Base-Promoted Stereoselective Hydrogenation of Ynamides with Sulfonyl Hydrazide to Give Z-Enamides

Sulfonyl Hydrazide to Give Z ‑Enamides

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Base-Promoted Stereoselective Hydrogenation of Ynamides with

Zemin Zhao, Qingyu Tian, Yanhui Chen, Si Wen, Yuqing Zhang, and Guolin Cheng*

Cite This: J. Org. Chem. 2021, 86, 10407 −10413

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sı Supporting Information

ABSTRACT: A base-mediated semihydrogenation of ynamides

using p-toluenesulfonyl hydrazide as an inexpensive and easy-to-

handle hydrogen donor is reported. This transition-metal-free

protocol avoids overhydrogenation and reduction of other

functional groups, generating the thermodynamically unfavorable

Z-enamides exclusively.

INTRODUCTION

Scheme 1. Synthesis of Enamides

■

Enamides are versatile motifs that have been widely found in

biologically active natural products. In addition, they also

serve as valuable building blocks in organic synthesis.

Traditional approaches to these motifs are mainly through

the condensation reactions of carbonyl compounds with

amides, in which relatively harsh conditions were usually

required. In the past decades, the transition metal (TM)-

catalyzed cross-coupling reactions have emerged as powerful

strategies to access enamide moieties. These strategies include

(

1) the Ullmann-type reaction of alkenyl bromides with amides

Scheme 1a, route 1); (2) the Chan−Lam-type reaction

between alkenyltriﬂuoroborate salts and amides (Scheme 1a,

route 2); (3) the oxidative cross-coupling between electron-

deﬁcient alkenes with amides (Scheme 1a, route 3); and (4)

the addition of N−H bonds of amides to alkynes (Scheme 1a,

route 4). However, the above-mentioned protocols commonly

gave the thermodynamically favorable E-enamides as the major

isomers.

The TM-catalyzed semihydrogenation of alkynes is one of

the most commonly used methods to obtain Z-oleﬁns. In

006, Hsung and co-workers documented the synthesis of Z-

enamides from ynamides using a Lindlar catalyst (Scheme 1b,

route 5). Miesch reported that the semihydrogenation of

ynamides using 1.2 equiv of NiP2 could give Z-enamides

exclusively (Scheme 1b, route 6). Recently, Pd/HCO NH

and Au/HCO NH catalytic systems have been developed for

the semihydrogenation of ynamides to give Z-enamides with

high stereoselectivity by Swamy’s and Xu’s groups, respectively

(

Scheme 1b, routes 7 and 8). However, these methods also

Received: May 9, 2021

Published: July 27, 2021

possess several disadvantages such as the requirement of noble

metal catalysts, overhydrogenation, reduction of other func-

tional groups, and the formation of non-negligible E-isomers in

some cases. Thus, the development of TM-free and

stereoselective hydrogenation of ynamides is highly desirable.

Herein, we report a base-promoted hydrogenation of ynamides

2021 American Chemical Society

J. Org. Chem. 2021, 86, 10407−10413

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The Journal of Organic Chemistry

Article

using inexpensive and easy-to-handle sulfonyl hydrazide as the

hydrogenating source to deliver Z-enamides with exclusive

stereoselectivily (Scheme 1c).

as follows: 1a (0.1 mmol), 2a (2 equiv), and Na CO (1.5

2 3

equiv) in tert-butanol (1 mL) at 80 °C under a nitrogen

atmosphere for 12 h (entry 17).

With the optimal conditions in hand, we investigated the

scope and limitations of this semihydrogenation reaction

RESULTS AND DISCUSSION

We initially studied the stereoselective semihydrogenation

reaction by investigating the model reaction of ynamide 1a

■

(

Scheme 2). In addition to the Ms-protected ynamide 1a, Ts-

(

0.1 mmol), p-toluenesulfonyl hydrazide 2a (2 equiv), and

Scheme 2. Scope of Ynamides

K CO (2 equiv) in DMF (1 mL) at 100 °C under a nitrogen

atmosphere for 12 h. To our delight, the desired product 3a

was acquired in 50% yield (Table 1, entry 1). Then we

Table 1. Optimization of the Reaction Conditions

entry

solvent

DMF

DMSO

tert-butanol

acetonitrile

toluene

base

yield (%)

K CO

trace

85 (84)

K CO

DCE

dioxane

K CO

tert-butanol

KOH

K PO

Li CO

Cs CO

Na CO

a (0.1 mmol), 2a (0.2 mmol), solvent (1 mL), base (2.0 equiv) at

00 °C for 12 h, under N . The yields were determined by H NMR

analysis of the crude product using CH Br as the internal standard.

Isolated yield is shown in parentheses. At 80 °C. 2a (1.5 equiv). 2a

(2.5 equiv). Na CO (1.5 equiv). Na CO (1.0 equiv).

2 3 2 3

screened a range of solvents under the above conditions. It can

be observed that the yields increased obviously to 68% in both

DMSO and tert-butanol, probably because polar solvents

favored this transformation (entries 2 and 3). No expected

product was observed or the yields dropped slightly with 1,2

dichloroethane, toluene, 1,4-dioxane, and acetonitrile as the

solvents (entries 4−7). Next, we surveyed the inﬂuence of

bases on the reactivity of this reaction using tert-butanol as

solvent. When K CO was replaced with KOH and K PO , the

Reaction conditions: 1 (0.1 mmol), 2a (0.2 mmol), tert-butanol (1

mL), Na CO (1.5 equiv), 80 °C, 12 h, under N .

and Cbz-protected ynamides smoothly convert to the

corresponding Z-enamides in good yields (3b, 3c). It should

yield dropped clearly to 53% and 45%, separately (entries 8

and 9). When Li CO and Cs CO were used, a trace of 3a was

be noted that the Cbz− group could not survive under Pd/H

discovered (entries 10 and 11). It is noteworthy that the yield

improved slightly to 74% when Na CO was used (entry 12).

hydrogenation reaction conditions. Ynamides with an electron-

donating (3d) and electron-withdrawing group (3h) on N-

arenes were both well compatible. Halogens (F−, Cl−, and

Br−) were also tolerated to give the desired products in 66−

70% yields (3e−g). It is gratifying that the introduction of N-

alkyl groups did not cause signiﬁcant eﬀects, good yields were

generally observed, and the stereoselectivity remains the same

However, only a 12% yield of 3a was formed in the absence of

Na CO (entry 13). The screening of the reaction temperature

showed that the yield of 3a was increased slightly at 80 °C

entry 14). We further investigated the loading of 2a and

Na CO , and the optimized reaction conditions were obtained

(

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The Journal of Organic Chemistry

3k−n). In the further course of the evaluation of the substrate

obtained in 83% yield (eq 1 ). It is worth mentioning that the

Article

(

Scheme 3. Proposed Reaction Pathway

scope, we noticed that a variety of N-alkynyl oxazolidin-2-ones

were suitable substrates to give the corrsponding (Z)-3-

styryloxazolidin-2-ones in good to excellent yields (3p−s). It

should be noted that exclusive Z-isomers were formed in all

cases of the aforementioned semihydrogenation reactions, as

indicated by the X-ray structures of 3s. We also evaluated the

semihydrogenation reaction of (phenylethynyl)(p-tolyl)-

sulfane, and low yield and poor stereoselectivity (Z/E =

.4:1) were observed (3t). However, alkyl alkyne (3u), indole-

based ynamide (3v), and 1,2-diphenylethyne (3w) failed to

deliver the reduction products. In addition, sulﬁnyl alkyne

completely decomposed under the reaction conditions (3x).

No reaction occurred when phosphoryl alkyne (3y) was

subjected to the reaction system, probably because phosphoryl

alkyne is a poor electrophilic Michael acceptor that is unlikely

to be attacked by hydrazide.

deprotonation of B. Finally, the sequential release of a TsNa

and a N from B leads to the desired Z-enamide 3.

To verify the generality of this reaction, we applied the

reaction system in a gram-scale synthesis of 3a, which was

CONCLUSIONS

■

In summary, we have discovered a transition-metal-free

semihydrogenation reaction of ynamides using p-toluenesul-

fonyl hydrazide as an inexpensive and commercially available

hydrogen donor. A broad range of Z-enamides were

synthesized in moderate to excellent yields with exclusive

stereoselectivity. This eco-friendly protocol proceeded under

transition-metal-free conditions using alcohol as solvents,

avoiding overhydrogenation and reduction of other functional

groups.

EXPERIMENTAL SECTION

■

General Information. All commercially available solvents were of

analytical grade and used as received.The other commercial chemicals

were used without further puriﬁcation. All reactions were performed

under an inert atmosphere of nitrogen in ﬂame-dried glassware, unless

otherwise stated. Analytical thin layer chromatography was performed

on 0.25 mm silica gel 60-F254. Visualization was carried out with UV

light and Vogel’s permanganate. Preparative TLC was performed on

.0 mm silica gel. H NMR spectra were recorded on a Bruker Avance

III instrument (500 MHz). C NMR spectra were recorded on a

Bruker Avance III instrument (126 MHz) and were fully decoupled

by broad band proton decoupling. High-resolution mass spectra

(

HRMS) were recorded on an Agilent 1290 Mass spectrometer using

ESI-TOF (electrospray ionization time-of-ﬂight). Crystal structure

and data were recorded on an Agilent Gemini E diﬀractometer. NMR

spectra were recorded in CDCl . H NMR spectra were referenced to

residual CHCl at 7.26 ppm, and C NMR spectra were referenced to

generation of sodium 4-methylbenzenesulﬁnate (NaTs) was

the central peak of CDCl at 77.0 ppm. Chemical shifts (δ) are

conﬁrmed by H and C{1H} NMR (eq 2). To further

explore the mechanism of the reaction, we conducted the

deuteration experiments. The ynamide 1a was subjected to the

reported in ppm, and coupling constants (J) are in hertz (Hz).

Multiplicities are reported using the following abbreviations: s =

singlet, d = doublet, t = triplet, q = quartet, m = multiplet. ₁₄

Typical Procedure for the Synthesis of Ynamide 1a. To a

dried ﬂask were added N-(p-tolyl)methanesulfonamide (0.906 g, 5.0

mmol), bromoalkyne (1.08 g, 6.0 mmol), CuSO ·5H O (0.125 g, 0.5

standard reaction conditions using CD OD as a solvent,

leading to H/D exchange occurring at the alkenyl position of

the corresponding product (eq 3). In addition, the

incorporation of deuterium at the alkenyl position did not

occur when 3a was subjected to the deuteration conditions in

the obsence of p-toluenesulfonyl hydrazide (eq 4). Meawhile,

full deuterium incorporation on the Ms group of the above-

mentioned expriments was observed.

mmol), 1,10-phenanthroline (0.18 g, 1.0 mmol), K CO (1.38 g, 10.0

mmol), and toluene (30 mL). The ﬂask was charged with nitrogen,

and the solution was heated at 80 °C in oil bath for 12 h. After

completion, the crude reaction mixture was cooled to room

temperature, ﬁltered through Celite, and concentrated. Puriﬁcation

of the crude residue using silica gel ﬂash column chromatography gave

a as yellow solid (0.989 g, 69%).

General Procedure 3. A dried 10 mL Schlenk tube was charged

According to the above experiments, we propose a

mechanism as outlined in Scheme 3. First, keteniminium

with ynamide 1 (0.1 mmol, 1 equiv), 4-methylbenzenesulfonohy-

drazide (37.2 mg, 0.2 mmol, 2.0 equiv), Na CO (15.9 mg, 0.15

ionic species A is formed under basic conditions from ynamide

Then the nucleophilic addition of p-toluenesulfonyl

mmol, 1.5 equiv), and tert-butanol (1 mL) under a nitrogen

atmosphere. The reaction mixture was heated to 80 °C on a heating

plate for 12 h with vigorous stirring. Upon completion, the reaction

mixture was cooled to room temperature, diluted with ethyl acetate,

hydrazide to A, which is highly regio- and stereoselective,

occurred at the sterically less hindered face to give

intermediate B. Subsquently, N anion C is generated through

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Article

and ﬁltered through a pad of Celite. The ﬁltrate was concentrated

under vacuum, and the resulting residue was puriﬁed by preparative

thin layer chromatography (PTLC) with ethyl acetate:hexane to give

the corresponding products 3.

(Z)-N-(4-Bromophenyl)-N-styrylmethanesulfonamide (3g). (23.4

mg, 66%) was prepared from the typical procedure (ethyl

acetate:hexane = 1:20) as a yellow solid; mp 125−126 °C.

H NMR (500 MHz, Chloroform-d) δ = 7.28−7.26 (m, 2H),

(

Z)-N-Styryl-N-(p-tolyl)methanesulfonamide (3a). (24.1 mg,

7.16−7.14 (m, 3H), 7.14−7.04 (m, 4H), 6.65 (d, J = 9.0 Hz, 1H),

4%) was prepared from the typical procedure (ethyl acetate:hexane

6.16 (d, J = 9.0 Hz, 1H), 2.93 (s, 3H); C{ H} NMR (126 MHz,

Chloroform-d) δ = 138.1, 133.5, 132.0, 128.8, 128.2, 127.8, 127.5,

125.8, 122.3 (d, J = 2.0 Hz), 120.7, 37.2; IR (ATR) ν 2925 (m) 2853

(m) 1590 (w) 823 (m) 759 (m) 700 (m) 535 (m) HRMS (ESI-

1:20) as a yellow solid; mp 92−93 °C.

H NMR (500 MHz, Chloroform-d) δ = 7.14−7.09 (m, 4H),

.04−6.97 (m, 3H), 6.91−6.86 (m, 2H), 6.59 (d, J = 9.0 Hz, 1H),

.04 (d, J = 9.0 Hz, 1H), 2.83 (s, 3H), 2.14 (s, 3H); C{ H} NMR

13 1

TOF) m/z: [M + H] calcd for C H BrNO S 352.0001, found

(126 MHz, Chloroform-d) δ = 137.1, 136.4, 133.8, 129.4, 128.9,

352.0002.

27.6, 127.1, 126.7, 126.3, 121.7, 36.7, 20.8; IR (ATR) ν 2926 (m)

Ethyl (Z)-4-(N-Styrylmethylsulfonamido)benzoate (3h). (9.1 mg,

54%) was prepared from the typical procedure (ethyl acetate:hexane

= 1:20) as a yellow oil.

614 (w) 813 (m) 764 (m) 700 (m) HRMS (ESI-TOF) m/z: [M +

H] calcd for C H NO S 288.1053; found 288.1052.

(Z)-4-Methyl-N-styryl-N-(p-tolyl)benzenesulfonamide (3b). (25.2

H NMR (500 MHz, Chloroform-d) δ = 7.87−7.84 (m, 2H),

mg, 67%) was prepared from the typical procedure (ethyl

acetate:hexane = 1:20) as a white solid; mp 110−111 °C.

7.41−7.38 (m, 2H), 7.21−7.18 (m, 2H), 7.12−7.05 (m, 3H), 6.65 (d,

J = 8.9 Hz, 1H), 6.26 (d, J = 8.8 Hz, 1H), 4.32 (q, J = 7.1 Hz, 2H),

H NMR (500 MHz, Chloroform-d) δ = 7.48−7.44 (m, 2H), 7.22

2.95 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); C{ H} NMR (126 MHz,

Chloroform-d) δ = 165.7, 143.2, 133.3, 130.3, 128.7, 128.4, 127.9,

127.8, 125.3, 125.2, 124.3, 61.1, 37.6, 14.3; IR (ATR) ν 2925 (m)

(

td, J = 5.9 Hz, 2.8 Hz, 4H), 7.09−7.02 (m, 3H), 6.91−6.84 (m, 4H),

.53 (d, J = 9.1 Hz, 1H), 6.03 (d, J = 9.0 Hz, 1H), 2.40 (s, 3H), 2.18

s, 3H); ¹³C{ H} NMR (126 MHz, Chloroform-d) δ = 143.9, 136.9

(

2852 (m) 1712 (s) 1604 (m) 855 (m) 768 (m) 696 (m) HRMS

(d, J = 9.1 Hz), 134.0 (d, J = 14.9 Hz), 129.4, 129.0, 127.9, 127.5,

(ESI-TOF) m/z: [M + H] calcd for C18

20NO

S 346.1108, found

127.4, 127.0, 126.7, 122.0, 21.5, 20.9; IR (ATR) ν 2921 (m) 1598

346.1107.

(w) 812 (m) 768 (m) 703 (m) HRMS (ESI-TOF) m/z: [M + H]

(Z)-N-Styryl-N-(m-tolyl)methanesulfonamide (3i). (16.1 mg,

57%) was prepared from the typical procedure (ethyl acetate:hexane

= 1:20) as a yellow oil.

calcd for C H NO S 364.1366, found 364.1367.

Benzyl (Z)-Styryl(p-tolyl)carbamate (3c). (19.7 mg, 57%) was

prepared from the typical procedure (ethyl acetate:hexane = 1:20) as

a colorless oil.

H NMR (500 MHz, Chloroform-d) δ = 7.18−7.15 (m, 2H),

7.11−7.04 (m, 5H), 7.03 (d, J = 8.1 Hz, 1H), 6.89−6.86 (m, 1H),

6.67 (d, J = 9.1 Hz, 1H), 6.11 (d, J = 9.1 Hz, 1H), 2.92 (s, 3H), 2.19

(d, J = 0.8 Hz, 3H); C{ H} NMR (126 MHz, Chloroform-d) δ =

140.3, 136.0, 130.6, 130.3, 129.7, 129.0, 128.6, 126.8, 126.4, 125.4,

111.8, 39.4, 21.3; IR (ATR) ν 2925 (m) 2854 (m) 1608 (w) 780 (m)

762 (m) 692 (s) HRMS (ESI-TOF) m/z: [M + H]⁺calcd for

H NMR (500 MHz, Chloroform-d) δ = 7.31−7.27 (m, 3H), 7.20

(

dd, J = 7.3 Hz, 2.3 Hz, 2H), 7.14−7.05 (m, 7H), 6.96 (d, J = 8.0 Hz,

H), 6.59−6.45 (m, 1H), 6.11 (d, J = 9.1 Hz, 1H), 5.08 (s, 2H), 2.22

s, 3H); ¹³C{ H} NMR (126 MHz, Chloroform-d) δ = 154.3, 137.5,

(

36.0, 135.5, 134.9, 129.0, 128.3 (d, J = 11.5 Hz), 128.0, 127.8, 127.3,

27.0, 125.5 (d, J = 14.0 Hz), 67.8, 20.8; IR (ATR) ν 2922 (m) 2852

18NO

S 288.1053, found 288.1051.

(m) 1709 (s) 1643 (w) 816 (m) 762 (m) 694 (m) HRMS (ESI-

(Z)-N-Styryl-N-(o-tolyl)methanesulfonamide (3j). (21.1 mg, 72%)

TOF) m/z: [M + H] calcd for C H NO 344.1645, found

was prepared from the typical procedure (ethyl acetate:hexane =

1:20) as a yellow oil.

44.1643.

Z)-N-(4-Methoxyphenyl)-N-styrylmethanesulfonamide (3d).

22.7 mg, 75%) was prepared from the typical procedure (ethyl

¹H NMR (500 MHz, Chloroform-d) δ = 7.05 (dd, J = 7.8 Hz, 1.3,

1H), 6.96−6.91 (m, 5H), 6.89 (dd, J = 7.3 Hz, 1.9 Hz, 1H), 6.84−

6.80 (m, 2H), 6.79 (d, J = 9.9 Hz, 1H), 5.93 (d, J = 9.8 Hz, 1H), 3.01

(

acetate:hexane = 1:20) as a yellow solid; mp 88−89 °C.

H NMR (500 MHz, Chloroform-d) δ = 7.16 (ddd, J = 13.0 Hz,

(s, 3H), 2.24 (s, 3H); C{ H} NMR (126 MHz, Chloroform-d) δ =

137.5, 136.5, 134.1, 131.2, 129.4, 128.3, 127.1, 126.3, 126.2 (d, J = 6.4

Hz), 115.1, 38.5, 19.0; IR (ATR) ν 2928 (m) 1585 (w) 1495 (m) 734

(m) 700 (m) HRMS (ESI-TOF) m/z: [M + H]⁺calcd for

7.3 Hz, 1.9 Hz, 4H), 7.10−7.02 (m, 3H), 6.69 (d, J = 9.2 Hz, 1H),

6.67−6.63 (m, 2H), 6.06 (d, J = 9.1 Hz, 1H), 3.69 (s, 3H), 2.90 (s,

H); ¹³C{ H} NMR (126 MHz, Chloroform-d) δ = 158.5, 133.8,

131.4, 128.8, 128.6, 127.5, 127.0, 126.5, 120.2, 114.0, 55.3, 36.5; IR

18NO

288.1053, found 288.1050.

(ATR) v 2935 (m) 2839 (m) 1608 (w) 823 (m) 766 (m) 699 (m)

(Z)-N-Benzyl-N-styrylmethanesulfonamide (3k). (19.4 mg, 65%)

HRMS (ESI-TOF) m/z: [M + H] calcd for C H NO S 304.1002,

found 304.1003.

was prepared from the typical procedure (ethyl acetate:hexane =

1:20) as a yellow solid; mp 65−66 °C.

(Z)-N-(4-Fluorophenyl)-N-styrylmethanesulfonamide (3e). (20.2

H NMR (500 MHz, Chloroform-d) δ = 7.44−7.40 (m, 2H),

mg, 70%) was prepared from the typical procedure (ethyl

acetate:hexane = 1:20) as a yellow solid; mp 90−91 °C.

7.36−7.32 (m, 2H), 7.30−7.23 (m, 4H), 7.20−7.17 (m, 2H), 6.19 (d,

J = 8.7 Hz, 1H), 6.13 (d, J = 8.7 Hz, 1H), 4.52 (s, 2H), 2.81 (s, 3H);

C{ H} NMR (126 MHz, Chloroform-d) δ = 135.7, 134.4, 128.9,

H NMR (500 MHz, Chloroform-d) δ = 7.25−7.22 (m, 2H),

.12−7.05 (m, 5H), 6.84−6.80 (m, 2H), 6.70 (d, J = 9.1 Hz, 1H),

.10 (d, J = 9.1 Hz, 1H), 2.92 (s, 3H); C{ H} NMR (126 MHz,

128.7, 128.4, 128.1, 127.9, 125.5, 125.0, 52.3, 39.1; IR (ATR) ν 2926

(m) 1701 (w) 1455 (m) 733 (m) 696 (m); HRMS (ESI-TOF) m/z:

Chloroform-d) δ = 161.3 (d, J = 247.9 Hz), 134.7 (d, J = 3.2 Hz),

33.6, 129.0 (d, J = 8.7 Hz), 128.7, 127.6, 127.2, 126.3, 120.6, 115.7

[M + H] calcd for C16

18NO

S 288.1053, found 288.1053.

(Z)-N-Styryl-N-(2,2,2-triﬂuoroethyl)methanesulfonamide (3l).

(15.3 mg, 55%) was prepared from the typical procedure (ethyl

acetate:hexane = 1:20) as a white solid; mp 65−66 °C.

(

d, J = 23.0 Hz), 36.9; IR (ATR) ν 2927 (m) 1605 (w) 1321 (s) 830

m) 759 (m) 700 (m) HRMS (ESI-TOF) m/z: [M + H] calcd for

C H FNO S 292.0802, found 292.0802.

H NMR (500 MHz, Chloroform-d) δ = 7.48−7.44 (m, 2H),

(Z)-N-(4-Chlorophenyl)-N-styrylmethanesulfonamide (3f). (21.1

7.41−7.37 (m, 2H), 7.35−7.31 (m, 1H), 6.38 (d, J = 8.4 Hz, 1H),

6.18 (d, J = 8.4 Hz, 1H), 3.93 (q, J = 8.6 Hz, 2H), 3.03 (s, 3H);

C{ H} NMR (126 MHz, Chloroform-d) δ = 133.5, 128.9, 128.8,

mg, 68%) was prepared from the typical procedure (ethyl

acetate:hexane = 1:20) as a yellow oil.

H NMR (500 MHz, Chloroform-d) δ = 7.23−7.20 (m, 2H),

128.6, 128.1, 124.0, 124.0 (q, J = 281.4 Hz), 48.8 (q, J = 34.4 Hz),

39.4; IR (ATR) ν 2926 (m) 1643 (w) 1342 (s) 724 (m) 690 (m)

.16−7.07 (m, 7H), 6.66 (d, J = 9.0 Hz, 1H), 6.15 (d, J = 9.0 Hz,

H), 2.93 (s, 3H); C{ H} NMR (126 MHz, Chloroform-d) δ =

37.5, 133.6, 132.8, 128.9 (d, J = 25.5 Hz), 127.9 (d, J = 25.6 Hz),

13 1

HRMS (ESI-TOF) m/z: [M + H] calcd for C H F NO S

280.0614, found 280.0613.

27.5, 125.9, 122.0, 37.1, 29.7; IR (ATR) ν 2926 (m) 1639 (w) 826

(Z)-N-Cyclohexyl-N-styrylmethanesulfonamide (3m). (11.0 mg,

40%) was prepared from the typical procedure (ethyl acetate:hexane

= 1:20) as a white solid; mp 88−89 °C.

(m) 770 (m) 732 (s) 699 (m) HRMS (ESI-TOF) m/z: [M + H]

calcd for C H ClNO S 308.0507, found 308.0506.

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https://pubs.acs.org/doi/10.1021/acs.joc.1c01085.

Article

H NMR (500 MHz, Chloroform-d) δ = 7.75−7.71 (m, 2H),

(ESI-TOF) m/z: [M + H] calcd for C H FNO 208.0768, found

11 11 2

208.0770.

.35−7.28 (m, 3H), 6.54 (d, J = 8.3 Hz, 1H), 5.94 (d, J = 8.4 Hz,

H), 3.94−3.88 (m, 1H), 2.85 (s, 3H), 1.92−1.88 (m, 2H), 1.75 (dt,

(Z)-Styryl(p-tolyl)sulfane (3t). (Z:E = 2.4:1) (7.2 mg, 34%) was

prepared from the typical procedure (ethyl acetate:hexane = 1:20) as

a yellow oil.

J = 14.4 Hz, 3.3 Hz, 2H), 1.58 (d, J = 7.5 Hz, 3H), 1.50−1.43 (m,

H), 1.31 (dt, J = 13.4 Hz, 3.6 Hz, 1H), 1.01 (dt, J = 13.1 Hz, 3.7 Hz,

H); ¹³C{ H} NMR (126 MHz, Chloroform-d) δ = 135.2, 134.1,

29.7, 128.7, 128.3, 122.1, 60.2, 39.1, 30.7, 25.8, 25.2; IR (ATR) ν

H NMR (500 MHz, Chloroform-d) δ = 7.55−7.50 (m, 2H),

7.41−7.20 (m, 5H), 7.16 (d, J = 7.8 Hz, 2H), 6.54 (d, J = 10.7 Hz,

928 (s) 2853 (m) 1667 (w) 765 (m) HRMS (ESI-TOF) m/z: [M +

1H), 6.46 (d, J = 10.8 Hz, 1H), 2.35 (s, 3H); C{ H} NMR (126

MHz, Chloroform-d) δ = 137.3, 136.7, 131.1, 130.6, 130.5, 129.9,

H] calcd for C H NO S 280.1366, found 280.1364.

28.6, 127.4, 125.9, 124.4, 21.1; IR (ATR) ν 2922 (m) 2853 (m)

596 (m) 804 (s) 740 (m) 688 (m) HRMS (ESI-TOF) m/z: [M +

H] calcd for C H S 227.0889, found 227.0884.

Gram-Scale Synthesis of 3a. A dried 100 mL Schlenk tube was

charged with N-(phenylethynyl)-N-(p-tolyl)methanesulfonamide 1a

1.43 g, 5.0 mmol, 1 equiv), 4-methylbenzenesulfonohydrazide

(1.8664 g, 10 mmol, 2.0 equiv), Na CO (0.7957 g, 7.5 mmol, 1.5

equiv), and tert-butanol (50 mL). In a nitrogen atmosphere, the

reaction mixture was heated to 80 °C in an oil bath for 24 h under

vigorous stirring. Upon completion, the reaction mixture was cooled

to room temperature, diluted with ethyl acetate, and ﬁltered through a

pad of Celite. The ﬁltrate was concentrated under vacuum, and the

resulting residue was puriﬁed by chromatography with ethyl

acetate:petroleum ether = 1:20 to give the corresponding products

(Z)-N-Cyclopropyl-N-styrylmethanesulfonamide (3n). (18.9 mg,

8%) was prepared from the typical procedure (ethyl acetate:hexane

1:20) as a white solid; mp 100−101 °C.

15 15

H NMR (500 MHz, Chloroform-d) δ = 7.45−7.42 (m, 2H),

.31−7.24 (m, 3H), 6.25 (d, J = 8.6 Hz, 1H), 6.04 (d, J = 8.7 Hz,

(

H), 2.97 (s, 3H), 2.53 (tt, J = 7.0 Hz, 3.6 Hz, 1H), 0.77−0.73 (m,

H), 0.60−0.56 (m, 2H); C{ H} NMR (126 MHz, Chloroform-d)

δ = 135.1, 129.0, 128.1, 127.8, 125.5 (d, J = 5.5 Hz), 37.7, 31.2, 8.2;

IR (ATR) ν 2923 (w) 1640 (w) 761 (m) 693 (m) HRMS (ESI-TOF)

m/z: [M + H] calcd for C H NO S 238.0896, found 238.0895.

(

Z)-N-(4-Methoxystyryl)-N-(p-tolyl)methanesulfonamide (3o).

(

24.5 mg, 67%) was prepared from the typical procedure (ethyl

acetate:hexane = 1:20) as a yellow oil.

H NMR (500 MHz, Chloroform-d) δ = 7.28−7.23 (m, 5H), 7.02

a (1.19 g, 83%) as a yellow oil.

Conﬁrmation of Sodium 4-Methylbenzenesulﬁnate. A dried

(

d, J = 8.2 Hz, 2H), 6.70−6.65 (m, 2H), 6.51 (d, J = 8.7 Hz, 1H),

.12 (d, J = 8.7 Hz, 1H), 3.74 (d, J = 1.2 Hz, 3H), 2.90 (d, J = 1.2 Hz,

H), 2.24 (s, 3H); C{ H} NMR (126 MHz, Chloroform-d) δ =

58.9, 137.0 (d, J = 6.2 Hz), 130.5, 129.6, 126.3 (d, J = 24.8 Hz),

24.3, 123.9, 113.3, 55.2, 36.5, 20.9; IR (ATR) ν 2927 (m) 1607 (w)

10 mL Schlenk tube was charged with ynamide 1a (0.2 mmol, 1

equiv), 4-methylbenzenesulfonohydrazide (74.4 mg, 0.4 mmol, 2.0

equiv), Na CO (31.8 mg, 0.3 mmol, 1.5 equiv), and tert-butanol (2

mL) under a nitrogen atmosphere. The reaction mixture was heated

to 80 °C on a heating plate for 12 h with vigorous stirring. Upon

completion, the reaction mixture was cooled to room temperature,

16 (m) 731 (m) 700 (m) HRMS (ESI-TOF) m/z: [M + H] calcd

for C H NO S 318.1158, found 318.1159.

(Z)-3-Styryloxazolidin-2-one (3p). (12.9 mg, 67%) was prepared

diluted with H O (10 mL), and extracted with DCM (3 × 10 mL).

The aqueous phase was concentrated under vacuum to give the crude

from the typical procedure (ethyl acetate:hexane = 1:20) as a colorless

oil.

NaTs.

¹H NMR (500 MHz, Chloroform-d) δ = 7.32 (dd, J = 8.1 Hz, 6.7

Hz, 2H), 7.27−7.20 (m, 3H), 6.66 (d, J = 9.8 Hz, 1H), 5.99 (d, J =

H NMR (500 MHz, D O) δ = 7.42−7.38 (m, 1H), 7.19 (d, J =

.9, 1H), 2.22 (s, 1H); C{ H} NMR (126 MHz, D O) δ = 150.5,

(

.7 Hz, 1H), 4.28−4.24 (m, 2H), 3.39−3.35 (m, 2H); C{ H} NMR

41.1, 129.6, 123.5, 20.5.

126 MHz, Chloroform-d) δ = 157.2, 135.5, 129.2, 127.9, 127.1,

24.2, 112.8, 62.6, 45.0; IR (ATR) ν 2921 (m) 1746 (s) 1599 (w)

ASSOCIATED CONTENT

sı Supporting Information

The Supporting Information is available free of charge at

756 (m) 698 (m) HRMS (ESI-TOF) m/z: [M + H] calcd for

■

C H NO 190.0863, found 190.0862.

(Z)-3-(4-Methylstyryl)oxazolidin-2-one (3q). (17.5 mg, 85%) was

prepared from the typical procedure (ethyl acetate:hexane = 1:20) as

a white solid; mp 72−73 °C.

H NMR (500 MHz, Chloroform-d) δ = 7.14−7.09 (m, 4H), 6.62

General experimental procedures, characterization data,

(

d, J = 9.7 Hz, 1H), 5.96 (d, J = 9.6 Hz, 1H), 4.28−4.24 (m, 2H),

and H and C NMR spectra of new compounds

(PDF )

.41−3.37 (m, 2H), 2.35 (s, 3H); C{ H} NMR (126 MHz,

Chloroform-d) δ = 157.2, 136.9, 132.4, 129.1, 128.6, 123.8, 113.1,

2.6, 44.9, 21.1; IR (ATR) ν 2920 (m) 1747 (s) 1608 (w) 817 (m)

Accession Codes

HRMS (ESI-TOF) m/z: [M + H] calcd for C H NO 204.1019,

found 204.1020.

CCDC 2081409 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif , or by emailing

data_request@ccdc.cam.ac.uk , or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

(Z)-3-(4-Methoxystyryl)oxazolidin-2-one (3r). (17.5 mg, 80%) was

prepared from the typical procedure (ethyl acetate:hexane = 1:20) as

a white solid; mp 90−91 °C.

H NMR (500 MHz, Chloroform-d) δ = 7.16−7.12 (m, 2H),

.88−6.83 (m, 2H), 6.58 (d, J = 9.6 Hz, 1H), 5.95 (d, J = 9.6 Hz,

H), 4.29−4.25 (m, 2H), 3.81 (s, 3H), 3.42−3.37 (m, 2H); C{ H}

13 1

AUTHOR INFORMATION

NMR (126 MHz, Chloroform-d) δ = 158.6, 157.3, 130.3, 127.7,

■

123.6, 113.4, 113.1, 62.6, 55.2, 44.9; IR (ATR) ν 2924 (m) 1751 (s)

Corresponding Author

1654 (w) 831 (m) HRMS (ESI-TOF) m/z: [M + H] calcd for

Guolin Cheng − Xiamen Key Laboratory of Optoelectronic

Materials and Advanced Manufacturing, College of Materials

Science and Engineering, the Instrumental Analysis Center,

Huaqiao University, Xiamen, Fujian 361021, China;

orcid.org/0000-0003-1013-2456; Email: glcheng@

hqu.edu.cn

C H NO 220.0968, found 220.0967.

(Z)-3-(4-Fluorostyryl)oxazolidin-2-one (3s). (19.0 mg, 92%) was

prepared from the typical procedure (ethyl acetate:hexane = 1:20) as

a white solid; mp 72−73 °C.

H NMR (500 MHz, Chloroform-d) δ = 7.22−7.17 (m, 2H),

.05−6.99 (m, 2H), 6.65 (d, J = 9.7 Hz, 1H), 5.94 (d, J = 9.7 Hz,

H), 4.31−4.26 (m, 2H), 3.38−3.34 (m, 2H); C{ H} NMR (126

13 1

Authors

MHz, Chloroform-d) δ = 161.8 (d, J = 247.1 Hz), 157.1, 131.4 (d, J =

3.4 Hz), 130.8 (d, J = 8.0 Hz), 124.5, 114.9 (d, J = 21.5 Hz), 111.7,

Zemin Zhao − Xiamen Key Laboratory of Optoelectronic

Materials and Advanced Manufacturing, College of Materials

62.6, 44.9; IR (ATR) ν 2920 (m) 1744 (s) 1601 (w) 833 (m) HRMS

0411

J. Org. Chem. 2021, 86, 10407−10413

The Journal of Organic Chemistry

(5) Bolshan, Y.; Batey, R. A. Enamide synthesis by copper-catalyzed

Article

Science and Engineering, the Instrumental Analysis Center,

Huaqiao University, Xiamen, Fujian 361021, China

Qingyu Tian − Xiamen Key Laboratory of Optoelectronic

Materials and Advanced Manufacturing, College of Materials

Science and Engineering, the Instrumental Analysis Center,

Huaqiao University, Xiamen, Fujian 361021, China

Yanhui Chen − Xiamen Key Laboratory of Optoelectronic

Materials and Advanced Manufacturing, College of Materials

Science and Engineering, the Instrumental Analysis Center,

Huaqiao University, Xiamen, Fujian 361021, China

Si Wen − Xiamen Key Laboratory of Optoelectronic Materials

and Advanced Manufacturing, College of Materials Science

and Engineering, the Instrumental Analysis Center, Huaqiao

University, Xiamen, Fujian 361021, China

cross-coupling of amides and potassium alkenyltrifluoroborate salts.

Angew. Chem., Int. Ed. 2008, 47, 2109−2112.

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Oxidative Sulfamidation: A Stereoselective Synthesis for Enesulfona-

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Liu, Y.; Liu, Y.; Shi, F.; Wang, X.; Kan, Y.; Wang, C. Aza-Wacker-

Type Reaction between Electron-Deficient Olefins and N-Alkylsulfo-

namides. J. Org. Chem. 2015, 80, 2842−2847.

(7) (a) Herrero, M. T.; de Sarralde, J. D.; SanMartin, R.; Bravo, L.;

Dominguez, E. Cesium Carbonate-Promoted Hydroamidation of

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Yuqing Zhang − Xiamen Key Laboratory of Optoelectronic

Materials and Advanced Manufacturing, College of Materials

Science and Engineering, the Instrumental Analysis Center,

Huaqiao University, Xiamen, Fujian 361021, China

8) (a) Oger, C.; Balas, L.; Durand, T.; Galano, J.-M. Are Alkyne

006, 71, 9506−9509.

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.1c01085

Reductions Chemo-, Regio-, and Stereoselective Enough To Provide

Pure (Z)-Olefins in Polyfunctionalized Bioactive Molecules? Chem.

Rev. 2013, 113, 1313−1350. (b) Swamy, K. C. K.; Reddy, A. S.;

Sandeep, K.; Kalyani, A. Advances in chemoselective and/or

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Notes

The authors declare no competing ﬁnancial interest.

018, 59, 419−429.

9) (a) Zhou, B.; Tan, T.-D.; Zhu, X.-Q.; Shang, M.; Ye, L.-W.

Reversal of Regioselectivity in Ynamide Chemistry. ACS Catal. 2019 ,

, 6393 −6406. (b) Chen, C.; Cui, S. BF -promoted annulation of

H.; Zhu, G.-Y.; Zhu, X.-Q.; Lu, X.; Liu, R.-S.; Ye, L.-W. Copper-

ACKNOWLEDGMENTS

■

This work was supported by the NSF of China (22071068).

azonaphthalenes and ynamides for synthesis of benzo e indoles. Chin.

Chem. Lett. 2021, 32, 421−424. (c) Hong, F.-L.; Chen, Y.-B.; Ye, S.-

Catalyzed Asymmetric Reaction of Alkenyl Diynes with Styrenes by

Formal 3 + 2 Cycloaddition via Cu-Containing AllCarbon 1,3-

Dipoles: Access to Chiral Pyrrole-Fused Bridged 2.2.1 Skeletons. J.

Am. Chem. Soc. 2020, 142, 7618−7626. (d) Wang, K.; Zhuang, Z.; Ti,

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0413