Palladium-catalyzed reactions of allenes with 2-iodobenzenesulfonamides: Simple synthesis of benzosultams under green conditions

Article abstract of DOI:10.1055/s-0033-1340821

A palladium-catalyzed reaction for the synthesis of benzosultams from allenes and 2-iodobenzenesulfonamides in poly(ethylene glycol) medium is described. This route is compared with a second method involving an internal Heck reaction of alkene-functionalized 2-iodobenzenesulfonamides. Key products were characterized by single-crystal X-ray crystallography. Georg Thieme Verlag Stuttgart? New York.

Full text of DOI:10.1055/s-0033-1340821

PAPER
▌1091
paper
Palladium-Catalyzed Reactions of Allenes with 2-Iodobenzenesulfonamides:
Simple Synthesis of Benzosultams under Green Conditions
Benzosultams from Allenes
M. Nagarjuna Reddy, K. C. Kumara Swamy*
School of Chemistry, University of Hyderabad, Hyderabad 500 046, A. P., India
Fax +91(40)23012460; E-mail: kckssc@uohyd.ac.in; E-mail: kckssc@uohyd.ernet.in; E-mail: kckssc@yahoo.com
Received: 15.11.2013; Accepted after revision: 23.01.2014
intramolecular Heck reactions of the N-alkenyl sulfon-
Abstract: A palladium-catalyzed reaction for the synthesis of ben-
amides 3a and 3b (Figure 2).
zosultams from allenes and 2-iodobenzenesulfonamides in po-
ly(ethylene glycol) medium is described. This route is compared
O
with a second method involving an internal Heck reaction of al-
kene-functionalized 2-iodobenzenesulfonamides. Key products
were characterized by single-crystal X-ray crystallography.
O
O
O
N
O
S
O
S
S
S
OMe
S
H2N
Key words: palladium, catalysis, allenes, sulfonamides, green
Cl
N
chemistry
NH2
I
II
HIV integrase
inhibitor
carbonic anhydrase
inhibitor
Among sulfur-containing compounds, sulfonamides and
their derivatives have had a profound influence on the de-
velopment of chemistry, particularly biological chemis-
try.1 In particular, benzosultams (cyclic sulfonamides) are
important structural motifs that are widely encountered in
the drug-development process.2 Examples of biologically
important sultams include the HIV integrase inhibitor I
(Figure 1),3a the carbonic anhydrase inhibitor II,3b the cal-
pain I inhibitor III,3c the antiviral, antibacterial, and anti-
microbial agent IV,3d and the nonsteroidal
antiinflammatory agent V.3e In addition to their medicinal
value, sultams are indispensable as chiral auxiliaries,4a,b
artificial sweeteners (saccharin),4c and agrochemicals.4d
Consequently, a wide range of methods have been devised
for synthesizing benzosultams and related structures.5
O
O
O
O
R
S
S
Et
O
O
N
H
N
CHO
O
N
N
N
Ph
O
III
calpain I inhibitor
IV
antimicrobial and
antibacterial agent
O
S
Me
N
H
N
N
OH
O
V
nonsteroidal antiinflammatory drug
Figure 1 Examples of pharmaceutically important benzosultams
In recent decades, significant progress has been made on
palladium-catalyzed annulation reactions.6 Allenes can
participate in such reactions to give carbocycles or hetero-
cycles.7 For the synthesis of benzosultams, diverse meth-
ods have been developed,5a,8 but there have been only two
reports on the use of allenes in syntheses of these com-
pounds.9 These involve nickel-catalyzed annulation reac-
tions of 2-methyl-2H-1,2,3,4-benzothiatriazine 1,1-
dioxide with allenes,9a and the palladium-catalyzed reac-
tion of 2-iodobenzenesulfonamide with allene (one exam-
ple), respectively.9b The development of a new and
efficient method for synthesizing benzosultams by using
allenes is therefore an important challenge. In this context,
and in continuation of our interest in metal-catalyzed an-
nulation reactions of allenes,10,11 we report mild and envi-
ronmentally benign conditions for the synthesis of
benzosultams from allenes 1a–h and 2-iodobenzenesul-
fonamides 2a–f; we also report the synthesis of sultams by
Ph
R1
I
R
H
R
I
H
N
R2
S
N
O
S
Me
O
R = BnO (1a)
1 = Me, R2 = Me (2a)
1 = Me, R2 = i-Pr (2b)
1 = Me, R2 = Bn (2c)
O
R
R
R
R
R
R
O
R = 4-BrC6H4CH2O (1b)
R = 2-BrC6H4CH2O (1c)
R = n-C8H17 (1d)
R = BnOCH2 (1e)
R = Bn(Ts)N (1f)
R = Me 3a (72%)
R = t-Bu 3b (68%)
1 = OMe, R2 = Me (2d)
1 = t-Bu, R2 = Me (2e)
1 = Ph, R2 = Me (2f)
R = Ph (1g)
R = 4-MeC6H4 (1h)
Figure 2 Precursors used in the present study
Initially, we examined the reaction of (benzyloxy)allene
(1a) with 2-iodo-N,4-dimethylbenzenesulfonamide (2a)
in the presence of a palladium catalyst in acetonitrile. To
our delight, this strategy gave the (β,α)-cyclized product
5, along with the noncyclized α-addition product 4
(Scheme 1). In the 13C NMR spectrum of compound 5, the
peak associated with C-I was absent, as expected. The ab-
sence of the NH peak and the disappearance of the allenic
CH peak in the 1H NMR spectrum in 5, with concomitant
appearance of an OCH peak, are clearly indicative of ring
SYNTHESIS 2014, 46, 1091–1099
Advanced online publication: 12.02.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340821; Art ID: SS-2013-T0747-OP
© Georg Thieme Verlag Stuttgart · New York

1092
M. Nagarjuna Reddy, K. C. Kumara Swamy
PAPER
formation. Compound 4 is a monosubstituted alkene; its none of the (β,γ)-cyclized product. We were pleased that
formation is possible only when the sulfonamide attacks PEG-400 worked well as a solvent, because it is known to
at the α-position of the allene.12b
be an environmentally friendly medium.13 PEG is also
known to generate and stabilize nanoparticles of palladi-
um in the course of the reaction.14
I
OBn
H
+
Under our optimized conditions, the annulation reaction
of allenes 1a–e with 2-iodobenzenesulfonamides 2a–f
gave the corresponding benzosultams 5–14 (Table 2). All
these compounds are the (β,α)-cyclized products. The ini-
tial attack of the arylpalladium species occurs at the β-po-
sition of the allene,15 and cyclization then takes place
regiospecifically at the α-position utilizing the sulfon-
amide-NH. The (β,α)-cyclization route was confirmed by
X-ray crystallographic analysis of sultam 12 (Figure 3).
N
γ
β
α
S
Me
O
1a
O
2a
γ
γ
β
I
OBn
α
β
OBn
Me
α
N
+
N
S
S
Me
O
O
O
O
4 (36%)
5 (42%)
Table 2 : Scope of the Palladium-Catalyzed Annulations Reaction of
Allenes 1a–e with 2-Iodobenzenesulfonamides 2a–f
Scheme 1 Palladium-catalyzed reaction of (benzyloxy)allene (1a)
with 2-iodo-N,4-dimethylbenzenesulfonamide (2a). Reagents and
conditions: Pd(OAc)2 (5 mol%), Ph3P (10 mol%), K2CO3 (2.0 equiv),
MeCN, 80 °C, 12 h.
γ
R1
I
R1
R3
R2
R3
+
β
α
N
H
N
γ
β
α
1a–e
S
R2
S
Inspired by these results, we screened various palladium
catalysts, bases, and solvents to optimize the reaction con-
ditions (Table 1). Of the solvents tested, poly(ethylene
glycol) (molecular weight 400; PEG-400) was the best. In
the absence of a phosphine ligand, the yield decreased
(entry 10). The best combination involved palladium(II)
acetate and triphenylphosphine as the catalyst system, po-
tassium carbonate as the base, and PEG-400 as the solvent
(entry 4); this gave benzosultam 5 regiospecifically with
O
O
O
O
5–14
2a–f
Entry Reactants Product R1
R2
R3
Yielda
(%)
1
2
1a + 2a
1a + 2b
1a + 2c
1a + 2d
1a + 2e
1a + 2f
5
6
Me
Me
i-Pr
Bn
OBn
OBn
OBn
OBn
OBn
OBn
77
77
69
81
75
67
Me
Me
3
7
Table 1 Effects of Various Catalysts, Bases, and Solvents on the
Yield of Sultam 5
4
8
OMe Me
5
9
t-Bu Me
OBn
I
OBn
Me
6
10
Ph
Me
Me
Me
Me
Me
+
H
γ
β
α
N
N
7
1b + 2a 11
1c + 2a
12b
1d + 2a 13
1e + 2a 14
Me
Me
Me
Me
OCH2C6H4-4-Br 65
OCH2C6H4-2-Br 63
S
Me
S
1a
O
2a
O
O
O
8
5
9
n-C8H17
85
62
Entrya
Catalyst
Base
Solvent
Yieldb (%)
10
CH2OBn
1
2
Pd(OAc)2
Pd(OAc)2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K3PO4
CsF
DMF
45
56
–
a Yields of the isolated products.
b Structure confirmed by x-ray crystallography.
toluene
3
Pd(OAc)2
Et2CO3
In contrast to the above, the annulation reaction of the
aminoallene 1f with 2-iodobenzenesulfonamides 2a, 2b,
2d, and 2e in the presence of the palladium catalyst gave
the (β,γ)-cyclized products 15–18 in good yields (Scheme
2). In this case, a proton shift from the γ-carbon to the α-
carbon was observed. The structure of compound 16 was
confirmed by X-ray crystallography (Figure 4). The C(7)–
C(8) bond length [1.334(4) Å] indicated that it is a double
bond, whereas that of C(7)–C(9) [1.489(4) Å] indicated
that this is a single bond, confirming that isomerization
had occurred. Generally O- and N-substituted allenes give
(β,α)-cyclized products.12 The difference in reactivity ob-
served in the case of 1f might therefore be due to the bulk
Pd(OAc)2
4
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
77
62
55
49
56
49
45c
5
PdCl2
6
PdCl2(MeCN)2
Pd2(dba)3
7
8
Pd(OAc)2
9
Pd(OAc)2
10
Pd(OAc)2
a Reaction conditions: Pd catalyst (5 mol%), Ph3P (10 mol%), base
(2.0 equiv), solvent (1 mL), 80 °C (oil bath), 12 h.
b Isolated yield.
c In the absence of Ph3P.
Synthesis 2014, 46, 1091–1099
© Georg Thieme Verlag Stuttgart · New York

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Benzosultams from Allenes
1093
Figure 3 ORTEP drawing of benzosultam 12. Selected bond lengths
(with estimated standard deviations in parentheses): C(6)–C(7)
1.480(4), C(7)–C(8) 1.496(4), C(7)–C(17) 1.311(5), C(8)–N(1)
1.483(4), S(1)–O(2) 1.427(3), S(1)–N(1) 1.619(3) Å.
Figure 4 ORTEP drawing of benzosultam 16 (hydrogen atoms are
omitted for clarity). Selected bond lengths with estimated standard
deviations in parentheses: C(6)–C(7) 1.453(4), C(7)–C(8) 1.334(4),
C(7)–C(9) 1.489(4), C(9)–N(2) 1.459(4), S(1)–N(1) 1.627(3), C(8)–
N(1) 1.383(4), S(2)–N(2) 1.629(3) Å.
of the substituents around the nitrogen atom, which favors
the (β,γ)-cyclized product. A highlight of the current work
is that one product is formed regioselectively by using an
environmentally benign (green) solvent, PEG-400.
I
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
Ar
H
+
N
γ
β
α
Ts
N
S
Me
K2CO3, PEG-400
80 °C, 12 h
1g–h
O
O
Ts
α
Bn
2a
R1
I
β
N
R1
γ
α
Bn
H
Ar
N
+
α
β
γ
N
R2
β
γ
S
R2
S
β
O
Ar
O
O
O
γ
α
R1 = Me, R2 = Me 15 (62%)
R
R
R
1 = Me, R2 = Me (2a)
1 = Me, R2 = i-Pr (2b)
1 = OMe, R2 = Me (2d)
1 = t-Bu, R2 = Me (2e)
+
1f
R
R
R
R
N
N
1 = Me, R2 = i-Pr 16 (67%; X-ray)
1 = OMe, R2 = Me 17 (61%)
1 = t-Bu, R2 = Me 18 (68%)
S
Me
S
Me
O
O
O
O
Ar = Ph
Ar = 4-MeC6H4
19 (65%, X-ray)
21 (67%)
20 (16%)
22 (12%)
Ts
via
R1
Scheme 3 Palladium-catalyzed reactions of aryl allenes 1g and 1h
N
α
Bn
γ
β
isomerization
N
R2
S
O
O
not isolated
Scheme 2 Palladium-catalyzed reactions of allene 1f with 2-iodo-
benzenesulfonamides. Reagents and conditions: Pd(OAc)2 (5 mol%),
Ph3P (10 mol%), K2CO3 (2.0 equiv), PEG-400 (1 mL), 80 °C, 12 h.
Having successfully used heteroatom- and alkyl-substitut-
ed allenes in our cyclization, we turned our attention to the
use of aryl-substituted allenes. Palladium-catalyzed annu-
lation reactions of aryl allenes 1g and 1h with 2a gave the
(β,γ)-cyclized product 19 and 21 predominantly, along
with minor quantities of the corresponding (β,α)-cyclized
products 20 and 22 after isomerization (Scheme 3). The
structure of compound 19 was confirmed by X-ray crys-
tallography (Figure 5).
In contrast to the above, treatment of 5,5-dimethyl-2-(1-
phenylpropa-1,2-dien-1-yl)-1,3,2-dioxaphosphinane 2-
oxide with 2-iodo-N-methyl-4-methylbenzenesulfon-
amide (2a) in the presence of a palladium catalyst gave the
Figure 5 ORTEP drawing of benzosultam 19. Selected bond lengths
with estimate standard deviations in parentheses: C(6)–C(7) 1.473(3),
C(7)–C(9) 1.329(4), S(1)–O(1) 1.414(2), S(1)–N(1) 1.630(2) Å.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1091–1099

1094
M. Nagarjuna Reddy, K. C. Kumara Swamy
PAPER
nucleophilic addition product 23 (Scheme 4). We have
CuI (10 mol%)
1,10-phenanthroline
previously reported similar reactions.16
O
I
O
K2CO3, toluene
110 °C, 12 h
S
N
HN
S
Me
Me
O
O
O
25 (82%)
P
O
O
α
β
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
Ph
I
O
O
P
O
2a
+ 2a
γ
O
O
γ
α
β
K2CO3, MeCN
80 °C, 12 h
N
Ph
S
Me
S
MeHN
O
O
Pd(OAc)2 (5 mol%)
23 (72%)
NHMe
S
Ph3P, K2CO3, toluene
110 °C, 12 h
Scheme 4 Palladium-catalyzed reaction of an allenylphosphonate
with 2-iodobenzenesulfonamide 2a to give addition product 23
O
O
26 (10%)
We then examined an alternative method for synthesizing
similar products from a single sulfonamide substrate in
the presence of a palladium catalyst. We prepared the N-
alkenyl sulfonamides 3a and 3b by the Mitsunobu reac-
tion,17 and subjected them to a Heck reaction in the pres-
ence of a palladium catalyst. In PEG-400 medium the
substrate 3a remained even after 12 hours (based on the
1H NMR spectrum of the crude mixture), whereas when
N,N-dimethylformamide was used as the solvent, the re-
action was complete in 12 hours. This reaction gave the
cyclized products 19 and 24 in reasonable yields (Scheme
5). However, many steps are required to synthesize sub-
strates with substituents on the NCH2 carbon, and there-
fore this route is not convenient for synthesizing
substituted benzosultams of the type obtained from al-
lenes.
Scheme 6 Formation of self-coupled products 25 and 26 from 2a in
the presence of copper and palladium catalysts
zation products were predominant. Similar benzosultams
were also synthesized by means of a Heck protocol, but
this route may be restricted to the synthesis of less-substi-
tuted products.
R1
I
H
N
S
R2
O
O
γ
α
γ
α
β
β
N(Ts)Bn
X
Ts
N
X = OR, alkyl
Ph
Ph
Bn
R2
R1
X
R1
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
R
I
R
N
N
O
N
O
N
O
S
R2
S
K2CO3, DMF
80 °C, 12 h
S
Me
S
Me
O
O
O
O
O
R = Me (3a)
R = t-Bu (3b)
R = Me (19, 75%)
R = t-Bu (24, 72%)
(4 examples)
(10 examples)
Scheme 7 Overall summary of the synthesis of benzosultams from
allenes. Reaction conditions: Pd(OAc)2 (5 mol%), Ph3P (10 mol%),
K2CO3 (2.0 equiv), PEG-400 (1 mL), 80 °C, 12 h.
Scheme 5 Heck reaction on substrates 3a and 3b
Finally, we checked the reactivity and stability of sub-
strate 2a in the presence of palladium catalysts and copper
catalysts (Scheme 6). In the presence of a copper catalyst,
sulfonamide 2a gave the self-coupled product 25, with
formation of a new C–N bond. In the presence of palladi-
um catalyst, however, the coupled product 26 was isolated
in 10% yield along with unreacted 2a.
Solvents were dried by known methods as appropriate.18 1H and 13
C
NMR spectra were recorded at 400 and 100 MHz, respectively, by
using a Bruker AV-400 spectrometer in CDCl3 (unless otherwise
stated); shifts are referenced to Me4Si (δ = 0 ppm). IR spectra were
recorded on a Jasco model 5300 FTIR spectrophotometer. Melting
points were determined by using a local hot-stage melting-point ap-
paratus and are uncorrected. High-resolution mass spectra were re-
corded by using Bruker maXis mass spectrometer operated in the
ESI–QTOF-II mode. Single-crystal X-ray diffraction data were col-
lected with an Oxford diffractometer using Mo Kα (λ = 0.71073 Å)
radiation. The structure was solved and refined by standard meth-
ods.19–20 The syntheses of precursors 1a–h,7c,21 2a–f,5b,22 3a, and
3b17 are described in the Supporting Information.
In conclusion, we have developed a simple method for the
palladium-catalyzed regiospecific annulation reactions of
allenes with 2-iodobenzenesulfonamides in PEG-400 to
give benzosultams in good yields (Scheme 7). The (β,α)-
cyclization product is preferred in the case of O-substitut-
ed or alkyl allenes 1a–e, whereas (β,γ)-cyclized products
are formed and undergo a subsequent proton shift the case
of the N-substituted allene 1f. The aryl allenes 1g and 1h
showed an intermediate behavior in which the (β,γ)-cycli-
N-[1-(Benzyloxy)prop-2-en-1-yl]-2-iodo-N,4-dimethylbenzene-
sulfonamide (4)
A Schlenk tube was charged with allene 1a (110 mg, 0.75 mmol),
sulfonamide 2a (156 mg, 0.5 mmol), Pd(OAc)2 (0.025 mmol), Ph3P
Synthesis 2014, 46, 1091–1099
© Georg Thieme Verlag Stuttgart · New York

PAPER
Benzosultams from Allenes
1095
(0.05 mmol), and K2CO3 (139 mg, 1.0 mmol). MeCN (1 mL) was
added, and the mixture was heated at 80 °C (oil-bath temperature)
for 12 h then cooled to r.t. The mixture was diluted with EtOAc (5
mL) and passed through a pad of Celite (~1 g), which was washed
with additional EtOAc (20 mL). The organic phases were combined
and concentrated to give a residue that was purified by column chro-
matography [silica gel, hexane–EtOAc (4:1)] to give 4. Product 5
(42%) was also isolated along with compound 4 (see below).
2-Benzyl-3-(benzyloxy)-6-methyl-4-methylene-3,4-dihydro-2H-
1,2-benzothiazine 1,1-Dioxide (7)
Gummy liquid; yield: 0.140 g (69%).
IR (neat): 2932, 1600, 1562, 1463, 1332, 1238, 1167, 1058, 882,
762, 701 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 8.0 Hz, 1 H, Ar-H),
7.55 (s, 1 H, Ar-H), 7.42–7.44 (m, 2 H, Ar-H), 7.25–7.35 (m, 7 H,
Ar-H), 7.13–7.15 (m, 2 H, Ar-H), 6.06 (s, 1 H, alkene-H), 5.86 (s, 1
H, alkene-H), 5.80 (s, 1 H, OCH), 4.57 (d, J = 11.6 Hz, 1 H,
OCHaHb), 4.48 (d, J = 11.6 Hz, 1 H, OCHaHb), 4.28 (d, J = 15.2 Hz,
1 H, NCHaHb), 4.15 (d, J = 15.2 Hz, 1 H, NCHaHb), 2.44 (s, 3 H,
CH3).
13C NMR (100 MHz, CDCl3): δ = 143.2, 137.7, 136.6, 135.6, 132.4,
131.4, 130.4, 128.7, 128.5, 128.4, 128.3, 128.1, 127.4, 125.8, 125.3,
116.5, 87.4, 70.1, 47.7, 21.8.
Gummy liquid; yield: 0.082 g (36%).
IR (neat): 2926, 2844, 1732, 1584, 1490, 1452, 1342, 1162, 910,
811 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 8.0 Hz, 1 H, Ar-H),
7.95 (s, 1 H, Ar-H), 7.28–7.35 (m, 6 H, Ar-H), 5.82–5.90 (m, 1 H,
HC=CH2), 5.72–5.73 (m, 1 H, OCH), 5.52 (dd, J = 18.8 and 1.6 Hz,
1 H, HC=CHaHb), 5.33 (dd, J = 10.8 and 1.6 Hz, 1 H, HC=CHaHb),
4.77 (d, J = 12.0 Hz, 1 H, OCHaHb), 4.54 (d, J ≈ 12.0 Hz, 1 H,
OCHaHb), 2.77 (s, 3 H, CH3), 2.37 (s, 3 H, CH3).
HRMS (ESI): m/z [M + H]+ calcd for C24H24NO3S: 406.1478;
found: 406.1473.
13C NMR (100 MHz, CDCl3): δ = 144.6, 143.6, 138.8, 137.7, 133.7,
131.7, 129.0, 128.4, 127.8, 127.7, 119.3, 92.3, 85.3, 69.7, 28.6,
20.8.
HRMS (ESI): m/z [M + Na]+ calcd for C18H20INNaO3S: 480.0107;
found: 480.0110.
3-(Benzyloxy)-6-methoxy-2-methyl-4-methylene-3,4-dihydro-
2H-1,2-benzothiazine 1,1-Dioxide (8)
Gummy liquid; yield: 0.139 g (81%).
IR (neat): 2975, 2860, 1726, 1627, 1458, 1315, 1222, 1162, 811,
762 cm–1.
3-(Benzyloxy)-2,6-dimethyl-4-methylene-3,4-dihydro-2H-1,2-
benzothiazine 1,1-Dioxide (5); Typical Procedure
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 8.4 Hz, 1 H, Ar-H),
7.33–7.44 (m, 5 H, Ar-H), 7.19 (s, 1 H, Ar-H), 7.00 (dd, J ≈ 8.4 and
2.4 Hz, 1 H, Ar-H), 6.00 (s, 1 H, alkene-H), 5.88 (s, 1 H, alkene-H),
5.80 (s, 1 H, OCH), 4.95 (d, J = 12.0 Hz, 1 H, OCHaHb), 4.74 (d,
J = 12.0 Hz, 1 H, OCHaHb), 3.88 (s, 3 H, CH3), 2.63 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 162.6, 136.7, 135.0, 133.3, 128.7,
128.3, 128.2, 127.5, 126.0, 116.6, 115.5, 110.0, 86.1, 69.8, 55.7,
29.1.
A Schlenk tube containing sulfonamide 2a (156 mg, 0.5 mmol),
Pd(OAc)2 (0.025 mmol), Ph3P (0.05 mmol), K2CO3 (0.139 g, 1.0
mmol), and PEG-400 (1 mL) was evacuated for 15 min, and then al-
lene 1a (110 mg, 0.75 mmol) was added. The contents were then
heated at 80 °C for 12 h. The resulting mixture was diluted with
H2O (10 mL) and extracted with Et2O (4 × 10 mL). The organic ex-
tracts were dried (Na2SO4), filtered, and concentrated under vacuum
to give a residue that was purified by column chromatography [sil-
ica gel, hexane–EtOAc (4:1)] to give a gummy liquid; yield: 0.126
g (77%).
HRMS (ESI): m/z [M + H]+ calcd for C18H20NO4S: 346.1114;
found: 346.1111.
3-(Benzyloxy)-6-tert-butyl-2-methyl-4-methylene-3,4-dihydro-
2H-1,2-benzothiazine 1,1-Dioxide (9)
White solid; yield: 0.139 g (75%); mp 108–110 °C.
IR (neat): 2926, 2882, 1605, 1457, 1336, 1161, 1090, 914, 816, 701
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 8.0 Hz, 1 H, Ar-H),
7.55 (s, 1 H, Ar-H), 7.28–7.45 (m, 6 H, Ar-H), 6.04 (s, 1 H, alkene-
H), 5.88 (s, 1 H, alkene-H), 5.81 (s, 1 H, OCH), 4.97 (d, J = 9.6 Hz,
1 H, OCHaHb), 4.76 (d, J = 9.6 Hz, 1 H, OCHaHb), 2.65 (s, 3 H,
CH3), 2.44 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 143.1, 136.7, 134.8, 131.1, 130.8,
130.5, 128.6, 128.2, 128.1, 125.5, 116.2, 86.0, 69.8, 29.0, 21.7.
IR (KBr): 2964, 2877, 1600, 1556, 1479, 1342, 1167, 1090, 899,
756, 701 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.73–7.77 (m, 2 H, Ar-H), 7.51–
7.53 (m, 1 H, Ar-H), 7.33–7.45 (m, 5 H, Ar-H), 6.03 (s, 1 H, alkene-
H), 5.87 (s, 1 H, alkene-H), 5.79 (s, 1 H, OCH), 4.96 (d, J = 12.0 Hz,
1 H, OCHaHb), 4.75 (d, J = 12.0 Hz, 1 H, OCHaHb), 2.65 (s, 3 H,
CH3), 1.35 [s, 9 H, C(CH3)3].
13C NMR (100 MHz, CDCl3): δ = 156.2, 136.7, 135.2, 130.9, 128.7,
128.3, 128.2, 127.3, 125.3, 121.8, 116.0, 86.0, 69.7, 35.4, 31.1,
29.0.
HRMS (ESI): m/z [M + Na]+ calcd for C18H19NNaO3S: 352.0984;
found: 352.0986.
3-(Benzyloxy)-2-isopropyl-6-methyl-4-methylene-3,4-dihydro-
2H-1,2-benzothiazine 1,1-Dioxide (6)
Gummy liquid; yield: 0.137 g (77%).
HRMS (ESI): m/z [M + H]+ calcd for C21H26NO3S: 372.1634;
found: 372.1636.
IR (neat): 3030, 2926, 2860, 1715, 1627, 1458, 1321, 1167, 816,
740, 690 cm–1.
3-(Benzyloxy)-2-methyl-4-methylene-6-phenyl-3,4-dihydro-
2H-1,2-benzothiazine 1,1-Dioxide (10)
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 7.6 Hz, 1 H, Ar-H),
7.27–7.44 (m, 7 H, Ar-H), 5.86 (s, 1 H, alkene-H), 5.72 (s, 1 H, al-
kene-H), 5.58 (s, 1 H, OCH), 4.86 (d, J ≈ 12.0 Hz, 1 H, OCHaHb),
4.72 (d, J = 12.0 Hz, 1 H, OCHaHb), 4.17–4.21 [m, 1 H, CH(CH3)2],
2.42 (s, 3 H, CH3), 1.37 (d, J = 6.8 Hz, 3 H, CH3), 1.02 (d, J = 6.8
Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ =142.8, 137.5, 137.4, 135.1, 132.8,
129.9, 128.6, 128.1, 127.9, 126.4, 123.4, 115.6, 85.8, 68.0, 49.5,
23.0, 21.7, 19.9.
Gummy liquid; yield: 0.131 g (67%).
IR (neat): 3036, 2926, 1600, 1551, 1458, 1332, 1162, 1096, 888,
767, 699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.92 (m, 2 H, Ar-H), 7.69 (d,
J = 8.4 Hz, 1 H, Ar-H), 7.59 (d, J = 8.0 Hz, 2 H, Ar-H), 7.30–7.52
(m, 8 H, Ar-H), 6.12 (s, 1 H, alkene-H), 5.93 (s, 1 H, alkene-H), 5.86
(s, 1 H, OCH), 4.98 (d, J = 12.0 Hz, 1 H, OCHaHb), 4.78 (d, J ≈ 12.0
Hz, 1 H, OCHaHb), 2.69 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 145.7, 139.5, 136.7, 134.9, 132.2,
131.7, 129.2, 128.7, 128.6, 128.3, 127.7, 127.4, 126.1, 123.9, 116.7,
86.1, 69.9, 29.1.
HRMS (ESI): m/z [M + H]+ calcd for C20H24NO3S: 358.1478;
found: 358.1480.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1091–1099

1096
M. Nagarjuna Reddy, K. C. Kumara Swamy
PAPER
HRMS (ESI): m/z [M + H]+ calcd for C23H22NO3S: 392.1321;
found: 392.1292.
1 H, CHaHb), 4.62 (s, 2 H, CH2), 3.98 (dd, J = 10.0 and 5.6 Hz, 1 H,
CHaHb), 2.77 (s, 3 H, CH3), 2.43 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 143.0, 137.8, 135.2, 133.2, 131.2,
130.2, 128.6, 127.9, 127.1, 125.8, 125.2, 116.3, 73.4, 71.0, 62.9,
34.8, 21.8.
HRMS (ESI): m/z [M + Na]+ calcd for C19H21NNaO3S: 366.1140;
found: 366.1149.
3-[(4-Bromobenzyl)oxy]-2,6-dimethyl-4-methylene-3,4-di-
hydro-2H-1,2-benzothiazine 1,1-Dioxide (11)
White solid; yield: 0.132 g (65%); mp 81–83 °C.
IR (KBr): 2926, 1595, 1485, 1326, 1151, 1090, 882, 816 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.0 Hz, 1 H, Ar-H),
7.50–7.54 (m, 3 H, Ar-H), 7.29–7.32 (m, 3 H, Ar-H), 6.02 (s, 1 H,
=CH), 5.82 (s, 1 H, =CH), 5.75 (s, 1 H, OCH), 4.89 (d, J = 12.0 Hz,
1 H, CHaHb), 4.70 (d, J = 12.0 Hz, 1 H, CHaHb), 2.62 (s, 3 H, CH3),
2.42 (s, 3 H, CH3).
N-Benzyl-N-[(2,6-dimethyl-1,1-dioxido-2H-1,2-benzothiazin-4-
yl)methyl]-4-methylbenzenesulfonamide (15)
White solid; yield: 0.149 g (62%); mp 152–154 °C.
IR (KBr): 3057, 2937, 1627, 1600, 1463, 1326, 1156, 1090, 926,
877, 679 cm–1.
13C NMR (100 MHz, CDCl3): δ = 143.2, 135.7, 134.7, 131.8, 131.0,
130.8, 130.6, 129.9, 125.5, 122.2, 116.1, 86.0, 69.0, 29.1, 21.8.
HRMS (ESI): m/z [M + Na]+ calcd for C18H18BrNNaO3S: 430.0089
and 432.0247; found: 430.0090 and 432.0073.
1H NMR (400 MHz, CDCl3): δ = 7.75–7.78 (m, 3 H, Ar-H), 7.32 (d,
J = 8.0 Hz, 2 H, Ar-H), 7.21–7.27 (m, 5 H, Ar-H), 7.12–7.14 (m, 2
H, Ar-H), 5.90 (s, 1 H, =CH), 4.37 (s, 2 H, CH2), 4.31 (s, 2 H, CH2),
3.17 (s, 3 H, CH3), 2.45 (s, 3 H, CH3), 2.33 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 143.6, 142.9, 137.3, 135.9, 134.3,
132.0, 129.9, 128.7, 128.5, 128.2, 127.7, 127.4, 124.3, 122.1, 110.4,
50.4, 46.7, 33.9, 21.9, 21.6.
3-[(2-Bromobenzyl)oxy]-2,6-dimethyl-4-methylene-3,4-di-
hydro-2H-1,2-benzothiazine 1,1-Dioxide (12)
White solid; yield: 0.128 g (63%); mp 90–92 °C. Crystallization
[EtOAc–hexane (1:1)] at 4 °C gave crystals suitable for X-ray struc-
ture determination.
HRMS (ESI): m/z [M + H]+ calcd for C25H27N2O4S2: 483.1413;
found: 483.1413.
IR (KBr): 2926, 1599, 1451, 1331, 1166, 1084, 1024, 881, 750 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 8.0 Hz, 1 H, Ar-H),
7.52–7.61 (m, 3 H, Ar-H), 7.35 (t, J ≈ 7.6 Hz, 1 H, Ar-H), 7.29 (d,
J = 8.0 Hz, 1 H, Ar-H), 7.21 (t, J = 7.6 Hz, 1 H, Ar-H), 6.05 (s, 1 H,
=CH), 5.91 (s, 1 H, =CH), 5.84 (s, 1 H, OCH), 5.02 (d, J = 12.4 Hz,
1 H, CHaHb), 4.81 (d, J = 12.4 Hz, 1 H, CHaHb), 2.65 (s, 3 H, CH3),
2.43 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 143.2, 136.1, 134.6, 133.0, 131.1,
130.8, 130.6, 130.2, 129.8, 127.6, 125.6, 125.5, 123.7, 116.4, 86.5,
69.6, 29.2, 21.8.
N-Benzyl-N-[(2-isopropyl-6-methyl-1,1-dioxido-2H-1,2-benzo-
thiazin-4-yl)methyl]-4-methylbenzenesulfonamide (16)
White solid; yield: 0.170 g (67%); mp 123–125 °C. Crystallized
[CH2Cl2–hexane (1:1)] at 4 °C to give crystals suitable for X-ray
structure determination.
IR (KBr): 2975, 1616, 1594, 1446, 1314, 1216, 1150, 1035, 881 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.75–7.79 (m, 3 H, Ar-H), 7.23–
7.32 (m, 7 H, Ar-H), 7.15–7.17 (m, 2 H, Ar-H), 6.12 (s, 1 H, =CH),
4.55–4.59 [m, 1 H, CH(CH3)2], 4.38 (s, 4 H, 2 CH2), 2.44 (s, 3 H,
CH3), 2.31 (s, 3 H, CH3), 1.20 [d, J = 6.8 Hz, 6 H, HC(CH3)2].
HRMS (ESI): m/z [M + Na]+ calcd for C18H18BrNO3SNa: 430.0089
and 432.0247; found: 430.0089 and 432.0070.
13C NMR (100 MHz, CDCl3): δ = 143.6, 142.6, 137.5, 135.8, 131.6,
129.9, 128.9, 128.6, 128.5, 128.4, 128.3, 127.6, 127.3, 124.3, 121.8,
111.7, 49.9, 47.9, 46.5, 22.5, 21.8, 21.6.
HRMS (ESI): m/z [M + Na]+ calcd for C27H30N2NaO4S2: 533.1545;
found: 533.1545.
X-ray crystal data: colorless block, C18H18BrNO3S, M = 408.30, tri-
clinic, space group P1, a = 7.6487(9), b = 10.6266(14), c =
11.6799(16) Å, α = 67.77(13), β = 86.971(10), γ = 78.624(10)°,
V = 861.26(19) Å3, Z = 2, μ = 2.524 mm–1; data/restraints/parame-
ters: 3519/0/219, R indices [I > 2σ(I)]: R1 = 0.0502, wR2 (all data) =
0.099.
X-ray crystal data: colorless block, C27H30N2O4S2, M = 510.65, tri-
clinic, space group P1, a = 9.5321(13), b = 11.7426(16),
c = 12.4656(16) Å, α = 71.077(12), β = 73.117(12), γ = 85.644(11)°,
2,6-Dimethyl-4-methylene-3-octyl-3,4-dihydro-2H-1,2-benzo-
thiazine 1,1-Dioxide (13)
Gummy liquid; yield: 0.142 g (85%).
V = 1262.7(3) Å3 Z = 2, μ = 0.247 mm–1; data/restraints/parameters:
,
5134/0/320, R indices [I > 2σ(I)]: R1 = 0.0622, wR2 (all data) =
0.1119.
IR (neat): 2926, 2849, 1611, 1468, 1332, 1167, 910, 811, 745, 707
cm–1.
N-Benzyl-N-[(6-methoxy-2-methyl-1,1-dioxido-2H-1,2-benzo-
thiazin-4-yl)methyl]-4-methylbenzenesulfonamide (17)
White solid; yield: 0.152 g (61%); mp 125–127 °C.
IR (KBr): 2967, 1621, 1584, 1439, 1320, 1209, 1121, 1015, 872 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.74–7.81 (m, 3 H, Ar-H), 7.33–
7.35 (m, 3 H, Ar-H), 7.15–7.16 (m, 3 H, Ar-H), 6.97–7.01 (m, 3 H,
Ar-H), 5.87 (s, 1 H, =CH), 4.32 and 4.34 (2 s, 4 H, 2 CH2), 3.91 (s,
3 H, OCH3), 3.17 (s, 3 H, CH3), 2.47 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 162.7, 143.8, 136.9, 135.8, 134.8,
134.2, 130.0, 128.4, 128.1, 127.6, 127.2, 124.0, 123.1, 115.6, 110.0,
107.7, 56.2, 50.6, 47.9, 33.8, 21.6.
1H NMR (400 MHz, CDCl3): δ = 7.70 (d, J = 7.6 Hz, 1 H, Ar-H),
7.47 (s, 1 H, Ar-H), 7.26–7.28 (m, 1 H, Ar-H), 5.92 (s, 1 H, alkene-
H), 5.33 (s, 1 H, alkene-H), 4.65 (t, J ≈ 7.6 Hz, 1 H, CH), 2.62 (s, 3
H, CH3), 2.41 (s, 3 H, CH3), 1.84 (q, J ≈ 7.6 Hz, 2 H, CH2), 1.28–
1.57 (m, 12 H, 6 CH2), 0.88 (t, J = 6.0 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 142.7, 137.4, 133.4, 131.5, 130.4,
125.5, 115.0, 61.0, 31.9, 30.6, 29.7, 29.5, 29.3, 25.5, 22.7, 21.7,
14.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H30NO2S: 336.1998;
found: 336.1996.
3-[(Benzyloxy)methyl]-2,6-dimethyl-4-methylene-3,4-dihydro-
2H-1,2-benzothiazine 1,1-Dioxide (14)
Gummy liquid; yield: 0.106 g (62%).
HRMS (ESI): m/z [M + Na]+ calcd for C25H26N2NaO5S2: 521.1181;
found: 521.1181.
N-Benzyl-N-[(6-tert-butyl-2-methyl-1,1-dioxido-2H-1,2-benzo-
thiazin-4-yl)methyl]-4-methylbenzenesulfonamide (18)
White solid; yield: 0.179 g (68%); mp 111–113 °C.
IR (KBr): 2962, 1618, 1591, 1443, 1318, 1226, 1130, 1025, 885 cm–1.
IR (neat): 2926, 2860, 1605, 1441, 1332, 1173, 1058, 910, 740 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.71 (d, J = 8.0 Hz, 1 H, Ar-H),
7.48 (s, 1 H, Ar-H), 7.29–7.38 (m, 6 H, Ar-H), 5.93 (s, 1 H, =CH),
5.43 (s, 1 H, =CH), 5.84 (s, 1 H, CH), 4.81 (dd, J = 10.0 and 6.8 Hz,
Synthesis 2014, 46, 1091–1099
© Georg Thieme Verlag Stuttgart · New York

PAPER
Benzosultams from Allenes
1097
1H NMR (400 MHz, CDCl3): δ = 7.97 (s, 1 H, Ar-H), 7.81 (d, J =
8.4 Hz, 1 H, Ar-H), 7.74 (d, J = 8.4 Hz, 2 H, Ar-H), 7.52 (dd, J =
8.4 and 1.6 Hz, 1 H, Ar-H), 7.32 (d, J = 8.0 Hz, 2 H, Ar-H), 7.09–
7.14 (m, 3 H, Ar-H), 6.95–6.97 (m, 2 H, Ar-H), 5.91 (s, 1 H, =CH),
4.38 and 4.31 (2 s, 4 H, 2 CH2), 3.18 (s, 3 H, CH3), 2.45 (s, 3 H,
CH3), 1.38 [s, 9 H, C(CH3)3].
13C NMR (100 MHz, CDCl3): δ = 156.3, 143.7, 136.9, 135.8, 134.0,
131.8, 130.0, 128.7, 128.3, 128.1, 127.5, 127.3, 125.4, 121.8, 121.7,
110.9, 50.6, 50.0, 35.7, 33.8, 31.2, 21.6.
IR (KBr): 2926, 1600, 1509, 1447, 1326, 1162, 1068, 910, 816, 701,
559 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 8.0 Hz, 1 H, Ar-H),
7.62 (s, 1 H, Ar-H), 7.43 (s, 1 H, alkene-H), 7.27–7.28 (m, 1 H, Ar-
H), 7.23 (d, J ≈ 8.0 Hz, 2 H, Ar-H), 7.17 (d, J = 8.0 Hz, 2 H, Ar-H),
4.66 (s, 2 H, NCH2), 2.68 (s, 3 H, CH3), 2.46 (s, 3 H, CH3), 2.40 (s,
3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 143.0, 138.4, 134.3, 132.7, 131.6,
130.3, 129.7, 129.5, 129.3, 125.5, 125.0, 52.1, 36.4, 21.9, 21.4.
HRMS (ESI): m/z [M + Na]+ calcd for C28H32N2NaO4S2: 547.1701;
found: 547.1700.
HRMS (ESI): m/z [M + H]+ calcd for C18H20NO2S: 314.1215;
found: 314.1213.
(4Z)-4-Benzylidene-2,6-dimethyl-3,4-dihydro-2H-1,2-benzothi-
azine 1,1-Dioxide (19) and 2,4,6-Trimethyl-3-phenyl-2H-1,2-
benzothiazine 1,1-Dioxide (20)
These compounds were prepared from sulfonamide 2a (156 mg, 0.5
mmol) and phenylallene (1g; 87 mg, 0.75 mmol) by following a
route similar to that used to prepare sultam 5. The products were
separated by chromatography using a hexane–EtOAc mixture
(90:10 for 19; 95:5 for 20).
2,4,6-Trimethyl-3-(4-tolyl)-2H-1,2-benzothiazine 1,1-Dioxide
(22)
White solid; yield: 0.019 g (12%); mp 160–162 °C.
IR (KBr): 2921, 1923, 1595, 1452, 1337, 1173, 1145, 1014, 844,
816, 553 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 8.0 Hz, 1 H, Ar-H),
7.39–7.42 (m, 3 H, Ar-H), 7.34 (d, J = 7.6 Hz, 1 H, Ar-H), 7.27–
7.28 (m, 2 H, Ar-H), 2.82 (s, 3 H, CH3), 2.50 (s, 3 H, CH3), 2.43 (s,
3 H, CH3), 2.20 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 142.5, 139.8, 139.2, 135.5, 131.8,
130.1, 129.7, 129.2, 128.7, 125.9, 122.2, 117.0, 35.0, 22.1, 21.5,
16.5.
(4Z)-4-Benzylidene-2,6-dimethyl-3,4-dihydro-2H-1,2-benzothi-
azine 1,1-Dioxide (19)
White solid; yield: 0.097 g (65%); mp 108–110 °C. Crystallization
from EtOAc–hexane (1:1) at 4 °C gave crystals suitable for X-ray
structure determination.
IR (KBr): 2926, 1595, 1496, 1332, 1162, 1140, 926, 822, 690 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C18H20NO2S: 314.1215;
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.0 Hz, 1 H, Ar-H),
7.64 (s, 1 H, Ar-H), 7.36–7.47 (m, 4 H, Ar-H), 7.27–7.31 (m, 3 H,
vinyl-H + Ar-H), 4.66 (s, 2 H, NCH2), 2.69 (s, 3 H, CH3), 2.46 (s, 3
H, CH3).
13C NMR (100 MHz, CDCl3): δ = 143.0, 135.6, 134.1, 131.5, 130.5,
129.9, 129.3, 128.8, 128.3, 126.3, 125.6, 125.1, 52.0, 36.4, 21.9.
found: 314.1214.
N-{1-[(5,5-Dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phe-
nyl)methyl]vinyl}-2-iodo-N,4-dimethylbenzenesulfonamide
(23)
This compound was prepared from 5,5-dimethyl-2-(1-phenylpropa-
1,2-dien-1-yl)-1,3,2-dioxaphosphinane 2-oxide23 (132 mg, 0.5
mmol) and sulfonamide 2a (187 mg, 0.6 mmol) by following a route
similar to that used to prepare compound 4. The compound was iso-
lated by chromatography with hexane–EtOAc (3:2) as the eluent.
HRMS (ESI): m/z [M + H]+ calcd for C17H18NO2S: 300.1059;
found: 300.1059.
X-ray crystal data: colorless block, C17H17NO2S, M = 299.38,
monoclinic, space group P21/c, a = 12.054(2), b = 15.383(3),
White solid; yield: 0.207 g (72%); mp 106–108 °C.
c = 8.0462(13) Å, β = 104.651(17)°, V = 1443.4(4) Å3 Z = 4,
IR (KBr): 3036, 2964, 1715, 1638, 1595, 1458, 1353, 1260, 1156,
1058, 1008, 833, 785 cm–1.
,
μ = 0.228 mm–1; data/restraints/parameters: 2453/0/192, R indices
[I > 2σ(I)]: R1 = 0.0478, wR2 (all data) = 0.106.
1H NMR (400 MHz, CDCl3): δ = 7.89 (s, 1 H, Ar-H), 7.82 (d, J =
8.0 Hz, 1 H, Ar-H), 7.50–7.52 (m, 2 H, Ar-H), 7.29–7.35 (m, 3 H,
Ar-H), 7.20 (d, J = 8.0 Hz, 1 H, Ar-H), 5.74 (s, 1 H, alkene-H), 5.02
(s, 1 H, alkene-H), 4.67 (d, J = 22.4 Hz, 1 H, PCH), 4.27 (dd, J =
11.2 and ~7.0 Hz, 1 H, OCHaHb), 4.08 (dd, J = 15.6 and ~7.0 Hz, 1
H, OCHaHb), 3.88–3.90 (m, 2 H, OCH2), 3.05 (s, 3 H, CH3), 2.33 (s,
3 H, CH3), 1.19 and 0.91 (2 s, 6 H, 2 CH3).
13C NMR (100 MHz, CDCl3): δ = 144.8, 144.1, 143.8, 136.9, 133.6
(d, J = 7.0 Hz), 132.4, 129.9 (d, J = 7.0 Hz), 128.9, 128.8, 127.9,
119.4, 92.2, 48.2 [d, 1J(PC) = 28.0 Hz], 40.3, 32.5 (d, J = 7.0 Hz),
21.9, 20.9, 20.7.
2,4,6-Trimethyl-3-phenyl-2H-1,2-benzothiazine 1,1-Dioxide
(20)
White solid; yield: 0.024 g (16%, minor product); mp 108–110 °C.
IR (KBr): 2926, 1600, 1436, 1326, 1173, 1145, 1019, 827, 756 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.80 (d, J = 8.0 Hz, 1 H, Ar-H),
7.43–7.57 (m, 6 H, Ar-H), 7.35 (d, J = 8.0 Hz, 1 H, Ar-H), 2.82 (s,
3 H, CH3), 2.51 (s, 3 H, CH3), 2.20 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 142.5, 135.4, 134.7, 130.2, 129.8,
129.2, 128.8, 128.5, 126.0, 122.3, 117.4, 35.0, 22.0, 16.5.
31P NMR (162 MHz, CDCl3): δ = 16.7.
HRMS (ESI): m/z [M + H]+ calcd for C22H28INO5PS: 576.0471;
HRMS (ESI): m/z [M + H]+ calcd for C17H18NO2S: 300.1059;
found: 300.1058.
found: 576.0473.
(4Z)-2,6-Dimethyl-4-(4-methylbenzylidene)-3,4-dihydro-2H-
1,2-benzothiazine 1,1-Dioxide (21) and 2,4,6-Trimethyl-3-(4-
methylphenyl)-2H-1,2-benzothiazine 1,1-Dioxide (22)
These compounds were prepared from sulfonamide 2a (156 mg, 0.5
mmol) and 4-tolylallene (1h; 98 mg, 0.75 mmol) by following a
route similar to that used to prepare 5. The products were separated
by chromatography using a hexane–EtOAc mixture (90:10 for 21;
95:5 for 22).
(4Z)-4-Benzylidene-2,6-dimethyl-3,4-dihydro-2H-1,2-benzothi-
azine 1,1-Dioxide (19; Alternative Procedure); Typical Proce-
dure
A Schlenk tube was charged with sulfonamide 3a (214 mg, 0.5
mmol), Pd(OAc)2 (0.025 mmol), Ph3P (0.05 mmol), K2CO3 (139
mg, 1.0 mmol), and DMF (1 mL), and the mixture was heated at
80 °C for 12 h. The resulting mixture was diluted with H2O (10 mL)
and extracted with Et2O (4 × 10 mL). The extracts were combined,
dried (Na2SO4), filtered, and concentrated in a vacuum. The residue
was purified by column chromatography [silica gel, hexane–EtOAc
(2:1)] to give a white solid; yield: 0.112 g (75%).
(4Z)-2,6-Dimethyl-4-(4-methylbenzylidene)-3,4-dihydro-2H-
1,2-benzothiazine 1,1-Dioxide (21)
White solid; yield: 0.105 g (67%); mp 159–161 °C.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1091–1099

1098
M. Nagarjuna Reddy, K. C. Kumara Swamy
PAPER
HRMS (ESI): m/z [M + H]+ calcd for C17H18NO2S: 300.1059;
found: 300.1057.
Acknowledgment
We thank the Department of Science and Technology (DST, New
Delhi) for financial support and the single-crystal X-ray diffracto-
meter facility, and the University Grants Commission (UGC, New
Delhi) for equipment under the UPE and CAS programs. M.N.R.
thanks the Council of Scientific and Industrial Research (CSIR,
New Delhi) for a fellowship. K.C.K. thanks the DST for a J. C. Bose
fellowship.
Other data were as reported above.
(4Z)-4-Benzylidene-6-tert-butyl-2-methyl-3,4-dihydro-2H-1,2-
benzothiazine 1,1-Dioxide(24)
Prepared in a similar manner to 19 (above) from sulfonamide 3b
(234 mg, 0.5 mmol) as a white solid; yield: 0.123 g (72%); mp 148–
150 °C.
IR (KBr): 2959, 2871, 1589, 1496, 1479, 1332, 1178, 1151, 1118,
921, 701, 674 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79–7.81 (m, 2 H, Ar-H), 7.53
(dd, J = 8.4 and 1.6 Hz, 1 H, Ar-H), 7.42–7.47 (m, 3 H, Ar-H), 7.36
(t, J ≈ 7.6 Hz, 1 H, Ar-H), 7.27–7.30 (m, 2 H, alkene-H+Ar-H), 4.66
(s, 2 H, NCH2), 2.71 (s, 3 H, CH3), 1.39 [s, 9 H, C(CH3)3].
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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References
13C NMR (100 MHz, CDCl3): δ = 156.0, 135.5, 133.8, 131.5, 130.5,
129.3, 128.8, 128.3, 126.7, 126.6, 125.2, 121.4, 52.0, 36.3, 35.4,
31.2.
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A Schlenk tube was charged with sulfonamide 2a (156 mg, 0.5
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0.10 g (82%); mp 132–134 °C.
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707, 674 cm–1.
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7.94 (s, 1 H, Ar-H), 7.58 (d, J = 8.0 Hz, 1 H, Ar-H), 7.32 (d, J = 8.0
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6.05 (br s, 1 H, NH), 3.36 (s, 3 H, CH3), 2.82 (d, J = 4.8 Hz, 3 H,
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N,N',5,6′-Tetramethylbiphenyl-2,3′-disulfonamide (26)
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1091–1099