Ag Catalyzed C4–H Sulfonylation of 1

Oct 17, 2017 - This C4 sulfonylation proceeded smoothly at room temperature under Ru/Cu photoredox catalysis or Cu/Ag cocatalysis and could tolerate v...
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Ru/Cu Photoredox or Cu/Ag Catalyzed C4−H Sulfonylation of 1‑Naphthylamides at Room Temperature Peirong Bai,† Suyan Sun,† Zexian Li,† Huijie Qiao,† Xiaoxue Su,† Fan Yang,*,† Yusheng Wu,*,‡ and Yangjie Wu*,† †

The College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, P. R. China ‡ Tetranov Biopharm, LLC. & Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou 450052, P. R. China S Supporting Information *

ABSTRACT: A mild and efficient protocol for C4−H sulfonylation of 1-naphthylamine derivatives with sodium sulfinates has been described. This C4 sulfonylation proceeded smoothly at room temperature under Ru/Cu photoredox catalysis or Cu/Ag cocatalysis and could tolerate various functional groups. In addition, control experiments suggested that this C4−H sulfonylation reaction might proceed via a single-electron-transfer process.

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INTRODUCTION Sulfone derivatives have attracted enormous attention because they exist in a number of compounds relevant to pharmaceuticals, agrochemicals, and advanced functional materials.1 The general synthetic methods include the oxidation of sulfides, alkylation of sulfinates, Friedel−Crafts type sulfonlyation of arenes, and electrophilic substitution of aromatics with sulfonyl halides or sulfonic acids.2 These classic methods usually involve strong oxidants or strong acids or are limited by the electronic effect of the starting materials. Along with great progress in transition-metal-catalyzed C−H functionalization, a series of transformations from C−H to C−C and C−heteroatom bonds have been demonstrated.3 After the first palladium-catalyzed ortho-sulfonylation of 2-phenylpyridines with arylsulfonyl chlorides was demonstrated by Dong4a and co-workers, various transition-metal-catalyzed and transitionmetal-free procedures were described.4 For example, Tan,4b Shi,4c and Manolikakes4d independently developed copper-mediated or catalyzed C(sp2)−H sulfonylations of arene derivatives with sodium sulfinates assisted by different removable directing groups such as AQ (8-aminoquinolinyl), PIP (2-pyridinyl isopropyl), and Oxa (amide-oxazoline), and this type of sulfonylation is observed in an exclusive ortho-position of the directing group in three cases. Simultaneously, Wei,4e Manolikakes,4f Zhang,4g and our group4h reported copper-catalyzed C(sp2)−H sulfonylations of 8-aminoquinoline auxiliary with arylsulfonyl chlorides or sodium sulfinates, and the sulfonylation exclusively takes place at the C5 site in the quinoline ring. Compared with the above direct C−H functionalization of arenes or 8-aminoquinoline, the development on the direct C−H functionalization of the naphthalene ring lags behind.5 Until recently, the Manolikakes group mentioned a coppercatalyzed C4−H sulfonylation of 1-naphthylamides with © 2017 American Chemical Society

sodium or lithium sulfinates via picolinamide (PA) directed remote C−H activation (Scheme 1a).5a However, the reaction Scheme 1. Direct Sulfonylation of 1-Naphthylamides at the C4 Site

still suffered from an excess of manganese salt and sodium sulfinate. During the preparation of this manuscript, the Lu group developed a copper-catalyzed C4−H functionalization of 1-naphthylamides with arylsulfonyl chlorides at higher reaction temperature (Scheme 1b).5b Therefore, it is still meaningful and challenging to develop a green reaction pattern and go through a new mechanism to fulfill this sulfonylation. In recent years, visible-light photoredox catalysis has emerged as a robust and reliable tool due to its environmental compatibility and versatility in green chemistry.6 Herein, we demonstrate a Received: July 31, 2017 Published: October 17, 2017 12119

DOI: 10.1021/acs.joc.7b01917 J. Org. Chem. 2017, 82, 12119−12127

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The Journal of Organic Chemistry

(Table 1, entry 15). Among the various Ag salts examined, Ag2CO3 was the best choice (Table 1, entries 15−18). In the above Cu/Ru photocatalysis and Cu/Ag cocatalysis, both the oxidant and copper salt are indispensable for the successful sulfonylation, and the reaction did not occur at all without K2S2O8 or Cu(OAc)2·H2O (Table 1, entries 13, 14, 19, 20, and Table S1). In addition, decrease of catalyst or oxidant loading would lead to products in reduced yields (Table S1). With the optimized conditions, we next explored the applicability of the present sulfonylation protocol for N-(naphthalen-1-yl) picolinamide derivatives (Scheme 2). First, the PA moiety bearing a methyl group could result in the product in a good yield (3ba). The quinoline-2-carboxamide also showed an excellent directing group in the presence of sodium pivalate (PivONa) (3ca), while isoquinoline-1-carboxamide as the directing group provided the product in a slightly lower yield possibly due to the steric effect between the carbonyl group and C8−H at the isoquinoline ring (3da). Under both sets of the optimal reaction conditions, auxiliaries bearing either an electron-withdrawing or -donating substituent at the C2, C5, C7, and C8 position of the 1-naphthylamine ring were well tolerated (3ea−3ja), especially the sensitive hydroxyl group, which is easily oxidized, and the bromine atom tends to take part in traditional couplings (3ga and 3ja). In addition, 8-aminoquinoline amides could also afford the desired product in a high yield using PivONa as an additive (3ka); the addition of PivONa would possibly accelerate the generation of copper coordination complex due to the replacement of NH → Cu by N− → Cu.7 However, the treatment of 2-naphthylamine derivatives with 2a afforded C1-sulfonylated products (3la and 3ma) in moderate yields.5a

simple and mild protocol for remote C−H sulfonylation of 1-naphthylamides under either a Ru/Cu photocatalysis or a traditional Cu/Ag cocatalysis system (Scheme 1c).

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RESULTS AND DISCUSSION Initially, we commenced our investigation by the reaction of N-(naphthalen-1-yl)picolinamide (1a) with sodium benzenesulfinates (2a) as a model reaction (Table 1 and Table S1). After extensive experimentation, gratifyingly, the desired product 3aa was obtained in 60% yield when 20 mol % of Cu(OAc)2· H2O as a catalyst and K2S2O8 as an oxidant were selected at room temperature in a mixed solvent (acetone/H2O = 1:1) under air for 3 h (Table 1, entry 1, and Table S1). The structure of 3aa was unambiguously confirmed by single crystal X-ray diffraction. We were pleased to find that the desired product 3aa was obtained in 99% yield at 100 °C (Table 1, entry 2). However, the high temperature means high energy consumption and does not conform to the demand of green chemistry. Thus, we were committed to fulfilling the reaction at room temperature by the aid of photoredox catalysis. To our surprise, in the presence of Ru(bpy)3(PF6)2 as a photosensitizer under household light irradiation for 3 h, the desired product 3aa was obtained in up to 98% isolated yield (Table 1, entry 3). The absence of the light irradiation led to a decrease of the isolated yield (Table 1, entry 4). Other photocatalysts did not exhibit higher catalytic activity (Table 1, entries 5−9 vs entry 3), and several other wavelength light sources generated the desired product in lower yields (Table 1, entries 10−12 vs entry 3). On the other hand, a catalytic amount of Ag salt could also play a central role to promote reaction in the absence of photocatalyst, almost quantitatively affording desired product in 99% yield Table 1. Screening of Reaction Conditionsa

entry 1 2c 3 4d 5 6 7 8 9 10e 11f 12g 13h 14i 15 16 17 18 19h 20i

photocatalyst

Ag catalyst

yieldb (%)

Ag2CO3 AgNO3 Ag2O AgOAc Ag2CO3 Ag2CO3

60 99 98 58 62 58 60 62 63 76 61 61 NR NR 99 87 83 87 NR NR

Ru(bpy)3(PF6)2 Ru(bpy)3(PF6)2 Eosin Y Eosin B Acid red 87 Rose bengal Ru(bpy)3Cl2·6H2O Ru(bpy)3(PF6)2 Ru(bpy)3(PF6)2 Ru(bpy)3(PF6)2 Ru(bpy)3(PF6)2 Ru(bpy)3(PF6)2

a Reaction conditions: 1a (0.1 mmol), 2a (0.2 mmol), Cu(OAc)2·H2O (20 mol %), photocatalyst (3 mol %, 26 W household light), Ag catalyst (20 mol %), and K2S2O8 (2 equiv) in 1 mL of acetone:H2O (1:1) at room temperature in air for 3 h. NR: No reaction. bIsolated yield. cAt 100 °C d In the dark. eUnder green light. fUnder red light. gUnder blue light. hWithout K2S2O8. iWithout Cu(OAc)2·H2O.

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DOI: 10.1021/acs.joc.7b01917 J. Org. Chem. 2017, 82, 12119−12127

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The Journal of Organic Chemistry Scheme 2. Substrate Scope of 1-Naphthylamidesa,b

a

Reaction condition A: 1 (0.1 mmol), 2a (0.2 mmol), Ru(bpy)3(PF6)2 (3 mol %), under 26 W household light. Condition B: 1 (0.1 mmol), 2a (0.2 mmol), Ag2CO3 (20 mol %). bIsolated yield. cWith the addition of 1 equiv of PivONa. dWith the addition of 50 mol % of Ag2CO3 and 1 equiv of PivONa.

The directing group can subsequently be removed by hydrolysis to give the medicinally useful intermediate of 4-sulfonylnaphthyl amine in 92% yield (Scheme 4b). A series of control experiments were conducted in order to gain insight into the reaction mechanism (Schemes 5 and 6). Several designed substrates were examined under the standard reaction conditions, but no sulfonylation products were detected (Scheme 5). For example, N-methyl 4a or acetyl 5a analogue of 1-naphthylamides did not favor this reaction, and thus the bidentate chelation nature of the picolinamide in directing group was critical in this transformation and we can also exclude electrophilic aromatic substitution from the possible reaction pathways. Meanwhile, 1-naphthol, benzylamine, and aniline derivatives did not contribute to the functionality of the system (6a, 7a, and 8a). Then, performing the reaction under a nitrogen or an oxygen atmosphere instead of air afforded the product 3aa in similar yields, which showed that oxygen might have no effect on this sulfonylation (Scheme 6a). In addition, the addition of radical inhibitor tetramethylpiperidine-1-oxyl (TEMPO) or butylated hydroxytoluene (BHT) resulted in inhibition of the reaction (Scheme 6b). Furthermore, when the reaction of 4-methylbenzenesulfinate (TsNa) with BHT was performed under standard conditions, the product 10a could be detected

Subsequently, the scope of sodium sulfinates was explored under the standard reaction conditions (Scheme 3). Sodium benzenesulfinates possessing an electron-donating group could smoothly generate target products in excellent yield (3ab and 3ac). This Cu/Ag catalyzed sulfonylation of sodium sulfinates with an acetylamino group afforded the product in a lower yield of 41% (3ad). Sodium benzenesulfinates bearing halogen atoms such as fluorine and chlorine could also be performed in this reaction, resulting in desired products in high yields (3ae and 3af). A strong electron-withdrawing group such as NO2 could also be applied to this sulfonylation, although it led to a decrease in isolated yields (3ag and 3ah). Moreover, sodium 2-naphthylsulfinate also proceeded smoothly to generate the product in a moderate yield of 50% (3ai). Note that the substrate scope can be extended to the aliphatic sodium sulfinate, generating target product in an up to 95% yield (3aj). Additionally, a heterocyclic sulfinate, sodium thiophene-2-sulfinate, has been employed in this reaction and was converted into the corresponding product 3ka in a low yield of 32%. A gram-sale reaction of N-(naphthalen-1-yl)picolinamide (1a) was carried out to demonstrate the synthetic applications of this protocol, and the C4−H sulfonylation product was obtained in 91% yield under the standard conditions (Scheme 4a). 12121

DOI: 10.1021/acs.joc.7b01917 J. Org. Chem. 2017, 82, 12119−12127

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The Journal of Organic Chemistry Scheme 3. Substrate Scope of Sodium Sulfinatesa,b

a

Reaction condition A: 1 (0.1 mmol), 2a (0.2 mmol), and Ru(bpy)3(PF6)2 (3 mol %) under 26 W household light. Condition B: 1 (0.1 mmol), 2a (0.2 mmol), Ag2CO3 (20 mol %). bIsolated yield. cAt 60 °C.

Ag(II) cycle in the presence of K2S2O8 (path b); (iii) the direct oxidation of sodium benzenesulfinate 2a by K2S2O8 (path c). Then, the intermediate D is generated by a radical combination between intermediate C and the benzenesulfonyl radical F. Finally, the proton transfer process of the intermediate D takes place to give intermediate E, dissociation of which leads to the desired product 3aa, along with the regeneration of copper acetate to fulfill the catalytic cycle.

Scheme 4. Synthetic Applications

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CONCLUSIONS In summary, we have developed two types of catalysis (Cu/Ru photoredox catalysis or Cu/Ag cocatalysis) for the remote C−H sulfonylation of 1-naphthylamides at room temperature, mostly affording the desired products in excellent yields. The superiorities of these protocols are simple, mild, environmentally friendly reaction conditions, lower energy consumption, and good functional group tolerance.

Scheme 5. Unreactive Substrates for Mechanistic Study

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EXPERIMENTAL SECTION

General Information. 1H, 13C, and 19F NMR spectra were recorded on a Bruker DPX-400 spectrometer using CDCl3 or DMSO as the solvent and TMS as an internal standard. Melting points were measured using a WC-1 microscopic apparatus and are uncorrected. Mass spectra were measured on an LC-MSD-Trap-XCT instrument. IR spectra were recorded on a PerkinElmer FT/IR spectrometer. High resolution mass spectra were ensured on a MALDI-FTMS. All solvents were used directly without further purification. Petroleum ether, ethyl acetate, and hexane were used for column chromatography. Chemical shift multiplicities are represented as follows: s = singlet, d = doublet, t = triplet, m = multiplet, dd = double doublet, td = three doublets. Unless otherwise mentioned, all materials were commercially obtained and used without further purification. Preparation of Naphthalene and Quinoline Substrates. (a) All of the naphthalene substrates were prepared from the corresponding pyridine carboxylic acids and naphthylamine according to the reported procedure.9 (b) Quinoline substrates were prepared from the corresponding acids and 8-aminoquinoline according to the reported procedure.10 Preparation of Sodium Sulfinates. Sodium sulfite (2.50 g, 20 mmol), sodium hydrogen carbonate (1.68 g, 20 mmol), and sulfonyl chlorides (10 mmol) were added to water (10 mL). After stirring at

by HR-MS, which indicates that the reaction might proceed via a radical process (Scheme 6c). On the basis of these experimental results and previous reports,5a,b,8 a plausible mechanism is illustrated in Scheme 7. First, the coordination of 1a with copper acetate affords a chelated intermediate A. An oxidative process of the intermediate A in the presence of K2S2O8 occurs to give a putative Cu(III) species B followed by intramolecular electron oxidation transfer to generate complex C. Meanwhile, the benzenesulfonyl radical F can be generated via the following three pathways: (i) the oxidation of sodium benzenesulfinate 2a via the photoredox catalytic cycle in the presence of Ru(bpy)3(I) and K2S2O8 (path a); (ii) the oxidation of sodium benzenesulfinate 2a via a Ag(I)/ 12122

DOI: 10.1021/acs.joc.7b01917 J. Org. Chem. 2017, 82, 12119−12127

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The Journal of Organic Chemistry Scheme 6. Control Experiment

Scheme 7. Proposed Mechanism

80 °C for 4 h, water was removed by rotary evaporator. Then, the remaining solid was extracted and recrystallized by ethanol to obtain a white solid as the desired product. Other sodium sulfinates were prepared through a similar route from their corresponding sulfonyl chlorides. General Experimental Procedure for C−H Sulfonylation of Naphthylamine Derivatives. A 25 mL Schlenk tube was equipped with a magnetic stir bar and charged with N-(naphthalen-1-yl) picolinamide derivative 1 (0.1 mmol), sodium sulfinate 2 (0.2 mmol), Cu(OAc)2·H2O (4.0 mg, 0.02 mmol)/Ru(bpy)3(PF6)2 (5.2 mg, 0.003 mmol) or Cu(OAc)2·H2O (4.0 mg, 0.02 mmol)Ag2CO3 (5.6 mg, 20 mol %), and K2S2O8 (54.1 mg, 0.2 mmol) in acetone/H2O(1:1) (1.0 mL). The resulting mixture was stirred at room temperature under air for 3 h. Upon completion, the mixture was added into H2O (20 mL) and extracted with ethyl acetate (10 mL) three times. The combined organic layer was dried over anhydrous Na2SO4 and filtered. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100−200 mesh) using petroleum ether/ethyl acetate as an eluent (2:1, V/V) to afford the pure product 3.

N-(4-(Phenylsulfonyl)naphthalen-1-yl)picolinamide (3aa). The resultant residue was purified by flash silica gel column chromatography to afford 3aa as a white solid (A, 38.1 mg; 98%; B, 38.4 mg, 99%); eluent, petroleum ether/ethyl acetate (2:1); mp 193−195 °C; 1 H NMR (400 MHz, CDCl3) δ 11.14 (s, 1H), 8.76−8.70 (m, 3H), 8.61 (d, J = 8.3 Hz, 1H), 8.36 (d, J = 7.8 Hz, 1H), 8.17−8.15 (m, 1H), 8.0−7.96 (m, 3H), 7.68−7.61 (m, 2H), 7.59−7.45 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.4, 148.3, 142.1, 138.5, 138.0, 133.0, 131.3, 131.0, 129.5, 129.1, 128.3, 127.3, 127.1, 126.0, 125.4, 122.8, 120.9, 115.3; IR 3335 (w), 1700 (s), 1571 (m), 1529 (s), 1500 (s), 1447 (m), 1438 (m), 1362 (m), 1330 (m), 1315 (m), 1289 (m), 1199 (m), 1153 (s), 1137 (m), 1084 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H17N2O3S 389.0954, found 389.0955. 3-Methyl-N-(4-(phenylsulfonyl)naphthalen-1-yl)picolinamide (3ba). The resultant residue was purified by flash silica gel column chromatography to afford 3ba as a white solid (A, 32.6 mg, 81%; B, 31.4 mg, 78%); eluent, petroleum ether/ethyl acetate (2:1); mp 199−203 °C; 1 H NMR (400 MHz, CDCl3) δ 11.43 (s, 1H), 8.71−8.68 (m, 2H), 8.59 (d, J = 8.4 Hz, 1H), 8.54 (d, J = 3.8 Hz, 1H), 8.14−8.11 (m, 1H), 7.97−7.95 (m, 2H), 7.69 (d, J = 7.5 Hz, 1H), 7.64−7.58 (m, 2H), 7.52−7.42 (m, 4H), 2.8 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 12123

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The Journal of Organic Chemistry

δ 162.5, 155.0, 149.3, 148.3, 142.0, 138.0, 137.0, 133.0, 131.3, 129.1, 128.4, 128.2, 127.2, 127.2, 127.0, 124.3, 122.7, 120.1, 116.3, 104.0; IR 3345 (w), 1691 (s), 1626 (m), 1588 (m), 1538 (m), 1506 (s), 1432 (m), 1305 (m), 1281 (m), 1224 (m), 1150 (m), 1131 (s), 1080 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H17N2O4S 405.0904, found 405.0914. N-(8-Morpholino-4-(phenylsulfonyl)naphthalen-1-yl)picolinamide (3ha). The resultant residue was purified by flash silica gel column chromatography to afford 3ha as a light yellow solid (A, 42.6 mg, 90%; B, 44.5 mg, 94%); eluent, petroleum ether/ethyl acetate (1:1); mp 220−225 °C; 1H NMR (400 MHz, CDCl3) δ 14.25 (s, 1H), 9.28 (d, J = 8.6 Hz, 1H), 8.73 (d, J = 4.2 Hz, 1H), 8.58 (d, J = 8.6 Hz, 1H), 8.48−8.45 (m, 1H), 8.39 (d, J = 7.8 Hz, 1H), 7.99−7.95 (m, 3H), 7.58−7.41 (m, 6H), 4.26−4.20 (m, 2H), 3.85 (d, J = 10.6 Hz, 2H), 3.16 (d, J = 12.0 Hz, 2H), 3.02−2.96 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 164.0, 150.4, 149.9, 148.1, 142.1, 141.6, 137.8, 132.9, 131.7, 131.5, 130.1, 129.1, 127.9, 127.3, 127.0, 123.8, 121.8, 119.9, 117.8, 114.5, 65.5, 54.4; IR 1672 (m), 1576 (m), 1516 (s), 1490 (s), 1445 (m), 1338 (m), 1302 (s), 1266 (m), 1147 (s), 1111 (s), 1084 (s); HRMS (ESI-TOF) m/z [M + H]+ calcd for C26H24N3O4S 474.1482, found 474.1484. N-(8-(Phenylsulfonyl)quinolin-5-yl)picolinamide (3ia). The resultant residue was purified by flash silica gel column chromatography to afford 3ia as a light yellow solid (A, 25.3 mg, 65%; B, 28.8 mg, 74%); eluent, petroleum ether/ethyl acetate (2:1); mp 232−236 °C; 1H NMR (400 MHz, CDCl3) δ 11.04 (s, 1H), 8.97 (dd, J = 4.2, 1.5 Hz, 1H), 8.77−8.68 (m, 3H), 8.40 (dd, J = 8.7, 1.5 Hz, 1H), 8.31 (d, J = 7.4 Hz, 1H), 8.22−8.20 (m, 2H), 7.96 (td, J = 8.6, 1.6 Hz, 1H), 7.58− 7.55 (m, 1H), 7.52−7.43 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 162.3, 150.9, 148.9, 148.3, 144.3, 142.1, 138.5, 138.1, 133.0, 133.0, 132.8, 129.2, 129.0, 128.3, 127.4, 122.8, 121.7, 121.0, 115.8; IR 3331 (w), 1694 (s), 1591 (m), 1566 (m), 1525 (s), 1489 (s), 1438 (m), 1356 (m), 1305 (s), 1286 (m), 1206 (m), 1159 (s), 1150 (s), 1141 (s), 1089 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C21H16N3O3S 390.0907, found 390.0911. N-(5-Bromo-4-(phenylsulfonyl)quinolin-5-yl)picolinamide (3ja). The resultant residue was purified by flash silica gel column chromatography to afford 3ja as a white solid (A, 25.7 mg, 55%; B, 23.8 mg, 51%); eluent, petroleum ether/ethyl acetate (3:1); mp 215−218 °C; 1H NMR (400 MHz, CDCl3) δ 10.86 (s, 1H), 8.94 (d, J = 1.68 Hz, 1H), 8.84 (s, 1H), 8.71−8.69 (m, 1H), 8.34 (d, J = 7.8 Hz, 1H), 8.12−8.06 (m, 3H), 7.99−7.94 (m, 2H), 7.58−7.52 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 162.3, 149.2, 148.3, 141.2, 140.3, 138.0, 134.6, 133.4, 132.0, 131.9, 129.4, 129.4, 129.1, 128.1, 127.1, 125.5, 124.4, 122.7, 120.6, 115.7; IR 3318 (w), 1690 (s), 1616 (m), 1539 (s), 1489 (m), 1442 (m), 1393 (m), 1315 (s), 1146 (s), 1098 (m), 1081 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H16BrN2O3S 467.0060, found 467.0061. N-(5-(Phenylsulfonyl)quinolin-8-yl)benzamide (3ka). The resultant residue was purified by flash silica gel column chromatography to afford 3ka as a light yellow solid (A, 34.5 mg, 89%; B, 36.9 mg, 95%); eluent, petroleum ether/ethyl acetate (2:1); mp 175−180 °C; 1 H NMR (400 MHz, CDCl3) δ 10.91 (s, 1H), 9.01−8.97 (m, 2H), 8.81 (dd, J = 4.2, 1.6 Hz, 1H), 8.51 (d, J = 8.4 Hz, 1H), 8.00−7.98 (m, 2H), 7.90−7.87 (m, 2H), 7.57−7.39 (m, 7H); 13C NMR (100 MHz, CDCl3) δ 165.8, 148.8, 141.9, 140.1, 138.5, 134.3, 133.5, 133.2, 132.5, 132.4, 129.3, 129.1, 128.9, 127.4, 127.2, 124.3, 123.5, 114.3; IR 3315 (w), 1685 (s), 1570 (m), 1525 (s), 1496 (m), 1485 (m), 1446 (m), 1388 (m), 1330 (m), 1301 (s), 1267 (m), 1196 (m), 1145 (s), 1132 (s), 1082 (m), 1070 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H17N2O3S 389.0954, found 389.0955. N-(1-(Phenylsulfonyl)naphthalen-2-yl)picolinamide (3la). The resultant residue was purified by flash silica gel column chromatography to afford 3la as a light yellow solid (A, 18.3 mg, 47%; B, 18.6 mg, 48%); eluent, petroleum ether/ethyl acetate (2:1); mp 155−158 °C; 1 H NMR (400 MHz, CDCl3) δ 12.99 (s, 1H), 8.95 (d, J = 8.9 Hz, 1H), 8.91 (d, J = 9.2, Hz, 1H), 8.80 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 7.8 Hz, 1H), 8.09 (d, J = 9.2 Hz, 1H), 7.96−7.91 (m, 3H), 7.82 (d, J = 7.6 Hz, 1H), 7.58−7.52 (m, 2H), 7.48−7.44 (m, 2H), 7.38−7.34 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 163.5, 149.8, 148.7, 142.5,

163.7, 146.1, 145.6, 142.1, 141.7, 139.0, 136.8, 133.0, 131.3, 130.5, 129.5, 129.1, 128.3, 127.3, 127.0, 126.7, 126.1, 125.2, 121.1, 114.8, 20.9; IR 3350 (w), 1698 (s), 1567 (m), 1525 (s), 1496 (s), 1441 (m), 1355 (m), 1305 (s), 1194 (m), 1150 (s), 1083 (s), 1024 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C23H19N2O3S 403.1111, found 403.1102. N-(4-(Phenylsulfonyl)naphthalen-1-yl)quinoline-2-carboxamide (3ca). The resultant residue was purified by flash silica gel column chromatography to afford 3ca as a white solid (A, 39.4 mg, 90%; B, 41.6 mg, 95%); eluent, petroleum ether/ethyl acetate (2:1); mp 225−230 °C; 1H NMR (400 MHz, CDCl3) δ 11.33 (s, 1H), 8.77−8.73 (m, 2H), 8.62 (d, J = 8.3 Hz, 1H), 8.44−8.40 (m, 2H), 8.25 (t, J = 8.9 Hz, 2H), 8.00−7.97 (m, 2H), 7.95−7.93 (m, 1H), 7.87−7.83 (m, 1H), 7.71−7.62 (m, 3H), 7.54−7.45 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 162.5, 149.1, 146.2, 142.0, 138.5, 138.4, 133.0, 131.3, 131.0, 130.7, 129.9, 129.7, 129.5, 129.1, 128.7, 128.4, 128.0, 127.3, 127.2, 126.1, 125.4, 120.9, 118.8, 115.3; IR 3338 (w), 1706 (s), 1592 (m), 1538 (s), 1526 (s), 1496 (s), 1448 (m), 1428 (m), 1365 (m), 1330 (m), 1299 (m), 1289 (m), 1199 (m), 1150 (s), 1137 (m), 1085 (s), 1047 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C26H19N2O3S 439.1111, found 439.1112. N-(4-(Phenylsulfonyl)naphthalen-1-yl)isoquinoline-1-carboxamide (3da). The resultant residue was purified by flash silica gel column chromatography to afford 3da as a white solid (A, 27.2 mg, 62%; B, 29.8 mg, 68%); eluent, petroleum ether/ethyl acetate (2:1); mp 230−235 °C; 1H NMR (400 MHz, CDCl3) δ 11.56 (s, 1H), 9.78−9.75 (m, 1H), 8.75 (d, J = 8.4 Hz, 1H), 8.72−8.70 (m, 1H), 8.64−8.60 (m, 2H), 8.18 (d, J = 7.8 Hz, 1H), 7.99−7.97 (m, 2H), 7.92−7.90 (m, 2H), 7. 79−7.73 (m, 2H), 7.66−7.59 (m, 2H), 7.53−7.44 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 163.8, 146.6, 142.1, 140.1, 138.8, 137.8, 133,0, 131.3, 131.0, 130.8, 129.5, 129.4, 129.1, 128.3, 127.6, 127.5, 127.3, 127.2, 127.1, 126.3, 125.7, 125.3, 121.2, 115.2; IR 3333 (w), 1688 (s), 1581 (m), 1527 (s), 1504 (s), 1448 (m), 1330 (m), 1304 (m), 1151 (s), 1136 (m), 1034 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C26H19N2O3S 439.1111, found 439.1113. N-(2-Methyl-4-(phenylsulfonyl)naphthalen-1-yl)picolinamide (3ea). The resultant residue was purified by flash silica gel column chromatography to afford 3ea as a white solid (A, 37.0 mg, 92%; B, 39.4 mg, 98%); eluent, petroleum ether/ethyl acetate (2:1); mp 240−245 °C; 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 8.70 (d, J = 4.4 Hz, 1H), 8.62−8.59 (m, 1H), 8.51 (s, 1H), 8.30 (d, J = 9.8 Hz, 1H), 8.03−7.93 (m, 4H), 7.58−7.46 (m, 6H), 2.58 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ162.8, 149.1, 148.4, 141.7, 137.9, 136.3, 134.4, 133.2, 133.1, 132.1, 131.3, 129.2, 127.9, 127.6, 127.4, 127.0, 124.6, 123.6, 122.8, 19.2; IR 3294 (w), 1682 (s), 1590 (m), 1567 (m), 1486 (s), 1447 (m), 1429 (m), 1305 (s), 1293 (m), 1184 (m), 1144 (s), 1126 (m), 1083 (s); HRMS (ESI-TOF) m/z [M + H]+ calcd for C23H19N2O3S 403.1111, found 403.1117. N-(8-Methyl-4-(phenylsulfonyl)naphthalen-1-yl)picolinamide (3fa). The resultant residue was purified by flash silica gel column chromatography to afford 3fa as a yellow solid (A, 37.4 mg, 93%; B, 38.2 mg, 95%); eluent, petroleum ether/ethyl acetate (2:1); mp 172−175 °C; 1H NMR (400 MHz, CDCl3) δ 10.99 (s, 1H), 8.67−8.65 (m, 1H), 8.61−8.55 (m, 3H), 8.38−8.36 (m, 1H), 7.99−7.93 (m, 3H), 7.56−7.40 (m, 5H), 7.34 (d, J = 7.0 Hz, 1H), 3.06 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 162.1, 149.5, 148.2, 142.0, 139.9, 138.0, 133.4, 132.9, 132.4, 131.2, 130.5, 129.1, 127.6, 127.3, 126.9, 123.5, 122.9, 118.9, 25.7; IR 3354 (w), 1693 (s), 1578 (m), 1525 (s), 1506 (m), 1448 (m), 1338 (m), 1298 (s), 1282 (m), 1141 (s), 1086 (m); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H18N2NaO3S 425.0930, found 425.0927. N-(7-Hydroxyl-4-(phenylsulfonyl)naphthalen-1-yl)picolinamide (3ga). The resultant residue was purified by flash silica gel column chromatography to afford 3ga as a light yellow solid (A, 32.3 mg, 80%; B, 34.3 mg, 85%); eluent, petroleum ether/ethyl acetate (2:1); mp 220−225 °C; 1H NMR (400 MHz, CDCl3) δ 10.80 (s, 1H), 8.65 (d, J = 4.3 Hz, 1H), 8.57−8.54 (m, 2H), 8.37 (d, J = 8.3 Hz, 1H), 8.33 (d, J = 7.8 Hz, 1H), 7.96−7.93 (m, 3H), 7.54−7.40 (m, 5H), 7.17 (dd, J = 9.3, 2.1 Hz, 1H), 6.89 (s, 1H); 13C NMR (100 MHz, CDCl3) 12124

DOI: 10.1021/acs.joc.7b01917 J. Org. Chem. 2017, 82, 12119−12127

Article

The Journal of Organic Chemistry

(m, 1H), 7.17−7.11 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 165.2 (d, JC−F = 254.0 Hz), 162.4, 149.2, 148.3, 138.6, 138.1, 138.1, 131.3, 130.8, 130.1 (d, JC−F = 9.3 Hz), 129.3, 128.5, 127.2, 127.2, 126.0, 125.1, 122.8, 121.0, 116.4 (d, JC−F = 22.6 Hz), 115.2; 19F NMR (376 MHz, CDCl3) δ −104.5; IR 3343 (w), 1702 (m), 1588 (m), 1569 (m), 1527 (s), 1494 (s), 1364 (m), 1331 (m), 1312 (s), 1291 (m), 1229 (m), 1148 (m), 1135 (s), 1083 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H16FN2O3S 407.0860, found 407.0869. N-(4-((4-Chlorophenyl)sulfonyl)naphthalen-1-yl)picolinamide (3af). The resultant residue was purified by flash silica gel column chromatography to afford 3af as a white solid (A, 39.3 mg, 93%; B, 38.4 mg, 91%); eluent, petroleum ether/ethyl acetate (2:1); mp 210− 213 °C; 1H NMR (400 MHz, CDCl3) δ 11.14 (s, 1H), 8.75−8.70 (m, 2H), 8.67−8.64 (m, 1H), 8.59−8.57 (m, 1H), 8.35−8.33 (m, 1H), 8.17−8.14 (m, 1H), 7.98−7.94 (m, 1H), 7.89 (d, J = 8.6 Hz, 2H), 7.68−7.54 (m, 3H), 7.43−7.41 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.2, 148.3, 140.6, 139.6, 138.7, 138.1, 131.5, 130.4, 129.5, 129.3, 128.8, 128.5, 127.2, 127.2, 126.0, 125.1, 122.7, 121.0, 115.1; IR 3361 (w), 1695 (m), 1569 (m), 1526 (s), 1500 (s), 1479 (m), 1357 (w), 1318 (s), 1289 (m), 1154 (s), 1140 (m), 1083 (s); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H16ClN2O3S 423.0565, found 423.0567. N-(4-((4-Nitrophenyl)sulfonyl)naphthalen-1-yl)picolinamide (3ag). The resultant residue was purified by flash silica gel column chromatography to afford 3ag as a yellow solid (B, 17.4 mg, 40%); eluent, petroleum ether/ethyl acetate (2:1); mp 225−227 °C; 1H NMR (400 MHz, CDCl3) δ 11.22 (s, 1H), 8.82 (d, J = 8.4 Hz, 1H), 8.74 (d, J = 4.4 Hz, 1H), 8.67−8.63 (m, 2H), 8.38 (d, J = 7.8 Hz, 1H), 8.30 (d, J = 8.8 Hz, 2H), 8.20 (d, J = 7.8 Hz, 1H), 8.14 (d, J = 8.9 Hz, 2H), 8.00 (td, J = 7.7, 1.5 Hz, 1H), 7.72−7.65 (m, 2H), 7.61−7,58 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 162.4, 150.2, 149.2, 148.3, 147.9, 139.4, 138.1, 132.3, 129.4, 129.1, 128.9, 128.5, 127.4, 127.3, 125.9, 124.8, 124.4, 122.8, 121.2, 115.1; IR 3307 (w), 1708 (m), 1571 (m), 1532 (s), 1506 (s), 1440 (m), 1360 (m), 1335 (m), 1305 (s), 1154 (s), 1137 (s), 1081 (s); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H16N3O5S 434.0805, found 434.0807. N-(4-((3-Nitrophenyl)sulfonyl)naphthalen-1-yl)picolinamide (3ah). The resultant residue was purified by flash silica gel column chromatography to afford 3ah as a yellow solid (B, 19.5 mg, 45%); eluent, petroleum ether/ethyl acetate (2:1); mp 205−207 °C; 1H NMR (400 MHz, CDCl3) δ 11.21 (s, 1H), 8.83−8.81 (m, 2H), 8.73 (d, J = 4.3 Hz, 1H), 8.70−8.66 (m, 2H), 8.37 (d, J = 8.0 Hz, 2H), 8.28−8.26 (m, 1H), 8.21−8.19 (m, 1H), 8.00 (td, J = 7.7, 1.6 Hz, 1H), 7.71−7.67 (m, 3H), 7.61−7.58 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.2, 148.3, 148.3, 144.4, 139.4, 138.1, 132.8, 132.3, 130.6, 129.4, 129.2, 128.9, 127.5, 127.4, 127.3, 126.0, 124.7, 122.8, 122.5, 121.2, 115.1; IR 3312 (w), 1702 (s), 1606 (m), 1541 (m), 1519 (s), 1463 (m), 1437 (m), 1351 (s), 1335 (m), 1317 (m), 1157 (s), 1142 (m), 1111 (m), 1065 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C22H16N3O5S 434.0805, found 434.0802. N-(4-(Naphthalen-2-ylsulfonyl)naphthalen-1-yl)picolinamide (3ai). The resultant residue was purified by flash silica gel column chromatography to afford 3ai as a white solid (B, 21.9 mg, 50%); eluent, petroleum ether/ethyl acetate (2:1); mp 218−220 °C; 1H NMR (400 MHz, CDCl3) δ 11.14 (s, 1H), 8.80−8.77 (m, 2H), 8.72−8.71 (m, 1H), 8.69 (d, J = 8.4 Hz, 1H), 8.65 (s, 1H), 8.36 (d, J = 7.8 Hz, 1H), 8.16−8.13 (m, 1H), 8.00−7.96 (m, 2H), 7.88−7.80 (m, 3H), 7.64−7.55 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.3, 148.3, 138.9, 138.5, 138.1, 134.9, 132.1, 131.4, 130.9, 129.5, 129.4, 129.0, 128.6, 128.4, 127.9, 127.6, 127.1, 126.0, 125.3, 122.8, 122.5, 120.9, 115.2; IR 3319 (w), 1701 (s), 1570 (m), 1530 (s), 1504 (m), 1463 (m), 1435 (m), 1305 (s), 1286 (m), 1260 (m), 1151 (m), 1125 (s), 1068 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C26H19N2O3S [M + H]+: 439.1111, found 439.1110. N-(4-((4-Cyclopropyl)sulfonyl)naphthalen-1-yl)picolinamide (3aj). The resultant residue was purified by flash silica gel column chromatography to afford 3aj as a white solid (A, 33.5 mg, 95%; B, 33.5 mg, 95%); eluent, petroleum ether/ethyl acetate (2:1); mp 195− 200 °C; 1H NMR (400 MHz, CDCl3) δ 11.12 (s, 1H), 8.96−8.92 (m, 1H), 8.72 (d, J = 4.6 Hz, 1H), 8.65 (d, J = 8.3 Hz, 1H), 8.34

139.7, 137.6, 135.9, 133.3, 130.9, 130.1, 129.1, 129.0, 128.7, 126.9, 126.4, 125.6, 124.6, 122.9, 121.3, 120.0; IR 3227 (w), 1687 (s), 1620 (m), 1558 (m), 1496 (s), 1423 (m), 1320 (s), 1305 (m), 1288 (m), 1152 (m), 1142 (s), 1082 (m); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C22H16N2NaO3S 411.0774, found 411.0773. N-(1-Tosylnaphthalen-2-yl)picolinamide (3ma). The resultant residue was purified by flash silica gel column chromatography to afford 3ma as a light yellow solid (A, 26.2 mg, 65%; B, 26.2 mg, 65%); eluent, petroleum ether/ethyl acetate (2:1); mp 142−145 °C; 1 H NMR (400 MHz, CDCl3) δ 13.01 (s, 1H), 8.97 (d, J = 8.5 Hz, 1H), 8.90 (d, J = 9.2 Hz, 1H), 8.80 (d, J = 4.4 Hz, 1H), 8.30 (d, J = 7.8 Hz, 1H), 8.07 (d, J = 9.2 Hz, 1H), 8.93 (td, J = 7.7, 1.6 Hz, 1H), 7.86−7.80 (m, 3H), 7.57−7.51 (m, 2H), 7.47−7.43 (m, 1H), 7.14 (d, J = 8.2 Hz, 2H), 2.29 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.5, 149.9, 148.7, 144.2, 139.6, 139.5, 137.5, 135.7, 130.9, 130.0, 129.7, 129.0, 128.6, 126.8, 126.4, 125.5, 124.6, 122.9, 121.2, 120.5, 21.5; IR 3242 (w), 1698 (s), 1622 (m), 1603 (m), 1561 (m), 1499 (s), 1428 (s), 1324 (s), 1303 (m), 1284 (m), 1218 (m), 1137 (s), 1084 (m); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C23H18N2NaO3S 425.0930, found 425.0929. N-(4-Tosylnaphthalen-1-yl)picolinamide (3ab). The resultant residue was purified by flash silica gel column chromatography to afford 3ab as a white solid (A, 37.4 mg, 93%; B, 37.1 mg, 92%); eluent, petroleum ether/ethyl acetate (2:1); mp 230−233 °C; 1H NMR (400 MHz, CDCl3) δ 11.12 (s, 1H), 8.73−8.71 (m, 3H), 8.59 (d, J = 8.4 Hz, 1H), 8.36 (d, J = 7.8 Hz, 1H), 8.17−8.14 (m, 1H), 8.98 (td, J = 7.7, 1.6 Hz, 1H), 7.86 (d, J = 8.3 Hz, 2H), 7.67−7.60 (m, 2H), 7.59−7.56 (m, 1H), 7.26 (d, J = 8.0 Hz, 2H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.3, 148.3, 143.9, 139.1, 138.3, 138.0, 131.4, 131.0, 129.8, 129.4, 128.3, 127.4, 127.1, 127.1, 126.0, 125.4, 122.7, 120.9, 115.2, 21.6; IR 3329 (w), 1693 (m), 1568 (m), 1528 (m), 1481 (m), 1465 (m), 1329 (m), 1302 (m), 1289 (s), 1137 (s), 1082 (s); HRMS (ESI-TOF) m/z [M + H]+ calcd for C23H19N2O3S 403.1111, found 403.1119. N-(4-((4-(tert-Butyl)phenyl)sulfonyl)naphthalen-1-yl)picolinamide (3ac). The resultant residue was purified by flash silica gel column chromatography to afford 3ac as a white solid (A, 40.9 mg, 92%; B, 40.4 mg, 91%); eluent, petroleum ether/ethyl acetate (2:1); mp 230−235 °C; 1H NMR (400 MHz, CDCl3) δ 11.12 (s, 1H), 8.80−8.77 (m, 1H), 8.73−8.71 (m, 2H), 8.59 (d, J = 8.3 Hz, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.17−8.14 (m, 1H), 7.99−7.95 (m, 1H), 7.90 (d, J = 8.6 Hz, 2H), 7.66−7.64 (m, 2H), 7.56 (dd, J = 7.5, 4.7 Hz, 1H), 7.47 (d, J = 8.6 Hz, 2H), 1.27 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 162.3, 156.8, 149.3, 148.3, 139.0, 138.3, 138.0, 131.5, 131.1, 129.5, 128.3, 127.2, 127.1, 127.1, 126.2, 126.0, 125.5, 122.7, 120.9, 115.3, 35.2, 31.0; IR 3349 (w), 1703 (s), 1570 (m), 1527 (s), 1502 (s), 1468 (m), 1435 (m), 1400 (m), 1363 (m), 1329 (m), 1311 (s), 1153 (s), 1140 (m), 1106 (m), 1081 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C26H25N2O3S 445.1580, found 445.1588. N-(4-((4-(Acetamino)phenyl)sulfonyl)naphthalen-1-yl)picolinamide (3ad). The resultant residue was purified by flash silica gel column chromatography to afford 3ad as a white solid (B, 20.5 mg, 46%); eluent, petroleum ether/ethyl acetate (2:1); mp 249−250 °C; 1 H NMR (400 MHz, DMSO) δ 11.25 (s, 1H), 10.37 (s, 1H), 8.84−8.83 (m, 1H), 8.62−8.59 (m, 1H), 8.52 (d, J = 8.2 Hz, 1H), 8.31 (d, J = 8.2 Hz, 1H), 8.25−8.22 (m, 1H), 8.18−8.11 (m, 2H), 7.95 (d, J = 8.9 Hz, 2H), 7.79−7.70 (m, 5H), 2.05 (s, 3H), 13C NMR (100 MHz, DMSO) δ 169.6, 163.4, 149.6, 149.2, 144.2, 139.6, 138.9, 135.0, 132.6, 130.5, 129.1, 128.8, 128.0, 127.9, 127.6, 124.7, 123.5, 123.1, 119.3, 118.9, 24.6; IR 3343 (w), 3304 (w), 1713 (m), 1682 (m), 1623 (m), 1586 (m), 1526 (s), 1505 (m), 1319 (m), 1310 (m), 1148 (m), 1135 (s); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C24H19N3NaO4S 468.0988, found 468.0990. N-(4-((4-Fluorophenyl)sulfonyl)naphthalen-1-yl)picolinamide (3ae). The resultant residue was purified by flash silica gel column chromatography to afford 3ae as a white solid (A, 37.4 mg, 92%; B, 38.2 mg, 94%); eluent, petroleum ether/ethyl acetate (2:1); mp 213-215 °C; 1H NMR (400 MHz, CDCl3) δ 11.14 (s, 1H), 8.75−8.68 (m, 3H), 8.58 (d, J = 7.9 Hz, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.18−8.15 (m, 1H), 8.00−7.95 (m, 3H), 7.69−7.61 (m, 2H), 7.58−7.55 12125

DOI: 10.1021/acs.joc.7b01917 J. Org. Chem. 2017, 82, 12119−12127

Article

The Journal of Organic Chemistry *E-mail: [email protected]. *E-mail: [email protected].

(d, J = 7.7 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 8.23−8.21 (m, 1H), 7.97 (td, J = 7.7, 1.6 Hz, 1H), 7.77−7.70 (m, 2H), 7.58−7.55 (m, 1H), 2.78−2.72 (m, 1H), 1.41−1.36 (m, 2H), 1.03−0.97 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.3, 148.3, 138.1, 138.0, 131.3, 130.4, 129.9, 128.4, 127.2, 127.1, 126.2, 125.5, 122.7, 121.1, 115.4, 33.3, 6.3; IR 3335 (w), 1703 (s), 1622 (m), 1571 (m), 1532 (s), 1501 (s), 1463 (m), 1435 (m), 1363 (m), 1315 (m), 1292 (m), 1283 (s), 1191 (m), 1144 (s), 1115 (s), 1055 (m), 1033 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C19H17N2O3S 353.0954, found 353.0954. N-(4-(Thiophen-2-ylsulfonyl)naphthalen-1-yl)picolinamide (3ak). The resultant residue was purified by flash silica gel column chromatography to afford 3ak as a white solid (A, 12.2 mg, 31%; B, 12.6 mg, 32%); eluent, petroleum ether/ethyl acetate (3:1); mp 204−207 °C; 1H NMR (400 MHz, CDCl3) δ 11.15 (s, 1H), 8.95−8.93 (m, 1H), 8.73−8.71 (m, 2H), 8.57 (d, J = 8.4 Hz, 1H), 8.37 (d, J = 7.8 Hz, 1H), 8.20−8.18 (m, 1H), 7.98 (td, J = 7.7, 1.6 Hz, 1H), 7.76 (dd, J = 3.8, 1.3 Hz, 1H), 7.74−7.68 (m, 2H), 7.59−7.56 (m, 2H), 7.04 (dd, J = 4.9, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 162.4, 149.3, 148.3, 138.1, 138.0, 131.3, 130.4, 129.9, 128.4, 127.2, 127.1, 126.2, 125.5, 122.7, 121.1, 115.4, 33.3, 6.3; IR 3328 (w), 1697 (s), 1622 (m), 1570 (m), 1528 (m), 1502 (s), 1464 (m), 1401 (m), 1308 (m), 1231 (m), 1147 (m), 1132 (s), 1117 (m), 1089 (m); HRMS (ESI-TOF) m/z [M + Na]+ calcd for C20H14N2NaO3S2 417.0338, found 417.0339. General Procedures for the Deprotection of Directing Groups. To a solution of 3aa (77.6 mg, 0.2 mmol) in ethyl alcohol (3 mL) was added NaOH (48.0 mg, 1.2 mmol), and the resulting mixture was stirred at 90 °C for 8 h. The solvent was removed by vacuum, and then 3 mL of H2O was added to the residue. The mixture was extracted with ethyl acetate (3 × 5 mL). The combined organic layer was dried over anhydrous Na2SO4 and filtered. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100−200 mesh) using petroleum ether/ethyl acetate (3:1, V/V) as an eluent to afford the pure product 9a as a light yellow solid (90% yield); mp 168−172 °C; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.3 Hz, 1H), 8.32 (d, J = 8.2 Hz, 1H), 7.92−7.89 (m, 2H), 7.76 (d, J = 8.1 Hz, 1H), 7.52−7.38 (m, 5H), 6.73 (d, J = 8.2 Hz, 1H), 4.81 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 148.9, 142.9, 132.5, 132.5, 130.1, 129.0, 128.3, 126.9, 125.5, 124.9, 123.2, 122.7, 121.4, 106.7; IR 3454 (w), 3371 (w), 1632 (m), 1566 (m), 1516 (m), 1442 (m), 1367 (m), 1284 (m), 1152 (m), 1135 (s), 1082 (m); HRMS (ESI-TOF) m/z [M + H]+ calcd for C16H14NO2S 284.0740, found 284.0739. A Gram-Scale Synthesis. A oven-dried, 250 mL round-bottom flask was equipped with a magnetic stir bar and charged with N-(naphthalen-1-yl)picolinamide 1a (5 mmol, 1.24 g), sodium sulfinate 2 (10 mmol, 1.65 g), Cu(OAc)2·H2O (1 mmol, 0.2 g), Ag2CO3 (1 mmol, 0.276 g), and K2S2O8 (10 mmol, 2.7 g) in acetone/ H2O(1:1) (50 mL). The resulting mixture was stirred at room temperature under air for 3 h. Upon completion, the mixture was added into H2O (50 mL) and extracted with ethyl acetate (40 mL) five times. The combined organic layer was dried over anhydrous Na2SO4 and filtered. After evaporation of the solvent under vacuum, the residue was purified by column chromatography on silica gel (100−200 mesh) using petroleum ether/ethyl acetate as an eluent (2:1, V/V) to afford the desired light yellow product 3aa in 1.76 g, 91% yield.

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ORCID

Yusheng Wu: 0000-0001-7023-9541 Yangjie Wu: 0000-0002-0134-0870 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (No. 21102134, 21172200) for financial support.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01917. Experimental details, characterizations, and 1H, 13C, and 19 F NMR spectra of new compounds (PDF) X-ray data for 3aa (CIF)

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REFERENCES

(1) (a) Curti, C.; Laget, M.; Carle, A. O.; Gellis, A.; Vanelle, P. Eur. J. Med. Chem. 2007, 42, 880. (b) Feng, M. H.; Tang, B. Q.; Liang, S. H.; Jiang, X. F. Curr. Top. Med. Chem. 2016, 16, 1200. (c) Harrak, Y.; Casula, G.; Basset, J.; Rosell, G.; Plescia, S.; Raffa, D.; Cusimano, M. G.; Pouplana, R.; Pujol, M. D. J. Med. Chem. 2010, 53, 6560. (d) Griffin, R. J.; Henderson, A.; Curtin, N. J.; Echalier, A.; Endicott, J. A.; Hardcastle, I. R.; Newell, D. R.; Noble, M. E. M.; Wang, L. Z.; Golding, B. T. J. Am. Chem. Soc. 2006, 128, 6012. (2) (a) Ueda, M.; Uchiyama, K.; Kano, T. Synthesis 1984, 1984, 323. (b) Patai, S.; Rappoport, C. Z.; Stirling, J. M. The Chemistry of Sulfones and Sulfoxides; Wiley: New York, 1988. (c) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon Press: Oxford, 1993. (d) Rezaeifard, A.; Jafarpour, M.; Naeimi, A.; Haddad, R. Green Chem. 2012, 14, 3386. (e) Kirihara, M.; Itou, A.; Noguchi, T.; Yamamoto, J. Synlett 2010, 2010, 1557. (f) Amarnath Reddy, M.; Surendra Reddy, P.; Sreedhar, B. Adv. Synth. Catal. 2010, 352, 1861. (g) Liu, N. M.; Liang, S.; Manolikakes, G. Synthesis 2016, 48, 1939. (h) Shen, C.; Zhang, P. F.; Sun, Q.; Bai, S. Q.; Hor, T. S. A.; Liu, X. G. Chem. Soc. Rev. 2015, 44, 291. (i) Shaaban, S.; Liang, S.; Liu, N. W.; Manolikakes, G. Org. Biomol. Chem. 2017, 15, 1947. (3) For reviews on transition-metal-catalyzed C−H bond functionalization, see: (a) Bellina, F.; Rossi, R. Chem. Rev. 2010, 110, 1082. (b) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (c) Gao, K.; Yoshikai, N. Acc. Chem. Res. 2014, 47, 1208. (d) Yang, L.; Huang, H. M. Chem. Rev. 2015, 115, 3468. (e) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (f) Ackermann, L. Chem. Rev. 2011, 111, 1315. (g) Shen, C.; Zhang, P. F.; Sun, Q.; Bai, S. Q.; Hor, T. S. A.; Liu, X. G. Chem. Soc. Rev. 2015, 44, 291. (4) (a) Zhao, X. D.; Dimitrijević, E.; Dong, V. M. J. Am. Chem. Soc. 2009, 131, 3466. (b) Liu, J. D.; Yu, L.; Zhuang, S. B.; Gui, Q. W.; Chen, X.; Wang, W. D.; Tan, Z. Chem. Commun. 2015, 51, 6418. (c) Rao, W. H.; Shi, B. F. Org. Lett. 2015, 17, 2784. (d) Liang, S.; Liu, N. W.; Manolikakes, G. Adv. Synth. Catal. 2016, 358, 159. (e) Liang, H. W.; Jiang, K.; Ding, W.; Yuan, Y.; Shuai, L.; Chen, Y. C.; Wei, Y. Chem. Commun. 2015, 51, 16928. (f) Liang, S.; Manolikakes, G. Adv. Synth. Catal. 2016, 358, 2371. (g) Xia, C. C.; Wang, K.; Xu, J.; Wei, Z. J.; Shen, C.; Duan, G. Y.; Zhu, Q.; Zhang, P. F. RSC Adv. 2016, 6, 37173. (h) Qiao, H. J.; Sun, S. Y.; Yang, F.; Zhu, Y.; Zhu, W. G.; Dong, Y. S.; Wu, Y. S.; Kong, X. T.; Jiang, L.; Wu, Y. J. Org. Lett. 2015, 17, 6086. (5) (a) Liang, S.; Bolte, M.; Manolikakes, G. Chem. - Eur. J. 2017, 23, 96. (b) Li, J. M.; Wang, Y. H.; Yu, Y.; Wu, R. B.; Weng, J.; Lu, G. ACS Catal. 2017, 7, 2661. (c) Li, Z. X.; Sun, S. Y.; Qiao, H. J.; Yang, F.; Zhu, Y.; Kang, J. X.; Wu, Y. S.; Wu, Y. J. Org. Lett. 2016, 18, 4594. (d) Shang, R.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2015, 137, 7660. (e) Grigorjeva, L.; Daugulis, O. Angew. Chem., Int. Ed. 2014, 53, 10209. (f) Huang, L. H.; Sun, X. D.; Li, Q.; Qi, C. Z. J. Org. Chem. 2014, 79, 6720. (6) For selected reviews on visible-light-induced photocatalysis, see: (a) Skubi, K. L.; Blum, T. R.; Yoon, T. P. Chem. Rev. 2016, 116, 10035. (b) Tiwari, D. K.; Maurya, R. A.; Nanubolu, J. B. Chem. - Eur. J. 2016, 22, 526. (c) Xuan, J.; Zhang, Z. G.; Xiao, W. J. Angew. Chem., Int. Ed. 2015, 54, 15632. (d) Meyer, A. U.; Jäger, S.; Hari, D. P.; König, B. Adv. Synth. Catal. 2015, 357, 2050. (e) Hopkinson, M. N.; Sahoo, B.; Li, J.

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*E-mail: [email protected]. 12126

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The Journal of Organic Chemistry L.; Glorius, F. Chem. - Eur. J. 2014, 20, 3874. (f) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (7) Qiao, H. J.; Sun, S. Y.; Zhang, Y.; Zhu, H. M.; Yu, X. M.; Yang, F.; Wu, Y. S.; Li, Z. X.; Wu, Y. J. Org. Chem. Front. 2017, 4, 1981. (8) (a) Cui, L.; Chen, H.; Liu, C.; Li, C. Z. Org. Lett. 2016, 18, 2188. (b) Liu, C.; Wang, X. Q.; Li, Z. D.; Cui, L.; Li, C. Z. J. Am. Chem. Soc. 2015, 137, 9820. (c) Shi, G. F.; Shao, C. D.; Pan, S. L.; Yu, J. X.; Zhang, Y. H. Org. Lett. 2015, 17, 38. (d) Mao, X. R.; Ma, X.; Zhang, S. W.; Hu, H. W.; Zhu, C. J.; Cheng, Y. X. Eur. J. Org. Chem. 2013, 2013, 4245. (9) Shang, R.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2015, 137, 7660. (10) Truong, T.; Klimovica, K.; Daugulis, O. J. Am. Chem. Soc. 2013, 135, 9342.

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