1-(N -acylamino)alkyl sulfones from N -acyl-α-amino acids or N -alkylamides

Article abstract of DOI:10.1021/jo500174a

A variety of N-(1-methoxyalkyl)amides or carbamates react readily with sodium aryl sulfinates in the presence of triphenylphosphonium tetrafluoroborate or bromide in CHCl₃ under mild conditions to give 1-(N-acylamino)alkyl sulfones in good yiel

Full text of DOI:10.1021/jo500174a

Note
pubs.acs.org/joc
1‑(N‑Acylamino)alkyl Sulfones from N‑Acyl-α-amino Acids or
N‑Alkylamides
Jakub Adamek,* Roman Mazurkiewicz, Agnieszka Pazdzierniok-Holewa, Mirosława Grymel, Anna Kuznik,
́
́
and Katarzyna Zielinska
́
Department of Organic Chemistry, Biochemistry and Biotechnology, Silesian University of Technology, B. Krzywoustego 4, 44-100
Gliwice, Poland
S
* Supporting Information
ABSTRACT: A variety of N-(1-methoxyalkyl)amides or carba-
mates react readily with sodium aryl sulfinates in the presence of
triphenylphosphonium tetrafluoroborate or bromide in CHCl3
under mild conditions to give 1-(N-acylamino)alkyl sulfones in
good yields. A combination of this reaction with the recently
described electrochemical decarboxylative α-methoxylation of N-
acyl-α-amino acids to give N-(1-methoxyalkyl)amides in the
presence of 3-(1-piperidino)propyl-functionalized silica gel
(SiO2−Pip) enables an effective two-pot transformation of N-acyl-α-amino acids to 1-(N-acylamino)alkyl sulfones. Alternatively,
N-(1-methoxyalkyl)amides can be obtained by electrochemical α-methoxylation of either N-alkylamides, lactams, or N-
alkylcarbamates.
α-Amidoalkylation of carbon and heteroatom nucleophiles
plays an important role in organic synthesis as a valuable
extension of the Mannich reaction that is employed, inter alia,
for the formation of a β-aminocarbonyl substructures and for
the construction of new carbocyclic or heterocyclic rings by
intramolecular α-amidoalkylation (e.g., Pictet−Spengler-type
cyclization) in the syntheses of natural products and in
pharmaceutical chemistry.1−6 In most α-amidoalkylation
reactions, highly reactive, short-lived N-acylimines or N-
acyliminium cations are considered to be the active
amidoalkylating intermediates. 1-(N-Acylamino)alkyl sulfones
3, usually 1-(N-alkoxycarbonylamino)alkyl aryl sulfones (R1 =
OAlk), have recently emerged as valuable amidoalkylating
reagents. 1-(N-Acylamino)alkyl sulfones are mostly stable,
crystalline compounds that are easy to isolate, purify, and store.
They easily eliminate the corresponding arylsulfinic acid under
basic conditions to generate reactive N-acylimines 4 (Scheme
1). Treatment of 1-(N-acylamino)alkyl sulfones with a Lewis
acid such as TiCl4 or SnCl4 enables the generation of highly
reactive N-acyliminium cations 5.3,7 Both N-acylimines and N-
acyliminium cations promptly react inter- or intramolecularly
with a variety of carbon and heteroatom nucleophiles as well as
with reducing agents.3 The usefulness of this reaction has been
recognized only recently. The synthesis and reactivity of these
compounds has been reviewed comprehensively by Petrini.3
The most frequently used method for the synthesis of 1-(N-
acylamino)alkyl sulfones 3, pioneered by Engberts and Strating
in 1964, consists of three-component condensation of primary
amides, carbamates, or carbamides (1, R1 = R, OR, or NHR,
respectively) with aldehydes 2 and sodium sulfinates (Scheme
1).8−11 O- or S-Thiocarbamates, dithiocarbamates, or thio-
carbamides have also been applied in a similar reaction.12,13
Other methods for synthesizing these compounds, such as
oxidation of the corresponding sulfides with H2O2, KMnO4, or
mCPBA,14−16 the Curtius-type rearrangement of α-sulfonylacyl
azides,17 and substitution of the chlorine anion in N-(1-
chloroalkyl)amides with p-toluenesulfinic acid,18 have found
only limited application.3 The structural diversity of 1-(N-
acylamino)alkyl sulfones synthesized using the Engberts and
Strating method is confined by the limited availability of
structurally diverse aldehydes 2. The structural diversity of
amide component 1 as well as of the sodium aryl sulfinate is of
less importance.
In this contribution, we report a new, effective, one-pot
condensation of N-(1-methoxyalkyl)amides or carbamates (8,
R1 = R or OR, respectively) with sodium aryl sulfinates in the
presence of triphenylphosphonium tetrafluoroborate or bro-
mide to give the corresponding 1-(N-acylamino)alkyl sulfones
3 (Scheme 2). Recently, we described an efficient method for
electrochemical decarboxylative α-methoxylation of N-acyl-α-
amino acids 6 in the presence of 3-(1-piperidino)propyl-
functionalized silica gel (SiO2−Pip) to give N-(1-
methoxyalkyl)amides 8.19 A combination of these two reactions
enables a convenient two-pot transformation of N-acyl-α-amino
acids 6 to 1-(N-acylamino)alkyl sulfones 3. The possibility of
employing a large range of natural α-amino acids (both
proteinogenic and nonproteinogenic) as well as an unlimited
number of unnatural α-amino acids in this synthesis potentially
provides easy access to a wide variety of structurally diverse 1-
(N-acylamino)alkyl sulfones, which significantly widens the
Received: January 24, 2014
Published: February 27, 2014
© 2014 American Chemical Society
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The Journal of Organic Chemistry
Note
Scheme 1. Synthesis and Reactivity of 1-(N-Acylamino)alkyl Sulfones 3
a
Scheme 2. Transformation of N-Acyl-α-amino Acids 6 or N-Alkylamides 7 into 1-(N-Acylamino)alkyl Sulfones 3
a
Reagents and conditions: (i) MeOH, SiO2−Pip, −2e, 10 °C;19 (ii) MeOH, Et4N+TsO−, −2e, 10 °C.
Table 1. Synthesis of 1-(N-Acylamino)alkyl Sulfones: Reaction Conditions and Yields
reaction product
N-(1-Methoxyalkyl)amide
yield (%)
entry
8
R1
R2
procedure
t (h)
X
3
Ar
based on 8
based on 6 or 7
1
2
8a
8a
8a
8a
8b
8b
8c
8d
8e
8f
t-Bu
t-Bu
t-Bu
t-Bu
Me
Me
Me
Me
Me
Me
Me
Me
A
A
A
A
A
B
A
A
A
A
A
A
A
A
A
A
B
A
B
B
A
A
A
A
2
72
4
BF4
Br
3a
3a
3b
3b
3c
3c
3d
3e
3f
p-Tol
p-Tol
Ph
90
76
82
87
91
91
82
75
77
90
78
75
76
69
79
75
75
90
90
82
91
87
74
80
84
85
50
80
74
75
83
73
69
70
63
73
73
61
87
73
66
86
3
BF4
Br
4
66
2
Ph
5
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
Br
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
Ph
6
Me
2
7
Ph
2
8
BnO
BnO
t-BuO
BnO
BnO
BnO
BnO
BnO
Ph
2
9
i-Pr
2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
i-Pr
2
3g
3h
3i
8g
8h
8h
8h
8i
i-Bu
3
p-Tol
p-Tol
Ph
Bn
2
Bn
3
3j
Bn
66
2
3j
Ph
a
CH2CONH2
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
BF4
3k
3l
p-Tol
p-Tol
p-Tol
Ph
8j
(CH2)2
2
8j
(CH2)2
(CH2)2
(CH2)2
(CH2)4
2
3l
8j
2
3m
3m
3n
3o
3p
3q
3r
8j
2
Ph
8k
8l
2
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
BnO
BnO
BnO
BnO
CH2O-t-Bu
2
b
b
8m
8n
8o
CH2CO2-t-Bu
2
65
62
(CH2)2CO2-t-Bu
2
83
81
p-CH2C6H4OBn
2
76
61
a
b
The reaction was carried out in acetonitrile. The yield was estimated from the 1H NMR spectrum of the crude product, which also contained the
corresponding (E)-enamide 10p (23% yield based on 8). Attempts to isolate the product 3p failed.
scope of possible synthetic applications of these important α-
amidoalkylating agents.
The syntheses of N-(1-methoxyalkyl)amides by electro-
chemical decarboxylative α-methoxylation of N-acyl-α-amino
acids in the presence of SiO2−Pip were performed in MeOH at
10 °C in the presence of a substoichiometric amount of SiO2−
Pip (0.075 mol of piperidine per mole of substrate) at a current
density of 0.3 A/dm2 and a charge consumption of 3.5−3.75 F/
mol (procedure A), as we recently described.19 The crude
products were obtained in very good to excellent yields.
Alternatively, N-(1-methoxyalkyl)amides 8 can also be
obtained by electrochemical α-methoxylation of N-alkylamides
or lactams or N-alkylcarbamates (7, R1 = R, OR),20−23 which
additionally extends the structural diversity of 1-(N-acylamino)-
alkyl sulfones 3 that can be synthesized in this way.
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Note
Alternatively, a few N-(1-methoxyalkyl)amides were synthe-
sized by electrochemical α-methoxylation of N-alkylamides or
lactams in MeOH at 10 °C in the presence of tetraethylammo-
nium p-toluenesulfonate (Et4N+OTs−) in good to very good
yields (procedure B).
the reaction was much slower in that case (cf. Table 1, entries 2,
4, and 14). It seems that the bromide anion, in contrast to the
non-nucleophilic tetrafluorobrate anion, is able to recombine
with the intermediate N-acylimine or N-acyliminium cation to
form the less reactive N-(1-bromoalkyl)amide.
As we have already reported,19,24 the dissolution of N-(1-
methoxyalkyl)amides 8 in CHCl3 and the addition of
triphenyphosphonium tetrafluoroborate at 20 °C causes the
complete disappearance of 8 and the formation of methanol
and the corresponding 1-(N-acylamino)alkyltriphenylphos-
phonium salt 9 in a few minutes in very good yield. Recently,
we also demonstrated that 1-(N-acylamino)alkyltriphenylphos-
phonium salts under basic conditions display strong α-
amidoalkylating properties toward a variety of N, O, S, P, and
C nucleophiles.25−27 Now we state that the addition of sodium
sulfinate to crude 1-(N-acylamino)alkyltriphenylphosphonium
salt 9a, obtained in situ from N-(1-methoxyalkyl)amide 8a and
triphenyphosphonium tetrafluoroborate, after 2 h at 20 °C gave
an equilibrium mixture containing, apart from the expected 1-
(N-acylamino)alkyl sulfone 3a (35%), also the starting N-(1-
methoxyalkyl)amide 8a (41%). The latter compound was
evidently formed by the reverse substitution of the
triphenylphosphonium group in phosphonium salt 9a with
methanol under basic conditions. We previously observed and
reported a similar reverse substitution of the triphenylphos-
phonium group in phosphonium salts 9 with methanol under
In conclusion, a new, effective, one-pot condensation of N-
(1-methoxyalkyl)amides or carbamates (8, R1 = R or OR,
respectively) with sodium aryl sulfinates in the presence of
triphenylphosphonium tetrafluoroborate or bromide to give 1-
(N-acylamino)alkyl sulfones 3 has been developed. A
combination of this reaction with the recently described
efficient electrochemical decarboxylative α-methoxylation of
N-acyl-α-amino acids 6 to N-(1-methoxyalkyl)amides 819
enables a convenient two-pot transformation of N-acyl-α-
amino acids 6 to 1-(N-acylamino)alkyl sulfones 3. It has also
been demonstrated that, alternatively, N-(1-methoxyalkyl)-
amides 8 can be obtained by electrochemical α-methoxylation
of either N-alkylamides or lactams 7. The developed trans-
formation of N-(1-methoxyalkyl)amides or carbamates 8
provides easy access to a wide variety of structurally diverse
1-(N-acylamino)alkyl sulfones 3 that would be difficult to
obtain using the classical Engberts and Strating method and
therefore significantly widens the scope of possible synthetic
applications of these important α-amidoalkylating agents.
EXPERIMENTAL SECTION
■
the influence of Hunig’s base [Et(i-Pr) N)].24 In order to
̈
2
General Methods. Melting points were determined in capillaries
achieve full conversion of N-(1-methoxyalkyl)amides 8 to 1-(N-
acylamino)alkyl sulfones 3, evaporation of methanol with
chloroform under reduced pressure prior to repeated
dissolution of the residue in chloroform and the addition of
sodium sulfinate was proved necessary. The 1-(N-acylamino)-
alkyl sulfones 3 obtained in this manner were easily isolated and
purified by evaporation of the chloroform and crystallization of
the sulfone from ethyl acetate, acetonitrile, or toluene, with the
exception of compound 3p, which was obtained in a mixture
with the corresponding enamide 10p (Table 1).
and are uncorrected. IR spectra were measured on an FT-IR
1
spectrophotometer (ATR method). H and 13C NMR spectra were
recorded at operating frequencies of 600 or 400 and 150 or 100 MHz,
respectively, using TMS as the resonance shift standard. All chemical
shifts (δ) are reported in parts per million, and coupling constants (J)
are reported in hertz.
Decarboxylative α-Methoxylation of N-Acyl-α-amino Acids to N-
(1-Methoxyalkyl)amides 8 (Procedure A).19 To an undivided
cylindrical glass electrolyzer (85 cm3) with a thermostatic jacket and
equipped with a magnetic stirrer along with a cylindrical Pt mesh
anode (47 cm2) and a similar cathode (44 cm2), arranged
concentrically to one another at a distance of 2.5
0.5 mm, were
By using this method, we were able to obtain a variety of 1-
(N-acylamino)alkyl sulfones 3 in good to very good yields
based on N-acyl-α-amino acids 6 (procedure A) or in satisfying
yields based on N-alkylamides or lactams 7 (procedure B).
Only in the case of compound 3p was a mixture of the expected
product (65%) and the corresponding (E)-enamide 10p (23%)
obtained.28 Attempts to isolate pure product 3p from the
mixture by crystallization or by column chromatography failed.
The special tendency for the formation of enamide 10p in this
particular case can be explained as a result of the especially
effective push−pull resonance stabilization of the enamide with
the participation of the electron-donating acylamine group and
the electron-withdrawing tert-butoxycarbonyl group (the
captodative effect) (Figure 1).
added methanol (30 cm3), N-acyl-α-amino acid 6 (3.0 mmol), and
SiO2−Pip (200 mg, 0.22 mmol). The electrolysis was carried out with
stirring at a current density of 0.3 A/dm2 at 10 °C until a charge of
2.4−3.75 F/mol had passed. SiO2−Pip was filtered off, and methanol
was evaporated under reduced pressure to obtain N-(1-methoxyalkyl)-
amide 8.
Electrochemical α-Methoxylation of N-Alkylamides and Lactams
(Procedure B). To an undivided cylindrical glass electrolyzer (85 cm3)
with a thermostatic jacket and equipped with a magnetic stirrer along
with a cylindrical Pt mesh anode (47 cm2) and a similar cathode (44
cm2), arranged concentrically to one another at a distance of 2.5 0.5
mm, were added methanol (40 cm3), N-alkylamide or lactam 7 (8.0
mmol) and Et4N+OTs− (40.7 mg, 0.135 mmol). The electrolysis was
carried out with stirring at a current density of 1.0 A/dm2 at 10 °C
until a charge of 9.0, 5.0, or 5.5 F/mol had passed for compound 8b,
8j, or 8k, respectively. The solvent was evaporated under reduced
pressure, and the product was isolated by column chromatography
(CH2Cl2/MeOH, 9:1 with 2% Et3N). The crystalline crude
compounds 8j and 8k were recrystallized from toluene.
Reaction of N-(1-Methoxyethyl)pivaloylamide (8a) with Sodium
p-Toluenesulfinate. To a solution of N-(1-methoxyethyl)-
pivaloylamide 8a (159.2 mg, 1 mmol) in deuterated chloroform (2
cm3) was added sodium p-toluenesulfinate (178.2 mg, 1 mmol). After
2 h the reaction mixture did not contain any traces of the expected
sulfone (1H NMR).
It is worth noting that the transformation of N-(1-
methoxyalkyl)amides to 1-(N-acylamino)alkyl sulfones can
also be carried out by using triphenylphosphonium bromide
instead of triphenylphosphonium tetrafluoroborate. However,
General Procedure for the Transformation of N-(1-
Methoxyalkyl)amides 8 to 1-(N-Acylamino)alkyl Sulfones 3. To a
solution of N-(1-methoxyalkyl)amide 8 (1 mmol) in chloroform (2
Figure 1. Resonance structures of (E)-enamide 10p.
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Note
cm3) was added triphenylphosphonium tetrafluoroborate or bromide
(1 mmol). After a homogeneous solution was obtained, the solvent
was evaporated to dryness. The residue was again dissolved in
chloroform (2 cm3), and sodium sulfinate (1 mmol) was added. After
the mixture was stirred for the time given in Table 1 at 20 °C, sodium
tetrafluoroborate or sodium bromide was filtered off, and the solvent
was evaporated under reduced pressure. The crude product was
recrystallized from toluene (3a−d, 3f, 3h−r), acetonitrile (3e), or
ethyl acetate (3g).
7.64 (m, 2H), 7.63−7.58 (m, 2H), 7.45−7.29 (m, 8H), 7.25−7.19 (m,
2H), 6.03 (d, J = 10.4 Hz, 1H), 4.92 (d, J = 12.8 Hz, 1H), 4.86 (d, J =
12.8 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 155.2,
144.5, 136.7, 133.7, 130.4, 129.6, 129.5, 129.3, 129.1, 128.3, 128.1,
127.9, 127.6, 74.9, 66.0, 21.1; IR (ATR) 3367, 2972, 1698, 1509, 1317,
1304, 1148, 1085, 1039, 702 cm−1.
Benzyl N-[2-Methyl-1-(p-toluenesulfonyl)propyl]carbamate
(3f).32 Colorless crystals (278.4 mg, 77% yield), mp 95.5−98.0 °C.
1H NMR (400 MHz, CDCl3) δ 7.77−7.67 (m, 2H), 7.41−7.27 (m,
The analytical and spectral data for N-(1-methoxyalkyl)amides 8a,
8b, 8d−i, and 8l−o were reported in our previous paper.19
N-(1-Methoxyethyl)benzamide (8c).29 Pale-yellow crystals
5H), 7.24−7.18 (m, 2H), 5.35 (d, J = 10.8 Hz, 1H), 4.93 (d, J = 12.0
Hz, 1H), 4.86 (d, J = 12.0 Hz, 1H), 4.74 (dd, J = 11.0, 3.0 Hz, 1H),
2.82−2.72 (m, 1H), 2.40 (s, 3H), 1.13 (d, J = 6.8 Hz, 3H), 1.08 (d, J =
6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 155.2, 144.8, 135.7,
133.8, 129.7, 128.8, 128.5, 128.4, 128.1, 74.8, 64.7, 26.9, 21.7, 20.7,
16.8; IR (ATR) 3320, 2959, 1722, 1527, 1283, 1230, 1138, 1081, 742
cm−1.
1
(procedure A, 526.8 mg, 98% yield), mp 86.0−88.0 °C. H NMR
(400 MHz, CDCl3) δ 7.83−7.77 (m, 2H), 7.56−7.50 (m, 1H), 7.48−
7.43 (m, 2H), 6.30 (d, J = 8.4 Hz, 1H), 5.51 (dq, J = 9.6, 5.9 Hz, 1H),
3.41 (s, 3H), 1.45 (d, J = 6.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
167.2, 134.0, 131.8, 128.6, 127.0, 78.3, 55.8, 21.7; IR (ATR) 3310,
1647, 1530, 1337, 1284, 1134, 1082 cm−1.
tert-Butyl N-[2-Methyl-1-(phenylsulfonyl)propyl]carbamate
(3g).33 Colorless crystals (282.1 mg, 90% yield), mp 115.5−116.5
5-Methoxypyrrolidin-2-one (8j).23 Colorless crystals (procedure
A, 334.9 mg, 97% yield; procedure B, 745.8 mg, 81% yield), mp 59.0−
60.0 °C. 1H NMR (400 MHz, CDCl3) δ 7.87 (br s, 1H), 4.89 (ddd, J
= 6.4, 1.4, 1.4 Hz, 1H), 3.32 (s, 3H), 2.57−2.46 (m, 1H), 2.35−2.19
(m, 2H), 2.12−2.02 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 179.5,
87.1, 54.4, 28.3, 27.9; IR (ATR) 3178, 1671, 1283, 1251, 1098, 1056,
1043, 995, 796, 761 cm−1.
°C. H NMR (400 MHz, CDCl3) δ 7.94−7.85 (m, 2H), 7.69−7.48
1
(m, 3H), 5.13 (d, J = 11.2 Hz, 1H), 4.74 (dd, J = 11.2, 3.6 Hz, 1H),
2.84−2.73 (m, 1H), 1.23 (s, 9H), 1.14 (d, J = 6.8 Hz, 3H), 1.08 (d, J =
6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.1, 138.1, 133.7,
129.0, 128.9, 80.7, 74.3, 28.0, 26.7, 20.7, 16.9; IR (ATR) 3348, 2969,
1712, 1510, 1307, 1238, 1162, 1139, 1083, 686 cm−1.
Benzyl N-[3-Methyl-1-(p-toluenesulfonyl)butyl]carbamate
(3h). Colorless crystals (292.9 mg, 78% yield), mp 129.0−130.0 °C.
1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 3.2 Hz, 2H), 7.38−7.32
2-Methoxy-ε-caprolactam (8k).23 Colorless crystals (procedure
1
B, 916.5 mg, 80% yield), mp 62.0−63.0 °C. H NMR (400 MHz,
CDCl3) δ 6.52 (br s, 1H), 4.31 (ddd, J = 5.6, 5.6, 2.0 Hz, 1H), 3.36 (s,
3H), 2.67−2.59 (m, 1H), 2.46−2.39 (m, 1H), 2.15−2.05 (m, 1H),
2.03−1.89 (m, 1H), 1.86−1.65 (m, 3H), 1.62−1.49 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 178.5, 83.6, 55.3, 37.3, 34.2, 23.7, 23.2; IR
(ATR) 3197, 2934, 2918, 1663, 1625, 1433, 1356, 1079, 1068, 719
cm−1.
(m, 2H), 7.25−7.19 (m, 5H), 5.11 (d, J = 10.8 Hz, 1H), 4.91 (ddd, J =
11.2, 11.1, 2.9 Hz, 1H), 4.91 (d, J = 12.0 Hz, 1H), 4.85 (d, J = 12.4 Hz,
1H), 2.41 (s, 3H), 2.06−1.96 (m, 1H), 1.81−1.66 (m, 2H), 0.99 (d, J
= 6.4 Hz, 3H), 0.93 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 154.7, 145.0, 135.7, 133.6, 129.7, 129.2, 128.5, 128.3, 128.1, 70.1,
67.3, 34.9, 24.7, 23.3, 21.7, 21.1; IR (ATR) 3271, 2959, 1692, 1538,
1316, 1290, 1268, 1243, 1145, 1039, 752, 700 cm−1; HRMS (TOF-
ESI) calcd for C20H25NO4SNa [M + Na]+ 398.1402, found 398.1393.
Benzyl N-[2-Phenyl-1-(p-toluenesulfonyl)ethyl]carbamate
(3i).32 Colorless crystals (307.1 mg, 75% yield), mp 136.0−137.0
N-[1-(p-Toluenesulfonyl)ethyl]pivaloylamide (3a). Colorless
crystals (255.1 mg, 90% yield or 215.4 mg, 76% yield; see Table 1),
1
mp 146.5−147.5 °C. H NMR (400 MHz, CDCl3) δ 7.79−7.75 (m,
2H), 7.33 (d, J = 8.0 Hz, 2H), 5.96 (d, J = 10.0 Hz, 1H), 5.41 (dq, J =
10.2, 7.0 Hz, 1H), 2.42 (s, 3H), 1.62 (d, J = 7.0 Hz, 3H), 1.01 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 176.9, 145.1, 133.6, 129.7, 129.2, 64.3,
38.7, 27.2, 21.7, 13.2; IR (ATR) 3371, 2973, 1677, 1516, 1308, 1287,
1136, 1083, 1017, 724 cm−1; HRMS (TOF-ESI) calcd for
C14H21NO3SNa [M + Na]+ 306.1140, found 306.1142.
1
°C. H NMR (400 MHz, CDCl3) δ 7.80−7.74 (m, 2H), 7.33−7.17
(m, 10H), 7.12−7.05 (m, 2H), 5.31 (d, J = 10.8 Hz, 1H), 5.14 (ddd, J
= 11.0, 11.0, 3.5 Hz, 1H), 4.79 (d, J = 12.4 Hz, 1H), 4.74 (d, J = 12.4
Hz, 1H), 3.63 (dd, J = 14.6, 3.4 Hz, 1H), 3.01 (dd, J = 14.6, 11.0 Hz,
1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.6, 145.1,
135.7, 134.6, 133.4, 129.8, 129.3, 129.2, 128.7, 128.4, 128.2, 127.8,
127.2, 71.8, 67.1, 32.8, 21.7; IR (ATR) 3276, 2932, 1695, 1549, 1446,
1309, 1264, 1129, 1081, 1044, 754 cm−1.
Benzyl N-[2-Phenyl-1-(phenylsulfonyl)ethyl]carbamate
(3j).34 Colorless crystals (300.6 mg, 76% yield or 272.9 mg, 69%
yield; see Table 1), mp 118.5−119.5 °C. 1H NMR (400 MHz, CDCl3)
δ 7.93−7.87 (m, 2H), 7.63−7.56 (m, 1H), 7.48−7.40 (m, 2H), 7.33−
7.17 (m, 8H), 7.11−7.04 (m, 2H), 5.25 (d, J = 10.8 Hz, 1H), 5.17
(ddd, J = 10.8, 10.8, 3.2 Hz, 1H), 4.76 (d, J = 12.0 Hz, 1H), 4.72 (d, J
= 12.4 Hz, 1H), 3.65 (dd, J = 14.6, 3.4 Hz, 1H), 3.02 (dd, J = 14.8,
10.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 154.5, 136.5, 135.6,
134.5, 134.1, 129.3, 129.2, 129.1, 128.8, 128.5, 128.3, 128.0, 127.3,
71.8, 67.2, 32.6; IR (ATR) 3339, 1732, 1518, 1315, 1298, 1230, 1146,
1135, 1079, 1038, 995, 740, 684 cm−1.
N-[1-(Phenylsulfonyl)ethyl]pivaloylamide (3b). Colorless crys-
tals (220.9 mg, 82% yield or 234.4 mg, 87% yield; see Table 1), mp
145.5−147.0 °C. 1H NMR (400 MHz, CDCl3) δ 7.93−7.88 (m, 2H),
7.67−7.61 (m, 1H), 7.57−7.51 (m, 2H), 5.96 (d, J = 9.6 Hz, 1H), 5.45
(dq, J = 10.2, 7.0 Hz, 1H), 1.64 (d, J = 7.0 Hz, 3H), 0.99 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 176.9, 136.6, 134.0, 129.1, 129.0, 64.3,
38.7, 27.2, 13.1; IR (ATR) 3362, 2975, 1677, 1510, 1316, 1291, 1259,
1147, 1135, 1083, 732 cm−1; HRMS (TOF-ESI) calcd for
C13H19NO3SNa [M + Na]+ 292.0983, found 292.0983.
N-[1-(p-Toluenesulfonyl)ethyl]acetamide (3c). Colorless crys-
tals (219.6 mg, 91% yield), mp 125.0−126.5 °C. 1H NMR (400 MHz,
CDCl3) δ 7.79−7.75 (m, 2H), 7.37−7.32 (m, 2H), 6.10 (d, J = 10.0
Hz, 1H), 5.35 (dq, J = 10.4, 7.0 Hz, 1H), 2.44 (s, 3H), 1.84 (s, 3H),
1.60 (d, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 168.7, 145.3,
133.4, 129.8, 129.1, 64.8, 22.8, 21.7, 13.3; IR (ATR) 3346, 1690, 1522,
1304, 1286, 1247, 1135, 1084, 728 cm−1; HRMS (TOF-ESI) calcd for
C11H15NO3SNa [M + Na]+ 264.0670, found 264.0670.
Benzyl N-[2-Carbamoyl-1-(p-toluenesulfonyl)ethyl]-
carbamate (3k). Colorless crystals (297.4 mg, 79% yield), mp
1
126.0−127.0 °C. H NMR (400 MHz, DMSO-d6) δ 8.34 (d, J = 9.6
N-[1-(p-Toluenesulfonyl)ethyl]benzamide (3d).30 Colorless
Hz, 1H), 7.70−7.64 (m, 2H), 7.46 (br s, 1H), 7.41−7.29 (m, 5H),
7.23−7.17 (m, 2H), 7.03 (br s, 1H), 5.20 (ddd, J = 9.8, 9.8, 3.1 Hz,
1H), 4.89 (d, J = 12.4 Hz, 1H), 4.82 (d, J = 12.8 Hz, 1H), 2.78 (dd, J =
15.6, 3.2 Hz, 1H), 2.52 (dd, J = 15.6, 10.4 Hz, 1H), 2.40 (s, 3H); 13C
NMR (100 MHz, DMSO-d6) δ 168.9, 154.9, 144.6, 136.4, 133.5,
129.6, 129.0, 128.3, 127.8, 127.6, 69.4, 65.7, 32.7, 21.1; IR (ATR)
3431, 3322, 1688, 1667, 1539, 1305, 1256, 1143, 1084, 1050, 695
cm−1; HRMS (TOF-ESI) calcd for C18H20N2O5SNa [M + Na]+
399.0991, found 399.0995.
1
crystals (248.8 mg, 82% yield), mp 126.0−127.5 °C. H NMR (400
MHz, CDCl3) δ 7.80−7.75 (m, 2H), 7.64−7.58 (m, 2H), 7.54−7.48
(m, 1H), 7.43−7.37 (m, 2H), 7.29−7.23 (m, 2H), 6.67 (d, J = 10.0
Hz, 1H), 5.57 (dq, J = 10.2, 7.0 Hz, 1H), 2.39 (s, 3H), 1.72 (d, J = 6.8
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.1, 145.2, 133.4, 132.9,
132.2, 129.8, 129.1, 128.7, 127.0, 65.3, 21.7, 13.3; IR (ATR) 3257,
1645, 1523, 1321, 1311, 1293, 1141, 1129, 1084, 697 cm−1.
Benzyl N-[1-Phenyl-1-(p-toluenesulfonyl)methyl]carbamate
(3e).31 Colorless crystals (296.6 mg, 75% yield), mp 158.5−159.5 °C.
1H NMR (400 MHz, DMSO-d6) δ 9.11 (d, J = 10.8 Hz, 1H), 7.71−
5-(p-Toluenesulfonyl)pyrrolidin-2-one (3l). Colorless crystals
1
(179.5 mg, 75% yield), mp 149.0−150.0 °C. H NMR (400 MHz,
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Note
1
CDCl3) δ 7.82−7.78 (m, 2H), 7.41 (d, J = 8.0 Hz, 2H), 6.63 (br s,
1H), 4.65 (ddd, J = 8.4, 1.6, 1.6 Hz, 1H), 2.59−2.40 (m, 2H), 2.47 (s,
3H), 2.15 (ddd, J = 17.6, 10.0, 2.8 Hz, 1H), 1.98 (ddd, J = 17.6, 9.9,
9.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 177.7, 146.1, 131.6,
130.4, 129.6, 74.3, 27.8, 21.8, 21.7; IR (ATR) 3344, 2923, 1700, 1412,
1286, 1231, 1130, 1083, 719 cm−1; HRMS (TOF-ESI) calcd for
C11H13NO3SNa [M + Na]+ 262.0514, found 262.0511.
°C. H NMR (400 MHz, CDCl3) δ 7.70 (dd, J = 13.6, 12.0 Hz, 1H),
7.38−7.33 (m, 5H), 7.10 (d, J = 12.0 Hz, 1H), 5.28 (d, J = 14.0 Hz,
1H), 5.19 (s, 2H), 1.47 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
166.4, 152.7, 138.1, 135.2, 128.7, 128.7, 128.4, 102.3, 80.1, 68.1, 28.3;
IR (ATR) 3300, 2971, 1740, 1685, 1632, 1321, 1266, 1222, 1139, 993,
975, 851 cm−1.
5-(Phenylsulfonyl)pyrrolidin-2-one (3m).35 Colorless crystals
ASSOCIATED CONTENT
1
■
(202.8 mg, 90% yield), mp 138.0−140.0 °C. H NMR (400 MHz,
S
* Supporting Information
CDCl3) δ 7.96−7.91 (m, 2H), 7.77−7.71 (m, 1H), 7.66−7.60 (m,
2H), 6.31 (br s, 1H), 4.67 (ddd, J = 8.4, 1.6, 1.6 Hz, 1H), 2.62−2.42
(m, 2H), 2.17 (ddd, J = 17.6, 10.0, 2.8 Hz, 1H), 2.06−1.95 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 177.4, 134.8, 134.7, 129.8, 129.6, 74.2,
27.7, 21.8; IR (ATR) 3219, 1685, 1446, 1308, 1187, 1146, 1084, 716
cm−1.
1H and 13C NMR spectra and IR spectra of all new 1-(N-
acylamino)alkyl sulfones 3. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
2-(p-Toluenesulfonyl)-ε-caprolactam (3n). Colorless crystals
1
Corresponding Author
(219.2 mg, 82% yield), mp 124.5−126.0 °C. H NMR (400 MHz,
CDCl3) δ 7.80−7.76 (m, 2H), 7.40−7.37 (m, 2H), 6.10 (d, J = 4.0 Hz,
1H), 4.33 (ddd, J = 5.2, 4.2, 2.6 Hz, 1H), 2.77−2.71 (m, 1H), 2.46 (s,
3H), 2.43−2.35 (m, 1H), 2.32−2.26 (m, 1H), 2.20−2.12 (m, 2H),
1.78−1.69 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 176.8, 145.7,
133.4, 130.2, 129.1, 73.3, 35.9, 27.2, 25.6, 22.4, 21.7; IR (ATR) 3200,
3072, 2935, 1671, 1311, 1291, 1143, 1080 cm−1; HRMS (TOF-ESI)
calcd for C13H17NO3SNa [M + Na]+ 290.0827, found 290.0821.
Benzyl N-[2-tert-Butoxy-1-(p-toluenesulfonyl)ethyl]-
carbamate (3o). Colorless crystals (369.0 mg, 91% yield), mp
*Fax: (+48) 032-237-2094. E-mail: jakub.adamek@polsl.pl.
Notes
The authors declare no competing financial interest.
REFERENCES
■
(1) Katritzky, A. R.; Lan, X.; Yang, J. Z.; Denisko, O. V. Chem. Rev.
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1
93.5−95.0 °C. H NMR (400 MHz, CDCl3) δ 7.76−7.70 (m, 2H),
7.39−7.26 (m, 5H), 7.25−7.21 (m, 2H), 5.67 (d, J = 10.4 Hz, 1H),
5.03 (d, J = 12.4 Hz, 1H), 5.02−4.96 (m, 1H), 4.96 (d, J = 12.0 Hz,
1H), 4.08 (dd, J = 10.4, 3.2 Hz, 1H), 3.75 (dd, J = 10.4, 4.0 Hz, 1H),
2.41 (s, 3H), 1.14 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 154.9,
144.8, 135.8, 134.7, 129.5, 129.3, 128.4, 128.3, 128.2, 74.3, 71.4, 67.4,
58.1, 27.2, 21.7; IR (ATR) 3326, 2973, 1725, 1533, 1230, 1138, 1079,
1045, 744 cm−1; HRMS (TOF-ESI) calcd for C21H27NO5SNa [M +
Na]+ 428.1508, found 428.1513.
́
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Zielinska, K. Adv. Heterocycl. Chem. 2014, 111, 43−94.
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1
(7) Ollevier, T.; Li, Z. Org. Biomol. Chem. 2006, 4, 4440−4443.
(8) Engberts, J. B. F. N.; Strating, J. Recl. Trav. Chim. Pays-Bas 1964,
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ethyl]carbamate (3p). H NMR (600 MHz, CDCl3) δ 7.75 (d, J
= 8.4 Hz, 2H), 7.34−7.28 (m, 3H), 7.25−7.18 (m, 4H), 5.87 (d, J =
10.2 Hz, 1H), 5.28−5.24 (m, 1H), 4.92 (d, J = 12.6 Hz, 1H), 4.88 (d, J
= 12.0 Hz, 1H), 3.07 (dd, J = 15.9, 4.5 Hz, 1H), 2.76 (dd, J = 15.9, 8.7
Hz, 1H), 2.41 (s, 3H), 1.41 (s, 9H); 13C NMR (150.5 MHz, CDCl3) δ
167.8, 154.4, 145.3, 135.7, 133.1, 129.8, 129.3, 128.5, 128.3, 128.1,
82.4, 68.4, 67.3, 33.4, 27.9, 21.7; HRMS (TOF-ESI) calcd for
C22H27NO6SNa [M + Na]+ 456.1457, found 456.1451.
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Benzyl N-[3-tert-Butoxycarbonyl-1-(p-toluenesulfonyl)-
(12) Engberts, J. B. F. N.; Olijnsma, T.; Strating, J. Recl. Trav. Chim.
Pays-Bas 1966, 85, 1211−1222.
propyl]carbamate (3q). Colorless crystals (371.4 mg, 83% yield),
1
mp 136.0−137.0 °C. H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.4
(13) Meijer, H.; Tel, R. M.; Strating, J.; Engberts, J. B. F. N. Recl.
Trav. Chim. Pays-Bas 1973, 92, 72−82.
Hz, 2H), 7.38−7.29 (m, 3H), 7.28−7.17 (m, 4H), 5.36 (d, J = 10.8
Hz, 1H), 4.95−4.87 (m, 1H), 4.92 (d, J = 12.4 Hz, 1H), 4.86 (d, J =
12.0 Hz, 1H), 2.55−2.46 (m, 1H), 2.45−2.32 (m, 2H), 2.41 (s, 3H),
2.15−2.01 (m, 1H), 1.41 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
171.3, 154.9, 145.1, 135.6, 133.5, 129.7, 129.2, 128.5, 128.3, 128.0,
81.2, 70.8, 67.3, 31.2, 28.0, 22.2, 21.7; IR (ATR) 3326, 1728, 1716,
1531, 1258, 1229, 1141, 1053, 742 cm−1; HRMS (TOF-ESI) calcd for
C23H29NO6SNa [M + Na]+ 470.1613, found 470.1620.
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Benzyl N-[2-(4-Benzyloxyphenyl)-1-(p-toluenesulfonyl)-
(19) Mazurkiewicz, R.; Adamek, J.; Pazdzierniok-Holewa, A.;
́
ethyl]carbamate (3r). Colorless crystals (391.9 mg, 76% yield),
1
́
Zielinska, K.; Simka, W.; Gajos, A.; Szymura, K. J. Org. Chem. 2012,
mp 148.0−149.0 °C. H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4
77, 1952−1960.
Hz, 2H), 7.44−7.27 (m, 8H), 7.25−7.19 (m, 2H), 7.14−7.07 (m, 4H),
6.92−6.84 (m, 2H), 5.22 (d, J = 10.8 Hz, 1H), 5.08 (ddd, J = 10.8,
10.8, 3.6 Hz, 1H), 5.02 (s, 2H), 4.80 (d, J = 12.4 Hz, 1H), 4.76 (d, J =
12.4 Hz, 1H), 3.56 (dd, J = 14.4, 3.6 Hz, 1H), 2.96 (dd, J = 14.4, 10.8
Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.1, 154.6,
145.1, 136.9, 135.7, 133.6, 130.3, 129.8, 129.2, 128.6, 128.5, 128.2,
128.0, 127.9, 127.5, 126.7, 115.1, 71.9, 70.0, 67.1, 32.0, 21.7; IR (ATR)
3278, 1694, 1550, 1513, 1310, 1295, 1266, 1238, 1129, 1043, 818, 737
cm−1; HRMS (TOF-ESI) calcd for C30H29NO5SNa [M + Na]+
538.1664, found 538.1663.
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́
(E)-Benzyl N-(2-tert-Butoxycarbonylethenyl)carbamate
(10p).28 Colorless crystals (63.8 mg, 23% yield), mp 115.5−119.5
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Note
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2770
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