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Synthesis 2021; 53(18): 3361-3371
DOI: 10.1055/a-1401-4486
special topic
Bond Activation – in Honor of Prof. Shinji Murai

Intermolecular C–H Amidation of Alkenes with Carbon Monoxide and Azides via Tandem Palladium Catalysis

Zheng-Yang Gu‡
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), University of Chinese Academy of Sciences, Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
b   College of Textiles and Clothing & Key Laboratory for Advanced Technology in Environmental Protection of Jiangsu Province, Yancheng Institute of Technology, Yancheng, 224051, P. R. of China
,
Yang Wu‡
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), University of Chinese Academy of Sciences, Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
,
Feng Jin
c   College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. of China
,
Xiaoguang Bao∗
c   College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. of China
,
Ji-Bao Xia  ∗
a   State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), University of Chinese Academy of Sciences, Chinese Academy of Sciences, Lanzhou 730000, P. R. of China
› Author Affiliations

We acknowledge financial support from NSFC (21772208, 22001226, 21633013), Natural Science Foundation of Jiangsu Province (BK20201183), Key Research Program of Frontier Sciences of CAS (QYZDJSSW-SLH051), The Natural Science Foundation of the Jiangsu Higher Education Institutions of China (20KJB150016), and Funding for School-Level Research Projects of Yancheng Institute of Technology (xjr2019032).
› Further Information
 
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Abstract

An atom- and step-economic intermolecular multi-component palladium-catalyzed C–H amidation of alkenes with carbon monoxide and organic azides has been developed for the synthesis of alkenyl amides. The reaction proceeds efficiently without an ortho-directing group on the alkene substrates. Nontoxic dinitrogen is generated as the sole by-product. Computational studies and control experiments have revealed that the reaction takes place via an unexpected mechanism by tandem palladium catalysis.


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Key words

C–H carbonylation - amidation - palladium - alkene - amides

The amide motif is undoubtedly one of the most important structural units in nature. It not only plays an essential role in life as the backbone of proteins but also presents in numerous marketed drugs and materials.[1] Among them, the alkenyl amides are widely found in natural products and pharmaceuticals (Scheme [1]A).[2] In addition, alkenyl amides are also reliable and versatile synthetic intermediates for the synthesis of a variety of useful chemicals, such as amines, isonitriles, ketones, and hetorocycles.[3] Conventional route for the preparation of alkenyl amides relies on condensation of carboxylic acids and amines in the presence of a stoichiometric ‘coupling’ reagent.[4] However, the production of large quantities of waste is the major concern in this traditional amide synthesis.[5] Therefore, the development of catalytic, atom-economic, and efficient methods to produce alkenyl amides are of great significance and rewarding.

Zoom Image
Scheme 1 Intermolecular C–H amidation of alkenes

To overcome the low atom economy in traditional alkenyl amide synthesis, catalytic condensation of the alkenyl carboxylic acids and amines has been developed using boronic acid as a catalyst.[6] Recently, many strategies have been developed for the catalytic synthesis of alkenyl amides using other easily accessed raw materials other than carboxylic acids, such as hydroaminocarbonylation of alkynes with carbon monoxide (CO) and amines.[7] Use of inexpensive and abundant CO gas for catalytic carbonylation is one of the most straightforward and powerful strategies to prepare carbonyl compounds.[8] Aminocarbonylation of alkenyl halides (pseudohalide) or alkenyl organometallic reagents is another well-established methods for the synthesis of alkenyl amides.[9] Obviously, direct C–H carbonylation of alkenes to produce alkenyl amides is much attractive and atom-economic due to utilization of simple olefin as the substrate. However, all of the reported C–H aminocarbonylation of alkenes needed substrates bearing an NH functionality as an intramolecuar ortho-directing group.[10] Transition-metal-catalyzed intermolecular aminocarbonylation of alkenes with free amines generally produced the corresponding alkyl amides, which has been well developed (Scheme [1]B).[11] Intermolecular C–H aminocarbonylation of alkenes with free amines to produce alkenyl amides has not been reported yet.[12]

Transition-metal-catalyzed C–N bond-forming reactions via a metal-nitrene intermediate is a powerful method to prepare various N-containing chemicals.[13] Readily available organic azides are one class of convenient nitrene precursors, which expel N2 as the sole byproduct in the nitrene transfer reactions.[14] Catalytic carbonylation of azides has been utilized for the synthesis of ureas and carbamates, avoiding direct utilization of air- and moisture-sensitive isocyanate compounds.[15] We recently reported a convenient approach for Rh-catalyzed C–H amidation of electron-rich (hetero)arenes with CO and azides to produce aryl amides.[16] This finding inspired us that C–H amidation of alkenes might be achieved with CO and azides via suitable metal catalysis. We now report a Pd-catalyzed multi-component intermolecular C–H amidation of alkenes with organic azides under 1 atm of CO (Scheme [1]C). This method has the advantages of synthetic simplicity, high efficiency, atom- and step-economy, thus providing cost-efficient and straightforward access to valuable alkenyl amides under mild additive-free conditions.

Given the important role and wide presence of oxygen heterocycles in pharmaceutical industry,[17] we began by investigating the C–H amidation of dihydropyran (DHP, 1) with CO (balloon pressure) and p-toluenesulfonyl azide (2) in the presence of various metal catalysts. Both Pd(II) and Pd(0) can catalyze this reaction. The desired amidation product 3 was obtained in 78% yield with 5 mol% Pd(OAc)2 as the catalyst in MeCN at 80 °C (Table [1], entry 1). The use of Pd(0) catalysts, Pd2(dba)3, or Pd(PPh3)4 were less effective (entries 2, 3). No olefin aziridination product was observed in the reaction.[18] Moderate efficiency was observed when [Rh(cod)Cl]2 was used as the catalyst (entry 4). The yield of 3 was increased to 90% when the amount of 2 was increased to 1.5 equivalents (entry 7). A slightly lower yield (81%) was obtained when the reaction temperature was decreased to 60 °C (entry 8). Lower yields were obtained when other solvents were tested, such as toluene and THF (entries 10, 11). The acetonitrile as solvent may serve as a good coordinative ligand for palladium catalyst. Control experiment showed that no reaction occurred without Pd catalyst, demonstrating the essential role of the Pd catalyst in promoting the reaction (entry 12).

Table 1 Catalytic C–H Amidation of Alkenea

Entry

Catalyst

Solvent

Temp (°C)

Yield (%)b

 1

Pd(OAc)2

MeCN

80

78

 2

Pd2(dba)3

MeCN

80

48

 3

Pd(PPh3)4

MeCN

80

44

 4

[Rh(cod)Cl]2

MeCN

80

55

 5

Cu(OAc)2

MeCN

80

trace

 6

Co2(CO)8

MeCN

80

trace

 7c

Pd(OAc)2

MeCN

80

90

 8c

Pd(OAc)2

MeCN

60

81

 9c

Pd(OAc)2

MeCN

25

12

10c

Pd(OAc)2

toluene

80

trace

11c

Pd(OAc)2

THF

80

19

12c

–

MeCN

80

 0

a Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), CO (balloon), catalyst (5 mol%), MeCN (3 mL), 12 h.

b Determined by 1H NMR analysis using 1,1,2,2-tetrachloroethane as an internal­ standard.

c With 0.75 mmol of 2.

With the optimal reaction conditions in hand, we first investigated a wide range of alkenes in this C–H amidation reaction under 1 atm of CO (Scheme [2]). Overall, good to excellent yields of acrylamides were obtained. It was gratifying to observe that 2-methoxy-DHP and 2-[(benzyl­oxy)methyl]-DHP exhibited good reactivity producing the corresponding products 4 and 5 in 80% and 86% yield, respectively. Amidation of 2,3-dihydrofuran also occurred smoothly affording the desired product 6 in 61% yield. A variety of linear alkoxyethenes, such as ethoxy-, propoxy-, butoxy-, isobutoxy-, cyclohexoxy-, and benzyloxyethene displayed moderate to good reactivity, furnishing the corresponding products 7–12 in 44–82% yields. Remarkably, amidation of (2-chloroethoxy)ethene produced chlorine-containing acrylamide derivative 13 in 63% yield, which could be easily functionalized for further transformation. It should be noted that amidation of an E/Z mixture of 1-ethoxy-1-propene gave E-alkenyl amide 14 in 76% yield as a single stereoisomeric product. Excellent yield of (E)-15 was obtained as the sole stereoisomeric product in the amidation of 1,1-disubstituted olefin (2-ethoxy-1-propene). The aryloxyethene can also be used as a substrate, delivering the desired product 16 in moderate yield. However, no reaction occurred with vinyl acetate, which might due to its property of electron deficiency (→ 17, 0%). Notably, this C–H amidation reaction is not restricted to vinyl ester substrates, as stryene derivatives are also amenable to the reaction. We found that electron-rich styrenes displayed good reactivity in this reaction. For example, a variety of styrenes bearing amino group all worked very well, and the corresponding C–H amidation products 18–22 were isolated in 76–91% yields. Unfortunately, no reaction occurred when simple aliphatic unactivated olefins, styrenes with electron-withdrawing groups, dienes, and simple cycloalkenes were used under current conditions

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Scheme 2 Scope of C–H amidation of alkenes. Reagents and conditions: alkene (0.5 mmol), azide (0.75 mmol), CO (balloon), Pd(OAc)2 (5 mol%), MeCN (3 mL), 80 °C, 12 h. Isolated yields are shown.

We then investigated the scope of organic azides in the amidation of DHP (1). It was found that arylsulfonyl azides with both electron-donating group (Me, OMe), electron-withdrawing group (CF3), or halogen substituents on the benzene ring showed good reactivity, leading to the desired products 24–29 in 71–83% yield. The reaction of naphthylsulfonyl and heteroarylsulfonyl azides occurred smoothly (→ 30–32). Furthermore, the alkylsulfonyl azides also exhibited good reactivity in this transformation (→ 33–37). Unfortunately, no reaction occurred with azidobenzene or (azidomethyl)benzene as the substrate under the standard conditions. Finally, late stage C–H amidation of olefin-containing complex molecules was carried out. Amidation of 3,4,6-tri-O-benzyl-d-glucal occurred smoothly generating the corresponding amide 38 in 67% yield. And selective C–H amidation of vinyl ester derived from natural stigmasterol produced the target product 39 in moderate yield, without touching the other two double bonds in the molecule.

To demonstrate the synthetic utility of this method, a scale-up reaction for C–H amidation of DHP (1) was carried out. The desired product 3 was obtained in 86% yield (Scheme [3a]). Then, Ir-catalyzed alkenylation of 3 with alkyne occurred smoothly generating functionalized 1,3-diene 40 in good yield (Scheme [3b]). Indole-containing heterocycles are widely present in pharmaceutical compounds and biologically active molecules.[19] We found that reaction of alkenyl amide 7 with 1H-indole produced polycyclic indole derivative 41 in good yield using AlCl3 as a Lewis acid catalyst via transamidation and double addition reactions (Scheme [3c]). The product 15 could be easily converted to β-ketoamides 42 in excellent yield under acidic conditions at room temperature (Scheme [3d]). Antidiabetic Glibenclamide is a sulfonamide-containing small molecular drug, one of the top 200 most prescribed medication in US in2016.[20] Amidation of DHP (1) with sulfonyl azide 43 produced the analogue 44 of Glibenclamide in 78% yield under the standard conditions (Scheme [3e]).

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Scheme 3 Synthetic applications

Computational studies were carried out to gain a mechanistic insight into this reaction (see SI for detailed computational details). When Pd(OAc)2 is considered as an active catalyst, the formation of the intermediate of isocyanate is evaluated via two possible mechanistic pathways. The first pathway is the Pd(II)-catalyzed denitrogenation of TsN3 via TS1a to afford the palladium nitrene species (path a, Figure S1 in Supporting Information). Subsequently, the generated INT2a can bind with CO to afford the isocyanate intermediate. The second pathway is that CO might coordinate with Pd(II) and undergo migratory insertion with TsN3 via TS1b followed by N2 dissociation to generate the isocyanate intermediate (path b). Computational results show that both of the Pd(II)-catalyzed pathways have substantially high activation barriers (larger than 30 kcal/mol, Figure S1). In addition, one may suggest that CO could reduce the Pd(II) catalyst to Pd(0). When Pd(0) species is employed to catalyze the reaction, the aforementioned pathways are also considered. It is interesting to find that the activation barrier catalyzed by Pd(0) is significantly lowered than that catalyzed by Pd(II) (Figure [1]). Thus, computational results imply that it is more feasible for Pd(0) species to promote the reaction to form the isocyanate intermediate. We found that activation barrier of Pd(0)-catalyzed migratory insertion with TsN3 to generate the isocyanate intermediate (Ts1b′, path b, Figure [1]) is much lower than that of Pd(0)-catalyzed denitrogenation of TsN3 (Ts1a′, path a, Figure [1]). Afterward, the substrate ethoxyethene (1′) could undergo migratory insertion with the formed isocyanate intermediate at the Pd(0) site. Two possible regioselectivities are considered and the corresponding transition states are shown as TS3a′ and TS3b′, respectively. The predicted activation barriers indicate that the insertion of the terminal carbon of 1′ with C atom of the isocyanate group is more favorable to occur. This result could be rationalized by HOMO analysis of 1′ that the electron density of alkene moiety is more localized at the terminal carbon due to the presence of O connected with the alkenyl group (Figure [2]). Similar character is also found in the HOMO of 1. Therefore, the formation of INT4′ is more ready to occur. The subsequent β-H elimination could follow to produce INT6′. Finally, the reductive elimination of INT6′ could proceed to furnish the final product. It should be noted that the formation of a β-lactam intermediate is detected between DHP (1) and sulfonyl isocyanate in the absence of Pd catalyst, which can be further transformed into alkenyl amides under high temperature.[21] However, the activation barriers is much higher than that of Pd-catalyzed process (Figure [2], TS3c′ and Figure S3 in Supporting Information).[22] Nevertheless, the formation of β-lactam intermediate is not necessary in the presence of Pd catalyst according to the computational studies.[23]

Zoom Image
Figure 1 Energy profiles for the Pd(0)-catalyzed C–H amidation of alkenes with CO and TsN3 (bond lengths are shown in Å)
Zoom Image
Figure 2 Highest occupied molecular orbitals (HOMO) for alkene 1′ and 1
Zoom Image
Scheme 4 Control experiments

Then, several control experiments were performed to understand the reaction mechanism (Scheme [4]). First, palladium-catalyzed carbonylation of tosyl azide (2) with CO occurred smoothly affording tosyl isocyanate (45), which was quickly converted into tosyl amine (46) by reaction with water during analysis by GC-MS (Scheme [4a]). We then tested carbonylation of DHP (1) with CO and tosyl amine (46), and no reaction occurred (Scheme [4b]). Reaction of THP (1) with tosyl isocyanate (45) in the presence of Pd(OAc)2/CO is much faster than that without Pd catalyst (Scheme [4c]). These results indicate that isocyanate should be the most possible reaction intermediate in the amidation of alkene with CO and azide. Next, Pd2(dba)3 can also catalyze the reaction albeit the reaction is slower than that with Pd(OAc)2 as catalyst, demonstrating the Pd(0) might be the active catalyst (Table [1], entry 2). In addition, when performing the kinetic isotope effect (KIE) experiment with benzyloxyethene and benzyloxyethene-d 5, the KIE value (k H/k D) was determined as 2.7 (Scheme [4d]). This result indicates that the terminal alkenyl C–H cleavage might be involved in the rate-determining step, which is consistent with the DFT calculations.

Based on the DFT calculations and control experiments, the plausible reaction pathway has been proposed in Scheme [5]. Initially, Pd(II) precatalyst is reduced to the active Pd(0) catalyst in the presence of CO, which may be stabilized by acetonitrile as the ligand. The organic azide undergoes ligand exchange with CO coordinated Pd(0) catalyst to form intermediate I. Subsequently, migratory insertion of CO into the azide generates palladacycle species II. After release of N2, palladium coordinated isocyanate species III is formed. Next, coordination of alkene substrate and regioselective migratory insertion generates palladacycle IV. The following β-H elimination produces amidopalladium intermediate V. Finally, reductive elimination leads to the alkenyl amide and regenerates the Pd(0) catalyst.

Zoom Image
Scheme 5 Plausible reaction pathway

In summary, we have developed an atom- and step-economic palladium-catalyzed intermolecular C–H amidation of olefins to produce alkenyl amides from an inexpensive and abundant carbonyl source (CO) and organic azides. This protocol provides a simple and practical strategy for the straightforward synthesis of alkenyl amides with a range of substrates. Remarkably, neither directing group on the alkenes or additive is needed for the reaction. Dinitrogen (N2) is generated as the only by-product. The mechanistic studies and control experiments have revealed a novel reaction mechanism involving tandem Pd-catalyzed in situ generation of isocyanate intermediate and subsequent cycloaddition and β-H elimination processes. However, no reaction occurred when simple aliphatic unactivated olefins, styrenes with electron-withdrawing groups, dienes and simple cycloalkenes were tested under our current conditions. And further investigations of C–H amidation of unactivated olefins are currently under study in our laboratory.

All intermolecular amidation reactions were carried out under atmospheric pressure of CO in oven-dried Schlenk tube. TLC analyses were done on glass 0.25 mm silica gel plates. Flash chromatography columns were packed with 200–300 mesh silica gel in PE (bp 60–90 °C). High-resolution MS analyses were performed on Thermo Fisher Scientific LTQ FT Ultra with DART Positive Mode or Agilent 6530 Accurate–Mass Q-TOF LC/MS with ESI mode. NMR spectra were recorded on a 400 MHz for 1H NMR and 100 MHz for 13C NMR, using TMS as an internal reference DMSO-d 6 and CDCl3 as solvent. Chemical shift values for protons are reported in parts per million (ppm, δ scale) downfield from TMS and are referenced to residual proton of DMSO-d 6 (δ = 2.50) and residual proton (δ = 7.26) in CDCl3. Multiplicities are indicated by standard abbreviations. 13C NMR spectra were recorded at 100 MHz. Chemical shifts for carbons are reported in parts per million (ppm, δ scale) downfield from TMS and are referenced to the carbon resonance of DMSO-d 6 (δ = 40.00) and CDCl3 (δ = 77.00). Materials were purchased from Tokyo Chemical Industry Co., Aldrich Inc., Alfa Aesar, Adamas, or other commercial suppliers and used as received, unless otherwise noted. Sulfonyl azides were purchased, if commercially available, or prepared from sulfonyl chlorides and NaN3 according to the well-established methods.

The experimental procedures for synthetic applications (Scheme [3]) and control experiments (Scheme [4]) are described in the Supporting Information.


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Amide Products; General Procedure

To an oven-dried Schlenk tube (10 mL) was added the organic azide (0.75 mmol), Pd(OAc)2 (5.6 mg, 5 mol%). The tube was purged and backfilled with CO (3 cycles) from a balloon. Anhyd MeCN (3.0 mL) was injected into the tube, and then alkene (0.5 mmol) was injected into the tube. After stirring at 80 °C for 12 h under CO atmosphere (balloon), the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (PE/EtOAc 3:1–1:1) to give the desired product.


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N-Tosyl-3,4-dihydro-2H-pyran-5-carboxamide (3)

Yield: 115.3 mg (82%); white solid; mp 241.3–243.1 °C.

1H NMR (400 MHz, CDCl3): δ = 8.71 (s, 1 H), 7.97 (d, J = 8.4 Hz, 2 H), 7.53 (s, 1 H), 7.33 (d, J = 8.2 Hz, 2 H), 4.00 (t, J = 5.2 Hz, 2 H), 2.43 (s, 3 H), 2.19 (t, J = 6.0 Hz, 2 H), 1.83 (tt, J = 6.0, 6.0 Hz, 2 H).

13C NMR (75 MHz, CDCl3): δ = 164.7, 155.5, 144.8, 135.8, 129.5, 128.4, 106.9, 66.7, 21.7, 20.7, 18.8.

HRMS (ESI): m/z calcd for C13H16NO4S [M + H]+: 282.0795; found: 282.0787.


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2-Methoxy-N-tosyl-3,4-dihydro-2H-pyran-5-carboxamide (4)

Yield: 124.5 mg (80%); Yellow oil.

1H NMR (400 MHz, CDCl3): δ = 8.49 (s, 1 H), 7.97 (d, J = 8.4 Hz, 2 H), 7.39 (s, 1 H), 7.33 (d, J = 8.0 Hz, 2 H), 4.98 (t, J = 2.9 Hz, 1 H), 3.43 (s, 3 H), 2.43 (s, 3 H), 2.27–2.15 (m, 2 H), 1.96–1.90 (m, 1 H), 1.75–1.67 (m, 1 H).

13C NMR (101 MHz, CDCl3): δ = 164.4, 152.1, 144.8, 135.8, 129.5, 128.5, 107.9, 98.8, 56.2, 25.1, 21.6, 15.1.

HRMS (ESI): m/z calcd for C14H17NO5SNa [M + Na]+: 334.0720; found: 334.0719.


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2-[(Benzyloxy)methyl]-N-tosyl-3,4-dihydro-2H-pyran-5-carboxamide (5)

Yield: 172.6 mg (86%); Yellow oil.

1H NMR (400 MHz, CDCl3): δ = 8.85 (s, 1 H), 7.97 (d, J = 8.4 Hz, 2 H), 7.54 (s, 1 H), 7.33–7.26 (m, 7 H), 4.54 (d, J = 2.0 Hz, 2 H), 4.07–4.01 (m, 1 H), 3.58 (dd, J = 10.4, 6.0 Hz, 1 H), 3.53 (dd, J = 10.4, 6.0 Hz, 1 H), 2.42 (s, 3 H), 2.30–2.24 (m, 1 H), 2.20–2.11 (m, 1 H), 1.94–1.87 (m, 1 H), 1.69–1.59 (m, 1 H).

13C NMR (101 MHz, CDCl3): δ = 164.7, 154.9, 144.8, 137.5, 135.9, 129.5, 128.4, 127.8, 127.7, 107.0, 75.7, 73.4, 71.2, 22.7, 21.6, 18.5.

HRMS (ESI): m/z calcd for C21H24NO5S [M + H]+: 402.1370; found: 402.1358.


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N-Tosyl-4,5-dihydrofuran-3-carboxamide (6)

Yield: 81.5 mg (61%); white solid; mp 227.6–228.8 °C.

1H NMR (400 MHz, CDCl3): δ = 9.32 (s, 1 H), 7.96 (d, J = 7.2 Hz, 2 H), 7.39–7.33 (m, 3 H), 4.50 (t, J = 9.8 Hz, 2 H), 2.80 (t, J = 9.6 Hz, 2 H), 2.43 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 161.6, 157.8, 144.9, 135.8, 129.5, 128.3, 110.5, 73.3, 27.4, 21.6.

HRMS (ESI): m/z calcd for C12H14NO4S [M + H]+: 268.0638; found: 268.0636.


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(E)-3-Ethoxy-N-tosylacrylamide (7)

Yield: 72.7 mg (54%); white solid; mp 214.5–216.3 °C.

1H NMR (400 MHz, CDCl3): δ = 9.32 (s, 1 H), 7.93 (d, J = 8.0 Hz, 2 H), 7.61 (d, J = 12.2 Hz, 1 H), 7.29 (d, J = 8.4 Hz, 2 H), 5.34 (d, J = 12.2 Hz, 1 H), 3.87 (q, J = 7.2 Hz, 2 H), 2.40 (s, 3 H), 1.26 (t, J = 7.2 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 165.0, 164.0, 144.6, 136.1, 129.4, 128.1, 96.4, 67.6, 21.5, 14.3.

HRMS (ESI): m/z calcd for C12H16NO4S [M + H]+: 270.0795; found: 270.0785.


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(E)-3-Propoxy-N-tosylacrylamide (8)

Yield: 83.6 mg (59%); white solid; mp 199.5–200.9 °C.

1H NMR (400 MHz, CDCl3): δ = 8.99 (s, 1 H), 7.94 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 12.4 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H), 5.32 (d, J = 12.0 Hz, 1 H), 3.78 (t, J = 6.4 Hz, 2 H), 2.42 (s, 3 H), 1.71–1.62 (m, 2 H), 0.91 (t, J = 7.4 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 164.8, 164.4, 144.8, 136.0, 129.5, 128.1, 96.2, 73.6, 22.2, 21.6, 10.1.

HRMS (ESI): m/z calcd for C13H18NO4S [M + H]+: 284.0951; found: 284.0961.


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(E)-3-Butoxy-N-tosylacrylamide (9)

Yield: 65.4 mg (44%); white solid; mp 191.3–193.5 °C.

1H NMR (400 MHz, CDCl3): δ = 9.09 (s, 1 H), 7.94 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 12.2 Hz, 1 H), 7.31 (d, J = 8.4 Hz, 2 H), 5.30 (d, J = 12.2 Hz, 1 H), 3.82 (t, J = 6.4 Hz, 2 H), 2.42 (s, 3 H), 1.65–1.58 (m, 2 H), 1.39–1.30 (m, 2 H), 0.88 (t, J = 7.4 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 164.8, 164.4, 144.7, 136.0, 129.5, 128.1, 96.1, 71.9, 30.8, 21.6, 18.8, 13.5.

HRMS (ESI): m/z calcd for C14H19NO4SNa [M + Na]+: 320.0927; found: 320.0920.

(E)-3-Isobutoxy-N-tosylacrylamide (10)

Yield: 77.3 mg (52%); white solid; mp 186.7–188.2 °C.

1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.0 Hz, 2 H), 7.61 (d, J = 12.4 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H), 5.31 (d, J = 12.0 Hz, 1 H), 3.59 (d, J = 6.4 Hz, 2 H), 2.41 (s, 3 H), 1.97–1.86 (m, 1 H), 0.90 (d, J = 6.8 Hz, 6 H).

13C NMR (101 MHz, CDCl3): δ = 165.0, 164.5, 144.6, 136.0, 129.5, 128.1, 96.1, 78.3, 27.9, 21.6, 18.7.

HRMS (ESI): m/z calcd for C14H19NO4SNa [M + Na]+: 320.0927; found: 320.0931.


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(E)-3-(Cyclohexyloxy)-N-tosylacrylamide (11)

Yield: 132.6 mg (82%); white solid; mp 242.2–243.4 °C.

1H NMR (400 MHz, CDCl3): δ = 8.24 (s, 1 H), 7.94 (d, J = 8.4 Hz, 2 H), 7.58 (d, J = 12.0 Hz, 1 H), 7.32 (d, J = 8.0 Hz, 2 H), 5.32 (d, J = 12.0 Hz, 1 H), 3.90 (tt, J = 8.8, 3.8 Hz, 1 H), 2.43 (s, 3 H), 1.86–1.82 (m, 2 H), 1.72–1.71 (m, 2 H), 1.48–1.40 (m, 2 H), 1.31–1.25 (m, 4 H).

13C NMR (101 MHz, CDCl3): δ = 164.9, 163.6, 144.7, 136.1, 129.5, 128.2, 96.9, 82.1, 31.7, 25.0, 23.2, 21.6.

HRMS (ESI): m/z calcd for C16H21NO4SNa [M + Na]+: 346.1083; found: 346.1089.


#

(E)-3-(Benzyloxy)-N-tosylacrylamide (12)

Yield:116.0 mg (70%); white solid; mp 208.1–209.9 °C.

1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 8.4 Hz, 2 H), 7.68 (d, J = 12.0 Hz, 1 H), 7.36–7.27 (m, 7 H), 5.42 (d, J = 12.4 Hz, 1 H), 4.88 (s, 2 H), 2.42 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 164.6, 163.7, 144.8, 135.9, 134.7, 129.5, 128.7, 128.6, 128.1, 127.8, 97.3, 73.7, 21.6.

HRMS (ESI): m/z calcd for C17H17NO4SNa [M + Na]+: 332.0951; found: 332.0957.


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(E)-3-(2-Chloroethoxy)-N-tosylacrylamide (13)

Yield: 95.7 mg (63%); white solid; mp 192.7–193.9 °C.

1H NMR (400 MHz, CDCl3): δ = 9.20 (s, 1 H), 7.92 (d, J = 8.4 Hz, 2 H), 7.62 (d, J = 12.4 Hz, 1 H), 7.32 (d, J = 8.2 Hz, 2 H), 5.40 (d, J = 12.0 Hz, 1 H), 4.09 (t, J = 5.6 Hz, 2 H), 3.67 (t, J = 6.0, 2 H), 2.42 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 164.5, 163.5, 145.0, 135.9, 129.7, 128.2, 97.5, 71.7, 41.5, 21.7.

HRMS (ESI): m/z calcd for C12H14ClNO4SNa [M + Na]+: 326.0224; found: 326.0231.


#

(E)-3-Ethoxy-2-methyl-N-tosylacrylamide (14)

Yield: 107.7 mg (76%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 9.00 (br s, 1 H), 7.96 (d, J = 8.4 Hz, 2 H), 7.34–7.30 (m, 3 H), 3.96 (q, J = 7.2 Hz, 2 H), 2.40 (s, 3 H), 1.67 (d, J = 1.2 Hz, 3 H), 1.22 (t, J = 7.2 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.1, 157.7, 144.6, 136.0, 129.4, 128.2, 106.6, 70.2, 21.5, 15.1, 8.7.

HRMS (ESI): m/z calcd for C13H18NO4S [M + H]+: 284.0951; found: 284.0962.


#

(E)-3-Ethoxy-N-tosylbut-2-enamide (15)

Yield: 123.2 mg (87%); colorless oil. The stereochemistry of 15 was confirmed by 2D NOESY analysis.

1H NMR (400 MHz, CDCl3): δ = 9.03 (s, 1 H), 7.95 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H), 5.03 (s, 1 H), 3.72 (q, J = 7.0 Hz, 2 H), 2.42 (s, 3 H), 2.20 (s, 3 H), 1.25 (t, J = 7.0 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 174.8, 164.5, 144.5, 136.3, 129.5, 128.0, 90.9, 64.2, 21.6, 19.6, 14.0.

HRMS (ESI): m/z calcd for C13H18NO4S [M + H]+: 306.0770; found: 306.0771.


#

(E)-3-(Naphthalen-2-yloxy)-N-tosylacrylamide (16)

Yield: 86.3 mg (47%); white solid; mp 238.2–239.6 °C.

1H NMR (400 MHz, CDCl3): δ = 7.96–7.93 (m, 3 H), 7.81 (d, J = 8.4 Hz, 2 H), 7.74 (d, J = 8.0 Hz, 1 H), 7.51–7.43 (m, 2 H), 7.39 (d, J = 2.8 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 2 H), 7.17 (dd, J = 8.8, 2.4 Hz, 1 H), 5.69 (d, J = 12 Hz, 1 H), 2.34 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 164.1, 160.4, 153.3, 145.0, 135.8, 133.8, 130.9, 130.3, 129.6, 128.3, 127.8, 127.4, 127.0, 125.6, 118.2, 113.5, 102.0, 21.7.

HRMS (ESI): m/z calcd for C20H18NO4S [M + H]+: 368.0951; found: 368.0962.


#

(E)-3-[4-(Dimethylamino)phenyl]-N-tosylacrylamide (18)

Yield: 130.9 mg (76%); yellow solid; mp > 300 °C.

1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 15.2 Hz, 1 H), 7.36 (d, J = 8.8 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 6.62 (d, J = 9.2 Hz, 2 H), 6.19 (d, J = 15.6 Hz, 1 H), 3.01 (s, 6 H), 2.41 (s, 3 H).

The other spectral and analytical data are in accordance with the literature.[1]


#

(E)-3-[4-(Diethylamino)phenyl]-N-tosylacrylamide (19)

Yield: 147.1 mg (79%); yellow solid; mp > 300 °C.

1H NMR (400 MHz, CDCl3): δ = 8.63 (br s, 1 H), 8.00 (d, J = 8.4 Hz, 2 H), 7.60 (d, J = 15.6 Hz, 1 H), 7.35–7.30 (m, 4 H), 6.58 (d, J = 8.8 Hz, 2 H), 6.18 (d, J = 15.2 Hz, 1 H), 3.37 (q, J = 7.2 Hz, 4 H), 2.41 (s, 3 H), 1.17 (t, J = 7.2 Hz, 6 H).

13C NMR (101 MHz, CDCl3): δ = 164.1, 149.9, 146.7, 144.7, 136.2, 130.7, 129.5, 128.3, 120.7, 111.2, 110.5, 44.5, 21.6, 12.5.

HRMS (ESI): m/z calcd for C20H24N2O3SNa [M + Na]+: 395.1400; found: 395.1403.


#

(E)-3-(4-Morpholinophenyl)-N-tosylacrylamide (20)

Yield: 160.4 mg (83%); yellow solid; mp > 300 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 11.99 (br s, 1 H), 7.85 (d, J = 8.4 Hz, 2 H), 7.47–7.41 (m, 5 H), 6.95 (d, J = 8.8 Hz, 2 H), 6.38 (d, J = 15.6 Hz, 1 H), 3.72–3.70 (m, 4 H), 3.22–3.19 (m, 4 H), 2.39 (s, 3 H).

13C NMR (101 MHz, DMSO-d 6): δ = 164.2, 153.0, 144.6, 144.5, 137.2, 130.1, 130.0, 128.1, 124.3, 114.69, 114.66, 66.3, 47.6, 21.5.

HRMS (ESI): m/z calcd for C20H23N2O4S [M + H]+: 387.1373; found: 387.1373.


#

(E)-3-[4-(4-Methylpiperazin-1-yl)phenyl]-N-tosylacrylamide (21)

Yield: 173.8 mg (87%); yellow solid; mp 294.7–295.5 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 7.81 (d, J = 8.4 Hz, 2 H), 7.41–7.36 (m, 5 H), 6.94 (d, J = 8.4 Hz, 2 H), 6.35 (d, J = 15.6 Hz, 1 H), 3.30–3.28 (m, 4 H), 2.63–2.60 (m, 4 H), 2.37 (s, 3 H), 2.35 (s, 3 H).

13C NMR (101 MHz, DMSO-d 6): δ = 165.5, 152.3, 143.6, 143.0, 138.6, 129.9, 129.6, 127.9, 124.6, 116.9, 115.1, 54.3, 46.9, 45.4, 21.5.

HRMS (ESI): m/z calcd for C21H26N3O3S [M + H]+: 400.1689; found: 400.1693.


#

(E)-3-[4-(Dimethylamino)phenyl]-N-tosylbut-2-enamide (22)

Yield: 163.1 mg (91%); yellow solid; mp > 300 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 11.78 (br s, 1 H), 7.84 (d, J = 8.0 Hz, 2 H), 7.43–7.38 (m, 4 H), 6.70 (d, J = 8.4 Hz, 2 H), 6.21 (s, 1 H), 2.93 (s, 6 H), 2.39 (s, 3 H), 2.37 (s, 3 H).

13C NMR (101 MHz, DMSO-d 6): δ = 164.6, 156.0, 151.7, 144.3, 137.5, 129.9, 128.0, 127.7, 127.7, 112.5, 112.1, 40.2, 21.5, 16.9.

HRMS (ESI): m/z calcd for C19H22N2O3SNa [M + Na]+: 367.1087; found: 367.1088.


#

N-(Phenylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (23)

Yield: 97.6 mg (73%); white solid; mp 202.3–204.1 °C.

1H NMR (400 MHz, CDCl3): δ = 8.91 (s, 1 H), 8.09 (d, J = 7.8 Hz, 2 H), 7.64–7.52 (m, 4 H), 3.99 (t, J = 5.2 Hz, 2 H), 2.19 (t, J = 6.4 Hz, 2 H), 1.84–1.81 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 164.9, 155.6, 138.9, 133.7, 128.8, 128.3, 106.9, 66.7, 20.7, 18.7.

HRMS (ESI): m/z calcd for C12H14NO4S [M + H]+: 268.0638; found: 268.0640.


#

N-[(4-Methoxyphenyl)sulfonyl]-3,4-dihydro-2H-pyran-5-carboxamide (24)

Yield: 121.9 mg (82%); white solid; mp 238.9–240.1 °C.

1H NMR (400 MHz, CDCl3): δ = 8.70 (s, 1 H), 8.02 (d, J = 8.6 Hz, 2 H), 7.53 (s, 1 H), 6.99 (d, J = 8.4 Hz, 2 H), 4.00 (t, J = 4.8 Hz, 2 H), 3.86 (s, 3 H), 2.19 (t, J = 6.0 Hz, 2 H), 1.86–1.81 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 164.8, 163.7, 155.4, 130.7, 130.2, 114.0, 106.9, 66.7, 55.6, 20.7, 18.8.

HRMS (ESI): m/z calcd for C13H16NO5S [M + H]+: 298.0744; found: 298.0753.


#

N-(Mesitylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (25)

Yield: 125.3 mg (81%); white solid; mp 268.6–269.3 °C.

1H NMR (400 MHz, CDCl3): δ = 8.85 (s, 1 H), 7.53 (s, 1 H), 6.97 (s, 2 H), 4.02 (t, J = 5.2 Hz, 2 H), 2.72 (s, 6 H), 2.29 (s, 3 H), 2.20 (t, J = 6.0 Hz, 2 H), 1.88–1.83 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 165.3, 155.2, 143.4, 140.3, 132.7, 132.0, 106.9, 66.6, 22.8, 21.0, 20.8, 18.9.

HRMS (ESI): m/z calcd for C15H19NO4SNa [M + Na]+: 332.0927; found: 332.0939.


#

N-{[4-(Trifluoromethyl)phenyl]sulfonyl}-3,4-dihydro-2H-pyran-5-carboxamide (26)

Yield: 145.7 mg (82%); white solid; mp 254.4–255.8 °C.

1H NMR (400 MHz, CDCl3): δ = 8.77 (s, 1 H), 8.23 (d, J = 8.4 Hz, 2 H), 7.81 (d, J = 8.0 Hz, 2 H), 7.56 (s, 1 H), 4.03 (t, J = 5.2 Hz, 2 H), 2.20 (t, J = 6.4 Hz, 2 H), 1.89–1.83 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 164.9, 156.0, 142.4, 135.3 (q, J = 32.7 Hz), 129.0, 126.0 (q, J = 3.5 Hz), 123.1 (q, J = 271.6 Hz), 106.8, 66.8, 20.7, 18.8.

HRMS (ESI): m/z calcd for C13H13F3NO4S [M + H]+: 336.0512; found: 336.0502.


#

N-[(4-Fluorophenyl)sulfonyl]-3,4-dihydro-2H-pyran-5-carboxamide (27)

Yield: 101.3 mg (71%); white solid; mp 208.9–210.3 °C.

1H NMR (400 MHz, CDCl3): δ = 8.61 (s, 1 H), 8.14–8.09 (m, 2 H), 7.53 (s, 1 H), 7.24–7.18 (m, 2 H), 4.02 (t, J = 5.2 Hz, 2 H), 2.19 (t, J = 6.4 Hz, 2 H), 1.86 (tt, J = 10.8, 5.2 Hz, 2 H).

13C NMR (101 MHz, CDCl3): δ = 165.7 (d, J = 255.1 Hz), 164.7, 155.7, 134.7 (d, J = 3.3 Hz), 131.4 (d, J = 9.7 Hz), 116.2 (d, J = 22.9 Hz), 106.8, 66.8, 20.7, 18.8.

HRMS (ESI): m/z calcd for C12H13FNO4S [M + H]+: 286.0544; found: 286.0547.


#

N-[(4-Chlorophenyl)sulfonyl]-3,4-dihydro-2H-pyran-5-carboxamide (28)

Yield: 113.1 mg (75%); white solid; mp 295.6–297.1 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 11.67 (br s, 1 H), 7.92 (d, J = 8.6 Hz, 2 H), 7.68 (d, J = 8.8 Hz, 3 H), 3.98 (t, J = 5.2 Hz, 2 H), 2.03 (t, J = 6.4 Hz, 2 H), 1.75–1.69 (m, 2 H).

13C NMR (101 MHz, DMSO-d 6): δ = 166.0, 156.0, 139.4, 138.7, 130.1, 129.7, 108.2, 66.9, 20.9, 18.8.

HRMS (ESI): m/z calcd for C12H12ClNO4SNa [M + Na]+: 324.0068; found: 324.0078.


#

N-[(4-Bromophenyl)sulfonyl]-3,4-dihydro-2H-pyran-5-carboxamide (29)

Yield: 143.7 mg (83%); white solid; mp 192.1–194.1 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 11.68 (s, 1 H), 7.86–7.81 (m, 4 H), 7.67 (s, 1 H), 3.98 (t, J = 4.8 Hz, 2 H), 2.03 (t, J = 6.0 Hz, 2 H), 1.75–1.69 (m, 2 H).

13C NMR (101 MHz, DMSO-d 6): δ = 166.0, 156.0, 139.9, 132.6, 130.1, 127.7, 108.2, 66.8, 20.9, 18.8.

HRMS (ESI): m/z calcd for C12H12BrNO4SNa [M + Na]+: 367.9563; found: 367.9560.


#

N-(Naphthalen-1-ylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (30)

Yield: 82.5 mg (52%); white solid; mp > 300 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 11.92 (s, 1 H), 8.69 (d, J = 8.6 Hz, 1 H), 8.34 (d, J = 7.6 Hz, 1 H), 8.28 (d, J = 8.4 Hz, 1 H), 8.11 (d, J = 8.0 Hz, 1 H), 7.80–7.65 (m, 4 H), 3.95 (t, J = 4.8 Hz, 2 H), 1.97 (t, J = 6.0 Hz, 2 H), 1.70–1.64 (m, 2 H).

13C NMR (101 MHz, DMSO-d 6): δ = 165.7, 155.6, 135.2, 135.1, 134.1, 131.6, 129.7, 128.7, 127.9, 127.3, 125.0, 124.3, 108.2, 66.7, 20.8, 18.8.

HRMS (ESI): m/z calcd for C16H15NO4SNa [M + Na]+: 340.0614; found: 340.0605.


#

N-(Naphthalen-2-ylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (31)

Yield: 127.0 mg (80%); white solid; mp 298.5–299.9 °C.

1H NMR (400 MHz, DMSO-d 6): δ = 11.68 (s, 1 H), 8.60 (d, J = 2.0 Hz, 1 H), 8.21 (d, J = 8.0 Hz, 1 H), 8.13 (d, J = 8.8 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.91 (dd, J = 8.8, 2.0 Hz, 1 H), 7.75–7.66 (m, 3 H), 3.97 (t, J = 4.8 Hz, 2 H), 2.01 (t, J = 6.4 Hz, 2 H), 1.73–1.67 (m, 2 H).

13C NMR (101 MHz, DMSO-d 6): δ = 166.0, 155.8, 137.6, 135.0, 131.9, 129.9, 129.7, 129.6, 128.3, 128.2, 123.1, 108.3, 66.8, 20.9, 18.8.

HRMS (ESI): m/z calcd for C16H15NO4SNa [M + Na]+: 340.0614; found: 340.0613.


#

N-(Thiophen-2-ylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (32)

Yield: 88.8 mg (65%); white solid; mp 182.7–183.3 °C.

1H NMR (400 MHz, CDCl3): δ = 8.80 (s, 1 H), 7.91 (dd, J = 4.0, 1.2 Hz, 1 H), 7.67 (dd, J = 4.8, 1.2 Hz, 1 H), 7.57 (s, 1 H), 7.10 (dd, J = 4.8, 4.0 Hz, 1 H), 4.03 (t, J = 4.8 Hz, 2 H), 2.22 (t, J = 6.0 Hz, 2 H), 1.89–1.84 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 164.8, 155.7, 139.1, 135.0, 133.7, 127.3, 106.9, 66.8, 20.7, 18.8.

HRMS (ESI): m/z calcd for C10H12NO4S2 [M + H]+: 274.0202; found: 274.0207.


#

N-(Benzylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (33)

Yield: 116.7 mg (83%); white solid; mp 183.7–184.5 °C.

1H NMR (400 MHz, CDCl3): δ = 7.97 (s, 1 H), 7.51 (s, 1 H), 7.38–7.26 (m, 5 H), 4.65 (s, 2 H), 4.10–4.03 (t, J = 5.2 Hz, 2 H), 2.18 (t, J = 6.4 Hz, 2 H), 1.90–1.85 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 166.0, 155.9, 130.7, 129.1, 128.8, 128.1, 106.8, 66.8, 59.0, 20.7, 18.7.

HRMS (ESI): m/z calcd for C13H16NO4S [M + H]+: 282.0795; found: 282.0801.


#

N-(Propylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (34)

Yield: 75.8 mg (65%); white solid; mp 184.4–186.1 °C.

1H NMR (400 MHz, CDCl3): δ = 8.60 (br s, 1 H), 7.58 (s, 1 H), 4.05 (t, J = 5.2 Hz, 2 H), 3.48–3.44 (m, 2 H), 2.24 (t, J = 6.0 Hz, 2 H), 1.91–1.81 (m, 4 H), 1.04 (t, J = 7.6 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 166.0, 155.8, 107.0, 66.7, 55.2, 20.7, 18.7, 16.9, 12.6.

HRMS (ESI): m/z calcd for C9H16NO4S [M + H]+: 234.0795; found: 234.0805.


#

N-(Butylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (35)

Yield: 86.6 mg (70%); white solid; mp 197.1–199.4 °C.

1H NMR (400 MHz, CDCl3): δ = 8.55 (br s, 1 H), 7.59 (s, 1 H), 4.06 (t, J = 5.2 Hz, 2 H), 3.51–3.47 (m, 2 H), 2.25 (t, J = 6.4 Hz, 2 H), 1.92–1.86 (m, 2 H), 1.82–1.74 (m, 2 H), 1.49–1.40 (m, 2 H), 0.93 (t, J = 7.2 Hz, 3 H).

13C NMR (101 MHz, CDCl3): δ = 165.9, 155.8, 107.0, 66.8, 53.3, 25.1, 21.2, 20.7, 18.8, 13.5.

HRMS (ESI): m/z calcd for C10H18NO4S [M + H]+: 248.0951; found: 248.0954.


#

N-(Isopropylsulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (36)

Yield: 88.6 mg (76%); white solid; mp 189.7–191.4 °C.

1H NMR (400 MHz, CDCl3): δ = 8.51 (br s, 1 H), 7.59 (s, 1 H), 4.05 (t, J = 5.2 Hz, 2 H), 3.97–3.90 (hept, J = 7.2 Hz, 1 H), 2.25 (t, J = 6.0 Hz, 2 H), 1.92–1.86 (m, 2 H), 1.39 (d, J = 6.8 Hz, 6 H).

13C NMR (101 MHz, CDCl3): δ = 165.9, 155.7, 107.1, 66.7, 53.9, 20.7, 18.8, 15.9.

HRMS (ESI): m/z calcd for C9H16NO4S [M + H]+: 234.0795; found: 234.0802.


#

N-[(1-Allylcyclopropyl)sulfonyl]-3,4-dihydro-2H-pyran-5-carboxamide (37)

Yield: 59.7 mg (44%); white solid; mp 210.2–211.5 °C.

1H NMR (400 MHz, CDCl3): δ = 7.98 (br s, 1 H), 7.57 (s, 1 H), 5.73 (ddt, J = 17.2, 10.0, 7.2 Hz, 1 H), 5.17–5.08 (m, 2 H), 4.08 (t, J = 5.2 Hz, 2 H), 2.65 (d, J = 6.8 Hz, 2 H), 2.26 (t, J = 6.4 Hz, 2 H), 1.95–1.89 (m, 2 H), 1.74–1.70 (m, 2 H), 1.01–0.97 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 164.6, 155.4, 132.8, 118.9, 107.1, 66.7, 40.0, 35.3, 20.8, 19.1, 11.7.

HRMS (ESI): m/z calcd for C12H18NO4S [M + H]+: 272.0951; found: 272.0946.


#

(2S,3R,4S)-3,4-Di(benzyloxy)-2-[(benzyloxy)methyl]-N-tosyl-3,4-dihydro-2H-pyran-5-carboxamide (38)

Yield: 205.6 mg (67%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 8.91 (s, 1 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.55 (s, 1 H), 7.39–7.24 (m, 17 H), 4.66 (s, 2 H), 4.57–4.44 (m, 5 H), 4.32 (d, J = 4.0 Hz, 1 H), 4.09 (t, J = 4.4 Hz, 1 H), 3.75–3.65 (m, 2 H), 2.41 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 163.7, 156.6, 144.6, 137.4, 137.0, 136.1, 135.9, 129.3, 128.9, 128.6, 128.5, 128.43, 128.39, 128.37, 128.2, 127.9, 127.7, 105.8, 77.0, 73.4, 72.2, 70.8, 70.5, 70.0, 67.0, 21.6.

HRMS (ESI): m/z calcd for C35H36NO7S [M + H]+: 614.2207; found: 614.2214.


#

(E)-3-({(3S,8S,9S,10R,13R,14S,17R)-17-[(2R,5S,E)-5-Ethyl-6-methylhept-3-en-2-yl]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl}oxy)-N-tosyl­acrylamide (39)

Yield: 67.4 mg (53%), with 0.2 mmol alkene substrate; colorless oil.

1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 11.6 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 2 H), 5.36–5.33 (m, 2 H), 5.15 (dd, J = 15.2, 8.4 Hz, 1 H), 5.02 (dd, J = 15.2, 8.4 Hz, 1 H), 3.79–3.71 (m, 1 H), 2.42 (s, 3 H), 2.31 (d, J = 7.6 Hz, 2 H), 2.07–1.84 (m, 6 H), 1.61–1.42 (m, 11 H), 1.28–1.13 (m, 6 H), 1.02 (d, J = 6.8 Hz, 3 H), 0.98 (s, 3 H), 0.85–0.79 (m, 9 H), 0.69 (s, 3 H).

13C NMR (101 MHz, CDCl3): δ = 164.9, 163.3, 144.6, 138.9, 138.2, 136.3, 129.5, 129.3, 128.2, 123.2, 97.3, 83.4, 56.8, 55.9, 51.2, 50.0, 42.2, 40.4, 39.6, 38.5, 36.7, 36.5, 31.8, 28.8, 28.1, 25.4, 24.3, 21.6, 21.2, 21.0, 19.2, 19.0, 12.2, 12.0.

HRMS (ESI): m/z calcd for C39H58NO4S [M + H]+: 636.4081; found: 636.4080.


#

N-({4-[2-(5-Chloro-2-methoxybenzamido)ethyl]phenyl}sulfonyl)-3,4-dihydro-2H-pyran-5-carboxamide (44)

Yield: 186.8 mg (78%); white powder; mp 190.5–192.1 °C.

1H NMR (400 MHz, CDCl3): δ = 8.88 (br s, 1 H), 8.12 (d, J = 2.8 Hz, 1 H), 8.01 (d, J = 8.0 Hz, 2 H), 7.88–7.84 (m, 1 H), 7.56 (s, 1 H), 7.39 (d, J = 8.0 Hz, 2 H), 7.37–7.34 (m, 1 H), 6.86 (d, J = 8.8 Hz, 1 H), 4.01 (t, J = 5.2 Hz, 2 H), 3.77–3.72 (m, 5 H), 3.00 (t, J = 7.2 Hz, 2 H), 2.18 (t, J = 6.4 Hz, 2 H), 1.87–1.81 (m, 2 H).

13C NMR (101 MHz, CDCl3): δ = 165.1, 164.2, 155.9, 155.5, 145.6, 137.4, 132.4, 131.7, 129.3, 128.6, 126.5, 122.4, 112.9, 107.2, 66.7, 56.2, 40.5, 35.5, 20.7, 18.7.

HRMS (ESI): m/z calcd for C22H23ClN2O6SNa [M + Na]+: 501.0858; found: 501.0847.


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Conflict of Interest

The authors declare no conflict of interest.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-1401-4486.
  • Supporting Information

Corresponding Authors

Xiaoguang Bao
College of Chemistry, Chemical Engineering and Materials Science, Soochow University
Suzhou, 215123
P. R. of China   

Ji-Bao Xia
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Center for Excellence in Molecular Synthesis, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), University of Chinese Academy of Sciences, Chinese Academy of Sciences
Lanzhou 730000
P. R. of China   

Publication History

Received: 07 February 2021

Accepted after revision: 26 February 2021

Accepted Manuscript online:
26 February 2021

Article published online:
29 March 2021

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Scheme 1 Intermolecular C–H amidation of alkenes
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Scheme 2 Scope of C–H amidation of alkenes. Reagents and conditions: alkene (0.5 mmol), azide (0.75 mmol), CO (balloon), Pd(OAc)2 (5 mol%), MeCN (3 mL), 80 °C, 12 h. Isolated yields are shown.
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Scheme 3 Synthetic applications
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Figure 1 Energy profiles for the Pd(0)-catalyzed C–H amidation of alkenes with CO and TsN3 (bond lengths are shown in Å)
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Figure 2 Highest occupied molecular orbitals (HOMO) for alkene 1′ and 1
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Scheme 4 Control experiments
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Scheme 5 Plausible reaction pathway