Transition-Metal-Free One-Step Synthesis of Ynamides - The Journal

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Transition-Metal-Free One-Step Synthesis of Ynamides Xianzhu Zeng, Yongliang Tu, Zhenming Zhang, Changming You, Jiao Wu, Zhiying Ye, and Junfeng Zhao J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 07 Mar 2019 Downloaded from http://pubs.acs.org on March 7, 2019

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The Journal of Organic Chemistry

Transition-Metal-Free One-Step Synthesis of Ynamides Xianzhu Zeng,† Yongliang Tu,† Zhenming Zhang, Changming You, Jiao Wu, Zhiying Ye, Junfeng Zhao* Key Laboratory of Chemical Biology of Jiangxi Province, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022, P. R. China Supporting Information ABSTRACT: A robust transition-metal-free one-step strategy for the synthesis of ynamides from sulfonamides and (Z)-1,2-dichloroalkenes or alkynyl chlorides is presented. This method is not only effective for internal ynamides but also amenable for terminal ynamides. Various functional groups, even the vinyl moiety, are compatible, and thus, this strategy offers the opportunity for further functionalization.

Ynamides have evolved into versatile building blocks and precursors for a broad range of organic transformations including addition reactions,1 tandem ring-closing metathesis,2 Pauson-Khand reactions,3 and coupling reactions4 because of their unique reactivities.5 As a consequence, a plethora of methods have been developed for the synthesis of ynamides.6 Among them, the coupling of amides with various halides represents a straightforward approach to these molecules. The pioneering work involving nucleophilic substitution of alkynyl chlorides with amines was reported by Reinstein’s group in 1964.7 The application of this strategy for ynamide synthesis is attractive but more challenging owing to the low nucleophilicity of amides.8 To overcome the inherently low reactivity, the use of a transition metal catalyst such as a copper catalyst is critical.9 For example, Hsung’s group10 and Danheiser’s group11 independently developed a general method to prepare ynamides via a copper-catalyzed cross-coupling reaction between alkynyl bromides and amides in 2003.12 However, this strategy suffered from some disadvantages such as limited substrate scope, harsh reaction conditions, and competition from the homocoupling side reaction of the alkyne component. Recently, Evano reported the Cu-catalyzed coupling of vinyl dibromides with amides for the synthesis of internal ynamides via oxidative cleavage of the trans C−Br bonds.13 Despite their contributions, these methods still needed a copper catalyst to increase the reactivity of amides and were limited to internal ynamides. Therefore, a novel and convenient synthetic strategy for the construction of ynamides without a transition metal catalyst remains highly desirable, but is elusive.14 Recently, our group became interested in ynamide synthesis because we have disclosed that ynamides can be used as racemization-free coupling reagents for amide and peptide synthesis under extremely simple reaction conditions.15 To make ynamides competitive coupling reagents, a simple, practical, and step-economic synthetic strategy to produce them at a reasonably low cost is highly desirable. Very recently, our group reported a robust transition-metal-free one-step approach to internal and terminal ynamides using 1,1-dichloro-1-alkenes as alkyne surrogates.16 A mechanistic study revealed that an alkynyl chloride intermediate formed in situ from a 1,1dichloro-1-alkene was involved in this transformation. Inspired by this, we envisioned that alkynyl chlorides and 1,2-dichloro1-alkenes, which can transform into alkynyl chlorides in situ under basic reaction conditions, could also be valid starting materials for the synthesis of ynamides. Herein, we report our

Cl EWG N H

+

R1

TM

Cl

R2 or R2

EWG N

base

Cl

R2

1

R R2 = H, Aryl

complementary study on a base-promoted transition-metal-free one-step strategy for the synthesis of internal and terminal ynamides from secondary amides and (Z)-1,2-dichloroalkenes or alkynyl chlorides. With this proposal in mind, we initiated our studies by examining the reaction of 4-methyl-Npropylbenzenesulfonamide (1a) with (Z)-1,2-dichloroethylene (2a) under basic reaction conditions. Fortunately, the desired product, N-ethynyl-4-methyl-N-propylbenzenesulfonamide (3a), was obtained in good yield (79%) with 5 equiv of NaH in dimethylformamide (DMF) (Table 1, entry 1). Base screening revealed that NaH was the best base; other organic bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) resulted in no reaction at all (Table 1, entries 2–6). Compared to DMF, other solvents were less effective (Table 1, entries 7–11). The yield of 3a was increased to 95% by increasing the reaction temper ature slightly to 80 °C (Table 1, entry 13). In addition, the amount of base had a very significant effect in this reaction, and 5 equiv of NaH gave the best yield (Table 1, entries 14–16). Table 1. Optimization of the Reaction Conditionsa Ts

H N

n-Pr

1a

+

Cl

Cl

base solvent

2a

Ts

n-Pr N 3a

Base Temp Time Yield Solvent (equiv) (°C) (h) (%)b 1 NaH (5) DMF 70 6 79 NaOH (5) 2 DMF 70 6 32 3 DBU (5) DMF 70 6 0 4 t-BuONa (5) DMF 70 6 63 5 Na2CO3 (5) DMF 70 6 0 6 Cs2CO3 (5) DMF 70 6 54 7 NaH (5) PhMe 70 6 trace 8 NaH (5) THF 70 6 0 9 NaH (5) CH3CN 70 6 40 10 NaH (5) NMP 70 6 49 11 NaH (5) DMSO 70 6 59 12 NaH (5) DMF 50 6 70 13 NaH (5) DMF 80 1 95 14 NaH (2) DMF 80 1 20 15 NaH (3) DMF 80 1 34 16 NaH (4) DMF 80 1 89 aReaction conditions: Unless otherwise specified, the reaction was carried out with 1a (0.2 mmol), 2a (0.4 mmol), and base in solvent (1.0 mL). bIsolated yield. Entry

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The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Scheme 1. Substrate Scope of Secondary Amides for Terminal Ynamidesa R1

H N

Cl

+

R2

n-Pr N

Ts

R2 N

R1

Me N

Ts

Et N

Ts

3c, 1 h, 96%

N

n-Bu N

3d, 1 h, 95%

Ts

Ts

R2

N

n-Pr Me O N S O

n-Pr Me O N S O

3j, 5 h, 69%

3k, 4 h, 76%

Me

n-Pr O N S O

n-Pr O N S O 3n, 1.5 h, 93%

Me 3l, 1 h, 74% n-Pr O N S O

O2N

Me N

Ts

5a Et N

conditions A

Ts

Ts

Ph 6e, 3 h, 93% 6e, 1 h, 75%

n-Pr N

Ph

N

3r, 1 h, 89%

6j, 1 h, 96% 6j, 1 h, 87%

Ts

N

N

n-Bu N

Ph 6d, 5 h, 90% 6d, 1 h, 75% O

p-FPh O S O N Me Ph

N

Ph 6h, 21 h, 81% 6h, 1 h, 67% p-ClPh O S O N Me

Ph 6k, 1 h, 66% 6k, 1 h, 72%

6l, 1 h, 92% 6l, 1 h, 87%

Ph

N

N

N

Ph Ph 6n, 23 h, 83% 6n, 1 h, 42% Me

Ts

Ts

Ph 6g, 1 h, 78% 6g, 1 h, 75%

N

3p, 1 h, 80%

N

Ts

O

O

N 3o, 1 h, 61%

Ph

6

Ph 6c, 1 h, 93% 6c, 1 h, 85%

Ts

p-t BuPh O S O N Me

O

O

N

Ph 6f, 23 h, 85% 6f, 1 h, 90%

o-MePh O S O N Me 6i, 3 h, 88% 6i, 1 h, 90%

R

R2 N

or conditions B

Ts

Ph 6b, 5 h, 94% 6b, 1 h, 86%

1

Ph

n-Oct N

Ph

Ph 6p, 1 h, 89% 6p, 1 h, 70%

6o, 9 h, 85% 6o, 1 h, 67% Ts

N 3q, 1 h, 91% aReaction conditions:

Ph

4a

Ph 6m, 24 h, 70% 6m, 1 h, 45% N

Cl

or

Cl

Ph

Ph b A: 6a, 1 h, 91% (82%) B: 6a, 1 h, 96%

N

3h, 0.5 h, 75%

Cl 3m, 1 h, 92%

N

3g, 4 h, 72%

n-Pr O N S O F

Ts

3f, 0.5 h, 75%

Ts

3i, 1 h, 83%

Cl

+

OTBS

N

Ts

H N 1

OMe

Bn N

Scheme 2. Substrate Scope of Secondary Amides for Internal Ynamidesa

3

3b, 1 h, 98%

3e, 1 h, 79%

Ts

R

2a

3a, 1 h, 95%

Ts

1

80 °C

1

Ts

NaH, DMF

Cl

Page 2 of 9

N

N

Ts

N

3s, 1 h, 68%

1 (0.2 mmol), 2a (2.0 equiv) and NaH (5.0 equiv) in DMF (1.0 mL) at 80 oC.

With the optimized reaction conditions in hand, the scope of amides 1 was examined with (Z)-1,2-dichloroethylene 2a as the model substrate to afford terminal ynamides (Scheme 1). The reaction was performed using a series of sulfonamides with linear groups and the corresponding products were afforded in good to excellent yields (3a–f). Notably, in the case of 3g, the vinyl moiety remained intact. When 4methylbenzenesulfonamide bearing a γ-O-tertbutyldimethylsilyl (γ-OTBS) group was selected as the substrate, corresponding product 3h was obtained in 75% yield. Notably, sulfonamides containing cyclic groups were tolerated, giving the products in good yields (3i and 3j). Hindered Npropylbenzenesulfonamides bearing o-methyl and o, m, ptrimethyl groups were compatible (3k and 3l). Moreover, moderate to excellent yields were achieved for Npropylbenzenesulfonamides with electron-withdrawing groups on the phenyl ring such as p-F, p-Cl, and even p-NO2 substituents (3m–o). N-Propylnaphthalene-2-sulfonamide afforded target product 3p in 80% yield in this reaction. Aromatic azacycles such as indole and carbazole were also well suitable in this reaction system, furnishing ynamines 3q and 3r in 91% and 89% yields, respectively. Terminal biynamide 3s was obtained in 68% yield using this method. These encouraging results prompted us to extend the reaction to the synthesis of internal ynamides. Unfortunately, only moderate yields of internal ynamides were obtained under the aforementioned reaction conditions. However, to our delight, we found that internal ynamide 6a could be obtained in up to 91% yield by using Cs2CO3 as the base and dimethyl sulfoxide (DMSO) as the solvent at 80 °C (Scheme 3, reaction conditions

Ph 6q, 1 h, 92% 6q, 1 h, 76%

Ph 6r, 1 h, 92% 6r, 1 h, 72%

Ph

Ph 6s, 13 h, 73% 6s, 2 h, 60%

aReaction

conditions A: 1 (0.2 mmol), 4a (0.4 mmol), and Cs2CO3 (5.0 equiv., 1.0 mmol) in DMSO (1.0 mL) at 80 oC. Reaction conditions B: 1 (0.2 mmol), 5a (0.4 mmol), and Cs2CO3 (4.0 equiv., 0.8 mmol) in DMSO (1.0 mL) at 70 oC. b10 mmol scale of 1a in parentheses.

A). Furthermore, a 10-mmol-scale synthesis of 6a was achieved in 82% yield under these reaction conditions. Next, the coupling reactions of (Z)-(1,2-dichlorovinyl)benzene 4a or phenylethynyl chloride 5a with various amides were investigated using our optimized conditions (Scheme 2). Using (Z)-(1,2-dichlorovinyl)benzene 4a, a broad range of ynamides (6a–e) was prepared in good to excellent yields without a transition metal catalyst. It appears that the steric hindrance of the alkyl group has little effect on the reaction efficiency (6f– h). The o-Me-, p-t-Bu-, p-F-, and p-Cl-substituted Nmethylbenzenesulfonamides turned out to be compatible and afforded the corresponding ynamides (6i–l) in excellent yields. Moreover, cyclic carbonates could also be tolerated to furnish ynamides (6m and 6n) in good yields by prolonging the reaction time to one day. Aromatic azacycles were also compatible under these reaction conditions, giving the internal ynamines (6o–r) in 85–92% yields. In addition, biynamide 6s was obtained in moderate yield using these reaction conditions. When phenylethynyl chloride 5a was employed as the substrate and only 4.0 equiv of Cs2CO3 were used at 70 oC (Scheme 3, reaction conditions B), this transformation also proceeded smoothly with various amides to afford the corresponding ynamide products in slightly lower yields than those with (Z)(1,2-dichlorovinyl)benzene (Scheme 2, red part). Next, a broad range of (Z)-1,2-dichloroalkenes 4 or alkynyl chlorides 5 were subjected to this reaction (Scheme 3). It is noteworthy to mention that (Z)-1,2-dichloroalkenes with the


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The Journal of Organic Chemistry Scheme 3. Substrate Scope of (Z)-1,2-Dichloroalkenes or Alkynyl Chlorides for Internal Ynamidesa Cl Ts

H N

+

Me

R

Me

Ts

Me N

■ CONCLUSIONS R

or conditions B 5

4

Me N

Ts

conditions A

or R

1a

Ts

Cl Cl

7

Me N Me

Ts

Me N

Ts

Me N

OMe A: 7a, 1 h, 87% B: 7a, 2 h, 80%

Ts

7b, 1 h, 90% 7b, 2 h, 79%

Me N

Ts

7c, 1 h, 85% 7c, 2 h, 73%

Me N

Ts

t-Bu 7e, 1 h, 87% 7e, 2 h, 80%

Ts

Me N

Ts

Ts

Me N

Cl

F

Br

7g, 1 h, 79% 7g, 2 h, 78%

Me N

S

Ts

7i, 1 h, 80% 7i, 2 h, 80%

7d, 1 h, 84% 7d, 1.5 h, 90%

Me N

7f, 1.5 h, 76% 7f, 2 h, 80%

7j, 1 h, 80% 7j, 2 h, 82%

Me N

7h, 2 h, 74% 7h, 1.5 h, 82%

H Ph

7k, 1 h, 68% 7k, 3 h, 75%

conditions A: 1a (0.2 mmol), 4 (0.4 mmol), and Cs2CO3 (5.0 equiv., 1.0 mmol) in DMSO (1.0 mL) at 80 oC. Reaction conditions B: 1a (0.2 mmol), 5 (0.4 mmol), and Cs2CO3 (4.0 equiv., 0.8 mmol) in DMSO (1.0 mL) at 70 oC..

benzene ring of electron-donating and electron-withdrawing groups all reacted smoothly and afforded the ynamides in good to excellent yields (7a-h). Heterocyclic aryl group and polycyclic aromatic group such as thiophene and naphthalene were also converted to the corresponding ynamides (7i and 7j) in high yields. Similar with that of 2-alkyl-vinyl dichloride,16 the conversion of substrate (4-chlorobut-3-yn-1-yl)benzene failed to furnish the target ynamide but β-chloroenamide 7k in 68% yield. Likewise, corresponding products (7a-k) were obtained in good to excellent yields when alkynyl chlorides 5 were used (Scheme 3, red part). Scheme 4. Proposed Reaction Mechanism

R1 N

Ts

II

Ts Cl

path II R2 = Alkyl

R2 B

R2

a Cl

b

Cl

R

H D

path I R2 = Aryl, H

R2 A

Base

Cl

Cl

Ts

H

R1

2

R

4

Cl

- Cl-

- HCl

Ts

2

R1 N Ts

I

5 H+

R1 N

N

In conclusion, we have developed a robust transition-metalfree strategy for the synthesis of ynamides in moderate to excellent yields from (Z)-1,2-dichloroalkenes as masked alkynes or alkynyl chlorides. A variety of functional groups and substituents are tolerated. Both internal and terminal ynamides can be obtained efficiently via one simple operation. Additionally, aliphatic (Z)-1,2-dichloroalkenes or aliphatic alkynyl chlorides employed as substrates can afford βchloroenamides via β-addition of alkynyl chlorides. It is foreseeable that this method will spur the further study of ynamide chemistry.

■ EXPERIMENTAL SECTION

Cl

aReaction

R1

contrast, when R2 is an alkyl group, a β-chloroenamide is generated.

R2

N C

On the basis of our experimental results, a plausible reaction mechanism was proposed and shown in Scheme 4. Under the basic reaction conditions, alkynyl chloride intermediate 5 would form in situ via elimination from (Z)-1,2-dichloroalkenes 4. The direct α-attack of the nitrogen nucleophile on alkynyl chloride 5 would give ynamide C (path I). In contrast, β-attack of the nitrogen nucleophile followed by protonation would generate β-chloroenamide D (path II). The R2 substituent determines the selectivity between path I and path II. When R2 is an aryl group, which can stabilize the negative charge of alkenyl chloride intermediate A, an ynamide is produced. In

All reactions were carried out in oven-dried glassware and monitored by thin-layer chromatography (TLC). Product purification was done using silica gel column chromatography. All reagents and solvents were purchased from commercial vendors and used without further purification. Starting material secondary amides 1 were either purchased or synthesized. All other starting materials (Z)-1,2-dichloroalkenes 4, and alkynyl chloride 5 were synthesized following literature procedures. 1H/13C NMR spectra were recorded on Bruker Avance 400 MHz and Bruker AMX 400 MHz spectrometer at 400/100 MHz, respectively, in CDCl3 unless otherwise stated, using either TMS or the undeuterated solvent residual signal as the reference. Chemical shifts are given in ppm and are measured relative to CDCl3 or DMSO-d6 as an internal standard. High resolution mass spectra (HRMS) were obtained by the electrospray ionization timeof-flight (ESI-TOF) mass spectrometry. Low resolution mass (LRMS) spectra were obtained on a Thermo Scientific LCQFLEET (ESI) unit or SHIMADZU AOC-20i (GC-MS) mass spectrometer. IR spectra were recorded on a Nicolet-6700 spectrophotometer. Flash column chromatography purification of compounds was carried out by gradient elution using ethyl acetate (EA) in light petroleum ether (PE). Procedure for the synthesis of sulfonamide 1. To a solution of NEt3 (10 mmol) and primary amine (5 mmol) in 4 mL of DCM was added sulfonyl chloride (5 mmol) step by step. Upon the reaction completion (monitored by TLC), the reaction mixture was quenched with 5 mL of water, extracted with ethyl acetate for three times, washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude material was purified by column chromatography to provide sulfonamides 1. Among them, starting materials 1-3b, 1-3q, 1-3r, 1-3s, 1-6m, 1-6n, 1-6o, and 1-6r were purchased from commercial vendors and used without further purification. Ethyl-4-methylbenzenesulfonamide (1-3c).17a 0.89 g, 90%, 1H NMR (400 MHz, CDCl3) δ 7.88–7.71 (m, 2H), 7.29 (d, J = 5.8 Hz, 2H), 5.57 (t, J = 5.0 Hz, 1H), 2.96 (ddd, J = 14.2, 8.6, 5.0 Hz, 2H), 2.40 (d, J = 2.8 Hz, 3H), 1.07 (td, J = 7.2, 3.2 Hz, 3H). N-Butyl-4-methylbenzenesulfonamide (1-3d).17b 1.00 g, 88%, 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 5.62 (t, J = 6.0 Hz, 1H), 2.75 (dd, J = 13.4, 6.6 Hz, 2H), 2.24 (s, 3H), 1.35–1.23 (m, 2H), 1.12 (dq, J = 14.4, 7.2 Hz, 2H), 0.66 (t, J = 7.2 Hz, 3H). N-Cyclopropyl-4-methylbenzenesulfonamide (1-3i).17a 0.95 g, 90%, 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 5.67 (s, 1H), 2.42 (s, 3H), 2.26–2.15 (m, 1H), 0.63–0.46 (m, 4H).



2,4,6-Trimethyl-N-propylbenzenesulfonamide (1-3l).17b 0.96 g, 80%, 1H NMR (400 MHz, CDCl3) δ 6.96 (s, 2H), 4.88 (d, J = 4.8 Hz, 1H), 2.95–2.81 (m, 2H), 2.65 (d, J = 1.4 Hz, 6H), 2.30 (s, 3H), 1.47 (dq, J = 7.1, 5.4 Hz, 2H), 0.85 (td, J = 7.3, 2.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.1, 139.1, 133.8, 131.9, 44.3, 23.0, 22.9, 20.9, 11.2. 4-Chloro-N-propylbenzenesulfonamide (1-3n).17c 0.99 g, 85%, 1H NMR (400 MHz, CDCl ) δ 7.60–7.51 (m, 2H), 7.27–7.10 (m, 3 2H), 5.27 (t, J = 5.4 Hz, 1H), 2.61 (dd, J = 12.6, 6.0 Hz, 2H), 1.31– 1.11 (m, 2H), 0.74–0.47 (m, 3H). 4-Nitro-N-propylbenzenesulfonamide (1-3o).17d 0.90 g, 74%, 1H NMR (400 MHz, DMSO) δ 8.42 (d, J = 8.8 Hz, 2H), 8.04 (d, J = 8.8 Hz, 2H), 7.97 (t, J = 5.6 Hz, 1H), 2.76 (dd, J = 13.0, 6.8 Hz, 2H), 1.39 (h, J = 7.2 Hz, 2H), 0.79 (t, J = 7.4 Hz, 3H). 4-Methyl-N-((tetrahydrofuran-2-yl)methyl)benzenesulfonamide (1-6h).17e 0.89 g, 70%, 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.2 Hz, 2H), 7.33–7.27 (m, 2H), 5.08–4.96 (m, 1H), 3.99–3.88 (m, 1H), 3.79–3.64 (m, 2H), 3.08–3.06 (m, 1H), 2.90–2.87 (m, 1H), 2.42 (s, 3H), 1.88–1.83 (m, 3H), 1.62–1.57 (m, 1H). 4-Methyl-N-octylbenzenesulfonamide (1-6e).17f 1.06 g, 75%, 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 7.1 Hz, 2H), 7.17 (d, J = 7.2 Hz, 2H), 5.60 (s, 1H), 2.78 (t, J = 8.2 Hz, 2H), 2.28 (s, 3H), 1.34–1.32 (m, 2H), 1.05–10.8 (m, 10H), 0.73–0.75 (m, 3H). N,2-Dimethylbenzenesulfonamide (1-6i).17g 0.85 g, 92%, 1H NMR (400 MHz, CDCl3) δ 7.94 (dd, J = 5.2, 3.0 Hz, 1H), 7.45 (t, J = 7.0 Hz, 1H), 7.34–7.27 (m, 2H), 5.02 (s, 1H), 2.62 (dd, J = 7.1, 4.2 Hz, 6H). 4-(Tert-butyl)-N-methylbenzenesulfonamide (1-6j).17a 1.01 g, 89%, 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.6 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 4.84 (d, J = 4.2 Hz, 1H), 2.65 (d, J = 5.2 Hz, 3H), 1.35 (s, 9H). 4-Fluoro-N-methylbenzenesulfonamide (1-6k).17a 0.85 g, 90%, 1H NMR (400 MHz, CDCl ) δ 7.86–7.73 (m, 2H), 7.10 (t, J = 8.6 3 Hz, 2H), 5.24 (d, J = 5.0 Hz, 1H), 2.53 (d, J = 5.2 Hz, 3H). 4-Chloro-N-methylbenzenesulfonamide (1-6l).17a 0.95 g, 93%, 1H NMR (400 MHz, CDCl ) δ 7.81 (d, J = 8.6 Hz, 2H), 7.50 (d, J 3 = 8.6 Hz, 2H), 4.76 (s, 1H), 2.66 (d, J = 5.2 Hz, 3H). Procedure for the synthesis of 4. To a solution of LiCl (425 mg, 10 mmol) and [(allyl)PdCl]2 (46 mg, 0.125 mmol) in 4 mL of HOAc was added cis,cis-1,5-cyclooctadiene (54 mg, 0.5 mmol) and alkynyl chloride (5 mmol). After stirring for 6 h at 80 oC, the reaction mixture was quenched with 5 mL of water, extracted with ethyl acetate, washed with brine, dried over anhydrous Na2SO4 and concentrated. The crude material was purified by column chromatography to provide (Z)-1,2-dichloroalkenes. (Z)-(1,2-Dichlorovinyl)benzene (4a).18a 0.60 g, 70%, 1H NMR (400 MHz, CDCl3) δ 7.56–7.50 (m, 2H), 7.37 (dd, J = 4.1, 2.5 Hz, 3H), 6.68 (s, 1H). (Z)-1-(1,2-Dichlorovinyl)-2-methylbenzene (4b).18a 0.61 g, 66%, 1H NMR (400 MHz, CDCl ) δ 7.32–7.24 (m, 1H), 7.19 (dt, J = 14.8, 3 7.4 Hz, 3H), 6.33 (s, 1H), 2.36 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 136.9, 136.2, 134.8, 130.6, 129.7, 125.9, 117.8, 19.7. (Z)-1-(1,2-Dichlorovinyl)-3-methylbenzene (4c).18a 0.64 g, 69%, 1H NMR (400 MHz, CDCl ) δ 7.30 (d, J = 10.6 Hz, 2H), 7.24 (t, J 3 = 7.5 Hz, 1H), 7.16 (d, J = 7.4 Hz, 1H), 6.64 (s, 1H), 2.35 (s, 3H); 13C{1H} (100 MHz, CDCl ) δ 138.4, 135.8, 135.8, 130.3, 128.6, 3 127.3, 123.8, 115.8. 21.4. (Z)-1-(1,2-Dichlorovinyl)-4-methylbenzene (4d).18a 0.60 g, 65%, 1H NMR (400 MHz, CDCl ) δ 7.39 (d, J = 8.2 Hz, 2H), 7.15 (d, J 3 = 8.0 Hz, 2H), 6.61 (s, 1H), 2.34 (s, 3H). (Z)-1-(1,2-Dichlorovinyl)-4-methoxybenzene (4e).18a 0.60 g, 60%, 1H NMR (400 MHz, CDCl3) δ 7.50–7.38 (m, 2H), 6.94–6.81 (m, 2H), 6.57 (s, 1H), 3.81 (s, 3H). (Z)-1-(tert-Butyl)-4-(1,2-dichlorovinyl)benzene (4f).18b 0.70 g, 62%, 1H NMR (400 MHz, CDCl3) δ 7.49–7.42 (m, 2H), 7.42–7.35 (m, 2H), 6.65 (s, 1H), 1.32 (s, 9H).

(Z)-1-(1,2-Dichlorovinyl)-4-fluorobenzene (4g).18a 0.49 g, 52%, NMR (400 MHz, CDCl3) δ 7.55–7.46 (m, 2H), 7.06 (t, J = 8.6 Hz, 2H), 6.63 (s, 1H). (Z)-1-Chloro-4-(1,2-dichlorovinyl)benzene (4h).18a 0.70 g, 68%, 1H NMR (400 MHz, CDCl ) δ 7.45 (d, J = 8.6 Hz, 2H), 7.34 (d, J 3 = 8.6 Hz, 2H), 6.69 (s, 1H). (Z)-1-Bromo-4-(1,2-dichlorovinyl)benzene (4i).18a 0.70 g, 56%, 1H NMR (400 MHz, CDCl ) δ 7.50 (d, J = 8.6 Hz, 2H), 7.38 (d, J 3 = 8.6 Hz, 2H), 6.70 (s, 1H). (Z)-2-(1,2-Dichlorovinyl)thiophene (4j).18a 0.53 g, 60%, 1H NMR (400 MHz, CDCl3) δ 7.49 (dd, J = 3.0, 1.2 Hz, 1H), 7.32 (dd, J = 5.1, 3.1 Hz, 1H), 7.19 (dd, J = 5.1, 1.2 Hz, 1H), 6.73 (s, 1H). (Z)-2-(1,2-Dichlorovinyl)naphthalene (4k).18a 0.70 g, 63%, 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 1.4 Hz, 1H), 7.90–7.77 (m, 3H), 7.58 (dd, J = 8.7, 1.9 Hz, 1H), 7.54–7.48 (m, 2H), 6.82 (s, 1H). (Z)-(3,4-Dichlorobut-3-en-1-yl)benzene (4l).18b 0.62 g, 62%, 1H NMR (400 MHz, CDCl3) δ 7.29 (t, J = 7.4 Hz, 2H), 7.24–7.11 (m, 3H), 6.28–5.49 (m, 1H), 2.88 (t, J = 7.6 Hz, 2H), 2.65 (t, J = 7.6 Hz, 2H). Procedure for the synthesis of 5. To the mixture of terminal alkyne (10 mmol), TBAF·3H2O (1 mmol) and K2CO3 (10 mmol), CCl4 (6 mL) was added and the mixture was stirred at room temperature for two hours. After completion of the reaction, the solution concentrated under reduced pressure. The residue was purified by column chromatography to give alkynyl chlorides. (Chloroethynyl)benzene (5a).19a 1.16 g, 85%, 1H NMR (400 MHz, CDCl3) δ 7.46–7.40 (m, 2H), 7.34–7.27 (m, 3H). 1-(Chloroethynyl)-2-methylbenzene (5b).19b 1.05 g, 70%, 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J = 7.6, 0.9 Hz, 1H), 7.25– 7.16 (m, 2H), 7.14–7.09 (m, 1H), 2.42 (s, 3H). 1-(Chloroethynyl)-3-methylbenzene (5c).19a 1.20 g, 80%, 1H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.3 Hz, 2H), 7.16 (t, J = 7.4 Hz, 1H), 7.11 (d, J = 7.4 Hz, 1H), 2.29 (s, 3H). 1-(Chloroethynyl)-4-methylbenzene (5d).19a 1.08 g, 72%, 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 8.2 Hz, 2H), 7.09 (d, J = 7.8 Hz, 2H), 2.32 (s, 3H). 1-(Chloroethynyl)-4-methoxybenzene (5e).19a 1.24 g, 74%, 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 8.8 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.77 (s, 3H). 1-(tert-Butyl)-4-(chloroethynyl)benzene (5f).19c 1.42 g, 74%, 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 7.8 Hz, 2H), 1.30 (d, J = 1.2 Hz, 9H). 1-(Chloroethynyl)-4-fluorobenzene (5g).19a 1.15 g, 75%, 1H NMR (400 MHz, CDCl3) δ 7.40 (dd, J = 8.8, 5.4 Hz, 2H), 6.99 (t, J = 8.6 Hz, 2H). 1-Chloro-4-(chloroethynyl)benzene (5h).18a 1.46 g, 86%, 1H NMR (400 MHz, CDCl3) δ 7.38–7.34 (m, 2H), 7.30–7.26 (m, 2H). 1-Bromo-4-(chloroethynyl)benzene (5i).19a 1.67 g, 78%, 1H NMR (400 MHz, CDCl3) δ 7.46–7.41 (m, 2H), 7.31–7.27 (m, 2H). 2-(Chloroethynyl)thiophene (5j).18a 1.15 g, 81%, 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 9.0, 4.0 Hz, 2H), 6.95 (dd, J = 5.0, 3.8 Hz, 1H). 2-(Chloroethynyl)naphthalene (5k).19d 1.41 g, 76%, 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.79–7.67 (m, 3H), 7.48–7.42 (m, 3H). General experimental procedure for the synthesis of terminal ynamides in Scheme 1: To an oven-dried Schlenk tube equipped with a magnetic stir bar was added secondary amides (0.2 mmol, 1.0 equiv), (Z)-1,2-dichloroethylene (0.4 mmol, 2.0 equiv), NaH (1.0 mmol, 5.0 equiv) in DMF (1.0 mL) at 80 oC. Upon the reaction completion (monitored by TLC), the residue was purified by silica gel chromatography to afford the desired products. N-Ethynyl-4-methyl-N-propylbenzenesulfonamide (3a).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3a as a White solid (45 mg, 95%). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.3 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 3.26 (t, J = 7.2 Hz, 2H), 2.72 (d, J = 1.2 Hz, 1H), 2.44 (s, 3H), 1.71-1.63 1H


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Page 5 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry (m, 2H), 0.90 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.8, 134.6, 129.8, 127.6, 76.0, 59.0, 52.8, 21.8, 21.1, 10.8; MS (EI) m/z 237, 195, 155, 130, 116, 91, 65. N-Ethynyl-N,4-dimethylbenzenesulfonamide (3b).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3b as a White solid (41 mg, 98%). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.2 Hz, 2H), 3.06 (s, 3H), 2.69 (s, 1H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.0, 133.2, 129.9, 127.8, 77.6, 57.5, 38.9, 21.7; MS (EI) m/z 209, 155, 130, 91, 65. N-Ethyl-N-ethynyl-4-methylbenzenesulfonamide (3c).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3c as a White solid (43 mg, 96%). 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.2 Hz, 2H), 3.39 (q, J = 7.2 Hz, 2H), 2.74 (s, 1H), 2.45 (s, 3H), 1.22 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 134.8, 129.8, 127.6, 75.7, 59.2, 46.4, 21.7, 13.0; MS (EI) m/z 223, 195, 155, 130, 116, 91, 65. N-Butyl-N-ethynyl-4-methylbenzenesulfonamide (3d).20 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3d as a Light yellow solid (48 mg, 95%). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 3.30 (t, J = 7.2 Hz, 2H), 2.73 (s, 1H), 2.45 (s, 3H), 1.64-1.61 (m, 2H), 1.34 (dd, J = 15.0, 7.4 Hz, 2H), 0.91 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 134.6, 129.8, 127.6, 76.1, 59.0, 50.9, 29.7, 21.7, 19.4, 13.5; MS (EI) m/z 251, 186, 155, 131, 105, 91, 65. N-Benzyl-N-ethynyl-4-methylbenzenesulfonamide (3e).20 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3e as a White solid. 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.4 Hz, 2H), 7.33–7.27 (m, 7H), 4.49 (s, 2H), 2.67 (s, 1H), 2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 134.8, 134.3, 129.7, 128.9, 128.5, 128.4, 127.7, 76.3, 59.7, 55.3, 21.6; MS (EI) m/z 285, 253, 220, 155, 130, 123, 91, 65. N-Ethynyl-N-(3-methoxypropyl)-4-methylbenzenesulfonamide (3f). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3f as a colorless liquid (40 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 3.33 (dd, J = 10.8, 6.4 Hz, 4H), 3.22 (s, 3H), 2.66 (s, 1H), 2.37 (s, 3H), 1.88–1.79 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 134.6, 129.8, 127.7, 76.1, 69.0, 59.1, 58.6, 48.5, 28.1, 21.6; IR (KBr) ν̃ 3300, 2877, 2136, 1595, 1452, 1363, 976, 815 cm-1; HRMS (ESI-TOF) calcd for C13H18NO3S [M+H]+: 268.1007; found: 268.1001. N-(But-3-en-1-yl)-N-ethynyl-4-methylbenzenesulfonamide (3g). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3g as a Light yellow solid (36 mg, 72%), mp 77–78 oC. 1H NMR (400 MHz, CDCl ) δ 7.80 (d, J = 8.2 Hz, 2H), 7.35 (d, J 3 = 8.0 Hz, 2H), 5.74-5.66 (m, 1H), 5.26–4.94 (m, 2H), 3.51–3.29 (m, 2H), 2.76 (s, 1H), 2.45 (s, 3H), 2.42–2.35 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.8, 134.7, 133.5, 129.8, 127.7, 117.8, 75.9, 59.4, 50.6, 32.0, 21.6; IR (KBr) ν̃ 3265, 3089, 2922, 2130, 1592, 1437, 1357, 955, 821; HRMS (ESI-TOF) calcd for C13H16NO2S [M + H]+: 250.0902; found: 250.0905. N-(2-((Tert-butyldimethylsilyl)oxy)ethyl)-N-ethynyl-4-methylbenzenesulfonamide (3h).21 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3h as a white solid (53 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.6 Hz, 2H), 7.30 (d, J = 7.8 Hz, 2H), 3.76 (t, J = 6.0 Hz, 2H), 3.40 (t, J = 6.0 Hz, 2H), 2.68 (s, 1H), 2.40 (s, 3H), 0.82 (s, 9H), -0.00 (s, 6H); 13C{1H} NMR (100 MHz, CDCl ) δ 144.7, 134.9, 129.8, 127.7, 3 76.3, 60.3, 58.8, 53.1, 25.8, 21.6, 18.3, -5.5; MS (EI) m/z 353, 246, 189, 147, 117, 91, 73. N-Cyclopropyl-N-ethynyl-4-methylbenzenesulfonamide (3i). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3i as a Light yellow solid (39 mg, 83%), mp 58–59 oC. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 6.4 Hz, 2H), 7.37 (d, J =

7.2 Hz, 2H), 2.73 (d, J = 2.0 Hz, 2H), 2.46 (s, 3H), 0.86 (s, 2H), 0.77 (d, J = 5.6 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 133.9, 129.8, 128.0, 75.6, 58.8, 32.5, 21.7, 6.6; IR (KBr) ν̃ 3279, 3095, 2122, 1595, 1494, 1369, 988, 866 cm-1; HRMS (ESI-TOF) calcd for C12H14NO2S [M + H]+: 236.0745; found: 236.0749. N-Cycloheptyl-N-ethynyl-4-methylbenzenesulfonamide (3j). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3j as a colorless liquid (40 mg, 69%). 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.2 Hz, 2H), 3.86– 3.73 (m, 1H), 2.69 (s, 1H), 2.37 (s, 3H), 1.67–1.54 (m, 6H), 1.461.31 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.4, 136.1, 129.8, 127.4, 74.3, 61.3, 60.6, 33.3, 27.7, 24.2, 21.6; IR (KBr) ν̃ 3306, 32928, 2130, 1601, 1494, 1369, 976, 812 cm-1; HRMS (ESITOF) calcd for C16H21NNaO2S [M + Na]+: 314.1191; found: 314.1197. N-Ethynyl-2-methyl-N-propylbenzenesulfonamide (3k). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3k as a colorless liquid (36 mg, 76%). 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 8.2 Hz, 1H), 7.54–7.46 (m, 1H), 7.34 (t, J = 7.6 Hz, 2H), 3.37–3.30 (m, 2H), 2.76 (s, 1H), 2.70 (s, 3H), 1.72 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.3, 136.3, 133.6, 132.9, 130.4, 126.2, 75.6, 59.8, 52.4, 21.2, 20.9, 10.7; IR (KBr) ν̃ 3297, 3065, 2139, 1595, 1455, 1354, 982, 809 cm-1; HRMS (ESI-TOF) calcd for C12H16NO2S [M + H]+ : 238.0902; found: 238.0899. N-Ethynyl-2,4,5-trimethyl-N-propylbenzenesulfonamide (3l). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3l as a Light yellow solid (39 mg, 74%), mp 67–68 oC. 1H NMR (400 MHz, CDCl3) δ 6.97 (s, 2H), 3.41–3.30 (m, 2H), 2.73 (s, 1H), 2.64 (s, 6H), 2.31 (s, 3H), 1.79-1.70 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.5, 140.8, 132.0, 131.8, 75.7, 60.1, 51.7, 23.0, 21.2, 21.0, 10.9; IR (KBr) ν̃ 3270, 2964, 2128, 1601, 1568, 1384, 976, 863 cm-1; HRMS (ESITOF) calcd for C14H20NO2S [M + H]+: 266.1215; found: 266.1217. N-Ethynyl-4-fluoro-N-propylbenzenesulfonamide (3m). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3m as a Light yellow solid (44 mg, 92%), mp 44–45 oC. 1H NMR (400 MHz, CDCl ) δ 8.01–7.92 (m, 2H), 7.26 (d, J = 8.6 3 Hz, 2H), 3.29 (t, J = 7.2 Hz, 2H), 2.75 (s, 1H), 1.71-1.66 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.7 (J C-F = 254.8 Hz), 133.7 (J C-F = 2.8 Hz), 130.4 (J C-F = 9.4 Hz), 116.5 (J C-F = 22.6 Hz), 75.7, 59.3, 53.0, 21.1, 10.7; IR (KBr) ν̃ 3282, 3106, 2139, 1592, 1497, 1357, 991, 836 cm-1; HRMS (ESITOF) calcd for C11H13FNO2S [M + H]+: 242.0651; found: 242.0658. N-Ethynyl-4-fluoro-N-propylbenzenesulfonamide (3n). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3n as a Light yellow solid (48 mg, 93%), mp 91–92 oC. 1H NMR (400 MHz, CDCl ) δ 7.90–7.84 (m, 2H), 7.56–7.52 (m, 3 2H), 3.29 (t, J = 7.2 Hz, 2H), 2.74 (s, 1H), 1.73-1.64 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.4, 136.1, 129.5 129.0, 75.6, 59.3, 53.0, 21.1, 10.8; IR (KBr) ν̃ 3276, 3095, 2136, 1586, 1473, 1363, 991, 833 cm-1; HRMS (ESI-TOF) calcd for C11H13ClNO2S [M + H]+: 258.0356; found: 258.0358 . N-Ethynyl-4-nitro-N-propylbenzenesulfonamide (3o). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3o as a Light yellow liquid (33 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.6 Hz, 2H), 8.12 (d, J = 8.6 Hz, 2H), 3.35 (t, J = 7.2 Hz, 2H), 2.78 (s, 1H), 1.71 (dd, J = 14.6, 7.2 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 150.7, 143.0, 128.9, 124.4, 74.9, 59.8, 53.4, 21.1, 10.7; IR (KBr) ν̃ 3309, 3116, 2140, 1610, 1542, 1352, 855, 745 cm-1; HRMS (ESITOF) calcd for C11H13N2O4S [M+H]+: 269.0596; found: 269.0593. N-Ethynyl-N-propylnaphthalene-2-sulfonamide (3p). Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 3p as a white solid (44 mg, 80%), mp 83–84 oC. 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 8.00 (d, J = 8.6 Hz, 2H), 7.92 (t, J = 8.6 Hz, 2H), 7.70–7.61 (m, 2H), 3.34 (t, J = 7.2 Hz, 2H), 2.75



(s, 1H), 1.74-1.65 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 135.3, 134.7, 132.0, 129.5, 129.3, 128.0, 127.7, 122.5, 76.0, 59.1, 53.0, 21.2, 10.8; IR (KBr) ν̃ 3261, 3056, 2964, 1589, 1500, 1351, 913, 830 cm-1; HRMS (ESI-TOF) calcd for C15H16NO2S [M+H]+: 274.0902; found : 274.0903. 1-Ethynyl-1H-indole (3q).16 Purification by chromatography (petroleum ether/EtOAc = 100:1) afforded 3q as a white solid (26 mg, 91%). 1H NMR (400 MHz, CDCl3) δ 7.91–7.83 (m, 2H), 7.62 (t, J = 7.6 Hz, 1H), 7.54–7.47 (m, 2H), 6.83 (d, J = 3.2 Hz, 1H), 3.41 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.1, 128.7, 127.6, 123.7, 122.1, 121.2, 111.2, 105.5, 74.3, 58.8; MS (EI) m/z 141, 114, 89, 63, 51. 9-Ethynyl-9H-carbazole (3r).16 Purification by chromatography (petroleum ether/EtOAc = 100:1) afforded 3r as a Colorless liquid (34 mg, 89%). 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 7.6 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 7.58–7.49 (m, 2H), 7.35 (dd, J = 11.0, 4.0 Hz, 2H), 3.45 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.4, 126.8, 123.5, 122.2, 120.4, 111.3, 72.7, 62.6; MS (EI) m/z 191, 163, 140, 113, 95, 63, 51. N,N'-(Pentane-1,5-diyl)bis(N-ethynyl-4-methylbenzenesulfonamide) (3s).16 Purification by chromatography (petroleum ether/EtOAc = 4:1) afforded 3s as a white solid (62 mg, 68%). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.2 Hz, 4H), 7.36 (d, J = 8.2 Hz, 4H), 3.27 (t, J = 7.2 Hz, 4H), 2.73 (s, 2H), 2.45 (s, 6H), 1.67 (dd, J = 14.8, 7.5 Hz, 4H), 1.36 (dd, J = 6.8, 2.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl ) δ 144.8, 134.5, 129.8, 127.6, 3 75.9, 59.2, 50.9, 27.1, 22.8, 21.6; MS (ESI) m/z [M + Na]+: 481. General experimental procedure for the synthesis of internal ynamides in Scheme 2 and 4: To an oven-dried Schlenk tube equipped with a magnetic stir bar was added secondary amides (0.2 mmol, 1.0 equiv), (Z)-1,2-dichloro alkenes or alkynyl chlorides 5 (0.4 mmol, 2.0 equiv), Cs2CO3 (1.0 mmol, 5.0 equiv) or (0.8 mmol, 4.0 equiv) in DMSO (1.0 mL) at 80 oC or 70 oC. Upon the reaction completion (monitored by TLC), the residue was purified by silica gel chromatography to afford the desired products. A 10 mmol scale synthesis of 6a. In 100 mL oven-dried Schlenk flask, a solution of N,4-dimethylbenzenesulfonamide 1a (1.85 g, 10 mmol), Cs2CO3 (16.2 g, 50 mmol), and (Z)-(1,2dichlorovinyl)benzene (3.44 g, 20 mmol) in DMSO (20 mL) was stirred at 80 oC for 6 h and monitored by TLC. Upon the reaction completion, the reaction solution was cooled to room temperature and quenched with H2O (300 mL). The aqueous layer was extracted three times with ethyl acetate. The combined organic layer was dried over MgSO4. The volatile solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel (petroleum ether/ ethyl acetate = 10:1) to afford pure 6a (2.34 g, 8.2 mmol) as a white solid in 82%. N, 4-Dimethyl-N-(phenylethynyl)benzenesulfonamide (6a).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6a as a white solid (52 mg, 91%). 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.2 Hz, 2H), 7.41–7.34 (m, 4H), 7.29 (dd, J = 5.0, 1.6 Hz, 3H), 3.15 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 133.3, 131.4, 129.8, 128.3, 127.9, 127.9 122.7, 84.0, 69.1, 39.3, 21.9; MS (EI) m/z 285, 187, 130, 105, 89, 65. N-Ethyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (6b).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6b as a white solid (56 mg, 94%). 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.38-7.33 (m, 4H), 7.30–7.24 (m, 3H), 3.48 (q, J = 7.2 Hz, 2H), 2.43 (s, 3H), 1.26 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 134.8, 131.4, 129.8, 128.3, 127.8, 127.7, 123.0, 82.2, 70.9, 46.8, 21.6, 13.3; MS (EI) m/z 299, 207, 180, 165, 144, 105, 89, 65. 4-Methyl-N-(phenylethynyl)-N-propylbenzenesulfonamide (6c).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6c as a white solid (58 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.37-7.26 (m, 7H), 3.36

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(t, J = 7.2 Hz, 2H), 2.43 (s, 3H), 1.81–1.66 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.5, 134.6, 131.2, 129.7, 128.2, 127.6, 127.6, 122.9, 82.4, 70.5, 53.2, 21.5, 21.3, 10.8; MS (EI) m/z 313, 207, 158, 143, 116, 89, 65. N-Butyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (6d).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6d as a white solid (59 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.41–7.15 (m, 7H), 3.39 (t, J = 7.2 Hz, 2H), 2.44 (s, 3H), 1.76–1.60 (m, 2H), 1.41-1.37 (m, 2H), 0.92 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.6, 134.7, 131.3, 129.8, 128.3, 127.7, 127.7, 123.0, 82.5, 70.7, 51.4, 30.0, 21.6, 19.5, 13.6; MS (EI) m/z 327, 207, 172, 144, 130, 105, 65. 4-Methyl-N-octyl-N-(phenylethynyl)benzenesulfonamide (6e).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6e as a white solid (50 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.38–7.26 (m, 7H), 3.39 (t, J = 7.2 Hz, 2H), 2.44 (s, 3H), 1.74–1.63 (m, 2H), 1.34–1.20 (m, 10H), 0.87 (t, J = 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.6, 134.6, 131.3, 129.8, 128.3, 127.7, 127.7, 123.0, 82.5, 70.7, 51.6, 31.6, 29.1, 29.1, 27.9, 26.3, 22.6, 21.6, 14.1; MS (EI) m/z 383, 271, 228, 207, 138, 105, 91. N-Cyclopropyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (6f).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6f as a white solid (53 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.24-7.20 (m, 4H), 7.16– 7.11 (m, 3H), 2.73-2.68 (m, 1H), 2.29 (s, 3H), 0.80–0.73 (m, 2H), 0.68–0.60 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.7, 132.8, 130.3, 128.7, 127.2, 126.9, 126.8, 121.8, 80.9, 69.6, 31.9, 20.6, 5.4; MS (EI) m/z 311, 246, 189, 174, 128, 91. N-Benzyl-4-methyl-N-(phenylethynyl)benzenesulfonamide (6g).22 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6g as a white solid (56 mg, 78%). 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.2 Hz, 2H), 7.34–7.27 (m, 7H), 7.22 (s, 5H), 4.57 (s, 2H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 134.8, 134.5, 131.2, 129.8, 128.9, 128.6, 128.4, 128.2, 127.8, 127.7, 122.9, 82.8, 71.5, 55.8, 21. 7; MS (EI) m/z 361, 297, 206, 179, 165, 106, 91. 4-Methyl-N-(phenylethynyl)-N-((tetrahydrofuran-2-yl)methyl) benzenesulfonamide (6h).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6h as a white solid (58 mg, 81%). 1H NMR (400 MHz, CD2Cl2) δ 7.73 (d, J = 8.2 Hz, 2H), 7.31–7.23 (m, 4H), 7.23–7.17 (m, 3H), 4.19–4.03 (m, 1H), 3.733.70 (m, 1H), 3.62 (dd, J = 14.3, 7.6 Hz, 1H), 3.44 (dd, J = 13.2, 6.8 Hz, 1H), 3.24 (dd, J = 13.2, 5.4 Hz, 1H), 2.34 (s, 3H), 1.94-1.91 (m, 1H), 1.86–1.74 (m, 2H), 1.66–1.51 (m, 1H); 13C{1H} NMR (100 MHz, CD2Cl2) δ 144.7, 134.4, 131.0, 129.6, 128.2, 127.7, 127.6, 122.7, 82.8, 76.1, 70.1, 67.9, 55.0, 29.0, 25.4, 21.3; MS (EI) m/z 355, 290, 200, 155, 130, 105, 71. N, 2-Dimethyl-N-(phenylethynyl)benzenesulfonamide (6i).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6i as a white solid (50 mg, 88%). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.4 Hz, 1H), 7.50 (t, J = 7.4 Hz, 1H), 7.38– 7.33 (m, 2H), 7.31–7.21 (m, 5H), 3.21 (s, 3H), 2.74 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.3, 135.4, 133.5, 132.8, 131.0, 130.4, 128.1, 127.6, 126.1, 122.6, 83.6, 69.7, 38.6, 20.9; MS (EI) m/z 285, 239, 224, 181, 155, 132, 118, 91. 4-(Tert-butyl)-N-methyl-N-(phenylethynyl)benzenesulfonamide (6j).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6j as a white solid (63 mg, 96%). 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.29 (dd, J = 6.4, 3.0 Hz, 2H), 7.21 (dd, J = 5.0, 1.8 Hz, 3H), 3.09 (s, 3H), 1.28 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 156.7, 132.4, 130.3, 127.3, 126.8, 126.7, 125.2, 121.8, 83.1, 68.1, 38.3, 34.3, 30.1; MS (EI) m/z 327, 248, 165, 130, 89. 4-Fluoro-N-methyl-N-(phenylethynyl)benzenesulfonamide (6k).16 Purification by chromatography (petroleum ether/EtOAc =


Page 7 of 9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Organic Chemistry 10:1) afforded 6k as a white solid (38 mg, 66%). 1H NMR (400 MHz, CDCl3) δ 8.01–7.94 (m, 2H), 7.38–7.33 (m, 2H), 7.32–7.27 (m, 4H), 7.26 (s, 1H), 3.17 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.9 (JC-F = 254.8 Hz), 132.3, 131.5, 130.6 (JC-F = 9.6 Hz), 128.3, 128.1, 122.4, 116.5 (JC-F = 22.6 Hz), 83.5, 69.3, 39.4; MS (EI) m/z 289, 276, 178, 130, 89, 63. 4-Chloro-N-methyl-N-(phenylethynyl)benzenesulfonamide (6l).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6l as a white solid (56 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 8.6 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H), 7.39–7.34 (m, 2H), 7.32–7.27 (m, 3H), 3.17 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.5, 134.7, 131.5, 129.6, 129.2, 128.4, 128.1, 122.4, 83.4, 69.4, 39.4; MS (EI) m/z 305, 226, 165, 130, 105, 89, 63. 3-(Phenylethynyl)oxazolidin-2-one (6m).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6m as a white solid (26 mg, 70%). 1H NMR (400 MHz, CDCl3) δ 7.47–7.41 (m, 2 H), 7.33–7.28 (m, 3 H), 4.49-4.45 (m, 2 H), 4.03–3.95 (m, 2 H); 13C{1H} NMR (100 MHz, CDCl3) δ 156.0, 131.6, 128.4, 128.2, 122.2, 79.0, 71.2, 63.1, 47.1; MS (EI) m/z 187, 143, 115, 88, 77, 51. (R)-4-phenyl-3-(phenylethynyl)oxazolidin-2-one (6n).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6n as a white solid (43.6 mg, 83%). 1H NMR (400 MHz, CDCl3) δ 7.55–7.36 (m, 5H), 7.30–7.17 (m, 5H), 5.14 (dd, J = 8.5, 7.2 Hz, 1H), 4.78 (t, J = 8.8 Hz, 1H), 4.31 (dd, J = 8.9, 7.1 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl ) δ 155.5, 136.1, 131.5, 129.6, 3 129.3, 128.1, 128.1, 126.9, 122.2, 78.0, 72.9, 70.7, 62.3; MS (EI) m/z 263, 218, 178, 128, 89, 77. 1-(Phenylethynyl)-1H-pyrrolo[2,3-b]pyridine (6o).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6o as a Colorless liquid (37 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 8.46 (dd, J = 4.8, 1.4 Hz, 1H), 7.92 (dd, J = 7.8, 1.4 Hz, 1H), 7.70–7.56 (m, 2H), 7.43–7.31 (m, 4H), 7.18 (dd, J = 7.8, 4.8 Hz, 1H), 6.57 (d, J = 3.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 149.5, 144.8, 132.0, 129.7, 129.6, 128.3, 122.4, 120.3, 118.0, 103.7, 100.0, 79.2, 71.7; MS (EI) m/z 218, 190, 163, 109, 91, 63. 9-(Phenylethynyl)-9H-carbazole (6p).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6p as a Colorless liquid (48 mg, 89%). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.6 Hz, 2H), 7.71 (d, J = 8.0k Hz, 2H), 7.65–7.59 (m, 2H), 7.55–7.47 (m, 2H), 7.41–7.31 (m, 5H); 13C{1H} NMR (100 MHz, CDCl3) δ 140.5, 131.5, 128.5, 128.0, 126.8, 123.6, 123.0, 122.1, 120.4, 111.3, 78.9, 74.7; MS (EI) m/z 267, 225, 207, 191, 155, 91, 80. 1-(Phenylethynyl)-1H-indole (6q).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6q as a Colorless liquid (40 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 7.69– 7.51 (m, 4H), 7.45–7.30 (m, 4H), 7.29–7.18 (m, 2H), 6.67–6.54 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.2, 131.5, 128.9, 128.5, 128.1, 127.9, 123.6, 122.7, 122.1, 121.3, 111.4, 105.6, 80.9, 70.7; MS (EI) m/z 217, 189, 163, 139, 108, 94. 3-Methyl-1-(phenylethynyl)-1H-indole (6r).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6r as a Colorless liquid (43 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 7.66– 7.49 (m, 4H), 7.39–7.31 (m, 4H), 7.24 (dd, J = 5.8, 2.0 Hz, 1H), 7.03 (d, J = 1.0 Hz, 1H), 2.32 (d, J = 1.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 138.5, 131.3, 128.7, 128.4, 127.8, 125.8, 123.5, 123.0, 121.5, 119.3, 114.9, 111.3, 81.2, 70.4, 9.6; MS (EI) m/z 231, 202, 178, 131, 91, 51. N,N'-(Pentane-1,5-diyl)bis(4-methyl-N-(phenylethynyl)benzenesulfonamide) (6s).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 6s as a white solid (89 mg, 73%). 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 4H), 7.44–7.36 (m, 8H), 7.34–7.28 (m, 6H), 3.42 (t, J = 7.2 Hz, 4H), 2.47 (s, 6H), 1.821.69 (m, 4H), 1.51-1.44 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3)

δ 144.6, 134.4, 131.3, 129.8, 128.2, 127.7, 127.6, 122.8, 82.2, 70.7, 51.3, 27.4, 22.9, 21.6; MS (ESI) m/z [M + Na]+: 633. N, 4-Dimethyl-N-(o-tolylethynyl)benzenesulfonamide (7a).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7a as a white solid (52 mg, 87%). 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.2 Hz, 2H), 7.36–7.26 (m, 3H), 7.13 (d, J = 4.0 Hz, 2H), 7.09–7.04 (m, 1H), 3.14 (s, 3H), 2.39 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.0, 139.7, 133.4, 131.4, 129.9, 129.5, 127.9, 127.8, 125.6, 122.6, 87.9, 68.1, 39.5, 21.6, 20.7; MS (EI) m/z 299, 144, 115, 103, 77, 51. N, 4-Dimethyl-N-(m-tolylethynyl)benzenesulfonamide (7b).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7b as a white solid (54 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.21– 7.13 (m, 3H), 7.09 (d, J = 6.2 Hz, 1H), 3.14 (s, 3H), 2.46 (s, 3H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.7, 137.9, 133.4, 132.0, 129.8, 128.7, 128.4, 128.1, 127.9, 122.5, 83.6, 69.2, 39.3, 21.6, 21.2; MS (EI) m/z 299, 220, 144, 119, 103, 77, 51. N, 4-Dimethyl-N-(p-tolylethynyl)benzenesulfonamide (7c).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7c as a white solid (51 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.14 (s, 3H), 2.45 (s, 3H), 2.33 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.8, 138.1, 133.3, 131.5, 129.8, 129.1, 127.9, 119.6, 83.3, 69.1, 39.4, 21.7, 21.4; MS (EI) m/z 299, 253, 144, 103, 77, 51. N-((4-Methoxyphenyl)ethynyl)-N,4-dimethylbenzenesulfonamide (7d).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7d as a white solid (53 mg, 84%). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 3.80 (d, J = 4.3 Hz, 3H), 3.13 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 159.6, 144.7, 133.4, 129.8, 129.7, 127.9, 114.6, 113.9, 82.5, 68.7, 55.3, 39.4, 21.6; MS (EI) m/z 315, 236, 160, 119, 91, 65. N-((4-(Tert-butyl)phenyl)ethynyl)-N,4-dimethylbenzenesulfonamide (7e).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7e as a white solid (59 mg, 87%). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H), 7.30 (s, 4H), 3.12 (s, 3H), 2.43 (s, 3H), 1.29 (s, 9H); 13C{1H} NMR (100 MHz, CDCl ) δ 151.3, 144.8, 133.3, 131.4, 3 129.8, 127.9, 125.3, 119.7, 83.4, 69.1, 39.4, 34.7, 31.2, 21.7; MS (EI) m/z 341, 326, 186, 171, 145, 115, 91. N-((4-Fluorophenyl)ethynyl)-N,4-dimethylbenzenesulfonamide (7f).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7f as a white solid (46 mg, 76%). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.42–7.30 (m, 4H), 6.97 (dd, J = 12.0, 5.2 Hz, 2H), 3.14 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.3 (JC-F = 247.6 Hz), 144.8 (JC-F = 5.8 Hz), 133.5 (JC-F = 8.2 Hz), 133.3, 129.9, 127.8, 118.8, 115.5 (JC-F = 22.0 Hz), 83.6, 68.0, 39.3, 21.6; MS (EI) m/z 303, 224, 148, 107, 91, 65. N-((4-Chlorophenyl)ethynyl)-N,4-dimethylbenzenesulfonamide (7g).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7g as a white solid (50 mg, 79%). 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.30–7.23 (m, 4H), 3.14 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 133.8, 133.3, 132.6, 129.7, 128.6, 127.8, 121.3, 84.9, 68.2, 39.2, 21.7; MS (EI) m/z 319, 280, 207, 167, 135, 88, 61. N-((4-Bromophenyl)ethynyl)-N,4-dimethylbenzenesulfonamide (7h).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7h as a white solid (54 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 8.2 Hz, 2H), 7.46–7.33 (m, 4H), 7.20 (d, J = 8.4 Hz, 2H), 3.14 (s, 3H), 2.45 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 133.3, 132.7, 131.5, 129.9, 127.8, 121.9, 121.8, 85.1, 68.3, 39.2, 21.7; MS (EI) m/z 363, 284, 208, 167, 114, 91, 65.



N, 4-Dimethyl-N-(thiophen-2-ylethynyl)benzenesulfonamide (7i).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7i as a white solid (47 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.28–7.22 (m, 1H), 7.16 (dd, J = 3.6, 1.0 Hz, 1H), 6.96 (dd, J = 5.2, 3.6 Hz, 1H), 3.14 (s, 3H), 2.47 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 133.3, 132.9, 129.8, 127.8, 127.7, 126.9, 122.7, 87.4, 62.5, 39.3, 21.6; MS (EI) m/z 291, 245, 212, 154, 136, 111, 95, 65. N, 4-Dimethyl-N-(naphthalen-2-ylethynyl)benzenesulfonamide (7j).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7j as a white solid (54 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 6.2 Hz, 3H), 7.77 (dd, J = 15.8, 9.0 Hz, 3H), 7.49–7.45 (m, 2H), 7.39 (t, J = 9.2 Hz, 3H), 3.19 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.8, 133.4, 133.4, 133.0, 132.6, 130.9, 129.9, 128.3, 127.9, 127.8, 127.6, 126.5, 126.5, 120.1, 84.3, 69.6, 39.4, 21.7; MS (EI) m/z 335, 271, 229, 180, 139. 91. (Z)-N-(1-chloro-4-phenylbut-1-en-2-yl)-N,4-dimethylbenzenesulfonamide (7k).16 Purification by chromatography (petroleum ether/EtOAc = 10:1) afforded 7k as a Colorless liquid (48 mg, 68%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.2 Hz, 2H), 7.28 (dd, J = 7.4, 5.8 Hz, 4H), 7.23–7.13 (m, 3H), 5.89 (s, 1H), 3.04 (s, 3H), 2.86–2.74 (m, 4H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.5, 142.6, 140.4, 136.5, 129.5, 128.4, 128.3, 127.5, 126.1, 116.2, 37.4, 36.8, 33.3, 21.5; MS (ESI) m/z [M + Na]+: 372.

■ ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at http://pubs.acs.org. Copies of 1H and 13C NMR spectra for all compounds

■ AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]

ORCID Zhenming Zhang: 0000-0001-8550-5398 Junfeng Zhao: 0000-0003-4843-4871 Author Contributions †X.Z., and Y.T contributed equally Notes The authors declare no competing financial interests.

■ ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China (21778025, 21762021), and the Science and Technology Project of Jiangxi Provincial Education Department (GJJ150297, GJJ150324).

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