Cooperative catalysis by bovine serum albumin-iodine towards cascade oxidative coupling-C(sp2)-H sulfenylation of indoles/hydroxyaryls with thiophenols on water

Article abstract of DOI:10.1039/c6ob00930a

Cooperative cascade catalysis by bovine serum albumin (BSA)-iodine allows for the first time the performance of C(sp²)-H sulfenylation of indole from readily available thiophenol (-SH bond) via in situ generation/cleavage of disulfide (S-S bond

Full text of DOI:10.1039/c6ob00930a

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Cooperative Catalysis by Bovine Serum Albumin-Iodine Towards
Cascade Oxidative Coupling-C(sp2)-H Sulfenylation of
Indoles/Hydroxyaryls with Thiophenols on water
Received 00th January 20xx,
Accepted 00th January 20xx
Saima,a,b Danish Equbal,a Aditya G. Lavekara and Arun K. Sinhaa,b
*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Cooperative cascade catalysis by Bovine serum albumin (BSA)-Iodine allows for the first time to perform C(sp2)-H
sulfenylation of indole from readily available thiophenol (-SH bond) via insitu generation/cleavage of disulfide (S-S bond) in
air under aqueous conditions whereas BSA or I2 individually does not permit these two steps sequence to occur in same
pot towards C-S bond formation. This green cooperative protocol is extendable for sulfenylation of hydroxyaryls (i.e. 2-
naphthol or 4-hydroxycoumarin) with diverse thiols (aryl/heteroaryl) without using any toxic metal catalysts, bases or
oxidants, thus rendering the process environmentally and economically reliable. Further gram scale synthesis of COX-2
inhibitor (3-(pyridin-2-ylthio)-1H-indole) besides regioselectivity and recyclability (upto four cycles) are the additional
merits of this cooperative cascade bio-chemocatalytic (BSA-I2) protocol. Moreover, HPLC and ESI-MS provide powerful
insights into mechanistic aspects of the above cascade sulfenylation reaction.
catalyst has not been explored so far due to the co-ordination
ability of the sulfur atom with metal catalysts (leading to catalyst
poisoning). Thus this new emerging cooperative biocatalytic
Introduction
In recent years, combination of two or more catalysts belonging
to pole opposite domains have emerged as promising strategies
due to their synergistic-cooperative1 effect thereby enabling access
approach towards formation of C-S bond in aqueous medium
without involvement of metal catalyst would be highly desirable.
Biocatalysis2 has now a days emerged as an elegant approach for
many challenging chemical transformations including cascade
reaction3 under aqueous medium,4 that allows the development of
eco-friendly processes within the basic principle of sustainable
chemistry. Among various biocatalysts2 (viz. whole cells,2i lipases,2c,f
immobilized enzymes2d and proteins2e etc.), bovine serum albumin
(BSA)5 (also known as "Fraction V") an inexpensive, non-enzymatic
transport protein derived from cows, that occupies a unique
position due to its hydrophobic pockets5a thus providing an
environment for a number of organic transformations5,6 including
cascade Aldol/Knoevenagel–Doebner condensation,6a oxidative
coupling–condensation reactions6c besides being compatible with
green solvents like ionic liquid6a and water.6c Thus the outstanding
biocatalytic properties of commercially available and recyclable6a
BSA has further encouraged us to explore its ability as a cooperative
catalyst with chemocatalyst2,7 like molecular iodine8 as a greener
approach towards unprecedented C-S bond formation, although
few reports disclosed molecular interaction9 between BSA and I2.
The C-S10 bond formation via C(sp2)-H functionalization has received
considerable interest in which 3-sulfenylated indole11 occupies an
upmost position due to its potential use as drug candidates in
several disease areas including breast cancer,11a HIV11b and bacterial
diseases11c (Figure 1).
towards diverse synthetic maneuver in
a single chemical
transformation to produce highly effective and selective complex
molecules which cannot be achieved either by individual catalyst or
in comparable yield by sequential reactions of the two catalyst. In
this context, combination of transition metal catalysts1e and
organocatalysts have emerged as a cooperative catalyst for many
unprecedented cascade transformations for the construction of C-C
bond.1c Increasing environmental concerns call for the search of
alternative and efficient biocatalyst1f-h where cytochrome P450 (a
metalloenzyme)1f and an organometallic complex work co-
operatively for cascade olefin metathesis as well as epoxidation in
single pot. To date this so called cooperative catalysis successfully
involves a transition metal catalyst with either organocatalyst1a or
metalloenzyme1f or oxidant1j for carbon-carbon1a-i and carbon-
nitrogen1j bond formation. However, construction of
complimentary carbon-sulfur bond under the influence of
cooperative cascade catalysis by a biocatalyst and a transition metal
a. Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute,
Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031(India).
b. Academy of Scientific and Innovative Research (AcSIR), New Delhi (India)
† E-mail: aksinha08@rediffmail.com, ak.sinha@cdri.res.in
Electronic Supplementary Information (ESI) available: Experimental procedures,
compound characterization data. See DOI: 10.1039/x0xx00000x
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found applicable for sulfenylation of hydroxyaryls20 such as 2-
naphthol and 4-hydroxycoumarin21 (Scheme 1).
Results and discussion
To prove the concept of two different catalytic systems (such as
BSA-Iodine) functioning cooperatively (Table 1), initially a mixture of
indole (1a, 0.25 mmol) and thiophenol (2a, 0.3 mmol) on water (600
µL) under aerobic condition was stirred in presence of BSA (50 mg)
at room temperature for 24h (Table 1, entry 1). GC-MS analysis of
crude product (see S.I.) revealed the presence of unreacted indole
(1a) (Scheme 1) without formation of desired product 3a (i.e. 3-
sulfenylated indole) (Table 1, entry 1) although thiophenol (-SH)
(2a) underwent self-oxidation to diphenyl disulfide (S-S) under the
influence of BSA.6c Similarly, iodine (50 mol%) alone in above
sulfenylation reaction (Table 1, entry 2) also did not provide
product (3a) (Scheme 1) whereas many side products (on GC-MS
basis) along with traces of disulfide were detected (S.I.). To our
Figure 1. Some biologically active 3-sulfenylated indole.
During the synthetic efforts12 for synthesis of 3-sulfenylindoles, a
variety of sulfenylating agents such as N-thioarylphthalimides, 12a
sulfonyl chloride,12b diaryldisulfides12c and aryl thiols12d have been
employed in the presence of either metal catalyst,12b,12d strong base
or Lewis acid12f and toxic organic solvent (DMSO/DMF). In addition,
some metal free protocols13 for sulfenylation of indole using N-
bromosuccinimide,13a
CeCl3/DMF,13b
iodine/DMSO,13c
K2CO3/DMSO13d and sulfinic acid/n-Bu4NI/DCE13e have also been
explored. Very recently, sulfonylhydrazide14 has emerged as an
effective sulfur electrophile for the successful sulfenylation of
indole14a as well as hydroxyaryls14b with catalytic amount of iodine,
while controlling the formation of side products including disulfide
and sulfonothioate.14a However, the low cost15 and commercial
availability of disulfides and thiophenols15a makes them most
demanding reagents for sulfenylation of indole. During our
delight, combination of BSA-Iodine as
a cooperative bio-
chemocatalyst (Table 1, entry 3) provided the desired product (3a)
with 78% yield (on HPLC/GC-MS basis, see S.I.) using indole (0.25
mmol) and thiophenol (0.3 mmol) as a sulfenylating agent on water
under air without the use of any oxidants or organic solvents.22
Further,
a detailed optimization study was conducted where
different biocatalyst (sheep, pig, rabbit etc.)6a,b (Table 1, entries 4-
8), chemocatalyst (such as NIS and KI)8b,12d (Table 1, entries 9-10),
solvents (protic and aprotic)8c,12d (Table 1, entries 11-13) and
variation in temperature (r.t. to 600C)8b (Table 1, entries 14-16)
besides varying molar ratio of iodine (from 50 to 30 mol%)8b (Table
1, entries 17-18) were taken into consideration under aerobic
condition. Interestingly, sulfenylation of indole (1a) under influence
of oxygen filled balloon (Table 1, entry 19) improved the yield of 3a
(upto 89%, by HPLC) in shorter reaction time of 6h at 50oC.
However, determined to further improve the yield of 3a and
encouraged by our recent report23 where phase transfer catalyst
(PTC) improved the yield of cascade Aldol-Suzuki/Heck adduct, we
decided to use TBAB or TBAI (10 mol %) (Table 1, entries 20-21) in
sulfenylation reaction which surprisingly led to an increase in the
yield of 3a upto 96% (HPLC basis) conjointly decreasing the reaction
time to 4h (Table 1, entry 20) under oxygen balloon. As expected
sulfenylation reaction of 1a in catalytic amount of I2 under nitrogen
atmosphere (Table 1, entry 22) or TBAB (Table 1, entry 23) (without
BSA) provided the product 3a in traces. which emphatically
confirms the crucial role of BSA and aerobic condition towards
formation of desired product (3a) in optimum yield (Table 1, entry
20).
Scheme 1. Cooperative cascade catalysis by BSA-Iodine for sulfenylation of
indole and hydroxyaryls (2-naphthol/4-OH coumarin).
investigation and preparation of manuscript, an elegant
heterogeneous catalytic system (Pd/Al2O3/CuCl2)16 utilizing disulfide
for direct C-S bond formation with heteroarenes including indole16
has been reported. However, the main problem of disulfide-based
sulfenylation of indole is prior synthesis of disulfides via the
oxidative coupling of thiols, which means use of additional catalyst
and operational step with low atom economics17 besides possibility
of metal catalyst poisoning18 by thiol thus resulting in lower yield of
the desired 3-sulfenylindoles as well as over oxidation of disulfide
into corresponding sulfone/sulfoxide.10b,14b Against this milieu, it is
a surprise that there is no report on the utilization of biocatalyst for
sulfenylation of indole directly from thiophenol. Hence, we herein
report
a
new bio-chemocatalytic19 route (Scheme 1) for
sulfenylation of indole by cooperative cascade catalysis of BSA-
iodine using thiophenol as a readily available sulfenylating agent in
which the intermediate disulfide (S-S bond) formed by insitu
oxidation of thiophenol, becomes the starting material for the
subsequent C(sp2)-H functionalization of indole through cleavage of
S-S bond in the same pot under aqueous and aerobic conditions
thus furnishing the desired 3-sulfenyl indoles without requirement
of toxic metal catalyst, oxidant, base and organic solvent.
Additionally the developed bio-chemocatalytic protocol was further
After having optimized conditions in hand (Table 1, entry 20),
further substrates scope were studied by changing the thiols
(aromatic/heteroaromatic) and indoles to obtain a series of desired
3-sulfenylated indoles (Table 2, 3a-3h, 5a-5h and 6h-6i). With
regards to the electronic effects, it was found that electron
donating (2a-2e) as well as electron withdrawing (2f-2h) thiophenol
smoothly underwent sulfenylation with indole (1a), providing the
corresponding products 3a-3h (Table 2) in good to high yield.
Aliphatic thiol (2i) did not provide product (3i) during sulfenylation
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with indole (1a) probably due to low hydrogen bonding24 ability of thiophenol (2a, 2.4 equiv.) (Table 2; 6h) and ii) reaction of C-3
aliphatic thiol in BSA-I2 catalytic system resulting in no formation of methyl substituted indole (0.25 mmol) with thiophenol (1.2 equiv.),
in-situ S-S bond. This chemoselectivity can be a significant addition however, bis-sulfenylindole26a (6h) or C-2 sulfenylindole26b (6i) did
to the growing arsenal for substrate selective sulfenylation not form in both cases (i-ii), thus these results clearly highlighted
(aromatic verses aliphatic, see S.I.) in total synthesis of complex regioselectivity of our protocol towards exclusively C-3 sulfenylation
organic compounds.
of indole.
Table 2: Scope of the protocol with substituted indoles and
diverse thiophenols.a,b
Table 1. Optimization study for sulfenylation of indole.a
Entry
Biocatalyst
Chemocatalyst
(mol%)
Oxidant
Solvent
Yield
(%)
1
2
3
4
BSA
-
-
O2
O2
O2
O2
H2O
H2O
H2O
H2O
nd
nd
78
55
I2(50)
I2(50)
I2(50)
BSA
Sheep
albumin
5
6
Pig albumin
I2(50)
I2(50)
O2
O2
H2O
H2O
52
48
Rabbit
albumin
PPL
7
I2(50)
I2(50)
NIS(50)
KI(50)
I2(50)
O2
O2
O2
O2
O2
O2
O2
O2
O2
H2O
H2O
42
nd
50
48
55
52
51
86
87
8
CAL-B
BSA
BSA
BSA
BSA
BSA
BSA
BSA
9
H2O
10
11
12
13
14
15
H2O
EtOH
DMF
DMSO
H2O
I2(50)
I2(50)
I2(50)C
I2(50)d
H2O
16
17
18
19
20
21
22
23
BSA
BSA
BSA
BSA
BSA
BSA
BSA
-
I2(50)e
I2(40)
O2
O2
O2
O2
O2
O2
-
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
70
86
I2(30)
I2(30)f
87
89
I2(30)+TBABg
I2(30)+TBAI
I2(30)+TBABh
I2(30)+TBAB
96(92)
90
a
traces
traces
Reaction condition: Indole (0.25 mmol), thiol (0.3 mmol), BSA (50 mg, 0.00075
b
mmol), I2 = 30mol%, H2O = 600 µL, TBAB = 10 mol%. Isolated yield after column
O2
purification.
a
Reaction condition: 1a=0.25 mmol; 2a = 0.3 mmol; Biocatalyst=50 mg;
Next we checked the feasibility of the developed sulfenylation
protocol with indole bearing acid (-COOH) and ester (-COOC2H5)
groups at 2-position of indole (Table 3) as synthesis of these
bioactive indole-2-carboxylate derivatives27 (Figure 1) required
strong base27a,b with harsh reaction conditions.27c
Chemocatalyst (50 -30 mol%); Solvent=600 µL; Stirred at rt for 24 h
(entries 1 to 13).b on the basis of HPLC; nd=not detected.c at 40oC.for 12
h.d at 50oC for 12 h.e at 60oC for 12 h under air.f 6 h at 50oC under oxygen
balloon (entries 17 to 22).g 10 mol% of PTC used and reaction time
reduced to 4h at 50oC.h under N2 atm; yield in parenthesis = isolated yield.
PPL=Porcine pancreatic lipase. CAL-B= Candida Lipase-B.
Table 3: Scope of protocol with indole and thiols containing acidic
proton.a,b
Further heteroatom embedded thiophenols (4a-4h) having high
therapeutic value25 also successfully provided desired products 5a-
5h (Table 2) in moderate to good yield. Similarly, electron deficient
(Table 2, 1b-1d) and electron rich (Table 2, 1e) substituted indole
underwent sulfenylation equally well with thiophenol (2a) to form
the desired products 6a-6d (Table 2). Interestingly, our bio-
chemocatalytic system also allow direct sulfenylation of 2-methyl
indole and N-methylindole12f to form desired product 6e-6g (Table
2) under neutral condition devoid of any acidic/basic catalyst.12f,13b
Further to validate regioselective26 C-3 verses C-2 sulfenylation of
indole in our BSA-I2 catalytic system, we performed two set of
reactions i) reaction of indole (1a, 0.25 mmol) with excess of
a
Reaction condition: Indole=0.25 mmol, thiol=0.3 mmol, BSA=50 mg; (0.00075
b
mmol), I2=30 mol%, H2O=600 µL, TBAB = 10mol%. Isolated yield after column
purification.
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To our satisfaction, the carboxylic derivatives of indole directly
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Interestingly, sulfenylation reaction of 1a with disulphide in BSA-
underwent sulfenylation with thiophenol providing the desired I2 on water also provided the product 3a in shorter reaction time of
products 7a-7b(Table 3) in good yield. Similarly, thiophenols having 4h which emphatically confirms the involvement of in situ
additional acidic protons (-OH, -NH2, -COOH etc.) also successfully generation/cleavage of disulphide during sulfenylation of 1a with
underwent sulfenylation with indole (1a) towards formation of thiolphenol (Scheme 1) on water. Moreover in the absence of
products 7c-7f (Table 3) avoiding the use of strong base28a or indole under same reaction condition formation of disulfide further
oxidant. 28b
confirmed our speculation for disulfide involvement in reaction
In order to investigate the scalability and economical aspects of pathway.
the developed bio-chemocatalytic (BSA-I2) cooperative system, a
With HPLC results in hand, sulfenylation of indole (1a) with
gram scale29 (Figure 2) reaction was conducted where indole (1a, 10 thiophenol (2a) was monitored in the presence of radical scavenger
mmol, 1.17g) reacts smoothly with thiophenols (2a or 4a) provided like TEMPO or BHT (10 mol%) where there was no loss in the yield
sulfenylated products 3a or 5a with 91 and 82 % yield respectively of desired product 3a (see S.I.). This clearly suggested that cascade
where 3-(pyridin-2-ylthio)-1H-indole25 (5a, CAS No 27933-94-4) is an oxidative coupling-sulfenylation reaction proceed through ionic
important COX-2 inhibitor. Further a recyclability study was carried rather than the free radical pathway. Further, in-situ
out for synthesis of 3a where BSA efficiently recycled up to four generation/cleavage of disulfide during cascade sulfenylation
consecutive cycles (92% to 83%, see S.I.) which highlighted the reaction was proved by electrospray ionization mass spectrometry
green and economical aspects of our catalytic system.
(ESI-MS)13f,14a technique. ESI-MS analysis of aliquots analyzed after
an time intervals of 2, 4 or 6 h (see S.I.) from crude reaction mixture
of 1a and 2a where mass spectra after 4 h (Figure 4) clearly shows
the formation of important intermediates: disulfide "A" (m/z=219),
phenylsulfenyl iodide14a "B" (m/z 235) along with ionic
intermediate13f “C” (m/z 350) (see S.I.) which finally led to the
formation of product "D" (m/z 225) as is evident from Figure 4.
Figure 2. Bio-chemocatalytic gram scale sulfenylation reaction.
To gain insights into the reaction pathway for cascade oxidative
coupling-C(sp2)-H sulfenylation reaction, two powerful analytical
techniques (HPLC and ESI-MS)23,30 were employed towards
establishing the formation of sulfenylated product 3a involving in-
situ generation/cleavage of disulfide (S-S bond) and formation of C-
S bond following either ionic or free radical pathway. HPLC23
analysis of aliquot collected after an interval of 2, 4, 5 and 6 h (see
S.I.) from crude reaction mixture of 1a and 2a where HPLC
chromatogram particularly after 2 h (Figure 3) clearly indicates the
simultaneous formation of intermediate disulfide21 (marked as "D"
in Figure 3) as well as product "C" along with decreasing
concentration of reactants "A" and "B" (Figure 3) which after 6 h
provided exclusively desired product "C" (Scheme 1) without any
side products.14a
Figure 4. ESI-MS analysis of crude reaction mixture of 1a & 2a after 4 h.
Having HPLC and ESI-MS analysis results in hand, and based on the
previous reports, it was presumed that amino acid on side chain of
BSA5f might be playing an significant role for sulfenylation of indole
via in-situ generation/cleavage of disulfide by cooperative cascade
catalysis of BSA and iodine on water under aerobic condition. In
fact, structurally BSA, nonspecific carrier protein, contains side
chains of acidic (Asp, Glu)5f and basic (Arg, Lys, His) amino acids
which could act as an ambiphile5g,23 on water. Hence to prove the
involvement of amino acids (acidic or basic) side chain present in
BSA for above sulfenylation reaction, we carried out sulfenylation of
1a with iodine on water using some amino acids where lysine
provided maximum yield of 3a (55%) while glutamic acid gave low
yield of 3a (36% ) (Table 4).
After 6h
After2h
D
C
B
C
A
D
Figure 3 HPLC showing in-situ generation/cleavage of disulfide bond during
sulfenylation of indole (1a) with thiophenol (2a) of crude reaction mixture
after 2h and 6 h, where chromatogram peaks are marked as A = thiophenol
(2a); B = indole (1a); C = product (3a); D = disulfide.
From Table 4, it was observed that basic amino acid i.e. lysine
gave slightly better of sulfenylated product (3a). This prompted us
to attempt the sulfenylatioin reaction using organic base such as
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triethyl amine10e (instead of lysine) which shown no significant (Figure 5) through in-situ generation and cleavage of disulphide,
improvement in yield of 3a.
formed via oxidation of thiophenol, whereas literature postulates
formation of such intermediate (PhSI) directly from thiophenol22
towards sulfenylation of indole with no such analytical proof.
To understand the importance of above cooperative catalysis,
we extended our BSA-I2 catalyzed protocol beyond sulfenylation of
indole (Table 2 and Table 3) towards sulfenylation of hydroxylaryls
(such as 2-naphthols and 4-hydroxycoumarins) with thiophenol on
water using oxygen as a green oxidant, thus improving the reported
procedure14b,20-21,26a,31 where toxic solvent or strong base31a is
required for sulfenylation of 2-naphthols and 4- hydroxycoumarins.
Therefore, under above analogous conditions (Table 2 and 3), the
reaction of 2-naphthol with different thiophenols were tested, in
which the corresponding products 10a-10d (Table 5) were obtained
in moderate to good yield.
Table 4: Sulfenylation reaction with different amino acids present
on side chain of BSA:a,b
S.No. Amino Acid
Yield
55%
S.No. Amino Acid
Yield
36%
1
L-Lysine
3
L-Glutamic
acid
2
L-Arginine
50%
4
L-Aspartic acid
41%
aReaction Conditions: Amino acid 50mg; Thiophenol(0.3mmol); Indole(0.25mmol); I2=
30mol%; Water 600 µL, open air, at 50oC for 4h; b=isolated yield.
Next we examined the sulfenylation of 4-hydroxycoumarins20,31d
to form sulfenylated 4-hydroxycoumarins20 derivatives which are
All these experiments support the synergetic role of both acidic
and basic amino acid functionalities present in BSA, thus, under
above catalytic system (Table 2) BSA interacts effectively with
iodine9c leading to formation of product (3a).
known for
a wide range of biological activities including
antibacterial, antioxidant and analgesic properties.
Hence based upon results of Table 4, a plausible mechanism of
cascade bio-chemocatalytic (BSA-I2) sulfenylation reaction is
proposed in Figure 5. Initially BSA catalyzes oxidative coupling of
thiophenol on water pooled by molecular oxygen forming in-situ
disulfide (“A”) which combined with I2 to afford an electrophilic
species PhSI marked as “B” (Figure 5). Subsequent insertion of
indole with "B" resulted ionic intermediate “C” then HI was
extruded out from “C” to generate the sulfenyl product “D” further
eliminated HI was oxidized by molecular oxygen to regenerate I2
which again enters the catalytic cycle.
Table 5: Scope of protocol with hydroxyaryl (2-naphthol and 4-
hydroxy coumarin) and thiols.a,b
Acidic site
Basic site
BSA
H
O
N
N
BSA
H
O
H
H
δ+
δ-
I
I
a
S
Reaction condition: substrate 8 or 9 (0.25 mmol), thiophenol (0.3 mmol),
S
I2
BSA (50 mg; 0.00075 mmol), 30 mol% of I2 and TBAB=10 mol% was taken in
{A}
H2O (600 µL). b Isolated yield after column purification.
Bovine serum
albumin
Acidic site
BSA
2PhSI
{B}
H2O
Interestingly, thiophenol bearing electron withdrawing, electron
releasing as well as heteroatom reacts smoothly with 4-
hydroxycoumarin, thus providing the desired products 11a-11h
(Table 5) in good yield.
SH
O
N
H
2
O
H
Basic site
O2
δ+
S
H
O
H
N
N
BSA
H
O
H
H
HI
Conclusions
S
δ-
In conclusion, by marrying two different classes of catalysts (i.e.
biocatalyst and chemocatalyst), we have introduced BSA-I2 as highly
efficient cooperative cascade catalyst for direct sulfenylation of
indole as well as hydroxyaryls (2-naphthol or 4-hydroxycoumarin)
with readily available thiophenols via in-situ generation/cleavage of
disulfide (S-S) bond followed by C-S bond formation in one-pot in
aqueous medium using oxygen. The significant features of this
unprecedented cooperative bio-chemocatalytic protocol are: (i)
atom efficiency, (ii) metal/base-free, (iii) oxygen as a green oxidant,
(iv) H2O as a solvent (v) recyclability (up to four cycles), regio- and
S
S
D
N
H
I
2
N
H
{C}
Figure 5. Plausible mechanism for BSA-I2 catalyzed cooperative cascade
sulfenylation reaction.
Moreover our HPLC-ESI-MS based mechanistic studies highlight
some important findings regarding formation of intermediate (PhSI)
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chemoselectivity (vi) broad substrate scope and tolerable for a 5 (a) D. C. M. Albanese and N. Gaggero, RSC Adv., 2015,
5
,
wide range of functional groups. More importantly, mechanistic
studies towards cascade oxidative coupling-C(sp2)-H sulfenylation
was further probed by HPLC and ESI-MS. Further investigation of
this cooperative catalytic system for both C-C and C-S bond in one
pot is currently underway in our laboratory.
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Acknowledgements
DE and AGL are indebted to UGC and CSIR New Delhi for the
award of research fellowships. We acknowledge Director CDRI,
Lucknow for their kind cooperation and encouragement. The
Yarovsky, Chem. Sci. 2013, 4, 928-937.
authors are also grateful to SAIF-CDRI for providing 6 (a) N. Sharma, U. K. Sharma, R. Kumar, N. Katoch, R. Kumar
spectroscopic data and Mr. R.K. Purshottam for HPLC data.
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