Efficient and recyclable dendritic Buchwald-type catalyst for the Suzuki reaction

Article abstract of DOI:10.1039/b710289e

A Buchwald-type ligand attached to a star-shape molecule was synthesized in high yield, and its catalytic properties for the Suzuki reactions are shown to be excellent (down to 50 ppm with a simple chloroarene) including recovery/re-use of this hexa ligan

Full text of DOI:10.1039/b710289e

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Efficient and recyclable dendritic Buchwald-type catalyst for the Suzuki
reaction{
Julietta Lemo, Karine Heuze´* and Didier Astruc*
Received (in Cambridge, UK) 5th July 2007, Accepted 25th July 2007
First published as an Advance Article on the web 13th August 2007
DOI: 10.1039/b710289e
Functionalization of Merrifield resin, used as an heterogeneous
support, by 2-dialkylphosphinobiphenyl has been applied to
palladium-catalyzed amination and Suzuki reactions, however.
This heterogeneously supported catalyst was efficient for the
coupling of unactivated aryl iodides, bromides and chlorides, and
it could be recycled four or five times by filtration in the case of
aryl bromides.16
A Buchwald-type ligand attached to a star-shape molecule was
synthesized in high yield, and its catalytic properties for the
Suzuki reactions are shown to be excellent (down to 50 ppm
with a simple chloroarene) including recovery/re-use of this
hexa ligand.
One of the major applications of dendrimers1 is catalysis, because
homogeneous dendritic catalysts (DC) can be recovered by
precipitation or ultracentrifugation and re-used2 unlike mono-
metallic homogeneous catalysts. Since the seminal work in this
area,3 it has indeed been shown that re-use of DCs was possible4
and that small ones were ideal5 in order to avoid steric constraints
among the multiple catalytic metal centers at the termini of tethers
in high-generation dendrimers.6 A variety of classic Pd-catalyzed
C–C coupling reactions have thus been disclosed with DCs that
could be recycled once or a few times.1,2 However, DCs could not
so far achieve highly challenging C–C coupling such as those
involving unactivated aryl chloride containing ortho methyl
substituents. The Suzuki–Miyaura7 cross-coupling reaction is a
powerful tool for the synthesis of carbon–carbon bonds. It
provides a general method for the formation of various biaryls that
are for example largely widespread for the growing of natural
products8 and various materials.9 This reaction is highly efficient,
proceeds with mild protocols, and occurs between innocuous
boronic acids that are usually non-toxic and thermally-, air- and
moisture-stable. Phosphine or N-heterocyclic carbene (NHC)-
based catalysts are currently used, but new, more efficient catalysts
that are environmentally compatible are continuously sought.10 In
the past few years, highly active palladium catalysts with bulky and
electron-rich phosphine ligands were indeed reported by the
groups of Buchwald (2-dialkylphosphinobiaryls),11 Fu (trialkyl-
phosphines),12 Hartwig (ferrocenyldialkylphosphines),13 Guram14
and others.15 These systems allowed the coupling between
unactivated and hindered aryl chlorides, heterocycle chlorides
with alkyl boronic acids and hindered unactivated arylboronic
acids.
The synthesis of the dendritic hexaphosphine ligand 6, starting
by the CpFe+-induced hexa p-bromobenzylation of C6Me6,17 is
shown in Scheme 1 that involves classic steps in good yields.18–21
Palladium-catalyzed Suzuki reactions were performed with
unactivated hindered aryl chlorides and phenyl boronic acid or
2-methylphenyl boronic acid using a mixture of Pd(OAc)2 and 6
We report here the synthesis, catalytic properties for the Suzuki
reactions and recovery/re-use of a dendritic Buchwald-type ligand
6 containing six dicyclohexylphosphinobiphenyl groups at the
periphery (Scheme 1).{ This is the first example of a Buchwald
type ligand attached to
a star-shaped or dendritic core.
Institut des Sciences Mole´culaires, Universite´ Bordeaux 1, UMR CNRS
No 5255 - 351 cours de la Libe´ration, 33405, Talence cedex, France.
E-mail: k.heuze@ism.u-bordeaux1.fr; d.astruc@ism.u-bordeaux1.fr;
Fax: +33 540 00 69 94
{ Electronic supplementary information (ESI) available: Syntheses and
characterization of compounds 4–6, recovery/re-use experiments and GC
spectra of the reactions described in Table 1. See DOI: 10.1039/b710289e
Scheme 1 Synthesis of the star-shape ligand 6. Reagents and conditions:
(i) p-C6H4CH2Br, KOH, DME, 40 uC, 6 d, 80%; (ii) PPh3, MeCN, 24 h
(Xe lamp), 84%; (iii) CuI, KI, DMF reflux,
4 d, 54%; (iv)
o-BrC6H4B(OH)2, Pd(PPh3)4, K2CO3, RT, 15 h, 70%; (v) n-BuLi,
ClPCy2, 278 uC, 62%. For details, see ESI.{
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Table 1 Suzuki coupling of unactivated or hindered aryl chloridesa
catalyst have been investigated by precipitation of the catalyst after
each cycle (Table 2). High yields are maintained until the fourth
cycle followed by a decrease of the reactivity. A second way of
recovery/re-use of the catalyst has been investigated by addition of
substrates after each cycle, and quantitative yields have been
obtained until the fourth cycles before the reactivity decreased.21
This does not only result from Pd leaching, because the addition of
Pd(OAc)2 after the sixth cycle did not reactivate the catalyst. In
both cases, 31P NMR analysis of the unreactive catalyst showed
peaks between 27 and 48 ppm probably corresponding to
degradation of the phosphine due to aerobic oxidation and
cyclometalation25 of the catalyst destroying activity.11c
Entry Halide
1
Boronic acid Product
Time/h Yield (%)
0.5
3
91
97
92
93
2
3
4
3
5
In conclusion, the star-shape catalyst is as efficient as the free
ligand described by Buchwald. The major additional points are (i)
the recoverability by precipitation of the metallodendritic catalyst
with an efficient re-use at least four times and (ii) the dramatic
efficiency with down to 50 ppm with a simple chloroarene.
5
6
7
a
24
95b
96b
93c
Notes and references
{ Synthesis of hexakis(2-bicyclohexylphosphinobiphenylethyl)benzene 6:
Hexakis(2-bromobiphenylethyl)benzene 5 (0.2 mmol) was dissolved in
THF and cooled to 278 uC under nitrogen, n-butyllithium (2.5 M in
hexane, 1.2 mmol) was then added dropwise under stirring. The resulting
yellowish solution was stirred at 278 uC for 3–4 h, and a yellow precipitate
appeared. A solution of dicyclohexylchlorophosphine (1.4 mmol) in THF
was added dropwise over 30 min to the reaction mixture at 278 uC. The
solution was then warmed slowly to RT overnight. The reaction was
quenched with a saturated NH4Cl solution and extracted with diethyl ether
and precipitated with methanol to give 6 as a white precipitate, 62% yield.
1H NMR (300 MHz, CDCl3) d 1.33–1.45 (11H, m, Cy), 1.83 (11H, m, Cy),
3.21 (2H, m), 3.40 (2H, m), 7.52 (7H, m), 7.80 (1H, m). 13C NMR
(75.5 MHz, CDCl3) d 26.2 (CH2, m), 27.0 (CH2, m), 29.0 (CH2, m), 30.0–
30.4 (CH2, m), 32.7 (CH2, m), 34.4–34.7 (CH2, d), 37.6–37.8 (CH2, m),
126.0–126.6 (CH, m), 127.0–127.4 (CH, m), 128.4 (CH, s), 128.9 (CH, s),
128.1–128.6 (CH, s), 130.4–130.7 (CH, m), 132.2–132.7 (CH, m), 136.6 (Cq,
s), 139.2 (Cq, m), 140.9–140.3 (Cq, m), 142.2 (Cq, s) (observed complexity
due to P–C splitting). 31P NMR (121.4 MHz, CDCl3) d 213,1 (PCy2, s).
MS-MALDI. Calc. for C162H204P6O6 ([M + Na]+): 2454.40. Found
2455.43 (the compound was found in its oxidized form due to the MS-
MALDI experimental procedure).
General procedure for the Suzuki coupling of aryl halides: In an oven-dried
Schlenk tube cooled to room temperature under an argon purge, Pd(OAc)2
(0.06 mmol, 3 mol%), ligand 6 (0.01 mmol, 0.5 mol%) were dissolved in
THF. A solution of boronic acid (3 mmol) and K3PO4 (6 mmol) in THF–
H2O (2 : 1) was then added as well as the chloroarene (2 mmol). The
reaction mixture was heated at 70 uC until the starting chloroarene has been
completely consumed as judged by GC analysis. Water was added, the
product was extracted with CH2Cl2 and was purified by flash chromato-
graphy on silica gel. The structure of each product was confirmed by GC-
MS.
24
7
1.0 equiv. aryl chloride (ArCl), 1.5 equiv. boronic acid, 3.0 equiv.
K3PO4, cat. Pd(OAc)2 (3 mol%), cat. ligand 6 (0.5 mol%), L : Pd =
1 : 1, THF–H2O (3 : 1) (20 mL mol21 of ArCl), 70 uC, yield from
GC. THF–H2O (1 : 1) (10 mL mol21 of ArCl), 83 uC. Cat.
Pd(OAc)2 (1 mol%), cat. ligand 6 (1 mol%), L : Pd = 6 : 1, THF–
H2O (1 : 3) (10 mL mol21 ArCl), 95 uC.
b
c
(Pd/ligand = 1, base: K3PO4) as catalyst. Water–THF mixtures
were used as solvents (‘‘Green chemistry’’ conditions)22 in
accordance with hydrophilic properties of many substrates for
cross-coupling reactions of pharmaceutical compounds.10c,23
The results in Table 1 show the data for all substrates, including
electron rich and/or ortho-substituted substrates, for which
coupling occured in nearly quantitative yields.21 These results are
comparable to those obtained by Buchwald with his free
monophosphine ligand.11a,b Note that, for entry 1, down to
0.005 mol% (50 ppm) of Pd was used to give the desired product in
81% yield (TON: 16200).24 The recovery and the re-use of the
Recycling/re-use procedure of the catalyst: In a typical recycling/re-use
procedure by precipitation of the catalyst, the reaction proceeds as
described above. From the initially homogeneous THF–H2O medium,
demixion occurs, because the aqueous phase becomes loaded with NaCl.
The organic layer was separated, and pentane added in order to precipitate
the catalyst and extract the product. Pentane extraction was carried out
three times, then the remaining precipitate dried under vacuum and re-used.
After each cycle, the 31P NMR spectrum of the remaining precipitate shows
the signal of the catalyst (d 42 ppm) which is similar to that of the initial
mixture (6/Pd(OAc)2) signal before catalysis.
Table 2 Recovery and re-use of the catalyst in Suzuki couplinga
Substrates
Cycleb
Time/h
Yield (%)
1
2
3
4
5
7
17
48
72
96
93
87
89
74
48
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a
1.0 equiv. of ArCl, 1.5 equiv. Ar9B(OH)2, 3.0 equiv. K3PO4, cat.
Pd(OAc)2 (1 mol%), cat. ligand 6 (1 mol%) : Pd = 6 : 1, THF–H2O
(1 : 3) (10 mL mol21 of ArCl), 95 uC, yields according to GC.
b
Precipitation of the catalyst with pentane after each cycle.
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(10 mL mol21 of halide) at reflux, 24 h (for Table 1, entry 5), and
only 26% yield (for Table 1, entry 6).
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