Deoxyalkoxyamination of Alcohols for the Synthesis of N-Alkoxy-N-alkylbenzenesulfonamides

Article abstract of DOI:10.1002/ejoc.201800526

A novel protocol for the deoxyalkoxyamination of alcohols has been developed, using N-alkoxybenzenesulfonimide (NOSI) as both a sulfonyl transfer reagent and an alkoxyamine source, accessing a diverse range of N-alkoxy-N-alkylbenzenesulfonamides with excellent isolated yields. This method is characterized by metal-free reaction, scalability, and waste-balance. Chiral substrates are converted with excellent levels of stereochemical inversion. NOSI could be generated in situ during the reaction as a stable reagent if a three-component one-pot reaction was designed. Exploiting this approach to run intramolecular reactions offered various N-protected isoxazolidines. In addition, valuable O-alkyl hydroxylamines (or isoxazolidines) were obtained through a neutral strategy of desulfonylation of the products.

Full text of DOI:10.1002/ejoc.201800526

DOI: 10.1002/ejoc.201800526
Full Paper
Deoxyalkoxyamination
Deoxyalkoxyamination of Alcohols for the Synthesis of
N-Alkoxy-N-alkylbenzenesulfonamides
Qi-An Sun,[a][‡] Ze-Hai Lu,[b][‡] Xiao-Qiu Pu,[a] Hui-Lian Hu,[a] Jia-heng Zhang,*[c] and
Xian-Jin Yang*[a,b]
Abstract: A novel protocol for the deoxyalkoxyamination of al- chemical inversion. NOSI could be generated in situ during the
cohols has been developed, using N-alkoxybenzenesulfonimide reaction as a stable reagent if a three-component one-pot reac-
(NOSI) as both a sulfonyl transfer reagent and an alkoxyamine tion was designed. Exploiting this approach to run intramolec-
source, accessing a diverse range of N-alkoxy-N-alkylbenzene- ular reactions offered various N-protected isoxazolidines. In ad-
sulfonamides with excellent isolated yields. This method is char- dition, valuable O-alkyl hydroxylamines (or isoxazolidines) were
acterized by metal-free reaction, scalability, and waste-balance. obtained through a neutral strategy of desulfonylation of the
Chiral substrates are converted with excellent levels of stereo- products.
Introduction
chiometric triphenylphosphane (PPh3) and diisopropyl azodi-
carboxylate (DIAD) were needed in the Mitsunobu reaction.
N-alkoxy-N-alkylbenzenesulfonamides, as sulfohydroxamic acids
(Piloty's acid)[1] derivatives, are of great importance in the phar-
maceutical field. The incorporation of this N-O-alkyl substituent
that is often similar to their analogous alkylamines, might pro-
vide a novel pharmacophore compared to alkylamines.[2] N-alk-
oxy-N-alkylbenzenesulfonamides have been reported to have
biological activities, such as inhibitors of matrix metalloprotein-
ases (MMPs),[3] CXCR2,[4] and NAMPT.[5] Some recent studies[6]
reported the biological mechanism of Piloty's acid, which de-
composes to HNO through a base-catalyzed deprotonation[7] or
releases NO upon oxidation.[8] Recently, Porcheddu synthesized
a series of Piloty's acid derivatives through the formation of
N–S bond under mild conditions (Scheme 1a).[9] However, the
preparation of O-alkyl hydroxylamine hydrochlorides with vari-
ous substituents was not convenient. Another protocol for the
synthesis of this compound is alkylation with alcohol under Mit-
sunobu conditions,[3] or with alkyl bromide in the presence of
K2CO3 in DMSO (Scheme 1b).[5] However, this protocol involved
two steps, namely sulfonylation and alkylation. In addition, stoi-
[a] Key Lab for Advanced Material & Institute of Fine Chemicals,
East China University of Science and Technology,
130 Meilong Road, Shanghai 200237, China
Scheme 1. One-pot deoxyalkoxyamination of alcohols for the synthesis of
E-mail: yxj@ecust.edu.cn
N-alkoxy-N-alkylbenzenesulfonamides.
[b] Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences,
Isoxazolidines, with N–O bond embedded in
a five-
345 Lingling Road, Shanghai 200032, China
membered ring, can be found in natural products, such as
dactylicapnosine[10] and pyrinodemin A.[11] Considerable effort
in synthesizing isoxazolidines has been made in developing
methods for [3+2] nitrone cycloadditions.[12] Other methods,
such as metal-catalyzed cyclizations of δ-hydroxylamino alk-
enes and δ-hydroxylamino allenes using palladium,[13] cop-
per,[14] silver,[15] iron[16] have been studied. However, the con-
[c] State Key Laboratory of Advanced Welding and Joining and
Research Center of Flexible Printed Electronic Technology, Harbin Institute
of Technology,
Shenzhen 518055, People's Republic of China
E-mail: zhangjiaheng@hit.edu.cn
[‡] These authors contributed equally to this work.
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201800526.
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struction of N-alkoxy-N-alkylbenzenesulfonamides and isox- conversion of alcohol (Table 1, entries 11–12), and obtained the
azolidines from alcohols, which are widely found in natural complete conversion and optimum yield (Table 1, entries 12).
The experiments above emphasized the key role of NOSI1 in
the conversion, which was facilely generated and tardily con-
sumed. For further research, we synthesized NOSI1 (Scheme 2a)
and it was scaled up to 20.0 grams, no column purification was
needed for the isolation of the product.[17] We then examined
the reactivity of NOSI1 with phenethanol (Scheme 2b). Using
the standard conditions, the corresponding deoxymethoxy-
amination product was obtained in a yield of 85 %. Thus, the
NOSI1 generated in situ in the studied system, showed excellent
reactivity to phenethanol.
products and chemical materials, was rarely reported. Herein,
we report a novel protocol for deoxyalkoxyamination of various
alcohols.
Results and Discussion
In our initial attempt, a three-component reaction, including
benzenesulfonyl chloride (BsCl), alkoxyamine hydrochloride and
phenethanol, was designed (see the Supporting Information for
details). With the formation of N- and O-sulfonylation com-
pounds, the desire product should be obtained with the cleav-
age of the former C–O bond. This method might provide a
neutral, atom-economical and metal-free one-pot strategy for
synthesizing N-alkoxy-N-alkylbenzenesulfonamide.
While treating this mixture with K2CO3 (3.2 equiv.) for 6 h at
room temperature (room temp.) (Table 1, entry 1), no N-alkoxy-
N-alkylbenzenesulfonamide (6) was detected. However, N-
methoxybenzenesulfonimide (NOSI1, 7) was generated with a
yield of 97 %. Increasing the quantity of K2CO3 (4.5 equiv.), less
than 5 % of 6 was produced (Table 1, entry 2). When this reac-
tion was heated to 60 °C for 0.5 h, 7 was generated with a yield
1
Scheme 2. Preparation and reactivity test of NOSI1.
of 97 % according to H-NMR analysis (Table 1, entry 3). When
the reaction time was extended, 6 was obtained with a yield of
41 %, while the yield of 7 was decreased to 50 % (Table 1, entry
4). Besides, higher temperature was unfavorable for the reaction
(Table 1, entry 5). With other bases, such as Cs2CO3, LiOH,
NaOH, triethylamine (Et3N), or pyridine, 6 was also formed, with
incomplete conversion of 7. In addition, when using Cs2CO3, 6
was obtained with a yield of 61 % as the best result (Table 1,
entries 6–10). We then optimized the conditions to ensure full
The examination of NOSI1 showed it is highly stable. No de-
composition event occurred after exposure to air for several
months. It is also stable in various solvents, including CH2Cl2,
THF, DMSO, DMF and H2O. Thermogravimetric analysis (TGA)
experiments indicated that there was no thermal event below
195 °C.
As NOSI1 is stable and easy to handle, it was prepared in
large-scale and used as a reagent to broaden the scope of the
substrates (Table 2). Various alcohols showed excellent reactiv-
ity with NOSI1 under identical conditions. In the cases of pri-
mary alcohols with short alkyl chain, 1a and 1b were obtained
in unmatched yields (95 and 98 %, respectively). As for the
benzyl alcohols (1f–1k,1m–1n, 2c, 2f, 2h), room temp. is ade-
quate to drive this reaction. Alcohol with six or five-membered
ring could generate the products 1c, 1e in 76 % and 73 % yield,
respectively. The stereospecificity of the process was investi-
gated using (R)-1-(4-bromophenyl)ethanol. Under standard re-
action conditions, 1n was formed in 60 % yield and 99 % enan-
tiomeric excess (ee). The structure was confirmed by single-crys-
tal X-ray crystallography (see the Supporting Information for
details),[18] which indicated the inversion of the chiral carbon.
The electronic effect was also investigated (1h–1l). It was found
that alcohols with electron-withdrawing substituents (1i,1j)
gave the target products in good yields compared to electron-
donating substituents. Instead, no product formed and 40 %
yield of 4-nitrobenzaldehyde was obtained when substrates
with strong electron-withdrawing group were employed (1l).
This reaction performs well upon scale-up, with the formation
of N-benzyl-N-methoxybenzenesulfonamide (1h) successfully
on 10.0 grams scale and with a yield of 89 %.
Table 1. Optimization of the deoxyalkoxyamination protocol.[a,b]
Entry
Base ([equiv.])
T [°C]
t [h]
7 [%]
6 [%]
1
2
3
4
5
6
7
8
K2CO3 (3.3)
K2CO3 (4.5)
K2CO3 (4.5)
K2CO3 (4.5)
K2CO3 (4.5)
Cs2CO3 (4.5)
LiOH (4.5)
NaOH (4.5)
Et3N (4.5)
Pyridine (4.5)
Cs2CO3 (4.5)
Cs2CO3 (4.5)
room temp.
room temp.
6
6
0.5
6
8
6
6
6
8
97
96
97
50
55
17
41
23
97
90
0
0
<5
<5
41
37
61
32
28
<5
6
60
60
80
60
60
60
60
60
60
60
9
10
11
12[c]
8
12
12
73
84
0
[a] Reaction conditions: BsCl (2.1 equiv.), alkoxyamine hydrochloride
(1.0 equiv.), alcohol (1.0 equiv.), all the reactions were run on a 0.5 mmol
scale with 3 mL of CH3CN. [b] The yield was determined by 1H-NMR analysis
on the crude reaction mixture. [c] BsCl (2.3 equiv.), alkoxyamine hydro-
chloride (1.1 equiv.), alcohol (1.0 equiv.) were needed for full conversion of
alcohol.
We next exchanged the methoxy group of this reagent with
another alkoxyl group (Table 2). To our delight, with various
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Table 2. Reactions of NOSI with various alcohols.[a]
Information for details). As depicted in Table 3, the reaction
conditions were applied to an array of γ-hydroxylamino alco-
hols to form the corresponding isoxazolidines 3a–3e. In terms
of 2-(phenylsulfonyl)-isoxazolidine (3a) without substituent, a
yield of 82 % was obtained. The reaction of 3b showed that the
steric effect resulted in much lower yield, but with the addition
of 10 mol-% pyridine, the yield was increased to 47 %. Under
standard reaction conditions, (S)-3-methyl-2-(phenylsulfonyl)-
isoxazolidine (3e) was produced in a yield of 63 % (91 % ee).
Noteworthy, a six-membered ring (3f) was also formed through
the cyclization of 4-(aminooxy)butan-1-ol.
Table 3. Synthesis of N-protected isoxazolidines.[a]
[a] The reaction conditions are as follows: alcohol (0.30 mmol), NOSI
(0.36 mmol), Cs2CO3 (0.39 mmol), CH3CN (3 mL), 60 °C. [b] Alcohol
(0.36 mmol), NOSI (0.30 mmol) for the isolation convenience. [c] Room tem-
perature.
[a] The reaction conditions are as follows: γ-hydroxylamino alcohols
(1.0 equiv.), BsCl (2.1 equiv.), Cs2CO3 (3.3 equiv.), CH3CN (2–3 mL), 60 °C, 12 h.
[b] Hydrochloride raw material and 4.3 equiv. Cs2CO3 was used. [c] 10 mol-%
pyridine was added.
alkoxyl groups, reagents (N-alkoxybenzenesulfonimide, NOSI)
Then, an asymmetrical N-alkoxybenzenesulfonimide (9) was
could totally be transformed with alcohols and gave the prod- synthesized. We wondered which product we could obtain. If
ucts in excellent yields. As shown in Table 2, functional groups 9b was selectively formed, desulfonylation of the product
including tertiary amine, N-Boc, thiophene, chloride, indole and would be facile with a thiophenol and potassium carbonate
cinnamyl were well tolerated under identical conditions. Even system.[12b,19] Unfortunately, both of the N–S bonds broke. Fur-
bulky benzhydrol could produce the product 2g in 37 % yields. thermore, the aromatic ring was attacked by alcohol and gave
However, tertiary butanol failed to react under these experi- 9c with a yield of 13 % (Scheme 3). Other substituent groups,
mental conditions. Apparently, steric-hindrance effect has a such as Boc and benzoyl (Bz), instead of p-nitrophenylsulfonyl
great impact on the reaction yield.
(Ns) resulted in a complex mixture.
After assessing the scope of this protocol using various alco-
We then considered the methods used for deprotection of
hols and reagents. We wondered whether this new deoxyalk- the N-SO2Ph group (see the Supporting Information for details).
oxyamination could be transferred to intramolecular reaction. Regarding the acetic acid solution containing HBr,[20] the N–S
To investigate this hypothesis, we synthesized some γ-hydroxyl- bond cleavage occurred and 10b was isolated with a yield of
amino alcohols (8) from different substrates (see the Supporting 70 %. Adding phenol (5.0 equiv.) into this reaction[21] made the
Scheme 3. Reactivity test of asymmetrical NOSI.
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post treatment inconvenient, which led to a lower yield (67 %).
Treatment of 1h with Mg in MeOH[22] with sonication resulted
in incomplete conversion of 1h. Fortunately, we found that ad-
dition of iodine as an initiator was effective to trigger this reac-
tion. Compound 1h was sonicated at room temp. until total
consumption of the starting material, and after the workup, the
desulfonylated compound 10b was isolated in 86 % yield, with
no detectable products resulting from the cleavage of the
N–O bond. Accordingly, we concluded that this method can be
considered as a versatile and general approach.
Table 4. Desulfonylation of products.[a,b]
Under these conditions, we created a simple test for the de-
sulfonylation of N-alkoxy-N-alkyl-benzenesulfonamide (Table 4).
This procedure was easily reproducible on heterocyclic and N-
protected isoxazolidine, to give the corresponding product 10c
and 10d, respectively. Simple molecule product, 10a was iso-
lated as the hydrochloride in moderate yield (46 % yield), which
could be explained by the low boiling point of amine. With the
removal of the N-SO2Ph groups on N-alkoxy-N-alkylbenzene-
sulfonamide, O-alkyl hydroxylamines exhibited a variety of bio-
logical properties,[23] which have great potential in pharmaceu-
tical areas.
To gain more insight into the reaction mechanism, we con-
ducted some preliminary studies. Treatment of methyl benz-
enesulfonate with N-methoxybenzenesulfonamine (4) results in
the formation of 11 (Scheme 4a). When 4 was added in a stan-
dard reaction (Scheme 4b), 12 and 11 were detected with a
[a] The reaction conditions are as follows: substrate (1.0 equiv.), Mg powder
(10.0 equiv.), 1–2 grains of iodine crystals, MeOH, room temp., sonication,
30 min. [b] Obtained yields are based on the starting material.
Scheme 4. Mechanism studies.
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molar ratio of 0.56:1 upon 1H-NMR analysis of the mixture prod-
uct (11 was the major product which could be explained by
the higher initial concentration of 4). The results may indicate
an intermolecular pathway. Based on the findings from these
experiments, we proposed the mechanism depicted in
Scheme 4c. Path A: initial N- to O-sulfonyl transfer between
NOSI and alcohol, to give alkyl sulfonate, which has been di-
rectly observed during optimization studies when low polar sol-
vent was used (see the Supporting Information for details), fol-
lowed by a recombination of the resulting methoxyamide anion
and alkyl sulfonate to access configuration turning products.
Path B: N- and O-sulfonylated compounds were generated si-
multaneously, and the product was obtained by the cleavage
of former C–O bond. This process is usually secondary (Table 1,
entry 2). Nevertheless, if the synthesis of bis(benzene)sulfon-
imide intermediate turned out to be difficult (Table 3, com-
pound 3b), in the presence of pyridine (which may promote
the generation of sulfonate), this process was likely to be the
major one.
The reaction was then quenched with water, extracted with DCM
(3 ×). The organic phase was combined and washed with brine,
dried with sodium sulfate. The solvent was removed under reduced
pressure and the product was obtained as a white solid.
Standard Procedure for the Reaction with Alcohols: To a mixture
of alcohol (0.30 mmol. 1.0 equiv.) and Cs2CO3 (0.39 mmol, 1.3 equiv.)
in acetonitrile (3.0 mL) was added N-alkoxy-N-(phenylsulfonyl)-
benzenesulfonamide (0.36 mmol, 1.2 equiv.), and the mixture was
stirred at 60 °C. The reaction was monitored by TLC. After the com-
plete conversion of alcohol, the solvent was removed under re-
duced pressure and the crude product was further purified by flash
column chromatography.
Standard Procedure for the Synthesis of N-Protected Isoxazol-
idines: To a mixture of γ-hydroxylamino alcohols (0.50 mmol.
1.0 equiv.) and Cs2CO3 (1.65 mmol, 3.3 equiv.) in acetonitrile
(5.0 mL) was added benzenesulfonyl chloride (1.05 mmol,
2.1 equiv.). The mixture was stirred at 60 °C. and the reaction was
monitored by TLC. After the complete conversion of benzenesulf-
onyl chloride, the solvent was removed under reduced pressure and
the crude product was further purified by flash column chromatog-
raphy.
General Procedure for Desulfonylation of Products: To a solution
of N-alkyl-N-methoxybenzenesulfonamide (1.0 equiv.) and Mg pow-
Conclusions
der (10 equiv.) in MeOH (0.3
M) were added 1–2 crystals of iodine
In summary, we developed a new operationally simple protocol
for the deoxyalkoxyamination of alcohols using NOSI as both a
sulfonyl transfer reagent and an alkoxyamine source, accessing
a diverse range of N-alkoxy-N-alkylbenzenesulfonamides and
N-protected isoxazolidines resulting in excellent yields. Chiral
substrates are converted with excellent levels of stereochemical
inversion. In addition, we introduce an improved method to
remove the N-SO2Ph group, producing O-alkyl hydroxylamines
and isoxazolidines in excellent yields.
as an initiator, giving a yellow color. The reaction mixture was soni-
cated until persistent bubbles were seen and the yellow color disap-
peared. Then the reaction was removed from sonication and al-
lowed to continue at room temperature. The reaction mixture
turned to be gel like and the Mg powder was dissolved when the
reaction completed. 1
M HCl was added to adjust the mixture pH
to 1. Then saturated solution of sodium carbonate was added to
the reaction mixture until no gas evolution happened. The mixture
was extracted with EA (5 ×). The organic phase was combined and
dried with sodium sulfate. The solvent was removed under reduced
pressure and the crude product was purified by flash chromatogra-
phy on silica gel.
Experimental Section
3. Analytical Data for the Products
1. General Information: Unless stated otherwise, all the starting
chemicals were commercially available and used without further
purification. Substrates were purchased from Energy chemical Co.
Ltd. and Adamas-beta Co. Ltd. Dry acetonitrile was obtained by
refluxing with CaH2, dry THF was obtained by refluxing with
Na. Flash column chromatography was performed on silica gel
(300–400 mesh). All 1H NMR spectra were recorded on a Bruker
spectrometer at 400 MHz. The 13C NMR spectra were recorded on
a Bruker spectrometer at 100 MHz. Chemical shifts are reported as
parts per million (ppm) using residual solvent signals as internal
standard (CHCl3, δ = 7.26 ppm for 1H NMR, δ = 77.16 ppm
for 13C NMR). J values are reported in Hz. IR spectrum (Film) were
recorded on a Nicolet 6700 spectrophotometer in the range of
400–4000 cm–1. HRMS (EI) spectra were recorded on a Waters GCT
Premier mass spectrometer with electron impact.
N-Ethyl-N-methoxybenzenesulfonamide (1a): Colorless liquid;
98 % Yield. H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 7.2 Hz, 2 H),
1
7.65 (t, J = 7.6 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 2 H), 3.87 (s, 3 H), 2.92
(s, 2 H), 1.20 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 133.80, 133.23, 129.60, 128.86, 65.70, 48.06, 12.37 ppm. IR (neat):
ν = 2984, 1463, 1378, 1177, 1022, 741, 582 cm–1. HRMS-EI (m/z)
˜
calcd. for (C9H13NO3S) 215.0616, found 215.0617.
N-Methoxy-N-methylbenzenesulfonamide (1b): Colorless liquid;
95 % Yield. 1H NMR (400 MHz, CDCl3): δ = 7.90–7.83 (m, 2 H), 7.70–
7.61 (m, 1 H), 7.60–7.51 (m, 2 H), 3.79 (s, 3 H), 2.77 (s, 3 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 133.89, 132.25, 129.74, 128.87, 63.78,
39.27 ppm. IR (neat): ν = 3445, 2984, 1402, 1161, 733, 582 cm–1
HRMS-EI (m/z) calcd. for (C8H11NO3S) 201.0460, found 201.0459.
.
˜
N-Cyclohexyl-N-methoxybenzenesulfonamide (1c): Colorless liq-
1
2. Experimental Details
uid; 76 % Yield. H NMR (400 MHz, CDCl3): δ = 7.95–7.91 (m, 2 H),
7.65–7.60 (m, 1 H), 7.55–7.50 (m, 2 H), 3.77 (s, 3 H), 3.61–3.53 (m, 1
H), 1.70–1.57 (m,4 H), 1.42–1.17 (m, 5 H), 1.08–0.96 (m, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 133.75, 133.50, 128.96, 128.95, 63.36,
Preparation of N-Alkoxy-N-(phenylsulfonyl)benzenesulfon-
amide (NOSI) (7 as an Example): In a round-bottomed flask
equipped with a magnetic stir bar, alkoxyamine hydrochloride
(1.0 equiv.) and potassium carbonate (3.3 equiv.) were dissolved as
much as possible in MeCN (0.2 M). To this cloudy solution was slowly
added benzenesulfonyl chloride (2.2 equiv.) at room temperature.
The reaction was stirred at room temperature and was monitored
61.67, 25.69, 25.47 ppm. IR (neat): ν = 2938, 1449, 1371, 1172, 746,
˜
578 cm–1. HRMS-EI (m/z) calcd. for (C13H19NO3S) 289.1086, found
269.1088.
N-[2-(Dimethylamino)ethyl]-N-methoxybenzenesulfonamide
by TLC until the complete conversion of benzenesulfonyl chloride. (1d): Yellow oil; 75 % Yield. 1H NMR (400 MHz, CDCl3): δ = 7.90–
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7.84 (m, 2 H), 7.69–7.61 (m, 1 H), 7.59–7.51 (m, 2 H), 3.88 (s, 3 H),
2.99 (br., 2 H), 2.53 (t, J = 6.9 Hz, 2 H), 2.25 (s, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 133.89, 133.15, 129.64, 128.94, 65.49, 56.32,
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.62, 133.92, 133.58,
131.07, 129.69, 129.03, 126.60, 113.96, 65.49, 56.57, 55.38 ppm. IR
(neat): ν = 2984, 2941, 2912, 1612, 1513, 1351, 1284, 1166, 742, 583,
˜
51.48, 45.72 ppm. IR (neat): ν = 2943, 2771, 1448, 1356, 1171, 1015,
535 cm–1. HRMS-EI (m/z) calcd. for (C15H17NO4S) 307.0878, found
˜
742, 690, 574 (·) cm–1. HRMS-EI (m/z) calcd. for (C11H18N2O3S) 307.0880.
258.1038, found 258.1042.
(R)-N-Methoxy-N-(1-phenylethyl)benzenesulfonamide (1m):
White solid; 56 % Yield; 99 % ee; m.p. 71.5–72.3 °C. 1H NMR
(400 MHz, [D6]DMSO): δ = 8.03–7.63 (m, 3 H), 7.55 (br., 2 H), 7.40–
7.00 (m, 5 H), 4.78 (q, J = 6.0 Hz, 1 H), 3.56 (br., 3 H), 1.23 (br., 3 H),
4.22 (br., 2 H), 3.62 (s,3 H) ppm. 13C NMR (100 MHz, [D6]DMSO): δ =
139.98, 135.51, 133.73, 128.96, 128.63, 128.10, 127.60, 127.56, 65.66,
tert-Butyl (R)-3-(N-Methoxyphenylsulfonamido)pyrrolidine-1-
carboxylate (1e): Colorless oil; 75 % Yield; 99 % ee. 1H NMR
(400 MHz, CDCl3): δ = 7.95–7.87 (m, 2 H), 7.71–7.64 (m, 1 H), 7.60–
7.53 (m, 2 H), 4.00–3.88 (m, 1 H), 3.85 (s, 3 H), 3.46–3.36 (m,1 H),3.28
(br., 2 H), 3.24–3.12 (m, 1 H), 1.94 (br., 2 H), 1.40 (s, 9 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 154.26, 134.79, 134.15, 129.39, 129.13,
79.60, 77.36, 66.12, 60.71, 60.65, 60.17, 44.37, 43.79, 28.50 ppm. IR
60.28, 17.23, 15.13 ppm. IR (neat): ν = 3059, 2940, 1450, 1353, 1164,
˜
1083, 728, 595, 556 cm–1. HRMS-EI (m/z) calcd. for (C15H17NO3S)
(neat): ν = 3465, 2976, 2937, 1696, 1407, 1172, 757, 578 cm–1. HRMS-
˜
291.0929, found 291.0930.
EI (m/z) calcd. for (C16H24N2O5S) 356.1406, found 356.1402.
(R)-N-[1-(4-Bromophenyl)ethyl]-N-methoxybenzenesulfon-
amide (1n): White solid; 60 % Yield; 99 % ee; m.p. 112.3–112.8 °C.
1H NMR (400 MHz, [D6]DMSO): δ = 7.95–7.61 (br., 3 H), 7.61–7.46
(br., 2 H), 7.46–7.30 (br., 2 H), 7.30–6.90 (br., 2 H), 4.77 (q, J = 6.9 Hz,
1 H), 3.62 (br., 3 H), 1.22 (br., 3 H) ppm. 13C NMR (100 MHz,
[D6]DMSO): δ = 139.22, 135.26, 133.69, 130.93, 129.80, 128.92,
N-Methoxy-N-(naphthalen-1-ylmethyl)benzenesulfonamide
(1f): White solid; 75 % Yield; m.p. 143.0–143.4 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.37 (d, J = 8.5 Hz, 1 H), 8.07–7.97 (m, 2 H), 7.86 (dd, J =
12.3, 8.2 Hz, 2 H), 7.80–7.71 (m, 1 H), 7.68–7.59 (m, 3 H), 7.57–7.50
(m, 1 H), 7.42–7.34 (m, 1 H), 7.30 (d, J = 6.3 Hz, 1 H), 4.47 (br., 2 H),
3.23 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 134.06, 133.91,
133.48, 132.16, 129.91, 129.72, 129.50, 129.17, 129.14, 128.64,
126.84, 126.15, 125.14, 124.47, 77.16, 65.41, 55.32 ppm. IR (neat):
128.65, 120.86, 65.82, 59.80, 17.71, 14.23 ppm. IR (neat): ν = 3445,
˜
3005, 2936, 1354, 1169, 1078, 740, 601, 566 cm–1. HRMS-EI (m/z)
calcd. for (C15H16BrNO3S) 369.0034, found 369.0035.
ν = 3422, 2938, 1446, 1354, 1170, 781, 581 cm–1. HRMS-EI (m/z)
˜
calcd. for (C18H17NO3S) 327.0929, found 327.0930.
N-[2-(7-Ethyl-1H-indol-3-yl)ethyl]-N-methoxybenzenesulfon-
amide (1o): Colorless oil; 71 % Yield. 1H NMR (400 MHz, CDCl3): δ =
8.02 (br., 1 H), 7.92–7.82 (m, 2 H), 7.69–7.60 (m, 1 H), 7.56–7.49 (m,
2 H), 7.44–7.38 (m, 1 H), 7.13–7.01 (m, 3 H), 3.96 (s, 3 H), 3.23 (br., 2
H), 3.11 (dd, J = 9.5, 5.4 Hz, 2 H), 2.86 (q, J = 7.6 Hz, 2 H), 1.36 (t,
J = 7.6 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 135.08, 133.84,
133.22, 129.59, 128.94, 127.09, 126.75, 121.93, 120.76, 119.89,
N-Methoxy-N-(thiophen-2-ylmethyl)benzenesulfonamide (1g):
Yellow solid; 68 % Yield; m.p. 65.4–67.1 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.95–7.89 (m, 2 H), 7.73–7.67 (m, 1 H), 7.63–7.55 (m, 2
H), 7.28 (dd, J = 5.1, 1.2 Hz, 1 H), 6.99 (d, J = 3.3 Hz, 1 H), 6.95 (dd,
J = 5.1, 3.5 Hz, 1 H), 4.22 (br., 2 H), 3.62 (s,3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 136.45, 134.08, 133.37, 129.72, 129.09, 128.47,
116.41, 112.86, 65.84, 53.79, 24.08, 23.44, 13.92 ppm. IR (neat): ν =
˜
126.88, 126.69, 65.69, 51.61 ppm. IR (neat): ν = 2949, 1445, 1352,
˜
3406, 2966, 1445, 1346, 1169, 740, 581 cm–1. HRMS-EI (m/z) calcd.
1161, 1005, 729, 582, 554 cm–1. HRMS-EI (m/z) calcd. for
for (C16H19NO3S) 358.1351, found 358.1353.
(C16H19NO3S) 305.1086, found 305.1087.
N-Ethoxy-N-phenethylbenzenesulfonamide (2a): White solid;
77 % Yield; m.p. 79.1–80.1 °C. H NMR (400 MHz, CDCl3): δ = 7.90–
7.83 (m, 2 H), 7.68–7.63 (m, 1 H), 7.58–7.50 (m, 2 H), 7.32–7.26 (m,
2 H), 7.25–7.15 (m, 3 H), 4.18 (q, J = 7.1 Hz, 2 H), 3.14 (br., 2 H), 2.93
(t, J = 7.8 Hz, 2 H), 1.23 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 138.21, 133.82, 133.30, 129.70, 128.94, 128.92, 128.71,
N-Benzyl-N-methoxybenzenesulfonamide (1h): White solid; 89 %
Yield; m.p. 69.1–69.5 °C. 1H NMR (400 MHz, CDCl3): δ = 7.98–7.92
(m, 2 H), 7.74–7.68 (m, 1 H), 7.63–7.58 (m, 2 H), 7.36–7.30 (m, 5 H),
4.00 (br., 2 H), 3.47 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
134.64, 133.98, 133.46, 129.75, 129.68, 129.05, 128.58, 128.25, 65.49,
1
57.18 ppm. IR (neat): ν = 3425, 2994, 1359, 1210, 725, 603 cm–1
.
˜
126.72, 73.62, 54.62, 33.80, 13.85 ppm. IR (neat): ν = 2981, 2901,
HRMS-EI (m/z) calcd. for (C14H15NO3S) 277.0773, found 277.0774.
˜
1449, 1349, 1176, 754, 580 cm–1. HRMS-EI (m/z) calcd. for
N-(4-Chlorobenzyl)-N-methoxybenzenesulfonamide (1i): White
solid; 81 % Yield; m.p. 103.0–104.1 °C. 1H NMR (400 MHz, CDCl3):
δ = 7.96–7.90 (m, 2 H), 7.74–7.68 (m, 1 H), 7.64–7.57 (m, 2 H), 7.34–
7.26 (m, 4 H), 3.96 (br., 2 H), 3.49 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 134.27, 134.09, 133.34, 133.22, 131.12, 129.70, 129.10,
(C16H19NO3S) 305.1086, found 305.1087.
N-(2-Chloroethyl)-N-ethoxybenzenesulfonamide (2b): White
1
solid; 70 % Yield; m.p. 57.9–58.4 °C. H NMR (400 MHz, CDCl3): δ =
7.91–7.85 (m, 2 H), 7.72–7.64 (m, 1 H), 7.62–7.54 (m, 2 H), 4.19 (q,
J = 7.1 Hz, 2 H), 3.63 (t, J = 6.6 Hz, 2 H), 3.22 (br., 2 H), 1.22 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 134.13, 133.10,
128.83, 65.56, 56.50 ppm. IR (neat): ν = 2943, 1582, 1491, 1344,
˜
1170, 1090, 1008, 763, 570 cm–1. HRMS-EI (m/z) calcd. for
(C14H14ClNO3S) 311.0383, found 311.0385.
129.66, 129.08, 73.72, 54.82, 39.99, 13.79 ppm. IR (neat): ν = 3058,
˜
2984, 2900, 1447, 1344, 1171, 745, 673, 578 cm–1. HRMS-EI (m/z)
calcd. for (C10H14ClNO3S) 263.0383, found 263.0385.
N-(4-Bromobenzyl)-N-methoxybenzenesulfonamide (1j): White
solid; 88 % Yield; m.p. 110.3–111.2 °C. 1H NMR (400 MHz, CDCl3):
δ = 7.96–7.90 (m, 2 H), 7.74–7.68 (m, 1 H), 7.64–7.57 (m, 2 H), 7.49–
7.43 (m, 2 H), 7.25–7.19 (m, 2 H), 3.94 (br., 2 H), 3.49 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 134.27, 134.09, 133.34, 133.22,
N-Cinnamyl-N-ethoxybenzenesulfonamide (2c): Yellow solid;
1
87 % Yield; m.p. 77.6–78.0 °C. H NMR (400 MHz, CDCl3): δ = 7.96–
7.88 (m, 2 H), 7.72–7.64 (m, 1 H), 7.62–7.54 (m, 2 H), 7.35–7.26 (m,
4 H), 7.26–7.22 (m, 1 H), 6.50 (dt, J = 15.8, 1.3 Hz, 1 H), 6.20 (dt, J =
15.8, 6.9 Hz, 1 H), 4.09 (q, J = 7.1 Hz, 2 H), 3.70 (br., 2 H), 1.15 (t, J =
7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.46, 135.48,
133.86, 133.66, 129.73, 128.98, 128.76, 128.15, 126.59, 122.32, 73.49,
131.12, 129.70, 129.10, 128.83, 65.56, 56.50 ppm. IR (neat): ν = 3093,
˜
2941, 1487, 1344, 1170, 1009, 755, 564 cm–1. HRMS-EI (m/z) calcd.
for (C14H14BrNO3S) 354.9878, found 354.9879.
N-Methoxy-N-(4-methoxybenzyl)benzenesulfonamide (1k):
White solid; 65 % Yield; m.p. 84.8–85.7 °C. 1H NMR (400 MHz, CDCl3):
55.71, 13.86 ppm. IR (neat): ν = 3064, 2981, 2894, 1447, 1353, 1174,
˜
δ = 7.99–7.90 (m, 2 H), 7.75–7.65 (m, 1 H), 7.65–7.56 (m, 2 H), 7.29– 767, 580 cm–1. HRMS-EI (m/z) calcd. for (C17H19NO3S) 317.1086,
7.22 (m, 2 H), 6.89–6.83 (m, 2 H), 3.94 (br., 2 H), 3.80 (s, 3 H), 3.46
found 317.1084.
Eur. J. Org. Chem. 0000, 0–0
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6
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Full Paper
N-Butyl-N-ethoxybenzenesulfonamide (2d): Colorless liquid;
1 H), 2.30 (dddd, J = 11.9, 8.1, 6.6, 5.3 Hz, 1 H), 1.76 (dddd, J = 11.9,
63 % Yield. 1H NMR (400 MHz, CDCl3): δ = 7.90–7.84 (m, 2 H), 7.68– 8.7, 7.9, 7.1 Hz, 1 H), 1.23 (d, J = 6.1 Hz, 3 H) ppm. 13C NMR
7.61 (m, 1 H), 7.59–7.51 (m, 2 H), 4.14 (q, J = 7.1 Hz, 2 H), 2.86 (br.,
2 H), 1.62–1.52 (m, 2 H), 1.43–1.31 (m, 2 H), 1.21 (t, J = 7.1 Hz, 3 H),
(100 MHz, CDCl3): δ = 135.90, 133.98, 129.36, 129.14, 77.90, 48.13,
35.60, 19.02 ppm. IR (neat): ν = 2983, 2905, 1448, 1351, 1170, 755,
˜
0.91 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 133.69, 614, 565 cm–1. HRMS-EI (m/z) calcd. for (C10H13NO3S) 227.0616,
133.41, 129.66, 128.84, 73.50, 53.09, 29.10, 20.07, 13.87, 13.80 ppm. found 227.0617.
IR (neat): ν = 2961, 2935, 2873, 1740, 1356, 1177, 578 cm–1. HRMS-
˜
2-(Phenylsulfonyl)-5-propylisoxazolidine (3d): Colorless liquid;
EI (m/z) calcd. for (C12H19NO3S) 257.1086, found 257.1087.
67 % Yield. 1H NMR (400 MHz, CDCl3): δ = 8.00–7.93 (m, 2 H), 7.70–
N-Isopropoxy-N-methylbenzenesulfonamide (2e): White solid;
76 % Yield; m.p. 50.3–51.0 °C. H NMR (400 MHz, CDCl3): δ = 7.91–
7.82 (m, 2 H), 7.70–7.62 (m, 1 H), 7.60–7.53 (m, 2 H), 4.48–4.35 (m,
1 H), 2.77 (s, 3 H), 1.21 (d, J = 6.2 Hz, 6 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 133.79, 123.54, 129.91, 128.85, 78.56, 41.25, 21.01 ppm.
7.62 (m, 1 H), 7.59–7.52 (m, 2 H), 4.16–4.07 (m, 1 H), 3.87 (ddd, J =
11.7, 8.1, 7.3 Hz, 1 H), 3.60 (ddd, J = 11.6, 8.7, 5.1 Hz, 1 H), 2.31–
2.20 (m, 1 H), 1.84–1.73 (m, 1 H), 1.59–1.21 (m, 4 H), 0.88 (t, J =
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 135.86, 133.95,
129.37, 129.10, 81.60, 47.97, 35.69, 34.04, 19.43, 14.06 ppm. IR
1
˜
(neat): ν = 2960, 2874, 1585, 1448, 1357, 1170, 1089, 690, 570 cm–
IR (neat): ν = 2978, 2934, 1724, 1446, 1350, 1166, 744, 694, 584,
˜
526 cm–1. HRMS-EI (m/z) calcd. for (C10H15NO3S) 229.0773, found
1. HRMS-EI (m/z) calcd. for (C12H17NO3S) 255.0929, found 255.0930.
229.0775.
(S)-3-Methyl-2-(phenylsulfonyl)isoxazolidine (3e): Colorless liq-
uid; 63 % Yield; 91 % ee. 1H NMR (400 MHz, CDCl3): δ = 8.02–7.96
(m, 2 H), 7.69–7.62 (m, 1 H), 7.59–7.51 (m, 2 H), 4.40–4.29 (m, 1 H),
4.04–3.91 (m, 2 H), 2.41–2.31 (m, 1 H), 1.99–1.88 (m, 1 H), 1.39 (d,
J = 6.5 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 136.23, 133.91,
N-Benzyl-N-isopropoxybenzenesulfonamide (2f): White solid;
61 % Yield; m.p. 57.9–58.9 °C. H NMR (400 MHz, CDCl3): δ = 7.97–
7.90 (m, 2 H), 7.73–7.66 (m, 1 H), 7.64–7.56 (m, 2 H), 7.30 (s, 5 H),
4.24–4.12 (m, 1 H), 0.81 (br., 6 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 134.81, 133.82, 133.59, 130.50, 129.82, 128.94, 128.37, 128.24,
1
129.27, 129.12, 69.94, 55.64, 36.57, 21.64 ppm. IR (neat): ν = 2982,
˜
2900, 1583, 1448, 1357, 1169, 1089, 732, 575 cm–1. HRMS-EI (m/z)
calcd. for (C10H13NO3S) 227.0616, found 227.0617.
78.85, 58.17, 20.88 ppm. IR (neat): ν = 3061, 2977, 2914, 1449, 1357,
˜
1174, 744, 580 cm–1. HRMS-EI (m/z) calcd. for (C16H19NO3S)
305.1086, found 305.1084.
1
2-(Phenylsulfonyl)-1,2-oxazinane (3f): White solid; 75 % Yield. H
N-Benzhydryl-N-isopropoxybenzenesulfonamide (2g): White
solid; 37 % Yield; m.p. 95.9–96.7 °C. H NMR (400 MHz, CDCl3): δ =
7.54–7.47 (m, 2 H), 7.44–6.85 (m, 13 H), 6.04 (s, 1 H), 4.17–4.04 (m,
1 H), 1.47–1.01 (m, 3 H), 0.53 (br., 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 135.81, 132.64, 130.07, 129.22, 128.47, 128.02, 127.52,
NMR (400 MHz, CDCl3): δ = 7.93–7.83 (m, 2 H), 7.71–7.62 (m, 1 H),
7.61–7.52 (m, 2 H), 4.19–3.99 (m, 2 H), 3.23–3.05 (m,2 H), 1.91–1.81
(m, 2 H), 1.60–1.51 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
133.77, 129.48, 128.92, 72.85, 49.40, 24.12, 23.10 ppm. HRMS-EI
(m/z) calcd. for (C10H13NO3S) 227.0616, found 227.0618.
1
127.35, 80.14, 69.40, 21.44, 20.66 ppm. IR (neat): ν = 3086, 2976,
˜
2932, 1585, 1448, 1357, 1171, 088, 585 cm–1. HRMS-EI (m/z) calcd.
Supporting Information (see footnote on the first page of this
article): Experimental procedures, characterization of new com-
pounds, and crystal structure data.
for (C18H17NO3S) 381.1399, found 381.1396.
N-Benzyl-N-(benzyloxy)benzenesulfonamide (2h): White solid;
72 % Yield; m.p. 121.5–122.4 °C. 1H NMR (400 MHz, CDCl3): δ = 7.97–
7.90 (m, 2 H), 7.70–7.62 (m, 1 H), 7.59–7.52 (m, 2 H), 7.40–7.32 (m,
5 H), 7.30–7.21 (m, 3 H), 7.05–7.97 (m, 2 H), 4.46 (s, 2 H), 4.05 (br., 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 134.83, 134.53, 133.94,
133.44, 130.09, 129.77, 129.76, 129.09, 128.69, 128.62, 128.47,
Note: The authors declare no competing financial interests.
Acknowledgments
We are grateful to the National Natural Science Foundation
of China (NSFC) (grant number 21372077), The Shenzhen
128.38, 80.31, 57.35 ppm. IR (neat): ν = 3422, 2896, 1452, 1356,
˜
1172, 739, 694, 603, 580 (·) cm–1. HRMS-EI (m/z) calcd. for
Science
and
Technology
Innovation
Committee
(C20H19NO3S) 353.1086, found 353.1087.
(JCYJ20151013162733704), and Fundamental Research Funds
for the Central Universities for financial support.
2-(Phenylsulfonyl)isoxazolidine (3a): White solid; 88 % Yield. 1H
NMR (400 MHz, CDCl3): δ = 8.02–7.95 (m, 2 H), 7.70–7.63 (m, 1 H),
7.60–7.52 (m, 2 H), 4.01 (td, J = 7.2, 1.9 Hz, 2 H), 3.74 (td, J = 7.3,
1.5 Hz, 2 H), 2.23 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
136.00, 134.05, 129.28, 129.16, 69.77, 47.30, 28.69 ppm. HRMS-EI
(m/z) calcd. for (C9H11NO3S) 341.0392, found 341.0391.
Keywords: Alcohols · Deoxyalkoxyamination ·
Sulfonamides · Synthesis design · Isoxazolidines
5-Phenyl-2-(phenylsulfonyl)isoxazolidine (3b): White solid; 47 %
Yield; m.p. 59.9–60.1 °C. 1H NMR (400 MHz, CDCl3): δ = 8.05–7.98
(m, 2 H), 7.69–7.62 (m, 1 H), 7.60–7.51 (m, 2 H), 7.38–7.27 (m, 5 H),
5.21 (t, J = 7.5 Hz, 1 H), 4.12 (ddd, J = 11.8, 8.1, 6.5 Hz, 1 H), 3.77
(ddd, J = 11.8, 8.6, 5.8 Hz, 1 H), 2.64 (dddd, J = 12.2, 8.1, 7.2, 5.8 Hz,
1 H), 2.23 (dddd, J = 12.2, 8.6, 7.8, 6.5 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 138.09, 135.81, 134.07, 129.42, 129.17, 128.74,
[1] O. Piloty, Ber. Dtsch. Chem. Ges. 1896, 29, 1559.
[2] R. G. Sherrill, E. S. Furfine, R. J. Hazen, J. F. Miller, D. J. Reynolds, D. M.
Sammond, A. Spaltenstein, P. Wheelan, L. L. Wright, Bioorg. Med. Chem.
Lett. 2005, 15, 3560.
[3] E. Nuti, A. R. Cantelmo, C. Gallo, A. Bruno, B. Bassani, C. Camodeca, T.
Tuccinardi, L. Vera, E. Orlandini, S. Nencetti, E. A. Stura, A. Martinelli, V.
Dive, A. Albini, A. Rossello, J. Med. Chem. 2015, 58, 7224.
[4] B. Martin, X. Lai, U. Baettig, E. Neumann, T. Kuhnle, D. Porter, R. Robinson,
J. Hatto, A.-M. D′Souza, O. Steward, S. Watson, N. J. Press, Org. Process
Res. Dev. 2015, 19, 1038.
[5] M. K. Christensen, K. D. Erichsen, U. H. Olesen, J. Tjornelund, P. Fristrup,
A. Thougaard, S. J. Nielsen, M. Sehested, P. B. Jensen, E. Loza, I. Kalvinsh,
A. Garten, W. Kiess, F. Bjorkling, J. Med. Chem. 2013, 56, 9071.
[6] K. M. Miranda, Coord. Chem. Rev. 2005, 249, 433.
128.71, 126.81, 82.98, 48.27, 36.87 ppm. IR (neat): ν = 3061, 2954,
˜
1446, 1360, 1162, 1017, 757, 688, 607, 566 (·) cm–1. HRMS-EI (m/z)
calcd. for (C15H15NO3S) 289.0773, found 289.0774.
5-Methyl-2-(phenylsulfonyl)isoxazolidine (3c): White solid; 79 %
Yield; m.p. 49.7–50.5 °C. 1H NMR (400 MHz, CDCl3): δ = 8.01–7.95
(m, 2 H), 7.69–7.63 (m, 1 H), 7.60–7.52 (m, 2 H), 4.37–4.25 (m, 1 H),
3.91 (ddd, J = 11.7, 8.1, 7.1 Hz, 1 H), 3.63 (ddd, J = 11.7, 8.7, 5.3 Hz,
[7] F. T. Bonner, Y. Ko, Inorg. Chem. 1992, 31, 2514.
Eur. J. Org. Chem. 0000, 0–0
www.eurjoc.org
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Full Paper
[8] a) M. J. Lee, D. W. Shoeman, D. J. Goon, H. T. Nagasawa, Nitric Oxide
2001, 5, 278; b) J. S. Stamler, D. J. Singel, J. Loscalzo, Science 1992, 258,
1898; c) T. T. Conway, E. G. DeMaster, M. J. C. Lee, H. T. Nagasawa, J. Med.
Chem. 1998, 41, 2903.
[9] A. Porcheddu, L. De Luca, G. Giacomelli, Synlett 2009, 2009, 2149.
[10] G.-L. Zhang, G. Ruecker, E. Breitmaier, M. Nieger, R. Mayer, C. Steinbeck,
Phytochemistry 1995, 40, 299.
[11] a) M. Tsuda, K. Hirano, T. Kubota, J. i. Kobayashi, Tetrahedron Lett. 1999,
40, 4819; b) H. Ishiyama, M. Tsuda, T. Endo, J. i. Kobayashi, Molecules
2005, 10, 312; c) K. Hirano, T. Kubota, M. Tsuda, Y. Mikami, J. i. Kobayashi,
Chem. Pharm. Bull. 2000, 48, 974.
[12] a) K. V. Gothelf, K. A. Jorgensen, Chem. Commun. 2000, 1449; b) K. M.
Partridge, M. E. Anzovino, T. P. Yoon, J. Am. Chem. Soc. 2008, 130, 2920;
c) D. H. Ess, G. O. Jones, K. N. Houk, Adv. Synth. Catal. 2006, 348, 2337;
d) L. M. Stanley, M. P. Sibi, Chem. Rev. 2008, 108, 2887.
[13] a) B. R. Rosen, J. E. Ney, J. P. Wolfe, J. Org. Chem. 2010, 75, 2756; b) G. S.
Lemen, N. C. Giampietro, M. B. Hay, J. P. Wolfe, J. Org. Chem. 2009, 74,
2533; c) R. W. Bates, K. Sa-Ei, Org. Lett. 2002, 4, 4225; d) P. Merino, T.
Tejero, V. Mannucci, G. Prestat, D. Madec, G. Poli, Synlett 2007, 944; e)
M. B. Hay, J. P. Wolfe, Angew. Chem. Int. Ed. 2007, 46, 6492; Angew. Chem.
2007, 119, 6612.
[14] S. D. Karyakarte, T. P. Smith, S. R. Chemler, J. Org. Chem. 2012, 77, 7755.
[15] a) R. W. Bates, Y. Lu, Org. Lett. 2010, 12, 3938; b) R. W. Bates, Y. Lu, J. Org.
Chem. 2009, 74, 9460.
[16] J. Cornil, A. Guerinot, S. Reymond, J. Cossy, J. Org. Chem. 2013, 78, 10273.
[17] K. Brink, R. Mattes, Chem. Ber. 1985, 118, 564.
[18] CCDC 1587902 (for 1n) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre.
[19] T. Kan, T. Fukuyama, Chem. Commun. 2004, 353.
[20] B. E. Haskell, S. B. Bowlus, J. Org. Chem. 1976, 41, 159.
[21] D. I. Weisblat, B. J. Magerlein, D. R. Myers, J. Am. Chem. Soc. 1953, 75,
3630.
[22] B. Nyasse, L. Grehn, U. Ragnarsson, Chem. Commun. 1997, 1017.
[23] a) M. J. Miller, Chem. Rev. 1989, 89, 1563; b) C. T. Behrendt, A. Kunfer-
mann, V. Illarionova, A. Matheeussen, M. K. Pein, T. Grawert, J. Kaiser, A.
Bacher, W. Eisenreich, B. Illarionov, M. Fischer, L. Maes, M. Groll, T. Kurz,
J. Med. Chem. 2011, 54, 6796; c) P.-P. Kung, R. Bharadwaj, A. S. Fraser,
D. R. Cook, A. M. Kawasaki, P. D. Cook, J. Org. Chem. 1998, 63, 1846; d)
H. Kohn, K. N. Sawhney, P. LeGall, D. W. Robertson, J. D. Leander, J. Med.
Chem. 1991, 34, 2444; e) S. H. Rosenberg, K. P. Spina, K. W. Woods, J.
Polakowski, D. L. Martin, Z. Yao, H. H. Stein, J. Cohen, J. L. Barlow, D. A.
Egan, K. A. Tricarico, W. R. Baker, H. D. Kleinert, J. Med. Chem. 1993, 36,
449; f) T. Maruyama, A. Tanaka, M. Oda, T. Suzuki, T. Oritani, Biosci. Bio-
technol. Biochem. 1993, 57, 803.
Received: April 2, 2018
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Deoxyalkoxyamination
Q.-A. Sun, Z.-H. Lu, X.-Q. Pu,
H.-L. Hu, J.-h. Zhang,*
X.-J. Yang* ............................................ 1–9
Deoxyalkoxyamination of Alcohols
for the Synthesis of N-Alkoxy-N-
alkylbenzenesulfonamides
A novel protocol for deoxyalkoxy- accessing a diverse range of N-alkoxy-
amination of alcohols was developed, N-alkylbenzenesulfonamides.
DOI: 10.1002/ejoc.201800526
Eur. J. Org. Chem. 0000, 0–0
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim