Ru (II)-Catalyzed Coupling-Cyclization of Sulfoximines with alpha-Carbonyl Sulfoxonium Ylides as an Approach to 1,2-Benzothiazines

Article abstract of DOI:10.1002/adsc.201800753

A Ru(II)-catalyzed approach for the rapid assembly of 1,2-benzothiazines has been developed to enable the coupling-cyclization of aryl Csp²?H bonds with α-carbonyl sulfoxonium ylides via Csp²?H activation process. The present method could be further applied to the construction of the 4-substituted 1,2-benzothiazine skeletons. (Figure presented.).

Full text of DOI:10.1002/adsc.201800753

Title: Ru (II)-Catalyzed Coupling-Cyclization of Sulfoximines with
alpha-Carbonyl Sulfoxonium Ylides as an Approach to 1,2-
Benzothiazines
Authors: Wei Zeng, Haisheng Xie, Jianyong Lan, Jiao Gui, Fengjuan
Chen, and Huanfeng Jiang
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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the VoR from the journal website shown below when it is published
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800753
Link to VoR: http://dx.doi.org/10.1002/adsc.201800753

10.1002/adsc.201800753
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Ru (II)-Catalyzed Coupling-Cyclization of Sulfoximines with
alpha-Carbonyl Sulfoxonium Ylides as an Approach to 1,2-
Benzothiazines
Haisheng Xie, Jianyong Lan, Jiao Gui, Fengjuan Chen, Huangfeng Jiang, and Wei
Zeng*
Key Laboratory of Functional Molecular Engineering of Guangdong Province, Guangdong Engineering Research
Center for Green Fine Chemicals, School of Chemistry and Chemical Engineering, South China University of
Technology, Guangzhou 510641, China
Fax: (+86)-20-2223-6337; e-mail: zengwei@scut.edu.cn
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A Ru(II)-catalyzed approach for the rapid
assembly of 1,2-benzothiazines has been developed to enable
the coupling-cyclization of aryl Csp2-H bonds with -
carbonyl sulfoxonium ylides via Csp2-H activation process.
The present method could be further applied to the
construction of the 4-substituted 1,2-benzothiazine skeletons.
Keywords: Ruthenium catalysis; Sulfoximines; Sulfur
ylides; Coupling-cyclization; 1,2-Benzothiazines
metal-catalyzed
cascade
C-H
activation/C-H
Introduction
carbenoid insertion provides an atom- and step-
economical strategy for constructing C-X bonds (X =
C, N, S and O, etc).[7] Up to now, the coupling
reactions of C-H bonds with diazo compounds have
been well developed for furnishing structurally
complex heterocycles. Among them, various ligand-
functional groups including ammonium salts,[8]
pyridine,[9] amide,[10] indole,[11] ketoimine,[12]
omines,[13] hydroxamic acids,[14] and others[15] have
been widely employed as chelation-assisted platforms
to enable the C-H bond carbenoid insertion using
diazo compounds as carbene precursors. In
Sulfoximines are ubiquitous in many bioactive
molecules.[1] Especially for the sulfoximine-
containing benzothiazines (SBTs), these compounds
have ever attracted attention in medicinal chemistry
due to their benzo-fused sulfur-nitrogen heterocyclic
skeletons decades ago (Figure 1).[2] However, these
heterocycles have been rather neglected in recent
years mainly because efficient synthetic strategies for
particular benzothiazine skeletons were not well
established. Since Cram reported a combined
imidation-Schmidt rearrangement/cyclization of S-
arylsulfoxides with sodium azides in 1973,[3] only
Harmata[4] and Bolm[5] successively realized the
Pd(II)- or Rh(III)-catalyzed coupling cyclization of S-
aryl sulfoximines with alkynes to assemble 1,2-
benzothiazines (Scheme 1a). In view of the fact that
SBTs possess potential usefulness as scaffolds in drug
chemistry, developing a novel procedure for the
conversion of different coupling partners into SBTs is
desirable.
comparsion,
carbenoid
sulfoximine-directed
C-H
bond
almost
functionalization remains
undeveloped. Up to now, only Bolm reported a
Rh(III)-catalyzed coupling reaction of aryl C-H
bonds with -diazo--ketoesters, in which the
combined directing character and nucleophilicity of
sulfoximines was fully utilized to allow rapid
assembly of SBTs (Scheme 1b).[16] Meanwhile, sulfur
ylides are a more practical and safe alternative to
diazo compounds, and sulfur ylide-based C-H
carbenoid insertion has recently aroused increasing
interest due to their distinctive chemical
reactivities.[17] Given the deficiencies of synthetic
methodology for diverse benzothiazine libraries,
herein we plan to develop a highly regioselective
approach to 1,2-benzothiazines through the Ru(II)-
catalyzed coupling-cyclization of S-aryl sulfoximines
with sulfur ylides.[18] More importantly, we expect the
afforded SBTs could be further converted into diverse
4-substituted 1,2-benzoazines through downstream
transformations (Scheme 1c).
Figure 1. Selected examples of bioactive benzothiazines
Metal carbenes belong to a very important type of
C1-synthons in organic chemistry,[6] and transition
1
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10.1002/adsc.201800753
Advanced Synthesis & Catalysis
a) Rh(III)-catalyzed cross-coupling of S-aryl sulfoximines with alkynes
o
equiv) in 1,2-dichloroethane (DCE) at 100 C under
O
O
S
NH
S
Ar atmosphere for 12 h (Table 1, entries 1-6).
Gratifyingly, we soon found that RuL2 afforded 12%
yield of 1-methyl-3-phenyl-1,2-benzothiazine 1-oxide
(3a). Other catalysts such as RuCl3, Co(acac)3 and
Cu(OAc)2 could not produce 3a at all (compare
entries 1-2 and 4-6 with 3). Subsequently, a variety of
silver salts including AgClO4, AgNTf2, AgBF4 and
AgSbF6, were evaluated in the presence of [RuCl2(p-
cymene)]2 catalysts in order to increase the reaction
conversion, and AgSbF6 was shown to be the most
efficient (compare entries 7-10 with 11), significantly
improving the yield of 3a from 12% to 51% (compare
entry 3 with 11). To maximize the conversion of the
reaction, the additional optimization of proton acids
revealed that pivalic acid could further increase the
yield to 75% (compare entries 11-13 with 14), but
other acids, such as AcOH and adamantane-1-
carboxylic acid (AdCO2H), gave inferior results
(compare entries 12-14 with 15). It should be noted
that the reaction yield was decreased to 56% in the
absence of protic acid (compare entry 14 with 15),
and using other solvents including toluene and
CF3CH2OH led to poorer reaction conversions
Rh(III) cat.
N
1
+
R
R
1
H
R
R
R = H , alkyl and aryl
b) Rh(III)-catalyzed cross-coupling of aryl C-H bonds with diazo compounds
O
S
O
S
O
2
2
R
1
1
R
R
R
EtO C
2
Rh(III) cat.
3
NH
N
R
+
N
2
3
H
R
CO Et
2
c) This work: Ru(II)-catalyzed cross-coupling of aryl C-H bonds with sulfur ylides
O
S
O
O
2
2
2
1
R
R
1
1
R
downstream
transformation
O
O
S
R
R
R
S
S
Ru(II) cat.
N
NH
N
+
3
R
3
3
R
H
R
R
R = Br and NO
2
Scheme 1. Synthetic strategies toward 1,2-benzothiazines
Results and Discussion
To demonstrate the feasibility of our approach, we
first screened various Ru(II), Co(III) and Cu(II)
catalysts that could possibly enable the aryl C-H bond
carbenoid functionalization of S-phenyl sulfoximine
(1a) with -benzoyl sulfoxonium ylide (2a) in the
presence of AgOAc (20 mol %) and PhCO2H (1.0
(compare
entries
16-17
with
14).
Table 1. Optimization of the reaction parameters [a]
O
O
S
O
O
S
cat. (10 mol %)
S
N
Ag salt (20 mol %)
NH
+
Ph
additive (100 mol %)
DCE, 100 oC, Ar, 12 h
Ph
H
2a
1a
3a
Entry
1
2
3
4
5
6
7
8
Catalyst
RuCl3
Ag salts
AgOAc
AgOAc
AgOAc
AgOAc
Additives
PhCO2H
Yield (%) [b]
0
0
12
0
c
RuL1
RuL2
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
AcOH
AdCO2H
PivOH
‒
PivOH
PivOH
d
Co(acac)3
Cp*Co(CO)I2 AgOAc
0
0
Cu(OAc)2
RuL2
RuL2
RuL2
RuL2
RuL2
RuL2
RuL2
RuL2
RuL2
RuL2
RuL2
AgOAc
AgClO4
Ag2CO3
AgNTf2
AgBF4
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
32
27
46
49
51
8
63
75
56
42[e]
73[f]
9
10
11
12
13
14
15
16
17
[a]Unless otherwise noted, all the reactions were carried out using sulfoximine (1a) (0.10 mmol)
and -carbonyl ylide (2a) (0.20 mmol) in the presence of catalysts (5 mol %) with additive (100
mol %) in DCE (2.0 mL) at 100 oC for 12 h under Ar in a sealed reaction tube. Followed by flash
chromatography on SiO2.
[b]Isolated yield.
[c]RuL1 refers to RuHCl(CO)(PPh3).
[d]RuL2 refers to [RuCl2(p-cymene)]2.
[e]Using toluene as solvent.
[f] Using CF3CH2OH as solvent.
With these optimized reaction parameters in hand,
we first investigated the reactivity of various
sulfoxonium ylides with S-phenyl sulfoximine (1a).
As shown in Table 2, -substituted benzoyl
sulfoxonium ylides bearing halide substituents (4-F,
4-Cl and 4-Br), electron-donating groups (4-methyl
2
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10.1002/adsc.201800753
Advanced Synthesis & Catalysis
and 4-tBu) and electron-withdrawing group (4-CF3)
all smoothly underwent coupling-cyclization to afford
the corresponding 3-aryl 1,2-benzothiazines in good
to excellent yields (3a, 3b and 3f‒3k, 59-82%).
Moreover, -(3-methylbenzoyl)- and -(3,5-
dimethylbenzoyl)-substituted sulfur ylides also
allowed for this transformation and assembled SBTs
in 85% (3c) and 81% yields (3e), respectively, but -
(2-methylbenzoyl)sulfoxonium ylide led to lower
yield of the product 3d (36%) owing to the steric
hindrance of ortho-methyl substitution. On the other
hand, -pentafluorobenzoyl sulfoxonium ylide, -2-
naphthoyl sulfoxonium ylide and -2-thienoyl
sulfoxonium ylide could also be applied to this
reaction system, installing pentafluorophenyl, 2-
naphthyl and 2-thienyl groups at the 3-position of
1,2-benzothiazines (3l‒3n) in 58-98% yields. More
importantly, besides the -aroyl sulfoxonium ylides,
we could also extend the chemistry to reactions with
the -fattyacyl sulfoxonium ylides which produced
the desired 3-alkyl 1,2-benzothiazines (3o‒3q) in 45-
56% yields. By the way, the structure of 3k was
already unambiguously assigned by its single crystal
X-ray analysis.[19]
reaction tube. Followed by flash chromatography on
SiO2.
[b] Isolated yield.
[c]
The data in parentheses is the ratio of C-H
functionalization from C3-position and C1-position of
naphthalene ring.
Subsequently, we evaluated the scope of S-alkyl
substituted-S-phenylsulfoximines. Compared with the
S-methyl-S-phenylsulfoximine (3a, 75% yield), S-
ethyl, S-benzyl and S-cyclopropyl group-substituted
sulfoximines could be transferred into the target
compounds (3r‒3t) in lower yields (40-62%). On the
contrary, except for S-2-naphthylsulfoximine (30% of
3u), other S-arylsulfoximines such as S-(4-
methlyphenyl)sulfoximine,
sulfoximine and
S-(4-methoxylphenyl)
S-monohalo-substituted
phenylsulfoximines could more efficiently couple
with -benzoyl sulfoxonium ylide 2a to provide the
corresponding 5-, 6- or 8-substituted 1,2-
benzothiazines (3v‒3v-2) in good yields (68-88%),
regardless of the type of substituents and substitution
position on the phenyl ring. It should be noted that
the electron-deficient S-phenylsulfoximines including
Table 2. Substrate Scope [a, b]
S-(4-nitrophenyl)sulfoximine
acetylphenyl)sulfoximine,
and
S-(4-
did not afford the
corresponding 1,2-benzothiazines. Moreover, S-(2-
pyridyl)sulfoximine did not also tolerate the reaction
system possibly due to that Ru(II) salts coordinated
with pyridine “N” and imine “N” and lost their
catalytic activity.
O
S
O
S
O
S
N
N
F
F
F
N
F
F
3
R
3l, 98%
3m, 78%
It is well known that C-Br bond can undergoes
diverse chemical transformations in organic
synthesis.[20] The synthetic applications of this
coupling cyclization demonstrated that bromine
group could be easily installed into the 4-position of
1,2-benzothiazine 3a to form 3-bromo-1,2-
benzothiazine 4 in 50% yield in the presence of 1.0
equiv of NBS. Moreover, employing 2.0 equiv of
NBS could further enable the bromomethylation of
3a to afford dibromide 5 in 19% yield. Meanwhile,
nitro group could be also regioselectively induced
into the 4-position of 1,2-benzothiazine 3a to
produce nitro-substituted benzothiazine (6) in 42%
yield (see Scheme 2).
3
3a, R = Ph, 75%
3
3b, R = 4-Me-C H , 76%
6
4
3
3c, R = 3-Me-C H , 85%
6
4
3
3d, R = 2-Me-C H , 36%
6
4
3
3e, R = 3,5-dimethyl-C H , 81%
6
3
3
3f, R = 4-tBu-C H , 70%
6
4
3
3g, R = 4-Ph-C H , 75%
6
4
3
3h, R = 4-F-C H , 59%
6
4
3
3i, R = 4-Cl-C H , 82%
6
4
3
3j, R = 4-Br-C H , 75%
6
4
3
3k, R = 4-CF -C H , 78%
single crystal structure of 3k
3
6 4
O
S
O
S
O
S
N
N
N
S
Ph
3n, 58%
3q, 52%
3t, 40%
Ph
O
S
O
R2
N
O
S
N
S
N
S
O
N
R3
Ph
3o, R3 = iPr, 45%
3p, R3 = tBu, 56%
O
Ph
3u, 30% (3:1)c
3r, R2 = Et, 62%
3s, R2 = Bn, 45%
O
S
O
S
O
Br
S
NBS (1.0 eq.)/AIBN
NBS (2.0 eq.)/AIBN
N
N
N
unsuccessful substrates:
O
R1
CCl , 12 h, reflux
4
50% yield
CCl , 12 h, reflux
4
S
Ph
Ph
Ph
19% yield
N
S
3a
HNO /AcOH
3
5-10 C, 10 h
Br
Br
5
4
NH
o
Ph
3v, R1 = 6-Me, 81%
O2N
H
42% yield
1m
3w, R1 = 6-MeO, 88%
3x, R1 = 6-F, 79%
3y, R1 = 6-Cl, 68%
3z, R1 = 6-Br, 77%
3z-1, R1 = 5-Br, 70%
3z-2, R1 = 8-Br, 72%
O
O
S
S
O
S
N
N
NH
NH
Ph
O
H
NO
2
H
6
1n
1o
Scheme 2. Synthetic application of this transformation
[a]
Unless otherwise noted, all the reactions were carried
out using sulfoximines (1) (0.10 mmol) and alpha-
carbonyl ylide (2a) (0.20 mmol) in the presence of
[RuCl2(p-cymene)]2 (5 mol %) with PivOH (100 mol %)
in DCE (2.0 mL) at 100 oC for 12 h under Ar in a sealed
Several control experiments were conducted to
elucidate the reaction mechanism. Initially,
performing the H/D exchange of S-
phenylsulfoximine 1a with CH3OD in the absence of
sulfoxonium ylide (2a) led to the formation of the
3
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10.1002/adsc.201800753
Advanced Synthesis & Catalysis
deuterated d2-1a in which 19% deuterium
incorporation at the ortho-position of benzene ring of
1a was observed, implying that a reversible C-H bond
activation process was involved in the carbene
transfer reaction (Scheme 3a). The subsequent
coupling-cyclization of S-phenylsulfoximine 1a with
-benzoyl sulfoxonium ylide 2a in the presence of
CH3OD could incorporate the deuterium (15% D)
into the 4-position[21] of the 1,2-benzothiazine (d3-3a)
(Scheme 3b),[22] but the treatment of 1,2-
benzothiazine (3a) with MeOD (1.5 equiv) under the
standard conditions did not result in the H/D
exchange at the 4-position of d2-3a (Scheme 3c).[22]
The combined facts (Scheme 3b and 3c) indicated
that metal protonation process was possibly involved
in the transformation, and sulfoxide group could not
lead to the C-H activation and H/D exchange at the 8-
belongs to the rate-limiting step of this reaction, and
the amount of deuterium at the ortho-position on the
substituted phenyl ring of the recovered d1-1a′ was
decreased from 99% D to 55% D (Scheme 3d).
Moreover, the competitive cross-coupling between
electron-rich
and
electron-deficient
S-
phenylsulfoximines (1g vis 1i) led to the formation of
3w and 3y with a ratio of 1.75:1 (3w/3y),[23] implying
that the aryl Csp2-H bond activation possibly
proceeded through electrophilic ruthenation instead
of concerted metallation-deprotonation (CMD)
process (Scheme 3e). Finally, the competitive
coupling-cyclization
of
-(4-methylbenzoyl)-
sulfoxonium ylide and -(4-trifluomethylbenzoyl)
sulfoxonium ylide with S-phenylsulfoximine (1a)
(3b/3k = 1:1.5) suggested that electron-deficient
sulfur ylide more easily forms a ruthenium-carbene,
which cyclizes with sulfoximine 1a to afford 1,2-
benzothiazine 3k in better conversion (Scheme 3f)
(see SI for more details).
[5]
position of 3a. Then, the kinetic isotope effect
between d1-1a and 2a (KH/KD = 1.56) confirmed that
the step of aryl Csp2-H bond breaking possibly
19% D H(D) O
O
S
[RuCl2(p-cymene)]2 (10 mol %)
AgSbF6 (20 mol %)
S
NH
(a)
NH
NH
Pivalic acid (100 mol %)
DCE, 100 oC, Ar, 12 h
CH3OD (1.5 eq.)
H(D)
19% D
H(D) O
H
d2-1a
1a
1a
0% D
23.5% D
H(D)
O
S
S
[RuCl2(p-cymene)]2 (10 mol %)
AgSbF6 (20 mol %)
O
O
S
N
(b)
(c)
+
Ph
2a
Pivalic acid (100 mol %)
DCE, 100 oC, Ar, 2 h
CH3OD (1.5 eq.)
H
15% D
d3-3a
H(D)
(D)H
23.5% D
0% D
O
S
H(D)
30% D
H(D)
O
S
[RuCl2(p-cymene)]2 (10 mol %)
AgSbF6 (20 mol %)
N
N
Pivalic acid (100 mol %)
DCE, 100 oC, Ar, 2 h
CH3OD (1.5 eq.)
0% D
H(D)
(D)H
30% D
O
d2-3a
3a
2a (1.0 equiv)
[RuCl2(p-cymene)]2 (10 mol %)
AgSbF6 (20 mol %)
H
H
O
S
H
O
S
D
O
S
S
N
NH
NH
N
(d)
(e)
(f)
+
+
Pivalic acid (100 mol %)
Ph
D
DCE, 100 oC, Ar, 1 h
D
Ph
99% D
55% D
3a
d1-1a
d1-3a
d1-1a'
KIE = 1.56
O
O
[RuCl2(p-cymene)]2 (10 mol %)
AgSbF6 (20 mol %)
O
O
S
S
S
3w, R1 = MeO
3y, R1 = Cl
NH
N
+
Ph
Pivalic acid (100 mol %)
DCE, 100 oC, Ar, 2 h
R1
H
R1
Ar
2a (1.5 eq.)
1g/1i = 1:1
3w/3y = 1.75:1
O
S
O
[RuCl2(p-cymene)]2 (10 mol %)
AgSbF6 (20 mol %)
O
O
S
S
NH
N
3b, Ar = 4-MePh
3k, Ar = 4-CF3Ph
+
Ar
Pivalic acid (100 mol %)
DCE, 100 oC, Ar, 2 h
H
Ar
2b = 2k = 3.0 eq.
2b/2k = 1:1
1a (0.1 mmol)
3b/3k = 1:1.5
Scheme 3. Control experiments
On the basis of the above observations and the
known Ru(II)-catalyzed Csp2-H bond activation
process,[24] we proposed a plausible mechanism in
Scheme 4. The initial coordination of sulfoximine
nitrogen of substrate 1a to an active Ru(II) catalyst
and subsequent Csp2-H activation via electrophilic
ruthenation afford a five-membered ruthenacycle A.
Then nucleophilic attack of sulfur ylide 2a on Ru(II)
complex A generates Ru(II) carbene B with the loss
of DMSO, Ru(II) carbene B further undergoes
carbene migratory insertion to produce another six-
membered ruthenacycle intermediate C. Finally,
metal protonation followed by an intramolecular
nucleophilic attack of imine to carbonyl group
produces 1,2-benzothiazine 3a with release of the
Ru(II) catalysts.
4
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10.1002/adsc.201800753
Advanced Synthesis & Catalysis
[RuCl (p-cymene)]
O
S
2
O
S
AgSbF
6
-H O
N
2
O
NH
AgCl
O
S
1a
Ph
Ru(II)X
2
3a
D
Ph
HN
-
-
X = SbF or PivO
6
+
H
+
H
O
S
N
O
O
S
Ru(II)
A
O
S
N
Ru
Ph
C
O
O
S
N
Ph
Ru
2a
O
DMSO
ligands (X) of Ru(II) cation are omitted for clarity
B Ph
Scheme 4. Possible mechanism for the transformation
h. Next, the solvent was evaporated, and water (15 mL)
and ethyl acetate (20 mL) were added to the resulting
slurry. The layers were separated and the aqueous layer
was washed with ethyl acetate (2 × 30 mL) and the organic
layers were combined. The organic solution was dried over
anhydrous sodium sulphate (Na2SO4), filtered over a
sintered funnel, and evaporated to dryness. The crude
product was purified by flash chromatography over silica
gel using EtOAc/MeOH (95:5) to afford the corresponding
sulfoxonium ylides 2a-2q.
Conclusion
In conclusion, we have developed a ruthenium(II)-
catalyzed coupling-cyclization of S-arylsulfoximines
with -carbonyl sulfoxonium ylides. This
transformation proceeds through a sequential aryl C-
H carbenoid insertion/cyclization and provides an
efficient access to 1,2-benzothiazine skeletons.
Moreover, the afforded 1,2-benzothiazines could be
converted into various 4-substituted analogues for
versatile synthetic applications.
Synthesis of S-arylsulfoximines [26]
S-Arylsulfoximines 1a-1o were prepared according to the
reported procedures.26 To a stirred solution of sulfides (1
mmol) in MeOH (10 mL) was added the (NH4)2CO3 (1.5
equiv.). Subsequently, PhI(OAc)2 (2.3 equiv) was added
and the solution was stirred at room temperature. After the
disappearance of the sulfides (checked by TLC), the
solvent was removed under reduced pressure. The crude
product was purified by flash column chromatography (10
mmol sulfide and 100 mL of MeOH were used for the
gram-scale reaction) to product S-arylsulfoximines 1a-1o.
Experimental Section
General Information
Unless otherwise noted, all experiments were performed
under argon atmosphere. Solvents were treated with 4 Å
molecular sieves or sodium and distilled prior to use. Flash
chromatography was performed on silica gel (40~63 mm)
by standard technique. 1H and 13C NMR spectra were
recorded on a 400 MHz NMR spectrometer (400 MHz for
1 H and 100 MHz for 13 C). Splitting patterns are designated
as singlet (s), doublet (d), triplet (t), quartet (q). Splitting
patterns that could not be interpreted or easily visualized
are designated as multiple (m). Low resolution mass
spectra were recorded using HPLC Mass Spectrometer.
High resolution exact mass measurements (HR-MS) were
performed on a TOF spectrometer. Infrared spectra (IR)
were reported as wavelength numbers (cm-1). Infrared
spectra were recorded by preparing a KBr pellet containing
the title compound. Crystal data were obtained by
employing graphite monochromated Mo - Kα radiation (λ
= 1.54178 Å) at 571 (2) K and operating in the φ-ω scan
mode. The structure was solved by direct methods
SHELXS-97.
Synthesis of sulfoximines d1-1a [26, 27]
2-Bromothioanisole (2.03 g, 10 mmol) was dissolved in
o
dry THF (20 mL), the solution was cooled to –78 C, and
n-BuLi (6.25 mL, 1.6 M, 10 mmol) was added drop wise.
o
After stirring for 1 h at –78 C. D2O (4.0 mL) was added
drop wise and stirring was continued while the Dewar flask
was removed 10 min. After the addition. The mixture was
allowed to stir for additional 4 h at room temperature. Then,
H2O (20 mL) was added, the phases were separated, and
the aqueous layer was extracted DCM (3 × 20 mL). The
combined organic layers were dried over anhydrous
MgSO4, filtered, concentrated and crude product was used
without further purification.
To a stirred solution of sulfide (1 mmol) in MeOH (10
ml) was added the (NH4)2CO3 (1.5 equiv.). Subsequently,
PhI(OAc)2 (2.3 equiv) was added and the solution was
stirred at room temperature. After the disappearance of the
sulfide (checked by TLC), the solvent was removed under
reduced pressure. The crude product was purified by flash
column chromatography to produce d1-1a (10 mmol
sulfide and 100 mL of MeOH were used for the gram-scale
reaction)
The Procedure for the Preparation of sulfoxonium
ylides
Ylides 2a-2q were prepared according to the reported
procedures.[25] To a stirred solution of potassium tert-
butoxide (3.0 g, 27.2 mmol) in THF (30 mL) was added
trimethylsulfoxonium iodide (5.0 g, 20.6 mmol) at room
temperature. The resulting mixture is refluxed for 2 h.
Then reaction mixture is cooled to 0 °C, followed by
addition of acyl chlorides (7 mmol) in THF (5 mL). The
reaction was allowed to room temperature and stirred for 3
Sulfoximine d1-1a: 1H NMR (400 MHz, CDCl3) δ 8.00 (d,
J = 7.5 Hz, 1H), 7.65 – 7.59 (m, 1H), 7.58 – 7.50 (m, 2H),
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800753
Advanced Synthesis & Catalysis
4.16 (s, 1H), 3.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
284.1104, found: 284.1095; IR (KBr): 3233, 3049, 2923,
1599, 1531, 1476, 1354, 1210, 1108, 973, 849, 794, 695,
143.2, 133.1, 129.3, 129.2, 127.7, 127.4, 127.2, 46.0. HR-
MS (ESI) calcd for [M + 1]+: C7H8DNOS: 157.0546, found: 509, 481 cm-1.
157.0536.
3-(4-(Tert-butyl)phenyl)-1-methylbenzo[e][1,2]thiazine
1-oxide (3f): Yellow solid, 43.6 mg, 70% yield, mp
1
206−208 °C. H NMR (400 MHz, CDCl3) δ 7.79 (d, J =
General Procedure for the Synthesis of the 1,2-
Benzothioazines
7.7 Hz, 2H), 7.69 (d, J = 8.0 Hz, 1H), 7.45 (t, J = 7.6 Hz,
1H), 7.35 (d, J = 7.7 Hz, 2H), 7.28 (dd, J = 16.8, 8.2 Hz,
2H), 6.55 (s, 1H), 3.49 (s, 3H), 1.26 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 152.1, 147.3, 136.9, 135.8, 132.6,
127.1, 126.3, 126.1, 125.3, 123.4, 118.5, 97.7, 45.4, 34.7,
31.3. HR-MS (ESI) calcd for [M + 1]+: C19H22NOS:
312.1417, found: 312.1404; IR (KBr): 3033, 2924, 1615,
1532, 1487, 1363, 1175, 1105, 787, 554, 479 cm-1.
3-([1,1'-Biphenyl]-4-yl)-1-
A Schlenk tube (20 mL) equipped with a stir bar was
loaded with the sulfoximine (0.2 mmol), sulfoxonium ylide
(0.4 mmol), [RuCl2(p-cymene)]2, (10 mol %, 12.2 mg) and
AgSbF6 (20 mol %, 14.3 mg), PivOH (1 equiv, 40.8 mg).
Under an Ar atmosphere (1 atm), dry DCE (4.0 mL), was
added, and the reaction mixture was allowed to stir at
100 °C for 12 h. After cooling to room temperature, the
mixture was filtered through a short Celite pad. The filtrate
was concentrated, and the product was purified by column
chromatography using silica gel and a mixture of hexanes
and ethyl acetate as eluent.
methylbenzo[e][1,2]thiazine 1-oxide (3g): Yellow solid,
1
49.7 mg, 75% yield, mp 148−150 °C. H NMR (400 MHz,
CDCl3) δ 7.93 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.0 Hz, 1H),
7.59 – 7.51 (m, 4H), 7.44 (t, J = 7.6 Hz, 1H), 7.35 (t, J =
7.5 Hz, 2H), 7.32 – 7.23 (m, 3H), 6.61 (s, 1H), 3.48 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 146.7, 141.6, 140.7,
137.5, 136.7, 132.7, 128.9, 127.5, 127.3, 127.1, 127.1,
127.0, 126.4, 123.5, 118.8, 98.3, 45.4. HR-MS (ESI) calcd
for [M + 1]+: C21H18NOS: 332.1104, found: 332.1095; IR
(KBr): 3031, 2928, 1631, 1530, 1482, 1398, 1199, 1002,
853, 764, 694, 490 cm-1.
1-Methyl-3-phenylbenzo[e][1,2]thiazine 1-oxide (3a):
1
Yellow solid, 38.2 mg, 75% yield, mp 96−97 °C. H NMR
(400 MHz, CDCl3) δ 7.88 (d, J = 7.3 Hz, 2H), 7.72 (d, J =
7.8 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.38 – 7.25 (m, 5H),
6.59 (s, 1H), 3.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
147.1, 138.5, 136.7, 132.7, 128.9, 128.4, 127.2, 126.5,
126.4, 123.4, 118.7, 98.3, 45.5. HR-MS (ESI) calcd for [M
+ 1]+: C15H14NOS: 256.0777, found: 256.0791; IR (KBr):
3233, 3050, 3006, 2924, 1639, 1586, 1532, 1475, 1360,
1199, 1030, 782, 684, 475 cm-1.
3-(4-Fluorophenyl)-1-methylbenzo[e][1,2]thiazine
1-oxide (3h): Yellow solid, 32.3 mg, 59% yield, mp
148−150 °C. 1H NMR (400 MHz, CDCl3) δ 7.89 – 7.82 (m,
2H), 7.70 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.1 Hz, 1H), 7.32
(d, J = 7.7 Hz, 2H), 7.01 (t, J = 8.7 Hz, 2H), 6.52 (s, 1H),
3.51 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.6, 162.1,
1-Methyl-3-(p-tolyl)benzo[e][1,2]thiazine 1-oxide (3b):
1
Yellow solid, 40.8 mg, 76% yield, mp 123−125 °C. H
2
146.1, 136.6, 134.7, 134.6 (d, JC-F = 12.0 Hz), 132.7,
NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.2 Hz, 2H), 7.80
(d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.40 (dd, J =
14.1, 7.5 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 6.66 (s, 1H),
3.61 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
147.2, 138.9, 136.8, 135.7, 132.6, 129.1, 127.1, 126.4,
126.1, 123.4, 118.6, 97.7, 45.4, 21.3. HR-MS (ESI) calcd
for [M + 1]+: C16H16NOS: 270.0947, found: 270.0936; IR
(KBr): 3043, 2925, 1612, 1530, 1486, 1363, 1176, 1105,
786, 545, 475 cm-1.
2
128.4, 128.3 (d, JC-F = 32.8 Hz), 127.2, 126.4, 123.4,
118.6, 115.2 (d, JC-F = 85.6 Hz), 98.0, 45.3. 19F NMR (376
MHz, CDCl3) δ -112.94, -112.95, -112.96, -112.97, -
112.97, -112.98, -112.99, -113.00, -113.01. HR-MS (ESI)
calcd for [M + 1]+: C15H13FNOS: 274.0696, found:
274.0688; IR (KBr): 3043, 2925, 1585, 1472, 1372, 1210,
1099, 975, 856, 798, 537, 477 cm-1.
3-(4-Chlorophenyl)-1-methylbenzo[e][1,2]thiazine 1-
oxide (3i): Yellow solid, 47.5 mg, 82% yield, mp
1-Methyl-3-(m-tolyl)benzo[e][1,2]thiazine 1-oxide (3c):
1
168−140 °C. H NMR (400 MHz, CDCl3) δ 7.91 (d, J =
1
Yellow solid, 45.7 mg, 85% yield, mp 108−110 °C. H
8.5 Hz, 2H), 7.79 (s, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.46 –
7.37 (m, 4H), 6.65 (s, 1H), 3.61 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 145.8, 137.0, 136.4, 134.7, 132.8, 128.5,
127.8, 127.3, 126.6, 123.4, 118.8, 98.4, 45.3. HR-MS
(ESI) calcd for [M + 1]+: C15H13ClNOS: 290.0401, found:
290.039155; IR (KBr): 3043, 2953, 1531, 1475, 1356,
1194, 1003, 805, 783, 530, 479 cm-1.
NMR (400 MHz, CDCl3) δ 7.84 – 7.74 (m, 3H), 7.58 (t, J
= 7.5 Hz, 1H), 7.46 – 7.37 (m, 2H), 7.33 (t, J = 7.6 Hz, 1H),
7.21 (d, J = 7.4 Hz, 1H), 6.68 (s, 1H), 3.62 (s, 3H), 2.45 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 147.3, 138.5, 138.0,
136.7, 132.6, 129.7, 128.3, 127.3, 127.2, 126.3, 123.6,
123.4, 118.7, 98.2, 45.4, 21.5. HR-MS (ESI) calcd for [M
+ 1]+: C16H16NOS: 270.0947, found: 270.0936; IR (KBr):
3050, 2924, 1639, 1532, 1475, 1360, 1199, 1102, 860, 782,
684, 505, 475 cm-1.
3-(4-Bromophenyl)-1-methylbenzo[e][1,2]thiazine 1-
oxide (3j): Yellow solid, 50.1 mg, 75% yield, mp
1
173−175 °C. H NMR (400 MHz, CDCl3) δ 7.73 (dd, J =
1-Methyl-3-(o-tolyl)benzo[e][1,2]thiazine
1-oxide
13.9, 8.3 Hz, 2H), 7.52 – 7.43 (m, 3H), 7.34 (t, J = 6.6 Hz,
2H), 6.57 (s, 1H), 3.53 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 145.8, 137.4, 136.4, 132.8, 131.5, 128.1, 127.3,
126.7, 123.4, 123.1, 118.8, 98.4, 45.4. HR-MS (ESI) calcd
for [M + 1]+: C15H13BrNOS: 334.9921, found: 334.9927;
IR (KBr): 3008, 2923, 1614, 1534, 1484, 1362, 1177, 1005,
786, 552, 488 cm-1.
1
(3d): Yellow liquid, 19.4 mg, 36% yield. H NMR (400
MHz, CDCl3) δ 7.72 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.6
Hz, 1H), 7.37 – 7.32 (m, 2H), 7.28 (d, J = 8.0 Hz, 1H),
7.21 – 7.10 (m, 4H), 6.15 (s, 1H), 3.53 (s, 3H), 2.40 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 149.7, 139.8, 136.5,
136.4, 132.6, 130.7, 128.9, 128.4, 127.0, 126.4, 125.7,
123.3, 118.1, 101.8, 45.1, 20.3. HR-MS (ESI) calcd for [M
+ 1]+: C16H16NOS: 270.0947, found: 270.0937; IR (KBr):
3046, 2925, 1628, 1531, 1488, 1397, 1174, 1072, 1003,
787, 554,480 cm-1.
1-Methyl-3-(4-
(trifluoromethyl)phenyl)benzo[e][1,2]thiazine 1-oxide
(3k): Yellow solid, 50.4 mg, 78% yield, mp 189−190 °C.
1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.2 Hz, 2H),
7.84 (d, J = 8.2 Hz, 1H), 7.68 (d, J = 8.2 Hz, 2H), 7.62 (t, J
= 7.5 Hz, 1H), 7.47 (dd, J = 7.5, 4.6 Hz, 2H), 6.74 (s, 1H),
3.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 145.4, 141.9,
3-(3,5-Dimethylphenyl)-1-methylbenzo[e][1,2]thiazine
1-oxide (3e): Yellow solid, 45.9 mg, 81% yield, mp
1
151−153 °C. H NMR (400 MHz, CDCl3) δ 7.80 (d, J =
8.0 Hz, 1H), 7.62 (s, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.44 –
7.35 (m, 2H), 7.05 (s, 1H), 6.68 (s, 1H), 3.61 (s, 3H), 2.42
(s, 6H); 13C NMR (100 MHz, CDCl3) δ 147.4, 138.5, 137.9,
136.7, 132.6, 130.7, 127.2, 126.2, 124.5, 123.4, 118.7, 98.2,
45.3, 21.5. HR-MS (ESI) calcd for [M + 1]+: C17H18NOS:
2
136.2, 132.9, 127.5, 127.1, 126.7, 125.3 (q, JC-F = 14.8.0
Hz), 125.2, 123.5, 119.2, 99.5, 45.4; 19F NMR (376 MHz,
CDCl3) δ -62.5. HR-MS (ESI) calcd for [M + 1]+:
C16H13F3NOS: 323.0696, found: 323.0682; IR (KBr): 3042,
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800753
Advanced Synthesis & Catalysis
2927, 1614, 1532, 1484, 1362, 1176, 1005, 785, 557, 427
cm-1.
5H), 6.63 (s, 1H), 3.87 – 3.75 (m, 1H), 3.71 – 3.58 (m, 1H),
1.28 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
147.7, 138.7, 138.0, 132.8, 128.8, 128.4, 127.2, 126.5,
126.2, 123.9, 115.7, 97.5, 51.3, 8.7. HR-MS (ESI) calcd
for [M + 1]+: C16H16NOS: 270.0947, found: 270.0933; IR
(KBr): 3046, 2927, 1615, 1533, 1486, 1364, 1176, 1005,
785, 552, 494 cm-1.
1-Methyl-3-(perfluorophenyl)benzo[e][1,2]thiazine 1-
oxide (3l): Yellow solid, 67.7 mg, 98% yield, mp
1
129−131 °C. H NMR (400 MHz, CDCl3) δ 7.86 (d, J =
8.0 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.54 (t, J = 7.6 Hz,
1H), 7.42 (d, J = 8.0 Hz, 1H), 6.35 (s, 1H), 3.62 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 135.2, 133.1, 128.0, 127.2,
123.5, 119.1, 105.5, 45.2; 19F NMR (376 MHz, CDCl3) δ -
140.97, -140.99, -141.03, -141.05, -154.51, -154.56, -
154.62, -162.14, -162.16, -162.19, -162.21, -162.25, -
162.27. HR-MS (ESI) calcd for [M + 1]+: C15H9F5NOS:
346.0302, found: 346.0295; IR (KBr): 3008, 2926, 1664,
1505, 1454, 1326, 1157, 1094, 817, 665, 508, 457 cm-1.
1-Methyl-3-(naphthalen-2-yl)benzo[e][1,2]thiazine 1-
oxide (3m): Yellow solid, 47.6 mg,78% yield, mp
1-Benzyl-3-phenylbenzo[e][1,2]thiazine 1-oxide (3s):
1
Yellow liquid, 29.8 mg, 45% yield. H NMR (400 MHz,
CDCl3) δ 7.93 (d, J = 7.2 Hz, 2H), 7.63 (d, J = 8.0 Hz, 1H),
7.50 (t, J = 7.6 Hz, 1H), 7.47 – 7.36 (m, 4H), 7.33 – 7.25
(m, 3H), 7.22 – 7.17 (m, 3H), 6.37 (s, 1H), 4.78 (d, J =
13.9 Hz, 1H), 4.65 (d, J = 13.9 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 148.0, 138.8, 138.5, 133.1, 131.2, 128.8,
128.8, 128.4, 128.3, 128.0, 126.7, 126.3, 125.9, 125.1,
115.4, 97.4, 64.7. HR-MS (ESI) calcd for [M + 1]+:
C21H18NOS: 332.1104, found: 332.1097; IR (KBr): 3030,
3027, 1603, 1532, 1486, 1356, 1174, 1103, 787, 690, 556
cm-1.
1
164−166 °C. H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H),
7.93 (dd, J = 8.7, 1.5 Hz, 1H), 7.88 – 7.81 (m, 1H), 7.79 –
7.69 (m, 3H), 7.47 (t, J = 7.6 Hz, 1H), 7.42 – 7.37 (m, 2H),
7.37 – 7.27 (m, 2H), 6.72 (s, 1H), 3.54 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 146.8, 136.7, 135.7, 133.7, 133.4,
132.7, 128.8, 127.9, 127.6, 127.3, 126.5, 126.4, 126.3,
126.2, 123.9, 123.5, 118.9, 98.8, 45.4. HR-MS (ESI) calcd
for [M + 1]+: C19H16NOS: 306.0947, found: 306.0941; IR
(KBr): 3046, 2923, 1615, 1531, 1487, 1363, 1176, 1005,
786, 695, 560, 481 cm-1.
1-Cyclopropyl-3-phenylbenzo[e][1,2]thiazine 1-oxide
1
(3t): Yellow liquid, 22.5 mg, 40% yield. H NMR (400
MHz, CDCl3) δ 7.99 (d, J = 7.6 Hz, 2H), 7.89 (d, J = 8.0
Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.48 – 7.36 (m, 5H), 6.70
(s, 1H), 3.01 – 2.92 (m, 1H), 1.92 – 1.82 (m, 1H), 1.43 –
1.31 (m, 2H), 1.27 – 1.16 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 147.1, 138.8, 136.9, 132.4, 128.8, 128.3, 127.0,
126.5, 126.2, 123.7, 119.4, 98.2, 32.9, 6.6, 5.0. HR-MS
(ESI) calcd for [M + 1]+: C17H16NOS: 282.0947, found:
282.0931; IR (KBr): 3029, 2924, 1630, 1530, 1486, 1355,
1175, 1003, 786, 690, 551 cm-1.
1-Methyl-3-(thiophen-2-yl)benzo[e][1,2]thiazine
1-
oxide (3n): Yellow solid, 30.3 mg, 58% yield, mp
1
128−129 °C. H NMR (400 MHz, CDCl3) δ 7.77 (d, J =
7.9 Hz, 1H), 7.60 (dd, J = 3.6, 0.9 Hz, 1H), 7.55 (t, J = 7.6
Hz, 1H), 7.39 – 7.32 (m, 3H), 7.09 (dd, J = 5.0, 3.7 Hz,
1H), 6.61 (s, 1H), 3.59 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 144.0, 142.1, 136.4, 132.8, 127.8, 126.9, 126.7,
126.1, 125.1, 123.5, 118.9, 97.1, 45.2. HR-MS (ESI) calcd
for [M + 1]+: C13H12NOS2: 262.0238, found: 262.0230; IR
(KBr): 3234, 3094, 2990, 2927, 1628, 1486, 1397, 1174,
1003, 786, 553 cm-1.
1-Methyl-3-phenylnaphtho[2,3-e][1,2]thiazine
1-
oxide (3u): Yellow solid, 18.3 mg, 30% yield, mp
1
149−151 °C. H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H),
8.06 (d, J = 7.4 Hz, 1H), 8.00 (d, J = 7.4 Hz, 2H), 7.92 (d, J
= 8.2 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.83 (s, 1H), 7.74
(d, J = 5.0 Hz, 1H), 7.68 (dd, J = 6.2, 3.2 Hz, 1H), 7.57 (t, J
= 7.5 Hz, 1H), 7.47 – 7.41 (m, 4H), 7.40 – 7.34 (m, 1H),
3.69 (s, 1H), 3.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
149.4, 145.6, 139.1, 138.7, 135.7, 134.8, 132.2, 131.7,
129.2, 129.0, 128.9, 128.8, 128.8, 128.5, 128.4, 127.8,
127.4, 126.9, 126.5, 126.4, 126.0, 124.7, 124.5, 123.9,
121.3, 119.2, 98.8, 93.7, 45.8, 45.4. HR-MS (ESI) calcd
for [M + 1]+: C19H16NOS: 306.0947, found: 306.0938; IR
(KBr): 3030, 2923, 1615, 1532, 1488, 1363, 1175, 1105,
787, 613, 575, 468 cm-1.
3-Isopropyl-1-methylbenzo[e][1,2]thiazine
1-oxide
(3o): Yellow solid, 19.9 mg, 45% yield, mp 100−101 °C.
1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 1H),
7.51 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.27 (d, J
= 8.2 Hz, 1H), 5.98 (s, 1H), 3.50 (s, 3H), 2.65 (dt, J = 13.6,
6.8 Hz, 1H), 1.25 (d, J = 6.8 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 157.5, 136.9, 132.5, 126.4, 125.6, 123.4, 117.9,
96.3, 45.1, 36.4, 21.4. HR-MS (ESI) calcd for [M + 1]+:
C12H16NOS: 222.0947, found: 222.0941; IR (KBr): 3008,
2927, 1616, 1585, 1487, 1363, 1176, 1005, 786, 680, 519,
494 cm-1.
1,6-Dimethyl-3-phenylbenzo[e][1,2]thiazine 1-oxide
1
(3v): Yellow liquid, 43.6 mg, 81% yield. H NMR (400
MHz, CDCl3) δ 7.86 (d, J = 7.8 Hz, 2H), 7.60 (d, J = 8.5
Hz, 1H), 7.33 (t, J = 7.5 Hz, 2H), 7.30 – 7.24 (m, 1H), 7.12
(d, J = 6.8 Hz, 2H), 6.51 (s, 1H), 3.48 (s, 3H), 2.35 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 147.1, 143.4, 138.6, 136.9,
128.8, 128.4, 127.8, 126.9, 126.5, 123.4, 116.4, 98.1, 45.6,
21.8. HR-MS (ESI) calcd for [M + 1]+: C16H16NOS:
270.0947, found: 270.0937; IR (KBr): 3036, 2987, 1615,
1532, 1487, 1363, 1175, 1105, 787, 558, 489 cm-1.
3-(tert-Butyl)-1-methylbenzo[e][1,2]thiazine 1-oxide
1
(3p): Yellow liquid, 26.4 mg, 56% yield. H NMR (400
MHz, CDCl3) δ 7.61 (d, J = 8.0 Hz, 1H), 7.39 (t, J = 7.6
Hz, 1H), 7.20 (dd, J = 17.7, 8.2 Hz, 2H), 5.97 (s, 1H), 3.37
(s, 3H), 1.19 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 159.7,
137.0, 132.3, 126.8, 125.8, 123.2, 117.8, 95.2, 45.0, 37.3,
28.9. HR-MS (ESI) calcd for [M + 1]+: C13H18NOS:
236.1104, found: 236.1099; IR (KBr): 3009, 2953, 1615,
1534, 1487, 1363, 1175, 1005, 805, 787, 554, 479 cm-1.
3-((3r,5r,7r)-Adamantan-1-yl)-1-
6-Methoxy-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
oxide (3w): Yellow solid, 50.2 mg, 88% yield, mp
1
123−125 °C. H NMR (400 MHz, CDCl3) δ 7.97 (d, J =
methylbenzo[e][1,2]thiazine 1-oxide (3q): Yellow solid,
7.6 Hz, 2H), 7.72 (d, J = 8.8 Hz, 1H), 7.48 – 7.36 (m, 3H),
6.96 (d, J = 8.7 Hz, 1H), 6.79 (s, 1H), 6.59 (s, 1H), 3.90 (s,
3H), 3.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.7,
147.8, 139.3, 138.6, 128.9, 128.4, 126.6, 125.6, 115.7,
111.7, 108.0, 98.7, 55.6, 46.1. HR-MS (ESI) calcd for [M
+ 1]+: C16H16NO2S: 286.0896, found: 286.0887; IR (KBr):
3030, 3004, 2927, 1594, 1532, 1467, 1203, 1099, 855, 762,
690, 519, 427 cm-1.
1
32.6 mg, 52% yield, mp 145−147 °C. H NMR (400 MHz,
CDCl3) δ 7.71 (d, J = 8.0 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H),
7.31 (dd, J = 15.0, 7.8 Hz, 2H), 6.00 (s, 1H), 3.46 (s, 3H),
2.09 (s, 3H), 1.95 (q, J = 12.2 Hz, 6H), 1.83 – 1.71 (m,
6H); 13C NMR (100 MHz, CDCl3) δ 159.7, 137.1, 132.3,
126.8, 125.7, 123.2, 118.0, 95.1, 45.0, 40.7, 38.7, 37.0,
28.7. HR-MS (ESI) calcd for [M + 1]+: C19H24NOS:
314.1573, found: 314.1565; IR (KBr): 3046, 2927, 1615,
1531, 1486, 1363, 1176, 1005, 787, 508, 481 cm-1.
6-Fluoro-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
oxide (3x): Yellow solid, 43.2 mg, 79% yield, mp
1
1-Ethyl-3-phenylbenzo[e][1,2]thiazine 1-oxide (3r):
139−141 °C. H NMR (400 MHz, CDCl3) δ 7.86 (d, J =
1
Yellow solid, 33.4 mg, 62% yield, mp 120−121 °C. H
7.4 Hz, 2H), 7.71 (dd, J = 8.6, 5.3 Hz, 1H), 7.38 – 7.26 (m,
3H), 6.99 (dd, J = 20.9, 10.1 Hz, 2H), 6.52 (s, 1H), 3.49 (s,
NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.4 Hz, 2H), 7.75
(d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.49 – 7.33 (m, 3H). 13C NMR (100 MHz, CDCl3) δ 166.1, 163.6, 148.6,
7
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10.1002/adsc.201800753
Advanced Synthesis & Catalysis
139.8, 139.7, 138.1, 129.3, 128.4, 126.6, 126.6, 115.0,
4-Bromo-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
2
114.9, 114.8 (d, JC-F = 8.4 Hz), 114.7, 112.1, 111.9, 97.8， oxide (4): Yellow solid, 33.4 mg, 50% yield, mp
2
1
97.7 (d, JC-F = 10.4 Hz), 45.9. 19F NMR (376 MHz,
120−121 °C. H NMR (400 MHz, CDCl3) δ 8.12 (d, J =
CDCl3) δ -105.03, -105.05, -105.06, -105.07, -105.08, -
105.09. HR-MS (ESI) calcd for [M + 1]+: C15H13FNOS:
274.0696, found: 274.0690; IR (KBr): 3008, 2927, 1588,
1532, 1479, 1360, 1202, 1106, 835, 799, 512, 476 cm-1.
6-Chloro-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
8.4 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.75 (t, J = 7.7 Hz,
1H), 7.68 (d, J = 7.6 Hz, 2H), 7.55 (t, J = 7.6 Hz, 1H),
7.49 – 7.39 (m, 3H), 3.64 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 147.6, 140.5, 134.8, 133.3, 129.5, 128.6, 128.0,
127.8, 127.3, 123.1, 120.9, 96.1, 44.4. HR-MS (ESI)
calcd for [M + 1]+: C15H13BrNOS: 333.9896, found:
333.9892; IR (KBr): 3009, 2923, 1613, 1533, 1485, 1363,
1177, 1006, 786, 547, 425 cm-1.
oxide (3y): Yellow solid, 39.4 mg, 68% yield, mp
1
140−142 °C. H NMR (400 MHz, CDCl3) δ 7.96 (d, J =
7.5 Hz, 2H), 7.74 (d, J = 8.5 Hz, 1H), 7.48 – 7.39 (m, 4H),
7.35 (dd, J = 8.5, 1.9 Hz, 1H), 6.61 (s, 1H), 3.61 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 148.7, 138.9, 138.3, 138.1,
129.3, 128.4, 126.6, 126.6, 126.3, 125.1, 116.6, 97.4, 45.6.
HR-MS (ESI) calcd for [M + 1]+: C15H13ClNOS: 290.0402,
found: 290.0388; IR (KBr): 3009, 2927, 1615, 1564, 1454,
1390, 1198, 1027, 785, 692, 484 cm-1.
Preparation
of
4-bromo-1-(bromomethyl)-3-
phenylbenzo[e][1,2]thiazine 1-oxide[28]
A mixture of 3a (0.4 mmol, 77.2 mg), NBS (0.8 mmol,
142 mg) and AIBN (0.08 mmol, 13.2 mg) in CCl4 (8 mL)
was heated to reflux for 12 h. The reaction mixture was
cooled to room temperature and filtered. The filtrate was
washed with saturated NaHCO3 and brine, and the
organic layer was dried over Na2SO4, filtered, and
concentrated. The product was purified by flash column
chromatography on silica gel with n-pentane/ethyl acetate
(15:1) as eluent to give product 5.
6-Bromo-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
oxide (3z): Yellow solid, 51.5 mg, 77% yield, mp
1
167−169 °C. H NMR (400 MHz, CDCl3) δ 7.85 (d, J =
7.4 Hz, 2H), 7.56 (d, J = 8.5 Hz, 1H), 7.50 (s, 1H), 7.43 –
7.29 (m, 4H), 6.50 (s, 1H), 3.50 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 148.6, 138.4, 138.1, 129.4, 129.3, 128.5,
127.4, 126.6, 125.0, 117.0, 97.3, 45.6. HR-MS (ESI) calcd
for [M + 1]+: C15H13BrNOS: 333.9896, found: 333.9883;
IR (KBr): 3008, 2925, 1614, 1531, 1487, 1363, 1176, 1005,
787, 563, 479 cm-1.
4-Bromo-1-(bromomethyl)-3-phenylbenzo[e][1,2]
thiazine 1-oxide: (5): yellow liquid, 15.7 mg, 19% yield.
1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.4 Hz, 1H),
7.91 (d, J = 7.9 Hz, 1H), 7.80 (t, J = 7.8 Hz, 1H), 7.67 (d, J
= 7.6 Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H), 7.50 – 7.40 (m, 3H),
5.03 (d, J = 12.1 Hz, 1H), 4.85 (d, J = 12.1 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 148.7, 140.3, 137.7, 134.7,
129.2, 128.8, 128.0, 127.9, 127.7, 125.1, 116.0, 96.1, 47.3.
HR-MS (ESI) calcd for [M + 1]+: C15H12Br2NOS:
411.9001, found: 411.9000; IR (KBr): 3009, 2927, 1614,
1531, 1487, 1363, 1176, 1005, 786, 553, 494 cm-1.
5-Bromo-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
oxide(3z-1): Yellow solid, 48.1 mg, 72% yield, mp
1
185−187 °C. H NMR (400 MHz, CDCl3) δ 7.99 (d, J =
7.0 Hz, 2H), 7.62 – 7.56 (m, 1H), 7.45 (dd, J = 13.8, 6.3
Hz, 3H), 7.39 (dd, J = 6.7, 2.6 Hz, 2H), 6.67 (s, 1H), 3.90
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.8, 139.9, 137.8,
132.9, 131.7, 129.2, 128.4, 127.4, 126.5, 118.8, 118.6, 98.0,
49.9. HR-MS (ESI) calcd for [M + 1]+: C15H13BrNOS:
333.9896, found: 333.9892; IR (KBr): 3006, 2925, 1617,
1512, 1488, 1366, 1264, 1098, 1002, 811, 689, 519, 479
cm-1.
Synthesis
of
1-methyl-4-nitro-3-
phenylbenzo[e][1,2]thiazine 1-oxide [29]
It was introduced by nitration of 3a (0.2 mmol, 51 mg )
with concentrated nitric acid ( 0.4 mmol, 50.4 mg )in acetic
acid at temperature below 15°C. The mixture was allowed
to stir for 10 h at room temperature. Then, H2O (10 mL)
was added, the phases were separated, and the aqueous
layer was extracted DCM (3 × 20 mL). The combined
organic layers were dried over anhydrous MgSO4, filtered,
concentrated and the oily crude product was purified by
flash column chromatography on silica gel to give product
6 in 42% yield.
8-Bromo-1-methyl-3-phenylbenzo[e][1,2]thiazine 1-
oxide(3z-2): Yellow solid, 50.1 mg, 75% yield, mp
1
127−129 °C. H NMR (400 MHz, CDCl3) δ 7.99 (d, J =
7.0 Hz, 2H), 7.62 – 7.56 (m, 1H), 7.45 (dd, J = 13.8, 6.3
Hz, 3H), 7.39 (dd, J = 6.7, 2.6 Hz, 2H), 6.67 (s, 1H), 3.90
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.8, 139.9, 137.8,
132.9, 131.7, 129.2, 128.4, 127.4, 126.5, 118.8, 118.6, 98.0,
49.9. HR-MS (ESI) calcd for [M + 1]+: C15H13BrNOS:
333.9896, found: 333.9863; IR (KBr): 3008, 2925, 1604,
1531, 1487, 1356, 1218, 1174, 1103, 773, 558, 463 cm-1.
1-Methyl-4-nitro-3-phenylbenzo[e][1,2]thiazine
1-
1
oxide: (6): yellow liquid, 25.2 mg, 42% yield. H NMR
(400 MHz, CDCl3) δ 7.88 (d, J = 7.9 Hz, 1H), 7.76 (d, J =
2.1 Hz, 2H), 7.64 – 7.56 (m, 3H), 7.47 – 7.38 (m, 3H), 3.65
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 136.4, 134.3, 130.1,
129.2, 128.7, 128.0, 127.8, 124.0, 122.2, 117.5, 29.7. HR-
MS (ESI) calcd for [M + 1]+: C15H13N2O3S: 301.0641,
found: 301.0642; IR (KBr): 3219, 3007, 2925, 1615, 1528,
1486, 1363, 1176, 1005, 786, 520, 435 cm-1.
Synthetic Applications of This Transformation
Preparation
of
4-bromo-1-methyl-3-
phenylbenzo[e][1,2]thiazine 1-oxide[28]
A mixture of 3a (0.4 mmol, 77.2 mg), NBS (0.4 mmol, 71
mg) and AIBN (0.08 mmol, 13.2 mg) in CCl4 (8 mL) was
heated to reflux for 12 h. The reaction mixture was cooled
to room temperature and filtered. The filtrate was washed
with saturated NaHCO3 and brine, and the organic layer
was dried over Na2SO4, filtered, and concentrated. The
product was purified by flash column chromatography on
silica gel with n-pentane/ethyl acetate (3:1) as eluent to
give product 4.
Acknowledgements
The authors thank National Key Research and Development
Program of China (No. 2016YFA0602900), the NSFC (No.
21372085) and Guangdong Province Science Foundation (No.
2017B090903003) for financial support.
8
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10.1002/adsc.201800753
Advanced Synthesis & Catalysis
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FULL PAPER
Ru (II)-Catalyzed Coupling-Cyclization of
Sulfoximines with alpha-Carbonyl Sulfoxonium
Ylides as an Approach to 1,2-Benzothiazines
Adv. Synth. Catal. 2018, Volume, Page – Page
Haisheng Xie, Jianyong Lan, Jiao Gui, Fengjuan
Chen, Huangfeng Jiang, Wei Zeng*
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