D-Glucosamine as an efficient and green additive for palladium-catalyzed Heck reaction

Article abstract of DOI:10.2478/s11696-013-0367-z

The Heck coupling of haloarenes with various alkenes was successfully performed in the presence of 0.5 mole % Pd(OAc)₂ and 1.0 mole % d-glucosamine as an additive with K₂CO₃ as the optimal base in a mixture of H₂O/iPrOH (φ _r = 2: 1) as the reaction solvent at 80 C after 6 h. d-Glucosamine was found to be an inexpensive, air-stable, easy to available, and efficient additive in palladium-catalyzed Heck reactions of aryl iodides (67-95 % conversion) and bromides (38-72 % conversion).

Full text of DOI:10.2478/s11696-013-0367-z

Chemical Papers 67 (7) 759–763 (2013)
DOI: 10.2478/s11696-013-0367-z
SHORT COMMUNICATION
D
-Glucosamine as an efficient and green additive
for palladium-catalyzed Heck reaction
Mojtaba Amini*, Hossein Etemadi
Department of Chemistry, Faculty of Science, University of Maragheh, P.O. Box 55181–83111731, Maragheh, Iran
Received 17 October 2012; Revised 4 January 2013; Accepted 16 January 2013
The Heck coupling of haloarenes with various alkenes was successfully performed in the presence
of 0.5 mole % Pd(OAc)
2
and 1.0 mole %
D
-glucosamine as an additive with K
2
CO
3
as the optimal
-Glucosamine
◦
base in a mixture of H O/iPrOH (ϕ
2
r
= 2 : 1) as the reaction solvent at 80 C after 6 h.
D
was found to be an inexpensive, air-stable, easy to available, and efficient additive in palladium-
catalyzed Heck reactions of aryl iodides (67–95 % conversion) and bromides (38–72 % conversion).
ꢀ
c 2013 Institute of Chemistry, Slovak Academy of Sciences
Keywords: -glucosamine, Pd(OAc) , Heck reaction, aqueous medium
D
2
Palladium-catalyzed arylation of olefins, the Heck
reaction, as one of the most versatile methods for
C—C bond formation is an extremely useful and gen-
eral technique in the preparation of biologically active
functionalized olefins which are important intermedi-
ates or products in drug discovery, pharmaceuticals,
and agricultural compounds (Heck, 1987; Wolfson &
Dlugy, 2007; Bräse & Meijere, 1998; Bagherzadeh et
al., 2012).
Driven by environmental and economic concerns,
numerous efforts have been devoted to the devel-
opment of the Heck reaction under benign condi-
tions, e.g. with water as the solvent (Li & Chan,
gained great attention because of their potential appli-
cations as advanced soft materials in syntheses, drug
delivery, enzyme immobilization, etc. (Diéguez et al.,
2007; Monopoli et al., 2010). Despite their obvious
potential for ligand degradation, many carbohydrate
decorated ligands seem to be relatively stable under
aerobic reaction conditions (Bradshaw et al., 2011;
Makhubela et al., 2011). The low costs but especially
the high environmental friendly nature and water sol-
ubility of D-glucosamine (D-GlcN) as one of the most
naturally abundant molecules (Thakur et al., 2011)
has led us to explore its usefulness as an additive
in palladium-catalyzed Heck reactions in an aqueous
medium.
1
997; Cornils & Herrmann, 1998; Grieco, 1998). Al-
though there are some reports on the Heck reaction
in mixed aqueous organic solvents in the presence
of Pd-catalysts with water soluble phosphine ligands
To develop a general catalyst for palladium-
catalyzed Heck reactions, the application of
Pd(OAc) /D-GlcN as an efficient system in the Heck
2
(Genet & Savignac, 1999; Iranpoor et al., 2010), how-
coupling reaction of olefins with aryl halides is re-
ever, most phosphine-based ligands are water and/or
air-sensitive (Phan et al., 2006; Andersen & Keay,
ported herein (Fig. 1).
Firstly, a model reaction involving iodobenzene
and butyl acrylate was performed to optimize the re-
action conditions. Various parameters including bases,
solvents and palladium salts were investigated.
In the initial investigations, the effect of bases on
the Heck reaction in N,N-dimethylformamide (DMF)
2
001; Martin & Buchwald, 2008). Therefore, it is
highly desirable to design water soluble, efficient and
phosphine-free ligands to avoid the use of expensive
and water and/or air-sensitive phosphines in palla-
dium catalyzed coupling reactions (Allam & Singh,
◦
2
011).
In recent years, carbohydrate derivatives have
as the solvent at 80 C was examined. Various bases in-
cluding KOH, K CO , Na CO , K PO , NaOAc, and
2
3
2
3
3
4
*Corresponding author, e-mail: mamini@maragheh.ac.ir

7
60
M. Amini, H. Etemadi/Chemical Papers 67 (7) 759–763 (2013)
Fig. 1. The Heck reaction of arylhalides and olefins with the Pd(OAc)2/D-GlcN catalytic system.
Table 1. Effect of solvent and Pd salt on the Heck reactiona
b
Entry
Solvent
Pd salt
D-GlcN/mole %
Yield /%
1
2
3
4
5
6
7
8
9
H2O
CH3CN
THF
iPrOH
EtOH
DMF
H2O/iPrOHc
H2O/iPrOHc
H2O/iPrOH
H2O/iPrOHc
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
K2PdCl4
PdCl2
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
–
61
21
15
48
41
90
88
75
81
55
c
1
0
Pd(OAc)2
a) Reaction conditions: 1.0 mmol of iodobenzene, 1.2 mmol of butyl acrylate, 2 mmol of K2CO3, 0.5 mole % of Pd(OAc)2, 1.0
◦
mole % of D-GlcN, 80 C, 6 h, 3 mL of solvent; b) determined by GC; c) ϕr = 2 : 1.
performing the model reaction in different solvents
while the selection of solvents with low toxicity was of
primary interest. Water alone or in association with
iPrOH represents the most economical and safety-
conscious solvent combination. Solvents such as H2O,
CH3CN, tetrahydrofuran (THF), iPrOH, and EtOH
gave low to moderate yields ranging from 15 % to
6
1 % (Entries 1–5, Table 1). However, when the or-
ganic/aqueous solvent was used, satisfactory results
were obtained. As shown in Table 1, DMF and a mix-
ture of H2O/iPrOH (ϕr = 2 : 1) were found to be
the best choice in the presence of K CO as the base
Fig. 2. Effects of bases on the Heck reaction. Reaction con-
ditions: 1.0 mmol of iodobenzene, 1.2 mmol of butyl
acrylate, 2 mmol of bases, 0.5 mole % of Pd(OAc)2, 1.0
2
3
(Entries 6 and 7, Table 1). The significant role of the
◦
mole % of D-glucosamine, 80 C, 6 h, 3 mL, DMF; a)
determined by GC.
co-solvent is attributed to the good solubility of the
organic reactants and inorganic bases.
Palladium salt screening for better performance of
the reaction was carried out and Pd(OAc)2 was found
as the best palladium salt for the coupling reaction of
iodobenzene and butyl acrylate (Entries 7–9, Table 1).
Previously, we reported that Pd(OAc)2 alone is
NEt3 were investigated. As can be seen from Fig. 2,
K2CO3 showed the best results and the corresponding
coupling product was obtained in 90 % yield.
Then, a series of reactions was investigated by

M. Amini, H. Etemadi/Chemical Papers 67 (7) 759–763 (2013)
Table 2. The Heck reaction between aryl halides and olefinsa
761
b
c
Entry
ArX
Olefin
Conversion /%
Yield /%
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
PhI
PhI
PhI
PhI
PhI
PhI
4-MeO-PhI
4-MeO-PhI
2-MeO-PhI
4-MeCO-PhBr
4-MeCO-PhBr
4-MeO-PhBr
4-MeO-PhBr
2-MeO-PhBr
PhBr
PhCH—CH2
95d
88
91
90
85
81
83
84
67
72
70
59
63
44
38
19
25
5
87e
81
–
–
–
–
–
–
–
65
65
–
–
–
–
–
–
–
H2C—CH—COOBu
H2C—CH—COOMe
H2C—CH—COOEt
4-Me-PhCH—CH2
4-MeO-PhCH—CH2
H2C—CH—COOBu
PhCH—CH2
H2C—CH—COOBu
PhCH—CH2
H2C—CH—COOBu
H2C—CH—COOBu
PhCH—CH2
H2C—CH—COOBu
H2C—CH—COOBu
PhCH—CH2
H2C—CH—COOBu
H2C—CH—COOBu
1
1
1
1
1
1
1
1
1
4-MeCO-PhCl
4-MeCO-PhCl
PhCl
a) Reaction conditions: 1.0 mmol of aryl halide, 1.2 mmol of olefins, 2 mmol of K2CO3, 0.5 mole % of Pd(OAc)2, 1.0 mole % of
◦
D-GlcN, 80 C, 3 mL of mixture H2O/iPrOH (ϕr = 2 : 1) as the solvent; b) determined by GC, based on aryl halides; c) isolated
yield; d) ratio (Z/E) is 9 : 91; e) (E)-stilbene.
Table 3. Physico–chemical data of some of the Heck reaction productsa
wi(calc.)/%
wi(found)/%
M.p.
Compound
Formula
Mr
◦
C
H
C
(
(
(
(
E)-Stilbene
C14H12
C13H16O2
C16H14O
C15H18O3
180.3
240.3
222.1
246.1
93.29
6.71
6.78
7.90
7.81
6.35
6.31
7.37
7.41
123–125
142–144
134–136
Yellow oil
9
3.18
76.44
6.37
86.45
6.37
73.15
3.06
E)-n-Butyl cinnamate
E)-4-Acetylstilbene
7
8
E)-Butyl-3-(4-acetylphenyl)acrylate
7
a) The elemental analysis (C, H) of compounds were obtained from a Carlo ERBA Model EA 1108 analyzer (Italy). Melting points
were taken on a Gallenkamp melting point apparatus (UK).
also an active catalyst for the Heck reaction in some
solvents such as DMSO, DMF, and the mixture of
H2O/DMSO (ϕr = 2 : 1) at 80 C in the presence
(Entry 10, Table 1), while the addition of 1.0 mole %
of D-GlcN has a significant effect on the coupling of
iodobenzene with butyl acrylate. D-GlcN is proposed
◦
0
of K2CO3 as the base (Amini et al., 2012). In this case,
to strengthen the stabilization of Pd species and pre-
0
the Pd species generated from Pd(OAc)2 seems to be
venting their agglomeration (Grasa et al., 2003).
To survey the generality of the catalytic protocol,
the reaction was investigated using a variety of aryl
halides coupled with olefins under the optimized con-
dition. As shown in Table 2, a wide range of functional
groups was also tolerated in the reaction.
very active and sufficiently stable in these solvents in
order to support the oxidative addition. However, in
the mixture of H2O/iPrOH (ϕr = 2 : 1), the activity
of the Pd(OAc)2 catalyst decreased significantly and
only a 55 % yield was obtained after 6 h of the reaction

7
62
M. Amini, H. Etemadi/Chemical Papers 67 (7) 759–763 (2013)
Table 4. Spectral data of some of the Heck reaction productsa
Compounds
Spectral data
(E)-Stilbene
1H NMR (500 MHz, CDCl3), δ: 7.60 (d, 4H, J = 1.0 Hz), 7.43 (t, 4H, J = 7.5 Hz), 7.32 (t, 2H, J =
7
.2 Hz,), 7.19 (s, 2H)
C NMR (125 MHz, CDCl3), δ: 137.8, 129.2, 129.1, 128.1, 127.0
1
3
(
E)-n-Butyl cinnamate 1H NMR (500 MHz, CDCl3), δ: 7.72 (d, 1H, J = 16.0 Hz), 7.56 (q, 2H, J = 3.7 Hz), 7.41 (t, 3H,
J = 1.0 Hz), 6.48 (d, 1H, J = 16.0 Hz), 4.26 (t, 2H, J = 6.7 Hz), 1.76–1.72 (m, 2H), 1.51–1.47 (m,
2
H), 1.01 (t, 3H, J = 7.4 Hz)
13
C NMR (125 MHz, CDCl3), δ: 167.5, 145.0, 134.9, 130.6, 129.3, 128.5, 118.8, 64.8, 31.2, 19.6, 14.2
1H NMR (500 MHz, CDCl3), δ: 7.90 (d, 2H, J = 8.4 Hz), 7.53 (d, 2H, J = 8.4 Hz), 7.50–7.47 (m,
(
E)-4-Acetylstilbene
E)-Butyl-3-(4-acetyl-
2H), 7.37–7.34 (m, 2H), 7.30–7.27 (m, 1H), 7.17 (d, 1H, J = 16.3 Hz), 7.07 (d, 1H, J = 16.3 Hz),
2
.55 (s, 3H)
1
3
C NMR (125 MHz, CDCl3), δ: 197.3, 141.9, 136.6, 135.9, 131.4, 128.8, 128.7, 128.2, 127.4, 126.7,
126.4, 29.6
(
1H NMR (500 MHz, CDCl3), δ: 7.98–7.94 (m, 2H), 7.69 (d, 1H, J = 16.0 Hz), 7.60–7.57 (m, 2H),
phenyl)acrylate
6.53 (d, 1H, J = 16.0 Hz), 4.22 (t, 2H, J = 6.6 Hz,), 2.57 (s, 3H), 1.71–1.68 (m, 2H), 1.47–1.44 (m,
2
H), 0.96 (t, 3H, J = 7.4 Hz)
13
C NMR (125 MHz, CDCl3), δ: 197.3, 166.6, 143.0, 138.8, 137.9, 128.8, 128.1, 120.8, 64.7, 30.7,
6.7, 19.2, 13.7
2
a) The 1H NMR and 13C NMR spectra were recorded on a Bruker FT-NMR 500 MHZ spectrometer (Germany).
The coupling of aryl iodides and bromides was su-
perior and afforded the desired products in good to
excellent yields (Entries 1–15, Table 2). As expected,
the catalytic activity depended on the halide, while
the electron-withdrawing groups on the aryl ring in-
creased the reaction rate. The activity decreases in
order: COCH3, H, OCH3, suggesting that the rate-
determining step in the Heck reaction is the oxida-
tive addition of the aryl halides to the palladium cat-
alyst. Using 4-substituted aryl iodides and bromides
led to good yields of the desired products. Although,
due to the crowding effect of aryl halides substituted
at the ortho position, 2-methoxy iodo- bromobenzene
provided only low yields. The reaction of styrene oc-
curred easily and E-stilbene was obtained in a good
yield (87 %).
Spectral and physico–chemical data of some of the
Heck reaction products are shown in Tables 3 and 4.
The scope of this method on aryl chlorides was also
investigated; however, the coupling of 4-acetylchloro-
benzene with styrene and butyl acrylate resulted in
low yields (19 % and 25 %, respectively) even when
the reaction time was extended from 6 h to 24 h.
Nonetheless, the combination of Pd(OAc)2 and D-
GlcN showed no activity for the Heck coupling reac-
tion of chlorobenzene and only trace amounts of the
coupling product were obtained (Entry 19, Table 2).
This proved to be the only limitation of the method
presented.
additive is inexpensive, air-stable and easy to avail-
able.
Acknowledgements. M. Amini thanks the Research Council
of the University of Maragheh for funding of this work.
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