Synergistic dual activation catalysis by palladium nanoparticles for epoxide ring opening with phenols

Article abstract of DOI:10.1039/c3cc42507j

Synergistic dual activation catalysis has been devised for epoxide phenolysis wherein palladium nanoparticles induce electrophilic activation via coordination with the epoxide oxygen followed by nucleophilic activation through anion-π interaction with the aromatic ring of the phenol, and water (reaction medium) also renders assistance through 'epoxide-phenol' dual activation.

Full text of DOI:10.1039/c3cc42507j

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Synergistic Dual Activation Catalysis by Palladium Nanoparticles for
Epoxide Ring Opening with Phenols
Kapileswar Seth, Sudipta Raha Roy, Bhavin V. Pipaliya, and Asit K. Chakraborti*
Received (in XXX, XXX)
First published on
DOI:
no epoxide phenolysis takes place. The use of sodium 4-
methoxyphenolate (25 mol%) instead of K2CO3 gave 10%
yield (entry 1, footnote e) and 11% yield was obtained when
all components (K2CO3, TBAB, PdCl2, 1a and 2a) were added
55 at a time (entry 1, footnote f). In these cases the PdNP
formation was not observed (absence of blackening of the
reaction mixture).
5
Synergistic dual activation catalysis has been devised for epoxide
phenolysis wherein palladium nanoparticles induce electrophilic
activation via coordination with the epoxide oxygen followed by
nucleophilic activation through anion-π interaction with the
aromatic ring of the phenol and water (reaction medium) also
10 renders assistance through ‘epoxide-phenol’ dual activation.
Table 1. The phenolysis of the epoxide ring of 1a with 2a to form 3a.a
Epoxide ring opening by phenols is a challenging task due
to the poor nucleophilicity of phenols and necessitates
suitable activation protocol. The nucleophilic activation
strategy requires basic conditions and use a large amount of
15 the phenolate or the base and stoichiometric or excess
quantities of a phase transfer catalyst.1 A more effective
strategy has been reported for activation of the electrophile
(epoxide) and the nucleophile (phenol) through metal Lewis
acid-based catalyst system in which the central metal ion
20 activates the epoxide and the nucleophilic activation is
achieved through a basic moiety present either as an integral
structural feature (covalently attached to the metal ion) of the
catalyst system2 or an associated counter anion but requires
excess of the epoxide.3 Herein we report a new model for
25 electrophile-nucleophile synergistic dual activation catalysis
by palladium nanoparticles (PdNP).
In a model study, the 4-chlorophenyl glycidyl ether 1a was
treated with 4-methoxyphenol 2a under various conditions
(Table 1). The best result was obtained in the presence of
30 PdCl2 (1 mol%), K2CO3 (25 mol%), and TBAB (25 mol%) at
60 °C in water after 3.5 h (entry 1). The PdCl2 alone was not
effective (entry 3) and needs to be present alongwith K2CO3
and TBAB as the reaction did not occur using either K2CO3
(entry 4) or TBAB (entry 5). The reaction mixture becomes
35 dark black when both K2CO3 and TBAB are present along
with PdCl2. This indicated the formation of PdNP and was
supported by the absorption at 283 nm in the UV.4,5 The TEM
analysis of the reaction mixture identified PdNPs (≈ 30 nm)
and was characterised by EDX spectra.5 The TBAB is
40 required as the stabilizer to prevent agglomeration of the
PdNPs through electrosteric stabilisation6 as otherwise poor
result was obtained even using one equiv of K2CO3 (entries 4
and 14). The lack of formation of any significant amount of
3a in using stoichiometric amount of K2CO3 in the presence
45 (entry 4) and absence (entry 6) of PdCl2 suggests that it is not
a base-promoted (pKa driven) event1 to generate the phenolate
anion and that a distinct catalytic effect is rendered by the
PdNP. The role of K2CO3 can be envisaged as a reducing
agent7 to form the PdNP. In the absence of K2CO3 (entry 5) or
50 replacement of K2CO3 by a Brönsted acid (entry 1, footnote d)
60 Entry
Pre-catalyst
(mol %)b
PdCl2 (1)
None
PdCl2 (1)
PdCl2 (1)
K2CO3
TBAB
Yield
(%)c
(equiv)b (equiv)b
1
2
3
65 4
5
6
0.25
0.25
None
1.0
None
1.0
0.25
0.25
0.25
0.25
0.25
0.1
0.25
1.0
0.25
0.25
0.25
0.25
0.25
0.25
None
None
1.0
None
0.25
0.25
0.25
0.25
0.25
0.1
0.25
None
0.25
0.25
0.25
0.25
74d,e,f
10
0
10
0
0
PdCl2 (1)
None
7
8
PdCl2 (1)
PdCl2 (1)
PdCl2 (1)
PdCl2 (0.5)
PdCl2 (2)
PdCl2 (1)
Pd(OAc)2 (1)
Pd(OAc)2 (1)
Na2PdCl4 (1)
Pd(PPh3)2Cl2 (1)
Pd(PPh3)4 (1)
Pd/C (1)
18g
59h
78i
53
75
54
70
16
20
18
53
20
70 9
10
11
12
13
75 14
15
16
17
18
80 aThe mixture of K2CO3 (except for entries 3 and 5), the pre-catalyst
(except for entries 2 and 6) and TBAB (except for entries 3, 4, 6, and 14)
in water (8 mL) was stirred magnetically for 15 min followed by addition
of 1a (2 mmol) and 2a (2 mmol) at 60 °C (except for entry 7) and stirring
for further 3.5 h (except for entries 8 and 9). bThe amount of the pre-
85 catalyst used with respect to 3a. cIsolated yield of 3a. dNo epoxide
phenolysis took place in using pivalic acid (25 mol%) instead of K2CO3.
e3a was formed in 10% yield in using pre-formed sodium 4-
f
methoxyphenolate (25 mol%) instead of K2CO3. 3a was formed in 11%
yield when the reaction was performed in mixing K2CO3, PdCl2, TBAB,
90 1a and 2a at a time. gThe reaction was performed at 40 °C. hThe reaction
was carried out for 1.5 h. iThe reaction carried out for overnight.
Other Pd compounds were used (entries 13-17) and only
Pd(OAc)2 gave comparable yield (entry 13). The necessity to
use TBAB was further indicated by the fact that when the
95 reaction was performed using Pd(OAc)2 (1 mol%) in the
absence of TBAB poor result was obtained even using one
equiv of K2CO3 (entry 14) and further demonstrated that the
reaction is not pKa driven (formation of phenolate anion). The
use of Pd(0) species such as Pd(PPh3)4 (entry 17) and
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Table 2. The PdNP-catalysed phenolysis of epoxides with phenols.a
palladium adsorbed on carbon (entry 18) indicate the specific
activation rendered by the PdNP. Various anionic (SDS,
SDOSS), cationic (tetrabutylammonium salts, CTAB, and
Triton X 100), and neutral (Tween 40, Span 80 and PEGs8)
surfactants were used as stabiliser.5 In general the
tetraalkylammonium halides exhibited prominent effect and
TBAB afforded the best result. Replacement of K2CO3 by
other alkali metal carbonates (Li, Na, and Cs) led to lesser
yields (63-70%). The other bases such as KOH, LiOH,
10 KHCO3 and other potassium salts such as KBr and KI were
also less effective (38-59% yield).5 The solvent played a
crucial role and the best results were obtained in water. Other
solvents such as hexane, PhMe, THF, dioxane, MeCN, DCE,
MeNO2 were either ineffective or afforded inferior yields. The
15 use of PEG 400 gave poor yields (22-25%)5 in the presence or
absence of TBAB.8 The amount of water also has some
implication on the yield and 4 mL/mmol of the substrate was
found to be the optimal.5
The general applicability is demonstrated by Table 2. The
20 reactions with phenols bearing electron withdrawing
substituents (entries 4-8, 11, 12, 16, 18, 20, and 21) took
lesser time indicating that the reaction is not dictated by the
relative nucleophilicity of the phenol (or phenolate anion).
The presence of ortho substituent exhibited steric hindrance as
25 the reactions required longer time (entries 15, 17, and 19).
The steric effect is also reflected by the longer time required
with 1-naphthol than that of 2-naphthol (entries 22 and 23).
No competitive epoxide9/ester hydrolysis was observed
(entries 6 and 20) demonstrating chemoselectivity. The PdNPs
30 can be recycled up to five consecutive uses to afford 72, 71,
69, 66, and 60% yields of 3a, respectively.5
For evaluating regioselectivity, styrene oxide 4 was treated
with a few representative electron rich and electron deficient
phenols (Table 3). In each case regioselective formation of the
35 Aα product was observed in contrary to the Aβ product
obtained during the base promoted reactions.1c The
regioselective formation of the Aα product is in conformity
with the regioselectivity observed during the Lewis acid-
catalysed reaction with aromatic amines/thiols.10 These
40 suggest electrophilic activation of the epoxide ring and is
implied by the shorter reaction time and better regioselectivity
with poor nucleophilic phenols (entries 3 and 4).
Entry Epoxide
Phenol
Time
(h)
Yield
(%)b
5
55
1
2
3
4
Ar = 4-Cl-C6H4
R1 = R2 = H
3.5
83
74
82
86
86
89
86
88
86
84c
91d
90
87
82
87
89
82
87
84
88
87
R1 = H, R2 = OCH3 3.5
R1 = H, R2 = Br
3
2
2
R1 = H, R2 = CHO
R1 = H, R2 = COCH3
60 5
6
7
R1 = H, R2 = CO2CH3 2.5
R1 = H, R2 = CN
R1 = H, R2 = NO2
R1 = R2 = H
2.5
2
3
3
2
8
9
Ar = 4-COCH3-C6H4
Ar = Ph
65 10
11
12
13
14
70 15
16
17
18
19
75 20
21
R1 = H, R2 = OCH3
R1 = H, R2 = NO2
R1 = H, R2 = COCH3
R1 = R2 = H
2
3.5
R1 = H, R2 = OCH3 3.5
R1 = OCH3, R2 = H
R1 = H, R2 = CHO
R1 = CHO, R2 = H
R1 = H, R2 = COCH3
4
2
4.5
2
R1 = COCH3, R2 = H 4.5
R1 = H, R2 = CO2CH3 2
R1 = H, R2 = NO2
2
4
22
90
23
24
2
4
89
69
89
R = tBu
R1 = H, R2 = OCH3
80 25
Ar = 2-Furfuryl
R1 = H, R2 = OCH3 3.5
26
27
Ar = 1-Naphthyl
4.5
4.5
83
88
aThe mixture of PdCl2 (1 mol%), K2CO3 (25 mol%), and TBAB (25
mol%) in water (8 mL) was stirred magnetically at 60 oC for 15 min
85 followed by addition of the epoxide (2 mmol) and the phenol (2 mmol).
bThe isolated yield of the desired product. cThe reaction of the (S)-4-
acetyl phenyl glycidyl ether (optical purity 80.06%) gave the
corresponding product in 85% yield with 76.85% ee. dThe reaction of the
(S)-4-acetyl phenyl glycidyl ether (optical purity 80.06%) gave the
90 corresponding product in 91% yield with 82.79% ee.
Table 3. PdNP-Catalysed regioselective ring opening of 4 with phenols.a
The applicability of the PdNP-catalyzed epoxide phenolysis
is demonstrated by synthesis of a few representative drugs
45 guaifenesin (5) used for the treatment of cough and cold,
mefenesin (6) and chlorofenesin (7) used as muscle relaxants
by phenolysis of glycidol (8) with appropriate phenol (Scheme
1).
Entry Phenol
Time
(h)
4.5
3
2.5
2.5
Ratio
Yield
(%)c
86 (54)
71 (48)
70 (51)
81 (60)
95
(Aα : Aβ)b
1
2
3
4
R = OCH3
R = Br
R = CN
R = NO2
65 : 35
69 : 31
74 : 26
75 : 25
100 aThe mixture of PdCl2 (1 mol%), K2CO3 (25 mol%), and TBAB (25
mol%) in water (8 mL) was stirred magnetically at 60 oC for 15 min
b
50
Scheme 1. Synthesis of a few representative drug molecules.
followed by addition of 4 (2 mmol) and the phenol (2 mmol). The α/β
c
ratio was determined by GCMS. Isolated yield of the mixture of α- and
β- regioisomers with the yield of the purified α-isomer in the parenthesis.
105
2
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The necessity of the PdNP as the catalyst and water as the
Notes and references
reaction medium suggest specific role played by the PdNP and
water in epoxide phenolysis. The PdNP activates the epoxide
ring through coordination with one of the lone pair of
electrons of the epoxide ring oxygen.11 The rate enhancement
of organic reaction in water has been popularly attributed to
the hydrogen bonding (HB) effect.12 The water molecule
further activates the epoxide through HB formation13 with the
second lone pair of electrons of the epoxide ring oxygen. The
55 aDepartment of Medicinal Chemistry, National Institute of
Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S.
Nagar 160 062, Punjab, India. E-mail: akchakraborti@niper.ac.in;
akchakraborti@rediffmail.com
† Electronic Supplementary Information (ESI) available: Spectroscopic
60 data of all compounds, scanned spectra of new compounds. See
DOI: 10.1039/b000000x/
5
1
(a) B. Das, M. Krishnaiah, P. Thirupathi and K. Laxminarayana,
Tetrahedron Lett., 2007, 48, 4263; (b) M. A. Brimble, Y.-C.
(William) Liu and M. Trzoss, Synthesis, 2007, 1392; (c) K. Surendra,
N. S. Krishnaveni, Y. V. D. Nageswar and K. Rama Rao, J. Org.
Chem., 2003, 68, 4994; (d) Epoxide phenolysis catalysed by
polystyrene-supported strong base requires prolonged reaction time
(A. Zvagulis, S. Bonollo, D. Lanari, F. Pizzo and L. Vaccaro, Adv.
Synth. Catal., 2010, 352, 2489).
10 oxygen atom of the water molecule in turn forms HB with the
OH of the phenol and induces nucleophilic activation14 and
brings the phenolic oxygen in close proximity to the activated
65
epoxide ring for nucleophilic attack.
A charge transfer
interaction between the electron rich PdNP and the aromatic
15 ring of the phenol15 provides rigidity to the transition state I
(Scheme 2). Thus, the PdNP and water constitute a synergistic
dual activation model for simultaneous activation of the
epoxide and the phenol to promote the epoxide phenolysis.
70 2 S. Matsunaga, J. Das, J. Roels, E. M. Vogl, N. Yamamoto, T. Iida, K.
Yamaguchi and M. Shibasaki, J. Am. Chem. Soc., 2000, 122, 2252.
3
(a) D. N. Annis and E. N. Jacobsen, J. Am. Chem. Soc., 1999, 121,
4147; (b) Extension of the similar strategy using porphyrin-based
ligand reports GC-based conversion (K. Venkatasubbaiah, X. Zhu, E.
Kays, K. I. Hardcastle and C. W. Jones, ACS Catal., 2011, 1, 489).
J. Xu, A. R. Wilson, A. R. Rathmell, J. Howe, M. Chi and B. J.
Wiley, ACS Nano, 2011, 5, 6119.
75
80
4
5
6
See supporting information.
(a) D. Astruc, F. Lu and J. R. Aranzaes, Angew. Chem. Int. Ed., 2005,
44, 7852; (b) A. Roucoux, J. Schultz and H. Patin, Chem. Rev., 2002,
102, 3757.
20
Scheme 2. Synergistic epoxide-phenol dual activation by PdNP and
7
(a) R. E. Huie, C. L. Clifton and P. Neta, Radiat. Phys. Chem., 1991,
38, 477; (b) B. G. Ershov, E. Janata, M. Michaelis and A. Henglein,
J. Phys. Chem., 1991, 95, 8996.
water.
The poor nucleophilicity of the phenolic hydroxyl group
requires assistance by Lewis/Brönsted acids to activate the
electrophile (leaving group) that results in C-C bond
85 8 W. Han, C. Liu and Z. Jin, Adv. Synth. Catal., 2008, 350, 501.
9
M. Tokunga, J. F. Larrow, F. Kakiuchi and E. N. Jacobsen, Science,
1997, 277, 936.
25 formation through the para-position of the phenolic moiety.16
No C-C bond formation between the phenol and the epoxide
moiety takes place and signifies the involvement of the
hydrogen-bonded structure I as it would direct C-O bond
formation involving the phenolic OH group and the epoxide
30 ring and would not facilitate any C-C bond formation with the
phenolic moiety. The lesser reaction time required for phenols
with electron withdrawing group is due to their better HB
donor ability as well as better electronic charge acceptor
ability (through the anionic-π interaction with the electron
35 rich PdNP) in forming a more rigid transition state I. The
implication of HB involving the phenolic OH group is realised
by the fact that no epoxide alcoholysis took place in replacing
the phenol separately by MeOH, EtOH, and benzyl alcohol.
The 83:17 selectivity towards the epoxide phenolysis product
40 of 1a with 4-nitrophenol during the treatment of 1a with
equimolar mixture of 4-methoxyphenol and 4-nitrophenol
provided further evidence for the involvement of hydrogen
bond of the phenolic OH group in the transition state (Scheme
2).5
10 (a) B. Pujala, S. Rana and A. K. Chakraborti, J. Org. Chem., 2011,
76, 8768; (b) Shivani, B. Pujala and A. K. Chakraborti, J. Org.
Chem., 2007, 72, 3713; (c) Shivani and A. K. Chakraborti, J. Mol.
Catal. A: Chem., 2007, 263, 137; (d) A. K. Chakraborti, A.
Kondaskar and S. Rudrawar, Tetrahedron, 2004, 60, 9085; (e) A. K.
Chakraborti, S. Rudrawar and A. Kondaskar, Eur. J. Org. Chem.,
2004, 3597; (f) A. K. Chakraborti, S. Rudrawar and A. Kondaskar,
Org. Biomol. Chem., 2004, 2, 1277; (g) A. K. Chakraborti and A.
Kondaskar, Tetrahedron Lett., 2003, 44, 8315.
11 The AgNPs activate sulfur in organosulfur compounds [W. Gan, B.
Xu and H.-L. Dai, Angew. Chem. Int. Ed., 2011, 50, 6622].
12 (a) Y. Zheng and J. Zhang, ChemPhysChem, 2010, 11, 65; (b) Jung,
Y. and R. A. Marcus, J. Am. Chem. Soc., 2007, 129, 5492.
90
95
100
13 (a) D. N. Kommi, D. Kumar, K. Seth and A. K. Chakraborti, Org.
Lett., 2013, 15, 1158; (b) D. N. Kommi, D. Kumar and A. K.
Chakraborti, Green Chem., 2013, 15, 756; (c) I. Viotijevic and T. F.
Jamison, Science, 2007, 317, 1189.
105 14 HB-assisted dual activation by water for other organic reactions [(a)
D. N. Kommi, P. S. Jadhavar, D. Kumar and A. K. Chakraborti,
Green Chem., 2013, 15, 798; (b) D. N. Kommi, D. Kumar, R. Bansal,
R. Chebolu and A. K. Chakraborti, Green Chem., 2012, 14, 3329; (c)
E. Vohringer-Martinez, B. Hansmann, H. Hernandez, J. S. Francisco,
110
J. Troe and B. Abel, Science, 2007, 315, 497; (d) S. V. Chankeshwara
and A. K. Chakraborti, Org. Lett., 2006, 8, 3259; (e) G. L. Khatik, R.
Kumar and A. K. Chakraborti, Org. Lett., 2006, 8, 2433; (f) A. K.
Chakraborti, S. Rudrawar, K. B. Jadhav, G. Kaur and S. V.
Chankeshwara, Green Chem., 2007, 9, 1335].
45
In conclusions, a new model for epoxide-phenol dual
activation through the synergistic action of PdNP and water
has been devised to provide an efficient protocol for epoxide
phenolysis that finds application for the synthesis of drug
molecules. This work represents the first example of metal
115 15 Cation-π interactions between aromatic molecules and NP surface-
bound Au+ [A. Kumar, S. Mandal, S. P. Mathew, P. R. Selvakannan,
A. B. Mandale, R. V. Chaudhari and M. Sastry, Langmuir, 2002, 18,
6478].
50 NP-catalysed epoxide ring activation.
16 (a) C. Piemontesi, Q. Wang and J. Zhu, Org. Biomol. Chem., 2013,
The authors K. S. and S. R. R. thank CSIR (New Delhi) for
senior research fellowships and B. V. P. thanks UGC (New
Delhi) for junior research fellowship.
120
11, 1533; (b) B. Alcaide, P. Almendros, M. T. Quirós; R. López, M.
I. Menéndez and A. Sochacka-Ćwikła, J. Am. Chem. Soc., 2013, 135,
898; (c) F. Zhou, Z.-Y. Cao, J. Zhang, H.-B. Yang and J. Zhou,Chem.
Asian J., 2012, 7, 233.
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