Palladium-catalyzed/Lewis acid-promoted alkene dimerization and cross-coupling with alcohols via C-H bond activation

Article abstract of DOI:10.1002/adsc.200700439

The cross-couplings of alcohols to alkenes with the palladium/Lewis acid system are reported. This reaction occurs in a successive alkene dimerization, direct C-H activation of alcohol and sp³-sp³ bond forming sequence via an interesting domino process.

Full text of DOI:10.1002/adsc.200700439

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DOI: 10.1002/adsc.200700439
Palladium-Catalyzed/Lewis Acid-Promoted Alkene Dimerization
À
and Cross-Coupling with Alcohols via C H Bond Activation
Yi-Jun Jiang,a Yong-Qiang Tu,a,* En Zhang,a Shu-Yu Zhang,a Ke Cao,a and Lei Shia
a
State Key Laboratory of Applied OrganicChemistry and Department of Chemistry, Lanzhou University, Lanzhou
730000, Peopleꢀs Republicof China
Fax : (+86)-931-891-2557; e-mail: tuyq@lzu.edu.cn
Received: September 3, 2007; Revised: November 20, 2007; Published online: February 18, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
À
Abstract: The cross-couplings of alcohols to alkenes
with the palladium/Lewis acid system are reported.
This reaction occurs in a successive alkene dimeri-
zation, direct C H activation of alcohol and sp sp
bond forming sequence via an interesting domino
Lewis acid-promoted domino[5] C C bond coupling of
alkenes and alcohols was recently discovered which
involved the selective dimerization of alkenes[6] and
the sp C H activation of alcohols. To the best of our
knowledge, this kind of intermolecular domino cou-
pling reactions containing two different C C forma-
3
3
3
À
À
À
À
process.
3
À
tion processes, the alkene dimerization and the sp C
À
À
Keywords: C C bond formation; C H activation;
domino reactions; Lewis acids; palladium
H bond activation, have not been reported previously.
This combined palladium/Lewis acid catalyst system[7]
is unique and plays pivotal dual roles for the two
chemical transformations above, in which two new
non-contiguous C C bonds can be created in one op-
eration. Herein, we present our preliminary results of
À
À
C C bond formation reactions based on the transition this investigation.
metal-catalyzed sp C H bond activation have been
3
À
We initially conducted the coupling reaction of sty-
one of the most challenging and active areas of re- rene and ethanol in toluene by using of catalytic
search in modern organic chemistry due to their sig- amount of Pd(OAc)2 in the presence of the Lewis
A
nificant impact on both industrial and academic re- acid BF3·OEt2. A small amount of known cross-cou-
search.[1] Although remarkable progress has been pling product 2a was observed (Table 1, entry 1).[3c]
3
À
A
bonds adjacent to a nitrogen atom,[2] the activation of reaction (Table 1, entry 2), a different product 1a,
sp C H bonds adjacent to oxygen accompanied with which was resulted from the head-to-tail dimerization
subsequent C C bond formation is still under devel- of styrenes and subsequent cross-coupling with etha-
opment.[3]
À
In connection with our recent investigation of C C domino sequence involving selective dimerization and
bond forming reactions via C H bond activation of C H bond activation was unprecedent under the
alcohols
us to further optimize the current reaction conditions.
A survey of reaction conditions with variation of sol-
vent, palladium source and ligand is summarized in
Table 1. The reaction medium was found to have a
dramatic influence on this domino reaction (entries 2–
4), and the desired product 1a could be obtained in
35% yield when CH3NO2 was used as a solvent
(entry 4). It should be noted that the ratio of Pd-
A
col. For example, the yield of 1a could further be im-
proved from 35% to 50% by changing the ratio of
À
Pd(OAc)2/PPh3 from 1:2 to 1:1.5 (entries 4 and 5).
Among the palladium catalysts investigated (en-
A
Scheme 1. Cross-coupling of alcohols to alkenes via C H ac -
tivation.
552
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Adv. Synth. Catal. 2008, 350, 552 – 556

Palladium-Catalyzed/Lewis Acid-Promoted Alkene Dimerization and Cross-Coupling
COMMUNICATIONS
Table 1. Optimization of reaction condition.[a]
Entry
Catalyst
Solvent
Product (yield [%])[b]
1a
2a
1
2
3
4
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
C
Toluene
Toluene
CH2Cl2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
0
8
10
0
0
0
0
0
0
16
0
5
10
35
50
60
30
0
5
6[c]
7[d]
8[e]
9[f]
10 g]
G
20
5
[a]
Reaction conditions: styrene (3.0 mmol), ethanol (15.0 mmol), catalyst (0.3 mmol), acid (7.5 mmol) and solvent (12 mL)
at 608C for 20 h.
Isolated yields.
TFA=trifluoroacetate.
acac=acetylacetonate.
dba=dibenzylidene-acetone.
Mesityl=2,4,6-trimethylphenyl.
dppp=1,3-bis(diphenylphosphanyl)-propane.
[b]
[c]
[d]
[e]
[f]
[g]
tries 5–8), Pd
A
When para-chlorostyrene with an electron-with-
60% yield of 1a (entry 6), wherein Pd
AHCTREUNG
unable to produce the expected product 1a and only (entry 9), however, the expected 1i was only obtained
resulted in a low yield of the undesired simple cross- in a lower yield (30%) with longer reaction time
coupling product 2a (entry 8). Phosphanes [e.g., P- (48 h), which might due to the unfavorable electronic
ACHTREUNG
yield of 1a was observed. Other acid promoters tested chosen to react with styrene and ethanol under the
instead of BF3·OEt2 were proved to be not effective standard conditions (entry 10), the heterodimeriza-
to this reaction (for more optimization studies see tion/cross-coupling product 1j was isolated gratifying-
Supporting Information).
ly with a reasonable yield.
Based on the optimized conditions (entry 6,
As an insight into the mechanism of this reaction, a
Table 1), the generality of this coupling reaction was deuterium-labeling experiment between styrene and
then examined and these results are summarized in a-deuterated ethanol was performed to provide the
Table 2. Entries 1–4 indicated that primary aliphatic deuterated product 1k exclusively (Scheme 2). This
À
alcohols with different subsitituents, such as the clearly demonstrated the cleavage of C D bond of
bulkyl isopropyl group (entry 2) and the chain-type the deuterated ethanol and the regioselectivity of the
alkyl groups (entrie 3 and 4) were suitable for the subsequent cross-coupling during this domino process.
domino process. In addition, substrates containing the
Based on the experimental facts given above, a
cyclohexyl group (entry 5) as well as the phenyl group plausible mechanism involving two catalytic cycles
(entry 6) were also effective. Thus, various g-branched was proposed as shown in Scheme 3. In the catalytic
secondary alcohols 1a–f could be expeditiously gener- cycle of the dimerization of alkene, the Pd(II) cation
ated in moderate to good yields. Moreover, meta- and intermediate C was formed via the pathway described
para-methylstyrenes bearing an electron-donating by Shirakawa and co-workers.[6a] The following intra-
group on the aromaticring were also tested, and the
molecular nucleophilic attack afforded palladacycle
corresponding secondary alcohol 1g and 1h were D, which would undergo b-H elimination to give in-
formed efficiently in moderate yield (entries 7 and 8). termediate E or F with a dynamicequilibrium. Subse-
Adv. Synth. Catal. 2008, 350, 552 – 556
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553

Yi-Jun Jiang et al.
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Table 2. Domino synthesis of g-branched secondary alcohols.[a]
Entry
1
Substrate
Product
Yield [%][b]
60[c] (1:0.6)
R1, R2 =Ph, R3 =Me
1a
1b
2
R1, R2 =Ph, R3 =i-Pr
40 (1:0.8)
3
4
R1, R2 =Ph, R3 =n-Bu
1c
53 (1:0.7)
45 (1:0.5)
R1, R2 =Ph, R3 =n-C13H27
1d
5
6
7
R1, R2 =Ph, R3 =c-Hexyl
R1, R2 =Ph, R3 =CH2CH2Ph
R1, R2 =m-C6H4Me, R3 =Me
1e
1f
1g
68[d] (1:0.7)
70 (1:0.8)
51 (1:0.8)
8
9
R1, R2 =p-C6H4Me, R3 =Me
1h
56 (1:0.6)
R1, R2 =m-C6H4Cl, R3 =Me
R1 =Ph, R2 =n-C6H13, R3 =Me
1i
1j
30[e] (1:0.6)
27[c] (1:0.8)
10
[a]
Standard reaction conditions: 3 (1.5 mmol), 3ꢀ (1.5 mmol), 4 (15.0 mmol), Pd
BF3·OEt2 (7.5 mmol) and CH3NO2 (12 mL) at 608C for 20 h.
Isolated yields calculated on the basis of olefine 3; the ratio of two diastereoisomers determined by HNMR is given in
A
[b]
parenthesis.
[c]
[d]
[e]
The ratio of two diastereoisomers is calculated by isolated yields.
Reaction time: 8 h.
Reaction time: 48 h.
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Palladium-Catalyzed/Lewis Acid-Promoted Alkene Dimerization and Cross-Coupling
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In conclusion, we have developed a novel Pd-cata-
lyzed/Lewis acid-promoted coupling reaction between
primary alcohols and aromatic/aliphatic alkenes,
through which a series of g-branched secondary alco-
hols could be synthesized from simple and readily
available starting materials. Further studies towards a
deeper insight into the reaction mechanism, substrate
scope and the synthetic application are currently on-
going in our group.
Scheme 2. Deuterium labeling experiment.
quently, a reductive elimination gave the terminal
alkene G and the disubstituted alkene H.[8] It should Experimental Section
be noted that the alkene H, to some extent, could be
transformed to G via Pd(0)-catalyzed double bond General Remarks
migration in the current system.[9] Intermediate G re-
sulting from E or H was further consumed by C H
The solvents were purified prior to use. Other commercially
À
available materials were used as received. Flash column
chromatography was performed using 200–300 mesh silica
bond activation and cross-coupling in the second cata-
lytic cycle, from which the driving force made the
EQDQF equilibrium in Scheme 3 direct to the favor-
able formation of G in the first catalytic cycle again.
The less hindered alkene G then readily coordinated
to palladium catalyst to give the Pd(0)-alkene com-
1
gel. H and 13C NMR spectra were recorded on Varian Mer-
cury-plus 300 or 400 instruments in CDCl3 solution using
TMS as internal standard. MS were measured on an HP-
5988 spectrometer by direct inlet at 70 eV. High-resolution
mass spectral analysis (HR-MS) data were obtained on a
Bruker ApexII by means of the ESI technique.
À
plex I in the C H activation catalytic cycle. With si-
multaneous coordination of alcohol and Lewis acid,
À
the C H bond adjacent to oxygen in the alcohol was
Typical Procedure for the Cross-Coupling Reaction
activated by the palladium catalyst through the key
To a flame-dried 25-mL flask were sequentially added
CH3NO2 (12 mL), styrene (312 mg, 3.0 mmol), ethanol
(690 mg, 15.0 mmol), PPh3 (118 mg, 0.45 mmol) and Pd-
transition state J by Pd(0) oxidative addition.[10] The
À
subsequent olefin insertion into the Pd H bond by a
less hindered way afforded the intermediate K, which
underwent reductive elimination to provide the de-
sired product 1 with the release of Pd(0) catalyst into
the next cycle. These two catalytic cycles were realiz-
ed by the combination of Pd(0) and Lewis acid, and
therefore two different chemical transformations were
accomplished in one operation.
(OTFA)2 (100 mg, 0.3 mmol) under argon atmosphere. The
resulting mixture was stirred at 608C for 10 min, and then
freshly distilled BF3·OEt2 (0.9 mL, 7.5 mmol) was added.
After further stirring at 608C for 20 h, the mixture was
cooled to room temperature and diluted with ethyl acetate
(5 mL) followed by addition of saturated aqueous NaHCO3
solution (10 mL). The organiclayer was separated, and the
aqueous phase was re-extracted with ethyl acetate (2”
À
Scheme 3. Plausible mechanism for C H activation and the domino reactions.
Adv. Synth. Catal. 2008, 350, 552 – 556
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asc.wiley-vch.de
555

Yi-Jun Jiang et al.
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20 mL). The combined organic phase was washed with brine
(20 mL), dried over Na2SO4, concentrated under reduced
pressure and purified by the flash chromatography to afford
the product 1a; yield: 60% (229 mg, 1.8 mmol; diastereo-
mericratio 1:0.6).
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Supporting Information
Characterization data for all products and details of optimi-
zation studies are given in the Supporting Information.
[5] For reviews on domino reactions, see: a) A. Heumann,
M. Reglier, Tetrahedron 1996, 52, 9289; b) M. Malacria,
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[6] For the dimerization of alkenes catalyzed by the
Pd(II)/PPh3/Lewis acid system, see: a) T. Tsuchimoto,
S. Kamiyama, R. Negoro, E. Shirakawa, Y. Kawakami,
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[8] Alkene H could be separated as the main by-product
of the reaction.
[9] A supporting experiment was performed using the iso-
lated alkene 5 under current standard conditions, and
Acknowledgements
This work was supported by the NSFC (Nos. 30271488,
20911001) and the Chang Jiang Scholars program. Prof. Dr.
Yong-Min Liang and Dr. Chun-An Fan are gratefully ac-
knowledged for helpful discussions.
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À
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3
À
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À
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3
À
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3
À
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3
À
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[10] For a mechanism containing sp C H bond activation
3
À
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Adv. Synth. Catal. 2008, 350, 552 – 556