Cu(OAc)2-Et3N mediated oxidative coupling of α-azido ketones with pyridinium ylides: utilizing in situ generated imines for regioselective synthesis of imidazo[1,2-a]pyridines

Article abstract of DOI:10.1039/c5cc00815h

Phenacyl azides were reacted with pyridinium ylides in the presence of Cu(OAc)₂ (2 mol%) and Et₃N utilizing molecular oxygen as a green oxidant to yield imidazo[1,2-a]pyridines in exclusive regioselectivity. Following the optimized p

Full text of DOI:10.1039/c5cc00815h

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DOI: 10.1039/C5CC00815H
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ARTICLE TYPE
Cu(OAc)2/Et3N mediated oxidative coupling of αꢀazido ketones with
pyridinium ylides: Utilizing in situ generated imines for regioselective
synthesis of imidazo[1,2ꢀa]pyridines
Ahmed Kamal,*a,b Chada Narsimha Reddy,a Malasala Satyaveni,a D. Chandrasekhar,aJagadeesh Babu
5
Nanubolu,c Kiran Kumar Singarapud and Ram Awatar Maurya*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
sensitive reagents may not be used and the inconvenient access of
aryl glyoxals. A careful survey of the literature revealed that the
45 application of these reactive imines in organic synthesis is largely
unexplored. Only a few scattered examples mentioning their
dimerization, inter and intramolecular cyclization in several ways
leading to the formation of pyroles, imidazoles, and pyridines are
reported.5 Exploring the reactivity of these imines towards 1,3ꢀ
50 dipoles, which to the best of our knowledge is not investigated so
far, might open a new window for diverse valuable heterocycles.
We envisioned that the in situ generated imines II (from readily
available phenacyl azides) might be trapped by 1,3ꢀdipoles to
yield numerous heterocycles III (Scheme 2).
Phenacyl azides were reacted with pyridinium ylides in the
presence of Cu(OAc)2 (2 mol%) and Et3N utilizing molecular
10 oxygen as a green oxidant to yield imidazo[1,2ꢀa]pyridines in
exclusive regioselectivity. Following the optimized protocol,
28 different fused heterocycles were synthesized in high yields
(71ꢀ92%). In order to get mechanistic insight of the reaction,
a few control experiments were carried out and the role of
15 copper salt was discussed.
αꢀAzido ketones I are very important building blocks in organic
chemistry.1 In contrast to simple alkyl or aryl azides, these
organic synthons exhibit many peculiar chemical behaviours
which originate mainly from the increased acidity of the αꢀ
20 hydrogen due to the presence of oxo functionality. The synthetic
potential of these reactive species has been utilized in various
inter and intraꢀmolecular fashions to build numerous fine
chemicals, pharmaceuticals and natural products.2 These base
sensitive compounds have long been known to decompose readily
25 after deprotonation yielding highly reactive imines II (Scheme
1).3 Depending on the reaction conditions and structure of the αꢀ
azido ketones, the initially formed azomethine anions are
hydrolyzed, polymerized, or trapped with various electrophiles.
Despite long history, the potential of these reactive imines and
30 therefore of αꢀazido ketones for organic transformations has not
been explored much.
55
X
Y
Z
1,3ꢀdipolar
cycloaddition
X
Z
N3
HN
HN
O
Y
R
O
R
R
O
I
II
Generated in situ
III
Scheme 2. Proposed synthesis of heterocyclic molecules III through 1,3ꢀ
dipolar cycloaddition reaction of the imines II (generated in situ) with
1,3ꢀdipoles
60 For the proof of the concept, pyridinium ylides were taken as
typical 1,3ꢀdipoles. Herein, we disclose the results of
Cu(OAc)2/base mediated coupling of pyridinium ylides,
generated from pyridine and phenacyl bromides, with phenacyl
azides. Imines II were generated in situ and reacted with
65 pyridinium ylides to form cycloadducts which underwent facile
air oxidation yielding pharmaceutically valuable imidazo[1,2ꢀ
a]pyridines.6 Due to their significant medicinal importance,
numerous synthetic protocols for imidazo[1,2ꢀa]pyridines have
been developed.7 Most of these methods rely on the annulations
70 of 2ꢀaminopyridines with various reagents, therefore both
nitrogen atoms of the imidazo[1,2ꢀa]pyridine come from 2ꢀ
aminopyridines. It is notable that the synthetic route described
herein utilizes coupling of pyridines and phenacyl azides to yield
imidazo[1,2ꢀa]pyridines, hence the nitrogen atoms of the product
75 come from two different coupling partners. The current study not
only provides a convenient access to the imidazo[1,2ꢀa]pyridines
but also opens up the possibilities of reacting phenacyl azides
with many other 1,3ꢀdipoles for the synthesis of valuable
intermediates and heterocyclic motifs.
O
O
O
O
O
R
R
E
R
Base
R
N
N
N
N
N
N
R
N
N
N
I
ꢀN2
N
N
E
II
E = Electrophile/Proton
Scheme 1. Base mediated decomposition of αꢀazido ketones I into imines
35 II
Formation of the imine II from αꢀazido ketones under basic
medium was proposed first time by Boyer and Canter.3a
Characterization of such imines under photochemical and acid
catalyzed decomposition of αꢀazido ketones has also been
40 reported.3b Although generation of such imines from phenyl
glyoxal and ammonium salts are reported,4 their synthetic utility
is largely hampered by aqueous reaction medium where water
This journal is © The Royal Society of Chemistry [year]
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DOI: 10.1039/C5CC00815H
At the onset, an ylide of 3ꢀacetylpyridine was taken as the
model 1,3ꢀdipole to test the feasibility of the concept. The
pyridinium salt 1a was prepared by refluxing equimolar mixture
of 3ꢀacetylpyridine 4a and 2ꢀbromoꢀ4′ꢀchloroacetophenone 5a in
and K2CO3) decomposed the azide 2a but the desired product 3a
was not obtained. The azido ketone remained largely unꢀreacted
in the presence of organic bases (DIPEA and Et3N) even after 24
h at ambient temperature. However, we were pleased to achieve
5
EtOAc. Next the crude salt 1a was reacted with phenacyl azide 20 good yields of 3a using 5 mol% Cu(OAc)2 as an additive and 2
2a under various conditions to optimize the formation of
imidazo[1,2ꢀa]pyridine 3a (Table 1).
eq. of Et3N as base (Table 1, entry 7). Better yield of 3a was
obtained by using 3 eq. of Et3N as a base (Table 1, entry 8).
Furthermore, the loading of Cu(OAc)2 could be reduced to 2
mol% without affecting the product yield and reaction time
25 significantly (Table 1, entry 11). Among several solvents
screened, CH2Cl2 was found the best in terms of product yield
and purity. The yield of 3a was not much improved when the
reaction was carried out under oxygen atmosphere (Table 1, entry
12). However, the yield of 3a was drastically decreased when the
30 reaction was performed under nitrogen atmosphere (Table 1,
entry 13). Under nitrogen atmosphere, formation of 3a in very
low yields can be explained by considering oxidation by
Cu(OAc)2 or residual oxygen. AgOAc, AuCl3 and In(OTf)3 were
also attempted for the reaction but the desired product 3a was not
35 formed in these cases (Table 1, entry 14ꢀ16). Cu(OTf)2 and
CuSO4.5H2O were also screened for the reaction but the desired
product 3a was formed in poor yields (Table 1, entry 17ꢀ18). The
combination of inorganic bases and Cu(OAc)2 were also
attempted but the yields of 3a were not satisfactory (Table 1,
40 entry 19ꢀ20). These results indicated that presence of the copper
salt is crucial for the formation of the fused heterocyclic
compound 3a. Furthermore, formation of the only regioisomer 3a
confirmed the exclusive regioselective nature of the reaction.
Et3N/Cu(OAc)2 mediated annulations of 1a with phenacyl
45 azide 2a were better in CH2Cl2 than the same in EtOAc (Table 1).
The pyridinium salt 1a prepared from pyridine and phenacyl
bromide in EtOAc was sufficiently pure for next step reaction.
Therefore, after the formation of 1a was complete the solvent
(EtOAc) was removed under reduced pressure and the same
50 reaction vessel was charged with CH2Cl2, Cu(OAc)2 and
phenacyl azide 2a for further transformations. Thus, a pseudo
threeꢀcomponent, oneꢀpot strategy for the formation of
imidazo[1,2ꢀa]pyridine 3a could be achieved. The same strategy
was further utilised for the synthesis of a series of imidazo[1,2ꢀ
55 a]pyridines (Table 2). The protocol worked well with a series of
phenacyl azides bearing halogen and electron withdrawing as
well as electron donating groups in their aryl part leading to the
formation of imidazo[1,2ꢀa]pyridines in high yields (75ꢀ85%).
The reaction was not successful with ethyl azidoacetate. It can be
60 attributed to the difference in the acidity of αꢀhydrogen atoms of
ketones and esters, which might influence the mode of the
decomposition of corresponding azides. The difference in the
reactivity patterns of αꢀazido ketones and αꢀazido esters has
already been reported by many researchers.1a The reaction also
65 worked well with aliphatic αꢀazido ketone giving a good yield
(71%) of the corresponding imidazo[1,2ꢀa]pyridine 3a’ (Table 2,
entry 27).
Table 1. Optimization of the formation of imidazo[1,2ꢀa]pyridine 3a via
10 the reaction phenacyl azide 2a with pyridinium salt 1a a
Entry
Base
(loading)
Additive
(loading)
Solvent
Time
(h)
Yield of 3a
(%)b
1
2c
3
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
24
24
24
24
24
0
0
0
0
0
ꢀꢀ
NaOH (2 eq.)
K2CO3 (2 eq.)
4
5
DIPEA (2
eq.)
6
7
Et3N (2 eq.)
Et3N (2 eq.)
ꢀꢀ
EtOAc
EtOAc
24
6
0
Cu(OAc)2
(5 mol%)
Cu(OAc)2
(5 mol%)
Cu(OAc)2
(5 mol%)
Cu(OAc)2
(5 mol%)
Cu(OAc)2
(2 mol%)
Cu(OAc)2
(2 mol%)
(61)
8
9
Et3N (3 eq.)
Et3N (3 eq.)
Et3N (3 eq.)
Et3N (3 eq.)
Et3N (3 eq.)
Et3N (3 eq.)
Et3N (2 eq.)
Et3N (2 eq.)
Et3N (3 eq.)
Et3N (3 eq.)
Et3N (3 eq.)
EtOAc
THF
6
2
2
2
2
2
6
6
2
2
(72)
(55)
(83)
(83 )
(82)
10
10
11
12 d
13 e
14
15
16
17
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Cu(OAc)2
(5 mol%)
AgOAc
0
(5 mol%)
AuCl3
0
(5 mol%)
In(OTf)3
(5 mol%)
Cu(OTf)2
(5 mol%)
0
30
18
19
CuSO4.5H2O
(5 mol%)
CH2Cl2
CH2Cl2
2
2
8
K2CO3 (3
eq.)
Cu(OAc)2
(5 mol%)
Cu(OAc)2
(5 mol%)
34
20
NaOH (3 eq.)
CH2Cl2
2
64
a Reaction conditions: Pyridinium salt 1a (1 mmol), azide 2a (1.1 mmol), solvent
15 mL, base, additive, rt, stir, open atmosphere. b Yields were determined by 1
H
NMR analysis of the crude reaction product using anisole as internal standard;
c
A number of pyridinium ylides prepared from 3ꢀacetyl
pyridine, 3ꢀethoxycarbonyl pyridine, 4ꢀacetyl pyridine and
70 phenacyl bromides bearing halogen and electron withdrawing as
well as electron releasing groups in their aryl part gave high
yields of desired imidazo[1,2ꢀa]pyridines (Table 2, entry 1ꢀ24 &
27). Furthermore, pyridinium ylides derived from 3ꢀacetyl
Values in parentheses represent isolated yields. Reaction was done under
d
e
reflux condition. The reaction was done under oxygen atmosphere. The
reaction was done under nitrogen atmosphere.
No reaction between the pyridinium salt 1a and azide 2a was
observed in absence of a base either at ambient temperature or
15 reflux conditions (Table 1, entry 1, 2). Inorganic bases (NaOH
2
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DOI: 10.1039/C5CC00815H
pyridine and aliphatic αꢀbromo ketones such as 1ꢀadamantyl
bromomethyl ketone and 1ꢀbromopinacolone were also
successfully utilised for the formation of corresponding
imidazo[1,2ꢀa]pyridines (Table 2, entry 25ꢀ26).
The structure of the products 3aꢀ3b’ was confirmed by
MS/HRMS, IR, 1H and 13C NMR spectra. Further confirmation of
the regioselectivity was done by 2D NOESY of compound 3a and
20 single crystal Xꢀray analysis of compound 3d (For details of 2D
NMR and Xꢀray analysis, see supporting information).
5
The reaction was not successful with pyridine, 3ꢀ
bromopyridine
dimethylaminopyridine) and yielded
However, the corresponding reaction with quinolinium ylide 1b
gave a clean product 3b’ in 75% yield (Scheme 3).
or
electron
donating
pyridines
complex mixture.
(4ꢀ
In order to expand the synthetic competence of our strategy, a
gramꢀscale synthesis of 3a was performed under the standard
conditions. The desired imidazo[1,2ꢀa]pyridine 3a was isolated in
25 92% yield which indicates there is a potential industrial
application (Scheme 4).
a
10
Table 2. Scope of the oneꢀpot synthesis of imidazo[1,2ꢀa]pyridines via
the reaction of pyridines, αꢀbromo ketones and αꢀazido ketones a
Scheme 4. Synthetic application: Gram scale reaction
In order to get a better understanding of the annulations process,
30 we planned to study the role of copper salt by taking the reaction
of pyridinium salt 1c with phenacyl azide 2b as a model reaction
(Scheme 5). We were particularly interested in characterizing the
product of copperꢀfree reaction. After screening several
conditions, a good yield of enaminone 6 was obtained by
35 refluxing the reaction mixture in THF using 3 eq. of K2CO3.
En
try
R
R1
R2
Produ
ct
Yield
(%)b
1
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOOEt
3ꢀCOOEt
3ꢀCOOEt
4ꢀ COCH3
4ꢀ COCH3
4ꢀ COCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
3ꢀCOCH3
4ꢀClꢀC6H4
4ꢀClꢀC6H4
4ꢀClꢀC6H4
C6H5
C6H5
4ꢀClꢀC6H4
4ꢀCH3ꢀC6H4
C6H5
3a
3b
3c
3d
3e
3f
83
80
84
77
79
85
82
75
77
83
76
82
85
83
83
80
77
79
81
85
79
82
75
79
77
80
71
2
3
O
4
O
N3
5
C6H5
4ꢀClꢀC6H4
C6H5
O
Cl
6
4ꢀPhꢀC6H4
4ꢀNO2ꢀC6H4
4ꢀNO2ꢀC6H4
3ꢀNO2ꢀC6H4
3ꢀNO2ꢀC6H4
3ꢀNO2ꢀC6H4
4ꢀCH3ꢀC6H4
4ꢀFꢀC6H4
2b
N
Br
NH2
O
K2CO3 (3 eq.)
7
C6H5
3g
3h
3i
Cl
THF, Reflux, 12 h
O
6 (71%)
1c
8
4ꢀClꢀC6H4
C6H5
9
Scheme 5. Control experiment: Formation of enaminone 6 under copperꢀ
free conditions
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
4ꢀClꢀC6H4
3ꢀCH3OꢀC6H4
C6H5
3j
3k
3l
Formation of the enaminone 6 in copperꢀfree reaction and
40 imidazo[1,2ꢀa]pyridine 3 in copper mediated reaction might be
explained by a plausible mechanism depicted in Scheme 6. In
4ꢀClꢀC6H4
4ꢀClꢀC6H4
4ꢀClꢀC6H4
4ꢀClꢀC6H4
C6H5
3m
3n
3o
3p
3q
3r
2ꢀNaphthyl
4ꢀCNꢀC6H4
4ꢀCH3ꢀC6H4
4ꢀNO2ꢀC6H4
3ꢀNO2ꢀC6H4
4ꢀPhꢀC6H4
3ꢀNO2ꢀC6H4
4ꢀCNꢀC6H4
4ꢀPhꢀC6H4
C6H5
copperꢀfree reaction, imine
7
is generated from the
decomposition of phenacyl azide 2 by potassium carbonate. Next
it is attacked by pyridinium ylide 8 leading to the formation of an
45 intermediate 9. In the intermediate 9, intramolecular attack of the
amine (hard base) to the pyridinium imine (soft acid) is
disfavored.8 Such reactions are generally reversible and to the
best of our knowledge, they are not known to proceed under basic
conditions. Therefore under basic and reflux conditions, the
50 pyridyl group is eliminated yielding a thermodynamically stable
enaminone 6.
In the presence of Et3N and Cu(OAc)2, the phenacyl azide 2
decomposes to yield a chelated imine 10. The chelated imine is
attacked by pyridinium ylide 8 yielding an intermediate 11 which
55 rapidly isomerizes to another intermediate 12. Due to the
chelation, amine group (NH) of the intermediate 12 behaves as a
soft base and attacks the pyrinium imine (soft acid) to yield
another intermediate 13. Although Scheme 6 shows the formation
C6H5
C6H5
3s
3t
4ꢀClꢀC6H4
4ꢀClꢀC6H4
4ꢀClꢀC6H4
4ꢀCNꢀC6H4
4ꢀCNꢀC6H4
4ꢀPhꢀC6H4
4ꢀCH3ꢀC6H4
(CH3)3C
3u
3v
3w
3x
3y
3z
3a’
4ꢀClꢀC6H4
1ꢀadamantyl
(CH3)3C
27
3ꢀNO2ꢀC6H4
a
Reaction conditions: i) Pyridine 4 (1 mmol), αꢀbromo ketones 5 (1 mmol),
EtOAc (20 mL), reflux, 24 h, then evaporate the solvent under reduced
pressure, nextꢀ ii) azide 2 (1.1 mmol), CH2Cl2 15 mL, Et3N (3 mmol), Cu(OAc)2
(2 mol%), stir, open atmosphere. b Isolated yields.
of 13 by stepꢀwise process,
a concerted [3+2] dipolar
60 cycloaddition process for the same cannot be discounted. In the
presence of atmospheric oxygen, the intermediate 13 rapidly
aromatizes to imidazo[1,2ꢀa]pyridine 3.
15
Scheme 3. Reaction of phenacyl azides 2a with quinolinium ylide 1b
This journal is © The Royal Society of Chemistry [year]
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b
O
Catalytic Chemistry Chair, Chemistry Department, College of Science,
King Saud University, Riyadh 11451, Saudi Arabia
Centre for X-Ray Crystallography, CSIR-Indian Institute of Chemical
O
R
8
N
NH
R2
R2
X
c
N
O
H
7
R1
6
H2N
R2
Technology, Hyderabad-500007, India
ꢀN2
N
d
40 Centre for Nuclear Magnetic Resonance, CSIR-Indian Institute of
O
O
Chemical Technology, Hyderabad-500007, India
R
9
R2
N
† Electronic Supplementary Information (ESI) available: [general
experimental procedures, NMR data, and single crystal Xꢀray data]. See
DOI: 10.1039/b000000x/
N
N
R1
Br
1
O
45
50
55
60
65
1
a) T. Patonay, K. Konya and E. J. Toth, Chem. Soc. Rev., 2011, 40,
2797; b) S. Brase, C. Gil, K. Knepper and V. Zimmermann, Angew.
Chem. Int. Ed., 2005, 44, 5188.
No copper K2CO3
K2CO3
R
O
Cu
O
Air
[O]
2) For selected recent publications, see: a) R. A. Maurya, P. R. Adiyala,
D. Chandrasekhar, C. N. Reddy, J. S. Kapure and A. Kamal, ACS
Comb. Sci., 2014, 16, 466; b) E. J. Toth, G. Favi, O. A. Attanasi, A.
C. Benyei and T. Patonay, Synlett, 2014, 25, 2001; c) J. S. Dickschat,
H. Reichenbach, I. WagnerꢀDobler and S. Schulz, Eur. J. Org.
Chem., 2005, 4141; d) A. MartinezꢀCastaneda, K. Kedziora, I.
Lavandera, H. RodriguezꢀSolla, C. Concellon and V. del Amo, Chem.
Commun., 2014, 50, 2598; e) A. Cuetos, F. R. Bisogno, I. Lavandera,
and V. Gotor, Chem. Commun., 2013, 49, 2625; f) S. Liu, Y.ꢀM. Cui
and F.ꢀJ. Nan, Org. Lett., 2008, 10, 3765.
3) a) J. H. Boyer and F. C. Canter, Chem. Rev., 1954, 54, 1; b) O. E.
Edwards and K. K. Purushothaman, Canadian J. Chem., 1964, 42,
712; c) T. Patonay, E. JuhaszꢀToth and A. Benyei, Eur. J. Org.
Chem., 2002, 285.
4) P. A. Grieco, S. D. Larsen and W. F. Fobare, Tetrahedron Lett., 1986,
27, 1975.
5) a) X. Fan and Y. Zhang, Tetrahedron Lett., 2002, 43, 1863; b) B.
Batanero, J. Escudero and F. Barba, Org. Lett., 1999, 1, 1521; c) J. H.
Boyer and D. Straw, J. Am. Chem. Soc., 1952, 74, 4506; d) J. Chen,
W. Chen, Y. Yu and G. Zhang, Tetrahedron Lett., 2013, 54, 1572; c)
J. Chen, H. Ni, W. Chen, G. Zhang and Y. Yu, Tetrahedron, 2013,
69, 8069.
70 6) For selected recent publications over various biological activities of
imidazo[1,2ꢀa]pyridines, see: a) Y. B. Kim, C. W. Kang, S.
Ranatunga, H. Yang, S. M. Sebti and J. R. Del Valle, Bioorganic
Med. Chem. Lett., 2014, 24, 4650; b) G. C. Moraski, A. G. Oliver, L.
D. Markley, S. Cho, S. G. Franzblau and M. J. Miller, Bioorganic
N
R2
O
3
N
R2
N
N
N
R1
N
2
R
R1
8
O
ꢀEt3NH
ꢀN2
Cu(OAc)2
Et3N
13
O
Cu
O
Cu
8
NH
R2
O
N
R2
O
O
Cu
N
H
R2
N
N
R
R1
R
10
R1
12
11
Scheme 6. Proposed mechanism for the formation of imidazo[1,2ꢀ
a]pyridines 3 via copper mediated reaction and enaminone 6 in copperꢀ
free condition
5
Conclusions
In conclusion, the reactivity of a class of αꢀazido ketones towards
pyridinium ylides for the formation of pharmaceutically
important fused heterocycles has been explored for the first time.
10 Et3N/Cu(OAc)2 mediated oneꢀpot strategy for the synthesis of
valuable imidazo[1,2ꢀa]pyridines was developed and 28 different
chemical entities were synthesized in high yields (71ꢀ92%). The
experimental results revealed that copper salt plays an important
role for controlling the reactivity of in situ generated imines
15 towards pyridinium ylides. The reaction and the oneꢀpot protocol
we developed has the potential for scaleꢀup production of
imidazo[1,2ꢀa]pyridines. This novel reactivity pattern of αꢀazido
ketones towards 1,3ꢀdipoles opens up the possibilities of
synthesizing numerous valuable heterocycles as well as fine
20 chemicals in a manner that is atom economical, convenient and
scalable. Coupling of the phenacyl azides with other 1,3ꢀdipoles
is currently under investigation and the results will be
communicated in near future.
75
80
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25 Acknowledgment
R.A.M. is thankful to Department of Science & Technology,
India for financial support (GAP 0378 & GAP 0470). Financial
support in part from 12th Five Year Plan Project “Affordable
Cancer Therapeutics (ACTꢀCSCꢀ0301)” is also acknowledged.
30 C.N.R. acknowledges CSIRꢀ New Delhi, and M. S. acknowledges
NIPER India for financial support.
100 8) Although the observed reactivity was explained by Hard and Soft Acid
Base concept, HSAB theory was recently criticized, see: H. Mayr, M.
Breugst and A. R. Ofial, Angew. Chem. Int. Ed., 2011, 50, 6470.
Notes and references
a
Department of Medicinal Chemistry and Pharmacology, CSIR-Indian
Institute of Chemical Technology, Hyderabad-500007, India, E-mail:
35 ramaurya@iict.res.in (RA Maurya); ahmedkamal@iict.res.in (A Kamal)
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