N–H Cross-Coupling between

Note pubs.acs.org/joc

Visible-Light Mediated Oxidative C−H/N−H Cross-Coupling between Tetrahydrofuran and Azoles Using Air Lingling Zhang,†,§ Hong Yi,†,§ Jue Wang,† and Aiwen Lei*,†,‡ †

College of Chemistry and Molecular Sciences, The Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, China National Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang 330022, Jiangxi P. R. China

‡

S Supporting Information *

ABSTRACT: Tetrahydrofuran is a privileged structural moiety in many important organic compounds. In this work, we have developed a simple and mild catalytic oxidative amination of tetrahydrofuran mediated by visible-light catalysis. The C(sp3)-H bond of tetrahydrofuran was activated using molecular oxygen as a benign oxidant. Besides, a variety of azoles could be tolerated, providing a green route for N-substituted azoles.

N

Scheme 1. Photoredox-Mediated C−H Amination of THF

-substituted azoles not only are widely found in agriculture, antifungal, and pharmaceuticals,1 but also have been broadly used as precursors for N-heterocyclic carbenes (NHC) and ionic liquids.2 Considering the intriguing properties and important application of N-substituted azoles in organic chemistry, seeking a new approach to the synthesis of functional azoles is attractive and necessary. Traditionally, the N-alkylation of azoles is accomplished via the straightforward nucleophilic substitution of alkyl halides with azoles under basic conditions.3 However, the drawback of commercially nonavailable alkyl halides makes the reaction sometimes nonapplicable. In the past decade, the exploration and development of direct C−H functionalization have attracted a great deal of interest for C−C, C−O, and C−N bonds formation.4 This versatile protocol circumvents the preinstallation of functional groups and also takes advantage of atom economy. In this direction, Li and co-workers developed an iron-catalyzed N-alkylation of azoles with THF using TBHP as the oxidant.5 Later, Yang realized a Cu/DTBP-catalyzed C− H activation strategy for the N-alkylation of azoles.6 Hypervalent iodine reagent/tetrabutylammonium iodide (TBAI)mediated cross-dehydrogenative coupling of azoles also offered a convergent approach to synthesize hemiaminal ethers.7 To the best of our knowledge, the oxidative coupling reactions by using oxygen as oxidant have been less studied, and the pursuit of new oxidant system to achieve direct C−H functionalization is always an ongoing interest for organic chemists. Visible light photoredox catalysis has emerged as a powerful technique in organic synthesis in recent years,8 providing a mild condition for organic transformation. In continuation of our interest in the development of C−H activation/functionalization methods9 and mechanistic studies,10 seeking a mild and green way is always under operation in our lab. Herein, we report a simple and mild metal-free catalytic oxidative amination approach via α-C(sp3)-H activation of tetrahydrofuran mediated by visible-light using air as benign oxidant (Scheme 1). © 2017 American Chemical Society

Tetrahydrofuran is a privileged structural moiety in many important organic compounds.11 The direct functionalization of THF to construct complex organic compounds was an exploring and meaningful approach for the synthetic chemistry community.12 We started our evaluation of the reaction parameters with 3-phenyl-1H-pyrazole 1a as the model substrate using Acr+−Mes ClO4− as the photocatalyst, which has a strong oxidative ability.13 The anticipated product could be achieved in 82% yield in the presence of 3.0 mol% Acr+− Mes ClO4− using THF as the solvent under air atmosphere (Table 1, entry 1). Other data in Table 1 illustrated the impact of different conditions on the efficiency of this reaction. Other tested photocatalysts, such as methylene blue or fluorescein, did not get desired product (Table 1, entries 7 and 8). Eosin Y resulted in lower yield of desired product 3a (Table 1, entry 6). In the control experiments, no desired product was observed without photoredox catalyst or light, indicating that the photoredox catalysis is essential to this process (Table 1, entries 4 and 2). Additionally, no product was detected in the absence of air (Table 1, entry 3). A further optimization of reaction parameters was subsequently conducted. Prolonging or shortening the reaction time (Table 1, entries 12 and 13), and increasing or decreasing photocatalyst loading proved to be not beneficial to this process (Table 1, entries 9, 10, and 11). We have also tried the mixture solvents, but the results were not good. With the preliminary optimized reaction conditions in hand, we next tested the versatility of this catalyst system for the direct amination of azoles. Various azoles were investigated and Received: July 23, 2017 Published: September 1, 2017 10704

DOI: 10.1021/acs.joc.7b01841 J. Org. Chem. 2017, 82, 10704−10709

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The Journal of Organic Chemistry Table 1. Optimization of Reaction Conditionsa

entry 1 2d 3e 4 5f 6 7 8 9g 10h 11i 12 13

photocatalyst Acr −Mes Acr+−Mes Acr+−Mes +

ClO4− ClO4− ClO4−

Acr+−Mes ClO4− eosin Y methylene blue fluorescein Acr+−Mes ClO4− Acr+−Mes ClO4− Acr+−Mes ClO4− Acr+−Mes ClO4− Acr+−Mes ClO4−

time (h)

yield (%)b

24 24 24 24 24 24 24 24 24 24 24 12 36

82 n. d.c n. d.c n. d.c 37 57 n. d.c n.d.c 35 48 28 75 81

phenyl-1H-pyrazoles (3a, 3b) and 4-phenyl-1H-1,2,3-triazoles (3l−3p) were applied. However, the electron-deficient methyl aromatics was poor substrate (3h). The C−Cl, C−Br, and C−I groups were well tolerated under the reaction conditions, providing the possibility for further functionalization (3f, 3g, 3i, and 3j). The reason for the low yields were due to the low conversation of the substrates (3c, 3h, and 3k). The optimized conditions were also compatible with 2methyltetrahydrofuran giving corresponding coupled product 3q in 85% yield (eq 1). We have also tried other ethers, such as 1,4-dioxane, tetrahydropyrane, and diethyl ether. However, the results were not good under our standard conditions. From the profile of the reaction with the light off/on over time, it was observed that the transformation proceeded smoothly under irradiation with visible-light, but no further conversion was observed when the light source was removed (Figure 1). This result indicated that continuous irradiation of visible light is essential to this amination of tetrahydrofuran.

a

Reaction conditions: 1a (0.50 mmol), photocatalyst (3.0 mol%) in THF (3.0 mL) at room temperature in air under 3 W blue LEDs for 24 h. bDetermined by GC using biphenyl as an internal standard. c n.d.= no desired product. dWithout light. eUnder N2 atmosphere. f Under O2 atmosphere. gAcr+−Mes ClO4− (1 mol%). hAcr+−Mes ClO4− (5 mol%). iAcr+−Mes ClO4− (7 mol%).

To prove that the reaction proceeded through a radical pathway, a radical-trapping experiment was carried out (Scheme 3). No desired product was observed when the reaction was performed by the addition of a radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) under the standard reaction conditions, which implied that a radical

the results are summarized in Scheme 2. A variety of substituted azoles underwent the coupling smoothly. Pyrazoles and 1H1,2,3-triazoles led to the corresponding products with moderate to good yields. Moreover, good yields were obtained when 3Scheme 2. Reactions of Azoles with THFa

Reaction conditions: 1 (0.50 mmol), Acr+-Mer ClO4− (3.0 mol%) in THF (3 mL) at room temperature in air using 3 W Blue LEDs for 24 h. Isolated yields are shown. a

10705

DOI: 10.1021/acs.joc.7b01841 J. Org. Chem. 2017, 82, 10704−10709

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The Journal of Organic Chemistry

Figure 1. Profile of the reaction with the light off/on over time.

Scheme 3. Radical Inhibiting Experiment

Figure 3. Acr+−Mes ClO4− emission quenching with 3-phenyl-1Hpyrazole; I0 and I represent the intensities of the emission in the absence and presence of the quencher.

that 3-phenyl-1H-pyrazole could quench the excited state of Acr+−Mes ClO4−. These results suggested that the reaction might undergo an efficiently reductive quenching mechanism. To get more investigation of the reaction, a kinetic isotopic effect (KIE) experiment was also conducted (Scheme 4). In

mechanism was involved. However, no adduct with TEMPO was detected. Additionally, the radical mechanism of this transformation was also proven by an electron paramagnetic resonance (EPR) study. Under irradiation of green light, a radical intermediate was captured by using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as the spin trapping reagent (Figure 2). The spin

Scheme 4. Kinetic Isotopic Effect (KIE) Experiment

order to probe the dependence of C−H bond cleavage, a KIE of 5.0 was observed from a competition experiment between d8-THF and THF. This result revealed that the α-C−H bond cleavage of THF is likely to be the kinetically dependent ratelimiting step. Based on the previous reports15 and experimental results, a plausible mechanism is proposed in Scheme 5. First, the photocatalyst Acr+−Mes ClO4− is excited by visible light irradiation (3W blue LEDs) to generate the excited species [Acr+−MesClO4−]*, which then undergoes the single electron transfer (SET) process with pyrazole compound to generate nitrogen-center radical 4, and [Acr+−MesClO4−] radical anion. Subsequently, acridine radical Mes-Acr· can be oxidized by O2 to form the acridinium Mes-Acr+ along with the generation of superoxide O2·− The generated superoxide O2·− undergoes a hydrogen abstraction of C−H bond adjacent to an oxygen atom affords tetrahydrofuran radical 5. Finally, the radical−radical cross coupling between 5 and 4 affords the desired product 3 (path a). The radical 5 can also be further oxidized to cation intermediate 6 via the single oxidation process (path b). The direct coupling between 6 and 1 forms the product via the cross-dehydrogenative-coupling (CDC) mechanism. In conclusion, we have disclosed a simple and metal-free catalytic oxidative amination approach via α-C(sp 3)-H activation of tetrahydrofuran by visible-light using air as benign oxidant. This condition tolerates a variety of azoles, providing a

Figure 2. Electron paramagnetic resonance (EPR) study.

Hamiltonian parameters observed for this spin adduct were in agreement with the literature values for a nitrogen-centered radical.14 No EPR signal was observed in the absence of 3phenyl-1H-pyrazole. We proposed that this radical belonged to the nitrogen-centered radical, originating from 3-phenyl-1Hpyrazole. Furthermore, a series of emission quenching experiments were performed to acquire further insight into the photoredox catalytic cycle (Figure 3). This experiment revealed 10706

DOI: 10.1021/acs.joc.7b01841 J. Org. Chem. 2017, 82, 10704−10709

Note

The Journal of Organic Chemistry Scheme 5. Proposed Mechanism

2H), 6.49 (d, J = 2.4 Hz, 1H), 6.00 (dd, J = 6.4, 2.4 Hz, 1H), 4.20− 4.14 (m, 1H), 4.03−3.97 (m, 1H), 3.83 (s, 3H), 2.69−2.62 (m, 1H), 2.38−2.17 (m, 2H), 2.09−1.99 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 159.5, 152.0, 129.3, 127.2, 126.7, 114.2, 102.6, 90.4, 69.5, 55.6, 32.2, 24.6. 3-(2-Fluorophenyl)-1-(tetrahydrofuran-2-yl)-1H-pyrazole (3d). 57.9 mg (Colorless liquid, yield: 54%). 1H NMR (400 MHz, CDCl3) δ 7.58−7.52 (m, 3H), 7.36−7.31 (m, 1H), 7.00−6.95 (m, 1H), 6.55 (d, J = 2.4 Hz, 1H), 6.00 (dd, J = 6.4, 2.4 Hz, 1H), 4.19− 4.14 (m, 1H), 4.03−3.97 (m, 1H), 2.68−2.61 (m, 1H), 2.38−2.17 (m, 2H), 2.09−1.99 (d, J = 38.0 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 164.6, 162.2, 151.0 (d, J = 2.0 Hz), 136.1 (d, J = 8.0 Hz), 129.6, 121.5, 114.5, 112.6, 103.3, 90.5, 69.6, 32.2, 24.6. HRMS (ESI) calculated for C13H13FN2O [M+H]+: 233.1085; found: 233.1085. 4-Methyl-1-(tetrahydro-2-furanyl)-1H-pyrazole (3e).7 41.1 mg (Colorless liquid, yield: 37%). 1H NMR (400 MHz, CDCl3) δ 7.36 (s, 1H), 7.33 (s, 1H), 5.92 (dd, J = 6.8, 2.8 Hz, 1H), 4.12−4.06 (m, 1H), 3.99−3.94 (m, 1H), 2.63−2.55 (m, 1H), 2.35−2.14 (m, 2H), 2.07− 1.97 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 140.7, 127.2, 116.6, 90.1, 69.3, 31.6, 24.8, 9.2. 4-Bromo-1-(tetrahydro-2-furanyl)-1H-pyrazole (3f).7 58.6 mg (Colorless liquid, yield: 82%). 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.48 (s, 1H), 5.92 (dd, J = 6.6, 2.4 Hz, 1H), 4.11−4.05 (m, 1H), 3.99−3.93 (m, 1H), 2.58−2.50 (m, 1H), 2.33−2.23 (m, 1H), 2.15− 1.95 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 140.5, 128.4, 93.6, 90.8, 69.7, 31.9, 24.3 4-Chloro-1-(tetrahydro-2-furanyl)-1H-pyrazole (3g). 46.6 mg (Colorless liquid, yield: 67%). 1H NMR (400 MHz, CDCl3) δ 7.55 (s, 1H), 7.45 (s, 1H), 5.90 (dd, J = 6.8, 2.4 Hz, 1H), 4.11−4.06 (m, 1H), 4.00−3.94 (m, 1H), 2.59−2.52 (m, 1H), 2.33−2.24 (m, 1H), 2.16− 1.96 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 138.1, 126.0, 110.2, 90.7, 69.4, 31.6, 24.2. HRMS (ESI) calculated for C7H9ClN2O [M +H]+: 173.0476; found: 173.0470. 4-Nitro-1-(tetrahydro-2-furanyl)-1H-pyrazole (3h).7 49.5 mg (Colorless liquid, yield: 36%). 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 8.10 (s, 1H), 5.99 (dd, J = 6.4, 1.6 Hz, 1H), 4.26−4.19 (m, 1H), 4.09−4.03 (m, 1H), 2.63−2.56 (m, 1H), 2.44−2.34 (m, 1H), 2.11− 2.01 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 136.3, 127.2, 91.7, 70.4, 32.5, 23.8. 4-Bromo-3,5-dimethyl-1-(tetrahydro-2-furanyl)-1H-pyrazole (3i).7 66.2 mg (Colorless liquid, yield: 63%). 1H NMR (400 MHz, CDCl3) δ 5.88 (dd, J = 7.2, 3.6 Hz, 1H), 4.03−3.97 (m, 1H), 3.92− 3.87 (m, 1H), 2.82−2.74 (m, 1H), 2.36−2.17 (m, 8H), 2.04−1.94 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 146.5, 138.1, 95.6, 86.9, 68.9, 29.9, 25.4, 12.7, 10.4. 4-Iodo-3,5-dimethyl-1-(tetrahydro-2-furanyl)-1H-pyrazole (3j). 78.9 mg (Colorless liquid, yield: 50%). 1H NMR (400 MHz, CDCl3) δ 5.92 (dd, J = 7.2, 3.6 Hz, 1H), 4.05−3.99 (m, 1H), 3.93− 3.88 (m, 1H), 2.82−2.74 (m, 1H), 2.40−2.19 (m, 8H), 2.06−1.96 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 149.9, 141.7, 87.2, 69.0, 65.0, 30.2, 25.5, 14.5, 12.3. HRMS (ESI) calculated for C9H13IN2O [M +H]+: 293.0145; found: 293.0146. 4-(3-Bromophenyl)-1-(tetrahydrofuran-2-yl)-1H-1,2,3-triazole (3k).7 56 mg (Colorless liquid, yield: 38%). 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.67−7.65 (m, 2H), 7.54−7.52 (m, 2H), 6.32

green route for N-substituted azoles. We believe this oxidative reaction mediated by visible light will help chemists to design more and more interesting, useful, and sustainable reactions in the near future.

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EXPERIMENTAL SECTION

General Information. All manipulations were carried out by standard Schlenk techniques. Unless otherwise noted, analytical grade solvents and commercially available reagents were used to conduct the reactions. Thin layer chromatography (TLC) employed glass 0.25 mm silica gel plates. Flash chromatography columns were packed with 200−300 mesh silica gel in petroleum (boiling point is between 60 and 90 °C). Gradient flash chromatography was conducted eluting with a continuous gradient using petroleum ether and ethyl acetate. The known compounds were characterized by 1H NMR and 13C NMR. GC-MS spectra were recorded on a Varian GC-MS 3900−2100T. The 1 H and 13C NMR spectra were recorded on a Bruker Advance III 400 MHz NMR spectrometer with tetramethylsilane as an internal standard. The chemical shifts (δ) were given in part per million relative to internal tetramethyl silane (TMS, 0 ppm for 1H), CDCl3 (77.3 ppm for 13C). The photocatalyst Acr+ - Mes ClO4− is commercial available from the company of TokyoChemicalIndustry (TCI). The CAS number is 674783-97-2. The source of the blue LEDs is common LED lights. The power of each light is 3W. There is 3.0 cm distance between the reactor and LEDs. This reaction could be wellperformed using a round bottle (25 mL). Below we will add two pictures of our instrument. General Procedure for Visible Light Mediated Aerobic Oxidative C−H Amination of Tetrahydrofuran under Mild Conditions. In a dried Schlenk tube, azoles 1 (0.5 mmol), Acr+-Mes ClO4− (3 mol%, 0.015 mmol) were stirred in 3.0 mL THF for 24 h at room temperature under an air atmosphere irradiated by blue LEDs. After completion of the reaction, as indicated by TLC and GC-MS, the mixture was diluted by ethyl acetate. The pure product was obtained by flash column chromatography on silica gel using petroleum ether and ethyl acetate. 3-Phenyl-1-(tetrahydro-2-furanyl)-1H-pyrazole (3a).7 57.9 mg (Colorless liquid, yield: 82%). 1H NMR (400 MHz, CDCl3) δ 7.83− 7.80 (m, 2H), 7.57 (d, J = 2.4 Hz, 1H), 7.38 (m, 2H), 7.29 (m, 1H), 6.56 (d, J = 2.4 Hz, 1H), 6.01 (dd, J = 6.4, 2.5 Hz, 1H), 4.20−4.14 (m, 1H), 4.03−3.97 (m, 1H), 2.69- 2.62 (m, 1H), 2.38−2.17 (m, 2H), 2.08−1.99 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 152.1, 133.8, 129.4, 128.8, 127.9, 125.9, 103.1, 90.5, 69.6, 32.2, 24.6. 3-(4-Chlorophenyl)-1-(tetrahydro-2-furanyl)-1H-pyrazole (3b). 67.2 mg (Colorless liquid, yield: 78%). 1H NMR (400 MHz, CDCl3) δ 7.75−7.72 (m, 2H), 7.55 (d, J = 2.8 Hz, 1H), 7.35−7.32 (m, 2H), 6.51 (d, J = 2.4, 1H), 5.99 (dd, J = 6.4, 2.6 Hz, 1H), 4.18−4.12 (m, 1H), 4.01−3.95 (m, 1H), 2.65−2.58 (m, 1H), 2.36−2.14 (m, 2H), 2.07−1.97 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 150.9, 133.4, 132.3, 129.6, 128.9, 127.1, 103.0, 90.4, 69.5, 32.1, 24.5. HRMS (ESI) calculated for C13H13ClN2O [M+H]+: 249.0789; found: 249.0788. 3-(4-Methoxyphenyl)-1-(tetrahydro-2-furanyl)-1H-pyrazole (3c): 7 65.9 mg (Colorless liquid, yield: 24%). 1H NMR (400 MHz, CDCl3) δ 7.76−7.72 (m, 2H), 7.55 (d, J = 2.4 Hz, 1H), 6.94−6.90 (m, 10707

DOI: 10.1021/acs.joc.7b01841 J. Org. Chem. 2017, 82, 10704−10709

The Journal of Organic Chemistry

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(dd, J = 6.8, 2.8 Hz, 1H), 4.21−4.15 (m, 1H), 4.08−4.02 (m, 1H), 2.72−2.64 (m, 1H), 2.49−2.36 (m, 2H), 2.14−2.04 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 147.0, 132.0, 131.4, 129.3, 127.6, 122.5, 92.4, 69.7, 31.4, 24.5. 4-Phenyl-1-(tetrahydro-2-furanyl)-1H-1,2,3-triazole (3l).7 58.1 mg (Colorless liquid, yield: 64%). 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.81−7.79 (m, 2H), 7.44−7.40 (m, 2H), 7.37−7.33 (m, 1H), 6.34 (dd, J = 6.8, 2.8 Hz, 1H), 4.23−4.17 (m, 1H), 4.09−4.03 (m, 1H), 2.72−2.66 (m, 1H), 2.51−2.37 (m, 2H), 2.14−2.04 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 148.3, 131.7, 130.6, 129.1, 128.8, 126.3, 92.6, 69.8, 31.6, 24.7. HRMS (ESI) calculated for C14H13N3O [M+H]+: 216.1131; found: 216.1132. 1-(Tetrahydro-2-furanyl)-4-(p-tolyl)-1H-1,2,3-triazole (3m).7 61.9 mg (Colorless liquid, yield: 57%). 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.69−7.67 (m, 2H), 7.23−7.21 (m, 2H), 6.33 (dd, J = 6.8, 2.8 Hz, 1H), 4.21−4.16 (m, 1H), 4.07−4.02 (m, 1H), 2.71−2.66 (m, 1H), 2.48−2.35 (m, 5H), 2.13−2.02 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 148.3, 138.6, 131.5, 129.7, 127.7, 126.1, 92.5, 69.8, 31.5, 24.7, 21.6. 4-(4-Chlorophenyl)-1-(tetrahydro-2-furanyl)-1H-1,2,3-triazole (3n).7 67.4 mg (Colorless liquid, yield: 80%). 1H NMR (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.75−7.72 (m, 2H), 7.41−7.38 (m, 2H), 6.33 (dd, J = 6.8, 2.8 Hz, 1H), 4.22−4.17 (m, 1H), 4.09−4.04 (m, 1H), 2.71−2.66 (m, 1H), 2.51−2.38 (m, 2H), 2.15−2.06 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 147.3, 134.6, 131.6, 129.3, 129.1, 127.5, 92.7, 69.9, 31.6, 24.7. 4-(4-Fluorophenyl)-1-(tetrahydro-2-furanyl)-1H-1,2,3-triazole (3o).7 62.9 mg (Colorless liquid, yield: 60%). 1H NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.79−7.74 (m, 2H), 7.14−7.08 (m 2H), 6.33 (dd, J = 6.8, 2.8 Hz, 1H), 4.22−4.17 (m, 1H), 4.09−4.03 (m, 1H), 2.71−2.65 (m, 1H), 2.51−2.37 (m, 2H), 2.15−2.04 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 164.3, 161.9, 147.4, 131.4, 128.0 (d, J = 8.0 Hz), 126.8 (d, J = 7.0 Hz), 116.2, 116.0, 92.6, 69.8, 31.6, 24.7. 4-(4-(tert-butyl)phenyl)-1-(tetrahydrofuran-2-yl)-1H-1,2,3triazole (3p).7 78.3 mg(Colorless liquid, yield: 58%). 1H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.74−7.71 (m, 2H), 7.46−7.43 (m 2H), 6.33 (dd, J = 6.8, 2.4 Hz, 1H), 4.21−4.16 (m, 1H), 4.07−4.02 (m, 1H), 2.71−2.65 (m, 1H), 2.50−2.35 (m, 2H), 2.13−2.02 (m, 1H), 1.34 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 151.6, 148.1, 131.4, 127.5, 125.8, 125.8, 92.3, 69.6, 34.7, 31.4, 31.3, 24.5. 1-(2-Methyltetrahydro-2-furanyl)-3-phenyl-1H-pyrazole (3q). 61.6 mg (Colorless liquid, yield: 85%). 1H NMR (400 MHz, CDCl3) δ 7.82−7.80 (m, 2H), 7.67 (d, J = 2.4 Hz, 1H), 7.39−7.35 (m, 2H), 7.28−7.24 (m, 1H), 6.52 (d, J = 2.4 Hz, 1H), 4.09−3.97 (m, 2H), 3.09−3.01 (m, 1H), 2.11−1.85 (m, 3H), 1.78 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 151.4, 134.1, 128.7, 127.8, 127.6, 125.8, 102.4, 98.4, 69.4, 37.8, 27.5, 24.8. HRMS (ESI) calculated for C14H16N2O [M +H]+: 229.1335; found: 229.1334.

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ACKNOWLEDGMENTS This work was supported by the National Natural ScienceFoundation of China (21390400, 21520102003, 21272180, 21302148), the Natural Science Foundation of Hubei Province (2016CFB571). The Program of Introducing Talents of Discipline to Universities of China (111 Program) is also appreciated.

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REFERENCES

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01841. 1

H and 13C NMR spectra of all products (PDF)

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Note

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] ORCID

Aiwen Lei: 0000-0001-8417-3061 Author Contributions §

L.Z. and H.Y. contributed equally to this work.

Notes

The authors declare no competing financial interest. 10708

DOI: 10.1021/acs.joc.7b01841 J. Org. Chem. 2017, 82, 10704−10709

Note

The Journal of Organic Chemistry 5852. (b) Singh, P. P.; Gudup, S.; Aruri, H.; Singh, U.; Ambala, S.; Yadav, M.; Sawant, S. D.; Vishwakarma, R. A. Org. Biomol. Chem. 2012, 10, 1587. (c) Liu, D.; Liu, C.; Li, H.; Lei, A. Angew. Chem., Int. Ed. 2013, 52, 4453. (13) (a) Ohkubo, K.; Mizushima, K.; Iwata, R.; Souma, K.; Suzuki, N.; Fukuzumi, S. Chem. Commun. 2010, 46, 601. (b) Ohkubo, K.; Mizushima, K.; Iwata, R.; Fukuzumi, S. Chem. Sci. 2011, 2, 715. (14) Ke, J.; Tang, Y.; Yi, H.; Li, Y.; Cheng, Y.; Liu, C.; Lei, A. Lei. Angew. Chem., Int. Ed. 2015, 54, 6604. (15) (a) Xiang, M.; Meng, Q.-Y.; Gao, X.-W.; Lei, T.; Chen, B.; Tung, C.-H.; Wu, L.-Z. Org. Chem. Front. 2016, 3, 486. (b) Xiang, M.; Meng, Q.-Y.; Li, J.-X.; Zheng, Y.-W.; Ye, C.; Li, Z.-J.; Chen, B.; Tung, C.-H.; Wu, L.-Z. Chem. - Eur. J. 2015, 21, 18080. (c) Aruri, H.; Singh, U.; Kumar, M.; Sharma, S.; Aithagani, S. K.; Gupta, V. K.; Mignani, S.; Vishwakarma, R. A.; Singh, P. P. J. Org. Chem. 2017, 82, 1000.

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DOI: 10.1021/acs.joc.7b01841 J. Org. Chem. 2017, 82, 10704−10709