A simple and efficient method for the allylation of heteroarenes catalyzed by PdCl2

Article abstract of DOI:10.1016/j.tet.2012.06.038

The PdCl₂-catalyzed allylation of heteroarenes is presented. Various heteroarenes including O-, N-, and S-based ones were allylated efficiently with a rich range of allylic acetates in the presence of only 2 mol % of PdCl₂, without the need of bases/acids, additives, and external supporting ligands. In addition, the reactions were carried out under mild and simple conditions just by stirring the two reactants and catalyst in CH ₂Cl₂ at 60 °C. Moreover, the by-product produced was non-toxic acetic acid. Thus, the method presented in this work provides a general, clean, and operationally simple approach for the functionalization of heteroarenes. Finally, a preliminary mechanistic study suggested that the Pd(II) may be reduced in situ by the heteroarenes to Pd(0), which serves as the active metal center to catalyze the following allylations of heteroarenes via a Tsuji-Trost pathway.

Full text of DOI:10.1016/j.tet.2012.06.038

Tetrahedron 68 (2012) 6837e6842
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A simple and efficient method for the allylation of heteroarenes catalyzed by
PdCl2
,
,
,c,
*
Feng-Quan Yuan a b, Feng-Yi Sun a b, Fu-She Han a
a Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, People’s Republic of China
b Graduate School of Chinese Academy of Sciences, Beijing 100864, People’s Republic of China
c State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
The PdCl2-catalyzed allylation of heteroarenes is presented. Various heteroarenes including O-, N-, and
S-based ones were allylated efficiently with a rich range of allylic acetates in the presence of only
2 mol % of PdCl2, without the need of bases/acids, additives, and external supporting ligands. In addition,
the reactions were carried out under mild and simple conditions just by stirring the two reactants and
catalyst in CH2Cl2 at 60 ꢀC. Moreover, the by-product produced was non-toxic acetic acid. Thus, the
method presented in this work provides a general, clean, and operationally simple approach for the
functionalization of heteroarenes. Finally, a preliminary mechanistic study suggested that the Pd(II) may
be reduced in situ by the heteroarenes to Pd(0), which serves as the active metal center to catalyze the
following allylations of heteroarenes via a TsujieTrost pathway.
Received 27 March 2012
Received in revised form 3 June 2012
Accepted 8 June 2012
Available online 16 June 2012
Keywords:
Allylic acetates
Heteroarenes
Allylation
Ó 2012 Elsevier Ltd. All rights reserved.
Pd catalyst
TsujieTrost reaction
1. Introduction
As another well-established protocol, the Pd(0)1b or other
transition metals, such as Ni(0),14 Ru(0),15 Mo(0),16 and W(0)-
Allylic substitution is an important transformation in organic
synthesis for CꢁC, CꢁO, CꢁN, and CꢁS bond formation.1 Particu-
larly, the allylic alkylation of heteroarenes, such as furan-, pyrrole-,
and thiophene-based derivatives has captured much attention over
the past decades owing to the ubiquitous nature of these structural
motifs in a broad range of areas, such as natural products, bioactive
compounds, materials science, catalysis, and supramolecular and
coordination chemistry.2 Furthermore, the incorporated olefin
functionality may serve as a latent group for further diverse
transformations. While classic methods for this reaction mainly
relied on FriedeleCrafts reaction in the presence of stoichiometric
amounts of acids,3 a variety of Brønsted and Lewis acids have been
developed recently that allows for mild, atom-efficient, and clean
catalyzed TsujiꢁTrost-type allylation offers several advantages
over the acid-catalyzed version. For instance, these reactions are
generally tolerant of various functional groups. In addition, a wide
range of leaving groups in allylic compounds, such as halides,
ethers, acetates, sulfones, carbonates, carbamates, and phosphates
can be utilized. Therefore, the TsujieTrost reaction has recently
attracted considerable interests in the allylation of heteroarenes
including the asymmetric version.17 However, most of the efforts
have been focused on the NeH free indoles, the N-protected ana-
logues as well as O- and S-based heteroarenes have been less
considered. Concerning the electrophiles, the unsymmetrically
substituted allylic substrates have been less studied. In addition,
these pathways usually required the use of external ligands paired
with the presence of a large amount of activators, such as base/acid,
trialkyl boranes, and BSA. Finally, the formation of regioisomers,
such as N- and 3-allylindoles, or N,3-diallylated indole is also an
important concern.17a,b
Owing to the existing drawbacks of FꢁC or TsujiꢁTrost allylation
versus the great importance of allylated heteroarenes, the de-
velopment of a green, atom-economic, and generally applicable
method that is capable of allylating various heteroarenes is of con-
siderably interest.18 To this end, we have previously developed
a PdCl2 catalyst system that allows the allylation of various hetero-
arenes to proceed in a simple, clean, and atom-efficient manner.19
allylation of
a broad range of nucleophiles under catalytic
amount.4e12 In addition, the I2-mediated FriedelꢁCrafts-type re-
action has also been shown to be a prominent alternative.13 How-
ever, despite these significant advances, general use of these
methods in the allylation of heteroarenes remains to be de-
termined. For instance, the allylation of S-containing heteroarenes
has been largely unexplored.
* Corresponding author. Tel.: þ86 431 8526 2936; fax: þ86 431 8526 2926;
e-mail address: fshan@ciac.jl.cn (F.-S. Han).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.038

6838
F.-Q. Yuan et al. / Tetrahedron 68 (2012) 6837e6842
The reaction can be proceeded smoothly just by simply stirring the
heteroarenes and an equimolar or a slight excess of allylic acetates in
the presence of a catalytic amount of PdCl2 as low as 2 mol %. No
external bases (oracids), additives, and ligands were required. While
the generality for heteroarenes has been demonstrated therein, the
compatibility of the procedure to the structural diversity of allylic
acetates has not been fully exemplified. In addition, the possible
reaction mechanism of this transformation remained unclarified.
Thus, we set out a further investigation into these issues. The full
data toward the general application, along with a preliminary study
on the possible reaction mechanism will be presented herein.
Table 1
Preparation of various allylic acetates
2. Results and discussion
5
50
Ratio (5/50)
Our initial concept, although tentative, is that either based on
the TsujieTrost or FriedeleCrafts reaction mechanism, the key to-
ward the development of an efficient method for the allylation of
heteroarenes relies mainly on the discovery of an appropriate metal
1.2:1
catalyst whose
p-allylmetal complex A is sufficiently electrophilic
to various heteroarenes containing different heteroatoms (Eq. 1).
For the choice of such a suitable catalyst, the property of metal ions
as well as the ligated ligands or counter ions should be carefully
considered because the combination of these factors influences
dramatically the redox property and affinity of the metaleligand
complex,20 and ultimately, affecting the catalytic activity of the
catalysts. In addition, the coordination ability of the solvent with
metal ions would also be an important factor, which is proposed to
affect the interaction strength between the heteroarene and metal
ion.17b
1.3:1
1.6:1
1.6:1
With these preliminary assumptions in mind, we carried out an
extensive survey of an appropriate catalyst system by screening
different transition metals and solvents. These efforts eventually
led to the discovery of a very simple and highly active catalyst
system (i.e., 2 mol % of PdCl2 in CH2Cl2 or ClCH2CH2Cl under heat-
ing), which allows a rich range of heteroarenes, such as furan-,
pyrrole-, and thiophene-based compounds to be allylated smoothly
with allylic acetate 1 or the more challenging benzhydryl acetate 2
(Scheme 1), affording the desired adducts 3 and 4, respectively, in
good to excellent yields and high regioselectivity.19
1:1
d
d
d
Scheme 1. Allylation and benzhydrylation of various heteroarenes with allylic acetate
1 and benzhydryl acetate 2.
d
d
Having demonstrated the generality of the method for the
allylation of various heteroarenes, we next examined its feasibility
by varying the structure of allylic acetates. Accordingly, several al-
lylic acetates 5aei (Table 1) bearing different functional groups,
including electron-donating, electron-withdrawing, and sterically
differentiated groups, as well as a labile bromo group toward pal-
ladium catalyst, were synthesized smoothly according to the
known procedures.21 Accordingly, condensation reaction of an al-
dehyde with a methyl ketone in the presence of NaOH produced the
corresponding chalcone. Selective reduction of the carbonyl group

F.-Q. Yuan et al. / Tetrahedron 68 (2012) 6837e6842
6839
Table 2
with LiAlH4 followed by acetylation of the OH with Ac2O afforded
Allylation of O-containing heteroarenes with various allylic acetatesa
the allylic acetates 5. Here, it should be mentioned that in the
preparation of allylic acetate 5, inseparable regioisomers 50aed
corresponding to 5aed were formed as determined by 1H NMR
spectroscopic analysis. We assumed that the reaction efficiency
should not be influenced by the regioisomeric difference, and
therefore, the regioisomeric mixtures were used to examine the
efficacy of allylation reaction.
Thus, the allylation reaction of the O-containing heterocycles
and various allylic acetates was first investigated under the opti-
mized conditions developed previously.19 2-Methylfuran could be
allylated efficiently to produce regioisomeric mixtures composed of
the 2-allylated products 6 and 7 in high overall yields (Table 2,
entries 1ꢁ10). Both electron-donating groups, such as OMe and
withdrawing groups, such as Br and NO2 were tolerated. In addi-
tion, substrates decorated with a Br group at the para- or meta-
position of phenyl ring were also compatible with the reaction
conditions, affording the desired allylated products in excellent
yields. This is interesting because Br group is usually a prominent
leaving group in numerous Pd-catalyzed cross-couplings. More-
over, high yield (90%) could also be obtained when an aromatic
group was replaced by a simple Me (entries 7 and 8). Note that
although the allylic acetate derived from cinnamic alcohol (5h) was
less reactive (entry 9, 45% yield), its trifluoroacetate analogue 5i
reacted smoothly to give the allylated product in high yield (entry
10). The regioselectivity at the C-2 position of furan was confirmed
by the 1He1H COSY spectroscopy (see SI, Fig. S6). Finally, efficient
allylation of benzofuran with various allylic acetates in equimolar
ratio was also observed (entries 11ꢁ14). As a result, smooth re-
action of O-containing heteroarenes with an array of allylic acetates
and the good tolerance of different functional groups, such as
methoxy, bromo, and nitro groups render this transformation at-
tractive since these functional groups may serve as latent func-
tionalities for further modification. It should also be mentioned that
the high yields observed for all these transformations clearly
demonstrated our assumption, that is, the regioisomeric difference
between 5aed and 5a0ed0 does not affect the efficiency of the
allyaltion reaction (vide supra).
Entry
6
7
Yieldb Ratioc
(6þ7) (6/7)
1
84%
94%
93%
95%
1.2:1
2
3
4
2:1
1:1
1:1
5
96%
1:1
The regioselectivity between the allylated products 6 and 7 was
mainly controlled by the steric factor of both allylic acetates and
heteroarenes. This can be clearly observed from the reaction of
furan and benzofuran with allylic acetates 5eꢁi (entries 6ꢁ10 and
12ꢁ14). Typically, when R1 and R2 in allylic acetate 5e are similar
phenyl substituents, a low ratio of ca. 1.4:1 is obtained for the
allylated products 6e/7e (entry 6). However, when R1 group is al-
tered to a smaller Me or H group, the ratio between the products 6
and 7 is increased to 3.8:1 and 6:1, respectively (entries 7 vs 9 and
10). On the other hand, when R1 group was fixed as Me, but in-
crease the steric hindrance of aromatic group, e.g., by introducing
an ortho-OTBS substituent in the phenyl ring (entry 7 vs 8), the
ratio of 6g/7g was substantially increased to 7.1:1 from 3.8:1. This
trend can be observed more clearly for the sterically more en-
cumbered benzofuran nucleophile (entries 12ꢁ14). Namely, the
ratio of 6j/7j and 6k/7k is enlarged from 2.4:1 to 13:1 if a larger
nitro phenyl group was changed to a smaller Me (entries 12 and
13). Notably, only a single isomer 6l was obtained in 77% yield for
the allylation of benzofuran and the unsubstituted 5i (entry 14).
The results shown here would be useful for achieving high regio-
selective allylation reaction if allylic acetates are designed
appropriately.
6
7
93%
90%
1.4:1
3.8:1
8
97%
7.1:1
Having examined the allylation of O-heteroarenes with various
allylic acetates, our focus was then shifted to the N-containing
heteroarenes. Here, indole derivatives were employed to evaluate
the reaction efficiency with an array of allylic acetates. The results
showed that an array of indole derivatives could be allylated very
efficiently in the presence of an equimolar or a slight excess of
9
45%
5.8:1
6:1d
10
82%d
(continued on next page)

6840
F.-Q. Yuan et al. / Tetrahedron 68 (2012) 6837e6842
Table 2 (continued )
Table 3
Allylation of N-containing heteroarenes with various allylic acetatesa
Entry
6
7
Yieldb Ratioc
(6þ7) (6/7)
11
12
13
84%
86%
77%
77%d
1.1:1
2.4:1
13:1
d
Entry
8
9
Yieldb Ratioc
(8þ9) (8/9)
1
2
3
R¼H
94%
98%
93%
1.5:1
1.4:1
1.1:1
R¼Me
R¼Boc
14
4
5
R¼H
R¼Me
98%
1:1.4
100%
1:1.3
a
Reaction conditions: allylic acetate 5 (0.4 mmol), heteroarenes (2.0 mmol for 2-
methylfuran due to the volatile nature, 0.4 mmol for benzofuran), PdCl2 (2 mol %) in
CH2Cl2 (1.5 mL) at 60 ꢀC in sealed tube.
6
86%
1:1
b
Isolated yields of mixture.
c
The ratio between 6 and 7 was determined by 1H NMR spectroscopies.
d
Allylic trifluoroacetate was used instead of allylic acetate.
allylic acetates decorated by different functionalities. As sum-
marized in Table 3, the NeH free indole underwent smooth re-
action with several allylic acetates to afford exclusively the C-3
allylated products 8 and 9 in excellent yields (entries 1, 4, 6, 7, and
9). In this transformation, the N-allylated, or N- and C-3 dially-
lated by-products were not detected. However, such side-
reactions were observed in some reported procedures.17a,b
Moreover, both electron-donating group, such as OMe and
electron-withdrawing functionalities, such as Br and NO2 in the
allylic acetates were also tolerated. In addition, the indole de-
rivatives either protected by an electron-rich Me (entries 2, 5, 8,
and 10) or by an electron-deficient Boc group (entry 3) also
reacted well with a variety of allylic acetates. These results
showed that the allylating conditions exhibit a broad compati-
bility to indole derivatives. In comparison, the transition-metal-
catalyzed arylation of indoles is severely limited by the nature of
N-protecting groups. For instance, some studies have shown that
the electron-deficient N-acetylindole could react smoothly under
certain conditions. However, these conditions were inefficient for
the electron-rich N-alkylindoles or N-free indoles, leading to the
decomposition or self-dimerization of N-alkylindoles.22 Alterna-
tively, the reaction was not occurred when unprotected NeH free
indoles were used.
7
8
R¼H
R¼Me
94%
91%
1:1
1:1
9
10
R¼H
90%
91%
1.3:1
1:1
R¼Me
a
Reaction conditions: allylic acetate 5 (0.4 mmol), indoles (0.4 mmol, 1.0 equiv),
PdCl2 (2 mol %) in CH2Cl2 (1.5 mL) at 60 ꢀC in sealed tube.
b
Isolated yields of mixture.
c
The ratio between 8 and 9 was determined by 1H NMR spectroscopies.
a representative. Complete conversion as well as high to excellent
yield was observed for a broad range of allylic acetates in the
presence of an equimolar mole or a slight excess of allylic acetates
(Table 4). Similar to the O-based heteroarenes, the allylation oc-
curred exclusively at the 2-position of S-heteroarene (see SI,
Fig. S29), and the ratio of the products 10 to 11 was also affected
markedly by the steric factor of R1 and R2 substituents in the allylic
acetates (entry 6 vs 7).
It should be mentioned that, to compare with the O-hetero-
arenes whose allylation took place at the C-2 position, the allylation
of indole derivatives occurred regiospecifically at the C-3 position
as confirmed by the 1H NMR and 1He1H COSY spectroscopies (see
SI, Fig. S19 and S21). This is attributed to the differentiated nucle-
ophilicities of the O- and N-based heteroarenes as seen from the
reported results.4b,9b
Finally, the allylation of S-containing heteroarenes with various
allylic acetates was examined employing 2-methylthiophene as
It is now evident that PdCl2 as catalyst with a combination of
CH2Cl2 as solvent is a highly efficient system for the allylation of

F.-Q. Yuan et al. / Tetrahedron 68 (2012) 6837e6842
6841
Table 4
Allylation of S-containing heteroarenes with various allylic acetatesa
Entry
10
11
Yieldb
(10þ11) (10/11)
Ratioc
To address this issue, we carried out some control experiments.
In the absence of PdCl2, the reaction of 2-methylfuran with allylic
acetate 1 was sluggish, with only a small amount of product 3 was
observed after stirring the reaction mixture for about 36 h (Scheme
2). This result indicated that PdCl2 played a key role in promoting
the transformation. On the other hand, when a 2:1 molar ratio of
heteroarenes (indole was used here) and PdCl2 was stirred under
refluxing (CH2)2Cl2 for several hours, Pd black was generated as
seen by naked eyes. X-ray photoelectron spectroscopic analyses
(XPS) also confirmed that Pd(0) was formed in the system (see SI,
Fig. S30). In contrast, when the mixture of allylic acetate 1 and
PdCl2 was stirred under the identical conditions, Pd(0) was not
detected and 1 remains almost unchanged. These results suggest
that heteroarenes may be acting to reduce the Pd(II) to Pd(0) in the
reaction process, and consequently, the in situ formed Pd(0) serves
as the active metal center to promote the subsequent allylation
reaction.
1
92%
90%
95%
1.1:1
3.3:1
1:1
2
3
4
5
93%
96%
1.4:1
Scheme 2. Pd(0)-catalyzed allylation of 2-methylfuran with allylic acetate 1.
1:1
The assumption was further supported by the effective allylation
using Pd(0) as catalyst. As shown in Scheme 2, after a brief exami-
nation of several Pd(0) catalysts, we found that by employing
Pd(dba)2 or Pd2(dba)3 as catalysts, allylation of 4-methylfuran with
allylic acetate 1 occurred in good yield and regioselectivity to afford
thedesired C-2allylatedproduct3 in 60%and70%yield, respectively.
The Pd2(dba)3 exhibits equally good catalytic efficiency to PdCl2.19
Thus, the control experiments indicate that the PdCl2-mediated
allylation of heteroarenes with allylic acetates should involve
6
96%
92%
2.4:1
9.9:1
a
Pd(0)-catalyzed TsujieTrost pathway, although the Pd(II)-
catalyzed FꢁC reaction cannot be entirely ruled out at this stage
and awaits a further detailed clarification. A plausible catalytic cycle
is shown in Scheme 3 by taking the reaction of 2-methylfuran and
allylic acetate 1 as a representative. Initially, Pd(II) is reduced in situ
7
a
Reaction conditions: allylic acetates
5 (0.4 mmol), 2-methylthiophene
(0.4 mmol, 1.0 equiv), PdCl2 (2 mol %) in CH2Cl2 (1.5 mL) at 60 ꢀC in sealed tube.
b
Isolated yields of mixture.
c
The ratio between 10 and 11 was determined by 1H NMR spectroscopies.
various heteroarenes including O-, N-, and S-containing heterocy-
cles. Based on the Lewis acid property of PdCl2, we initially assumed
that the reaction may proceed via a typical FꢁC pathway. In fact,
a previous report has proposed that in the Pd(II)-catalyzed CꢁO
bond formation employing diarylmethyl alcohol as electrophile and
aliphatic alcohol as nucleophile,12 the reaction was affected mainly
by the Lewis acid property of Pd(II) (Eq. 2). However, the real ex-
perimental results were somewhat inconsistent with our initial
assumption because palladium black was observed in the reaction
system. Such observation implies that, unlike the CeO bond for-
mation, the Pd-catalyzed allylic CeC bond formation of hetero-
arenes presented here should involve an alternative reaction model
and therefore, raises the question of whether the reaction proceeds
via the Pd(0)- or the Pd(II)-catalyzed cycle.
Scheme 3. A possible mechanism for the PdCl2-catalyzed allylation of heteroarenes.

6842
F.-Q. Yuan et al. / Tetrahedron 68 (2012) 6837e6842
by heteroarenes to Pd(0) whose oxidative addition to allylic ace-
tates forms the
3-allylpalladium(II) complex B or C. Subsequently,
nucleophilic addition of heteroarenes to B or C affords the h2
allylpalladium(0) complex D. Finally, Pd(0) detaches from alkenes
to generate the corresponding allylated products 3, and the Pd(0)
thus regenerated goes into the next catalytic cycle.
Supplementary data
h
-
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.06.038.
References and notes
3. Conclusions
1. (a) Hegedus, L. S. Transition Metals in the Synthesis of Complex Organic Molecules;
University Sciences Books: Mill Valley, CA, 1994; (b) Trost, B. M.; Van Vranken,
D. L. Chem. Rev. 1996, 96, 395e422.
2. (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873e2920; (b) Eicher, T.;
Hauptmann, S. The Chemistry of Heterocycles; Wiley-VCH: Weinheim, 2003.
3. Yamamoto, H. Lewis Acids in Organic Synthesis; Wiley-VCH: Weinheim,
2000.
We have demonstrated that PdCl2 is a highly efficient catalyst for
the allylation of heteroarenes in the presence of 1:1 molar ratio of
reactants under base/acid, additive, and ligand-free conditions. The
results presented herein, together with our previous study19 clearly
illustrated that the protocol is generally applicable not only to a rich
range of N-, O-, and S-containing heteroarenes, but also to a broad
variety of allylic acetates. As a result, this method represents one of
the few examples for simple, universally applicable, clean, and
atom-efficient functionalization of heteroarenes. We believe that
due to the ubiquitous nature of heteroarenes in natural products,
pharmaceuticals, materials science, and coordination and catalytic
chemistry, the method presented herein would find practical ap-
plication in these areas. Currently, we are synthesizing some com-
plex natural products by using the protocol developed in this work.
Finally, mechanistic investigation showed that the reaction pro-
ceeds more likely via the Pd(0)-catalyzed TsujieTrost pathway. The
result would have further implications beyond this work and would
promote the development of more efficient processes for other
transition-metal-catalyzed cross-coupling reactions.
4. For selected examples using immobilized and nonimmobilized sulfonic acids,
ꢀ
ꢀ
see: (a) Sanz, R.; Martínez, A.; Miguel, D.; Alvarez-Gutierrez, J. M.; Rodríguez, F.
Adv. Synth. Catal. 2006, 348, 1841e1845; (b) Bras, J. L.; Muzart, J. Tetrahedron
2007, 63, 7942e7948; (c) Liu, Y.-L.; Liu, L.; Wang, Y.-L.; Han, Y.-C.; Wang, D.;
Chen, Y.-J. Green Chem. 2008, 10, 635e640.
5. For a representative example using Montmorillonite, see: Motokura, K.;
Nakagiri, N.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Org. Chem. 2007, 72,
6006e6015.
6. For an example using boronic acid, see: McCubbin, J. A.; Krokhin, O. V. Tetra-
hedron Lett. 2010, 51, 2447e2449.
7. For selected examples of In(III)-catalyzed allyaltions, see: (a) Yasuda, M.; Somyo,
T.; Baba, A. Angew. Chem., Int. Ed. 2006, 45, 793e796; (b) Yadav, J. S.; Reddy, B. V.
S.; Rao, K. V.; Rao, P. P.; Raj, K. S.; Prasad, A. R.; Prabhakar, A.; Jagadeesh, B. Synlett
2006, 3447e3450; (c) Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V.;
Prabhakar, A.; Jagadeesh, B. Tetrahedron Lett. 2005, 46, 639e641.
8. For AuCl3-catalyzed reactions, see: Rao, W.; Chan, P. W. H. Org. Biomol. Chem.
2008, 6, 2426e2433.
9. For Mo(II)- and Mo(IV)-catalyzed reactions, see: (a) Malkov, A. V.; Baxendale, I.
ꢁꢀ
ꢁ
ꢀ
R.; Dvorak, D.; Mansfield, D. J.; Kocovsky, P. J. Org. Chem. 1999, 64, 2737e2750;
ꢁ
ꢀ
(b) Malkov, A. V.; Davis, S. L.; Baxendale, I. R.; Mitchell, W. L.; Kocovsky, P. J. Org.
Chem. 1999, 64, 2751e2764; (c) Malkov, A. V.; Spoor, P.; Vinader, V.; Kocovsky, P.
J. Org. Chem. 1999, 64, 5308e5311.
ꢁ
ꢀ
4. Experimental section
4.1. General methods
10. For Ca(II)-catalyzed reaction, see: Niggemann, M.; Meel, M. J. Angew. Chem., Int.
Ed. 2010, 49, 3684e3687.
11. For Fe(III)-catalyzed reactions, see: (a) Thirupathi, P.; Kim, S. S. Tetrahedron 2010,
66, 2995e3003; (b) Jiang, Z.-Y.; Zhang, C.-H.; Gu, F.-L.; Yang, K.-F.; Lai, G.-Q.; Xu,
L.-W.; Xia, C.-G. Synlett 2010, 1251e1254.
12. For Pd(II)-catalyzed CꢁO bond formation of diaryl methyl alcohol with aliphatic
alcohols, see: Bikard, Y.; Mezaache, R.; Weibel, J.-M.; Benkouider, A.; Sirlin, C.;
Pale, P. Tetrahedron 2008, 64, 10224e10232.
13. Liu, Z.; Liu, L.; Shafiq, Z.; Wu, Y.-C.; Wang, D.; Chen, Y.-J. Tetrahedron Lett. 2007,
48, 3963e3967.
Solvents were purified and dried according to standard methods
prior to use. Reagents and catalysts were purchased from J&K
Chemical Ltd or Alfa Aesar, and were used without further purifi-
cation. Unless otherwise noted, the 1H NMR spectra were recorded
at 300, 400, 600 MHz in CDCl3 and the 13C NMR spectra were
recorded at 75, 100, 150 MHz in CDCl3 with TMS as internal stan-
dard. All shifts are given in parts per million. All coupling constants
(J values) were reported in Hertz (Hz). Column chromatography
was performed on silica gel 100 mesh.
14. Wenkert, E.; Angell, E. C.; Ferreira, V. F.; Michelotti, E. L.; Piettre, S. R.; Sheu, J.-H.;
Swindell, C. S. J. Org. Chem. 1986, 51, 2343e2351.
15. Onodera, G.; Imajima, H.; Yamanashi, M.; Nishibayashi, Y.; Hidai, M.; Uemura, S.
Organometallics 2004, 23, 5841e5848.
ꢁ
ꢀ
16. Malkov, A. V.; Baxendale, I. R.; Mansfield, D. J.; Kocovsky, P. J. Chem. Soc., Perkin
Trans. 1 2001, 10, 1234e1240.
17. (a) Billups, W. E.; Erkes, R. S.; Reed, L. E. Synth. Commun. 1980, 10, 147e154; (b)
Bandini, M.; Melloni, A.; Umani-Ronchi, A. Org. Lett. 2004, 6, 3199e3202; (c)
Kimura, M.; Futamata, M.; Mukai, R.; Tamaru, Y. J. Am. Chem. Soc. 2005, 127,
4592e4593; (d) Ma, S.; Yu, S.; Peng, Z.; Guo, H. J. Org. Chem. 2006, 71,
9865e9868; (e) Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128,
6314e6315; (f) Bandini, M.; Melloni, A.; Piccinelli, F.; Sinisi, R.; Tommasi, S.;
Umani-Ronchi, A. J. Am. Chem. Soc. 2006, 128, 1424e1425; (g) Cheung, H. Y.; Yu,
W.-Y.; Lam, F. L.; Au-Yeung, T. T.-L.; Zhou, Z.; Chan, T. H.; Chan, A. S. C. Org. Lett.
2007, 9, 4295e4298.
18. For general concept concerning efficient synthesis, see: (a) Trost, B. M. Science
1991, 254, 1471e1477; (b) Trost, B. M. Science 1983, 219, 245e250; (c) Trost, B.
M.; Dong, G. Nature 2008, 456, 485e488.
19. Yuan, F.-Q.; Gao, L.-X.; Han, F.-S. Chem. Commun. 2011, 5289e5291.
20. (a) Kalek, M.; Jezowska, M.; Stawinski, J. Adv. Synth. Catal. 2009, 351,
3207e3216; (b) Han, F.-S.; Higuchi, M.; Kurth, D. G. J. Am. Chem. Soc. 2008, 130,
2073e2081.
4.2. General procedure for the allylation of heteroarenes with
allylic acetates
A solution of allylic acetate (0.4 mmol), heteroarene (0.4 mmol,
1.0 equiv, 5.0 equiv of 2-methylfuran was used due to the volatile
nature), and PdCl2 (1.4 mg, 2 mol %) in DCM (1.5 mL) was stirred in
a sealed tube at 60 ꢀC. After the completion of the reaction as
monitored by TLC, the mixture was concentrated and isolated by
column chromatography on silica gel using a mixture of dichloro-
methane and petroleum as eluent to give the allylated products.
Characterization data and copies of 1H NMR spectra of 5 and ally-
lated products were provided in Supplementary data (SI).
21. (a) Siddiqui, N.; Alam, P.; Ahsan, W. Arch. Pharm. Chem. Life Sci. 2009, 342,
173e181; (b) Crawford, J. J.; Henderson, K. W.; Kerr, W. J. Org. Lett. 2006,
8, 5073e5076; (c) Ueda, M.; Miyaura, N. J. Org. Chem. 2000, 65,
4450e4452.
Acknowledgements
22. (a) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172e1175; (b) Potavathri, S.;
Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris, A. P.; DeBoef, B. J. Am. Chem. Soc.
2010, 132, 14676e14681.
Financial support from Hundred Talent Program of CAS and
State Key Laboratory of Fine Chemicals (KF1008) is acknowledged.