The aminocyclodextrin/Pd(OAc)2 complex as an efficient catalyst for the Mizoroki-Heck cross-coupling reaction

Article abstract of DOI:10.1002/chem.201301863

An aminocyclodextrin/Pd(OAc)₂ complex is used as an efficient, reusable catalyst in the Mizoroki-Heck reaction of aryl halides/triflates with olefins to give carbon-carbon-coupled products in good to excellent yields. This simple, efficient catalytic system is applicable to a wide range of aryl and heteroaryl halides/triflates and olefins. This environmentally benign procedure is less hazardous, milder, uses a catalytic amount of ligand and Pd(OAc) ₂, avoids an inert atmosphere, and catalyst recovery and reusability are achieved. Copyright

Full text of DOI:10.1002/chem.201301863

COMMUNICATION
DOI: 10.1002/chem.201301863
The Aminocyclodextrin/PdACHTUNTRGNEUNG(OAc)2 Complex as an Efficient Catalyst
for the Mizoroki–Heck Cross-Coupling Reaction
Kuppusamy Kanagaraj and Kasi Pitchumani*[a]
Palladium-catalyzed Heck reactions of aryl/vinyl halides
with olefins are one of the most important and versatile
transformations.[8] Selectively modified cyclodextrins are cur-
rently used as sensors as well as catalysts.[9]
À
tools for C C bond-forming processes in synthetic and me-
PeraminoCDs are homogeneous CD derivatives modified
by persubstitution on the “primary face” with amine pend-
ant groups, which display combined hydrophobic and elec-
trostatic binding of guest molecules relative to native CDs.
These compounds are employed as biomimetic catalysts for
Kemp elimination,[10a] deprotonation,[10b] and chiral-recogni-
tion processes.[10c] Aminocyclodextrins are known to be effi-
cient ligands for first-sphere coordination of metal ions, and
their complexes are used in aqueous organometallic cataly-
sis.[11] In our group, per-6-amino-b-cyclodextrin (per-6-
ABCD, 1b) has been extensively used as a supramolecular
chiral host and a base catalyst in the asymmetric Michael
addition of nitromethane and thiols to form a Micahel
adduct from trans-chalcones,[12a] the Henry reaction of nitro-
methane to form b-hydroxynitro compounds from aldehy-
des,[12b] the one-pot asymmetric synthesis of 2-aryl-2,3-dihy-
dro-4-quinolones,[12c] and in the multicomponent syntheses
of pyranopyrazole[13a] and 2-amino-4H-benzo[b]pyran deriv-
atives[13b] under solvent-free conditions at room temperature.
In addition, a novel, colorimetric and ratiometric sensor has
been developed for transition-metal cations Fe3+ and
Ru3+[14a] and phosphate/pyrophosphate anions in water[14b]
by using per-6-ABCD (1b) as the supramolecular host and
para-nitrophenol as the spectroscopic probe. Furthermore, a
fluorescent chemosensor for fenitrothion is reported that
uses a 1b/EuIII complex in aqueous media.[14c] Recently, we
have reported the use of 1b as an efficient ligand for the
CuI-catalyzed N-arylation of imidazoles with aryl and heter-
oaryl bromides[15a] and in the cyanation of aryl halides by
using K4[Fe(CN)6] as the cyanating reagent.[15b] Encouraged
by these results, we have used an aminocyclodextrin/Pd-
dicinal chemistry in the search for new derivatives with
wide-ranging therapeutic potential.[1,2] Over recent decades,
various homogeneous catalytic systems have been developed
for this transformation that each exhibit better activity and
selectivity.[3] Although many palladium–phosphine com-
plexes have been used as catalysts in this reaction, most of
them suffer from drawbacks such as high sensitivity of the
ligand to air and moisture, tedious multistep synthesis and
workup, high cost of the ligands, and use of various additives
and harmful organic solvents. Furthermore, the difficulties
of separation, recovery, and reusability, as well as metal
leaching of the expensive catalysts, are other important chal-
lenges.[4]
Studies on the heterogenization of this homogeneous
system show reduced selectivity, diminished catalytic activi-
ty, poor reproducibility, and/or tedious catalyst synthesis.[4]
Thus, the current challenge for palladium-catalyzed coupling
reactions is the development of high-performance, along
with sustainable and environmentally benign, reaction con-
ditions.[5] To circumvent these difficulties, naturally occuring
stabilizers/ligands may provide suitable supports for palladi-
um-catalysis cycles with high reactivity and selectivity in en-
vironmentally benign/acceptable media.[5]
Supramolecular chemistry, one of the fastest growing
areas of chemistry, contributes to the development of nu-
merous innovative concepts. This is especially true in orga-
nometallic catalysis in which host–guest interactions have
proved to be powerful tools to develop new strategies aimed
at improving the performance of catalytic entities.[6] Among
the various host systems, cyclodextrins (CDs) are naturally
occuring macrocyclic oligosaccharides with hydrophobic cav-
ities that selectively bind substrates and catalyze chemical
reactions through the formation of host–guest complexes by
using noncovalent interactions.[7] Furthermore, native b-CD
has been widely used as a host and catalyst for various
AHCTUNGRTEG(NNUN OAc)2 complex as an efficient and reusable catalyst in the
Mizoroki–Heck cross-coupling reaction between aryl/hetero-
aryl halides and triflates (X=I, Br, Cl, OTf) in water/DMF
(3:1 v/v) at 808C, under aerobic conditions. It is also inter-
esting to note that the catalyst can be recovered and reused
several times. A series of twelve aminocyclodextrin deriva-
tives (Figure 1) were also synthesized[16,17] and used as supra-
molecular hosts/ligands in the palladium-catalyzed Mizoro-
ki–Heck reaction.
[a] K. Kanagaraj, Prof. Dr. K. Pitchumani
School of Chemistry, Madurai Kamaraj University
Madurai 625021 (India)
Preliminary investigations into the Mizoroki–Heck cross-
coupling reaction were carried out by using aminocyclodex-
Fax : (+91)4522459181
E-mail: pit12399@yahoo.com
trin/Pd
ACHTUNGRTENUN(NG OAc)2 complex as the catalyst and bromobenzene
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201301863.
(2a) and styrene (3a) as the model substrates to optimize
Chem. Eur. J. 2013, 00, 0 – 0
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Figure 1. Various amino/guanidinocyclodextrin derivatives employed as ligands in the study.
Table 1. Optimization of reaction conditions.[a]
the reaction conditions; the results are summarized
in Table 1. The reaction carried out without the
ligand affords only a 12% yield of the desired prod-
uct (4a; Table 1, entry 1). The reaction yield in-
creased to 39% when b-cyclodextrin was used as
the ligand in DMF (Table 1, entry 2). Interestingly,
when carried out with 1b as the ligand in DMF, the
reaction became faster, providing an 86% yield of
4a (Table 1, entry 3), which indicates the impor-
tance of the amine groups in CD to stabilize Pd-
Entry
Ligand
Catalyst
Base
Solvent
T
[8C]
Yield[b]
[%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
none
b-CD
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
N
K2CO3
K2CO3
K2CO3
–
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
80
12
39
86
3
76
81
83
89
74
81
89
98
93
87
76
86
Cs2CO3
K3PO4
Na2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
ACHTUNGTRENNUNG(OAc)2 in this reaction. Interestingly, in the absence
of a base, the reaction failed completely (Table 1,
entry 4). Of the different inorganic bases used for
this coupling reaction (Table 1, entries 3 and 5–7),
K2CO3 afforded the best results. Potassium carbo-
nate sweeps the protons off the CDs and allows re-
duction and coordination with Pd. The extra amine
groups may coordinate the released acetate groups.
No product was obtained in the absence of a palla-
dium salt.
During solvent optimization, the reaction in vari-
ous pure solvents, including dimethylformamide, di-
methyl sulfoxide, methanol, acetonitrile, and water,
afforded only modest yield (Table 1, entries 8–11).
On the other hand, use of mixtures of the solvents
was found to be advantageous and, of the various
solvent mixtures tested (Table 1, entries 12–14),
water/DMF (3:1 v/v) was identified as the most
suitable, affording a 98% yield and indicating that
this coupling process is insensitive to the presence
of water (Table 1, entry 12). During the screening
MeOH
MeCN
water
water/DMF
water/DMSO
water/MeCN
water/DMF
water/DMF
water/DMF
water/DMF
water/DMF
water/DMF
water/DMF
water/DMF
water/DMF
PdCl2
PdI2
Pd
Pd
Pd
Pd
Pd
Pd
Pd
98
1a/1c
1d/1e/1 f
1g/1h/1i
1j/1k/1l
1b
80
80
80
80
80
80
78/94[c]
52/69/72[d]
81/98/96[e]
67/74/78[f]
98/98/98/98/81[g]
99/98/98/98/94[g]
1h
[a] Bromobenzene (0.1 mmol), styrene (0.13 mmol, 1.3 equiv), base (2 equiv), solvent
(2 mL), Pd salt (0.008 mmol, 8 mol%), ligand (0.010 mmol, 10 mol%), 14 h, unless
otherwise noted. [b] Yields of the isolated products. [c] Yields of the reaction carried
out with peraminocyclodextrins 1a and 1c as the ligand, respectively. [d] Yields of the
reaction carried out with monoaminocyclodextrins 1d, 1e, and 1 f as ligand, respec-
tively. [e] Yields of the reaction carried out with perguanidinocyclodextrins 1g, 1h,
and 1i as ligand, respectively. [f] Yields of the reaction carried out with monoguanidi-
nocyclodextrins 1j, 1k, and 1l as ligand, respectively. [g] Yields of the reaction carried
of palladium salts, PdACTHNUTRGNE(UNG OAc)2 showed the best cata-
lytic performance, providing a significant improve- out with 2, 1.5, 1, 0.5, and 0.3 equivalents of K2CO3, respectively.
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Mizoroki–Heck Cross-Coupling Reaction
COMMUNICATION
Table 2. Mizoroki–Heck reaction, catalyzed by the amino/guanidinocy-
ment in comparison to the other salts (Table 1, entries 15
and 16). Under these optimized conditions, the effect of
temperature was also recorded (Table 1, entry 17). At a tem-
perature below 808C, the yield of 4a decreases, whereas in-
creasing the temperature above 808C resulted in no change
in yield.
clodextrin/Pd
ACHTUNGRTEN(NNUG OAc)2 complex, of different aryl/alkyl halides with styre-
ne.[a]
Entry
Aryl/alkyl halide (2)
4
t
Yield[b]
[%]
A closer look at the results shows that the ligand plays a
major role in the reaction (Table 1, entry 1). With b-cyclo-
dextrin (containing only oxygen atoms as binding sites) as
the ligand, the yield was 39% (Table 1, entry 2), whereas
the use of 1b (containing both nitrogen and oxygen atoms
as binding sites) as the ligand drastically increased the yield
to 86% (Table 1, entry 3). This clearly indicates that the
nature of the ligand (number of amino/guanidino groups
and cavity size) can dramatically influence the efficiency of
this catalytic system. Hence, a series of twelve aminocyclo-
dextrin derivatives (1a–1l; Figure 1) were synthesized and
used as supramolecular ligands/hosts for the aforementioned
reaction (Table 1, entries 18–21). Both per-6-amino-b-cyclo-
dextrin (1b, yield 98%) and per-6-guanidino-b-cyclodextrin
(1h, yield 98%) are suitable ligands/hosts for this Mizoroki–
Heck cross-coupling reaction. Furthermore, 0.5 equivalents
of K2CO3 was found to facilitate the coupling reaction
(Table 1, entries 22 and 23). These observations show that
optimum results are obtained (yield 98%) when the reac-
tion is carried out in water/DMF (3:1 v/v) at 808C with
[h]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
bromobenzene
4a
4b
4c
4d
4e
4 f
4g
4h
4i
14
10
18
9
12
13
20
9
98
4-bromonitrobenzene
4-acetylbromobenzene
4-bromoaniline
4-bromotoluene
3-bromoanisole
4-bromo-2-methylaniline
3-bromobenzotrifluoride
4-bromo-2-methylbenzonitrile
1-bromo-4-(trifluoromethoxy)benzene
2-bromo-4-nitrotoluene
3-bromopyridine
2-amino-5-bromopyridine
5-bromopyrimidine
2-acetyl-5-bromothiophene
5-bromoindole
96 (98)
92 (96)
96
93
96 (98)
90
89
95
93 (96)
86
99
91
98
79 (84)
88
93
98
99
93 (94)
87
96 (97)
98
7
4j
4k
4l
10
12
11
18
7
11
12
14
8
4m
4n
4o
4p
4q
4r
4a
4s
4t
4u
4l
4v
4p
4q
2-bromonaphthalene
1-bromoadamantane
iodobenzene
7
4-iodophenol
11
10
9
5
10
9
ethyl 4-iodobenzoate
3,4-dimethyliodobenzene
3-iodopyridine
2-iodothiophene
5-iodoindole
3 mol% of 1b or 1h and 3 mol% of PdACTHNUTRGNENUG(OAc)2 under aero-
bic conditions.
89
91 (96)
96
To explore the scope of the catalytic system, various aro-
matic, heteroaromatic, and bicyclic bromides and iodides
were subjected to the optimized reaction conditions with
styrene and the results are given in Table 2. All reactions
proceeded to completion within 5–20 h, and products 4a–v
were isolated in moderate to excellent yields. Substrates
possessing electron-rich groups, such as p-CH3 and p-OCH3,
afforded coupling products in good yield, but after long re-
action times (upto 20 h; Table 2, entries 5–7). In contrast,
bromoarenes containing electron-withdrawing groups, such
as p-NO2, p-COCH3, m-CF3, p-CN, and p-OCF3, reacted
faster and gave excellent yields (Table 2, entries 2, 3, and 8–
10). This reaction worked very well for a wide range of
para-substituted aryl bromides and aryl iodides to afford
good to excellent yields (Table 2, entries 2–6, 10, 20, and
21). When substituents were present in the meta- and ortho-
positions (Table 2, entries 6, 8, and 23) and also when more
than one substituent was present on the phenyl ring
(Table 2, entries 7, 9, 11, and 22), the yield of the product
decreased and increased reaction times did not provide an
improvement. Heteroaromatic and bicyclic bromides/iodides
gave the corresponding products in excellent yields (Table 2,
entries 12–18 and 23–26). These results clearly suggest that
electronic and steric factors play a significant role in this
coupling reaction, with para-substituted aryl halides (which
may ensure stronger binding and deeper inclusion into the
CD cavity) giving higher yields.
2-bromonaphthalene
7
[a] Aryl/alkyl halide (0.1 mmol), styrene (3a, 0.13 mmol, 1.3 equiv),
K2CO3 (0.5 equiv), water/DMF (3:1 v/v; 2 mL), Pd(OAc)2 (0.003 mmol,
3 mol%), ligand (1b/1h, 0.003 mmol, 3 mol%), 808C, unless otherwise
noted. [b] Yields of the isolated products with 1b as the ligand; numbers
in parentheses are for reactions with 1h as the ligand.
AHCTUNGTRENNUNG
optimized conditions to give the corresponding products in
good yield and the results are summarized in Table 3. Differ-
ent substituted aromatic alkenes (Table 3, entries 1–3 and 7)
and heterocyclic alkenes (Table 3, entries 6, 7, 8, and 10) af-
forded moderate to excellent yield after long reaction times.
Notably, aliphatic alkenes, such as ethyl acrylate, acryloni-
trile, and 5-vinylbicycloACTHUNRGTNE[NUG 2.2.1]hept-2-ene, proceeded effi-
ciently to afford good yields of the coupling products
(Table 3, entries 4, 5, and 9).
As recyclability is important for application of a good cat-
alyst, reuse performance of the aminocyclodextrin (1b/1h)/
PdACTHUNTRGENNG(U OAc)2 complex was investigated and results are shown
in Table 4. After completion of the reaction, the solvent is
removed simply by use of a vacuum and the products are
extracted with ethyl acetate. The aminocyclodextrin/Pd-
AHCTUNGRTEG(NUNN OAc)2 complex is filtered, washed with ethyl acetate, dried
in a vacuum, and reused. It is noteable that the catalyst was
recovered even after the fifth reaction cycle, as evident from
the comparable activity.
Although various aryl halides[18] are used for Mizoroki–
Heck reactions, more attention has been paid to the devel-
opment of efficient catalyst systems for aryl chlorides since
To expand the scope of this protocol further, other substi-
tuted alkenes were coupled with bromobenzene under the
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K. Pitchumani and K. Kanagaraj
Table 3. Mizoroki–Heck reaction, catalyzed by the amino/guanidinocy-
clodextrin/Pd
(OAc)2 complex, of different olefins with bromobenzene.[a]
(DavePhos=2-dicyclohexylphosphino-2’-(N,N-dimethylami-
no)biphenyl) Heck reaction of aryl chlorides with olefins
and nBu4N+OAcÀ as base at 808C (reported for the first
time at this temperature) under an argon atmosphere.[21]
Thus, there is still a need to explore simple, milder, and
more efficient catalytic systems under aerobic conditions to
improve the scope and utility of the Mizoroki–Heck cou-
pling reaction of aryl chlorides (See Table S3 in the Support-
ing Information).
The aforementioned optimized reaction conditions were
extended to the Mizoroki–Heck cross-coupling reaction be-
tween chlorobenzene and styrene, affording a poor yield
(13%). As reported in earlier work,[21] the yields of the
products were increased by adding KI (see Figure 2 and
ACHTUNGTRENNUNG
Entry Olefin (3)
Product (4)
t
Yield[b]
[h] [%]
1
2
16 91 (92)
4w
4 f
11 73 (76)
13 89
3
4
5
4x
4y
19 92 (95)
12 97
6
7
4z
14 91 (90)
4aa 13 78
8
9
4bb 15 96 (94)
4cc 10 92
10
4dd 11 86 (90)
Figure 2. Yield of coupling product 4a [%] from the reaction between
chlorobenzene (0.1 mmol) and styrene (0.13 mmol) by using different cat-
alytic systems (aminocyclodextrin (1b/1h)/PdACTHNURTGNENG(U OAc)2) with different
amounts of KI [mol%] at 808C in water/DMF (3:1 v/v) under aerobic
[a] Bromobenzene (2a, 0.1 mmol), olefin (3b–k, 0.13 mmol, 1.3 equiv),
K2CO3 (0.5 equiv), water/DMF (3:1 v/v; 2 mL), Pd(OAc)2 (0.003 mmol,
3 mol%), ligand (1b/1h, 0.003 mmol, 3 mol%), 808C, unless otherwise
noted. [b] Yields of the isolated products with 1b as the ligand; the num-
bers in parentheses are for rections with 1h as the ligand.
AHCTUNGTRENNUNG
conditions. The percentage yield was calculated based on chlorobenzene.
Table S1 in the Supporting Information). The scope of this
catalytic system was extended to other substituted aryl
chlorides and heterocyclic and bicyclic chlorides and the re-
sults are depicted in Table 5. Efficient conversion was ob-
served in each case, affording the desired products in good
to excellent yields. Consequently, this reaction also worked
very well for aryl triflates, such as phenyl, pyridine-4-yl, and
naphthalen-2-yl triflates, with good yield (Table 5, en-
tries 12–14).
Table 4. Mizoroki–Heck reaction, catalyzed by the amino/guanidinocy-
clodextrin/Pd
ACHTUNGTRENNUNG
(OAc)2 complex, of styrene with bromobenzene.[a]
Cycle
1
2
3
4
5
yield [%][b]
yield [%][c]
98
99
91
95
86
91
84
89
79
84
[a] All of the reactions were carried out on a 4 mmol scale with bromo-
benzene (4 mmol), styrene (3a, 5.2 mmol, 1.3 equiv), K2CO3 (0.5 equiv),
water/DMF (3:1 v/v; 8 mL), PdACTHNUTRGNE(UNG OAc)2 (0.012 mmol, 3 mol%), and the
ligand (1b/1h, 0.012 mmol, 3 mol%), at 808C for 14 h. [b] 1b was used as
the ligand. [c] 1h was used as the ligand.
On the basis of these results, and in accordance with pre-
vious literature reports,[4,5,16] a plausible reaction pathway is
proposed as shown in Scheme 1. The aminocyclodextrin/Pd-
AHCTUNGTRENNUNG
aryl chlorides are more readily available and cheaper than
alternative aryl halides. However, most of the catalytic sys-
tems for Mizoroki–Heck reactions of unactivated aryl chlor-
ides require harsher conditions (T>1008C) and are ineffi-
cient for the reaction with unactivated olefins.[19,20] Recently,
Xu et al. have reported the Pd–DavePhos complex catalyzed
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
C46H83N7O32Pd, [Per-6-ABCD (1b)/PdACTHUNGRTNEUNG(OAc)2] complex,
[MÀH+]=1350.40) and another less intense peak at m/z=
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Mizoroki–Heck Cross-Coupling Reaction
COMMUNICATION
Table 5. Mizoroki–Heck reaction, catalyzed by amino/guanidinocyclo-
dextrin/Pd
range of aryl, heteroaryl, and bicyclic halides (X=I, Br, Cl,
and OTf) and olefins, providing excellent yields under
milder conditions. This catalytic system, reported for the
first time, for the Heck coupling of aryl chlorides with ole-
fins under aerobic conditions at 808C in aqueous media is
an alternative to reported routes that usually involve equi-
molar amounts of a ligand/Pd salt.
This catalytic system also has other advantages such as a
simpler procedure, milder reaction conditions, and a lack of
an inert atmosphere, which is a common prerequisite with
earlier works, as well as providing an attractive alternative
to conventionally used phosphine-based catalysts, which are
hazardous, corrosive, and polluting. The reaction is compati-
ble with a wide range of functional groups and this method-
ology avoids the use of an inert atmosphere. This reusable
catalytic system, involving a green and ecofriendly catalyst,
can replace metal salts or other heterogeneous catalysts, and
has potential value for synthetic and industrial applications.
ACHTUNGTRENNUNG
(OAc)2, of different aryl chlorides/triflates with styrene.[a]
Entry
Aryl chloride/triflate (6)
4
t
Yield[b]
[%]
[h]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
chlorobenzene
4-chlroaniline
4-acetylchlorobenzene
3-chloroanisole
2-chlorophenol
2-chloro-4-nitrotoluene
3-chloropyridine
2-chlorothiophene
4-chloropyrazole
5-chloroindole
2-chloronaphthalene
phenyl triflate
pyridin-3-yl triflate
naphthalen-2-yl triflate
4a
4d
4c
4 f
4s
16
24
19
13
21
16
12
19
24
14
19
16
14
17
96 (94)
91
87 (86)
91
87
92
89 (92)
94
91
82 (80)
71
89 (87)
93 (92)
91 (90)
4k
4l
4v
4ee
4p
4q
4a
4l
4q
[a] Aryl chloride/triflate (6, 0.1 mmol), styrene (3a, 0.13 mmol,
1.3 equiv), K2CO3 (0.5 equiv), water/DMF (3:1 v/v; 2 mL), Pd(OAc)2
AHCTUNGTRENNUNG
(0.003 mmol, 3 mol%), KI (0.005 mmol, 5 mol%), ligand (1b/1h,
0.003 mmol, 3 mol%), 908C, unless otherwise noted. [b] Yield of the iso-
lated product with 1b as the ligand; the numbers in parentheses are for
the reaction with 1h as the ligand.
Experimental Section
General procedure for the Mizoroki–Heck cross-coupling reaction be-
tween aryl bromides/iodides and olefins: A reaction tube equipped with
a magnetic stirring bar was charged with amino/guanidinocyclodextrin
(1b/1h; 0.003 mmol, 3 mol%) and Pd
persed in water/DMF (3:1 v/v; 2 mL) for 15 min. The aryl bromide/iodide
2a–q (0.1 mmol) was added to the in situ formed (1b/1h)/Pd(OAc)2 com-
ACHTUNGRTEN(NUNG OAc)2 (0.003 mmol, 3 mol%) dis-
1268.41 (m/z calcd for C42H81N7O30Pd, [Per-6-ABCD (1b)/
PdII]·2H2O, [MÀH+]=1268.39) in the ESI-MS (Figure S1 in
the Supporting Information), which correspond to the com-
AHCTUNGTRENNUNG
plex with constant stirring, which was continued for 30 min (to complete
complexation). An olefin 3a–j (1.3 equiv, 0.13 mmol) was added and the
mixture was allowed to stir at 808C under aerobic conditions for 7–20 h.
After completion of the reaction, the solvent was removed with the aid
of a rotary evaporator and the product was extracted with ethyl acetate,
filtered, dried with sodium sulphate, and concentrated under reduced
pressure. The resulting crude product was purified by passing it through
a column of silica gel 60–120 mesh using petroleum ether/ethyl acetate
(9:1 ratio) as the eluent, affording coupling product 4a–q as a light-
yellow to colorless solid, which was analyzed by NMR spectroscopy
(400 MHz, CDCl3, T=300 K, TMS=0 ppm) and ESI-MS. After extrac-
plex between aminocyclodextrin and PdACTHNUTRGENUG(N OAc)2, and its asso-
ciation constant is 2823mÀ1. Oxidative addition of an aryl
halide leads to a Pd-chelated complex, generating intermedi-
ate II, which undergoes dissociation of the halide through
the formation of a cationic p complex (III). Next, the syn-in-
sertion of the alkene through a carbometallation reaction,
providing linear s-alkyl PdII complex IV, occurs, which un-
dergoes a syn-b-hydride elimination to give rise to the Heck
product (4a), and simultaneously the catalytically active Pd0
complex I is regenerated in situ from a hydridopalladium
complex after reductive elimination by a base.
tion of the product, aminocyclodextrin/PdACTHNUGRTENNUG(OAc)2 ((1b/1h)/PdACHTUNGTRENNUNG(OAc)2)
complex was filtered, washed with ethyl acetate, dried under vacuum,
and reused.
General procedure for the Mizoroki–Heck cross-coupling reaction be-
tween aryl chlorides/triflates and olefins: A reaction tube equipped with
a magnetic stirring bar was charged with amino/guanidinocyclodextrin
(1b/1h; 0.003 mmol, 3 mol%) and PdACHTNUGRTENUNG(OAc)2 (0.003 mmol, 3 mol%) dis-
persed in water/DMF (3:1 v/v; 2 mL) for 15 min. An aryl chloride/triflate
A control experiment carried out with a 1b/PdACTHUNRGTNEUNG(OAc)2/
adamantane complex (binding constant 2926mÀ1) gave a
moderate yield (31%) of 4a, confirming the active partici-
pation of the cavity of 1b in enhancing the rate of the reac-
tion. As adamantane competes with the aryl halide to com-
plex with CD, a decrease in yield (31%) was noticed. Thus,
we believe that the cooperative binding and tighter fit of re-
actants inside the CD cavity ensure their close proximity.
This hypothesis was further supported by observing down-
field shifts of H3 and H5 protons by NMR spectroscopy in
6a–m (0.1 mmol) and KI (0.005 mmol, 5 mol%) were added to the in
situ formed (1b/1h)/PdACTHNUTRGNE(NUG OAc)2 complex with constant stirring, which was
continued for 30 min (to complete complexation). Styrene (3a; 1.3 equiv,
0.13 mmol) was then added and the mixture was allowed to stir at 808C
under aerobic conditions for 12–24 h. After completion of the reaction,
the solvent was removed with the aid of a rotary evaporator and the
product was extracted with ethyl acetate, filtered, dried with sodium sul-
phate, and concentrated under reduced pressure. The resulting crude
product was purified by passing over a column of silica gel 60–120 mesh
using petroleum ether/ethyl acetate (9:1 ratio) as the eluent, affording
coupling product 4 as a light-yellow to colorless solid, which was ana-
lyzed by NMR spectroscopy (400 MHz, CDCl3, T=300 K, TMS=0 ppm)
and ESI-MS. After extraction of the product, the aminocyclodextrin/Pd-
1b/PdACHTUNGTRENNUNG(OAc)2 after complexation with 2a (see the Support-
ing Information).
In summary, we have demonstrated that aminocyclodex-
trins (per-6-ABCD (1b)/per-6-AGCD (1h)), natural sugar
derivatives, act as efficient ligands for Pd
ACHTUNGRTEN(NGNU OAc)2 in catalysis
A
ACHTUNGRTEN(NUNG OAc)2) complex was filtered, washed with ethyl ace-
of the Mizoroki–Heck cross-coupling reaction for a wide
Chem. Eur. J. 2013, 00, 0 – 0
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K. Pitchumani and K. Kanagaraj
development and application of
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Scheme 1. Proposed mechanism for the aminocyclodextrin (1b)/PdACTHNUTRGENUG(N OAc)2-catalyzed Mizoroki–Heck reaction.
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Acknowledgements
The authors gratefully acknowledge financial assistance from University
Grants Commission-Basic Science Research and the Department of Sci-
ence and Technology, New Delhi, India, and K.K. thanks the Council of
Scientific and Industrial Research, New Delhi, for the award of a Senior
Research Fellowship.
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Keywords: aminocyclodextrins
halides/triflates Mizoroki–Heck reaction
catalysts · water chemistry
·
aqueous media
·
aryl
·
·
reusable
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Received: May 14, 2013
Revised: July 5, 2013
Published online: && &&, 0000
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K. Pitchumani and K. Kanagaraj
Catalysis
K. Kanagaraj,
K. Pitchumani* ............... &&&& — &&&&
The Aminocyclodextrin/PdACTHNURTGNENUG(OAc)2
Complex as an Efficient Catalyst for
the Mizoroki–Heck Cross-Coupling
Reaction
An aminocyclodextrin/Pd
(OAc)2 com-
halides/triflates and olefins. This envi-
ronmentally benign procedure is less
hazardous, milder, uses a catalytic
plex is used as an efficient, reusable
catalyst in the Mizoroki–Heck reaction
of aryl halides/triflates with olefins to
give carbon–carbon-coupled products
in good to excellent yields. This simple,
efficient catalytic system is applicable
to a wide range of aryl and heteroaryl
amount of ligand and PdACTHNUTRGENUN(G OAc)2,
avoids an inert atmosphere, and cata-
lyst recovery and reusability are ach-
ieved.
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These are not the final page numbers!