Palladium-catalyzed intramolecular oxidative coupling involving double C(sp2)-H bonds for the synthesis of annulated biaryl sultams

Article abstract of DOI:10.1021/jo5011334

The palladium-catalyzed intramolecular oxidative coupling described herein involves a double C(sp²)-H bond functionalization in sulfonanilides, providing a workable access to biaryl sultams annulated into a six-membered ring that are otherwise difficult to obtain by literature methods. The other synthetic applications of this protocol including the synthesis of biaryl sultams containing a seven-membered ring and analogous sultones are also presented.

Full text of DOI:10.1021/jo5011334

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Article
Palladium-Catalyzed Intramolecular Oxidative Coupling Involving
Double C(sp2)-H Bonds for the Synthesis of Annulated Biaryl Sultams
Joydev K. Laha, Krupal P. Jethava, and Neetu Dayal
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo5011334 • Publication Date (Web): 14 Aug 2014
Downloaded from http://pubs.acs.org on August 15, 2014
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Palladium-Catalyzed Intramolecular Oxidative Coupling Involving
Double C(sp2)-H Bonds for the Synthesis of Annulated Biaryl Sultams
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Joydev K. Laha,* Krupal P. Jethava, and Neetu Dayal
Department of Pharmaceutical Technology (Process Chemistry)
National Institute of Pharmaceutical Education and Research
S. A. S. Nagar, Punjab 160062
INDIA
Email: jlaha@niper.ac.in
ABSTRACT.
The palladiumꢀcatalyzed intramolecular oxidative coupling described herein involves a
double C(sp2)ꢀH bond functionalization in sulfonanilides providing a workable access to
biaryl sultams annulated into a six member ring that are otherwise difficult to obtain by
literature methods. The other synthetic applications of this protocol including the synthesis
of biaryl sultams containing a seven member ring and analogous sultones are also presented
.
INTRODUCTION
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Biaryl embedded in a ring is a key structural motif in many biologically active compounds,
natural products, and compounds used in materials science.1 Transition metalꢀcatalyzed oxidative
CꢀH coupling2 is a powerful variant of traditional crossꢀcouplings3 or direct arylations4 providing
expedient access to biaryls embedded in a ring. The synthesis of these biaryls through
intramolecular oxidative coupling (IOC) of two C(sp2)ꢀH bonds is a method of choice that
obviates the need for the use of prefunctionalized substrates and alleviates the generation of salt
waste, thereby rendering superior sustainability and environmental compatibility. Seminal work
since the year 2006 has established the wide applications of IOC in the synthesis of biaryls
embedded in a ring, including but not limited to the synthesis of Nꢀfused heterocycles,5
carbazoles,6 phenanthridinꢀ6ꢀones,7 and other related biaryls,8 which indicates the importance
and growing interest of this constantly evolving synthetic technology. Of particular importance,
biaryls embedded in cyclic sulfonamide (biaryl sultams) such as 1 and 2 have emerged as
privileged structures in drug discovery due to their inhibitory activities against a diverse array of
enzymes such as COXꢀ2, HIV integrase, lipoxygenase, Calpain 1, MMPꢀ2, and also play active
role in selective serotonin reuptake inhibition as well as in nuclear factorꢀκB (NFκB) down
regulation.9ꢀ11
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To the best of our knowledge, approach to the synthesis of biaryl sultam 3 via IOC is
unprecedented, despite the potential of biaryl sultams as active pharmaceutical component.
Among the repertoire of synthetic methods known for the synthesis of fused sultams,12 the
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significant approaches to biaryl sultams include intramolecular radical cyclization of Nꢀalkylꢀ2´ꢀ
bromoarylsulfonamides,13 palladiumꢀcatalyzed intramolecular direct arylation of Nꢀalkylꢀ2ꢀ
bromoarylsulfonamides,11,14 or intramolecular oxidative CꢀH amination of an elaborated
precursor 2ꢀphenylarylsulfonamide under metalꢀfree condition,15 thereby requiring several
reaction steps (Scheme 1). We reasoned that IOC of double C(sp2)ꢀH bonds in sulfonanilides
would represent an atomꢀeconomical green approach to the synthesis of biaryl sultams
considering that the starting materials could be easily prepared with synthetic convergency.
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Scheme 1. Concise approaches to biaryl sultams
Notably, only a few examples of ortho CꢀH functionalization in sulfonanilides under metalꢀ
catalyzed condition are known. While palladiumꢀ16 or copperꢀcatalyzed17 orthoꢀhalogenation has
been achieved in aniline ring, the only example of orthoꢀarylation of NꢀMs aniline18 has been
supplemented in a recent report. The pioneering study carried out by Yu and coꢀworkers
described the use of perfluoroaryl substitution in sulfonamides as competent directing group in
the palladiumꢀcatalyzed arylation of sulfonanilide with pinacol phenylboronate.19 A rhodiumꢀ
catalyzed ortho CꢀH activation of Nꢀacyl sulphonamides, and subsequent addition of internal
alkynes to give benzosultams has also been reported.20
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Scheme 2. ortho CꢀH functionalizations in sulfonanilides
Our renewed interest in the concise synthesis of fused nitrogenꢀcontaining heterocycles21
prompted us to develop a workable access to biaryl sultams with a free NH group that are
otherwise difficult to obtain by literature methods. Herein, we describe the first example of
palladiumꢀcatalyzed IOC involving double C(sp2)ꢀH bonds in sulfonanilides providing access to
annulated biaryl sultams with a free NH group that are amenable to functionalization at nitrogen.
The other synthetic applications of this protocol including the synthesis of biaryl sultams
containing a seven member ring and analogous sultones have also been demonstrated.
RESULTS AND DISCUSSION
Table 1. Optimization study on the IOC of 4 to 6a
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Entry
1
Oxidant
Cu(OAc)2
DDQ
Base
ꢀ
Solvent
Yield of 6 (%)b
AcOH:Xylene (1:3)
PivOH
0
0
2
ꢀ
9
3
Ag2O
ꢀ
AcOH
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4
AgOAc
Oxone
ꢀ
AcOH
5
ꢀ
AcOH
6
K2S2O8
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
Ag2O
ꢀ
AcOH
0
7
ꢀ
TFA
0
8
ꢀ
PivOH
60
67
81
77
73
85 (81)
45
Trace
66
78
55
0
9
Cs2CO3
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
PivOH
10
11c
12
13d
14
15e
16
17
18
19
20
21f
22g
PivOH
PivOH
PivOH:AcOH (1:1)
PivOH:AcOH (3:1)
PivOH:AcOH (1:3)
DMF+(PivOH:AcOH)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
Ag2CO3
AgF
AgNO3
AgOTf
AgOAc
AgOAc
0
0
70
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23h
24i
25j
26k
27l
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
KOBuꢀt
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
PivOH:AcOH (3:1)
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71 (of 7)
a Conditions: substrate (0.5 mmol), Pd(OAc)2 (10 mol%), oxidant (1.5 mmol), base (20 mol%, if
any), solvent (2 mL), 130 oC, 12 h; b GCꢀMS yield; KOBuꢀt (100 mol%); d 81% isolated yield;
c
e
f
PivOH:AcOH (3:1, 0.3 mL), DMF (1.7 mL); Used AgOAc (20 mol%) and a coꢀoxidant such
g
h
as oxone, K2S2O8, Cu(OAc)2, or Cu(OTf)2 (1.5 mmol);
Pd(TFA)2 (10 mol%); PdCl2 (10
mol%); i Pd(OAc)2 (5 mol%); without any Pdꢀcatalyst; AgOAc (1.0 mmol); l Benzanilide (0.5
j
k
mmol).
Our initial investigation on the IOC of 4 using a condition [5 mol% Pd(TFA)2, 10g benzoic
o
acid/mmol of 4, 120 C, 24 h, 1 atm O2] reported for related intramolecular oxidative CꢀH
coupling of benzanilide 5 to the synthesis of (NH)ꢀphenanthridinone 7 was futile.7b We began
our optimization study using Pd(OAc)2 as the catalyst and mild or strong oxidant (Table 1).
Among the mild oxidants [Cu(OAc)2 and/or air, DDQ, silver compounds] examined, the silver
oxidant proved effective (entries 1ꢀ4). While the IOC of 4 in the presence of Pd(OAc)2 and Ag2O
in acetic acid gave 6 albeit in low yield, substantial improvement in the yield was observed using
AgOAc (entries 3ꢀ4). Strong oxidant such as oxone or K2S2O8 did not give the desired product in
an isolable quantity (entries 5ꢀ6). While TFA did not produce the cyclized compound, pivalic
acid proved more effective (entries 7ꢀ8). A substoichiometric amount of a base, such as Cs2CO3
or KOBuꢀt further improved the yield (entries 9ꢀ10). However, the effect of use of a
stoichiometric quantity of KOBuꢀt was detrimental (entry 11). A mixture of acids can also be
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used in place of one acid (entries 12ꢀ14). However, not only the ratio, but also the concentration
of the acids is critical for better yield (compare 13 vs. 15). The effect of other silver compounds
was also examined (entries 16ꢀ20).22 While Ag2O, Ag2CO3, or AgF afforded compound 6 in
reduced yields, AgNO3 and AgOTf did not produce the compound 6 in an isolable quantity.
Similarly, a catalytic amount of AgOAc in combination with a coꢀoxidant was ineffective (entry
21). Other palladium (II) sources exhibited deleterious effect (entries 22ꢀ23). While lowering the
catalyst loading demonstrated negative effect, the desired product was not obtained without a Pdꢀ
catalyst (entries 24ꢀ25). A reduced molar quantity of AgOAc produced inferior result (entry
26).22 For comparison, benzanilide 5 under the optimized condition gave (NH)ꢀphenanthridinone
7 in 71% yield (entry 27), while 5 was reported to give 7 in 91% yield using the conditions
described by Ishida et al.7b However, our optimized conditions work for both the benzanilide and
the sulfonanilides, while those reported for the benzanilide7b apparently fail to work with the
sulfonanilides. This indicates that the new conditions described herein have broader scope of
substrates.
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With the optimized condition in hand [substrate (0.5 mmol), Pd(OAc)2 (10 mol%), AgOAc
o
(1.5 mmol), KOBuꢀt (20 mol%), PivOH:AcOH (3:1, 2 mL), 130 C, 12 h], we investigated the
scope of substrates. The substrates 8-26 were prepared by reacting commercially available
anilines and sulfonyl chlorides. It has been documented that a subtle change in the acidity of the
NH moiety, as a result of substituent effect on the aniline ring in sulfonanilide, can have a drastic
effect on the chemical reactivity.23 Under the optimized condition, the presence of electronꢀ
withdrawing substituents such as F or CF3 group at C2ꢀposition of the aniline ring resulted in
notable reduction in chemical yield affording sultams 27 and 28 in 65 and 67% yields,
respectively (Table 2). Similarly, Cl or NO2 group at the 4ꢀposition delivered biaryl sultams 29
and 30 also in reduced yields compared to the parent system (70 and 75%, respectively). In
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contrast, a strong electronꢀdonating OMe group at Cꢀ2 or Cꢀ4 position did not give the desired
biaryl sultam 31 and 32, respectively. However, sulfonanilide 14 containing a OMe group at Cꢀ3
position afforded the biaryl sultam 33 in 70% yield. The complete regioꢀcontrol in the IOC of 14
is particularly noteworthy. Interestingly, the presence of three OMe groups at 2,3 and 4ꢀ
positions, however, resulted in adverse effect on chemical reactivity of 15, thus the synthesis of
34 was unsuccessful.
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Table 2. Synthesis of various substituted biarylsultams
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To further confirm the electronic effect of OMe group at 2ꢀ or 4ꢀposition causes adverse effect
on chemical reactivity, we carried out the biaryl sultam formation using 3,5ꢀdimethyl aniline
sulfonamide 16. To our delight, biaryl sultam 35 was obtained in 76% isolated yield suggesting
that this IOC is independent of steric effect. A completely unsubstituted biaryl sultam 36 was
obtained in 69% yield. A pꢀnitrobenzenesulfonyl ring exhibited relatively less reactivity to that
of pꢀtoluenesulfonyl ring resulting in somewhat reduced yield of biaryl sultam 37. The presence
of an additional electronꢀwithdrawing group on the aniline ring further reduces the yield of
sultams 38 and 39. Sulfonanilide 21 with a methyl group at the 3ꢀposition underwent cyclization
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both at 2ꢀ and 6ꢀpositions giving rise to an inseparable mixture of biaryl sultam 40. However, a
4
5
small quantity of a pure sample of an isomer corresponding to cyclization at the 6ꢀposition was
6
7
1
obtained by chromatography. By comparing the H NMR spectrum of the isolated sample with
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the 1H NMR of their mixture, we were able to interpret each peak in the 1H NMR spectrum of 40
without any ambiguity and confirm the formation of two cyclised compounds (see the
Supporting Information). The ratio of the two regioisomers (Cꢀ2/Cꢀ6 = ca. 1:2) was determined
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from the H NMR of the crude product. Sulfonanilide 22 with a bromo group at the 3ꢀposition,
however, resulted in a different regioisomeric ratio (Cꢀ2/Cꢀ6 = ca. 3:1) of the biaryl sultam 41. In
this case, a pure sample of an isomer corresponding to cyclization at 2ꢀposition was obtained. By
1
1
comparing the H NMR spectrum of the isolated sample with the H NMR of their mixture, we
were able to interpret each peak in the 1H NMR spectrum of 41 and confirm the formation of two
cyclised compounds (see the Supporting Information). Interestingly, the bromo group remains
unaffected under our optimized condition. While the regioselectivity issue was observed with a
3ꢀsubstitution on the aniline ring, sulfonanilide with a substitution at the 3ꢀposition on the
benzenesulfonyl ring gave the sultam 42 exclusively. In our study, sulfonanilide with a free ꢀNH
moiety is essential to effect the cyclization. Thus, attempt syntheses of Nꢀsubstituted biaryl
sultams (Nꢀmethyl 43, Nꢀacetyl 44, or Nꢀtosyl 45) were unsuccessful.
Under the optimized condition, Nꢀtosyl diphenylamine 46 underwent cyclization uneventfully
with the deliberation of Nꢀtosyl carbazole 47 in 51% yield (Scheme 3).6 Notably, in this case
IOC occurs involving double CꢀH bonds present in phenyl rings directly attached to nitrogen.
Interestingly, 2ꢀphenylꢀNꢀtosylamide 48 under the same condition also gave 47 in 62% yield
suggesting that an IOC of NꢀH/CꢀH bonds is involved. However, a different palladium catalytic
cycle is likely to be operative in this case as opposed to the reported conversion of 48 to 47 in
which a strong oxidant oxone has been used and a PdII/PdIV catalytic cycle is proposed to be
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involved.24 Subsequent efforts to effect an intermolecular reaction of 4 and excess benzene under
the optimized condition resulted in the formation of 6 in 65% yield, which indicated the
intramolecular palladium catalyzed oxidative coupling is more competent than intermolecular
coupling.3
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10 mol% Pd(OAc)2
20 mol% KOBu-t
O
3 equiv AgOAc
N
Ph
N
S
O
O
PivOH:AcOH (3:1)
S
O
12 h, 130
C
N
46
Ts
Me
0%
47 51% (from 46)
47 62% (from 48)
Me
Oxone, PdII-PdIV
HN
O
or AgOAC, Pd0-PdII
S
O
48
Me
Me
H
O
S
10 mol% Pd(OAc)2
N
H
N
NHTs
20 mol% KOBu-t
O
S
+
or 47
O
3 equiv AgOAc
O
Ph
PivOH:AcOH (3:1)
4
6 (65%)
0%
12 h, 130
C
Me
Scheme 3. Cyclization of Nꢀphenyl or orthoꢀphenyl sulfonanilide under the optimized condition
The application of the present protocol was explored to the synthesis of biaryl sultones (Scheme
4).14a Under the optimized condition, phenyl benzene sulfonates 49 and 51 demonstrated
sluggish reactivity yielding the corresponding sultones 5025 and 52 in 47 and 52% yields,
respectively. However, tolyl benzyl sulfone 53 did not undergo IOC to produce the cyclic
sulfone 54, revealing ortho CꢀH bond functionalization in the benzyl ring was difficult.
Scheme 4. Synthesis of biaryl sultones, but not cyclic sulfones
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During the course of our current investigations, we also uncovered that this protocol could be
extended to the synthesis of seven member biaryl sultams.11 Under the optimized condition, the
sulfonamide 55 and 57 exhibited different reactivity towards IOC resulting in optically pure
biaryl sultams 56 and 58 in 63 and 83% yields, respectively (Scheme 5). Similar to our previous
observation in the synthesis of 42, sulfonamide 57 with a methyl group at 3ꢀposition of the
benzenesulfonyl ring gave 58 exclusively, resulted from the cyclization at 6ꢀposition.
Scheme 5. Synthesis of biaryl sultams with a seven member ring
Based on the above studies, the following mechanism is proposed (Scheme 6). The electrophilic
palladation of orthoꢀ CꢀH bond is likely to be facilitated in aniline ring compared to the
benzenesulfonyl ring,16ꢀ19 which could result in the formation of 59. Alternatively, the acidity of
NH moiety in sulfonanilide 4 could be a controlling factor to the formation of 60. Subsequent
cyclopalladation of 59 or 60 could lead to the formation of 61. The transmetallation in 61 by
CMD pathway could form 62, which upon reductive elimination could give 6 with concomitant
formation of palladium (0). Alternatively, 62 could be generated directly from 59 without
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involvement of 61. The palladium (II) may be regenerated by oxidation with AgOAc. A detailed
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mechanistic study to support the proposed mechanism is currently underway.
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Scheme 6. Proposed mechanism for the IOC
CONCLUSION
Incongruent to literature methods dealing with the preparation of Nꢀalkylated biaryl sultams, our
optimized condition opens a direct access to biaryl sultams with a free NHꢀgroup required for
late stage diversification in drug discovery. As demonstrated, the optimized condition was quite
resourceful warranting broad application to the synthesis of annulated biaryl sultams embedded
into a seven member ring, analogous biaryl sultones, and phenanthridinones. While our protocol
augurs interesting synthetic applications, understanding the detailed mechanism would be a
successive development to the current intramolecular oxidative coupling reactions.
EXPERIMENTAL SECTION
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General: Unless noted otherwise, all reagents and solvents were purchased from commercial
sources and used as received. All palladiumꢀcatalyzed reactions were performed in a screwꢀ
capped vial. The proton (1H) and carbon (13C) NMR spectra were obtained in CDCl3 using a 400
MHz spectrometer referenced to TMS and are reported in δ units. Coupling constants (J values)
are reported in Hz. Column chromatography was performed on silica gel (60ꢀ120 or 230ꢀ400
mesh). High Resolution Mass Spectra (HRMS) was obtained using Electron Spray Ionisation
(ESI) technique and as TOF mass analyser. All melting points were taken using a melting point
apparatus equipped with a calibrated thermometer and are uncorrected. New compounds were
characterized by melting point, 1H NMR, 13C NMR, IR, and HRMS data. pꢀToluenesulfonanilide
(4) and Nꢀphenylbenzamide (5) were purchased from commercial vendors.
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General Procedure for the Synthesis of Sulfonanilides Using Procedure A [8-10, 12-17, 19-
24, 46]. A suspension of, substituted benzene sulfonyl chloride (1 mmol), substituted aniline (1.2
mmol) and silica gel (1.0 g, 60ꢀ120 mesh) was stirred overnight at room temperature. Ethyl
acetate or CH2Cl2 (20 mL) was added and the resulting reaction mixture was filtered. The filtrate
was concentrated under reduced pressure which upon purification by column chromatography
[silica, ethyl acetate/ hexane = 1:9 ~ 2:8] afforded the desired product.
General Procedure for the Synthesis of Sulfonanilides Using Procedure B [11, 18]. A
solution of substituted benzene sulfonyl chloride (1 mmol), substituted aniline (1.2 mmol), and
pyridine (2 mmol) in CH2Cl2 (2.5 mL) was stirred at room temperature for 12 h. Water (20 mL)
was added and the reaction mixture was extracted with CH2Cl2 (2 x 10 mL). The organic layers
were combined, dried (Na2SO4), concentrated under reduced pressure, and purified by column
chromatography [silica, ethyl acetate/ hexane = 3:7) to give the desired product.
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General Procedure for the Synthesis of Benzene Sulfonates [49, 51] and Sulfonamide [55,
57] Using Procedure C. A solution of substituted benzene sulfonyl chloride (1 mmol),
substituted alcohol (1.1 mmol) or (S)ꢀ1ꢀphenylethanꢀ1ꢀamine (1.1 mmol), and triethylamine (1
mmol) in CH2Cl2 (5 mL) was stirred at 45 ºC for 6 h. Water (20 mL) was added and the reaction
mixture was extracted with CH2Cl2 (2 x 10 mL). The organic layers were combined, dried
(Na2SO4), concentrated under reduced pressure, and purified by column chromatography [silica
ethyl acetate/ hexane = 1:9 ~ 2:8) to give the desired product.
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General Procedure for the Palladium-Catalyzed Intramolecular Oxidative Coupling. A
mixture of substrate (0.5 mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), AgOAc (174 mg, 1.5 mmol),
and KOBuꢀt (11.2 mg, 0.1 mmol) in acid [PivOH:AcOH (3:1), 2 mL] was heated at 130 ºC for
12 h. The reaction mixture was passed through a celite bed and the bed was wahsed with ethyl
acetate (20 mL). The filtrate was neutralized by the addtion of saturated solution of NaHCO3 (10
mL) and ammonium chloride (20 mL) with constant stirring. Extraction with ethyl acetate (3 x
20 mL) followed by concentration of the organic layer gave a crude product, which upon
purifification by column chromatography [silica (230ꢀ400 mesh), ethyl acetate/ hexane = 1:9 ~
2:8] afforded the desired cyclised product.
2-Methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (6): Yield 85% (104 mg); off white solid;
mp.161ꢀ163 oC; 1H NMR:
δ
7.99 (d, J=7.32 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.77 (s, 1H), 7.36
13
ꢀ 7.42 (m, 2H), 7.28 ꢀ 7.32 (m, 1H), 7.11 (d, J=7.8 Hz, 1H), 2.52 (s, 3H); C NMR:
δ 145.0,
143.1, 136.9, 136.1, 135.6, 132.4, 130.0, 129.1, 125.3, 123.0, 122.1, 120.6, 21.7; HRMS: calcd
for C13H12NO2S [M+H]+ 246.0589, found 246.0588; IR (KBr): 3428, 3232, 2917, 1604, 1440
cmꢀ1.
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Phenanthridin-6(5H)-one (7):7b Yield 71% (69 mg); off white solid; H NMR (DMSOꢀd6):
δ
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11.70 (br. s, 1H), 8.52 (d, J=8.0 Hz, 1H), 8.40 (d, J=8.0 Hz, 1H), 8.34 (d, J=8.0 Hz, 1H), 7.84 ꢀ
6
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7.90 (m, 1H), 7.66 (t, J=7.5 Hz, 1H), 7.47 ꢀ 7.53 (m, 1H), 7.38 (d, J= 7.5 Hz, 1H), 7.25 ꢀ 7.30
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(m, 1H); C NMR (DMSOꢀd6):
δ 161.3, 137.0, 134.7, 133.3, 130.1, 128.4, 127.9, 126.1, 123.7,
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123.1, 122.8, 118.0, 116.6; HRMS: calcd for C13H10NO [M+H]+ 196.0762, found 196.0771; IR
(KBr): 3412, 2879, 1657, 1609 cmꢀ1.
N-(2-Fluorophenyl)-4-methylbenzenesulfonamide (8):27 Yield 95% (251 mg); off white solid;
mp. 110ꢀ112 °C; 1H NMR: δ 7.68 (d, J=8.0 Hz, 2H), 7.60 (td, J=8.0, 2.7 Hz, 1H), 7.24 (d, J=8.0
13
Hz, 2H), 7.06 ꢀ 7.11 (m, 2H), 6.95 ꢀ 6.99 (m, 1H), 6.84 (br. s, 1H), 2.39 (s, 3H); C NMR: δ
155.1 (d. J=243 Hz), 152.7, 144.2, 135.8, 129.7, 127.2, 126.0 (d, J=7 Hz), 124.7 (d, J=4 Hz),
123.2, 115.5, 115.3, 21.5; HRMS: calcd for C13H13FNO2S [M+H]+ 266.0651, found 266.0646;
IR (KBr): 3254, 1338, 1167 cm−1
.
4-Methyl-N-[2-(trifluoromethyl)phenyl]benzenesulfonamide (9):28 Yield 95% (299 mg); off
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white solid; mp. 115ꢀ117 °C; H NMR: δ 7.84 (d, J=8.0 Hz, 1H), 7.67 (d, J=8.0 Hz, 2H), 7.50 ꢀ
7.53 (m, 2H), 7.19 ꢀ 7.28 (m, 3H), 6.88 (br. s, 1H), 2.39 (s, 3H); 13C NMR: δ 144.3, 135.7, 134.5,
138.1, 129.6, 127.7, 126.6 (q, J=5 Hz), 124.9 (q, J=271 Hz), 124.8, 122.9, 120.6 (q, J=30 Hz),
21.5; HRMS: calcd for C14H13F3NO2S [M+H]+ 316.0619, found 316.0610; IR (KBr): 3313,
1321, 1120 cm−1
.
N-(4-Chlorophenyl)-4-methylbenzenesulfonamide (10):27 Yield 92% (258 mg); off white
solid; mp. 118ꢀ119 °C; 1H NMR:
δ
7.65 ꢀ 7.69 (m, 2H), 7.22 ꢀ 7.26 (m, 2H), 7.21 (s, 1H), 7.19 ꢀ
13
7.20 (m, 1H), 7.17 ꢀ 7.19 (m, 1H), 7.01 ꢀ 7.05 (m, 2H), 2.38 (s, 3H); C NMR:
δ 144.3, 135.6,
135.1, 130.9, 129.8, 129.4, 127.3, 122.9, 21.6; HRMS: calcd for C13H13ClNO2S [M+H]+
282.0356, found 282.0360; IR (KBr): 3235, 2905, 1599, 1489, 1329, 678 cm−1.
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4-Methyl-N-(4-nitrophenyl)benzenesulfonamide (11):28 Yield 94% (274 mg); yellow solid;
mp. 250ꢀ252 °C; 1H NMR: δ 8.11 (td, J=8.0, 3.0 Hz, 2H), 7.77 (dd, J=8.0, 1.7 Hz, 2H), 7.49 (br.
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s, 1H), 7.29 (d, J=8.0 Hz, 2H), 7.20 (td, J=8.0, 3.0 Hz, 2H), 2.40 (s, 3H); C NMR: δ 145.02,
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143.9, 142.6, 135.4, 130.1, 127.2, 125.4, 118.6, 21.6; HRMS: calcd for C13H13N2O4S [M+H]+
293.0596, found 293.0591; IR (KBr): 3334, 1522, 1339, 1160 cm−1.
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N-(2-Methoxyphenyl)-4-methylbenzenesulfonamide (12):30 Yield 88% (242 mg); off white
solid; 1H NMR: δ 7.66 (d, J=8.3 Hz, 2H), 7.53 (dd, J=7.9, 1.6 Hz, 1H), 7.20 (d, J=8.2 Hz, 1H),
7.04 (td, J=7.9, 1.5 Hz, 1H), 7.04 (br. s, 1H), 6.90 (t, J=7.8 Hz, 1H), 6.74 (d, J=8.1 Hz, 1H), 3.65
13
(s, 3H), 2.37 (s, 3H); C NMR: δ 149.5, 143.6, 136.2, 129.3, 127.2, 126.0, 125.3, 121.0, 110.6,
55.6, 21.4; HRMS: calcd for C14H16NO3S [M+H]+ 278.0851, found 278.0860; IR (KBr): 3401,
2917, 1591, 1432, 1371 cm−1.
N-(4-Methoxyphenyl)-4-methylbenzenesulfonamide (13):30 Yield 89% (246 mg); off white
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solid; H NMR: δ 7.60 (d, J=8.2 Hz, 2H), 7.23 (d, J=8.1 Hz, 2H), 7.98 (d, J=8.9 Hz, 2H), 6.77
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(d, J=8.9 Hz, 2H), 6.52 (br. s, 1H), 3.77 (s, 3H), 2.40 (s, 3H); C NMR: δ 157.9, 143.6, 136.0,
129.5, 128.9, 127.3, 125.4, 114.4, 55.4, 21.5; HRMS: calcd for C14H16NO3S [M+H]+ 278.0851,
found 278.0856; IR (KBr): 3401, 2917, 1591, 1432, 1371 cm−1.
N-(3-Methoxyphenyl)-4-methylbenzenesulfonamide (14):30 Yield 86% (238 mg); off white
solid; 1H NMR: δ 7.79 (br. s, 1H ), 7.76 (d, J=8.2 Hz, 2H), 7.20 (d, J=7.6 Hz, 2H), 7.09 (t, J=8.1
Hz, 1H), 6.77 (s, 1H), 6.72 (d, J=7.9 Hz, 1H), 6.61 (d, J=8.3 Hz, 1H), 3.7 (s, 3H), 2.33 (s, 3H);
13C NMR: δ 160.2, 143.9, 137.9, 135.9, 130.9, 129.6, 127.3, 113.1, 110.7, 106.6, 55.3, 21.5;
HRMS: calcd for C14H16NO3S [M+H]+ 278.0851, found 278.0861; IR (KBr): 3401, 2917, 1591,
1432, 1371 cm−1.
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4-Methyl-N-(3,4,5-trimethoxyphenyl)benzenesulfonamide (15):29 Yield 90% (303 mg); off
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white solid; mp. 117ꢀ119 °C; H NMR:
δ
7.69 (d, J=8.2 Hz, 2H), 7.26 (d, J=8.0 Hz, 2H), 6.86
153.4,
(br. s, 1H), 6.32 – 6.33 (m, 2H), 3.78 (s, 3H), 3.75. (s, 6H), 2.40 (s, 3H); 13C NMR:
δ
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143.9, 135.9, 135.7, 132.3, 129.6, 127.4, 99.7, 60.9, 56.1, 21.5; HRMS: calcd for C16H20NO5S
[M+H]+ 338.1062, found 338.1053; IR (KBr): 3237, 2961, 1598, 1504, 1391, 1150, 814 cm−1.
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N-(3,4-Dimethylphenyl)-4-methylbenzenesulfonamide (16):30 Yield 95% (260 mg); off white
solid; 1H NMR: δ 7.69 (d, J=8.0 Hz, 2H), 7.25 (d, J=8.0 Hz, 2H), 6.74 (s, 1H), 6.71 (s, 2H), 2.40
(s, 3H), 2.23 (s, 6H).
N-Phenyl benzenesulfonamide (17):14 Yield 97% (226 mg); off white solid; mp. 100ꢀ101 °C;
1H NMR:
δ
7.78 ꢀ 7.84 (m, 2H), 7.49 ꢀ 7.55 (m, 1H), 7.39 ꢀ 7.46 (m, 2H), 7.30 (s, 1H), 7.19 ꢀ
13
7.25 (m, 2H), 7.06 ꢀ 7.13 (m, 3H); C NMR:
δ 138.9, 136.4, 133.1, 129.4, 127.3, 125.4, 121.6;
HRMS: calcd for C12H12NO2S [M+H]+ 234.0589, found 234.0590; IR (KBr): 3213, 3065, 1597,
1475 cm−1.
4-Nitro-N-phenylbenzenesulfonamide (18):30 Yield 75% (208 mg); light yellow solid; mp. 86ꢀ
88 °C; 1H NMR:
δ 8.28 (d, J=8.8 Hz, 2H), 7.93 (m, J=8.5 Hz, 2H), 7.29 (t, J=7.5 Hz, 2H), 7.19
(t, J=7.3 Hz, 1H), 7.08 (d, J=7.5 Hz, 2H), 6.73 (br. s, 1H); 13C NMR: δ 144.6, 135.3, 129.7,
128.5, 126.6, 124.3, 122.5; HRMS: calcd for C12H10N2O4S [M]+ 278.0361, found 278.0363; IR
(KBr): 3280, 3054, 1594, 1378, 778 cm−1.
N-(2-Fluorophenyl)-4-nitrobenzenesulfonamide (19):31 Yield 88% (260 mg); yellow solid;
mp. 120ꢀ122 °C; 1H NMR: δ 8.30 (d, J=8.0 Hz, 2H), 7.96 (d, J=8.0 Hz, 2H), 7.61 ꢀ 7.65 (m, 1H),
7.16 ꢀ 7.19 (m, 2H), 6.98 ꢀ 7.03 (m, 1H), 6.91 (br. s, 1H); 13C NMR: δ 155.7 (d, J=244 Hz),
153.2, 150.4, 144.4, 128.5, 127.6 (d, J=8 Hz), 125.1 (d, J=4 Hz), 124.6, 124.3, 123.4, 123.2,
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115.8, 115.6; HRMS: calcd for C12H10FN2O4S [M+H]+ 297.0345, found 297.0341; IR (KBr):
3262, 1521, 1340 cm−1.
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4-Nitro-N-[2-(trifluoromethyl)phenyl]benzenesulfonamide (20): Yield 89% (308 mg); yellow
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solid; mp. 128ꢀ130 °C; H NMR: δ 8.29 (td, J=8.0, 2.3 Hz, 2H), 7.89 ꢀ 7.95 (m, 3H), 7.62 (t,
J=8.0 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.24 (t, J=8.0 Hz, 1H), 6.91 (br. s, 1H); 13C NMR
(DMSOꢀd6): δ 150.2, 147.0, 133.9, 133.7, 129.6, 128.7, 128.5, 127.6 (q, J=5 Hz), 127.3, 127.3(q,
J=30 Hz), 125.1, 124.9 (q, J=272 Hz), 123.8; HRMS: calcd for C13H10F3N2O4S [M+H]+
347.0313, found 347.0311; IR (KBr): 3290, 1526, 1321 cm−1.
4-Methyl-N-(m-tolyl)benzenesulfonamide (21):32 Yield 92% (240 mg); off white solid; mp.
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107ꢀ108 °C; H NMR:
δ
7.68 (d, J=8.3 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.09 (t, J=8.0 Hz, 1H),
13
6.85 ꢀ 6.93 (m, 4H), 2.37 (s, 3H), 2.26 (s, 3H); C NMR:
δ 143.8, 139.3, 136.5, 129.6, 129.1,
127.3, 126.1, 122.1, 118.3, 21.6, 21.4; HRMS: calcd for C14H16NO2S [M+H]+ 262.0902, found
262.0900; IR (KBr): 3257, 1592, 1400, 1153, 783 cm−1.
N-(3-Bromophenyl)-4-methylbenzenesulfonamide (22):33 Yield 87% (283 mg); off white
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solid; mp. 118ꢀ119 °C; H NMR:
δ 7.66 ꢀ 7.70 (m, 2H), 7.27 (d, J=0.8 Hz, 1H), 7.21 ꢀ 7.26 (m,
3H), 7.10 (t, J=7.9 Hz, 1H), 7.01 (qd, J=8.1, 1.1 Hz, 1H), 6.74 (br. s, 1H), 2.40 (s, 3H); 13C
NMR: 144.3, 137.9, 135.7, 130.6, 129.8, 128.3, 127.3, 123.9, 122.8, 119.5, 21.6; HRMS: calcd
δ
for C13H13BrNO2S [M+H]+ 325.9850, found 325.9850; IR (KBr): 3248, 2932, 1595, 1479, 1160,
563 cm−1.
3-Methyl-N-phenylbenzenesulfonamide (23): Yield 74% (183 mg); off white solid; mp. 88ꢀ90
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°C; H NMR:
δ 7.61 ꢀ 7.63 (m, 1H), 7.57 ꢀ 7.61 (m, 1H), 7.27 ꢀ 7.35 (m, 2H), 7.20 ꢀ 7.25 (m,
2H), 7.06 ꢀ 7.13 (m, 4H), 2.34 (s, 3H); 13C NMR:
δ
139.3, 138.9, 136.5, 133.8, 129.3, 128.9,
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127.6, 125.3, 124.4, 121.6, 21.3; HRMS: calcd for C13H14NO2S [M+H]+ 248.0745, found
248.0755; IR (KBr): 3265, 1482, 1151, 703 cmꢀ1.
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N,4-Dimethyl-N-phenylbenzenesulfonamide (24):27,34 Yield 94% (246 mg); off white solid;
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mp. 90ꢀ92 °C; H NMR: δ 7.44 (d, J=8.2 Hz, 2H), 7.24ꢀ7.34 (m, 5H), 7.10ꢀ 7.13 (m, 2H), 3.18
13
(s, 3H), 2.43 (s, 3H); C NMR: δ 143.5, 141.6, 133.5, 129.3, 128.8, 127.9, 127.2, 126.6, 38.0,
21.5; HRMS: calcd for C14H16NO2S [M+H]+ 262.0902, found 262.0902; IR (KBr): 3412, 2917,
1595, 1492, 1345 cm−1.
N-Phenyl-N-tosylacetamide (25):35 A stirred solution of pꢀtoluenesulfonanilide (0.494 g, 2
mmol) and triethylamine (0.242 g, 2.4 mmol) in dry CH2Cl2 (15 mL) was treated dropwise with
acetic anhydride (0.245 g, 2.4 mmol) over 15 min at room temperature. The progress of the
reaction was monitored by TLC. The reaction mixture was stirred at room temperature for 48 h.
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Concentration of the reaction gave an off white solid (274 mg, 95% yield); mp. 139ꢀ140 °C; H
NMR:
δ
7.91 ꢀ 7.95 (m, 2H), 7.48 ꢀ 7.51 (m, 3H), 7.32 ꢀ 7.37 (m, 2H), 7.25 ꢀ 7.29 (m, 2H), 2.46
13
(s, 3H), 1.87 (s, 3H); C NMR:
δ 170.1, 145.0, 136.9, 136.1, 130.0, 129.9, 129.4, 129.2, 25.1,
21.7; HRMS: calcd for C15H15NO3S [M]+ 289.0773, found 289.0777; IR (KBr): 3390, 2923,
1705, 1596, 1489, 1356 cm−1.
4-Methyl-N-phenyl-N-tosylbenzenesulfonamide (26): A solution of aniline (1 mmol), pꢀ
toluene sulfonyl chloride (2 mmol) in pyridine (2.5 mL) was heated at 45 ºC stirred for 5 h. The
reaction mixture was extracted with CH2Cl2 (2 x 10 mL). The combined organic layers was dried
(Na2SO4) and then concentrated under reduced pressure. Purification of the crude by column
chromatography [silica, ethyl acetate/ hexane = 1:4] gave an off white solid (284 mg, 88%
1
yield); mp. 167ꢀ169 °C; H NMR: δ 7.84 (d, J=8.0 Hz, 4H), 7.45 (t, J=7.4 Hz, 1H ), 7.34 ꢀ 7.43
(m, 6H), 7.05 (d, J=8.0 Hz, 2H), 2.49 (s, 6H); 13C NMR: δ 145.0, 136.6, 134.4, 131.6, 130.1,
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129.5, 129.1, 128.6, 21.7; HRMS: calcd for C20H20NO4S2 [M+H]+ 402.0834, found 402.0830; IR
(KBr): 3395, 3065, 1490, 1378 cm−1.
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7-Fluoro-2-methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (27): Yield 65% (85 mg); off
1
white solid; mp. 175ꢀ176 °C; H NMR: δ 7.95 (d, J=8.0 Hz, 1H), 7.80 (m, 2H), 7.50 ꢀ 7.53 (d,
J=8.0 Hz, 1H), 7.21 ꢀ 7.26 (m, 2H), 2.56 (s, 3H); 13C NMR: δ 153.5 (d, J=243 Hz), 151.1, 143.4,
132.1, 131.7, 129.6, 125.9, 124.1 (d, J= 8 Hz), 122.2, 120.4 (d, J=4 Hz), 115.9, 115.7, 21.9;
HRMS: calcd for C13H11FNO2S [M+H]+ 264.0495, found 264.0492; IR (KBr): 3227, 1373, 1246
cm−1.
2-Methyl-7-(trifluoromethyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (28): Yield 67% (104
1
mg); off white solid; mp. 210ꢀ211 °C; H NMR: δ 8.23 (d, J=8.0 Hz, 1H), 7.93 (d, J=8.0 Hz,
1H), 7.80 (s, 1H), 7.76 (d, J=8.0 Hz, 1H), 7.42 ꢀ 7.48 (m, 2H), 7.24 (br. s, 1H), 2.57 (s, 3H); 13C
NMR: δ 143.4, 133.3, 132.8, 131.4, 129.8, 129.3, 127.3 (q, J=5 Hz), 126.4 , 125.2, 124.8 (q,
J=272 Hz), 124.4, 122.1, 121.1 (q, J=30 Hz), 21.9; HRMS: calcd for C14H11F3NO2S [M+H]+
314.0463, found 314.0469; IR (KBr): 3432, 1324, 1131 cm−1.
9-Chloro-2-methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (29): Yield 70% (97 mg); off
o
white solid; mp. 155ꢀ158 C; 1H NMR (DMSOꢀd6):
δ
8.32 (d, J=2.3 Hz, 1H), 8.18 (s, 1H), 7.84
13
(d, J=7.8 Hz, 1H), 7.53 (dd, J=8.7, 2.1 Hz, 2H), 7.22 (d, J=8.6 Hz, 1H), 2.51 (s, 3H); C NMR
(DMSOꢀd6):
δ
143.9, 143.4, 136.7, 132.3, 130.9, 129.6, 128.5, 127.2, 126.7, 125.5.3, 121.8, 121.6, 21.6; HR
MS: calcd for C13H11ClNO2S [M+H]+ 280.0199, found 280.0194; IR (KBr): 3246, 1602, 1419,
1308, 577 cmꢀ1.
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2-Methyl-9-nitro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (30): Yield 75% (108 mg); orange
4
5
1
solid; mp. 256ꢀ257 °C; H NMR (DMSOꢀd6): δ 9.10 (d, J=8.0 Hz, 1H), 8.08 (s, 1H), 7.48 (d,
6
7
8
9
J=8.0 Hz, 1H), 7.46 (dd, J=8.0, 2.6 Hz, 1H), 7.40 (s, 1H), 7.22 (d, J=8.0 Hz, 1H ), 2.37 (s, 3H);
13C NMR (DMSOꢀd6): δ 152.9, 140.3, 139.5, 138.7, 131.9, 129.9, 128.1, 127.9, 123.5, 122.1,
121.1, 117.4, 21.9; HRMS: calcd for C13H11N2O4S [M+H]+ 291.0440, found 291.0448; IR
(KBr): 3335, 1467, 1343 cm−1.
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8-Methoxy-2-methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (33): Yield 70% (96 mg); mp.
1
156ꢀ158 °C; off white solid; H NMR (DMSOꢀd6): δ 11.2 (br. s, 1H), 8.11 (d, J=8.9 Hz, 1H),
7.96 (s, 1H), 7.76 (d, J=7.9 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 6.87 (dd, J=8.8, 2.5 Hz, 1H), 6.70
13
(s, 1H), 3.82 (s, 3H), 2.47 (s, 3H); C NMR (DMSOꢀd6): δ 161.1, 143.1, 138.6, 132.3, 131.2,
128.4, 127.2, 125.4, 121.5, 114.7, 111.0, 104.1, 55.9, 21.7; HRMS: calcd for C14H14NO3S
[M+H]+ 276.0694, found 276.0696; IR (KBr): 3417, 3170, 1736, 1614, 1304, 1163 cm−1.
2,8,10-Trimethyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (35): Yield 76% (103 mg); mp.
115ꢀ117 °C; off white solid; 1H NMR: δ 7.90 (d, J=7.9 Hz, 1H), 7.66 (s, 1H), 7.33 (d, J=8.7 Hz,
1H), 7.01 (s, 1H), 6.80 (s, 1H), 2.70 (s, 3H), 2.51 (s, 3H), 2.35 (s, 3H); 13C NMR: δ 141.6,139.5,
136.4, 135.9, 133.8, 132.8, 130.0, 129.6, 127.8, 122.0, 121.1, 118.8, 23.0, 22.0, 21.1. HRMS:
calcd for C15H16NO2S [M+H]+ 274.0902, found 274.0903; IR (KBr): 3277, 2924, 1616, 1599,
1453, 1358, 1313, 1164 cm−1.
6H-Dibenzo[c,e][1,2]thiazine 5,5-dioxide (36): Yield 69% (67 mg); off white solid; mp. 194ꢀ
195 °C; 1H NMR:
δ 7.98 ꢀ 8.03 (m, 3H), 7.72 (td, J=7.5, 1.3, 1H), 7.57 (td, J=7.6, 1.1, 1H), 7.42
(td, J=7.7, 1.5 Hz, 1H), 7.32 (td, J=7.7, 1.3 Hz, 1H), 7.17 (br. s, 1H), 7.14 (dd, J=7.9, 1.1 Hz,
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1H); C NMR:
δ
135.4, 134.9, 132.5, 130.4, 128.3, 125.4, 125.2, 123.1, 122.1, 120.7; HRMS:
4
5
6
7
calcd for C12H10NO2S [M+H]+ 232.0432, found 232.0440; IR (KBr): 3219, 2924, 1746, 1314
cm−1.
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2-Nitro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (37): Yield 75% (103 mg), light yellow solid;
1
mp. 182ꢀ184 °C; H NMR (DMSOꢀd6):
δ 8.97 (d, J=2.0 Hz, 1H), 8.44 (dd, J=8.5, 2.3 Hz, 1H),
8.39 ꢀ 8.42 (m, 1H), 8.22 (d, J=8.5 Hz, 1H), 7.56 ꢀ 7.61 (m, 1H), 7.36 ꢀ 7.42 (m, 1H), 7.28 (dd,
J=8.0, 2.1 Hz, 1H); 13C NMR (DMSOꢀd6):
δ
150.4, 138.8, 137.1, 133.9, 132.2, 126.6, 124.9,
123.9, 123.7, 121.4, 121.0, 120.4; HRMS: calcd for C12H9N2O4S [M+H]+ 277.0283, found
277.0280; IR (KBr): 3397, 1651, 764 cm−1.
7-Fluoro-2-nitro-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (38): Yield 64% (94 mg); yellow
1
solid; mp. 244ꢀ245 °C; H NMR (DMSOꢀd6): δ 8.98 (s, 1H), 8.48 (dd, J=8.0, 2.1 Hz, 1H), 8.27
(d, J=8.0 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.40 ꢀ 7.45 (m, 1H); 13C NMR
(DMSOꢀd6): δ 155.0 (d, J=244 Hz), 152.3, 150.4, 139.3, 133.3, 125.6 (d, J= 8 Hz), 124.4, 124.2,
122.3 (d, J=3 Hz), 122.0, 118.0, 117.9; HRMS: calcd for C12H8FN2O4S [M+H]+ 295.0189, found
295.0197; IR (KBr): 3174, 1534, 1317 cm−1.
2-Nitro-7-(trifluoromethyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (39): Yield 65% (111
1
mg); off white solid; mp. 183ꢀ185 °C; H NMR (DMSOꢀd6): δ 9.0 (s, 1H), 8.68 (d, J=8.0 Hz,
1H), 8.50 (dd, J=8.0, 2.0 Hz, 1H), 8.22 (d, J=8.0 Hz, 1H), 7.95 (d, J=8.0 Hz, 1H), 7.63 (t, J=8.3
13
Hz, 1H); C NMR (DMSOꢀd6): δ 150.4, 140.1, 135.0, 133.3, 131.3, 129.1 (q, J=5 Hz), 126.9,
126.6, 125.0 (q, J=30 Hz), 124.9 (q, J=272 Hz), 124.8, 124.5, 122.5; HRMS: calcd for
C13H8F3N2O4S [M+H]+ 345.0157, found 345.0152; IR (KBr): 3294, 1530, 1323 cm−1.
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2,8-Dimethyl-6H-dibenzo[c,e][1,2]thiazine
5,5-dioxide
and
2,10-dimethyl-6H
4
5
dibenzo[c,e][1,2]thiazine 5,5-dioxide (inseparable regioisomers) (40): Yield 73% (94 mg); off
6
7
8
1
white solid; H NMR:
δ 7.97 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.85 (d, J=8.4 Hz,1H), 7.82 (d,
9
J=8.0 Hz, 2H), 7.40 ꢀ 7.45 (m, 2H), 7.29 ꢀ 7.33 (m, 1H), 7.18 ꢀ 7.20 (m, 1H), 7.10 (dd, J=8.0, 1.0
Hz, 1H), 6.96 (br. s, 1H), 2.74 (s, 1H), 2.53 (s, 3H), 2.39 (s, 3H); 13C NMR:
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δ
143.0, 141.7,
140.9, 136.7, 136.0, 135.5, 134.1, 132.7, 131.9, 129.6, 129.0, 128.8, 128.6, 128.2, 127.9, 126.9,
125.0, 124.8, 124.7, 121.1, 119.5, 119.4, 23.21, 21.9, 21.5; HRMS: calcd for C14H14NO2S
[M+H]+ 260.0745, found 260.0750; IR (KBr): 3291, 2922, 2852, 1456 cm−1.
1
2,8-Dimethyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (40): H NMR:
δ 7.87 (d, J=7.96 Hz,
2H), 7.7 (s, 1H), 7.34 (d, J=8.6 Hz,1H), 7.12 (d, J=7.16 Hz, 1H), 6.91 (s, 1H), 6.96 (br. s, 1H),
13C
NMR:
2.51
(s,
3H),
2.40
(s,
3H);
δ
143.1, 140.9, 135.4, 132.5, 128.7, 126.2, 125.5, 125.3, 122.3, 121.0, 120.5, 22.0, 21.4.
8-Bromo-2-methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 10-bromo-2-methyl-
6
H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (inseparable regioisomers) (41): Yield 51%; off
white solid; 1H NMR:
δ
8.45 (s, 1H), 8.02 (dd, J=7.9, 1.3 Hz, 1H), 7.88 ꢀ 7.94 (m, 2H), 7.81
(s, 1H), 7.62 (dd,
Hz, 1H), 7.14 (dd,
NMR:
J
=8.0, 1.3 Hz, 1H), 7.39 ꢀ 7.44 (m, 2H), 7.30 ꢀ 7.36 (m, 1H), 7.23 (t,
J=7.9
J=8.0, 1.1 Hz, 1H), 7.11 (dd, J
=8.0, 1.3 Hz, 1H), 2.53 ꢀ 2.56 (m, 4H); 13C
δ
141.6, 137.4, 133.9, 131.9, 131.4, 130.3, 130.1, 129.3, 125.7, 121.8, 121.3, 120.0,
21.9; HRMS: calcd for C13H11BrNO2S [M+H]+ 323.9694, found 323.9699; IR (KBr): 3384,
2923, 2853, 1742, 1436, 1384 cm−1.
10-Bromo-2-methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (41)
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1H NMR:
δ
8.45 (s, 1H), 7.89 (dd, J=7.9, 1.3 Hz, 1H), 7.62 (dd, J=7.9, 1.2 Hz, 1H), 7.41 (td,
4
5
13
J=8.0, 1.36 Hz, 1H), 7.22 (t, J=8 Hz, 1H), 7.11 (dd, J=7.9, 1.3 Hz, 1H), 2.54 (s, 3H); C NMR:
6
7
8
δ
141.6, 137.3, 133.8, 131.8, 131.4, 130.3, 130.0, 129.3, 123.9, 121.7, 121.2, 120.0, 21.9.
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3-Methyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide (42): Yield 74% (90 mg); off white solid;
mp. 158ꢀ159 °C; 1H NMR (MeOD):
δ
8.08 (dd, J=8.0, 1.3 Hz, 1H), 8.03 (d, J=8.2 Hz, 1H), 7.77
(s, 1H), 7.59 (dd, J=8.0, 1.3 Hz, 1H), 7.42 (td, J=8.0, 1.3 Hz, 1H), 7.26 ꢀ 7.31 (m, 1H), 7.17 (dd,
13
J=8.0, 1.0 Hz, 1H), 2.50 (s, 3H); C NMR (MeOD): 138.7, 136.3, 134.7, 133.0, 129.7, 129.5,
125.0, 124.5, 123.8, 122.2, 121.0, 119.4, 19.7; HRMS: calcd for C13H12NO2S [M+H]+ 246.0589,
found 246.0595; IR (KBr): 3201, 2923, 2851, 1728, 1454 cm−1.
4-Methyl-N,N-diphenylbenzenesulfonamide (46): Yield 88%; off white solid; mp. 115ꢀ116 °C;
1H NMR: δ 7.62 (d, J=8.0 Hz, 2H), 7.26 ꢀ 7.36 (m, 12H), 2.46 (s, 3H); 13C NMR: δ 143.6, 141.6,
137.6, 129.5, 129.2, 128.6, 128.3, 127.8, 127.6, 127.4, 21.5; HRMS: calcd for C19H18NO2S
[M+H]+ 324.1058, found 324.1056; IR (KBr): 3060, 1593, 1487, 1351, 1157 cm−1.
1
9-Tosyl-9H-carbazole (47):6,36 Yield 51%; off white solid; H NMR: δ 8.35 (d, J=8.0 Hz, 2H),
7.93 (d, J=8.0 Hz, 2H), 7.71 (d, J=8.0 Hz, 2H), 7.51 (t, J=8.0 Hz, 2H), 7.38 (t, J=8.0 Hz, 2H),
7.11 (d, J=8.0 Hz, 2H), 2.28 (s, 3H); 13C NMR: δ 21.5, 115.1, 119.9, 123.8, 126.3, 126.4, 127.3,
129.6, 135.0, 138.4, 144.8; HRMS: calcd for C19H16NO2S [M+H]+ 322.0902, found 322.0901;
IR (KBr): 3401, 2917, 1591, 1432, 1371, cm−1.
N-([1,1'-Biphenyl]-2-yl)-4-methylbenzenesulfonamide (48):37 A solution of phenylboronic
acid (0.390 g, 3.20 mmol), K2CO3 (1.49 g, 10.8 mmol), PdCl2 (0.048 g, 0.32 mmol), and PPh3
(0.122 g, 0.64 mmol) in DMF and H2O (DMF : H2O = 5:1, 16 mL) was treated dropwise with 2ꢀ
bromoaniline (0.464 g, 2.7 mmol), and the resulting mixture was heated at 80 °C for 48 hours.
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Water (25 mL) was added to the reaction mixture and the aqueous layer was extracted with
CH2Cl2 (3 x 10 mL). The combined organic layer was dried (Na2SO4), followed by concentrated
to obtain a residue, which upon purification by column chromatography [silica EtOAc:hexane =
1:5] gave 2ꢀaminobiphenyl (280 mg, 61% yield). To a solution of 2ꢀaminobiphenyl (0.215 g) in
pyridine (3 mL) was added pꢀtoluenesulfonyl chloride (0.347 g) at 0 °C. After stirring at 25 °C
for 1 h, the reaction mixture was poured into water and the aqueous layer was extracted with
CH2Cl2 (3 x 10 mL). Drying (Na2SO4) followed by concentration of the organic layer gave a
residue, which upon chromatography [silica, EtOAc:hexane = 1:9] gave an off white solid (376
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44
45
46
47
48
49
50
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53
54
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56
57
58
59
60
1
mg, 92% yield). H NMR: δ 7.71 (dd, J=8.2, 0.9 Hz, 1H), 7.45 ꢀ 7.49 (m, 2H), 7.30 – 7.37 (m,
4H), 7.19 (d, J=8.0 Hz, 2H), 7.14 (td, J=7.6, 1.1 Hz, 1H), 7.09 (dd, J=7.6, 1,7 Hz, 1H), 6.85 ꢀ
6.87 (m, 2H), 6.57 (br. s, 1H), 2.40 (s, 3H); 13C NMR: δ 143.9, 137.2, 136.2, 133.9, 133.8, 130.3,
129.6, 129.1, 128.9, 128.7, 128.1, 127.2, 124.9, 121.3, 21.6; HRMS: calcd for C19H18NO2S
[M+H]+ 324.1058, found 326.1060; IR (KBr): 3335, 2916, 2848, 1595, 1477, 1333, 1163, 902,
664 cm−1.
1
Phenyl 4-methylbenzenesulfonate (49):38 Yield 97%; off white solid; mp. 89ꢀ90 °C; H NMR:
13
δ
7.73 (d, J=8.5 Hz, 2H), 7.25 ꢀ 7.35 (m, 5H), 6.99 ꢀ 7.03 (m, 2H), 2.47 (s, 3H); C NMR: δ
149.7, 145.3, 132.5, 129.7, 129.6, 128.5, 127.1, 122.4, 21.7; HRMS: calcd for C13H13O3S
[M+H]+ 249.0585, found 249.0588; IR (KBr): 3059, 1594, 1378, 777 cm−1.
9-Methyldibenzo[c,e][1,2]oxathiine 6,6-dioxide (50):25 Yield 47% (57 mg); off white solid;
1
mp. 172ꢀ174 °C; H NMR:
δ 7.94 (dd, J=7.8, 1.5 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.75 (s, 1H),
7.48 (dd, J=7.7, 1.6 Hz, 1H), 7.38 ꢀ 7.43 (m, 2H), 7.34 (dd, J=8.2, 1.4 Hz, 1H), 2.54 (s, 3H); 13C
NMR:
δ
149.9, 144.6, 131.6, 129.8, 128.5, 127.1, 126.5, 125.3, 124.2, 122.4, 121.7, 120.1, 22.1;
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HRMS: calcd for C13H11O3S [M+H]+ 247.0429, found 247.0433; IR (KBr): 3419, 2922, 1732,
1484, 1369, 1180, 793 cm−1.
5
6
7
8
1
4-Chlorophenyl 4-methylbenzenesulfonate (51):39 Yield 96%; yellow solid; mp. 75ꢀ78 °C; H
9
10
11
12
13
14
15
16
17
18
19
20
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22
23
24
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34
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38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NMR: δ 7.72 (d, J=8.0 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 7.26 (td, J=8.0, 3.1 Hz, 2H), 6.93 (td,
13
J=8.0, 3.2 Hz, 2H), 2.47 (s, 3H); C NMR: δ 148.0, 145.6, 132.7, 132.0, 129.8, 129.7, 128.5,
123.7, 21.7; HRMS: calcd for C13H12ClO3S [M+H]+ 283.0196, found 283.0190; IR (KBr): 3095,
1173, 1376, 753 cm−1.
2-Chloro-9-methyldibenzo[c,e][1,2]oxathiine 6,6-dioxide (52): Yield 52% (72 mg); yellow
1
solid; mp. 170ꢀ172 °C; H NMR: δ 7.92 (d, J=8.0 Hz, 2H), 7.73 (s, 1H), 7.44 ꢀ 7.47 (m, 2H),
7.31 (d, J=8.0 Hz, 1H), 2.57 (s, 3H); 13C NMR: δ 148.2, 144.9, 132.1, 130.8, 130.5, 130.3, 129.6,
125.3, 125.0, 124.3, 123.1, 121.4, 22.0; HRMS: calcd for C13H10ClO3S [M+H]+ 281.0039, found
281.0033; IR (KBr): 2921, 1363, 734 cm−1.
1-(Benzylsulfonyl)-4-methylbenzene (53):40 A stirred suspension of pꢀtoluenesulfonylchloride
(0.588 g, 3.00 mmol), sodium sulfite (0.752 g, 6.00 mmol), and NaHCO3 (0.504 g, 6.00 mmol) in
water (30 mL) was heated at reflux for 3 h. Benzyl bromide (0.641 g, 3.50 mmol) followed by
(nꢀBu)4NBr (0.165 g, 0.045 mmol) were added and the reaction mixture was stirred overnight at
o
70 C. Addition of water (10 mL) to the reaction mixture, extraction with CH2Cl2 (20 mL x 2),
and then drying (Na2SO4), followed by concentration of the combined organic layer gave a
residue, which upon purification [silica, EtOAc:hexane = 1:9] gave an off white solid: (530 mg,
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72%; yield); H NMR:
δ 7.49 ꢀ 7.54 (m, 2 H), 7.31 ꢀ 7.36 (m, 1 H), 7.27 ꢀ 7.31 (m, 2 H), 7.23 ꢀ
7.27 (m, 2 H), 7.08 ꢀ 7.13 (m, 2 H), 4.29 ꢀ 4.32 (m, 2 H), 2.43 (s, 3 H); 13C NMR: δ 144.7, 135.0,
130.8, 129.5, 128.7, 127.8, 127.0, 126.3, 62.9, 21.6; HRMS: calcd for C14H14O2S [M]+ 246.0715,
found 246.0718; IR (KBr): 3445, 3251, 2972, 1452, 1325 cm−1.
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(S)-3-Methyl-N-(1-phenylethyl)benzenesulfonamide (55):41 Yield 93% (255 mg); off white
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solid; mp. 116ꢀ117 °C; H NMR:
δ 7.57 (ddd, J=5.1, 3.5, 1.8 Hz, 1H), 7.50 (s, 1H), 7.27 ꢀ 7.31
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(m, 2H), 7.17 ꢀ 7.21 (m, 3H), 7.09 ꢀ 7.14 (m, 2H), 4.51 (q, J=6.8 Hz, 1H), 2.32 (s, 3H), 1.46 (d,
J=7.0 Hz, 3H); 13C NMR:
δ
142.0, 140.4, 138.9, 133.1, 128.7, 128.5, 127.5, 127.5, 126.1, 124.1,
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53.8, 23.7, 21.2; HRMS: calcd for C15H18NO2S [M+H]+ 276.1058, found 276.1054; IR (KBr):
3449, 3262, 2975, 1448, 1336 cm−1.
(S)-2,7-Dimethyl-6,7-dihydrodibenzo[d,f][1,2]thiazepine 5,5-dioxide (56): Yield 63% (86
1
mg); colorless crystal; mp.129ꢀ130 °C; H NMR: δ 8.07 (d, J=8.2 Hz, 2H), 7.81 (d, J=7.2 Hz,
1H), 7.65 ꢀ 7.69 (m, 1H), 7.45 ꢀ 7.51 (m, 2H), 7.36 (d, J=7.9 Hz, 2H), 5.32 – 5.37 (m, 1H), 2.45
(s, 3H), 1.82 (d, J=6.3 Hz, 3H); 13C NMR: δ 147.4, 145.0, 134.0, 129.5, 128.9, 128.8, 128.2,
124.9, 122.4, 58.6, 21.6, 21.4; HRMS: calcd for C15H16NO2S [M+H]+ 274.0902, found
274.0911; IR (KBr): 3446, 1596, 1358, 1169 cm−1.
(S)-4-Methyl-N-(1-phenylethyl)benzenesulfonamide (57): Yield 90% (247 mg); off white
1
solid; mp. 108ꢀ110 °C; H NMR: δ 7.63 (d, J=8.0 Hz, 2H), 7.19ꢀ7.25 (m, 5H), 7.11ꢀ7.13 (m,
13
2H), 4.85 (br. s, 1H), 4.45 – 4.52 (m, 1H), 2.41 (s, 3H), 1.45 (d, J=6.8 Hz, 3H); C NMR: δ
143.1, 142.0, 137.6, 129.4, 128.5, 127.4, 127.1, 126.1, 53.6, 23.5, 21.4; HRMS: calcd for
C15H18NO2S [M+H]+ 276.1058, found 276.1053; IR (KBr): 3251, 1596, 1437, 1319 cm−1.
(S)-3,7-Dimethyl-6,7-dihydrodibenzo[d,f][1,2]thiazepine 5,5-dioxide (58): Yield 83% (113
1
mg); off white solid; mp. 136ꢀ137 °C; H NMR:
δ 8.00 (td, J=1.5, 0.8 Hz, 1H), 7.95 ꢀ 7.99 (m,
1H), 7.82 (d, J=7.7 Hz, 1H), 7.67 (td, J=6.5, 1.1 Hz, 1H), 7.46 ꢀ 7.52 (m, 2H), 7.43 ꢀ 7.46 (m,
2H), 5.34 (q, J=6.5 Hz, 1H), 2.47 (s, 3H), 1.82 (d, J=6.5 Hz, 3H); 13C NMR:
δ
147.4, 139.3,
134.7, 134.1, 128.8, 128.5, 125.3, 125.0, 122.5, 58.7, 21.5, 21.4; HRMS: calcd for C15H16NO2S
[M+H]+ 274.0902, found 274.0905; IR (KBr): 3456, 1591, 1349, 1179 cm−1.
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ACKNOWLEDGEMENT
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We thank Dr. Ankur Gupta for helping with the initial optimization study. We greatly appreciate
the CSIR, New Delhi for financial support.
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ASSOCIATED CONTENT
Supporting Information
1H and 13C NMR spectra for all new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.REFERENCES
(1) a) Berger, O.; Petit, C.; Deal, E. L.; Montchamp, J.ꢀL. Adv. Synth. Catal. 2013, 355, 1361; b)
Wang, Z.; Gao, Z.; Feng, Y.; Liu, Y.; Yang, B.; Liu, D.; Lv, Y.; Lu, P.; Ma, Y. Polymer 2013,
54, 6191; also see review: c) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem. Int. Ed.
2012, 51, 8960; d) Schmidt, A. W.; Reddy, K. R.; Knölker, H. J. Chem. Rev. 2012, 112, 3193; e)
Fan, H.; Peng, J.; Hamann, M. T.; Hu, J. F. Chem. Rev. 2008, 108, 264; f) Hassan, J.; Vignon, M.
S.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
(2) Wu, Y.; Wang, J.; Mao, F.; Kwong, F. Y. Chem. Asian. J. 2014, 9, 26 and references cited
therein.
(3) See reviews for cross coupling reactions: a) Han, F.ꢀS. Chem. Soc. Rev. 2013, 42, 5270; b)
Modha, S. G.; Mehtaz, V. P.; Van der Eycken, E. V. Chem. Soc. Rev. 2013, 42, 5042; c) Liu, C.;
Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780; d) Kambe, N.; Iwasaki, T.; Terao, J.
Chem. Soc. Rev. 2011, 40, 4937.
(4) a) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879; b) McMurray,
L.; OꞌHara F.; Gaunt, M. J. Chem. Soc. Rev. 2011, 40, 1885; c) Baudoin, O. Chem. Soc. Rev.
2011, 40, 4902; d) Ackermann, L. Chem. Rev. 2011, 111, 1315; e) Bellina, F.; Rossi, R. Chem.
Rev. 2010, 110, 1082; f) René, O.; Fagnou, K. Org. Lett. 2010, 2116.
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