Silver(I)-catalyzed addition of pyridine-N-oxides to alkynes: a practical approach for N-alkenoxypyridinium salts

Xiaodong Tanga, Nan Wua, Rongliang Zhaib, Zheng Wub, Jiajia Mib, Renshi Luoc and Zhou Xu*ab
aDepartment of Chemistry, Xuzhou Medical University, Xuzhou 221004, China. E-mail: xuzhou@xzhmu.edu.cn
bJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China
cSchool of Pharmaceutical Sciences, Gannan Medical University, Ganzhou 341000, China

Received 21st November 2018 , Accepted 26th December 2018

First published on 26th December 2018


A smooth catalytic approach to N-alkenoxypyridinium salts by using pyridine-N-oxides as the nucleophilic partner with alkynes under acidic conditions has been developed. This method uses different Ag(I) salts, with 5% AgOAc being the most efficient, to provide an efficient, practical and alternative way to obtain valuable N-alkenoxypyridinium salts with good to excellent yields (up to 93%).


Introduction

Enolates have shown promise in C–C bond forming reactions in organic chemistry, such as silyl enols, which have been widely used in organic transformations.1–7 N-Alkenoxypyridinium salts are special types of enolates that were first reported by us in 2016.8 They show excellent umpolung reactivity and can behave as surrogates of a highly reactive acylcarbenium cation (Fig. 1).9,10 However, in our previous studies, the N-alkenoxypyridinium salts were synthesized using an expensive gold(I) catalyst and only one alkenoxypyridinium salt was isolated, which limited the usage of the salts. Some N-alkenoxypyridinium salts have also been isolated and identified by other groups.11 There is no doubt that more interesting transformations would be realized in the future using N-alkenoxypyridinium salts as the building blocks. Thus, with these ideas in mind, it is important and practical to discover cheap and efficient methods in which to obtain N-alkenoxypyridinium salts.
image file: c8ob02907e-f1.tif
Fig. 1 Structure of an N-alkenoxypyridinium salt and its enolate umpolung reactivity.

Silver salts have long been believed to have low activity, and have commonly served as co-catalysts. In recent years, some new applications of silver catalysts have emerged and silver(I)-catalysed reaction chemistry has become one of the frontier areas in organic chemistry.12–18 In addition, in comparison with other metals, such as gold and platinum, silver(I) catalysts have superiority in terms of price and therefore have the stronger potential for industrial application. Silver(I) catalyzed terminal alkyne reactions effectively avoid the disadvantages of other transition metal-catalysed terminal alkyne coupling reactions, and have become a hot research field for catalytic terminal alkyne C–H bond activation.19,20 It has also been reported that silver(I) species could exhibit both carbophilic and oxophilic Lewis acid characteristics with a slight preference for σ bond over π bond coordination.21,22 These features indicate that silver(I) catalysts could doubly activate C–H σ bonds and C–C triple bonds.

Herein, we report a practical method for the addition reaction between pyridine-N-oxides and terminal alkynes catalysed by commercially available, cheap and simple silver(I) salts to synthesize a series of enol salts in good to excellent yields under mild reaction conditions.

Results and discussion

At the outset of our investigation, 1-undecyne was chosen as the model substrate and the reaction parameters such as silver catalysts, acids, solvents, concentrations and reaction temperatures were screened. The results are shown in Table 1. First, the reaction was carried out without any silver(I) salt, and no product was observed in the 1H NMR spectra of the unpurified product mixture (entry 1). Considering that the catalyst tends to determine the reaction rate, we wondered whether the catalyst coordination anion has a direct effect on the reaction. So, a preliminary study of the anion effect on catalysis using silver catalysts was carried out (entries 2–10). Godet has reported that among a variety of silver salts with low pKa values, the stronger the transition metal catalytic activity, the easier it is to activate triple bonds.23 It is not surprising that our studies show a similar trend. Considering the efficiency of the transformation and the price of the salts, AgOAc was found to be the most suitable for use in further studies (entry 5). The best solvent for the reaction was found to be CF3CH2OH (TFA). Hexafluoroisopropanol (HFIP) was a little less efficient. The use of other solvents, such as dichloromethane (DCM), dimethylformamide (DMF) or toluene, resulted in worse reaction yields. The results indicate that the reaction favoured polar protic solvents with higher catalytic activity rather than aprotic solvents (entries 5 and 15 vs. 11–14). Upon lowering the reaction temperature to 25 °C, the reaction did not proceed, even when the reaction time was prolonged to 24 h (entry 16). 1-Undecyne was fully converted to product 4a at 90 °C within 2 h, but the reaction yield was poor due to the formation of side products at high temperature (entry 17). Substrate concentration also effects the reaction. Increasing or decreasing the concentration of 1a, resulted in lower yields (entries 18 and 19). Higher catalyst loadings led to faster conversion, affording the product in the same yield (entry 20), while lowering the catalyst loading to 2.5% made it difficult for the reaction to proceed (entry 21). Finally, the effects of the acidity of the acids on the reaction were studied. Inorganic acids, such as H2SO4, gave a complexed mixture, while other organic acids, such as MsOH and TFA, fared worse than Tf2NH in terms of reaction rate and efficiency (entries 22–24).
Table 1 Initial reaction discovery and optimization of the conditionsa

image file: c8ob02907e-u1.tif

Entry Catalyst Solvent Acid Time (h) Yieldb (%)
a Reactions were run in vials, 1a (0.2 mmol), 2a (0.24 mmol), acid (0.22 mmol), silver catalyst (5%), solvent (0.2 ml), 60 °C.b 1H NMR yields (diethyl phthalate was used as the internal reagent). The numbers in brackets are the isolated yields.c The reaction was carried out at 25 °C. N.R means no reaction.d The reaction was carried out at 90 °C.e The concentration of the alkyne was 0.5 M (0.4 ml CF3CH2OH).f The concentration of the alkyne was 2.0 M (0.1 ml CF3CH2OH).g The catalyst loading was 7.5 mol%.h The catalyst loading was 2.5 mol%.
1 CF3CH2OH Tf2NH 12 N.R
2 Ag2O CF3CH2OH Tf2NH 12 65
3 Ag2CO3 CF3CH2OH Tf2NH 12 71
4 AgBF4 CF3CH2OH Tf2NH 12 75
5 AgOAc CF3CH2OH Tf2NH 12 92(90)
6 CF3COOAg CF3CH2OH Tf2NH 12 79
7 AgOTf CF3CH2OH Tf2NH 12 83
8 AgSbF6 CF3CH2OH Tf2NH 12 76
9 CF3CF2CF2COOAg CF3CH2OH Tf2NH 12 78
10 AgNTf2 CF3CH2OH Tf2NH 12 83
11 AgOAc DCM Tf2NH 12 31
12 AgOAc THF Tf2NH 12 50
13 AgOAc DMF Tf2NH 12 60
14 AgOAc Toluene Tf2NH 12 65
15 AgOAc (CF3)2CHOH Tf2NH 12 73
16c AgOAc CF3CH2OH Tf2NH 24 N.R
17d AgOAc CF3CH2OH Tf2NH 2 54
18e AgOAc CF3CH2OH Tf2NH 12 61
19f AgOAc CF3CH2OH Tf2NH 12 74
20g AgOAc CF3CH2OH Tf2NH 10 86
21h AgOAc CF3CH2OH Tf2NH 24 45
22 AgOAc CF3CH2OH H2SO4 24 Mixture
23 AgOAc CF3CH2OH MsOH 20 55
24 AgOAc CF3CH2OH CF3COOH 18 50


With the optimal conditions developed in Table 1, we subsequently turned to explore the scope of the alkynes with pyridine-N-oxides as the nucleophile under model conditions. As can be seen from Table 2, we found that a broad range of alkynes possessing various functional groups could be smoothly transformed to the products in moderate to good yields. For example, with 5-phenyl-1-pentyne as the substrate, 4b was obtained in 76% isolated yield (entry 1). The reaction was not affected by an alkyne substrate with a shorter alkyl group and proceeded cleanly to afford the corresponding product 4c in good yield (entry 2).

Table 2 Substrate scopesa,b
a Reactions were run in vials, 1a (0.2 mmol), 2a (0.24 mmol), Tf2NH (0.22 mmol), AgOAc (5%), TFA (0.2 ml), 60 °C.b The numbers in brackets are the reaction times and isolated yields.c No product was observed.
image file: c8ob02907e-u2.tif


Other terminal alkynes with functional groups, such as esters, sulfonyl, and hydroxyl groups, were compatible with the transformation and the corresponding products were obtained in good yields and all the products were stable in air (entries 3–7). In the case of 1,9-decadiyne, the di-N-alkenoxypyridinium salt 4i was obtained (entry 8). For the alkynes containing aromatic rings, the N-alkenoxypyridinium salt products were achieved in good yields and no intramolecular Friedel–Craftsss reaction products were observed under standard conditions (entries 12–16). For pyridine N-oxide substituted with electron-donating groups, such as methoxyl or methyl groups, its nucleophilic capacity was enhanced, which further promoted the formation of enol salts in better yields (entries 17 and 18). For sterically hindered 2,6-lutidine N-oxide, the reaction also proceeded smoothly and gave the product in 93% isolated yield (entry 19). Unfortunately, for N-oxides substituted by electron-withdrawing groups, such as Cl, the reaction did not take place under the optimized reaction conditions (entry 20).

Conclusions

We have described a versatile and efficient method using silver catalysts to produce a broad range of functionalized N-alkenoxypyridinium salts under mild conditions. The method uses different Ag(I) catalysts, with AgOAc being the most efficient, to provide an easy, efficient and practical way to obtain valuable N-alkenoxypyridinium salts in good to excellent yields (up to 93%), which broadens the future applications of these enols.

Experimental

Materials and methods

Unless otherwise noted, commercially available reagents were used without further purification. Methanol and 1,2-dichloroethane were of ACS reagent grade, and were used as received unless otherwise stated. HFIP was purchased from Acros and used without further purification. Silver salts were obtained from Acros and Merck chemical companies. The thin layer chromatography (TLC) analysis of the reaction mixtures was performed on silica gel GF254 TLC plates. Flash chromatography was carried out on Shanghai Titan technology co., Ltd silica gel (300–400 mesh). 1H NMR, 13C NMR and 19F NMR spectra were recorded on JEOL JMTC-400/54/SS 400 MHz spectrometers using residue solvent peaks as the internal standards. Infrared spectra were recorded on a PerkinElmer FT-IR spectrum 2000 spectrometer and are reported in reciprocal centimeters (cm−1). Mass spectra were recorded using MicroTof-II electron spray ionization (MeOH as the solvent) or Waters GCT Premier time-of-flight mass spectrometers with a field ionization (FI) ion source.

General procedure for the synthesis of compounds 4a–4t

Pyridine N-oxide and Tf2NH were premixed in a molar ratio of 1.1/1.0 and then stored in a vial and used directly in the reaction.

In a vial, AgOAc (4.2 mg, 5% equiv.) was added into a mixture of undec-1-yne (78.5 mg, 0.5 mmol), the above premixed salt (207.0 mg, 1.1 equiv.) and CF3CH2OH (0.5 mL). The reaction mixture was then stirred at 60 °C, and the progress of the reaction was monitored by TLC (DCM/MeOH = 20/1). After the reaction was completed, the reaction mixture was concentrated, and the resulting residue was purified by flash chromatography on silica gel (eluent: DCM/MeOH = 50/1) to afford the desired product 4a.

1-(Undec-1-en-2-yloxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide (4a)

1H NMR (400 MHz, CDCl3): δ 8.86 (dd, J = 6.9, 0.9 Hz, 2H), 8.66 (td, J = 7.9, 1.2 Hz, 1H), 8.29 (t, J = 7.3 Hz, 2H), 4.51 (d, J = 5.6 Hz, 1H), 3.69 (d, J = 5.6 Hz, 1H), 2.38 (t, J = 7.6 Hz, 2H), 1.76–1.50 (m, 2H), 1.26 (m, 12H), 0.87 (t, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 166.2, 146.7, 142.0, 130.3, 119.7 (q, J = 319.1 Hz), 88.9, 31.8, 30.9, 29.3, 29.2, 29.1, 28.8, 26.4, 22.6, 14.0. 19F NMR (CDCl3, 376 MHz): δ −78.6. IR (cm−1): 2927, 2856, 1667, 1481, 1350, 1185, 1135, 1055, 616, 570. ESI+ calculated for [C16H26NO]+ (M − NTf2)+: 248.2009, found: 248.2017.

1-((5-Phenylpent-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide (4b)

1H NMR (400 MHz, CDCl3): δ 8.82–8.72 (m, 2H), 8.59 (q, J = 6.1 Hz, 1H), 8.22 (t, J = 7.1 Hz, 2H), 7.33–7.27 (m, 2H), 7.20 (d, J = 7.8 Hz, 3H), 4.52 (d, J = 3.6 Hz, 1H), 3.68 (d, J = 6.0 Hz, 1H), 2.71 (t, J = 3.6, 2H), 2.42 (t, J = 3.6, 2H), 1.98–1.78 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 165.6, 146.7, 141.9, 141.0, 130.2, 128.5, 126.2, 122.9 (q, J = 319.1 Hz), 89.4, 34.8, 30.4, 27.8. 19F NMR (CDCl3, 376 MHz): δ −78.8. IR (cm−1): 3118, 2959, 1671, 1620, 1480, 1348, 1178, 1133, 1052, 868, 739. ESI+ calculated for C16H18NO+ (M − NTf2)+: 240.1383, found: 240.1388.

1-((4-Phenylbut-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4c

1H NMR (400 MHz, CDCl3): δ 8.65 (d, J = 6.9 Hz, 2H), 8.57 (t, J = 7.8 Hz, 1H), 8.18 (t, J = 7.3 Hz, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.27–7.17 (m, 3H), 4.51 (d, J = 6.0 Hz, 1H), 3.67 (d, J = 6.0 Hz, 1H), 2.95 (t, J = 7.8 Hz, 2H), 2.71 (t, J = 7.8 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 164.9, 146.7, 141.9, 139.5, 130.2, 128.7, 128.5, 126.7, 119.7 (q, J = 320.1 Hz), 89.9, 32.8, 32.4. 19F NMR (CDCl3, 376 MHz): δ −78.8; IR (cm−1): 3118, 1668, 1608, 1348, 1178, 1132, 1052, 750, 612. ESI+ calculated for C15H16NO+ (M − NTf2)+: 226.1226, found: 226.1225.

1-((3-Acetoxyprop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4d

1H NMR (400 MHz, DMSO-d6): δ 9.45 (dd, J = 6.9, 1.4 Hz, 2H), 8.96–8.92 (m, 1H), 8.52 (t, J = 7.6 Hz, 2H), 5.15 (d, J = 5.6 Hz, 1H), 4.88 (s, 2H), 4.58 (d, J = 5.6 Hz, 1H), 2.06 (s, 3H). 13C NMR (100 MHz, DMSO-d6): δ 169.6, 159.6, 147.5, 142.4, 130.6, 120.2 (q, J = 319.1 Hz), 96.1, 60.4, 19.7. 19F NMR (DMSO-d6, 376 MHz): δ −79.8. IR (cm−1): 3121, 2960, 1743, 1676, 1610, 1481, 1347, 1226, 1132, 1052, 876, 510. ESI+ calculated for C10H12NO3+ (M − NTf2)+: 194.0812, found: 194.0812.

1-((5-Ethoxy-4-(ethoxycarbonyl)-5-oxopent-1-en-2-yl)oxy) pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4e

1H NMR (400 MHz, CDCl3): δ 8.97 (dd, J = 6.9, 0.8 Hz, 2H), 8.71 (t, J = 7.2 Hz, 1H), 8.30 (t, J = 7.2 Hz, 2H), 4.65 (d, J = 6.0 Hz, 1H), 4.24 (qd, J = 7.2, 2.8 Hz, 4H), 3.85 (d, J = 6.0 Hz, 1H), 3.80 (t, J = 7.8 Hz, 1H), 3.01 (d, J = 7.8 Hz, 2H), 1.30–1.26 (t, J = 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3): δ 167.9, 161.8, 147.2, 142.0, 130.4, 119.7 (q, J = 320.1 Hz), 91.6, 62.2, 49.6, 30.3, 13.6. 19F NMR (CDCl3, 376 MHz): δ −78.9. IR (cm−1): 3120, 1726, 1672, 1610, 1480, 1349, 1178, 1133, 1054, 878, 613, 569. ESI+ calculated for C15H20NO5+ (M − NTf2)+: 294.1336, found: 294.1320.

1-((3-(Phenylsulfonyl)prop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4f

1H NMR (400 MHz, CD3COCD3): δ 9.38 (d, J = 5.6 Hz, 2H), 9.00 (t, J = 7.6 Hz, 1H), 8.59 (t, J = 7.6 Hz, 2H), 8.06 (d, J = 7.2 Hz, 2H), 7.83 (t, J = 7.6 Hz, 1H), 7.72 (t, J = 7.6 Hz, 2H), 4.94 (d, J = 5.6 Hz, 1H), 4.64 (d, J = 5.6 Hz, 1H), 4.60 (s, 2H). 13C NMR (100 MHz, CD3COCD3): δ 154.3, 147.8, 142.3, 138.6, 134.6, 130.9, 129.6, 128.6, 120.2 (q, J = 320.1 Hz), 99.1, 57.3. 19F NMR (CD3COCD3, 376 MHz): δ −79.8. IR (cm−1): 3116, 2929, 1660, 1476, 1348, 1188, 597. ESI+ calculated for C14H14NO3S+ (M − NTf2)+: 276.0689, found: 276.0687.

1,1′-(Deca-1,9-diene-2,9-diylbis(oxy))bis(pyridin-1-ium) bis((trifluoromethyl)sulfonyl)amide 4g

1H NMR (400 MHz, CD3COCD3): δ 9.37 (dd, J = 6.9, 1.4 Hz, 4H), 8.92 (tt, J = 7.8, 1.1 Hz, 2H), 8.58–8.28 (m, 4H), 4.67 (d, J = 5.2 Hz, 2H), 3.96 (d, J = 5.2 Hz, 2H), 2.51 (t, J = 8.4 Hz, 4H), 1.86–1.65 (m, 4H), 1.62–1.46 (m, 4H). 13C NMR (100 MHz, CD3COCD3): δ 166.1, 147.3, 142.7, 130.4, 120.2 (q, J = 320.1 Hz), 88.5, 30.8, 28.4, 26.4. 19F NMR (CD3COCD3, 376 MHz): δ −79.8. IR (cm−1): 3121, 2939, 1667, 1611, 1481, 1347, 1178, 599. ESI+ calculated for C20H26N2O2+ (M − NTf2)+: 326.1983, found: 326.1987.

1-((4-Hydroxybut-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4h

1H NMR (400 MHz, CD3COCD3): δ 9.42(dd, J = 6.9, 0.9 Hz, 2H), 8.94–8.92 (m, J = 7.8, 1.1 Hz, 1H), 8.54–8.50 (m, 2H), 4.76 (d, J = 5.0 Hz, 1H), 4.08 (d, J = 5.0 Hz, 1H), 3.89 (t, J = 6.2 Hz, 2H), 2.68 (t, J = 6.2 Hz, 2H). 13C NMR (100 MHz, CD3COCD3): δ 164.1, 147.2, 142.7, 130.4, 120.2 (q, J = 320.1 Hz), 90.7, 58.6, 34.6. 19F NMR (CD3COCD3, 376 MHz): δ −79.8. IR (cm−1): 3537, 3121, 1670, 1611, 1481, 1347, 1179, 1131, 1051, 611, 569. ESI+ calculated for C9H12NO2+ (M − NTf2)+: 166.0863, found: 166.0864.

1-((11-Hydroxyundec-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4i

1H NMR (400 MHz, DMSO-d6): δ 9.40 (d, J = 5.6 Hz, 2H), 8.74 (t, J = 7.8, 1H), 8.31 (d, J = 7.2 Hz, 2H), 4.56 (d, J = 5.2 Hz, 1H), 4.28 (t, J = 5.2 Hz, 1H), 3.77 (d, J = 4.8 Hz, 2H), 3.35 (t,), 2.36 (t, J = 7.5 Hz, 2H), 1.58–1.56 (m, 2H), 1.39–1.25 (m, 12H). 13C NMR (100 MHz, CD3OD): δ 166.4, 146.7, 142.6, 129.8, 119.9 (q, J = 319.1 Hz), 87.7, 61.7, 32.3, 30.8, 29.4, 29.3, 29.0, 28.7, 26.5, 25.6. 19F NMR (CD3OD, 376 MHz): δ −76.6. IR (cm−1): 3544, 3120, 2929, 2857, 1667, 1610, 1481, 1349, 1185, 1056, 615, 570, 513. ESI+ calculated for C16H26NO2+ (M − NTf2)+: 264.1958, found: 264.1957.

1-((3-Hydroxyhept-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4j

1H NMR (400 MHz, CD3OD): δ 9.18 (d, J = 6.0 Hz, 2H), 8.66 (t, J = 7.8 Hz, 1H), 8.21 (t, J = 7.3 Hz, 2H), 4.81 (d, J = 6.8, 1H), 4.24 (dd, J = 8.3, 4.9 Hz, 1H), 4.00–3.99 (m, 1H), 1.76–1.73 (m, 1H), 1.72–1.59 (m, 1H), 1.51–1.26 (m, 4H), 0.88 (t, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CD3OD): δ 167.2, 146.7, 142.3, 129.8, 119.9 (q, J = 319.1 Hz), 89.9, 69.5, 33.9, 27.5, 22.2, 13.0. 19F NMR (CD3OD, 376 MHz): δ −80.5. IR (cm−1): 3512, 3121, 2961, 1667, 1610, 1481, 1348, 1182, 1053, 570. ESI+ calculated for C12H18NO2+ (M − NTf2)+: 208.1332, found: 208.1327.

1-((3-(Pentyloxy)prop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4k

1H NMR (400 MHz, CDCl3): δ 8.96 (d, J = 6.0 Hz, 2H), 8.65 (t, J = 7.8 Hz, 1H), 8.26 (t, J = 7.3 Hz, 2H), 5.02 (d, J = 4.8 Hz, 1H), 4.56 (d, J = 4.8 Hz, 1H), 4.14 (s, 2H), 3.44 (t, J = 6.6 Hz, 2H), 1.53–1.41 (m, 2H), 1.37–1.20 (m, 4H), 0.87 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 160.2, 146.6, 141.3, 130.1, 119.7 (q, J = 319.1 Hz), 98.4, 71.3, 67.5, 29.0, 28.0, 22.3, 13.9. 19F NMR (CDCl3, 376 MHz): δ −78.9. IR (cm−1): 2936, 1667, 1610, 1481, 1349, 1183, 1134, 1055, 789, 570. ESI+ calculated for C13H20NO2+ (M − NTf2)+: 222.1489, found: 222.1487.

1-((11-((2-(Pyridin-1-ium-1-yloxy)allyl)oxy)undec-1-en-2-yl) oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4l

1H NMR (400 MHz, CD3OD): δ 9.23–9.15 (m, 4H), 8.65 (t, J = 7.8 Hz, 2H), 8.20 (t, J = 7.2 Hz, 4H), 4.95 (d, J = 5.2 Hz, 1H), 4.50 (d, J = 5.2 Hz, 1H), 4.41 (d, J = 4.8 Hz, 1H), 4.15 (s, 2H), 3.71 (d, J = 5.0 Hz, 1H), 3.42 (t, J = 5.6 Hz, 2H), 2.38 (t, J = 7.8 Hz, 2H), 1.61–1.55 (m, 2H), 1.47 (t, J = 6.4 Hz, 2H), 1.36–1.26 (m, 8H). 13C NMR (100 MHz, CD3OD): δ 166.4, 161.0, 146.7, 142.6, 142.1, 129.8, 129.7, 119.9 (q, J = 319.1 Hz), 95.6, 87.8, 70.9, 67.4, 30.8, 29.3, 29.2(4), 29.2, 29.0, 28.7, 26.5, 25.8. F19 NMR (CD3OD, 376 MHz): δ −80.5. IR (cm−1): 3120, 2933, 1668, 1610, 1481, 1348, 1178, 1132, 1052, 867, 612, 569. ESI+ calculated for C24H34N2O3+ (M − NTf2)+: 398.2558, found: 398.2551.

1-((3-(Benzyloxy)prop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4m

1H NMR (400 MHz, CDCl3): δ 8.86–8.84 (m, 2H), 8.53 (t, J = 7.8 Hz, 1H), 8.14 (t, J = 7.0 Hz, 2H), 7.35–7.28 (m, 5H), 5.02 (d, J = 5.2 Hz, 1H), 5.56 (d, J = 4.8 Hz, 1H), 4.52 (s, 2H), 4.20 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 159.8, 146.5, 141.3, 136.7, 130.0, 128.6, 128.3, 128.1, 119.8 (q, J = 319.1 Hz), 99.0, 72.8, 66.8. 19F NMR (CDCl3, 376 MHz): δ −78.8. IR (cm−1): 3118, 2919, 1672, 1611, 1480, 1348, 1181, 1133, 1052, 867, 740, 612, 569. ESI+ calculated for C15H16NO2+ (M − NTf2)+: 242.1176, found: 242.1175.

1-((3-((2-Bromobenzyl)oxy)prop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4n

1H NMR (400 MHz, CDCl3): δ 8.92 (d, J = 6.0 Hz, 2H), 8.56 (t, J = 7.8 Hz, 1H), 8.17 (t, J = 7.3 Hz, 2H), 7.53 (d, J = 8.2 Hz, 1H), 7.34–7.28 (m, 2H), 7.22–7.09 (m, 1H), 5.07 (d, J = 4.8 Hz, 1H), 4.59 (s, 2H), 4.58 (d, J = 4.8 Hz, 1H), 4.26 (s, 2H). 13C NMR (100 MHz, CDCl3): δ 159.7, 146.5, 141.3, 136.0, 132.8, 130.0, 129.8, 127.7, 123.3, 121.3, 119.7 (q, J = 319.1 Hz), 98.9, 72.3, 67.3; 19F NMR(CDCl3, 376 MHz): δ −78.8; IR (cm−1): 3119, 1671, 1612, 1480, 1348, 1178, 1132, 1052, 750, 612; ESI+ calculated for C15H15BrNO2+ (M − NTf2)+: 320.0281, found: 320.0282.

1-((3-(1-(4-(Trifluoromethyl)phenyl)ethoxy)prop-1-en-2-yl) oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4o

1H NMR (400 MHz, CDCl3): δ 8.93 (dd, J = 6.9, 0.9 Hz, 2H), 8.62 (t, J = 7.8 Hz, 1H), 8.24 (t, J = 7.5 Hz, 2H), 7.62 (d, J = 7.8 Hz, 2H), 7.42 (d, J = 7.8 Hz, 2H), 4.98 (d, J = 5.2 Hz, 1H), 4.58 (q, J = 6.8 Hz, 1H), 4.50 (d, J = 4.6 Hz, 1H), 4.07 (s, 2H), 1.41 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 160.1, 146.6, 146.3, 141.4, 130.1, 126.6, 125.7, 125.6(7), 125.6, 119.8 (q, J = 319.1 Hz), 98.3, 77.8, 65.6, 23.5. 19F NMR (CDCl3, 376 MHz): δ −78.9, −62.4. IR (cm−1): 3120, 1680, 1620, 1481, 1349, 1324, 1182, 1129, 1053, 843, 739, 612, 569. ESI+ calculated for C17H17F3NO2+ (M − NTf2)+: 324.1206, found: 324.1221.

1-((3-Phenethoxyprop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4p

1H NMR (400 MHz, CDCl3): δ 8.51–8.48 (m, 3H), 8.03–7.99 (m, 2H), 7.32–7.29 (m, 2H), 7.25–7.23 (m, 3H), 4.97 (d, J = 4.8 Hz, 1H), 4.62 (d, J = 5.2 Hz, 1H), 4.07 (s, 2H), 3.70 (t, J = 6.2 Hz, 2H), 2.84 (t, J = 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 159.3, 146.3, 140.9, 140.0, 129.7, 129.0, 128.5, 126.4, 119.7 (q, J = 320.1 Hz), 99.7, 71.2, 67.1, 35.8. 19F NMR (CDCl3, 376 MHz): δ −78.8. IR (cm−1): 3121, 2958, 1667, 1609, 1480, 1351, 1190, 1135, 1056, 615, 570, 513. ESI+ calculated for C16H17NO2+ (M − NTf2)+: 256.1332, found: 256.1335.

1-((3-(2-Chlorophenethoxy)prop-1-en-2-yl)oxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4q

1H NMR (400 MHz, CDCl3): δ 8.70 (dd, J = 6.9, 1.4 Hz, 2H), 8.58–8.56 (m, 1H), 8.14 (t, J = 7.3 Hz, 2H), 7.36 (d, J = 9.1 Hz, 1H), 7.25–7.16 (m, 3H), 5.01 (d, J = 4.4 Hz, 1H), 4.68 (d, J = 2.7 Hz, 1H), 4.12 (s, 2H), 3.71 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 6.0 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 159.6, 146.5, 141.1, 136.0, 134.0, 131.4, 130.0, 129.5, 128.1, 126.9, 119.9 (q, J = 320.1 Hz), 99.6, 69.8, 67.4, 33.5. 19F NMR (CDCl3, 376 MHz): δ −78.8. IR (cm−1): 3119, 1672, 1609, 1477, 1348, 1181, 1133, 1058, 868, 760, 614. ESI+ calculated for C16H17ClNO2+ (M − NTf2)+: 290.0942, found: 290.0940.

4-Methoxy-1-(undec-1-en-2-yloxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4r

1H NMR (400 MHz, CDCl3): δ 8.55 (dd, J = 6.0 Hz, 1.8 Hz, 2H), 7.58 (dd, J = 6.0 Hz, 1.8 Hz, 2H), 4.43 (d, J = 5.2 Hz, 1H), 4.18 (s, 3H), 3.69 (d, J = 5.2 Hz, 1H), 2.34 (t, J = 7.8 Hz, 2H), 1.62–1.58 (m, 2H), 1.37–1.26 (m, 12H), 0.87 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 171.5, 165.7, 143.0, 119.7 (q, J = 320.1 Hz), 114.8, 87.8, 58.8, 31.8, 30.9, 29.3, 29.2, 29.1, 28.8, 26.5, 22.6, 14.0. 19F NMR (CDCl3, 376 MHz): δ −78.8. IR (cm−1): 3121, 1668, 1612, 1487, 1349, 1180, 1132, 1068, 867, 760, 615. ESI+ calculated for C17H28NO2+ (M − NTf2)+: 278.2115, found: 278.2117.

3-Methyl-1-(undec-1-en-2-yloxy)pyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4s

1H NMR (400 MHz, CDCl3): δ 8.66–8.61 (m, 2H), 8.45 (d, J = 8.0 Hz, 1H), 8.18–8.14 (m, 1H), 4.51 (d, J = 5.6 Hz, 1H), 3.74 (d, J = 5.6 Hz, 1H), 2.68 (s, 3H), 2.37 (d, J = 8.0 Hz, 2H), 1.65–1.61 (m, 2H), 1.37–1.28 (m, 12H), 0.88 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 166.1, 147.5, 142.6, 140.9, 139.2, 129.4, 124.6, 119.8 (q, J = 320.1 Hz), 88.9, 31.8, 31.0, 29.4, 29.2, 28.9, 26.5, 22.6, 18.7, 14.1. 19F NMR (CDCl3, 376 MHz): δ −75.9. IR (cm−1): 3120, 2940, 1660, 1613, 1488, 1350, 1181, 1133, 1070, 867, 761, 612. ESI+ calculated for C17H28NO+ (M − NTf2)+: 262.2165, found: 262.2166.

1-(But-1-en-2-yloxy)-2,6-dimethylpyridin-1-ium bis((trifluoromethyl)sulfonyl)amide 4t

1H NMR (400 MHz, CDCl3): δ 8.38 (t, J = 8.0 Hz, 1H), 7.91 (d, J = 7.6 Hz, 2H), 4.45 (d, J = 5.6 Hz, 1H), 3.57 (d, J = 5.6 Hz, 1H), 2.78 (s, 3H), 2.44 (t, J = 7.8 Hz, 2H), 1.72–1.65 (m, 2H), 1.46–1.28 (m, 12H), 0.89 (t, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 161.3, 153.6, 135.7, 129.0, 119.8 (q, J = 320.1 Hz), 87.0, 31.8, 31.0, 29.4, 29.2, 29.1(7), 29.1, 26.6, 22.6, 17.7, 14.1. 19F NMR (CDCl3, 376 MHz): δ −78.7. IR (cm−1): 3115, 2944, 2858, 1668, 1612, 1487, 1349, 1180, 1068, 867, 761, 572. ESI+ calculated for C18H30NO+ (M − NTf2)+: 276.2322, found: 276.2325.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors thank the National Natural Science Foundation of China (Grant No. 21602191) and the Natural Science Foundation of Jiangsu Province (Grants No. BK 20171175). The work is also sponsored by the Qing Lan Project of Jiangsu Province, the 333 Project of Jiangsu Province and the Jiangsu Six Talent Peaks Program (YY-042). Dr Tang acknowledges financial support from Xuzhou Medical University (D2016016).

Notes and references

  1. K. Inoue, R. Nakura, K. Okano and A. Mori, Eur. J. Org. Chem., 2018, 3343–3347 CrossRef CAS.
  2. (a) Z. W. Jiao, J. J. Beiger, Y. S. Jin, S. Z. Ge, J. S. Zhou and J. F. Hartwig, J. Am. Chem. Soc., 2016, 138, 15980–15986 CrossRef CAS PubMed; (b) B. M. Trost, J. Y. Xu and M. Reichle, J. Am. Chem. Soc., 2007, 129, 282–283 CrossRef CAS PubMed.
  3. Y. W. Wu, L. Hu, Z. Li and L. Deng, Nature, 2015, 523, 445–450 CrossRef CAS PubMed.
  4. R. M. Fedor and R. Tomislav, Nature, 2015, 523, 417–418 CrossRef PubMed.
  5. Y.-L. Chen, H. Redlich, K. Bergander and R. Fröhlich, Org. Biomol. Chem., 2007, 5, 3330–3339 RSC.
  6. X. Liu, A. Gao, L. Ding, J. Xu and B. Zhao, Org. Lett., 2014, 16, 2118–2121 CrossRef CAS PubMed.
  7. Some selective references on enolate umpolung. (a) K. Graf, C. L. Rühl, M. Rudolph, F. Rominger and A. S. K. Hashmi, Angew. Chem., Int. Ed., 2013, 52, 12727–12731 CrossRef CAS PubMed; (b) M. Lemmerer, C. J. Teskey, D. Kaiser and N. Maulide, Monatsh. Chem., 2018, 149, 715–719 CrossRef CAS PubMed; (c) J. D. Neuhaus, P. Angyal, R. Oost and N. Maulide, J. Org. Chem., 2018, 83, 2479–2485 CrossRef CAS PubMed; (d) D. Seebach, Angew. Chem., Int. Ed. Engl., 1979, 18, 239–258 CrossRef; (e) O. Miyata, T. Miyoshi and M. Ueda, Arkivoc, 2013, ii, 60–81 Search PubMed; (f) S. Arava, J. N. Kumar, S. Maksymenko, M. A. Iron, K. N. Parida, P. Fristrup and A. M. Szpilman, Angew. Chem., Int. Ed., 2017, 56, 2599–2603 CrossRef CAS PubMed.
  8. Z. Xu, H. Chen, Z. Wang, A. Ying and L. Zhang, J. Am. Chem. Soc., 2016, 138, 5515–5518 CrossRef CAS PubMed.
  9. Z. Xu, R. L. Zhai, T. Liang and L. Zhang, Chem. – Eur. J., 2017, 23, 14133–14137 CrossRef CAS PubMed.
  10. R. L. Zhai, Y. S. Xue, T. Liang, J. J. Mi and Z. Xu, J. Org. Chem., 2018, 83, 10051–10059 CrossRef CAS PubMed.
  11. (a) X. Xia, B. Chen, X. Zeng and B. Xu, Adv. Synth. Catal., 2018, 360, 4429–4434 CrossRef CAS; (b) X. Xia, B. Chen, X. Zeng and B. Xu, Org. Biomol. Chem., 2018, 16, 6918–6922 RSC.
  12. J. M. Weibel, A. Blanc and P. Pale, Chem. Rev., 2008, 108, 3149–3173 CrossRef CAS PubMed.
  13. M. Álvarez-Corral, M. Munoz-Dorado and I. Rodrıguez-Garcıa, Chem. Rev., 2008, 108, 3174–3198 CrossRef PubMed.
  14. M. Naodovic and H. Yamamoto, Chem. Rev., 2008, 108, 3132–3148 CrossRef CAS PubMed.
  15. Y. Yamamoto, Chem. Rev., 2008, 108, 3199–3222 CrossRef CAS PubMed.
  16. G. Fang and X. Bi, Chem. Soc. Rev., 2015, 44, 8124–8173 RSC.
  17. G. Abbiati and E. Rossi, Beilstein J. Org. Chem., 2014, 10, 481–513 CrossRef PubMed.
  18. K. Sekine and T. Yamada, Chem. Soc. Rev., 2016, 45, 4524–4532 RSC.
  19. (a) C. He, J. Hao, H. Xu, Y. Mo, H. Liu, J. Nan and A. Lei, Chem. Commun., 2012, 48, 11073–11075 RSC; (b) Z. Zheng, Z. Wang, Y. Wang and L. Zhang, Chem. Soc. Rev., 2016, 45, 4448–4458 RSC; (c) H. Yeom and S. Shin, Acc. Chem. Res., 2014, 47, 966–977 CrossRef CAS PubMed; (d) L. Zhang, Acc. Chem. Res., 2014, 47, 877–888 CrossRef CAS PubMed; (e) J. Xiao and X. Li, Angew. Chem., Int. Ed., 2011, 50, 7226–7236 CrossRef CAS PubMed; (f) B. Zhou and L. Ye, Synlett, 2016, 493–497 CAS.
  20. Recent representative examples on the N-oxide oxidation of alkynes: (a) J. M. Yang, Y. T. Zhao, Z. Q. Li, X. S. Gu, S. F. Zhu and Q. L. Zhou, ACS Catal., 2018, 8, 7351–7355 CrossRef CAS; (b) J. Zhao, W. Xu, X. Xie, N. Sun, X. Li and Y. Liu, Org. Lett., 2018, 20, 5461–5465 CrossRef CAS PubMed; (c) J. Li, H. Xing, F. Yang, Z. Chen and K. Ji, Org. Lett., 2018, 20, 4622–4626 CrossRef CAS PubMed; (d) X. Zeng, S. Liu, Z. Shi, G. Liu and B. Xu, Angew. Chem., Int. Ed., 2016, 55, 10032–10036 CrossRef CAS PubMed; (e) Y. Zhang, Y. Xue, G. Li, H. Yuan and T. Luo, Chem. Sci., 2016, 7, 5530–5536 RSC; (f) Y. Wang, Z. Zheng and L. Zhang, J. Am. Chem. Soc., 2015, 137, 5316–5319 CrossRef CAS PubMed; (g) H. Chen and L. Zhang, Angew. Chem., Int. Ed., 2015, 54, 11775–11779 CrossRef CAS PubMed; (h) L. Li, C. Shu, B. Zhou, Y. F. Yu, X. Y. Xiao and L. W. Ye, Chem. Sci., 2014, 5, 4057–4064 RSC.
  21. Y. Yamamoto, J. Org. Chem., 2007, 72, 7817–7831 CrossRef CAS PubMed.
  22. R. Sarkar and C. Mukhopadhyay, Eur. J. Org. Chem., 2015, 1246–1256 CrossRef CAS.
  23. T. Godet, C. Vaxelaire, C. Michel, A. Milet and P. Belmont, Chem. – Eur. J., 2007, 13, 5632–5641 CrossRef CAS PubMed.

Footnotes

Electronic supplementary information (ESI) available. See DOI: 10.1039/c8ob02907e
These authors contributed equally.

This journal is © The Royal Society of Chemistry 2019