Facile synthesis of (E)-alkenyl aldehydes from allyl arenes or alkenes via Pd(II)-catalyzed direct oxygenation of allylic C-H bond

Article abstract of DOI:10.1021/ol1030316

Palladium-catalyzed oxygenation of allyl arenes or alkenes has been developed to produce (E)-alkenyl aldehydes with high yields. Allylic C-H bond cleavages occur under the mild conditions during this process. Mechanistic studies show that oxygen source is water.(Figure Presented)

Full text of DOI:10.1021/ol1030316

ORGANIC
LETTERS
2011
Vol. 13, No. 5
992–994
Facile Synthesis of (E)-Alkenyl
Aldehydes from Allyl Arenes or Alkenes
via Pd(II)-Catalyzed Direct Oxygenation of
Allylic C-H Bond
Huoji Chen, Huanfeng Jiang,* Congbi Cai, Jia Dong, and Wei Fu
School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou 510640, P. R. China
jianghf@scut.edu.cn
Received December 14, 2010
ABSTRACT
Palladium-catalyzed oxygenation of allyl arenes or alkenes has been developed to produce (E)-alkenyl aldehydes with high yields. Allylic C-H
bond cleavages occur under the mild conditions during this process. Mechanistic studies show that oxygen source is water.
Transition-metal-catalyzed sequential oxidative clea-
vage and functionalization of an allylic C-H bond has
been an important methodology for the direct installation
of functionality into hydrocarbon frameworks.1 The prac-
tical utility of such processes for complex molecule synth-
esis is governed by their ability to operate with predictable
and high levels of chemo-, stereo-, and regioselectivity as
well as site selectivity. The strategic application of selective
C-H oxidation and functionalization reactions at late
stages of syntheses has been demonstrated to increase
product diversity.2
Recently, White,3 Shi,4 Ishii,5 and Liu6 made significant
progress in the allylic C-O/C-N/C-C formation via
Pd(II)-catalyzed C-H activation (eq 1). An allyl-palla-
dium species was proposed as the key intermediate in these
processes. To the best of our knowledge, direct oxygena-
tion of an allylic C-H bond via Pd-catalysis using H2O as
a nucleophilic reagent has not been disclosed to date.
˚
(1) (a) Hansson, S.; Heumann, A.; Rein, T.; Akermark, B. J. Org.
Chem. 1990, 55, 975. (b) Heumann, A.; Reglier, M.; Waegell, B. Angew.
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Chem., Int. Ed. 1982, 21, 366. (c) Heumann, A.; Akermark, B. Angew.
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Tetrahedron Lett. 1984, 25, 4187. (e) Akermark, B.; Larsson, E. M.;
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223.
On the other hand, few examples reported the synthesis
of alkenyl aldehydes from allyl arenes or alkenes.7 And
(2) Chen, M. S.; White, M. C. Science 2007, 318, 783.
(3) (a) Reed, S. A.; White, M. C. J. Am. Chem. Soc. 2008, 130, 3316.
(b) Fraunhoffer, K. J.; White, M. C. J. Am. Chem. Soc. 2007, 129, 7274.
(c) Delcamp, J. H.; White, M. C. J. Am. Chem. Soc. 2006, 128, 15076. (d)
Fraunhoffer, K. J.; Prabagaran, N.; Sirois, L. E.; White, M. C. J. Am.
Chem. Soc. 2006, 128, 9032. (e) Chen, M. S.; Prabagaran, N.; Labenz,
N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970. (f) Fraunhoffer,
K. J.; Bachovchin, D. A.; White, M. C. Org. Lett. 2005, 7, 223. (g) Chen,
M. S.; White, M. C. J. Am. Chem. Soc. 2004, 126, 1346. (h) Reed, S. A.;
Mazzotti, A. R; White, M. C. J. Am. Chem. Soc. 2009, 131, 11701.
(4) Lin, S.; Song, C. X.; Cai, G. X.; Wang, W. H.; Shi, Z. J. J. Am.
Chem. Soc. 2006, 130, 12901.
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(6) (a) Liu, G.; Yin, G.; Wu, L. Angew. Chem., Int. Ed. 2008, 47, 4733.
(b) Yin, G.; Wu, Y.; Liu, G. J. Am. Chem. Soc. 2010, 132, 11978.
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Patil, S. R. Tetrahedron Lett. 1982, 23, 4353. (c) Rav-Acha, C.; Choshen,
E.; Sarel, S. Helv. Chim. Acta 1986, 69, 1728.
r
10.1021/ol1030316
Published on Web 02/04/2011
2011 American Chemical Society

they were also limited to reactions with inferior results (low
chemo-, stereo-, and regioselectivity and low yields).
Therefore, the synthesis of alkenyl aldehydes from allyl
arenes or alkenes under mild conditions is desired. Herein,
we would like to disclose our preliminary results (eq 2).
We initially employed dioxygen (1 atm) as an oxidant to
investigate the transformation of allylbenzene (1a) in the
presence of PdCl2 (10 mol %) in 1,2-dichloroethane (DCE,
2.5 mL) at 50 °C, and none of the expected product (E)-3-
phenyl-2-propenealdehyde (2a) was detected (Table 1,
entry 1). We found that a small amount of product 2a
was obatained when using benzoquinone (BQ) or tert-
butyl hydroperoxide (TBHP) as an oxidant (Table 1, en-
tries 2, 3). To our delight, 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ) as the oxidant can greatly promote
the PdCl2-catalyzed transformation of 1a, leading to the
corresponding product in 100% GC yield with high stereo-
selectivity (Table 1, entry 4). The investigation on reaction
media showed that other solvents let to the inferior results,
and the isomers of 1a were detected (Table 1, entries 6-9).
Moreover, both PdCl2 and DDQ are essential for this
transformation (Table 1, entries 5, 10).
Table 2. PdCl2-Catalyzed Direct Oxygenation of 1 to 2a
Under the optimized conditions, various substrates were
examined, and the results are summarized in Table 2. In
addition to allylbenzene (1a), both (E)- and (Z)-propenyl-
benzene performed this transformation very well, convert-
ing to 2a with high stereoselectivity in 92 and 88% yields,
respectively (Table 2, entries 2 and 3). These results
indicated that π-allyl species are involved in this transfor-
mation. The substrate scope was tested by using a variety
of allyl arenes; the oxygenation afforded (E)-alkenyl alde-
hydes products in high yields, regardless of whether an
electron-withdrawing or electron-donating group was in-
troduced on the phenyl ring (Table 2, entries 4-10).
Table 1. Optimization of Reaction Conditions for Direct
Transformation of Allylbenzene (1a) to Cinnamoaldehyde (2a)a
a Reaction conditions: Substrate 1 (0.5 mmol), H2O (1.5 equiv), Pd
catalyst (10 mol %), and DDQ (2.0 equiv) in 2.5 mL of DCE for 2 h.
b Isolated yields. c The isomers of 1o were not detected, indicating that
the isomerization did not occur.
Substituents at the para, meta, and ortho positions of the
arene ring did not affect the efficiencies (Table 2, entries 4,
9, and 10). Notably, a heteroaryl-substituted propene,
1-allyl-2-thiophene (1k), provided 2k in 94% yield
(Table 2, entry 11). 3-Naphthylpropene gave the corre-
sponding product in moderate yield (Table 2, entry 12). It
is noteworthy that 2,3-disubstituted propene was tolerated
in this transformation, leading to the corresponding tri-
substituted (E)-alkenyl aldehyde 2m in high yield (Table 2,
entry 13). Additionally, the alkenyl-substituted propene 1o
survived well, generating 2n (Table 2, entry 14). However,
simple alkyl olefins such as 1-octene did not react in the
process (Table 2, entry 15).
entry
solvent
oxidant
yield of 2a/%b
1
DCE
DCE
DCE
DCE
DCE
Toluene
DMF
THF
H2O
O2
0
2
BQ
<10
<10
100 (96)
0
3
TBHP
DDQ
-
DDQ
DDQ
DDQ
DDQ
DDQ
4
5
6
92
7
13
8
30
9
10c
19
DCE
18
a Reaction conditions: All reactions were performed with 1a (0.5
mmol), H2O (1.5 equiv), Pd catalyst (10 mol %), and oxidant (2.0 equiv)
in 2.5 mL of DCE for 2 h. b Determined by GC. Number in parentheses is
isolated yield. c In the absence of PdCl2.
Several control experiments were performed to probe a
plausible reaction path (Scheme 1): (1) the reaction of 1a
was carried out using 1.0 equiv of DDQ as the oxidant,
Org. Lett., Vol. 13, No. 5, 2011
993

Scheme 1. Control Experiments
Scheme 2. Proposed Mechanism
through subsequent oxidation of 3a/3a0 by DDQ. Finally,
Pd(0) is reoxidized to generate active species Pd(II) by
DDQ.
affording 2a in 46% yield, and 48% of 1a was recovered.
Cinnamyl alcohol 3a was not detected; (2) the reaction of
1a with H2O18, under N2 atmosphere, afforded O18-labled
product 2a0 in 98% yield; (3) the reaction of 3a with 1.0
equiv of DDQ produces the desired product 2a. These
results suggest that the oxygen source is water, and 3a
might be the intermediate in this process; (4 and 5) both
intra- and intermolecular kinetic isotopic effects were
evident (kH/kD = 3.7 and 4.5, respectively). It indicated
that the cleavage of the allyl C(sp3)-H bond is involved in
the rate-determining step.
In summary, we have successfully developed a facile
synthesis of (E)-alkenyl aldehydes from allyl arenes or
alkenes via Pd(II)-catalyzed allylic C-H oxygenation. In
this process, water was used as a nucleophilic reagent and
an oxygen source for direct oxygenation of an allylic C-H
bond. This observation will provide a new synthetic tool
for constructing alkenyl aldehydes. Further studies to
clearly understand the reaction mechanism and the syn-
thetic applications are ongoing in our group.
On the basis of these results, a plausible mechanism for
the palladium-catalyzed oxygenation of allyl arenes or
alkenes is shown in Scheme 2. First, Pd(II) reacted with
allylbenzene 1a to produce the corresponding π-allyl-
palladium species I through the allylic C-H bond
activation.3-6 Next, intermediate I is subjected to the
nucleophilic attack of H2O to afford Pd(0) and the oxida-
tive allylic oxygenation product 3a and/or 3a0. 3a/3a0
would exist as an equilibrating mixture by [3,3]-sigmatro-
pic rearrangement.8 Product 2a is subsequently formed
Acknowledgment. We thank the National Natural
Science Foundation of China (20625205, 20772034, and
20932002), National Basic Research Program of China
(973 Program) (2011CB808600), Doctoral Fund of Min-
istry of Education of China (20090172110014), and
Guangdong Natural Science Foundation (10351064101-
000000) for financial support.
Supporting Information Available. Experimental pro-
cedure and characterization of compounds 2a-2l. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(8) (a) Gagneux, A.; Winstein, S.; Young, W. G. J. Am. Chem. Soc.
1960, 82, 5956. (b) Padwa, A.; Sa, M. M. Tetrahedron Lett. 1997, 38,
5087.
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