Synthesis of α,β-Unsaturated N-Sulfonyl Imides through Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl Ynamides

Article abstract of DOI:10.1021/acs.joc.5b01608

A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been developed. A variety of functionalized α,β-unsaturated N-sulfonyl imides are readily accessed by utilizing this approach, thus providing a viable alternative to synthetically

Full text of DOI:10.1021/acs.joc.5b01608

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Article
Synthesis of alpha,beta-Unsaturated N-Sulfonyl Imides through
Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl Ynamides
Fei Pan, Chao Shu, Yi-Fan Ping, Yi-Fei Pan, Peng-Peng Ruan, Qian-Ran Fei, and Long-Wu Ye
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b01608 • Publication Date (Web): 30 Sep 2015
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Synthesis of α,β-Unsaturated N-Sulfonyl Imides through
Zinc-Catalyzed Intermolecular Oxidation of N-Sulfonyl
Ynamides
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Fei Pan,† Chao Shu,† Yi-Fan Ping,† Yi-Fei Pan,† Peng-Peng Ruan,† Qian-Ran Fei,† and Long-Wu Ye*,†,‡
† State Key Laboratory of Physical Chemistry of Solid Surfaces & The Key Laboratory for Chemical
Biology of Fujian Province, Department of Chemistry, Xiamen University, Xiamen 361005, P. R. China
‡ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences Shanghai 200032, P. R. China
longwuye@xmu.edu.cn
RECEIVED DATE (to be automatically inserted after your manuscript is accepted if required according
to the journal that you are submitting your paper to)
R3
Zn(OTf)
2 (10 mol %)
N-oxide (2.0 equiv)
O
R3
R2
R1
R1
N
R2
dry PhCl, 80 oC, 1 h
N
PG
PG
15 examples
58-84% yield
oxidative non-noble metal catalysis
readily available starting materials
wide substrate scope
mild reaction conditions
valuable products
simple procedure
ABSTRACT: A novel zinc-catalyzed intermolecular oxidation of
developed. A variety of functionalized α,β-unsaturated
N
-sulfonyl ynamides has been
N
-sulfonyl imides are readily accessed by
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utilizing this approach, thus providing a viable alternative to synthetically useful α,β-unsaturated
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imides. Importantly, the reaction is proposed to proceed by a vinyligous E2-type elimination
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pathway, but not metal carbene pathway
.
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Introduction
α,β-Unsaturated amides represent an important type of organic compounds because of their frequent
occurrence in many bioactive natural products as well as pharmaceuticals.1 In addition, they can also
serve as valuable building blocks used in a wide range of organic reactions2 and in the synthesis of
polymeric materials.3 However, compared to the synthesis of α,β-unsaturated esters and amides, access
to α,β-unsaturated N-sulfonyl imides remains scarce.4 Therefore, the development of novel and general
methods for their efficient and practical synthesis of is highly desirable.
In recent years, particular attention has been paid to the gold-catalyzed intermolecular alkyne
oxidation by N-oxides.5-6 This approach has enabled an easy access to α,β-unsaturated carbonyl
compounds using readily available and safer alkynes to replace hazardous α–diazo ketones as precursors
in the realm of carbene chemistry.7 For example, Zhang and co-workers reported a gold-catalyzed
intermolecular alkyne oxidation, involving a gold carbene as the most likely intermediate, for the highly
regioselective synthesis of -unsaturated carbonyls, (Scheme 1a).8 Simultaneouly, Davies and co-
workers also described a general route for the synthesis of -unsaturated imides by a gold-catalyzed
intermolecular oxidation of ynamides, where a 1,2-C-H insertion into the gold carbenoid intermediate
was proposed (Scheme 1b).9 In our recent study on the ynamide chemistry,10-11 we developed the first
non-noble metal-catalyzed alkyne oxidation, leading to the highly site-selective synthesis of versatile
isoquinolones and β-carbolines.11a With this in mind, we envisioned that the synthesis of -
unsaturated imides might be achieved by a non-noble metal-catalyzed ynamide oxidation (Scheme 1c).12
In this context, we wish to report a zinc-catalyzed intermolecular oxidation of
N-sulfonyl ynamides
providing ready access to various -unsaturated N-sulfonyl imides in moderate to good yields.
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Importantly, mechanistic studies reveal that the reaction is proposed to occur by a vinyligous E2-type
elimination pathway, which is substantially different from the related gold-catalyzed alkyne oxidation.
Scheme 1. Synthesis of α,β-Unsaturated Imides by Intermolecular Oxidation of Ynamides
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a) Zhang et al. (ref. 8)
R4
O
R1
R2
R4
R3
[Au]
R1
R3
O
N-oxide
R2
b) Davies et al. (ref. 9)
[Au]
plausible
intermidiate
R2
O
PG
N
R1
R4
R3
[Au]
PG
N
R1
R3
N-oxide
c) Present Work
PG
R4
R3
R2
O
Zn(OTf)2
PG
N
N
R3
N-oxide
R1
R1
Results and Discussion
At the outset,
outlined in Table 1. To our delight, the initial catalyst investigation showed that most Lewis acid
catalysts displayed good reactivity to furnish the desired α,β-unsaturated -sulfonyl imide 2a (Table 1,
N-sulfonyl ynamide 1a was chosen as the model substrate and some of the results are
N
entries 1-6), and Zn(OTf)2 was found to be the best one (Table 1, entry 6). These results suggest that the
metal carbene pathway is less likely in such an oxidative catalysis. Notably, proton acids such as MsOH
and HOTf were not effective in promoting this reaction (Table 1, entries 7-8).13 A subsequent N-oxide
screening revealed that 8-ethylquinoline N-oxide 3a gave the best result, and E:Z selectivity slightly
varied with different N-oxides (Table 1, entry 9-13). In addition, it was found that the screening of the
amount of the N-oxide (Table 1, entries 14-15) and other solvents such as DCE and toluene (Table 1,
entries 16-17) could not further improve the reaction.
Table 1. Optimization of Reaction Conditionsa
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yield (%)c
3 4
entry
catalyst
oxidant ( / )
E/Zb
2.5/1
2.5/1
3a
3a
(R = Et)
(R = Et)
1
2
72
64
In(OTf)3
Sm(OTf)3
2.3/1
2.5/1
2.1/1
3a (R = Et)
3
4
5
66
62
69
Sc(OTf)3
Y(OTf)3
3a
3a
(R = Et)
(R = Et)
Yb(OTf)3
Zn(OTf)2
2.6/1
-
6
7
3a
3a
3a
3b
80
<5
22
61
77
56
(R = Et)
(R = Et)
(R = Et)
(R = Me)
MsOH
2.0/1
1.9/1
1.8/1
8
HOTf
9
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
i
10
3c
4a
(R = Pr)
11
12
13
2.2/1
2.1/1
2.1/1
(R' = H)
4b
(R' = 2-Br)
4c (R' = 2,6-Br2)
44
50
78
69
75
14d
2.0/1
2.6/1
1.4/1
2.1/1
3a
3a
3a
3a
(R = Et)
(R = Et)
(R = Et)
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
Zn(OTf)2
15e
16f
17g
a
51
(R = Et)
b
1
c
1a
Reaction conditions: [ ] = 0.05 M. Determined by crude H NMR.
1
d
Estimated by H NMR using diethyl phthalate as internal standard. 3.0
equiv of 3a was used. e 1.5 equiv of 3a was used. f In DCE. g In toluene.
With the optimized conditions established (Table 1, entry 6), the reaction scope was then studied. As
shown in Table 2, moderate to good yields (58-84%) of the corresponding α,β-unsaturated -sulfonyl
N
imides 2a-2o were obtained and the (E)-isomer was formed as the major, or sole product in all cases. Of
note, the reaction was tolerant of a range of functional groups including a remote chloro, protected
hydroxyl and amino (Table 2, entries 2−5). In addition, the investigation of the N-protecting groups
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demonstrated that this reaction could work well with different N-protecting groups, such as Ms, Bs (p-
bromobenzenesulfonyl), MBS (p-methoxylbenzenesulfonyl) and Ns (o-nitrobenzenesulfonyl) (Table 2,
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7
8
9
entries 11−14). Interestingly, it was found that conjugated
N
-sulfonyl ynamide 1o was also suitable
-sulfonyl
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substrate for this transformation, allowing the synthesis of the desired α,β,γ,δ-unsaturated
N
imide 2o in 68% yield (Table 2, entry 15).14 Thus, this protocol provides an efficient and practical route
for the construction of synthetically important α,β-unsaturated imide derivatives from readily accessible
materials. Attempts to expand this chemistry to oxazolidinone derived ynamide were not successful
presumably due to product inhibition as a good zinc chelate system is generated in this reaction system.
Table 2. Reaction Scope Studya
entry
1
substrate
1
product
O
2
E/Zb
yield (%)
78
5
Ts
Ts
1a
2a
2.6/1
N
N
4
Ph
Ph
O
3Cl
Ts
Ts
Cl
2
3
4
1b
1c
1d
2b
2c
2d
4.0/1
2.5/1
2.9/1
65
75
77
N
N
2
Ph
Ph
O
3OBoc
3OMs
Ts
Ts
Ts
Ts
OBoc
N
N
2
Ph
Ph
O
OMs
N
N
2
Ph
Ph
O
5NHBoc
Ts
Ts
NHBoc
2e
5
1e
2.3/1
73
N
N
4
Ph
Ph
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Table 2. (Continued)
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To further clarify the reaction mechanism, we also performed the deuterium-labeling studies, as
depicted in eq 1. It was found that in the presence of 3 equiv of D2O, >70% deuterium incorporation at
the alkenyl position was observed by using Zn(OTf)2 as catalyst while almost no deuterium was
incorporated by using IPrAuNTf2 as catalyst. These results further support that the reaction pathway of
the current zinc catalysis is distinctively different from the related gold catalysis, where the metal
carbenoid intermediate is presumably involved.8-9
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Ts
Bn
O
Ts
3a
[M],
(2.0 equiv)
N
N
(1)
dry PhCl, 80 oC, 1 h
Bn
D
1i
2i
Zn(OTf)2 (10 mol %), D2O (3 equiv): >70% D (70% yield)
IPrAuNTf2 (5 mol %), D2O (3 equiv): <1% D (77% yield)
On the basis of these experimental observations, a plausible mechanism to rationalize this zinc-
promoted oxidative catalysis is proposed, as illustrated in Scheme 2. Taking -sulfonyl ynamide 1i for
N
example, the N-oxide 3a first attacked the Zn-activated alkyne to form vinyl zinc intermediate A, which
could then undergo a vinyligous E2-type elimination to generate intermediate B.15 Finally,
protodemetallation ought to deliver the product 2i.
Scheme 2. Plausible Reaction Mechanism
Conclusion
In summary, we have developed a convenient and viable alternative for the synthesis of various α,β-
unsaturated
N-sulfonyl imides via a zinc-catalyzed alkyne oxidation. Importantly, the reaction is
proposed to proceed by a vinyligous E2-type elimination pathway, but not metal carbene pathway
.
Other notable features of this method include widespread availability of the substrates, compatibility
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with a broad range of functional groups, the simple procedure and mild reaction conditions. Further
application of this non-noble metal-promoted oxidative catalysis will be pursued in our laboratory.
Experimental Section
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General Information. Ethyl acetate (ACS grade), hexanes (ACS grade) and anhydrous 1, 2-
dichloroethane (ACS grade) were obtained commercially and used without further purification.
Methylene chloride, tetrahydrofuran and diethyl ether were purified according to standard methods
unless otherwise noted. Commercially available reagents were used without further purification. High-
resolution mass spectra were obtained using electrospray ionization using an ICR analyzer (ESI-MS).
1H NMR spectra were recorded in chloroform-d3. Chemical shifts are reported in ppm with the
internal TMS signal at 0.0 ppm as a standard. The data are being reported as (s = singlet, d = doublet, t
= triplet, m = multiplet or unresolved, brs = broad singlet, coupling constant(s) in Hz, integration).
13C NMR spectra were recorded in chloroform-d3. Chemical shifts are reported in ppm with the
internal chloroform signal at 77.0 ppm as a standard.
Representative Synthetic Procedures for the Preparation of
N-sulfonyl ynamides 1 (1b, 1h, 1l,
1o).11f,16 Alkynyl bromide (1.1 mmol) and DMEDA (0.2 mmol, 17.6 mg) were added to a stirred
solution of amide (1.0 mmol), K2CO3 (2.0 mmol, 276.4 mg), FeCl3·6H2O (0.1 mmol, 27.0 mg), and
toluene (5 mL) under air, and the resulting mixture was stirred at 90 °C for 12 h. The suspension was
filtered, and the residue was washed with diethyl ether (3 × 15 mL). The purification of products was
achieved by flash chromatography (eluent: hexanes/ethyl acetate) to afford the desired
ynamide 1.
N-sulfonyl
Representative Synthetic Procedures for the Preparation of
N-sulfonyl ynamides 1 (1a, 1c-1g,
1i-1k, 1m-1n).9 CuCl2 (0.1 mmol, 13.5 mg), amide (5.0 mmol) and Na2CO3 (3.0 mmol, 318.0 mg) were
added to a flame-dried 50 mL three-necked round-bottomed flask. The flask was purged with oxygen
for 15 min and a solution of pyridine (2.0 mmol, 158.2 mg) in dry toluene (10 mL) was added. A
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balloon filled with oxygen was connected to the flask and the stirred mixture was heated at 70 °C. After
15 min, a solution of alkyne (1 mmol) in dry toluene (10 mL) was added by syringe pump over 4 h. The
mixture was allowed to stir at 70 °C for another 4 h and was then cooled to rt. The reaction mixture was
concentrated under reduced pressure and the residue was purified by flash chromatography (eluent:
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hexanes/ethyl acetate) to afford the desired N-sulfonyl ynamide 1.
4-Methyl-N-(oct-1-yn-1-yl)-N-phenylbenzenesulfonamide (1a).11d Pale yellow oil (199.1 mg, 56%):
1H NMR (400 MHz, CDCl3) δ 7.58 (d, 2H, J = 8.4 Hz), 7.33 – 7.27 (m, 7H), 2.44 (s, 3H), 2.31 (t, 2H, J
13
= 7.2 Hz), 1.54 – 1.51 (m, 2H), 1.40 – 1.30 (m, 6H), 0.91 (t, 3H, J = 7.2 Hz); C NMR (100 MHz,
CDCl3) δ 144.5, 139.4, 133.1, 129.3, 128.8, 128.2, 127.8, 126.0, 73.8, 70.4, 31.3, 28.8, 28.4, 22.5, 21.6,
18.4, 14.0; IR (neat): 2930, 2253, 1592, 1489, 1373, 1177, 1092.
N-(5-Chloropent-1-yn-1-yl)-4-methyl-N-phenylbenzenesulfonamide (1b). Pale yellow oil (183.9 mg,
52%): 1H NMR (500 MHz, CDCl3) δ 7.55 (d, 2H, J = 8.4 Hz), 7.35 – 7.21 (m, 7H), 3.62 (t, 2H, J = 6.4
13
Hz), 2.50 (t, 2H, J = 6.8 Hz), 2.44 (s, 3H), 1.98 – 1.93 (m, 2H ); C NMR (125MHz, CDCl3) δ 144.8,
138.9, 132.7, 129.3, 128.9, 128.0, 127.9, 125.9, 74.8, 68.3, 43.5, 31.3, 21.5, 15.8; IR (neat): 2958, 2923,
2851, 2254, 1594, 1489, 1454, 1371, 1175; MS (ESI, m/z) 370 (M + Na+); HRMS (ESI) Calcd for
[C18H18ClNNaO2S]+ (M + Na+) 370.0639, found 370.0632.
tert-Butyl (5-(4-methyl-N-phenylphenylsulfonamido)pent-4-yn-1-yl) Carbonate (1c). Pale yellow oil
(300.7 mg, 70%): 1H NMR (400 MHz, CDCl3) δ 7.54 (d, 2H, J = 8.4 Hz), 7.33 – 7.20 (m, 7H), 4.12 (t,
2H, J = 6.4 Hz), 2.47 – 2.38 (m, 5H), 1.89 – 1.80 (m, 2H), 1.49 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
153.2, 144.6, 139.0, 132.7, 129.3, 128.8, 128.0, 127.8, 125.9, 81.7, 74.4, 68.6, 65.3, 27.8, 27.6, 21.4,
15.0; IR (neat): 2978, 2929, 2254, 1739(s), 1595, 1489, 1455, 1371, 1278, 1174; MS (ESI, m/z) 452 (M
+ Na+); HRMS (ESI) Calcd for [C23H27NNaO5S]+ (M + Na+) 452.1502, found 452.1501.
5-(4-Methyl-N-phenylphenylsulfonamido)pent-4-yn-1-yl Methanesulfonate (1d). Pale yellow oil
(256.7 mg, 63%): 1H NMR (400 MHz, CDCl3) δ 7.53 (d, 2H, J = 8.4 Hz), 7.36 – 7.19 (m, 7H), 4.32 (t,
2H, J = 6.0 Hz), 3.00 (s, 3H), 2.47 (t, 2H, J = 6.8 Hz), 2.42 (s, 3H), 1.99 – 1.90 (m, 2H); 13C NMR (100
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MHz, CDCl3) δ 144.8, 138.7, 132.6, 129.4, 128.9, 128.0, 127.8, 125.8, 75.0, 68.4, 67.8, 36.8, 28.0, 21.4,
14.6; IR (neat): 3030, 2937, 2851, 2254, 1594, 1489, 1454, 1358, 1174; MS (ESI, m/z) 430 (M + Na+);
HRMS (ESI) Calcd for [C19H21NNaO5S2]+ (M + Na+) 430.0753, found 430.0759.
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tert-Butyl (7-((4-methyl-N-phenylphenyl)sulfonamido)hept-6-yn-1-yl)carbamate (1e). White solid
(mp 78-80 oC, 241.9 mg, 53%): 1H NMR (400 MHz, CDCl3) δ 7.54 (d, 2H, J = 8.4 Hz), 7.34 – 7.19 (m,
7H), 4.65 (s, 1H), 3.18 – 3.01 (m, 2H), 2.42 (s, 1H), 2.29 (t, 2H, J = 6.8 Hz), 1.56 – 1.30 (m, 15H); 13C
NMR (100 MHz, CDCl3) δ 155.9, 144.6, 139.2, 132.9, 129.2, 128.8, 128.1, 127.8, 125.9, 78.8, 74.0,
69.9, 40.4, 29.4, 27.5, 25.8, 21.5, 18.3; IR (neat): 3418, 2932, 2253, 1715(s), 1595, 1489; MS (ESI, m/z)
479 (M + Na+); HRMS (ESI) Calcd for [C25H32N2NaO4S]+ (M + Na+) 479.1975, found 479.1972.
N-(Cyclohexylethynyl)-4-methyl-N-phenylbenzenesulfonamide (1f). Pale yellow oil (212.1 mg, 60%):
1H NMR (400 MHz, CDCl3) δ 7.54 (d, 2H, J = 8.0 Hz), 7.31 – 7.20 (m, 7H), 2.57 – 2.46 (m, 1H), 2.41
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(s, 3H), 1.83 – 1.72 (m, 2H), 1.71 – 1.61 (m, 2H), 1.53 – 1.42 (m, 2H), 1.37 – 1.23 (m, 4H); C NMR
(100 MHz, CDCl3) δ 144.6, 139.4, 132.7, 129.1, 128.7, 128.1, 127.7, 125.8, 74.2, 74.1, 32.6, 28.6, 25.8,
24.5, 21.5; IR (neat): 2929, 2853, 2246, 1595, 1488, 1448, 1373, 1175; MS (ESI, m/z): 376 (M + Na+);
HRMS (ESI) Calcd for [C21H23NNaO2S]+: 376.1342, found: 376.1341.
N-(Cyclopentylethynyl)-4-methyl-N-phenylbenzenesulfonamide (1g). Pale yellow oil (159.5 mg, 47%):
1H NMR (400 MHz, CDCl3) δ 7.53 (d, 2H, J = 8.4 Hz), 7.35 – 7.15 (m, 7H), 2.76 – 2.69 (m, 1H), 2.42
(s, 3H), 1.95 – 1.81 (m, 2H), 1.81 – 1.66 (m, 2H), 1.66 – 1.50 (m, 4H); 13C NMR (100 MHz, CDCl3) δ
144.6, 139.3, 132.7, 129.2, 128.8, 128.1, 127.7, 125.9, 74.5, 73.6, 33.8, 29.9, 24.7, 21.6; IR (neat): 2959,
2869, 2247, 1595, 1489, 1453, 1372, 1175; MS (ESI, m/z): 362 (M + Na+); HRMS (ESI) Calcd for
[C20H21NNaO2S]+: 362.1185, found: 362.1183.
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N-Benzyl-4-methyl-N-(oct-1-yn-1-yl)benzenesulfonamide (1h). Pale yellow oil (258.7 mg, 70%): H
NMR (400 MHz, CDCl3) δ 7.74 (d, 2H, J = 8.4 Hz), 7.34 – 7.22 (m, 7H), 4.44 (s, 2H), 2.43 (s, 3H),
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2.15 (t, 2H, J = 6.8 Hz), 1.42 – 1.32 (m, 2H), 1.30 – 1.13 (m, 6H), 0.86 (t, 3H, J = 7.2 Hz); C NMR
(100 MHz, CDCl3) δ 144.2, 134.8, 134.7, 129.4, 128.6, 128.3, 128.0, 127.6, 73.3, 70.8, 55.5, 31.2, 28.6,
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28.2, 22.4, 21.5, 18.3, 14.0; IR (neat): 2929, 2857, 2252, 1597, 1495, 1455, 1365, 1169; MS (ESI, m/z):
392 (M + Na+); HRMS (ESI) Calcd for [C22H27NNaO2S]+: 392.1655, found: 392.1654.
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N-Benzyl-N-(cyclohexylethynyl)-4-methylbenzenesulfonamide (1i). White solid (mp 68-70 C, 258.7
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mg, 70%): H NMR (400 MHz, CDCl3) δ 7.74 (d, 2H, J = 8.4 Hz,), 7.32 – 7.21 (m, 7H), 4.43 (s, 2H),
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2.43 (s, 3H), 2.40 – 2.35 (m, 1H), 1.68 – 1.60 (m, 2H), 1.55 – 1.48 (m, 2H), 1.47 – 1.17 (m, 6H); C
NMR (100 MHz, CDCl3) δ 144.2, 134.8, 134.7, 129.4, 128.8, 128.3, 128.0, 127.7, 74.8, 73.7, 55.6, 32.6,
28.6, 25.8, 24.4, 21.6; IR (neat): 2929, 2853, 1365, 1169, 599; MS (ESI, m/z): 390.1498 (M + Na+);
HRMS (ESI) Calcd for [C22H25NNaO2S]+: 390.1498, found: 390.1492.
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N-Allyl-4-methyl-N-(oct-1-yn-1-yl)benzenesulfonamide (1j). Pale yellow oil (210.9 mg, 66%): H
NMR (400 MHz, CDCl3) δ 7.78 (d, 2H, J = 8.0 Hz), 7.33 (d, 2H, J = 8.0 Hz), 5.77 – 5.67 (m, 1H), 5.27
– 5.13 (m, 2H), 3.91 (d, 2H, J = 6.4 Hz), 2.44 (s, 3H), 2.23 (t, 2H, J = 6.8 Hz), 1.52 – 1.42 (m, 2H), 1.39
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– 1.16 (m, 6H), 0.88 (t, 3H, J = 6.8 Hz); C NMR (100 MHz, CDCl3) δ 144.2, 134.7, 131.1, 129.5,
127.6, 119.4, 72.9, 70.4, 54.2, 31.2, 28.7, 28.2, 22.4, 21.5, 18.3, 13.9; IR (neat): 2929, 2857, 2251, 1643,
1597, 1494, 1454, 1366, 1170; MS (ESI, m/z): 342 (M + Na+); HRMS (ESI) Calcd for
[C18H25NNaO2S]+: 342.1498, found: 342.1497.
N-(Hex-1-yn-1-yl)-N-phenylmethanesulfonamide (1k).11b Pale yellow oil (145.8 mg, 58%): H NMR
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(400 MHz, CDCl3) δ 7.55 – 7.47 (m, 2H), 7.46 – 7.38 (m, 2H), 7.37 – 7.29 (m, 1H), 3.06 (s, 3H), 2.35 (t,
2H, J = 7.2 Hz), 1.58 – 1.51 (m, 2H), 1.48 – 1.37 (m, 2H), 0.92 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz,
CDCl3) δ 139.0, 129.1, 127.8, 125.2, 73.0, 70.9, 35.9, 30.7, 21.8, 18.0, 13.4; IR (neat): 2957, 2858, 2256,
1593, 1490, 1456, 1362, 1270, 1168, 1075, 1027.
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4-Bromo-N-(oct-1-yn-1-yl)-N-phenylbenzenesulfonamide (1l). Pale yellow oil (281.7 mg, 67%): H
NMR (400 MHz, CDCl3) δ 7.64 – 7.60 (m, 2H), 7.54 – 7.50 (m, 2H), 7.35 – 7.23 (m, 5H), 2.29 (t, 2H, J
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= 7.2 Hz), 1.54 – 1.45 (m, 2H), 1.41 – 1.21 (m, 6H), 0.89 (t, 3H, J = 7.2 Hz); C NMR (100 MHz,
CDCl3) δ 138.9, 134. 6, 131.9, 129.5, 128.9, 128.8, 128.0, 125.8, 73.3, 70.7, 31.1, 28.6, 28.3, 22.4, 18.2,
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13.9; IR (neat): 2929, 2857, 2253, 1592, 1573, 1488, 1470, 1389, 1377, 1183; MS (ESI, m/z): 442 (M +
Na+); HRMS (ESI) Calcd for [C20H22BrNNaO2S]+: 442.0447, found: 442.0446.
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4-Methoxy-N-(oct-1-yn-1-yl)-N-phenylbenzenesulfonamide (1m). Pale yellow oil (267.5 mg, 72%):
1H NMR (400 MHz, CDCl3) δ 7.62 – 7.56 (m, 2H), 7.34 – 7.22 (m, 5H), 6.95 – 6.88 (m, 2H), 3.84 (s,
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3H), 2.28 (t, 2H, J = 6.8 Hz), 1.55 – 1.44 (m, 2H), 1.41 – 1.30 (m, 6H), 0.88 (t, 2H, J = 6.8 Hz); C
NMR (100 MHz, CDCl3) δ 163.6, 139.3, 130.3, 128.8, 127.7, 127.3, 126.0, 113.7, 73.9, 70.3, 55.5, 31.2,
28.7, 28.3, 22.4, 18.3, 13.9; IR (neat): 2929, 2856, 2253, 1594, 1577, 1496, 1456, 1370, 1262, 1165; MS
(ESI, m/z): 394 (M + Na+); HRMS (ESI) Calcd for [C21H25NNaO3S]+: 394.1447, found: 394.1446.
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N-Methyl-2-nitro-N-(oct-1-yn-1-yl)benzenesulfonamide (1n). Pale yellow oil (259.5 mg, 80%): H
NMR (400 MHz, CDCl3) δ 8.13 (dd, 1H, J = 1.6, J = 7.6 Hz), 7.82 – 7.65 (m, 3H), 3.27 (s, 3H), 2.23 (t,
2H, J = 7.2 Hz), 1.50 – 1.39 (m, 2H), 1.35 – 1.18 (m, 6H), 0.88 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz,
CDCl3) δ 147.8, 134.5, 131.5, 131.2, 129.6, 124.0, 73.0, 69.9, 39.5, 31.0, 28.4, 28.1, 22.2, 18.0, 13.7; IR
(neat): 2930, 2857, 2256, 1589, 1548, 1465, 1440, 1374, 1181; MS (ESI, m/z): 347 (M + Na+); HRMS
(ESI) Calcd for [C15H20N2NaO4S]+: 347.1036, found: 347.1038.
N-(Cyclohex-1-en-1-ylethynyl)-N,4-dimethylbenzenesulfonamide (1o). Pale yellow oil (153.4 mg,
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53%): H NMR (400 MHz, CDCl3) δ 7.79 (d, 2H, J = 8.4 Hz), 7.36 (d, 2H, J = 8.0 Hz), 6.00 (s, 1H),
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3.05 (s, 3H), 2.45 (s, 3H), 2.03 – 2.13 (m, 4H), 1.69 – 1.51 (m, 4H); C NMR (100 MHz, CDCl3) δ
144.5, 134.1, 133.3, 129.6, 127.8, 119.8, 81.5, 70.6, 39.4, 29.4, 25.6, 22.3, 21.5, 21.4; IR (neat): 2929,
2857, 2225, 1363, 1165, 913; MS (ESI, m/z): 312 (M + Na+); HRMS (ESI) Calcd for [C16H19NNaO2S]+:
312.1029, found: 312.1031.
General Procedure of the Synthesis of α,β-Unsaturated N-sulfonyl Imide 2 from N-sulfonyl
Ynamide 1. 8-ethylquinoline N-oxide 3a (103.9 mg, 0.60 mmol) and Zn(OTf)2 (10.8 mg, 0.03 mmol)
were added to a solution of the N-sulfonyl ynamide 1 (0.30 mmol) in dry PhCl (6.0 mL) under N2 at
o
room temperature. The reaction mixture was stirred at 80 C and the progress of the reaction was
monitored by TLC. The reaction typically took 1 h. Upon completion, the mixture was then
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concentrated and the residue was purified by chromatography on silica gel (eluent: hexanes/ethyl
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acetate) to afford the desired product 2.
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(E)-N-Phenyl-N-tosyloct-2-enamide (2a). Pale yellow oil (62.8 mg, 56%): This compound is known
and the spectroscopic data match those reported.11d 1H NMR (400 MHz, CDCl3) δ 7.92 (d, 2H, J = 8.4
Hz), 7.48 – 7.46 (m, 3H), 7.32 (d, 2H, J = 8.4 Hz), 7.33 – 7.26 (m, 2H), 6.98 – 6.91 (m, 1H), 5.45 (d, 1H,
J = 15.2 Hz), 2.43 (s, 3H), 2.00 – 1.95 (m, 2H), 1.28 – 1.11 (m, 6H), 0.80 (t, 3H, J = 7.2 Hz); 13C NMR
(100 MHz, CDCl3) δ 165.2, 151.0, 144.6, 136.2, 140.0, 130.2, 129.5, 129.2, 129.1, 121.1, 32.1, 30.9,
27.4, 22.1, 21.5, 13.7.
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(Z)-N-Phenyl-N-tosyloct-2-enamide (2a). Pale yellow oil (24.5 mg, 22%): 1H NMR (400 MHz, CDCl3)
δ 7.92 (d, 2H, J = 8.4 Hz), 7.50 – 7.40 (m, 3H), 7.33 (d, 2H, J = 8.0 Hz), 7.25 – 7.21 (m, 2H), 6.01 –
5.92 (m, 1H), 5.43 – 5.37 (m, 1H), 2.61 – 2.50 (m, 2H), 2.44 (s, 3H), 1.37 – 1.29 (m, 2H), 1.29 – 1.18
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(m, 4H), 0.84 (t, 3H, J = 6.8 Hz); C NMR (100 MHz, CDCl3) δ 165.2, 151.4, 144.6, 136.4, 136.3,
130.2, 129.6, 129.5, 129.2, 129.0, 120.1, 31.3, 29.0, 28.4, 22.3, 21.6, 13.9; IR (neat): 2956, 1693 (s),
1625, 1595, 1489, 1364, 1174, 1158, 578; MS (ESI, m/z): 394 (M + Na+); HRMS (ESI) Calcd for
[C21H25NNaO3S]+: 394.1447, found: 394.1442.
(E)-6-Chloro-N-phenyl-N-tosylhex-2-enamide (2b). Pale yellow oil (70.9 mg, 65% combined yield):
1H NMR (400 MHz, CDCl3) δ 7.95 (d, 2H, J = 8.4 Hz), 7.56 – 7.47 (m, 3H), 7.36 (d, 2H, J = 8.4 Hz),
7.30 – 7.26 (m, 2H), 6.93 – 6.83 (m, 1H), 5.61 – 5.53 (m, 1H), 3.45 (t, 2H, J = 6.8 Hz), 2.53 – 2.44 (m,
5H); 13C NMR (100 MHz, CDCl3) δ 164.6, 145.1, 144.9, 136.0, 135.8, 130.3, 129.9, 129.7, 129.3, 129.2,
123.8, 42.0, 34.9, 21.6; IR (neat): 2919, 2850, 1692 (s), 1639, 1595, 1488, 1360, 1169, 574; MS (ESI,
m/z): 386 (M + Na+); HRMS (ESI) Calcd for [C18H18ClNNaO3S]+: 386.0588, found: 386.0591.
tert-Butyl (E)-(5-(4-methyl-N-phenylphenylsulfonamido)-5-oxopent-3-en-1-yl) Carbonate (2c). Pale
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yellow oil (100.2 mg, 75% combined yield): H NMR (400 MHz, CDCl3) δ 7.92 (d, 2H, J = 8.4 Hz),
7.53 – 7.44 (m, 3H), 7.34 (d, 2H, J = 8.0 Hz), 7.28 – 7.22 (m, 2H), 6.97 – 6.84 (m, 1H), 5.61 – 5.51 (m,
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1H), 3.97 (t, 2H, J = 6.4 Hz), 2.45 (s, 3H), 2.39 – 2.30 (m, 2H), 1.44 (s, 9H); C NMR (100 MHz,
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CDCl3) δ 164.6, 153.1, 145.4, 144.8, 136.1, 135.8, 130.3, 129.9, 129.7, 129.3, 129.2, 123.4, 82.2, 64.5,
31.5, 27.7, 21.6; IR (neat): 2925, 2853, 1740 (s), 1694 (s), 1639, 1595, 1488, 1454, 1367, 1163, 696,
575; MS (ESI, m/z): 468 (M + Na+); HRMS (ESI) Calcd for [C23H27NNaO6S]+: 468.1451, found:
468.1453.
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(E)-5-(4-Methyl-N-phenylphenylsulfonamido)-5-oxopent-3-en-1-yl methanesulfonate (2d). Pale
yellow oil (97.8 mg, 77% combined yield): 1H NMR (400 MHz, CDCl3) δ 7.90 (d, 2H, J = 8.4 Hz), 7.54
– 7.45 (m, 3H), 7.34 (d, 2H, J = 8.0 Hz), 7.29 – 7.20 (m, 2H), 6.92 – 6.77 (m, 1H), 5.62 (d, 1H, J = 15.2
Hz), 4.19 – 4.07 (m, 2H), 2.90 (s, 3H), 2.51 – 2.37 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 164.4, 144.9,
143.5, 135.9, 135.7, 130.2, 130.0, 129.7, 129.3, 129.1, 124.2, 66.8, 37.4, 31.8, 21.6; IR (neat): 2923,
2852, 2256, 1690, 1640, 1593, 1486, 1260; MS (ESI, m/z): 446 (M + Na+); HRMS (ESI) Calcd for
[C19H21NNaO6S2]+: 446.0702, found: 446.0707.
tert-Butyl (E)-(7-((4-methyl-N-phenylphenyl)sulfonamido)-7-oxohept-5-en-1-yl)carbamate (2e). Pale
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yellow oil (103.5 mg, 73% combined yield): H NMR (400 MHz, CDCl3) δ 7.92 (d, 2H, J = 8.4 Hz),
7.51 – 7.47 (m, 3H), 7.33 (d, 2H, J = 8.0 Hz), 7.26 – 7.23 (m, 2H), 6.94 – 6.87 (m, 1H), 5.44 (d, 1H, J =
15.2 Hz,), 4.48 (s, 1H), 3.07 – 2.92 (m, 2H), 2.44 (s, 3H), 2.04 – 1.98 (m, 2H), 1.41 (s, 9H), 1.35 – 1.27
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(m, 4H); C NMR (100 MHz, CDCl3) δ 165.0, 155.8, 150.2, 144.7, 136.1, 135.9, 130.3, 129.8, 129.6,
129.3, 129.1, 121.5, 67.9, 39.9, 31.8, 28.3, 25.5, 24.9, 21.6; IR (neat): 3407, 2928, 1695 (s), 1364, 1172,
697, 575; MS (ESI, m/z): 495 (M + Na+); HRMS (ESI) Calcd for [C25H32N2NaO5S]+: 495.1924, found:
495.1921.
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2-Cyclohexylidene-N-phenyl-N-tosylacetamide (2f). Pale yellow oil (93.1 mg, 84%): H NMR (400
MHz, CDCl3) δ 7.91 (d, 2H, J = 8.4 Hz), 7.51 – 7.42 (m, 3H), 7.32 (d, 2H, J = 8.0 Hz), 7.28 – 7.21 (m,
2H), 5.21 (s, 1H), 2.70 – 2.62 (m, 2H), 2.43 (s, 3H), 1.95 – 1.86 (m, 2H), 1.61 – 1.41 (m, 6H); 13C NMR
(100 MHz, CDCl3) δ 165.7, 164.7, 144.4, 136.6, 136.5, 130.2, 129.4, 129.2, 129.0, 114.0, 38.1, 30.0,
28.4, 27.6, 25.9, 21.6; IR (neat): 2925, 2855, 1692 (s), 1627, 1596, 1488, 1448, 1359; MS (ESI, m/z):
392 (M + Na+); HRMS (ESI) Calcd for [C21H23NNaO3S]+: 392.1291, found: 392.1291.
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2-Cyclopentylidene-N-phenyl-N-tosylacetamide (2g). Pale yellow oil (83.3 mg, 78%): H NMR (400
MHz, CDCl3) δ 7.92 (d, 2H, J = 8.4 Hz), 7.50 – 7.43 (m, 3H), 7.32 (d, 2H, J = 8.0 Hz), 7.28 – 7.23 (m,
2H), 5.44 – 5.41 (m, 1H), 2.78 – 2.72 (m, 2H), 2.44 (s, 3H), 2.22 – 2.15 (m, 2H), 1.70 – 1.62 (m, 2H),
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1.58 – 1.49 (m, 2H); C NMR (100 MHz, CDCl3) δ 172.5, 165.3, 144.3, 136.7, 136.6, 130.3, 129.5,
129.4, 129.2, 129.0, 111.5, 36.6, 33.2, 26.2, 25.1, 21.6; IR (neat): 2921, 2851, 1691 (s), 1629, 1595,
1488, 1452, 1363, 1168, 697, 565; MS (ESI, m/z): 378 (M + Na+); HRMS (ESI) Calcd for
[C20H21NNaO3S]+: 378.1134, found: 378.1130.
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(E)-N-Benzyl-N-phenyloct-2-enamide (2h). Pale yellow oil (85.6 mg, 74% combined yield): H NMR
(400 MHz, CDCl3) δ 7.63 (d, 2H, J = 8.4 Hz), 7.40 – 7.21 (m, 7H), 7.01 – 6.87 (m, 1H), 6.58 – 6.53 (m,
1H), 5.10 (s, 2H), 2.40 (s, 3H), 2.09 – 2.14 (m, 2H), 1.40 – 1.30 (m, 2H), 1.30 – 1.16 (m, 4H), 0.85 (t,
3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 166.0, 151.5, 144.6, 137.0, 136.7, 129.5, 128.5, 127.9,
127.7, 127.6, 121.3, 49.3, 32.5, 31.2, 27.5, 22.3, 21.5, 13.9; IR (neat): 2925, 2854, 1685 (s), 1633, 1597,
1495, 1454, 1356, 1162, 589; MS (ESI, m/z): 408 (M + Na+); HRMS (ESI) Calcd for [C22H27NNaO3S]+:
408.1604, found: 408.1602.
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N-Benzyl-2-cyclohexylidene-N-tosylacetamide (2i). Pale yellow oil (86.3 mg, 75%): H NMR (400
MHz, CDCl3) δ 7.62 (d, 2H, J = 8.0 Hz), 7.40 – 7.36 (m, 2H), 7.35 – 7.27 (m, 3H), 7.25 – 7.18 (m, 2H),
6.11 (s, 1H), 5.10 (s, 1H), 2.38 (s, 3H), 2.34 – 2.31 (m, 2H), 2.08 – 2.05 (m, 2H), 1.52 – 1.45 (m, 4H),
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1.40 – 1.32 (m, 2H); C NMR (100 MHz, CDCl3) δ 166.4, 161.5, 144.3, 137.0, 136.9, 129.3, 128.4,
127.8, 127.7, 127.4, 114.9, 49.0, 37.5, 30.4, 28.0, 27.4, 25.9, 21.4; IR (neat): 2930, 2855, 1682 (s), 1634,
1496, 1353, 1160, 588; MS (ESI, m/z): 406 (M + Na+); HRMS (ESI) Calcd for [C22H25NNaO3S]+:
406.1447, found: 406.1448.
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(E)-N-Allyl-N-phenyloct-2-enamide (2j). Pale yellow oil (69.4 mg, 69% combined yield): H NMR
(400 MHz, CDCl3) δ 7.81 (d, 2H, J = 8.0 Hz), 7.31 (d, 2H, J = 8.0 Hz), 7.04 – 6.88 (m, 1H), 6.50 (d, 1H,
J = 15.2 Hz), 5.98 – 5.82 (m, 1H), 5.36 – 5.21 (m, 2H), 4.49 (d, 2H, J = 5.2 Hz), 2.42 (s, 3H), 2.19 –
2.14 (m, 2H), 1.45 – 1.35 (m, 2H), 1.35 – 1.17 (m, 4H), 0.87 (t, 3H, J = 6.8 Hz); 13C NMR (100 MHz,
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CDCl3) δ 165.7, 151.3, 144.6, 137.0, 132.9, 129.5, 127.9, 121.1, 118.1, 48.3, 32.5, 31.2, 27.5, 22.3, 21.5,
13.8; IR (neat): 2925, 2927, 1686 (s), 1635, 1597, 1494, 1433, 1356, 1167, 666, 590; MS (ESI, m/z):
358 (M + Na+); HRMS (ESI) Calcd for [C18H25NNaO3S]+: 358.1447, found: 358.1449.
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(E)-N-(Methylsulfonyl)-N-phenylhex-2-enamide (2k). Pale yellow oil (57.7 mg, 72% combined yield):
1H NMR (400 MHz, CDCl3) δ 7.53 – 7.45 (m, 3H), 7.34 – 7.25 (m, 2H), 7.13 – 7.06 (m, 1H), 5.51 (d,
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1H, J = 15.2 Hz), 3.47 (s, 3H), 2.10 – 1.98 (m, 2H), 1.40 – 1.32 (m, 2H), 0.83 (t, 3H, J = 7.6 Hz); C
NMR (100 MHz, CDCl3) δ 166.3, 151.6, 135.2, 130.0, 129.9, 129.7, 121.0, 41.8, 34.3, 21.1, 13.4; IR
(neat): 2923, 2852, 1686 (s), 1635, 1592, 1488, 1353, 1155, 964, 695, 541; MS (ESI, m/z): 290 (M +
Na+); HRMS (ESI) Calcd for [C13H17NNaO3S]+: 290.0821, found: 290.0826.
(E)-N-((4-Bromophenyl)sulfonyl)-N-phenyloct-2-enamide (2l). Pale yellow oil (75.9 mg, 58%
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combined yield): H NMR (400 MHz, CDCl3) δ 7.94 – 7.88 (m, 2H), 7.74 – 7.65 (m, 2H), 7.58 – 7.43
(m, 3H), 7.27 – 7.22 (m, 2H), 7.01 – 6.91 (m, 1H), 5.45 – 5.38 (m, 1H), 2.04 – 1.96 (m, 2H), 1.33 – 1.24
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(m, 2H), 1.21 – 1.10 (m, 4H), 0.81 (t, 3H, J = 7.2 Hz); C NMR (125 MHz, CDCl3) δ 165.4, 151.8,
138.1, 135.7, 132.0, 130.7, 130.2, 130.0, 129.8, 129.0, 120.9, 32.3, 31.0, 27.4, 22.2, 13.8; IR (neat):
2920, 2851, 1692 (s), 1633, 1573, 1469, 1367, 1162, 746, 600, 596; MS (ESI, m/z): 458 (M + Na+);
HRMS (ESI) Calcd for [C20H22BrNNaO3S]+: 458.0396, found: 458.0399.
(E)-N-((4-Methoxyphenyl)sulfonyl)-N-phenyloct-2-enamide (2m). Pale yellow oil (93.0 mg, 80%
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combined yield): H NMR (400 MHz, CDCl3) δ 8.00 – 7.95 (m, 2H), 7.51 – 7.44 (m, 3H), 7.31 – 7.22
(m, 2H), 7.04 – 6.90 (m, 3H), 5.46 – 5.41 (m, 1H), 3.87 (s, 3H), 2.01– 1.92 (m, 2H), 1.32 – 1.21 (m, 2H),
1.21 – 1.09 (m, 4H), 0.81 (t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δ 165.3, 163.7, 150.9, 136.2,
131.5, 130.6, 130.3, 129.7, 129.6, 121.2, 113.8, 55.6, 32.2, 31.0, 27.4, 22.2, 13.8; IR (neat): 2926, 2854,
1691 (s), 1634, 1594, 1496, 1363, 1165, 912, 743; MS (ESI, m/z): 410 (M + Na+); HRMS (ESI) Calcd
for [C21H25NNaO4S]+: 410.1397, found: 410.1392.
(E)-N-((4-Bromophenyl)sulfonyl)-N-methyloct-2-enamide (2n). Pale yellow oil (66.3 mg, 65%
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combined yield): H NMR (400 MHz, CDCl3) δ 8.45 – 8.40 (m, 1H), 7.79 – 7.74 (m, 3H), 7.09 – 7.00
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(m, 1H), 6.32 (d, 1H, J = 15.2 Hz,), 3.46 (s, 3H), 2.28 – 2.19 (m, 2H), 1.49 – 1.39 (m, 2H), 1.35 – 1.23
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(m, 4H), 0.88 (t, 3H, J = 6.8 Hz); C NMR (100 MHz, CDCl3) δ 166.0, 152.9, 134.4, 134.2, 132.0,
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124.5, 119.7, 33.5, 32.7, 31.2, 27.6, 22.4, 13.9; IR (neat): 2919, 1683 (s), 1634, 1542, 1457, 1360, 1175;
MS (ESI, m/z): 363 (M + Na+); HRMS (ESI) Calcd for [C15H20N2NaO5S]+: 363.0985, found: 363.0989.
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(Z)-2-(Cyclohex-2-en-1-ylidene)-N-methyl-N-tosylacetamide (2o). Pale yellow oil (62.4 mg, 68%): H
NMR (400 MHz, CDCl3) δ 7.74 (d, 2H, J = 8.4 Hz), 7.30 (d, 2H, J = 8.0 Hz), 6.31 – 6.19 (m, 2H), 6.15
– 6.10 (m, 1H), 3.29 (s, 2H), 2.69 – 2.63 (m, 2H), 2.42 (s, 3H), 2.20 – 2.12 (m, 2H), 1.65 – 1.59 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 166.6, 153.5, 144.4, 138.4, 130.2, 129.7, 127.3, 116.3, 32.8, 27.1, 25.6,
21.7, 21.5; IR (neat): 2922, 1674 (s), 1355, 1160, 1035; MS (ESI, m/z): 328 (M + Na+); HRMS (ESI)
Calcd for [C16H19NNaO3S]+: 328.0978, found: 328.0980.
ASSOCIATED CONTENT
Supporting Information Available. H and 13C NMR spectra for all described compounds. This
1
material is available free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. We are grateful for financial support from the National Natural Science
Foundation of China (No. 21272191), the Natural Science Foundation of Fujian Province for
Distinguished Young Scholars (No. 2015J06003), the President Research Funds from Xiamen
University (No. 20720150045), PCSIRT, NFFTBS (No. J1310024) and XMU Training Program of
Innovation and Enterpreneurship for Undergraduates (Nos. 201510384008 and 201510384018).
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