Palladium nanoparticle catalyzed hiyama coupling reaction of benzyl halides

Article abstract of DOI:10.1021/jo1003373

An efficient Hiyama coupling reaction between benzylic halide and aryltrialkoxysilane using Pd nanoparticles has been developed. This procedure accommodates various functional groups to yield a diverse range of diarylmethanes which are ubiquitous units of natural products and pharmaceuticals.

Full text of DOI:10.1021/jo1003373

pubs.acs.org/joc
2
as macrocycles, catenanes, and rotaxanes. The common
methods for making diarylmethanes are reduction of diaryl
ketones or diarylcarbinols, Friedel-Crafts alkylation, and
transition metal-catalyzed coupling reactions (either a benzyl
Palladium Nanoparticle Catalyzed Hiyama Coupling
Reaction of Benzyl Halides
3
Dipankar Srimani, Ansuman Bej, and Amitabha Sarkar*
halide with an arylmetal species or an aryl halide with a
4
-11
benzylmetal species).
Transition-metal-catalyzed cross-coupling reactions have
emerged as a powerful method for the construction of
Department of Organic Chemistry, Indian Association for the
Cultivation of Science, Kolkata 700032
4
ocas@iacs.res.in
carbon-carbon bonds. However, benzylic halides have
been studied to a lesser extent compared to aryl halides in
coupling reaction. The most promising methods for diaryl-
methane synthesis have been the Suzuki-Miyaura-type
Received February 24, 2010
5
6a,b
coupling of benzyl halides, benzyl carbonates,
benzyl
6
phosphates, or benzyl acetate. Organozinc, organotin,
c
6d
7
8
9
and organoindium have also been used in such reactions.
Cu(I)-catalyzed cross-coupling reactions between Grignard
1
0a
10b
reagents and benzylic halides or phosphates and nickel-,
11a
1
1b
7
iron-, or cobalt-catalyzed cross-coupling with zinc orga-
nometallics have also been reported.
An efficient Hiyama coupling reaction between benzylic
halide and aryltrialkoxysilane using Pd nanoparticles has
been developed. This procedure accommodates various
functional groups to yield a diverse range of diaryl-
methanes which are ubiquitous units of natural products
and pharmaceuticals.
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Published on Web 05/21/2010
DOI: 10.1021/jo1003373
r 2010 American Chemical Society

Srimani et al.
JOCNote
a
TABLE 1. Hiyama Coupling of Benzyl Halide with Trialkoxysilane Catalyzed by Pd Nanoparticle
a
Reaction conditions: 1 mmol of benzyl halide, 2 mmol of siloxane, 4 mol % of K
2
PdCl , 1.16 mmol of PEG-600, 1.5 mL of 1 M TBAF in THF at
4
b
7
0 °C under argon. Yield of the isolated product.
It was originally believed that organosilicon compounds
are too stable to undergo cross-coupling reactions as the Si-C
bond has a significantly low polarity. Hiyama demonstrated
that arylfluorosilanes undergo palladium-catalyzed cross-
13
coupling reactions with aryl iodides. Use of organosilicon
compounds as transmetalation reagents has attracted atten-
tion since then because of their low cost, ready availability, low
12
14
toxicity, and chemical stability. Lee and Wolf successfully
applied organotrimethoxysilanes as efficient coupling reagents
in the Hiyama coupling reaction with aryl chlorides and
(
(
(
12) Negishi, E. Acc. Chem. Res. 1982, 15, 340.
13) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918.
14) (a) Hiyama, T. In Metal Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter 10. (b)
Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35, 835. (c) Hiyama, T.
J. Organomet. Chem. 2002, 653, 58. (d) Hatanaka, Y.; Fukushima, S.; Hiyama, T.
Chem. Lett. 1989, 1711–1714. (e) Hatanaka, Y.; Goda, K.; Okahara, Y.; Hiyama,
T. Tetrahedron 1994, 50, 8301–8316. (d) Hirabayashi, K.; Mori, A.; Kawashima,
J.; Suguro, M.; Nishihara, Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342–5349. (f)
Nakao, Y.; Oda, T.; Sahoo, A. K.; Hiyama, T. J. Organomet. Chem. 2003, 687,
15
bromides. DeShong reported efficient coupling reactions of
vinyl and aryl halides, aryl triflates, and allylic benzoates with
16
hypervalent silanes. Denmark and others have developed
(15) (a) Wolf, C.; Lerebours, R. Org. Lett. 2004, 6, 1147. (b) Lee, H. M.;
Nolan, S. P. Org. Lett. 2000, 2, 2053.
5
70–573.
J. Org. Chem. Vol. 75, No. 12, 2010 4297

Srimani et al.
JOCNote
Lewis base-promoted reactions using hypervalent silicates
1
7
24
β-hydrogen is present. Encouraged by recent reports where
aliphatic chloro compounds were found to participate in
coupling reactions, we decided to examine reactive benzyl
chlorides that have no β-hydrogen.
1
8
and demonstrated the use of alkenyl- and arylsilanols as
efficient coupling partners in Hiyama cross-coupling reactions.
However, the Hiyama coupling reaction using benzyl halide is
19
20
rare in the literature. Recently, Hiyama et al. reported the
cross-coupling reaction of benzylic carbonates with organo-
The cross-coupling of benzyl chloride with phenyltri-
methoxysilane with a palladium nanoparticle in THF was
investigated using a range of different base activators. Use of
1.5 equiv of TBAF as base yielded optimum results. CsF or
KF was not useful. Other bases such as K CO , Cs CO ,
[
2-hydroxymethyl)phenyl]dimethylsilanes using a combina-
3
5
tion of (η -cyclopentadienyl)(η -allyl)palladium [Cp(allyl)Pd]
and 1,1 -bis(diphenylphosphino)ferrocene (dppf).
0
2
3
2
3
In transition-metal-catalyzed reactions, ligands play a
significant role. Numerous phosphine and nonphosphine
ligands for palladium are described in the literature for
cross-coupling reactions. Several of these ligands are air
and moisture sensitive, difficult to prepare, and expensive.
Thus, catalysis by a ligand-free metal center is an area of high
K PO , NaOAc, and CsOAc also failed to promote the
3 4
cross-coupling reaction. It was observed that 2 equiv of
phenyltrimethoxysilane and 4 mol % of Pd were required
for 1 equiv of benzyl chloride to obtain 90% of the coupled
product consistently at 70 °CinTHFfor1.5h(Table1, entry1).
This condition was used for all of the examples in Table 1.
On decreasing the Pd concentration from 4 to 2 mol %, the
yield of diarylmethane dropped to 30% after 2 h, but it was
improved to 80% after stirring for 8 h at 70 °C. No product
was observed in the absence of any palladium catalyst. The
electronic influence of the aromatic substituents in the benzyl
chloride moiety was found to be minimal. No significant
steric effect was observed (Table 1, entries 5, 26, and 27).
The results summarized in the Table 1 show that a wide
variety of functional groups are compatible with this proce-
dure (Table 1, entries 9, 20-25). The reaction is completely
chemoselective: benzyl chlorides reacts in preference to aryl
chlorides (Table 1, entries 3, 4, 17-19). The arylalkyl chlor-
ides derived from naphthalene or heterocycles can also be
used as substrates (Table 1, entries 12-14, 19).
The scope of these coupling reactions could be extended to
benzylic tosylates, which gave coupled products in excellent
yield (Table 2). However, benzylic acetates and carbonate
are not suitable for this reaction.
Palladium-catalyzed allyl cross-coupling reaction of cin-
namyl chlorides with aryl siloxanes provides a powerful tool
for the synthesis of 1,3-diarylpropenes, which constitutes
an important structural assembly in many molecules of
2
1
importance. The catalytic system based on metal nanopar-
ticles appears to be a promising area because of the high
surface to volume ratio of such particles. Recently, we
successfully synthesized Pd nanoparticle of different sizes
and reported their catalytic properties in different C-C
2
2
cross-coupling reactions.
Herein, we report the first example of Hiyama coupling
reaction of benzyl halides and aryl trialkoxysilane with
nanosized Pd particles. PEG-600 was used as a stabilizing
agent as well as the reducing agent for the preparation of the
2
3
nanoparticle. The nanoparticles were prepared by stirring
1
7
4 mg of K PdCl with 700 mg of PEG-600 for 15 min at
2 4
0 °C. They were characterized by transmission electron
microscopy (TEM). SAED pattern reveals that the Pd
nanoparticles are polycrystalline in nature (see the Support-
ing Information).
3
C(sp )-chlorides suffer from poor activity in cross-coupling
reactions due to the low reactivity of the strong C-Cl bond
and serious competition from β-hydride elimination when
(
16) (a) Brescia, M.-R.; DeShong, P. J. Org. Chem. 1998, 63, 3156. (b)
Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684. (c) Mowery,
M. E.; DeShong, P. Org. Lett. 1999, 1, 2137. (d) DeShong, P.; Handy, C. J.;
Mowery, M. E. Pure Appl. Chem. 2000, 72, 1655. (e) Riggleman, S.;
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Handy, C. J.; DeShong, P. J. Org. Chem. 2005, 70, 8948.
TABLE 2. Hiyama Coupling of Benzyl Electrophile with Trialkoxysi-
lane Catalyzed by Pd Nanoparticle
a
(17) (a) Denmark, S. E.; Stavenger, R. A. J. Am. Chem. Soc. 2000, 122,
837. (b) Denmark, S. E.; Fujimori, S. Org. Lett. 2002, 4, 3473. (c) Denmark,
8
S. E.; Fujimori, S. Org. Lett. 2002, 4, 3477. (d) Denmark, S. E.; Sweis, R. F.
Acc. Chem. Res. 2002, 35, 835.
(
18) (a) Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc. 2001, 123, 6439.
b) Denmark, S. E.; Ober, M. H. Org. Lett. 2003, 5, 1357. (c) Denmark, S. E.;
Regens, C. S. Acc. Chem. Res. 2008, 41, 1486.
19) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishira, Y.;
Hiyama, T J. Org. Chem. 2000, 65, 5342.
20) Nakao, Y.; Ebata, S.; Chen, J.; Imanaka, H.; Hiyama, T. Chem. Lett.
007, 36, 606.
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Chem. Res. 2001, 34, 181. (b) Roucoux, A.; Schulz, J.; Patin, H. Chem. Rev.
(
(
(
2
(
2
002, 102, 3757. (c) Moreno-Ma n~ as, M.; Pleixats, R. Acc. Chem. Res. 2003,
36, 638. (d) Astruc, D.; Lu, F.; Aranzaes, J. R. Angew. Chem., Int. Ed. 2005,
44, 7852. (e) Astruc, D. Inorg. Chem. 2007, 46, 1884.
(
22) Srimani, D.; Sawoo, S.; Sarkar, A Org. Lett. 2007, 9, 3639. (b)
Sawoo, S.; Srimani, D.; Dutta, P.; Lahiri, R.; Sarkar, A. . Tetrahedron 2009,
5, 4367.
23) The amount of PEG is high, Pd/PEG 1:29, as precedented ( Luo, C.;
Zhang, Y.; Wang, Y. J. Mol. Catal. A: Chem. 2005, 229, 7–12. ).
24) (a) Su, C.-R.; Shen, Y.-C.; Kuo, P.-C.; Leu, Y.-L.; Damu, A. G.;
6
(
(
Wang, Y.-H.; Wu, T.-S. Bioorg. Med. Chem. Lett. 2006, 16, 6155. (b) Belley,
M.; Chan, C. C.; Gareau, Y.; Gallant, M.; Juteau, H.; Houde, K.; Lachance,
N.; Labelle, M.; Sawyer, N.; Tremblay, N.; Limontage, S.; Carri ꢁe re, M.-C.;
Denis, D.; Greig, G. M.; Slipez, D.; Gordon, R.; Chauret, N.; Lo, C.;
Zamboni, R. J.; Metters, K. M. Bioorg. Med. Chem. Lett. 2006, 16, 5639.
a
Reaction conditions: 1 mmol of benzyl electrophile, 2 mmol of
siloxane, 4 mol % of K PdCl , 1.16 mmol of PEG-600, 1.5 mL of 1 M
2 4
b
TBAF in THF at 70 °C under argon. Yield of the isolated product.
4
298 J. Org. Chem. Vol. 75, No. 12, 2010

Srimani et al.
JOCNote
TABLE 3. Hiyama Coupling of Allyl Halide with Trialkoxysilane
Catalyzed by Pd Nanoparticle
SCHEME 2. Synthetic Route to 2, 4-Bis(4-hydroxybenzyl)-
phenol
a
positions, and then its reaction with triethoxy(4-methoxyphenyl)-
28
27
silane afforded the desired coupled product. Demethylation
of this product has been reported to yield the natural product.
a
Reaction conditions: 1 mmol of allyl halide, 2 mmol of siloxane,
mol % of K PdCl , 1.16 mmol of PEG-600, 1.5 mL of 1 M TBAF in
In summary, we have developed a new attractive method for
preparing diarylmethanes from functionalized benzyl and
cinnamyl halides via the Hiyama coupling reaction using Pd
nanoparticles as catalyst. This operationally simple and rela-
tively inexpensive procedure shows good functional group
tolerance and affords the desired diarylmethane in high yield.
4
2 4
b
THF at 70 °C under argon. Yield of the isolated product.
SCHEME 1. Hiyama Coupling with Allyl Chloride
Experimental Section
General Procedure for the Preparation of Pd Nanoparticle and
Catalysis of Hiyama Coupling Reaction. A weighed amount of
K PdCl (13 mg, 0.04 mmol) and PEG 600 (700 mg, 1.16 mmol)
2 4
was heated at 70 °C for 15 min to complete the formation of Pd
nanoparticles. To this suspension of colloidal Pd at ambient
temperature were added aryltrialkoxysilane (2 mmol), benzyl
halide (1 mmol), and tetrabutylammonium fluoride The reac-
tion mixture was allowed to cool at room temperature, and THF
was removed. The residue was extracted with ether (15 mL ꢀ 3),
and the combined organic extract was dried over anhydrous
2 4
Na SO and concentrated in vacuum. The residue thus obtained
2
5
biological importance. The coupling reactions with allylic
halide proceeded to give excellent yield of the coupling
product despite the presence of the β-hydrogen in the allylic
substrate (Table 3).
Although mechanistically viable (Scheme 1), no allenic
byproduct was isolated from this reaction.
We successfully applied our methodology to synthesize
naturally occurring 2,4-bis(4-hydroxybenzyl)phenol from ani-
sole, a simple and inexpensive starting material (Scheme 2).
First, anisole was chloromethylated at the ortho and para
was subjected to flash column chromatography on silica gel
(230-400 mesh) with either petroleum ether or ethyl acetate
(2-10%) in petroleum ether as eluent.
2
6
Acknowledgment. We thank the reviewers for their extre-
mely valuable input. We thank CSIR, India, and UKIERI
for financial support. D.S. and A.B. are thankful to CSIR,
India, for Research Fellowships.
Supporting Information Available: Detailed experimental
1
13
procedures and characterization data ( H, C) of the coupling
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(
25) (a) Terao, J.; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N.
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(
26) When R-methylbenzyl bromide was used as substrate, the desired
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coupled product was not obtained; styrene was obtained instead as the major
product: Srimani, D. Unpublished work.
J. Org. Chem. Vol. 75, No. 12, 2010 4299