Highly regioselective palladium-catalysed oxidative allylic C-H carbonylation of alkenes

Article abstract of DOI:10.1039/c1cc15781g

Pd-catalysed direct oxidative carbonylation of allylic C-H bonds with carbon monoxide was first described. This new procedure shows that the inherent requirement for a leaving group in the Tsuji-Trost palladium-catalysed allylic carbonylation can be lifted, which provides a new route for accessing more synthetically useful β-enoic acid esters with high regioselectivity. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1cc15781g

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COMMUNICATION
Highly regioselective palladium-catalysed oxidative allylic C–H
carbonylation of alkenesw
Huoji Chen, Congbi Cai, Xiaohang Liu, Xianwei Li and Huanfeng Jiang*
Received 19th September 2011, Accepted 3rd October 2011
DOI: 10.1039/c1cc15781g
Pd-catalysed direct oxidative carbonylation of allylic C–H bonds
with carbon monoxide was first described. This new procedure
shows that the inherent requirement for a leaving group in the
Tsuji–Trost palladium-catalysed allylic carbonylation can be lifted,
which provides a new route for accessing more synthetically useful
b-enoic acid esters with high regioselectivity.
the total synthesis of a natural product which contains multiple
functional groups and allylic C–H bonds.8
We have recently reported a new palladium-catalysed direct
oxygenation of allylic C–H bonds of alkenes with water as
nucleophile.9 On the basis of these precedents, we initiated a
research program with the aim of exploring new transformation
involving a palladium-catalysed allylic C–H activation. We
envisioned using carbon monoxide (CO) as a nucleophile for
allylpalladium species; that is, Pd(II)-catalysed allylic C–H
bond activation with subsequent carbonylation in the presence
of alcohol would lead to alkenyl carboxylate esters, which would
provide a new allylic carbonylation in synthetic methodologies
and palladium chemistry (Scheme 1). Herein, we wish to report
the first example of regioselective Pd-catalysed directly oxidative
carbonylation of allylic C–H bonds of terminal olefines.
Optimization of the carbonylation conditions showed that
the oxidant plays a crucial role in the reaction’s efficiency and
selectivity (Table 1). Benzoquinone (BQ) was found to be an
effective oxidant for the carbonylation, and 2,3-dichloro-5,
6-dicyanobenzoquinone (DDQ) seems to prevent the second
carbonylation to 3a (entries 6–9). Further screening of the
ratio of BQ with DDQ showed that when BQ was used with
DDQ in a 4 : 1 ratio, the reaction can be tolerated mainly to
afford the desired carbonylation product 2a with an isolated
yield of 77% (entry 9).10 The use of BQ and DDQ without the
palladium catalyst only gave oxidative product 4a in lower
yield (entry 10).
One of the most widely used palladium-catalysed transformations
for the construction of C–C bonds is the Tsuji–Trost reaction,
owing to its generally high and predictable levels of chemo-,
regio-, and stereoselectivity.1 Generally, a functional group at
the allylic position is required in Tsuji–Trost alkylation to
serve as a reacting and leaving group.2 In this context, the
development of new allylic alkylation in synthetic efficiency
through avoiding unnecessary functional group manipulations
is attracting increasing attention.3
Transition metal-catalysed activation of allylic C–H bonds
of simple olefines followed by subsequent nucleophilic attack
presents a highly efficient approach for the synthesis of
functionalized olefins.4 Recent elegant work has been reported
on Pd(II)-catalysed oxidation of allylic C–H bonds into more
synthetically useful C–O,4i–k,5 C–C6 and C–N bonds7
(Scheme 1). Particularly, White and coworkers describe an
impressive example of a late-stage C–H oxidation strategy in
Thus, the optimal reaction conditions for allylic C–H bond
carbonylation involved treatment of allylbenzene (1a) under
CO (1 atm) in methanol/acetonitrile (1 : 4, v/v) at 50 1C in
the presence of palladium acetate (10 mol%) using DDQ
(0.5 equiv.) and BQ (2.0 equiv.) as oxidants.
With the optimized conditions in hand, various allyl arenes
with diverse functional groups were examined, and the results are
summarized in Table 2. It appears that the carbonylation
reaction of allyl arenes bearing electron-withdrawing or electron-
donating groups afforded the desired products (2a–2g) in
moderate to good yields, and the substituents at the para,
meta, and ortho positions of the arene ring did not affect the
efficiencies. 3-Naphthylpropene gave the corresponding product
in moderate yield (2h). The reaction was also amenable to a range
of substituent groups on the C–C double bond. When 2,3-
disubstituted propene 1i was examined in this transformation,
a pair of isomers 2ia and 2ib were obtained in a 2.5 : 1 ratio.11
Scheme 1 Reaction hypothesis.
School of Chemistry and Chemical Engineering, South China
University of Technology, Guangzhou, 510640, P. R. China.
Fax: (+86)20-8711-2906; E-mail: jianghf@scut.edu.cn
w Electronic supplementary information (ESI) available. See DOI:
10.1039/c1cc15781g
c
12224 Chem. Commun., 2011, 47, 12224–12226
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Table 1 Optimization of reaction conditions for the palladium-
catalysed carbonylation of allylbenzene (1a)a
good yields (2k–2n). Furthermore, sterically bulky substrate
1o also afforded ester 2o in 68% yield. However, terminal alkyl
olefins such as 1-octene led to the formation of ketones
through the Wacker process, instead of the carbonylation
product.6g
Other alcohols were tested in the reaction, and the yields
were deteriorated with a bulkier substituent (Scheme 2).
Yieldb (%)
2a
3a 4a
Entry Oxidant
1
2
3
4
5
6
DDQ (1.5 equiv.)
TBHP (1.5 equiv.)
AgOAc (1.5 equiv.)/Tempo (1.5 equiv.)
PhI(OAc)2 (1.5 equiv.)
Cu(OAc)2 (1.5 equiv.)
BQ (1.5 equiv.)
8
0
4
0
6
22
0
0
0
0
0
2
66
56
8
0
0
ð1Þ
0
7
8
BQ (2.0 equiv.)
BQ (2.5 equiv.)
BQ (2.0 equiv.)/DDQ (0.5 equiv.)
BQ (2.0 equiv.)/DDQ (0.5 equiv.)
48
30
82 (77)
0
17
33
3
0
0
5
16
9
10c
0
a
Reaction conditions: 1a (0.3 mmol), Pd(OAc)2 (10 mol%), and
oxidant in 2 mL of MeCN and 0.5 mL of MeOH under CO (1 atm)
b
for 24 h. Determined by GC. Number in parentheses is isolated
c
yield. In the absence of Pd(OAc)2.
Table 2 Pd(II)-catalysed oxidative carbonylation of 1 to 2a,b
ð2Þ
ð3Þ
ð4Þ
To get more information about the reaction mechanism,
substrate 1a was treated with CD3OD under standard reaction
conditions, and deuterated product d,d,d-2a was obtained in a
73% yield (eqn (1)). The reaction of d,d-1c afforded d-2c in a
22% yield, accompanying with the recovery of d,d-1c without
any isomerization or H/D scrambling (eqn (2)). These results
suggest that the allylic C–H bond activation is an irreversible
step to generate a p-allyl–Pd intermediate.7f
a
Reaction conditions: 1 (0.3 mmol), Pd(OAc)2 (10 mol%), and
oxidant (BQ: 2 equiv.; DDQ: 0.5 equiv.) in 2 mL of MeCN and
b
0.5 mL of MeOH under CO (1 atm) at 50 1C for 24 h. Isolated yield.
Ratio of two isomers were determined by H NMR.
c
1
Benzyl-substituted propene 1j gave two isomers 2ja and 2jb in
a 3 : 1 ratio.12 Very importantly, the carbonylation reaction of
a-methyl styrene and its derivatives proceeded efficiently under
the optimized conditions to afford methyl 3-butenoates in
Scheme 2 Oxidative carbonylation of allylbenzene in different alcohols.
Chem. Commun., 2011, 47, 12224–12226 12225
c
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Scheme 3 Plausible reaction mechanism.
Both intra- and intermolecular kinetic isotopic effects were
explored and a significant KIE effect was observed (kH/kD
=
2.5 and 2.9, respectively). It indicated that the cleavage of the
allylic C(sp3)–H bond is involved in the rate-determining step
(eqn (3) and eqn (4)).
On the basis of these preliminary results, we hypothesized a
reasonable mechanism for this direct allylic carbonylation of
terminal olefines as shown in Scheme 3.
First, intermediate I is formed through the coordination of
the olefin to palladium. Then, there is a competence between
allylic C–H activation and nucleophile-palladation13 in the
following step. The addition of DDQ may affect the selectivity
and make it more easy for allylic C–H activation,14 leading to
p-allylpalladium species II via an electrophilic allylic C–H
bond cleavage by the Pd(II) catalyst. Then, nucleophilic attack
by CO and MeOH subsequently occurred to afford the final
product 2a. Active Pd species was then regenerated by BQ/
DDQ to fulfill the catalytic cycle.
(j) L. T. Pilarski, P. G. Janson and K. J. Szabo
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6 For examples, see: (a) J. Franze
Soc., 2003, 125, 6056; (b) J. Piera, K. Narhi and J.-E. Backvall,
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´
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Angew. Chem., Int. Ed., 2006, 45, 6914; (c) S. Lin, C. X. Song,
G. X. Cai, W. H. Wang and Z. J. Shi, J. Am. Chem. Soc., 2008,
In summary, we have developed palladium-catalysed direct
oxidative carbonylation of allylic C–H bonds with carbon
monoxide. This observation provides a novel route for accessing
b-enoic acid esters with high regioselectivity. Preliminary results
from deuterium labelling experiments indicated that the allylic
C–H activation process is an irreversible rate-determining step.
Further studies to clearly understand the reaction mechanism
and the synthetic applications are ongoing in our group.
We thank the National Natural Science Foundation of China
(20932002 and 21172076), National Basic Research Program of
China (973 Program) (2011CB808600), Doctoral Fund of
Ministry of Education of China (20090172110014) and Guangdong
Natural Science Foundation (10351064101000000) for financial
support.
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10 See ESIw.
11 Although the precise reason remains to be elucidated, one plausible
explanation is that the p-allyl–palladium complex which conjugated
with the aromatic ring is more stable in the process, generates the
major product 2ia.
12 The results of 1j can be explained by a competence between
Pd–allyl migration and carbonylation in the second step, the first
being the lower energy way.
13 L. Jia, H. Jiang and J. Li, Green Chem., 1999, 1, 91.
14 Although the role of DDQ is unclear in the present stage, we
believe it affects the selectivity in the reaction.
Notes and references
1 For reviews of the Tsuji–Trost reaction, see: (a) J. Tsuji, Palladium
Reagents and Catalysts: New Perspectives for the 21st Century, Wiley,
Chichester, UK, 2004, ch. 4; (b) B. M. Trost and M. L. Crawley,
Chem. Rev., 2003, 103, 2921; (c) B. M. Trost, J. Org. Chem., 2004,
69, 5813; (d) Handbook of Organopalladium Chemistry for Organic
Synthesis, ed. E.-I. Negishi, Wiley-Interscience, New York, 2002.
2 (a) U. Kazmaier and M. Pohlman, in Metal-Catalyzed Cross-Coupling
Reactions, ed. A. De Meijere and F. Diederich, Wiley-VCH,
c
12226 Chem. Commun., 2011, 47, 12224–12226
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