A route to benzo-annelated δ-sultams through michael cyclization

Article abstract of DOI:10.1002/ejoc.201403416

A new approach to benzo-annelated δ-sultams containing an aryl-nitrogen bond is described. The method, which involves the intramolecular Michael cyclization of tert-butyl ortho-[N-(methoxycarbonylmethyl)sulfonylamino]cinnamates, allows the synthesis of secondary sultams as well as their tertiary analogues and bridged tricyclic derivatives efficiently and diastereoselectively.

Full text of DOI:10.1002/ejoc.201403416

Job/Unit: O43416
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Date: 14-01-15 19:12:47
Pages: 10
FULL PAPER
DOI: 10.1002/ejoc.201403416
A Route to Benzo-Annelated δ-Sultams through Michael Cyclization
Daria S. Grosheva,[a] Valentin A. Rassadin,[a] and Victor V. Sokolov*[a]
Keywords: Heterocycles / Sultams / Fused-ring systems / Michael addition / Cyclization
A new approach to benzo-annelated δ-sultams containing an
aryl–nitrogen bond is described. The method, which involves
the intramolecular Michael cyclization of tert-butyl ortho-[N-
(methoxycarbonylmethyl)sulfonylamino]cinnamates, allows
the synthesis of secondary sultams as well as their tertiary
analogues and bridged tricyclic derivatives efficiently and
diastereoselectively.
Introduction
Sultams have shown a wide spectrum of biological activi-
ties, such as anti-inflammatory,[1] antiviral (HIV-1 in vi-
tro),[2] antileukemic,[3] and antimicrobial[4] activities to
name just a few. Therefore, a simple and convenient method
for their synthesis has been required in order to access all Scheme 1. Benzo-annelated sultams.
that sultams have to offer. Currently, methods[5] that have
been used to prepare sultams include Diels–Alder reac-
tions,[6] radical cyclizations,[7] ring-closing metathesis reac-
tions,[8] nucleophilic aromatic substitutions,[9] cyclizations
of aminosulfonyl chlorides,[10] and intramolecular Heck re-
actions.[11]
The narrower class of benzo-annelated sultams is also
very important; 1,2,4-benzothiadiazin-3-one 1,1-dioxide de-
rivatives, for example, have demonstrated anti-HIV ac-
Scheme 2. Proposed approach to benzo-fused δ-sultams; EWG =
electron-withdrawing group.
tivity.[12] Approaches to benzosultams are more limited, but
they are currently being designed.[13]
The vast majority of methods for the synthesis of benzo-
sultams reported to date relate to compounds with an
Ar–S bond (Scheme 1, type I). The development of ap-
proaches to structures of type II is still in its infancy. Actu-
ally, synthetic routes to sultams of type II with n = 1 are
limited to an intramolecular oxidative cyclization of sulfon-
well as their tertiary analogues containing a p-meth-
oxybenzyl (PMB) group. The PMB group could easily be
removed later by acidic hydrolysis[15] or oxidatively by using
ceric ammonium nitrate.[16]
amides in the presence of hypervalent iodine compounds.[14] Results and Discussion
Thus the search for approaches to benzo-fused δ-sultams
The required sulfonamides were synthesized from the
containing an Ar–N bond is highly warranted.
corresponding ortho-iodoanilines in two steps (Scheme 3,
Table 1). Firstly, iodides 1 and 2[17] were coupled with tert-
butyl acrylate (3) in a Heck reaction to give ortho-aminocin-
namates 4 and 5. It is noteworthy that the Pd(OAc)2/P(o-
Tol)3/Et3N/MeCN system has previously been used for the
synthesis of 4a.[18] Gratifyingly, the replacement of
P(o-Tol)3 with the cheaper and more readily available Ph3P
still allowed us to obtain 4a as well as substituted analogues
4b, 4c, and 5b in good yields. However, compound 5c was
isolated together with the unexpected product of chlorine
substitution (i.e., 5cЈ). The reason for this unusual lack of
selectivity is definitely steric hindrance from the side of the
bulky ortho-substituent adjacent to the iodine atom. The
We decided to fill this gap, and we developed a synthetic
strategy using as a key step an intramolecular Michael cycli-
zation of sulfonamides bearing an additional C-nucleophilic
centre and an activated C=C bond (Scheme 2).
We have also been interested in studying of the influence
of a substituent on the nitrogen atom. Thus, we planned to
involve in the reaction secondary sulfonamides (R2 = H) as
[a] Institute of Chemistry, Saint Petersburg State University,
Universitetskii pr. 26, 198504 St. Petersburg, Russia
E-mail: vsokolo@mail.ru
http://www.chem.spbu.ru
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403416.
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D. S. Grosheva, V. A. Rassadin, V. V. Sokolov
FULL PAPER
mixture of 5c and 5cЈ was inseparable, and was used in the
next step directly. The E configurations of the C=C bonds
in cinnamates 4 and 5 were established based on the values
of the spin–spin coupling constants (J ≈ 16 Hz).
Scheme 4. Michael cyclization of sulfonamides 7 and 8. (a) K2CO3,
DMF, 70 °C; (b) MeI (1.0 equiv.) or BnCl (1.0 equiv.), K2CO3,
DMF, 70 °C; (c) MeI (2.0 equiv.) or BnCl (2.0 equiv.), K2CO3,
DMF, 70 °C.
The reactions of secondary sulfonamides 7 proved to be
more complex and interesting. We managed to obtain sec-
ondary sultams 10, but the reaction times increased dramat-
ically, and only the chloro-substituted analogue (i.e., 10c)
formed relatively quickly (see Table 2, entries 3–5). We sup-
pose that the presence of chlorine in aromatic ring can
make the C=C bond more electron deficient, and thus ac-
celerate the key cyclization step.
We believed that secondary sulfonamides would react
more slowly than their tertiary analogues, but the synthesis
of the latter is more complex, and involves one additional
step. Therefore we decided to add an alkylating agent (MeI
or BnCl) to the reaction mixture to obtain tertiary sulfon-
amides in situ, and thus accelerate the intramolecular cycli-
zation. Gratifyingly, this approach proved to be successful,
and allowed us to achieve the desired sultams (i.e., 11, by
using MeI, see Table 2, entries 6 and 7; and 12 by using
BnCl, see Table 2, entries 8 and 9) in good yields as cis/trans
mixtures of isomers as before, but much more quickly.
Interestingly, in the case of chloro-substituted sulfon-
amide 7c, the desired sultam (i.e., 11c) could not be isolated.
The reaction of sulfonamide 7c with 1.0 equiv. of MeI in
the presence of K2CO3 in DMF gave the starting material
and a product 13c containing an additional C-methyl group
in modest yield (see Table 2, entry 12). Nevertheless, sultam
11c was obtained through N-methylation of compound 10c
under standard K2CO3/DMF conditions, and was isolated
as a single trans diastereomer (Scheme 5).
Scheme 3. Preparation of sulfonamides 7 and 8.
Table 1. Preparation of sulfonamides 7 and 8.
Starting R1
material
R2
Cinnamate
(yield [%])
Sulfonamide
(yield [%])
1a
1b
1c
2b
2c
H
Me
Cl
Me
Cl
H
H
H
PMB
PMB
4a (64)
7a (84)
4b (86)
7b (61)
4c (70)
5b (85)
5c (59) + 5cЈ
7c (56)
8b (63)
8c (52) + 8cЈ
Aminocinnamates 4 and 5 were sulfonylated using
methyl (chlorosulfonyl)acetate (6) in MeCN at 60 °C. Un-
protected anilines 4a–4c were treated with an equimolar
amount of sulfonyl chloride 6 to avoid double N-sulfon-
ylation, and target sulfonamides 7a–7c were isolated in 56–
84% yields. With PMB-substituted anilines 5, which are no-
ticeably less reactive, at least a 2 equiv. of 6 was required to
achieve full conversion of the starting material. Compound
8c was isolated together with by-product 8cЈ, as expected.
Therefore, we obtained structures with two orthogonal ester
groups that could be modified independently.
Scheme 5. Synthesis of sultam 11c.
Initially, we planned to perform the Michael reaction on
PMB-substituted sulfonamides 8b and 8c, and we were de-
lighted to find that they did indeed cyclize in the presence
Thus, the possibility of an additional C-alkylation had
of K2CO3 in DMF[19] to give the corresponding sultams been demonstrated. Inspired by this result, we proved the
(i.e., 9b and 9c) in acceptable yields (see Scheme 4, Table 2, efficiency of the alkylation strategy, and performed one-pot
entries 1 and 2). As by-product 8cЈ could not react in a double alkylation to obtain sultam derivatives 13a and 14a.
Michael fashion, compound 9c was isolated in pure form. Encouragingly, the desired products were formed in reason-
It is noteworthy that sultams 9b and 9c were formed as able yields as single diastereomers (see Table 2, entries 10
cis/trans mixtures of diastereomers with a strong prevalence and 11).
of the latter. In some cases, the trans diastereomers could
An attempt to cycloalkylate secondary sultams such as
be isolated pure by recrystallization (for details, see below). 10a with a dihaloalkane was a logical continuation of our
2
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A Route to Benzo-Annelated δ-Sultams
Table 2. Michael cyclization of sulfonamides 7 and 8.
[a] Only the trans diastereomer was isolated.
studies of the intermolecular cycloalkylation of sultams,[20a] bromoethane to sultam 10a generated in situ from the cor-
and became the ultimate zest. This idea was even more at- responding sulfonamide (i.e., 7a) in the K2CO3/DMF sys-
tractive given that examples of bicyclic sultams with sulfur tem, we were excited to obtain the bridged sultam (i.e., 15a)
at the apex position and nitrogen at the bridgehead are as a single diastereomer in an acceptable yield (Scheme 6).
scarce.[7a,7e,11b,20] To the best of our knowledge, benzo- Thus, we managed to perform a three-step one-pot process,
annelated bridgehead sultams of the type mentioned above and the method has even more synthetic potential than we
have not been reported yet at all. Having added 1,2-di- had initially expected.
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D. S. Grosheva, V. A. Rassadin, V. V. Sokolov
FULL PAPER
group is smaller than any alkyl group [the values of the
conformational free energies (ΔG°) of the Me and CO2Et
groups are 1.8 and 1.1 kcal/mol, respectively].[22]
Conclusions
Scheme 6. Preparation of tricyclic sultam 15a.
We have developed a new efficient approach to benzo-
fused δ-sultams through intramolecular Michael cycliza-
tion. This method gives access to compounds function-
alized at several centres and bearing two orthogonal ester
groups simply and efficiently. Obviously, the synthetic po-
tential of this approach has not been exhausted yet, so it
unquestionably deserves further attention. We have also dis-
closed the stereochemical features of these transformations,
having proved the structures of key products by the results
of X-ray diffraction experiments.
The relative configuration of the substituents in products
10–14 was solved using 1D NOE NMR spectroscopy (for
details see Supporting Information). In the case of sultams
10–12, the trans isomer was always the major one in the
reaction mixture. For sultams 13 and 14, the compounds
with a 3R*,4S* configuration were the only stereoisomers
formed in the reactions. These results for 11a, 13a, and 14a
were proved using X-ray diffraction experiments (Figure 1).
Experimental Section
General Remarks: NMR spectra were recorded in CDCl3 at ambi-
ent temperature with a Bruker DPX 300 instrument at 300.13 MHz
(1H NMR) and 75.47 MHz (13C NMR, DEPT-135), a Bruker Av-
ance 400 instrument at 400.13 MHz (1H NMR, 1D-NOESY) and
100.61 MHz (13C NMR, DEPT-135), and a Varian Inova 600 in-
strument at 599.74 MHz (1H, 1D-NOESY). Chemical shifts (δ) are
given in ppm, and spectra were calibrated using the resonances of
the solvent signal (1H NMR: δ = 7.28 ppm for CHCl3; 13C NMR:
δ = 77.0 ppm for CDCl3). Spin–spin coupling constants (J) are
given in Hz. Multiplicities are described as s = singlet, d = doublet,
t = triplet, q = quadruplet, and m = multiplet. The multiplicities
of signals in the 13C NMR spectra were determined by DEPT-135.
The mass spectra were recorded with BrukerMicroTOF (ESI) and
Bruker maXis HRMS-ESI-QTOF instruments. Reagents were used
as purchased without further purification. Solvents were purified
and dried before use according to standard methods. Chromato-
graphic separations were carried out with Macherey–Nagel silica
gel 60M (230–400 mesh). Analytical TLC was carried out with Ma-
cherey–Nagel ready-to-use AluGram® Sil G/UV254 plates. Detec-
tion was achieved using a UV lamp. Melting points were deter-
mined using capillary tubes with a Stuart SMP30 apparatus. Ele-
mental analysis was carried out at the Analytical Laboratory of
the Department of Organic Chemistry, Institute of Chemistry, St.
Petersburg State University with a Euro EA 2000 automatic CHN
analyser. Analytical separations of diastereomeric mixtures were
carried out by LC–MS (if mentioned) on an Agilent 1200 instru-
ment with a Zorbax SB-C18 column and with a Bruker maXis
HRMS-ESI-QTOF mass spectrometer as a detector. Single-crystal
X-ray diffraction experiments for compounds 11a and 14a were
carried out with an Agilent Technologies Supernova diffractometer
Figure 1. X-ray diffraction molecular views of sultams 11a, 13a,
and 14a in the crystal state.[21]
Moreover, we also managed to obtain a crystal structure
of tricyclic sultam 15a, and we found that it has an exo
configuration (Figure 2). Several features of its molecular
geometry should be noted. The S–Cquat and C=O bonds of
the CO2Me group are eclipsed with a torsional angle S–C–
C–O of 0.2°. The extent of nitrogen pyramidality could be
derived from a comparison of the sums of the bond angles
at the nitrogen atoms (325.5°). This result resembles pre-
vious data obtained for methyl 1-aza-8-thiabicyclo[3.2.1]-
octane-5-carboxylate 8,8-dioxide (325.3°).[20a] It is also
interesting that the nitrogen and C-8 atoms are a little out
of the plane of the benzene ring (the torsion angle N–C-2–
C-7–C-8 is 3.0°).
at 100 K using microfocussed monochromated Cu-Kα (λ
=
0.154184 nm) radiation. Single-crystal X-ray diffraction experi-
ments for compounds 13a and 15a were carried out with an Agilent
Technologies Excalibur Eos diffractometer at 100 K using microfo-
cussed monochromated Mo-Kα (λ = 0.071073 nm) radiation. The
structures were solved by direct methods using the SHELXL pro-
gram[23] incorporated in the OLEX2 program package.[24] The car-
bon-bound hydrogen atoms were placed in calculated positions,
and were included in the refinement in the “riding” model approxi-
mation. An empirical absorption correction was applied in the
CrysAlisPro[25] program complex using spherical harmonics, im-
Figure 2. X-ray diffraction molecular view of sultam 15a in the
crystal state.[21]
The results concerning the stereochemistry can be gener-
alized as follows. Bicyclic sultams with the tert-butoxy-
carbonylmethyl group and the biggest vicinal substituent in
a trans orientation are formed preferentially. While for com-
pounds 10–12 this is clear enough, for analogues 13–14 this
conclusion is based on the fact that the methoxycarbonyl plemented in the SCALE3 ABSPACK scaling algorithm.
4
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A Route to Benzo-Annelated δ-Sultams
Typical Procedure for the Preparation of Sulfonamides 7 (TP 1): A MeCN (20 mL) was added dropwise to a solution of aniline 5b
solution of methyl (chlorosulfonyl)acetate 6 (2.44 g, 14.1 mmol) in
MeCN (20 mL) was added dropwise to a solution of aniline 4a
(3.00 g, 8.49 mmol) and pyridine (1.34 g, 17.0 mmol) in MeCN
(40 mL) at 60 °C, and the resulting mixture was stirred at this tem-
(3.10 g, 14.1 mmol) and pyridine (1.68 g, 21.2 mmol) in MeCN perature for 20 h. The reaction mixture was then concentrated un-
(40 mL) at 60 °C, and the resulting mixture was stirred at this tem-
perature for 20 h. The reaction mixture was then concentrated un-
der reduced pressure on a rotary evaporator. The residue was dis-
solved in CH2Cl2 (50 mL), and this solution was successively
der reduced pressure on a rotary evaporator, and the residue was
dissolved in CH2Cl2 (50 mL). This solution was successively
washed with HCl (5% aq.; 2ϫ 20 mL), water (3ϫ 30 mL), and
brine (30 mL), and then dried with Na2SO4. The solvents were re-
washed with HCl (5% aq.; 2ϫ 20 mL), water (3ϫ 30 mL), and moved under reduced pressure on a rotary evaporator, and the resi-
brine (30 mL), and then dried with Na2SO4. The solvents were re-
moved under reduced pressure on a rotary evaporator, and the resi-
due was subjected to flash column chromatography (EtOAc/hex-
ane, 1:3) followed by recrystallization from a mixture of EtOAc/
hexane (in the case of solid products).
due was subjected to flash column chromatography (EtOAc/hex-
ane, 1:3).
(E)-tert-Butyl
3-{2-[N-(4-Methoxybenzyl)-N-(methoxycarbonyl-
methyl)sulfonylamino]-5-methyl-phenyl}acrylate (8b): From methyl
(chlorosulfonyl)acetate 6 (2.93 g, 17.0 mmol), aniline 5b (3.00 g,
8.49 mmol), and pyridine (1.34 g, 17.0 mmol), TP 2 gave com-
pound 8b (2.60 g, 63%) as a brown oil. Rf = 0.2 (EtOAc/petroleum
(E)-tert-Butyl 3-[2-(Methoxycarbonylmethyl)sulfonylaminophenyl]-
acrylate (7a): From methyl (chlorosulfonyl)acetate
6 (2.44 g,
1
ether, 1:3). H NMR (300 MHz, CDCl3): δ = 1.53 (s, 9 H, CMe3),
14.1 mmol), aniline 4a (3.10 g, 14.1 mmol), and pyridine (1.68 g,
21.2 mmol), TP 1 gave compound 7a (4.20 g, 84%) as a brownish
2.35 (s, 3 H, Me), 3.75 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 4.06,
4.12 (ABq, J = 13.7 Hz, 2 H, NSO2CH2), 4.60, 4.89 (ABq, J =
13.8 Hz, 2 H, NCH2), 6.08 (d, J = 16.0 Hz, 1 H, HC=CH-CO2tBu),
6.71–6.76 (m, 2 H, H-Ar), 7.02–7.08 (m, 2 H, H-Ar), 7.20 (dd, J =
1.5, 8.0 Hz, 1 H, H-Ar), 7.34 (d, J = 8.0 Hz, 1 H, H-Ar), 7.38 (d,
J = 1.5 Hz, 1 H, H-Ar), 7.60 (d, J = 16.0 Hz, 1 H, HC=CH-
CO2tBu) ppm. 13C NMR (101 MHz, CDCl3): δ = 21.1 (Me), 28.1
(3 C, CMe3), 53.2 (OMe), 55.1 (OMe), 55.4 (CH2), 57.4 (CH2), 80.2
(CMe3), 113.7 (2 C, CH-Ar), 121.8, 127.2 (C-Ar), 127.7, 129.9,
130.9 (2 C, CH-Ar), 131.5, 134.6 (C-Ar), 135.7 (C-Ar), 138.9, 139.2
(C-Ar), 159.4 (C-Ar), 164.0 (CO), 165.5 (CO) ppm. HRMS (ESI):
calcd. for C25H31NNaO7S [M + Na]+ 512.1713; found 512.1715.
1
solid, m.p. 134–135 °C. H NMR (300 MHz, CDCl3): δ = 1.54 (s,
9 H, CMe3), 3.84 (s, 3 H, OMe), 4.09 (s, 2 H, CH2), 6.37 (d, J =
15.8 Hz, 1 H, HC=CH-CO2tBu), 7.25 (s, 1 H, NH), 7.28 (td, J =
1.0, 7.9 Hz, 1 H, H-Ar), 7.41 (td, J = 1.6, 7.9 Hz, 1 H, H-Ar), 7.60
(dd, J = 1.0, 7.9 Hz, 1 H, H-Ar), 7.63 (dd, J = 1.6, 7.9 Hz, 1 H, H-
Ar), 8.01 (d, J = 15.8 Hz, 1 H, HC=CH-CO2tBu) ppm. 13C NMR
(101 MHz, CDCl3): δ = 28.1 (3 C, CMe3), 53.4 (OMe), 54.5 (CH2),
80.9 (CMe3), 123.6, 125.2, 127.2 (C-Ar), 127.6, 130.2 (C-Ar), 130.8,
134.2 (C-Ar), 137.9, 164.1 (CO), 165.7 (CO) ppm. HRMS (ESI):
calcd. for C16H25N2O6S [M + NH4]+ 373.1428; found 373.1414.
C16H21NO6S (355.4): calcd. C 54.1, H 6.0, N 3.9; found C 54.0, H
5.8, N 3.6.
(E)-tert-Butyl
3-{5-Chloro-2-[N-(4-methoxybenzyl)-N-(methoxy-
carbonylmethyl)sulfonylamino]phenyl}acrylate (8c): From methyl
(chlorosulfonyl)acetate 6 (1.57 g, 9.09 mmol), mixture of anilines
5c and 5cЈ (1.70 g, 4.32 mmol), and pyridine (719 mg, 9.09 mmol),
TP 2 gave a mixture of 8c and 8cЈ (1.10 g, 5:1) as a colourless oil.
Rf = 0.2 (EtOAc/petroleum ether, 1:3). The yield of 8c (890 mg,
(E)-tert-Butyl 3-[2-(Methoxycarbonylmethyl)sulfonylamino-5-meth-
ylphenyl]acrylate (7b): From methyl (chlorosulfonyl)acetate
6
(2.22 g, 12.9 mmol), aniline 4b (3.00 g, 12.9 mmol), and pyridine
(1.53 g, 19.3 mmol), TP 1 gave compound 7b (2.90 g, 61%) as a
yellow solid, m.p. 102–103 °C. 1H NMR (400 MHz, CDCl3): δ =
1.55 (s, 9 H, CMe3), 2.39 (s, 3 H, Me), 3.86 (s, 3 H, OMe), 4.09 (s,
2 H, CH2), 6.38 (d, J = 15.8 Hz, 1 H, HC=CH-CO2tBu), 7.24 (s,
1 H, NH), 7.23 (d, J = 8.0 Hz, 1 H, H-Ar), 7.45–7.50 (m, 2 H, H-
Ar), 8.02 (d, J = 15.8 Hz, 1 H, HC=CH-CO2tBu) ppm. 13C NMR
(101 MHz, CDCl3): δ = 20.9 (Me), 28.1 (3 C, CMe3), 53.3 (OMe),
54.3 (CH2), 80.8 (CMe3), 122.9, 125.9, 127.9, 130.5 (C-Ar), 131.6
(2 C, CH-Ar, C-Ar), 137.4 (C-Ar), 138.2, 164.1 (CO), 165.8 (CO)
1
52%) was estimated by H NMR spectroscopy. Characteristic data
for major product 8c are described below. 1H NMR (400 MHz,
CDCl3): δ = 1.53 (s, 9 H, CMe3), 3.75 (s, 3 H, OMe), 3.90 (s, 3 H,
OMe), 4.09 (ABq, ΔδAB and J could not be calculated correctly, 2
H, NSO2CH2), 4.57 (d, J = 13.7 Hz, 1 H, NCHHЈ), 4.89 (d, J =
13.7 Hz, 1 H, NCHHЈ), 6.07 (d, J = 16.0 Hz, 1 H, HC=CH-
CO2tBu), 6.72–6.76 (m, 1 H, H-Ar), 7.02–7.06 (m, 1 H, H-Ar), 7.35
(dd, J = 2.0, 8.5 Hz, 1 H, H-Ar), 7.44 (d, J = 8.5 Hz, 1 H, H-
Ar), 7.53 (d, J = 2.0 Hz, HC=CH-CO2tBu), 7.54 (d, J = 16.0 Hz,
HC=CH-CO2tBu) ppm. 13C NMR (101 MHz, CDCl3): δ = 28.1 (3
C, CMe3), 53.3 (OMe), 55.1 (OMe), 55.5 (CH2), 57.5 (CH2), 80.6
(CMe3), 113.8 (2 CH-Ar), 123.3, 126.6 (C-Ar), 127.1, 130.5, 130.9
(2 CH-Ar), 131.7, 135.2 (C-Ar), 135.6 (C-Ar), 137.5, 137.9 (C-Ar),
159.6 (C-Ar), 163.9 (CO), 165.0 (CO) ppm. HRMS (ESI): calcd.
for C24H32ClN2O7S [M(35Cl) + NH4]+ 527.1613; found 527.1608.
ppm. HRMS (ESI): calcd. for C17H23NNaO6S [M
+
Na]+
392.1138; found 392.1130. C17H23NO6S (369.4): calcd. C 55.3, H
6.3, N 3.8; found C 55.2, H 6.3, N 4.1.
(E)-tert-Butyl
3-{5-Chloro-2-[(methoxycarbonylmethyl)sulfonyl-
amino]phenyl}acrylate (7c): From methyl (chlorosulfonyl)acetate 6
(2.04 g, 11.8 mmol), aniline 4c (3.00 g, 11.8 mmol), and pyridine
(1.40 g, 17.7 mmol), TP 1 gave compound 7c (2.60 g, 56%) as a
1
brownish solid, m.p. 113–114 °C. H NMR (300 MHz, CDCl3): δ
Typical Procedure for the Synthesis of Sultams 9 and 10 (TP 3): A
mixture of sulfonamide 8b (500 mg, 1.05 mmol) and K2CO3
(363 mg, 2.63 mmol) in DMF (10 mL) was stirred at 60–70 °C for
10–36 h, and the mixture was then concentrated on a rotary evapo-
rator. The residue was dissolved in CH2Cl2 (20 mL), and the re-
sulting solution was washed with HCl (5% aq.; 2ϫ 10 mL), water
(5ϫ 10 mL), and brine (10 mL), and then dried with Na2SO4. The
solvents were removed under reduced pressure on a rotary evapora-
tor, and the crude product was subjected to flash column
chromatography (EtOAc/hexane, 1:3) followed by recrystallization
from a mixture of EtOAc/hexane (in the case of solid products).
= 1.52 (s, 9 H, CMe3), 3.84 (s, 3 H, OMe), 4.09 (s, 2 H, CH2), 6.36
(d, J = 15.8 Hz, 1 H, HC=CHCO2tBu), 7.36 (dd, J = 2.2, 8.7 Hz,
1 H, H-Ar), 7.40 (br. s, 1 H, NH), 7.55 (d, J = 8.7 Hz, 1 H, H-Ar),
7.60 (d, J = 2.2 Hz, 1 H, H-Ar), 7.99 (d, J = 15.8 Hz, 1 H,
HC=CH-CO2tBu) ppm. 13C NMR (101 MHz, CDCl3): δ = 28.1 (3
C, CMe3), 53.4 (CO2Me), 54.7 (CH2), 81.2 (CMe3), 124.5, 126.9,
127.3, 130.6, 131.8 (C-Ar), 132.8 (C-Ar), 133.0 (C-Ar), 136.7, 164.0
(CO), 165.4 (CO) ppm. HRMS (ESI): calcd. for C16H20ClNNaO6S
[M(35Cl) + Na]+ 412.0592; found 412.0587. C16H20ClNO6S (389.8):
calcd. C 49.3, H 5.2, N 3.6; found C 49.0, H 5.2, N 3.5.
Typical Procedure for the Preparation of Sulfonamides 8 (TP 2): A Methyl
4-(tert-Butoxycarbonylmethyl)-1-(4-methoxybenzyl)-6-
solution of methyl (chlorosulfonyl)acetate 6 (2.93 g, 17.0 mmol) in methyl-3,4-dihydro-1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-Di-
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5

Job/Unit: O43416
/KAP1
Date: 14-01-15 19:12:47
Pages: 10
D. S. Grosheva, V. A. Rassadin, V. V. Sokolov
FULL PAPER
oxide (9b): From sulfonamide 8b (500 mg, 1.05 mmol) and K2CO3
(363 mg, 2.63 mmol), TP 3 (reaction time 10 h) gave compound 9b
(340 mg, 68%) as a mixture of trans and cis isomers (5:1), a colour-
less oil. Rf = 0.3 (EtOAc/petroleum ether, 1:3). HRMS (ESI): calcd.
CDCl3): δ = 28.0 (3 C, CMe3), 39.4 (C-4), 40.0 (CH2), 53.5 (OMe),
62.2 (C-3), 81.8 (CMe3), 121.5 (CH-Ar), 125.45 (CH-Ar), 125.54
(C-Ar), 128.3 (CH-Ar), 129.1 (CH-Ar), 135.6 (C-Ar), 166.1 (CO),
170.6 (CO) ppm. HRMS (ESI): calcd. for C16H21NNaO6S [M +
for C25H35N2O7S [M + NH4]+ 507.2159; found 507.2152. LC–MS: Na]+ 378.0982; found 378.0983. C16H21NO6S (355.4): calcd. C
tR = 12.1 min (trans isomer; found m/z = 507 [M + NH4]+), tR
12.4 min (cis isomer; found m/z = 507 [M + NH4]+).
=
54.1, H 6.0, N 3.9; found C 53.8, H 6.0, N 3.7.
Methyl 4-(tert-Butoxycarbonylmethyl)-3,4-dihydro-6-methyl-1H-
Data for the trans diastereomer: 1H NMR (400 MHz, CDCl3): δ =
1.40 (s, 9 H, CMe3), 2.30 (s, 3 H, Me), 2.57 (dd, J = 4.1, 16.8 Hz,
1 H, CHHЈ), 2.89 (dd, J = 8.4, 16.8 Hz, 1 H, CHHЈ), 3.80 (s, 3 H,
OMe), 3.88 (s, 3 H, OMe), 4.14 (ddd, J = 4.1, 6.5, 8.4 Hz, 1 H, 4-
H), 4.49 (d, J = 6.5 Hz, 1 H, 3-H), 4.79, 4.94 (ABq, J = 16.0 Hz,
2 H, NCH2), 6.82 (d, J = 8.1 Hz, 1 H, H-Ar), 6.88–6.92 (m, 2 H,
H-Ar), 6.97 (dd, J = 1.8, 8.1 Hz, 1 H, H-Ar), 7.07 (d, J = 1.8 Hz,
1 H, H-Ar), 7.30–7.32 (m, 2 H, H-Ar) ppm. 13C NMR (100 MHz,
CDCl3): δ = 20.78 (Me), 27.88 (3 C, CMe3), 38.3 (C-4), 40.0
(CH2CO2tBu), 53.4 (OMe), 54.2 (NCH2), 55.2 (OMe), 64.3 (C-3),
81.4 (CMe3), 114.1 (2 C, CH-Ar), 121.7 (CH-Ar), 127.7 (C-Ar),
128.2 (CH-Ar), 128.8 (2 C, CH-Ar), 128.97 (C-Ar), 129.00 (CH-
Ar), 135.0 (C-Ar), 137.3 (C-Ar), 159.2 (C-Ar), 165.6 (CO), 170.3
(CO) ppm.
benzo[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (10b): From sulfon-
amide 7b (500 mg, 1.41 mmol) and K2CO3 (486 mg, 3.52 mmol),
TP 3 (reaction time 36 h) gave compound 10b (330 mg, 66%) as a
mixture of trans and cis isomers (7:1), a colourless solid, m.p. 141–
142 °C. HRMS (ESI): calcd. for C17H27N2O6S [M + NH4]+
387.1584; found 387.1586. C17H23NO6S (369.4): calcd. C 55.3, H
6.3, N 3.8; found C 55.3, H 6.0, N 3.6.
Data for the trans diastereomer: 1H NMR (400 MHz, CDCl3): δ =
1.45 (s, 9 H, CMe3), 2.32 (s, 3 H, Me), 2.69 (dd, J = 3.8, 17.4 Hz,
1 H, CHHЈ), 3.29 (dd, J = 9.5, 17.4 Hz, 1 H, CHHЈ), 3.84 (s, 3 H,
OMe), 4.09 (ddd, J = 3.8, 3.9, 9.5 Hz, 1 H, 4-H), 4.56 (d, J =
3.9 Hz, 1 H, 3-H), 6.59 (br. s, 1 H, NH), 6.79 (d, J = 8.0 Hz, 1 H,
H-Ar), 6.99–7.14 (m, 2 H, H-Ar) ppm. 13C NMR (101 MHz,
CDCl3): δ = 20.8 (Me), 28.0 (3 C, CMe3), 39.3 (C-4), 40.1 (CH2),
53.5 (OMe), 62.1 (C-3), 81.7 (CMe3), 121.7 (CH-Ar), 125.4 (C-Ar),
129.0 (CH-Ar), 129.5 (CH-Ar), 133.1 (C-Ar), 135.2 (C-Ar), 166.3
(CO), 170.7 (CO) ppm.
Data for the cis diastereomer, characteristic signals: 1H NMR
(400 MHz, CDCl3): δ = 1.50 (s, 9 H, CMe3), 2.79 (dd, J = 9.0,
16.8 Hz, 1 H, CHHЈ), 3.04 (dd, J = 5.6, 16.8 Hz, 1 H, CHHЈ), 3.80
(s, 3 H, OMe), 4.54 (d, J = 6.3 Hz, 1 H, 3-H), 4.68 (d, J = 16.5 Hz,
1 H, NCHHЈ), 5.04 (d, J = 16.5 Hz, 1 H, NCHHЈ) ppm. 13C NMR
(75 MHz, CDCl3): δ = 20.83 (Me), 27.94 (3 C, CMe3), 37.1
(CH2CO2tBu), 37.3 (C-4), 52.9 (OMe), 54.1 (NCH2), 60.3 (OMe),
62.7 (C-3), 81.6 (CMe3), 120.6 (CH-Ar), 126.7 (C-Ar), 127.6 (CH-
Ar), 128.9 (CH-Ar), 129.5 (C-Ar), 134.4 (C-Ar), 137.6 (C-Ar),
159.0 (C-Ar), 164.9 (CO) ppm.
Data for the cis diastereomer, characteristic signals: 1H NMR
(400 MHz, CDCl3): δ = 4.15 (m, 1 H, 4-H), 4.61 (d, J = 4.3 Hz, 1
H, 3-H) ppm.
Methyl
4-(tert-Butoxycarbonylmethyl)-6-chloro-3,4-dihydro-1H-
benzo[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (10c): From sulfon-
amide 7c (500 mg, 1.33 mmol) and K2CO3 (466 mg, 3.33 mmol),
TP 3 (reaction time 10 h) gave compound 10c (260 mg, 52%) as a
mixture of trans and cis isomers (8:1), a brownish solid, m.p.
138–139 °C. HRMS (ESI): calcd. for C16H24ClN2O6S [M(35Cl) +
NH4]+ 407.1038; found 407.1037. C16H20ClNO6S (389.8): calcd. C
49.3, H 5.2, N 3.6; found C 49.5, H 5.0, N 3.4.
Data for the trans diastereomer: 1H NMR (400 MHz, CDCl3): δ =
1.45 (s, 9 H, CMe3), 2.69 (dd, J = 4.0, 17.5 Hz, 1 H, CHHЈ), 3.27
(dd, J = 9.1, 17.5 Hz, 1 H, CHHЈ), 3.85 (s, 3 H, OMe), 4.09 (ddd,
J = 4.0, 4.2, 9.1 Hz, 4-H), 4.57 (d, J = 4.2 Hz, 1 H, 3-H), 6.79 (d,
J = 8.5 Hz, 1 H, H-Ar), 6.91 (br. s, 1 H, NH), 7.19 (dd, J = 2.1,
8.5 Hz, 1 H, H-Ar), 7.29 (d, J = 2.1 Hz, 1 H, H-Ar) ppm. 13C
NMR (101 MHz, CDCl3): δ = 28.0 (3 C, CMe3), 39.2 (C-4), 39.8
(CH2), 53.7 (OMe), 61.9 (C-3), 82.1 (CMe3), 122.6 (CH-Ar), 127.1
(C-Ar), 128.4 (CH-Ar), 129.0 (CH-Ar), 130.6 (C-Ar), 134.4 (C-Ar),
166.0 (CO), 170.4 (CO) ppm.
Data for the cis diastereomer, characteristic signals: 1H NMR
(400 MHz, CDCl3): δ = 1.52 (s, 9 H, CMe3), 2.63 (dd, J = 8.6,
16.7 Hz, 1 H, CHHЈ), 3.07 (dd, J = 5.9, 16.7 Hz, 1 H, CHHЈ), 3.79
(s, 3 H, OMe), 4.24 (m, 1 H, 4-H), 4.52 (d, J = 5.9 Hz, 1 H, 3-H),
6.91 (br. s, 1 H, NH), 7.21–7.26 (m, 2 H, H-Ar) ppm. 13C NMR
(101 MHz, CDCl3): δ = 37.3 (CH2), 37.6 (C-4), 53.3 (OMe), 60.3
(C-3), 82.2 (CMe3), 122.5 (CH-Ar), 127.2 (CH-Ar), 128.5 (CH-Ar),
130.5 (C-Ar), 134.7 (C-Ar), 169.8 (CO) ppm.
Methyl
trans-4-(tert-Butoxycarbonylmethyl)-6-chloro-1-(4-meth-
oxybenzyl)-3,4-dihydro-1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-
Dioxide (9c): From the mixture of sulfonamides 8c and 8cЈ (500 mg,
952 μmol) and K2CO3 (348 mg, 2.52 mmol), TP 3 (reaction time
10 h) gave compound 9c (350 mg, 87%) as a single trans dia-
1
stereomer, a colourless solid, m.p. 68–69 °C. H NMR (400 MHz,
CDCl3): δ = 1.41 (s, 9 H, CMe3), 2.59 (dd, J = 4.0, 17.0 Hz, 1 H,
CHHЈ), 2.97 (dd, J = 8.2, 17.0 Hz, 1 H, CHHЈ), 3.83 (s, 3 H, OMe),
3.90 (s, 3 H, OMe), 4.12 (ddd, J = 4.0, 6.5, 8.2 Hz, 1 H, 4-H), 4.55
(d, J = 6.5 Hz, 1 H, 3-H), 4.79, 4.95 (ABq, J = 16.1 Hz, 1 H,
NCH2), 6.85 (d, J = 8.7 Hz, 1 H, H-Ar), 6.90–6.94 (m, 2 H, H-
Ar), 7.13 (dd, J = 2.2, 8.7 Hz, 1 H, H-Ar), 7.27 (d, J = 2.2 Hz, 1
H, H-Ar), 7.28–7.32 (m, 2 H, H-Ar) ppm. 13C NMR (101 MHz,
CDCl3): δ = 27.9 (3 C, CMe3), 38.3 (C-4), 39.6 (CH2CO2tBu), 53.6
(OMe), 54.2 (NCH2), 55.3 (OMe), 63.7 (C-3), 81.9 (CMe3), 114.3
(2 C, CH-Ar), 122.9 (CH-Ar), 128.2 (CH-Ar), 128.5 (2 C, CH-Ar,
C-Ar), 128.7 (2 C, CH-Ar), 129.6 (C-Ar), 130.7 (C-Ar), 138.7 (C-
Ar), 159.4 (C-Ar), 165.4 (CO), 170.1 (CO) ppm. HRMS (ESI):
calcd. for C24H32ClN2O7S [M(35Cl) + NH4]+ 527.1613; found
527.1619. C24H28ClNO7S (510.0): calcd. C 56.5, H 5.5, N 2.8;
found C 56.7, H 5.7, N 2.8.
Methyl trans-4-(tert-Butoxycarbonylmethyl)-3,4-dihydro-1H-benzo-
[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (10a): From sulfonamide
7a (1.00 g, 2.81 mmol) and K2CO3 (972 mg, 7.03 mmol), TP 3 (re-
action time 36 h) gave compound 10a (650 mg, 65%) as a single
trans diastereomer, a colourless solid, m.p. 118.5–119.5 °C. 1H
Typical Procedure for the Synthesis of Sultams 11–14 (TP 4): A
solution of MeI (397 mg, 2.80 mmol) in DMF (10 mL) was slowly
added over 30 min to a mixture of sulfonamide 7a (1.00 g,
NMR (400 MHz, CDCl3): δ = 1.44 (s, 9 H, CMe3), 2.70 (dd, J = 2.80 mmol) and K2CO3 (967 mg, 7.00 mmol) in DMF (30 mL) at
3.6, 17.5 Hz, 1 H, CHHЈ), 3.31 (dd, J = 9.4, 17.5 Hz, 1 H, CHHЈ), 60–70 °C. The resulting mixture was stirred for 2–10 h at this tem-
3.86 (s, 3 H, OMe), 4.13 (ddd, J = 3.6, 4.2, 9.4 Hz, 1 H, 4-H), 4.62 perature, and was then concentrated on a rotary evaporator. The
(d, J = 4.2 Hz, 1 H, 3-H), 6.56 (br. s, 1 H, NH), 6.89 (d, J = 7.8 Hz, residue was dissolved in CH2Cl2 (30 mL), and this solution was
1 H, H-Ar), 7.11–7.33 (m, 3 H, H-Ar) ppm. 13C NMR (101 MHz,
washed with HCl (5% aq.; 2ϫ 10 mL), water (5ϫ 10 mL), and
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43416
/KAP1
Date: 14-01-15 19:12:47
Pages: 10
A Route to Benzo-Annelated δ-Sultams
brine (10 mL), and then dried with Na2SO4. The solvents were re-
moved under reduced pressure on a rotary evaporator, and the
crude product was purified by flash chromatography (EtOAc/hex-
ane, 1:3) and recrystallized from a mixture of EtOAc/hexane.
(d, J = 16.6 Hz, 1 H, NCHHЈ), 5.05 (d, J = 16.6 Hz, 1 H, NCHHЈ),
6.88–6.95 (m, 1 H, H-Ar), 7.07–7.21 (m, 2 H, H-Ar), 7.22–7.35 (m,
2 H, H-Ar), 7.35–7.51 (m, 4 H, H-Ar) ppm. 13C NMR (101 MHz,
CDCl3): δ = 27.95 (3 C, CMe3), 38.6 (C-4), 39.9 (CH2), 53.5 (OMe),
54.6 (NCH2), 63.7 (C-3), 81.6 (CMe3), 121.1 (CH-Ar), 125.1 (CH-
Ar), 126.6 (C-Ar), 127.1 (2 C, CH-Ar), 127.3 (C-Ar), 127.7 (CH-
Ar), 128.1 (CH-Ar), 128.7 (CH-Ar), 128.9 (2 C, CH-Ar), 140.2 (C-
Ar), 165.7 (CO), 170.4 (CO) ppm.
Methyl trans-4-(tert-Butoxycarbonylmethyl)-3,4-dihydro-1-methyl-
1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (11a): From sul-
fonamide 7a (1.00 g, 2.80 mmol), K2CO3 (967 mg, 7.00 mmol) and
MeI (397 mg, 2.80 mmol), TP 4 (reaction time 2 h) gave compound
11a (800 mg, 77%) as a single trans diastereomer, a colourless solid,
m.p. 94–95 °C. 1H NMR (400 MHz, CDCl3): δ = 1.39 (s, 9 H,
Data for the cis diastereomer, characteristic signals: 1H NMR
(400 MHz, CDCl3): δ = 1.52 (s, 9 H, CMe3), 2.76 (dd, J = 9.3,
CMe3), 2.66 (br. s, J = 17.0 Hz, 1 H, CHHЈ), 3.21 (dd, J = 7.9, 16.7 Hz, 1 H, CHHЈ), 3.81 (s, 3 H, OMe), 4.27 (m, 1 H, 4-H), 4.76
17.0 Hz, 1 H, CHHЈ), 3.42 (s, 3 H, NMe), 3.92 (s, 3 H, OMe), 4.18
(d, J = 17.1 Hz, 1 H, NCHHЈ), 5.17 (d, J = 17.1 Hz, 1 H, NCHHЈ)
(m, 1 H, 4-H), 4.71 (d, J = 6.4 Hz, 1 H, 3-H), 7.11 (d, J = 8.0 Hz, ppm. 13C NMR (101 MHz, CDCl3): δ = 28.0 (3 C, CMe3), 37.3
1 H, H-Ar), 7.18–7.21 (m, 1 H, H-Ar), 7.29–7.36 (m, 2 H, H-Ar)
(C-4), 37.5 (CH2), 53.0 (OMe), 62.1 (C-3), 120.2 (CH-Ar), 124.6
ppm. 13C NMR (101 MHz, CDCl3): δ = 27.9 (3 C, CMe3), 36.0 (CH-Ar), 127.5 (CH-Ar), 128.3 (CH-Ar), 137.7 (C-Ar), 164.9 (CO),
(Me or C-4), 38.4 (Me or C-4), 39.2 (CH2), 53.5 (OMe), 63.0 (C-
3), 81.6 (CMe3), 120.6 (CH-Ar), 124.9 (CH-Ar), 127.2 (C-Ar),
128.2 (CH-Ar), 128.5 (CH-Ar), 140.5 (C-Ar), 165.5 (CO), 170.3
(CO) ppm. HRMS (ESI): calcd. for C17H27N2O6S [M + NH4]+
387.1584; found 387.1589. C17H23NO6S (369.4): calcd. C 55.3, H
6.3, N 3.8; found C 55.4, H 6.2, N 3.5.
170.2 (CO) ppm.
Methyl trans-1-Benzyl-4-(tert-butoxycarbonylmethyl)-3,4-dihydro-6-
methyl-1H-benzo[c][1,2]-thiazine-3-carboxylate 2,2-Dioxide (12b):
From sulfonamide 7b (500 mg, 1.35 mmol), K2CO3 (468 mg,
3.38 mmol), and BnCl (171 mg, 1.35 mmol), TP 4 (reaction time
4 h) gave compound 12b (300 mg, 48%) as a single trans dia-
1
stereomer, a colourless solid, m.p. 82–83 °C. H NMR (400 MHz,
Methyl 4-(tert-Butoxycarbonylmethyl)-3,4-dihydro-1,6-dimethyl-1H-
benzo[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (11b): From sulfon-
amide 7b (500 mg, 1.35 mmol), K2CO3 (468 mg, 3.38 mmol), and
MeI (192 mg, 1.35 mmol) TP 4 (reaction time 2 h) gave compound
11b (300 mg, 58%) as a mixture of trans and cis isomers (6:1), a
yellowish oil. Rf = 0.3 (EtOAc/petroleum ether, 1:3). HRMS (ESI):
calcd. for C18H25NNaO6S [M + Na]+ 406.1295; found 406.1289.
C18H25NO6S (383.5): calcd. C 56.4, H 6.6, N 3.7; found C 56.3, H
6.5, N 3.9.
CDCl3): δ = 1.42 (s, 9 H, CMe3), 2.30 (s, 3 H, Me), 2.61 (dd, J =
3.9, 16.9 Hz, 1 H, CHHЈ), 3.01 (dd, J = 8.6, 16.9 Hz, 1 H, CHHЈ),
3.89 (s, 3 H, OMe), 4.13 (ddd, J = 3.9, 6.0, 8.6 Hz, 1 H, 4-H), 4.55
(d, J = 6.0 Hz, 1 H, 3-H), 4.84, 5.02 (ABq, J = 16.4 Hz, 1 H,
NCH2), 6.78 (d, J = 8.1 Hz, 1 H, H-Ar), 6.96 (d, J = 8.1 Hz, 1 H,
H-Ar), 7.08 (s, 1 H, H-Ar), 7.18–7.48 (m, 5 H, H-Ar) ppm. 13C
NMR (101 MHz, CDCl3): δ = 20.8 (Me), 28.0 (3 C, CMe3), 38.5
(C-4), 40.0 (CH2), 53.5 (OMe), 54.7 (NCH2), 64.0 (C-3), 81.5
(CMe3), 121.3 (CH-Ar), 127.2 (3 C, 2 CH-Ar, C-Ar), 127.7 (CH-
Ar), 128.8 (2 C, CH-Ar), 128.9 (CH-Ar), 129.1 (CH-Ar), 134.9 (C-
Ar), 137.3 (C-Ar), 137.6 (C-Ar), 165.7 (CO), 170.4 (CO) ppm.
HRMS (ESI): calcd. for C24H29NO6S [M]+· 459.1710; found
459.1701.
Data for the trans diastereomer: 1H NMR (300 MHz, CDCl3): δ =
1.36 (s, 9 H, CMe3), 2.61 (dd, J = 3.7, 16.9 Hz, 1 H, CHHЈ), 3.15
(dd, J = 8.1, 16.9 Hz, 1 H, CHHЈ), 3.35 (s, 3 H, NMe), 3.87 (s, 3
H, OMe), 4.10 (ddd, J = 3.7, 6.6, 8.1 Hz, 1 H, 4-H), 4.63 (d, J =
6.6 Hz, 1 H, 3-H), 6.97 (d, J = 8.5 Hz, 1 H, H-Ar), 7.06–7.12 (m,
2 H, H-Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.8 (CMe),
27.9 (3 C, CMe3), 36.4 (NMe or C-4), 38.3 (NMe or C-4), 39.2
(CH2), 53.5 (OMe), 62.9 (C-3), 81.5 (CMe3), 120.8 (CH-Ar), 127.0
(C-Ar), 128.9 (2 CH-Ar), 134.6 (C-Ar), 138.0 (C-Ar), 165.6 (CO),
170.4 (CO) ppm.
Methyl (3R*,4S*)-4-(tert-Butoxycarbonylmethyl)-3,4-dihydro-1,3-
dimethyl-1H-benzo[c][1,2]-thiazine-3-carboxylate 2,2-Dioxide (13a):
From sulfonamide 7a (500 mg, 1.41 mmol), K2CO3 (486 mg,
3.52 mmol), and MeI (399 mg, 2.81 mmol), TP 4 (reaction time
10 h) gave compound 13a (460 mg, 85%) as a single 3R*,4S* dia-
stereomer, a colourless solid, m.p. 118.5–119.5 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.40 (s, 9 H, CMe3), 1.68 (s, 3 H, CMe),
2.71 (br. d, J = 5.2 Hz, 2 H, CH2), 3.28 (s, 3 H, NMe), 3.72 (s, 3
H, OMe), 3.95 (t, J = 5.2 Hz, 1 H, 4-H), 6.91 (d, J = 8.2 Hz, 1 H,
H-Ar), 7.02 (td, J = 0.9, 8.0 Hz, 1 H, H-Ar), 7.11–7.29 (m, 2 H,
H-Ar) ppm. 13C NMR (101 MHz, CDCl3): δ = 19.9 (CMe), 28.0
(3 C, CMe3), 34.1 (C-4), 39.4 (CH2), 44.3 (NMe), 53.2 (OMe), 67.4
(C-3), 81.4 (CMe3), 118.0 (CH-Ar), 124.0 (CH-Ar), 127.95 (CH-
Ar), 128.04 (C-Ar), 128.6 (CH-Ar), 139.4 (C-Ar), 167.5 (CO), 171.4
(CO) ppm. HRMS (ESI): calcd. for C18H25NNaO6S [M + Na]+
406.1295; found 406.1298. C18H25NO6S (383.5): calcd. C 56.4, H
6.6, N 3.7; found C 56.9, H 7.0, N 3.6.
Data for the cis diastereomer, characteristic signals: 1H NMR
(300 MHz, CDCl3): δ = 1.49 (s, 9 H, CMe3), 2.32 (s, 3 H, Me), 2.77
(m, 1 H, CHHЈ), 3.05 (dd, J = 5.9, 16.7 Hz, 1 H, CHHЈ), 3.78 (s,
3 H, OMe), 4.19 (m, 1 H, 4-H), 4.54 (d, J = 6.1 Hz, 1 H, 3-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 28.0 (3 C, CMe3), 34.8
(CH2, NMe or C-4), 37.0 (CH2, NMe or C-4), 37.1 (CH2, NMe or
C-4), 53.0 (OMe), 62.5 (C-3), 119.3 (CH-Ar), 127.6 (CH-Ar) ppm.
Methyl
1-Benzyl-4-(tert-butoxycarbonylmethyl)-3,4-dihydro-1H-
benzo[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (12a): From sulfon-
amide 7a (500 mg, 1.41 mmol), K2CO3 (486 mg, 3.52 mmol), and
BnCl (178 mg, 1.41 mmol), TP 4 (reaction time 4 h) gave com-
pound 12a (250 mg, 40%) as a mixture of trans and cis isomers
(5:1), a yellow oil. Rf = 0.35 (EtOAc/petroleum ether, 1:3). HRMS
(ESI): calcd. for C27H27N2O6S [M + NH4]+ 463.1897; found
463.1909. LC–MS tR = 11.5 min (trans isomer; found m/z = 463
[M + NH4]+), tR = 11.8 min (cis isomer; found m/z = 463 [M +
NH4]+).
Methyl (3R*,4S*)-4-(tert-Butoxycarbonylmethyl)-6-chloro-3,4-di-
hydro-1,3-dimethyl-1H-benzo[c]-[1,2]thiazine-3-carboxylate 2,2-Di-
oxide (13c): From sulfonamide 7c (500 mg, 1.28 mmol), K2CO3
(443 mg, 3.21 mmol), and MeI (182 mg, 1.28 mmol), TP 4 (reaction
time 10 h) gave compound 13c (190 mg, 35%) as a single 3R*,4S*
diastereomer,
a
yellowish solid, m.p. 108–109 °C. 1H NMR
Data for the trans diastereomer: 1H NMR (400 MHz, CDCl3): δ = (400 MHz, CDCl3): δ = 1.52 (s, 9 H, CMe3), 1.72 (s, 3 H, CMe),
1.41 (s, 9 H, CMe3), 2.63 (dd, J = 3.8, 17.0 Hz, 1 H, CHHЈ), 3.07 2.72, 2.78 (AB part of ABX system, d, JAB = 17.0 Hz, 2 H, CH2),
(dd, J = 8.6, 17.0 Hz, 1 H, CHHЈ), 3.90 (s, 3 H, OMe), 4.18 (ddd, 3.35 (s, 3 H, NMe), 3.80 (s, 3 H, OMe), 3.99 (X part of ABX
J = 3.8, 6.1, 8.6 Hz, 1 H, 4-H), 4.62 (d, J = 6.1 Hz, 1 H, 3-H), 4.89 system, JAX = 3.3, JBX = 7.3 Hz, 1 H, 4-H), 6.94 (d, J = 8.5 Hz, 1
Eur. J. Org. Chem. 0000, 0–0
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/KAP1
Date: 14-01-15 19:12:47
Pages: 10
D. S. Grosheva, V. A. Rassadin, V. V. Sokolov
1,2-dibromoethane (127 mg, 675 μmol) in DMF (5.0 mL) at 60–
FULL PAPER
H, H-Ar), 7.20–7.32 (m, 2 H, H-Ar) ppm. 13C NMR (101 MHz,
CDCl3): δ = 19.4 (CMe), 28.0 (3 C, CMe3), 34.5 (C-4), 39.0 (CH2), 70 °C. The resulting mixture was stirred at this temperature for
44.2 (NMe), 53.4 (OMe), 67.0 (C-3), 81.8 (CMe3), 119.4 (CH-Ar), 30 h, and was then concentrated under reduced pressure on a ro-
128.0 (CH-Ar), 128.4 (CH-Ar), 129.3 (C-Ar), 129.8 (C-Ar), 138.2 tary evaporator. The residue was dissolved in CH2Cl2 (8.0 mL), and
(C-Ar), 167.2 (CO), 171.1 (CO) ppm. HRMS (ESI): calcd. for
this solution was washed with HCl (5% aq.; 2ϫ 5.0 mL), and water
(5ϫ 8.0 mL), and dried with Na2SO4. The volatiles were removed
under reduced pressure, and the crude product was recrystallized
from a mixture of EtOAc/hexane to give 15a (60.0 mg, 28%) as a
C18H28ClN2O6S [M + NH4]+ 435.1351; found 435.1355.
Methyl (3R*,4S*)-4-[2-(tert-Butoxycarbonyl)methyl]-1,3-dibenzyl-
3,4-dihydro-1H-benzo[c][1,2]-thiazine-3-carboxylate
2,2-Dioxide
1
colourless solid, m.p. 165–166 °C. H NMR (400 MHz, CDCl3): δ
(14a): From sulfonamide 7a (500 mg, 1.41 mmol), K2CO3 (486 mg,
3.52 mmol), and BnCl (356 mg, 2.81 mmol), TP 4 (reaction time
10 h) gave compound 14a (500 g, 66%) as a single 3R*,4S* dia-
= 1.50 (s, 9 H, CMe3), 2.59 (ddd, J = 6.9, 10.7, 13.8 Hz, 1 H,
NCH2CHHЈ), 2.67 (dd, J = 3.5, 18.7 Hz, 1 H, CHHЈCO2tBu), 3.03
(ddd, J = 2.8, 9.4, 13.8 Hz, 1 H, NCH2CHHЈ), 3.24 (ddd, J = 2.8,
10.7, 12.6 Hz, 1 H, NCHHЈ), 3.59 (dd, J = 7.2, 18.7 Hz, 1 H, CHHЈ
CO2tBu), 3.80 (ddd, J = 6.9, 9.4, 12.6 Hz, 1 H, NCHHЈ), 3.88 (s,
3 H, OMe), 4.20 (dd, J = 3.5, 7.2 Hz, 1 H, 4-H), 7.17 (d, J =
7.5 Hz, 1 H, H-Ar), 7.25–7.38 (m, 3 H, H-Ar) ppm. 13C NMR
(101 MHz, CDCl3): δ = 28.1 (3 C, CMe3), 33.9 (C-10), 40.5
(CH2CO2tBu), 48.9 (C-8), 52.5 (C-11), 53.5 (OMe), 66.3 (C-9), 81.3
(CMe3), 127.5 (CH-Ar), 128.7 (CH-Ar), 128.9 (CH-Ar), 129.8
(CH-Ar), 133.1 (C-Ar), 144.9 (C-Ar), 167.0 (CO), 171.8 (CO) ppm.
HRMS (ESI): calcd. for C18H23KNO6S [M + K]+ 420.0878; found
420.0876.
stereomer,
a
colourless solid, m.p. 170–171 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.27 (s, 9 H, CMe3), 2.65 (dd, J = 8.4,
17.4 Hz, 1 H, CHHЈCO2tBu), 2.93 (dd, J = 1.9, 17.4 Hz, 1 H,
CHHЈCO2tBu), 2.98 (d, J = 13.8 Hz, 1 H, CCHHЈ), 3.63 (d, J =
13.8 Hz, 1 H, CCHHЈ), 3.72 (s, 3 H, OMe), 4.17 (dd, J = 1.9,
8.4 Hz, 1 H, 4-H), 4.80 (d, J = 16.9 Hz, 1 H, NCHHЈ), 5.16 (d, J
= 16.9 Hz, 1 H, NCHHЈ), 6.79 (d, J = 8.1 Hz, 1 H, H-Ar), 6.94–
7.03 (m, 3 H, H-Ar), 7.09 (t, J = 7.4 Hz, 1 H, H-Ar), 7.16–7.25 (m,
4 H, H-Ar), 7.24–7.34 (m, 3 H, H-Ar), 7.38 (d, J = 7.4 Hz, 2 H,
H-Ar) ppm. 13C NMR (101 MHz, CDCl3): δ = 28.0 (3 C, CMe3),
39.5 (CCH2), 39.9 (CCH2), 40.5 (C-4), 50.5 (NCH2), 53.0 (OMe),
72.7 (C-3), 80.7 (CMe3), 117.7 (CH-Ar), 123.8 (CH-Ar), 126.8 (2
C, CH-Ar), 127.6 (CH-Ar), 127.7 (C-Ar), 127.9 (CH-Ar), 128.2
(CH-Ar), 128.6 (2 C, CH-Ar), 128.9 (2 C, CH-Ar), 130.1 (CH-Ar),
130.2 (2 C, CH-Ar), 133.3 (C-Ar), 136.8 (C-Ar), 138.6 (C-Ar),
165.9 (CO), 171.2 (CO) ppm. HRMS (ESI): calcd. for
Acknowledgments
The authors thank Alexander Ivanov for recording 1D NOE NMR
experiments, Vladislav Gurzhiy and Andrey Zolotarev for prompt
performing of X-ray diffraction experiments, Victoria Karpenko
for mass spectra, and Natalia Danilkina for elemental analysis. The
authors are grateful to the following Saint Petersburg State Univer-
sity Research Resource Centres: Centre for Magnetic Resonance,
Research Centre for X-Ray Diffraction Studies, and Resource Cen-
tre “Methods of analysis of the composition of matter”.
C30H33NNaO6S [M
+
Na]+ 558.1921; found 558.1917.
C30H33NO6S (535.7): calcd. C 67.3, H 6.2, N 2.6; found C 67.6, H
6.2, N 2.7.
Methyl trans-4-(tert-Butoxycarbonylmethyl)-6-chloro-3,4-dihydro-1-
methyl-1H-benzo[c][1,2]thiazine-3-carboxylate 2,2-Dioxide (11c): A
solution of MeI (54.6 mg, 385 μmol) in DMF (5.0 mL) was slowly
added over 30 min to a mixture of sultam 10c (150 mg, 385 μmol)
and K2CO3 (132 mg, 962 μmol) in DMF (5.0 mL) at 60–70 °C. The
resulting mixture was stirred at this temperature for 20 h, and was
then concentrated on a rotary evaporator. The residue was dis-
solved in CH2Cl2 (10 mL), and this solution was washed with HCl
(5% aq.; 2ϫ 5.0 mL), water (5ϫ 8.0 mL), and brine (8.0 mL), and
then dried with Na2SO4. The solvents were removed under reduced
pressure on a rotary evaporator, and the crude product was sub-
jected to flash column chromatography (EtOAc/hexane, 1:3) fol-
lowed by recrystallization from EtOAc/hexane to give compound
trans-11c (120 mg, 77%) as a colourless solid, m.p. 91–92 °C. 1H
NMR (400 MHz, CDCl3): δ = 1.39 (s, 9 H, CMe3), 2.63 (dd, J =
3.8, 17.0 Hz, 1 H, CHHЈ), 3.16 (dd, J = 8.0, 17.0 Hz, 1 H, CHHЈ),
3.37 (s, 3 H, NMe), 3.89 (s, 3 H, OMe), 4.11 (ddd, J = 3.8, 6.6,
8.0 Hz, 1 H, 4-H), 4.64 (d, J = 6.6 Hz, 1 H, 3-H), 7.02 (d, J =
8.6 Hz, 1 H, H-Ar), 7.26–7.30 (m, 2 H, H-Ar) ppm. 13C NMR
[1] M. Inagaki, T. Tsuri, H. Jyoyama, T. Ono, K. Yamada, M.
Kobayashi, Y. Hori, A. Arimura, K. Yasui, K. Ohno, S.
Kakudo, K. Koizumi, R. Suzuki, M. Kato, S. Kawai, S. Matsu-
moto, J. Med. Chem. 2000, 43, 2040–2048.
[2] L. Zhuang, J. S. Wai, M. W. Embrey, T. E. Fisher, M. S. Eg-
bertson, L. S. Payne, J. Guare, J. P. Vacca Jr., D. J. Hazuda, P. J.
Felock, A. L. Wolfe, K. A. Stillmock, M. V. Witmer, G. Moyer,
W. A. Schleif, L. J. Gabryelski, Y. M. Leonard, J. J. Lynch,
S. R. Michelson Jr., S. D. Young, J. Med. Chem. 2003, 46, 453–
456.
[3] a) R. Silvestri, G. Marfè, M. Artico, G. La Regina, A. Lavec-
chia, E. Novellino, M. Morgante, C. Di Stefano, G. Catalano,
G. Filomeni, E. Abruzzese, M. R. Ciriolo, M. A. Russo, S. Am-
adori, R. Cirilli, F. La Torre, P. S. Salimei, J. Med. Chem. 2006,
49, 5840–5844; b) N. Lebegue, S. Gallet, N. Flouquet, P. Car-
ato, B. Pfeiffer, P. Renard, S. Léonce, A. Pierré, P. Chavatte, P.
Berthelot, J. Med. Chem. 2005, 48, 7363–7373.
(101 MHz, CDCl3): δ = 27.9 (3 C, CMe3), 36.1 (Me or C-4), 38.3 [4] M. Zia-ur-Rehman, A. J. Choudary, S. Ahmad, H. L. Siddiqui,
Chem. Pharm. Bull. 2006, 54, 1175–1178.
(Me or C-4), 39.1 (CH2), 53.7 (OMe), 62.6 (C-3), 81.9 (CMe3),
121.9 (CH-Ar), 128.4 (CH-Ar), 128.5 (CH-Ar), 129.1 (C-Ar), 130.3
(C-Ar), 139.3 (C-Ar), 165.3 (CO), 170.1 (CO) ppm. HRMS (ESI):
calcd. for C17H26ClN2O6S [M (35Cl) + NH4]+ 421.1195; found
421.1198. C17H22ClNO6S (403.9): calcd. C 50.6, H 5.5, N 3.5;
found C 50.6, H 5.8, N 3.4.
[5] For recent reviews on the synthesis of sultams, see: a) M. Szos-
tak, J. Aube, Chem. Rev. 2013, 113, 5701–5765; b) V. A. Rassa-
din, D. S. Grosheva, A. A. Tomashevskiy, V. V. Sokolov, Khim.
Geterosikl. Soedin. 2013, 47–74; English translation: Chem.
Heterocycl. Compd. 2013, 49, 39–65; c) K. C. Majumdar, S.
Mondal, Chem. Rev. 2011, 111, 7749–7773.
[6] a) V. O. Rogachev, P. Metz, Nat. Protoc. 2006, 1, 3076–3087;
b) V. O. Rogatchov, H. Bernsmann, P. Schwab, R. Fröhlich, B.
Wibbeling, P. Metz, Tetrahedron Lett. 2002, 43, 4753–4756; c)
I. R. Greig, M. J. Tozer, P. T. Wright, Org. Lett. 2001, 3, 369–
371; d) B. Plietker, D. Seng, R. Fröhlich, P. Metz, Tetrahedron
2000, 56, 873–879; e) P. Metz, D. Seng, R. Fröhlich, B. Wibbe-
ling, Synlett 1996, 741–742; f) V. O. Rogachev, V. D. Filimonov,
Methyl
exo-8-(tert-Butoxycarbonylmethyl)-12-thia-1-azatricyclo-
[7.2.1.02,7]dodeca-2,4,6-triene-9-carboxylate 12,12-Dioxide (15a): A
mixture of sulfonamide 7a (200 mg, 563 μmol), K2CO3 (194 mg,
1.41 mmol), and DMF (5.0 mL) was stirred for 36 h at 60–70 °C.
Further K2CO3 (233 mg, 1.69 mmol) was then added, followed by
the slow addition over 2 h using a syringe pump of a solution of
8
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A Route to Benzo-Annelated δ-Sultams
R. Fröhlich, O. Kataeva, P. Metz, Heterocycles 2006, 67, 589–
595.
Snieckus, J. Org. Chem. 2007, 72, 3199–3206; i) J. V. Ruppel,
R. M. Kamble, X. P. Zhang, Org. Lett. 2007, 9, 4889–4892; j)
X. Y. Liu, C. H. Li, C. M. Che, Org. Lett. 2006, 8, 2707–2710;
k) C. Moutrille, S. Z. Zard, Tetrahedron Lett. 2004, 45, 4631–
4634.
[7] a) L. A. Paquette, W. R. S. Barton, J. C. Gallucci, Org. Lett.
2004, 6, 1313–1315; b) M. Ueda, H. Miyabe, A. Nishimura, O.
Miyata, Y. Takemoto, T. Naito, Org. Lett. 2003, 5, 3835–3838;
c) L. A. Paquette, C. S. Ra, J. D. Schloss, S. M. Leit, J. C. Gal-
lucci, J. Org. Chem. 2001, 66, 3564–3573; d) S. M. Leit, L. A.
Paquette, J. Org. Chem. 1999, 64, 9225–9229; e) L. A. Paquette,
S. M. Leit, J. Am. Chem. Soc. 1999, 121, 8126–8127.
[8] a) M. Jiménez-Hopkins, P. R. Hanson, Org. Lett. 2008, 10,
2223–2226; b) S. Karsch, D. Freitag, P. Schwab, P. Metz, Syn-
thesis 2004, 1696–1712; c) D. Freitag, P. Schwab, P. Metz, Tet-
rahedron Lett. 2004, 45, 3589–3592; d) S. Hanessian, H. Sailes,
E. Therrien, Tetrahedron 2003, 59, 7047–7056; e) D. D. Long,
A. P. Termin, Tetrahedron Lett. 2000, 41, 6743–6747; f) C.
Lane, V. Snieckus, Synlett 2000, 1294–1296; g) M. D. McReyn-
olds, J. M. Dougherty, P. R. Hanson, Chem. Rev. 2004, 104,
2239–2258.
[9] a) K. Wojciechowski, S. Kosinski, Tetrahedron 2001, 57, 5009–
5014; b) S. Kosinski, K. Wojciechowski, Eur. J. Org. Chem.
2000, 1263–1270; c) K. Wojciechowski, M. Makosza, Synthesis
1992, 571–576.
[10] D. Enders, A. Moll, J. W. Bats, Eur. J. Org. Chem. 2006, 1271–
1284.
[11] a) S. Merten, R. Fröhlich, O. Kataeva, P. Metz, Adv. Synth.
Catal. 2005, 347, 754–758; b) P. Evans, T. McCabe, B. S. Mor-
gan, S. Reau, Org. Lett. 2005, 7, 43–46; c) R. Grigg, M. York,
Tetrahedron Lett. 2000, 41, 7255–7258; d) R. Grigg, V. Srid-
haran, M. York, Tetrahedron Lett. 1998, 39, 4139–4142.
[12] a) E. M. Arranz, J. A. Diaz, S. T. Ingate, M. Witvrouw, C.
Pannecouque, J. Balzarini, E. D. Clercq, S. Vega, Bioorg. Med.
[14]
[15]
a) Y. Ishimata, H. Togo, Tetrahedron Lett. 2009, 50, 5354–5357;
b) H. Togo, Y. Harada, M. Yokoyama, J. Org. Chem. 2000, 65,
926–929.
a) J. E. Semple, P. C. Wang, Z. Lusenko, M. M. Joullie, G.
Zhou, P. Ting, R. Aslanian, J. Piwinski, Org. Lett. 2008, 10,
2517–2520; b) V. O. Rogachev, P. Metz, ARKIVOC 2007, 5,
167–190.
J. Morris, D. Wishka, J. Org. Chem. 1991, 56, 3549–3556.
PMB-substituted ortho-iodoanilines were obtained in our
group previously. For details, see the Supporting Information.
S. G. Davies, N. Mujtaba, P. M. Roberts, A. D. Smith, J. E.
[16]
[17]
[18]
[19]
Thomson, Org. Lett. 2009, 11, 1959–1962.
For a full account of our studies of the alkylation of sulfon-
amides under different conditions, see: a) V. A. Rassadin, D. S.
Grosheva, I. A. Arefeva, A. A. Tomashevskiy, V. V. Sokolov,
A. de Meijere, Eur. J. Org. Chem. 2012, 5028–5037; b) V. A.
Rassadin, A. A. Tomashevskiy, V. V. Sokolov, A. Ringe, J. Ma-
gull, A. de Meijere, Eur. J. Org. Chem. 2009, 2635–2641; c)
V. A. Rassadin, A. A. Tomashevskiy, V. V. Sokolov, A. A. Pote-
khin, Khim. Geterotsikl. Soedin. 2008, 605–617; English trans-
lation: Chem. Heterocycl. Compd. 2008, 44, 474–485.
[20] a) V. A. Rassadin, D. S. Grosheva, A. A. Tomashevskiy, D. S.
Yufit, S. I. Kozhushkov, V. V. Sokolov, A. de Meijere, Eur. J.
Org. Chem. 2010, 3481–3486; b) A. J. Preston, J. C. Gallucci,
L. A. Paquette, J. Org. Chem. 2006, 71, 6573–6578.
Chem. 1999, 7, 2811–2822; b) W. R. Buckheit, V. Fliaka-Boltz, [21] CCDC-963153 (for 11a), -1006245 (for 13a), -1006246 (for
D. W. Decker, L. J. Roberson, C. A. Pyle, L. E. White, B. J.
Bowden, J. B. McMahon, M. R. Boyd, J. P. Bader, D. G. Nick-
ell, H. Barth, T. K. Antonucci, Antiviral Res. 1994, 25, 43–56.
[13] For selected examples of the synthesis of benzosultams, see: a)
14a), and -1018004 (for 15a) contain the crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Z. Yang, J. Xu, Chem. Commun. 2014, 50, 3616–3618; b) M. V. [22] F. A. Carey, R. J. Sundberg, Stereochemistry, Conformation,
Pham, B. Ye, N. Cramer, Angew. Chem. Int. Ed. 2012, 51,
10610–10614; Angew. Chem. 2012, 124, 10762–10766; c) T. Mi-
ura, M. Yamauchi, A. Kosaka, M. Murakami, Angew. Chem.
and Stereoselectivity, in: Advanced Organic Chemistry, part A,
5th ed., Springer, New York, 2007 p. 158.
[23] G. M. Sheldrick, Acta Crystallogr., Sect. A 2008, 64, 112–122.
Int. Ed. 2010, 49, 4955–4957; Angew. Chem. 2010, 122, 5075– [24] OLEX2: A complete structure solution, refinement and analy-
5077; d) N. G. Nørager, K. Juhl, Synthesis 2010, 4273–4281; e)
S. Rousseaux, S. I. Gorelsky, B. K. W. Chung, K. Fagnou, J.
Am. Chem. Soc. 2010, 132, 10692–10705; f) W. Zeng, S. R.
sis program: O. V. Dolomanov, L. J. Bourhis, R. J. Gildea,
J. A. K. Howard, H. Puschmann, J. Appl. Crystallogr. 2009, 42,
339–341.
Chemler, J. Am. Chem. Soc. 2007, 129, 12948–12949; g) A. [25] CrysAlisPro, version 1.171.36.20, Agilent Technologies, 2012.
Rolfe, K. Young, P. R. Hanson, Eur. J. Org. Chem. 2008, 5254–
5262; h) J. Blanchet, T. Macklin, P. Ang, C. Metallinos, V.
Received: October 31, 2014
Published Online: ᭿
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O43416
/KAP1
Date: 14-01-15 19:12:47
Pages: 10
D. S. Grosheva, V. A. Rassadin, V. V. Sokolov
FULL PAPER
Sultams
D. S. Grosheva, V. A. Rassadin,
V. V. Sokolov* ................................. 1–10
A Route to Benzo-Annelated δ-Sultams
through Michael Cyclization
The method described involves Michael
cyclization of sulfonamides, and gives ac-
cess to a wide range of benzo-annelated
six-membered sultams.
Keywords: Heterocycles / Sultams / Fused-
ring systems / Michael addition / Cycliz-
ation
10
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