Cu-catalyzed conversion of propargyl acetates to e-a,β-unsaturated amides via ketenimine formation with sulfonyl azides

Article abstract of DOI:10.1021/jo402570t

The reaction between readily accessible propargyl acetates and sulfonyl azides in the presence of CuI catalyst yields trans-a,β-unsaturated Ntosylamides via N-sulfonyl ketenimine formation followed by a probable 1,3- OAc migration ([3,3]-sigmatropic rearrangement). The reaction is very general, allowing all kinds of substitution, including alkyl, aryl (electrondonating, -withdrawing, and -neutral), heteroaryl, and vinyl groups, on the Cterminal of acrylamide. Also, the method affords the products at ambient temperature with excellent diastereoselectivity in moderate to good yields.

Full text of DOI:10.1021/jo402570t

Note
pubs.acs.org/joc
Cu-Catalyzed Conversion of Propargyl Acetates to E‑α,β-Unsaturated
Amides via Ketenimine Formation with Sulfonyl Azides
Yalla Kiran Kumar,† Gadi Ranjith Kumar,† and Maddi Sridhar Reddy*,†,‡
†Medicinal & Process Chemistry Division, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur
Road, P.O. Box 173, Lucknow 226031, India
‡Academy of Scientific and Innovative Research, New Delhi 110001, India
S
* Supporting Information
ABSTRACT: The reaction between readily accessible propargyl acetates and
sulfonyl azides in the presence of CuI catalyst yields trans-α,β-unsaturated N-
tosylamides via N-sulfonyl ketenimine formation followed by a probable 1,3-
OAc migration ([3,3]-sigmatropic rearrangement). The reaction is very
general, allowing all kinds of substitution, including alkyl, aryl (electron-
donating, -withdrawing, and -neutral), heteroaryl, and vinyl groups, on the C-
terminal of acrylamide. Also, the method affords the products at ambient
temperature with excellent diastereoselectivity in moderate to good yields.
he E-α,β-unsaturated amide subunit is found in a large
ketenimines successfully.7a−c Most recently, during the
preparation of our manuscript, Talukdar and co-workers
reported a 1,3-migration of a substituted amino group onto a
ketenimine generated in situ for the synthesis of acrylamidi-
nes.7b Along the same lines, and in continuation of our interest
in alkyne functionalization chemistry,8 we herein report a
practical method for the synthesis of N-sulfonyl E-α,β-
unsaturated amides from readily available propargyl acetates
(Scheme 1, eq 2).
Initially, we envisioned that the hydroxyl function of the
propargyl alcohol would attack (four-membered) on its in situ-
generated ketenimine, leading to double-bond isomerization to
afford the corresponding α,β-unsaturated amide. Cho and
Chang5d used propargyl alcohols for a similar reaction in the
presence of water as a ready external nucleophile to obtain β-
hydroxyamides (Scheme 1, eq 1). We wanted to pursue the
reaction in the absence of water to make the internal hydroxyl
group the only available nucleophile. To test the feasibility of
this transformation, the model substrate 1a and TsN3 were
selected.
T
number of natural products1 and synthetic compounds of
biological and pharmaceutical interest.2 Inspite of its wide
occurrence and usefulness, the synthetic viability developed to
date is very limited.3 Especially, the synthesis of 1° or 2° amides
is underdeveloped because of the presence of an acidic
hydrogen (N−H) in the corresponding starting materials,
which does not comfortably bear with basic conditions as in the
case of the conventional aldol condensation, Wittig, and
Horner−Wadsworth−Emmons reactions that are used for the
synthesis of their ester counterparts (i.e., α,β-unsaturated
esters). Condensation of amines with presynthesized α,β-
unsaturated acids (using the Perkin reaction) is one of the few
practical approaches available. Many of the methods reported
to date suffer from multiple steps, harsh conditions, limited
substitution tolerance, poor diastereoselectivity, etc. We herein
report a highly convenient method for the synthesis of alkyl/
vinyl/aryl/heteroaryl-substituted N-sulfonyl E-α,β-unsaturated
primary amides from readily available propargyl alcohols/
acetates and sulfonyl azides at ambient temperature under
affordable conditions. This method merits further attention in
light of the widespread importance of the sulfonamide moiety
in the design of pharmaceuticals.4 Over 30 drugs containing N-
arylsulfonamides are in clinical use as antibacterials, non-
nucleotide reverse transcriptase inhibitors, antitumor agents,
and HIV-1 protease inhibitors.4
The initial reaction was performed in the presence of 10 mol
% copper(I) iodide using K2CO3 as the base in acetonitrile at
room temperature. To our delight, the expected α,β-
unsaturated amide 3a was formed and was isolated in 32%
yield (Table 1, entry 1) after 24 h of reaction at room
temperature. The structure of 3a was confirmed by NMR (the
1
coupling constant of the olefinic protons in the H NMR
A recent breakthrough in the synthesis of ketenimines via a
copper-catalyzed azide−alkyne cycloaddition (CuAAC)5 has
opened a new pathway for the synthesis of diverse nitrogen-
containing cyclic and acyclic motifs of biological and
pharmaceutical interest. Chang,5 Wang,6 and others7 have
reported a number of elegant novel methods that involve
trapping of ketenimines obtained by this route. Most of them
have used amines, alcohols, and water as external nucleophiles.
Very few methods use internal nucleophiles to trap the
spectrum was J = 15.8 Hz) and by comparison to literature
data.9 Changing the catalyst or solvent (entries 2 and 3) led
only to decreases in the yield along with increased
decomposition. Neither the starting material nor any significant
byproducts were observed. We presume that the strain
Received: November 21, 2013
© XXXX American Chemical Society
A
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Note
Scheme 1. Synthesis of Amides from Propargyl Alcohols/Acetates
a
with their electron-poor counterparts 2l and 2m (60−65%).
The steric properties of the aryl ring did not appear to
significantly affect the yield or the stereoselectivity, as ortho-
functionalized aryl substrates 2d, 2h, 2j, 2l, and 2o performed
equally well in the reaction sequence. Variation in the
substitution on the sulfonyl azide moiety (i.e., using
benzenesulfonyl azide and methanesulfonyl azide rather than
toluenesulfonyl azide) also afforded the corresponding products
3p and 3q in good yields (63−70%). The cascade was then
tested for the synthesis of heteroaryl-substituted acrylamides 3r
and 3s, which were obtained in 60% and 62% yield,
respectively. Of particular note is the observation that the
cinnamyl-substituted propargyl acetate 2t also reacted smoothly
to afford the conjugated dienamide 3t as a single diastereomer
in 70% yield. Next, to find out that whether conjugation was
responsible for the exclusive formation of the trans product and
to expand the reaction generality, we conducted the reaction on
alkyl-substituted substrates. Pleasingly, the alkyl-substituted
acrylamides 3u, 3v and 3w were obtained with excellent
stereoselection, although in moderate yields of 50−65%.
A plausible mechanism for the exclusive formation of (E)-
acrylamides is depicted in Figure 1. As described in several
papers recently by Chang5, Wang,6 and others,7 CuAAC of
terminal alkynes generates N-sulfonyl ketenimines via triazole
formation followed by N2 expulsion. In the present case,
intermediate B (formed via A) probably undergoes a [3,3]-
sigmatropic rearrangement (1,3-acetyl migration) to afford the
trans adduct D, hydrolysis of which gives the corresponding
amide 3. The six-membered transition state C formed during
the migration might position the hydrogen atoms in axial
positions to minimize the steric hindrance and therefore yield
the (E)-acrylamide selectively.
Table 1. Optimization Studies
b
entry substrate catalyst
solvent
base
time (h) yield (%)
1
2
la
CuI
MeCN
DCE
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
TEA
24
24
24
12
12
12
12
12
12
12
12
32
15
25
78
35
50
10
12
50
52
62
la
CuI
3
la
CuBr
CuI
CuI
MeCN
MeCN
Toluene
THF
4
2a
2a
2a
2a
2a
2a
2a
2a
5
6
CuI
7
CuI
MeCN
MeCN
MeCN
MeCN
MeCN
8
CuI
DIPEA
Cs2CO3
K2CO3
K2CO3
9
CuI
10
11
CuCl
CuBr
a
Reaction conditions: TsN3 (1.2 mmol), 1a/2a (1.0 mmol), base (1.2
mmol), copper(I) salt (0.1 mmol), solvent (10 mL), rt, open air.
b
Isolated yields.
associated with the formation of the four-membered transition
state involved in the 1,3-OH migration process in the sensitive
ketenimine might have slowed down the formation of the end
product and thereby led to sidewise decomposition. We
envisaged that the exchange of the hydroxyl group with an
acetoxy group would create a spatially closer nucleophile, in the
form of the carbonyl of the acetyl group, that could decrease
the activation energy for the migration process and would lead
to the product in good yield. As anticipated, upon treatment
with 10 mol % CuI and 1.2 equiv of K2CO3 in MeCN, 2a10 and
tosyl azide produced 3a at ambient temperature in 78% yield
(entry 4). Organic bases (TEA or DIPEA) gave poorer yields of
product compared with inorganic bases (K2CO3 or Cs2CO3), as
is evident from entries 7 and 8. MeCN was found to be a better
choice of solvent than toluene (entry 5) or THF (entry 6).
Next, a range of substrates10 with variation in the substitution
(aryl, heteroaryl, alkyl, and vinyl) of both the propargyl acetate
and the sulfonyl azide were subjected to the cascade reaction to
validate its generality. As is evident from Table 2, all of them
were applicable in the cascade process, providing the
acrylamide derivatives 3 in yields of 50−85%. Initially, various
aryl-substituted propargyl acetates were screened. Unsubsti-
tuted and methyl-substituted substrates gave the corresponding
products 3a−c in consistently good yields (70−78%). All
halogen groups (bromo, chloro, and fluoro) at various positions
of the phenyl ring survived well in the reaction to produce 3d−
k in yields of 71−85%. Electron-rich phenyl substrates 2n and
2o furnished products with better yields (78−80%) compared
In conclusion, we have described an efficient route for the
preparation of trans-α,β-unsaturated N-tosylamides by a
copper-catalyzed reaction of propargyl acetates with sulfonyl
azides that proceeds through a cascade of CuAAC, ketenimine
formation, and a probable [3,3]-sigmatropic rearrangement
(1,3-acyl migration).
EXPERIMENTAL SECTION
■
General Information. All of the reagents and solvents were
purchased from commercial sources and used without purification.
NMR spectra were recorded with a 300 or 400 MHz spectrometer for
1H and 75 or 100 MHz for 13C. Chemical shifts are reported relative to
the residual signals of tetramethylsilane in CDCl3 or deuterated
solvent CDCl3/DMSO-d6 for 1H and 13C NMR spectroscopy,
respectively. Multiplicities are reported as follows: singlet (s), doublet
(d), broad singlet (bs), doublet of doublets (dd), doublet of triplets
(dt), triplet (t), quartet (q), multiplet (m). HRMS was performed
using QToF mass spectrometer. Column chromatography was
performed with silica gel (100−200 mesh) as the stationary phase.
B
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Note
ab
,
Table 2. Copper(I)-Catalyzed Synthesis of Amides 3 from Propargyl Acetates 2
a
Reaction conditions: Sulfonyl azide (1.2 mmol), 2 (1.0 mmol), base (2.0 mmol), CuI (0.1 mmol), MeCN (10 mL, 0.1 M solution), rt, open air.
Isolated yields are shown.
b
Figure 1. Plausible mechanism for the formation of (E)-acrylamides 3 from propargyl acetates 2.
All of the reactions were monitored by TLC. The purity and
characterization of compounds were further established by HRMS.
General Procedure for the Synthesis of 3 from 210 Using the
Synthesis of 3a as an Example. To the substrate 2a10 (174 mg, 1
mmol) dissolved in acetonitrile (10 mL) was added tosyl azide (236
mg, 1.2 mmol), copper iodide (19 mg, 0.1 mmol), and K2CO3 (165
mg, 1.2 mmol). The mixture was stirred at room temperature for 12 h.
Water (5 mL) and then brine solution (5 mL) were added, and the
reaction mixture was extracted with ethyl acetate (3 × 10 mL). The
combined extracts were dried over Na2SO4, filtered, and concentrated.
The crude solid product was washed with cold diethyl ether (2 × 3
mL) to remove some soluble impurities/byproducts, and the
remaining insoluble crude material was purified by column
chromatography (silica gel, 15−30% EtOAc in hexanes) to get the
pure product 3 (270 mg, 78% yield).
N-4-Toluenesulfonyl-(E)-3-phenylprop-2-enamide (3a).9 78%
yield (270 mg); white solid; mp 130−132 °C; Rf = 0.40 (SiO2, 30%
1
EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.26 (bs, 1H),
7.87 (d, J = 8.3 Hz, 2H), 7.59−7.54 (m, 3H), 7.45−7.42 (m, 5H), 6.61
(d, J = 15.9 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO) δ
163.8, 144.7, 144.3, 136.9, 134.3, 131.1, 130.1, 129.5, 128.6, 128.1,
119.4, 21.5; IR ν (cm−1) 3425, 2926, 1628, 1450, 1215, 867; HRMS
(ESI-TOF) calcd for C16H16NO3S [M + H]+ 302.0851, found
302.0847.
N-4-Toluenesulfonyl-(E)-3-(4-methylphenyl)prop-2-enamide
(3b).9 71% yield (238 mg); white solid; mp 172−174 °C; Rf = 0.40
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.17
C
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Note
(bs, 1H), 7.86 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 15.8 Hz, 1H), 7.47−
7.43 (m, 4H), 7.24 (d, J = 8.3 Hz, 2H), 6.55 (d, J = 15.8 Hz, 1H), 2.40
(s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, DMSO) δ 163.9, 144.7,
144.3, 141.2, 137.0, 131.6, 130.1, 129.9, 128.6, 128.1, 118.2, 21.5, 21.4;
IR ν (cm−1) 3423, 3021, 1627, 1408, 1215, 759; HRMS (ESI-TOF)
calcd for C17H18NO3S [M + H]+ 316.1007, found 316.1005.
15.9 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO) δ 163.8 (d,
J = 247 Hz), 163.8, 144.7, 143, 136.9, 131.0, 130.9 (d, J = 8 Hz), 128.1,
119.3,116.5 (d, J = 22 Hz), 21.5; IR ν (cm−1) 3430, 3023, 1631, 1406,
1216, 760; HRMS (ESI-TOF) calcd for C16H15FNO3S [M + H]+
320.0757, found 320.0757.
N-4-Toluenesulfonyl-(E)-3-(2,4-difluorophenyl)prop-2-enamide
(3j). 71% yield (228 mg); white solid; mp 161−163 °C; Rf = 0.25
N-4-Toluenesulfonyl-(E)-3-(3-methylphenyl)prop-2-enamide (3c).
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.31
70% yield (235 mg); white solid; mp 140−142 °C; Rf = 0.40 (SiO2,
1
(bs, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.76−7.70 (m, 1H), 7.54 (d, J =
16.0 Hz, 1H), 7.45 (d, J = 8.2 Hz, 2H), 7.40−7.34 (m, 1H), 7.21−7.16
(m, 1H), 6.68 (d, J = 16.0 Hz, 1H), 2.41 (s, 3H); 13C NMR (100
MHz, DMSO) δ 163.7, 163.5 (dd, J = 225, 13 Hz), 161.4 (dd, J = 228,
13 Hz), 144.8, 136.9, 135.9, 132.1 (dd, J = 4, 2 Hz), 130.0, 128.2,
121.9 (d, J = 7 Hz), 118.9 (dd, J = 12, 3 Hz), 113.0 (dd, J = 22, 3 Hz),
105.3 (t, J = 26 Hz), 21.5; IR ν (cm−1) 3396, 3022, 1622, 1429, 1215,
857; HRMS (ESI-TOF) calcd for C16H14F2NO3S [M + H]+ 338.0662,
found 338.0662.
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.19 (bs,
1H), 7.86 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 15.8 Hz, 1H), 7.44 (d, J =
8.3 Hz, 2H), 7.37−7.36 (m, 2H), 7.32 (t, J = 7.4 Hz, 1H), 7.25 (d, J =
7.4 Hz, 1H), 6.58 (d, J = 15.8 Hz, 1H), 2.40 (s, 3H), 2.32 (s, 3H); 13C
NMR (100 MHz, DMSO) δ 163.9, 144.7, 144.4, 138.8, 136.9, 134.2,
131.8, 130, 129.4, 129.2, 128.1, 125.7, 119.2, 21.5, 21.2; IR ν (cm−1)
3426, 2925, 1626, 1445, 1216, 859; HRMS (ESI-TOF) calcd for
C17H18NO3S [M + H]+ 316.1007, found 316.1005.
N-4-Toluenesulfonyl-(E)-3-(2-bromophenyl)prop-2-enamide (3d).
N-4-Toluenesulfonyl-(E)-3-(3,4-difluorophenyl)prop-2-enamide
78% yield (233 mg); white solid; mp 172−174 °C; Rf = 0.30 (SiO2,
1
(3k). 74% yield (237 mg); white solid; mp 178−180 °C; Rf = 0.25
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.37 (bs,
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.27
1H), 7.87 (d, J = 8.3 Hz, 2H), 7.77 (d, J = 15.7 Hz, 1H), 7.71 (dd, J =
7.9, 1.2 Hz, 1H), 7.67 (dd, J = 7.9, 1.6 Hz, 1H), 7.48−7.44 (m, 3H),
7.39−7.35 (m, 1H), 6.61 (d, J = 15.7 Hz, 1H), 2.41 (s, 3H); 13C NMR
(100 MHz, DMSO) δ 163.4, 144.9, 141.7, 136.8, 133.8, 133.8, 132.7,
130.1, 128.9,128.5, 128.2, 125.1, 122.6, 21.6; IR ν (cm−1) 3432, 3019,
1627, 1467, 1215, 757; HRMS (ESI-TOF) calcd for C16H15BrNO3S
[M + H]+ 379.9956, found 379.9954.
(bs, 1H), 7.86 (d, J = 8.3 Hz, 2H), 7.72−7.66 (m, 1H), 7.56−7.43 (m,
5H), 6.57 (d, J = 15.9 Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz,
DMSO) δ 163.6, 151.0 (dd, J = 249, 13 Hz) 150.0 (dd, J = 245, 13
Hz), 144.8, 141.9, 136.9, 132.2 (dd, J = 6, 4 Hz), 130.0, 128.1, 125.9
(d, J = 3 Hz), 120.9, 118.6 (d, J = 17 Hz), 117.4 (d, J = 18 Hz), 21.5;
IR ν (cm−1) 3423, 3021, 1632, 1427, 1215, 759; HRMS (ESI-TOF)
calcd for C16H14F2NO3S [M + H]+ 338.0662, found 338.0662.
N-4-Toluenesulfonyl-(E)-3-(2-nitrophenyl)prop-2-enamide (3l).9
60% yield (190 mg); yellow solid; mp 211−213 °C; Rf = 0.15
N-4-Toluenesulfonyl-(E)-3-(4-bromophenyl)prop-2-enamide
(3e).9 78% yield (233 mg); white solid; mp 219−221 °C; Rf = 0.3
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.28
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.44
(bs, 1H), 7.86 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.5 Hz, 2H), 7.56−7.51
(m, 3H), 7.44 (d, J = 8.3 Hz, 2H), 6.61 (d, J = 15.8 Hz, 1H), 2.40 (s,
3H); 13C NMR (100 MHz, DMSO) δ 163.7, 144.8, 142.9, 136.9,
133.6, 132.5, 130.5, 130.0, 128.1, 124.5, 120.2, 21.5; IR ν (cm−1) 3432,
3019, 1629, 1415, 1215, 849; HRMS (ESI-TOF) calcd for
C16H15BrNO3S [M + H]+ 379.9956, found 379.9954.
(bs, 1H), 8.09 (dd, J = 8.1, 0.9 Hz, 1H), 7.89−7.79 (m, 4H), 7.74−
7.67 (m, 2H), 7.46 (d, J = 8.1 Hz, 2H), 6.55 (d, J = 15.7 Hz, 1H), 2.42
(s, 3H); 13C NMR (100 MHz, DMSO) δ 163.4, 148.7, 144.9, 141.7,
136.8, 136.2, 134.6, 131.1, 130.0, 128.2, 125.2, 122.9, 122.4, 21.5; IR ν
(cm−1) 3433, 3019, 1633, 1404, 1215, 757; HRMS (ESI-TOF) calcd
for C16H15N2O5S [M + H]+ 347.0702, found 347.0706.
N-4-Toluenesulfonyl-(E)-3-(3-chlorophenyl)prop-2-enamide (3f).
76% yield (245 mg); white solid; mp 146−148 °C; Rf = 0.3 (SiO2,
N-4-Toluenesulfonyl-(E)-3-(3-nitrophenyl)prop-2-enamide (3m).
1
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.29 (bs,
65% yield (205 mg); yellow solid; mp 189−191 °C; Rf = 0.15
1
1H), 7.86 (d, J = 8.3 Hz, 2H), 7.65 (s, 1H), 7.57−7.53 (m, 2H), 7.51−
7.43 (m, 4H), 6.64 (d, J = 15.9 Hz, 1H), 2.40 (s, 3H); 13C NMR (100
MHz, DMSO) δ 163.6, 144.8, 142.6, 136.9, 136.6, 134.2, 131.3, 130.6,
130.0, 128.4, 128.2, 126.9, 121.1, 21.5; IR ν (cm−1) 3433, 3019, 1631,
1415, 1215, 850; HRMS (ESI-TOF) calcd for C16H15ClNO3S [M +
H]+ 336.0461, found 336.0454.
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.34
(bs, 1H), 8.42 (s, 1H), 8.26 (dd, J = 8.2, 1.5 Hz, 1H), 8.03 (d, J = 8.2
Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.75−7.68 (m, 2H), 7.45 (d, J = 8.3
Hz, 2H), 6.77 (d, J = 15.9 Hz, 1H), 2.41 (s, 3H); 13C NMR (100
MHz, DMSO) δ 166.1, 148.7, 144.9, 139.6, 136.8, 134.6, 131.5, 130.1,
129.9, 129.5, 128.2, 125.3, 123.9, 21.6; IR ν (cm−1) 3428, 3021, 1631,
1405, 1216, 760; HRMS (ESI-TOF) calcd for C16H15N2O5S [M + H]+
347.0702, found 347.0706.
(N-4-Toluenesulfonyl-(E)-3-(4-chlorophenyl)prop-2-enamide
(3g).9 85% yield (274 mg); white solid; mp 204−206 °C; Rf = 0.3
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.25
N-4-Toluenesulfonyl-(E)-3-(4-methoxyphenyl)prop-2-enamide
(3n).9 80% yield (260 mg); white solid; mp 198−200 °C; Rf = 0.25
(bs, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.5 Hz, 2H), 7.56 (d, J
= 15.9 Hz, 1H), 7.50 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 6.60
(d, J = 15.9 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO) δ
163.7, 144.8, 142.8, 136.9, 135.6, 133.2, 130.3, 130.0, 129.6, 128.2,
120.2, 21.5; IR ν (cm−1) 3430, 3021, 1628, 1413, 1215, 759; HRMS
(ESI-TOF) calcd for C16H15ClNO3S [M + H]+ 336.0461, found
336.0454.
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.10
(bs, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.54−7.49 (m, 3H), 7.44 (d, J = 8.2
Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.46 (d, J = 15.8 Hz, 1H), 3.79 (s,
3H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO) δ 164.1, 161.8,
144.6, 144.1, 137.1, 130.5, 129.9, 128.1, 126.9, 116.6, 115.0, 55.8, 21.5;
IR ν (cm−1) 3427, 3021, 1631, 1409, 1215, 759; HRMS (ESI-TOF)
calcd for C17H18NO4S [M + H]+ 332.0957, found 332.0961.
N-4-Toluenesulfonyl-(E)-3-(2-fluorophenyl)prop-2-enamide (3h).
70% yield (233 mg); yellow solid; mp 165−167 °C; Rf = 0.30 (SiO2,
N-4-Toluenesulfonyl-(E)-3-(2-methoxyphenyl)prop-2-enamide
1
(3o). 78% yield (253 mg); white solid; mp 168−170 °C; Rf = 0.25
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.33 (bs,
1
(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.18
1H), 7.87 (d, J = 8.3 Hz, 2H), 7.67−7.63 (m, 1H), 7.59 (d, J = 16.0
Hz, 1H), 7.51−7.48 (m, 1H), 7.45 (d, J = 8.3 Hz, 2H), 7.32−7.26 (m,
2H), 6.72 (d, J = 16.0 Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz,
DMSO) δ 163.7, 161.1 (d, J = 250 Hz), 144.8, 136.8 (d, J = 21 Hz),
133.0 (d, J = 8 Hz), 130.4, 130.0, 128.2, 125.6, 122.3, 122.1 (d, J = 11
Hz), 121.9, 116.6 (d, J = 21 Hz), 21.5; IR ν (cm−1) 3395, 3022, 1628,
1417, 1216, 759; HRMS (ESI-TOF) calcd for C16H15FNO3S [M +
H]+ 320.0757, found 320.0757.
(bs, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.71 (d, J = 15.9 Hz, 1H), 7.51−
7.39 (m, 4H), 7.09 (d, J = 8.2 Hz, 1H), 6.99 (t, J = 7.5 Hz, 1H), 6.71
(d, J = 15.9 Hz, 1H), 3.85 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz,
DMSO) δ 164.3, 158.7, 144.7, 139.5, 137.1, 132.7, 130.0, 129.6, 128.1,
122.6, 121.2, 119.8, 112.3, 56.1, 21.5; IR ν (cm−1) 3427, 3021, 1625,
1411, 1215, 759; HRMS (ESI-TOF) calcd for C17H18NO4S [M + H]+
332.0957, found 332.0961.
N-4-Toluenesulfonyl-(E)-3-(4-fluorophenyl)prop-2-enamide (3i).9
75% yield (250 mg); yellow solid; mp 190−192 °C; Rf = 0.3 (SiO2,
N-Phenylsulfonyl-(E)-3-(3-methylphenyl)prop-2-enamide (3p).
70% yield (224 mg); white solid; mp 124−126 °C; Rf = 0.40 (SiO2,
1
1
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.25 (bs,
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.28 (bs,
1H), 7.86 (d, J = 8.3 Hz, 2H), 7.66−7.63 (m, 2H), 7.57 (d, J = 15.9
Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.30−7.26 (m, 2H), 6.55 (d, J =
1H), 7.99−7.97 (m, 2H), 7.75−7.71 (m, 1H), 7.67−7.63 (m, 2H),
7.53 (d, J = 15.8 Hz, 1H), 7.38−7.36 (m, 2H), 7.32 (t, J = 7.4 Hz, 1H),
D
dx.doi.org/10.1021/jo402570t | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
7.23 (d, J = 7.4 Hz, 1H), 6.61 (d, J = 15.8 Hz, 1H), 2.32 (s, 3H); 13
C
1403, 1263, 760; HRMS (ESI-TOF) calcd for C17H18NO3S [M + H]+
316.1007, found 316.1000.
NMR (100 MHz, DMSO) δ 163.9, 144.5, 139.8, 138.8, 134.2, 134.1,
131.9, 129.6, 129.4, 129.2, 128.1, 125.7, 119.1, 21.3; IR ν (cm−1) 3424,
3021, 1627, 1412, 1282, 856; HRMS (ESI-TOF) calcd for
C16H16NO3S [M + H]+ 302.0851, found 302.0848.
ASSOCIATED CONTENT
■
S
* Supporting Information
N-Methylsulfonyl-(E)-3-(3-methylphenyl)prop-2-enamide (3q).
1H and 13C NMR and mass spectra for the products 3a−w.
This material is available free of charge via the Internet at
http://pubs.acs.org.
63% yield (160 mg); white solid; mp 138−140 °C; Rf = 0.40 (SiO2,
1
30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 11.87 (bs,
1H), 7.65 (d, J = 15.9 Hz, 1H), 7.43−7.41 (m, 2H), 7.35 (t, J = 7.5 Hz,
1H), 7.28 (d, J = 7.5 Hz, 1H), 6.66 (d, J = 15.9 Hz, 1H), 3.33 (s, 3H),
2.34 (s, 3H); 13C NMR (100 MHz, DMSO) δ 164.9, 144.3, 138.8,
134.3, 131.8, 129.5, 129.2, 125.8, 119.4, 41.7, 21.3; IR ν (cm−1) 3424,
3022, 1627, 1405, 1215, 759; HRMS (ESI-TOF) calcd for
C11H14NO3S [M + H]+ 240.0694, found 240.0688.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: msreddy@cdri.res.in, sridharreddymaddi@yahoo.com.
N-4-Toluenesulfonyl-(E)-3-(3-pyridyl)prop-2-enamide (3r). 60%
Notes
yield (207 mg); yellow solid; mp 217−219 °C; Rf = 0.1 (SiO2, 40%
1
The authors declare no competing financial interest.
EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.32 (bs, 1H),
8.77 (s, 1H), 8.60 (s, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 8.0
Hz, 2H), 7.61 (d, J = 15.9 Hz, 1H), 7.48−7.44 (m, 3H), 6.70 (d, J =
15.9 Hz, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO) δ 163.5,
151.6, 150.1, 144.8, 140.9, 136.9, 134.9, 130.2, 130.0, 128.2, 124.6,
121.4, 21.5; IR ν (cm−1) 3429, 3021, 1630, 1408, 1215, 759; HRMS
(ESI-TOF) calcd for C15H15N2O3S [M + H]+ 303.0803, found
303.0800.
ACKNOWLEDGMENTS
■
Y.K.K. and G.R.K. thank CSIR for the Ph.D. fellowships. We
thank Dr. T. K. Chakraborty, Director CDRI, for the
encouragement. CDRI Communication No. 8589. We thank
the SAIF Division of CSIR-CDRI for analytical support. We
gratefully acknowledge the financial support by CSIR-Network
Project “BSC0104i” (CSIR-CDRI-SPLenDID) and by DST
under “Fast Track Proposal Scheme for Young Scientists”.
N-4-Toluenesulfonyl-(E)-3-(2-furyl)prop-2-enamide (3s). 62%
yield (220 mg); yellow solid; mp 114−116 °C; Rf = 0.3 (SiO2, 30%
1
EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.19 (bs, 1H),
7.86−7.84 (m, 3H), 7.44 (d, J = 8.0 Hz, 2H), 7.36 (d, J = 15.5 Hz,
1H), 6.91 (d, J = 3.4 Hz, 1H), 6.63 (dd, J = 3.4, 1.8 Hz, 1H), 6.36 (d, J
= 15.5 Hz, 1H) 2.40 (s, 3H); 13C NMR (100 MHz, DMSO) δ 163.7,
150.6, 146.7, 144.7, 136.9, 130.9, 130.0, 128.1, 117.4, 115.9, 113.3,
21.5; IR ν (cm−1) 3426, 3021, 1632, 1409, 1215, 760; HRMS (ESI-
TOF) calcd for C14H14NO4S [M + H]+ 292.0644, found 292.0639.
N-4-Toluenesulfonyl-(2E,4E)-5-phenylpent-2,4-dienamide (3t).
70% yield (224 mg); yellow solid; mp 225−227 °C; Rf = 0.30
REFERENCES
■
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(SiO2, 30% EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.17
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8.3 Hz, 2H), 7.53 (d, J = 8.3 Hz, 2H), 6.88 (dd, J = 15.5, 6.5 Hz, 1H),
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+ H]+ 268.1007, found 268.1006.
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1
EtOAc/hexanes); H NMR (400 MHz, DMSO) δ 12.02 (bs, 1H),
7.82 (d, J = 8.2 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 6.75 (dd, J = 15.6,
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