO3, Ag2O, and Cu(OAc)2 (entries 10À12).
Moreover, the yields increased with increasing the amount
of catalyst and oxidant (entries 13 and 14). A lower
temperature gave a lower yield (entry 15). The desired
product 3a was obtained in 81% isolated yield under the
typical conditions: 1.0 equiv of styrene, 3.0 equiv of allyl
ester, 15 mol % Pd(OAc)2, 2.5 equiv of AgOAc, 5%
DMSO/ClCH2CH2Cl, 110 °C, 15 h. Entries 1À15 are only
a sampling of over 60 reactions which have been screened
by using different catalysts, ligands, additives, oxidants,
bases, and solvents (see Supporting Information).
good yields (3bÀ3j). Among them, electron-rich styrenes
gave slightly higher yields than the electron-poor ones
(3bÀ3e). The meta- and ortho-substituted styrenes gave
comparative yields to the para-substituted ones (3f, 3g).
The R-methyl and R-phenyl styrenes were tolerated in this
reaction (3h, 3i). In addition, an internal alkene reacted
with allyl acetate to furnish 3j in 60% isolated yield. The
2-vinylnaphthalene and 2-isopropenylnaphthalene were
also effective substrates, and the corresponding products
3k and 3l were obtained in 63% and 84% yields, respec-
tively. Surprisingly, heteroaryl-substituted ethylenes such
as 2-vinylthiophene and 2-vinylfuran were also success-
fully employed for the vinylic CÀH oxidative olefination
reaction which has never been reported before, and the
desired products 3m and 3n were isolated in 85% and 86%
yields, respectively. Moreover, the oxidative olefination of
aliphatic alkenes with allylic esters also gave good yields of
the corresponding dienes, though the conversion of ali-
phatic olefins was low (3o and 3p).
To examine the scope of this system, the coupling
reactions of various alkenes with substituted allylic esters
and acrylates were studied (Table 2). A variety of sub-
stituted styrenes gave the desired products in moderate to
1840
Org. Lett., Vol. 14, No. 7, 2012

On the other hand, various substituted allylic esters gave
moderate yields of the desired products in this reaction
(Table 2, 3qÀ3u). The coupling reaction of styrene with R-
methyl and β-methyl allyl acetates afforded products 3q
and 3r in 79% and 76% yields, respectively. Additionally,
allyl benzoate gave a good yield of 3s. Moreover, allyl
acrylate and allyl methacrylate also gave the allyl vinylic
CÀH bond olefination products3tand 3uin46%and 66%
yields, respectively. It is noteworthy that acrylates could
also be used as the olefination partners with styrene to
produce the desired dienes in moderate yields under the
reaction conditions (3v, 3w, and 3x). However, in the
system by Loh et al., olefination of styrene with acrylates
gave no desired products.12
Scheme 2. Mechanistic Studies on the Oxidative Olefination of
Alkenes with Allyl Esters
To investigate the mechanism for this oxidative olefina-
tion, an intermolecular competition reaction was carried
out (eq 1), which indicates that the difference between allyl
acetate and butyl acrylate in the olefination of styrene is
not remarkable. The same conclusion can be obtained
from an intramolecular competition reaction of allyl acry-
late with 5-vinylbenzo[d][1,3]dioxole under the typical
conditions (eq 2).
In conclusion, we developed a general and direct proto-
col to prepare conjugated dienes via a Pd(II)-catalyzed
oxidative olefination of unactivated alkenes with allylic
esters and acrylates. This strategy exhibits the broadest
substrate scope with respect to both alkenes and allylic
esters/acrylate partners among the existing systems. Var-
ious aryl and heteroaryl alkenes as well as aliphatic alkenes
all give the expected 1,3-dienes as the major products. In
addition, as the olefination partner, a series of substituted
allylic esters bearing another CdC bond such as allyl
acrylates also give moderate to good yields of the desired
products. Further investigation of this procedure is under-
way in our laboratory.
In addition, an intermolecular kinetic isotope effect
(KIE) experiment was carried out. As a result, a significant
KIE was observed with the kH/kD = 6.6 (Scheme 2). It
indicates that the CÀH bond cleavage is involved in the
rate-determining step of this procedure. A plausible mech-
anism that is consistent with the experimental data and
literature precedent is depicted in Scheme 2. Addition of
Pd(OAc)2 to alkene generates intermediate 1, which would
precede an elimination of HOAc to give an alkenyl-
Pd-OAc intermediate 2.10,12 The insertion of 2 to the double
bond of the allyl ester would form intermediate 3. The
desired product diene is obtained by β-H elimination, and
the catalyst is regenerated following oxidation of the low-
valent Pd complex.9,12,17
Acknowledgment. This project is supported by Na-
tional Science Foundation of China (No. 21002045) and
the Fundamental Research Funds for the Central Univer-
sities (lzujbky-2012-55). We also thank the State Key
Laboratory of Applied Organic Chemistry for financial
support.
Supporting Information Available. Full experimental
details and characterization data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 7, 2012
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