HETEROCYCLES

Paper | Regular issue | Vol. 89, No. 6, 2014, pp. 1441-1453
Received, 1st April, 2014, Accepted, 22nd April, 2014, Published online, 25th April, 2014.
DOI: 10.3987/COM-14-12996

■ Nickel-Catalyzed Ligand-Free Systhesis of Benzoxazoles and Oxazolines via Isocyanide Insertion

Jin-Mei Wang, Xiao Jiang, Ting Tang, Yong-Ming Zhu,* and Jing-Kang Shen*

School of Pharmaceutical Science, Soochow University, #199, Renai Road, Suzhou City 215123, China

Abstract

A novel and efficient route to benzoxazoles and oxazolines involving a nickel-catalyzed three-component coupling reaction of iodobenzene, an amino alcohol and tert-butyl isocyanide has been developed. A wide array of products have been prepared in good to excellent yields in the absence of ligand.

INTRODUCTION
Benzoxazoles and oxazolines exist widely in natural products1 and some of them have been shown to exhibit excellent bioactivities.2 They are also a subunit of many compounds from different areas of chemistry, such as fluorescent probes,3 heat-resistant polymers4 and other functional synthetics. Consequently, some synthetic routes to benzoxazoles have been reported involving transition metal catalyzed direct arylation of oxazoles,5,6 cyclization of o-haloanilides,7 and C-H activation of anilides.8 Oxazolines are generally prepared from the corresponding carboxylic acids, carboxylic esters, nitriles, or aldehydes.9 Nevertheless, many of their synthesis methods require the high catalyst loading or additives such as ligands and CuI.10 Recently, an alternative approach employing CO as a one-carbon unit has been reported,11 however, toxicity and poor maneuverability of CO remains a major drawback. Thus, the development of new and improved methods for the efficient synthesis of this type of skeleton is highly desired.
Since the pioneering work of Passerini12 and Ugi,13 isocyanides are considered as isoelectronic14 with carbon monoxide, therefore, they can be used as an alternative to carbon monoxide in the construction of many molecules. Many seminal papers describing two-component reactions15 and multicomponent reactions (MCRs)16 have been reported. Recently, reactions involving isocyanide insertion to form C-N,17-19 C-O20 and C-C21 bonds have become increasingly important. Nevertheless, most of the reactions via isocyanide insertion are catalyzed by palladium species. For example, Lang’s group describes a convenient palladium-catalyzed cascade process to give benzoxazoles and benzothiazoles in one step.18 Also, Suckling et al. demonstrate a powerful one-pot palladium-catalyzed multicomponent process for the preparation of oxazolines and benzoxazoles.19 In a continuation of our interest in the synthesis of heterocyclic compounds utilizing isocyanides, we are trying to explore more efficient and novel catalyst systems. To our delight, nickel catalysts might be considered because they have many characteristics similar to palladium catalysts as a kind of inexpensive transition metal.
Based on these findings, we envisage that a nickel-catalyzed coupling reaction of aryl iodides, amino alcohols, and tert-butyl isocyanide would allow an efficient access to benzoxazoles and oxazolines (Scheme 1). To the best of our knowledge, this methodology has not yet been reported. Herein, we disclose a nickel-catalytic system to construct intermolecular C-N bonds to give benzoxazoles and oxazolines in excellent yields.

RESULTS AND DISCUSSION
We commenced our investigation by screening different combinations of ligands, bases, solvents, and catalysts; selected results are summarized in Table 1. In our initial attempt, the product 2-phenylbenzo[d]oxazole (3a) was formed in 54% yield with NiCl2 as catalyst in the presence of 1,1’-bis(diphenylphosphino)ferrocene (La) and Cs2CO3 in anhydrous toluene (entry 1). Then, several ligands and ligand-free conditions were tested in the reaction. 3a was obtained in 91% yield in the absence of ligand, indicating that a ligand was not essential to the reaction (entries 2-4). Different bases were also examined, and Cs2CO3 was found to be superior to the others (entries 5-7). Solvent screening revealed that toluene appeared to be the best solvent (entries 8-10). Other catalysts, such as Ni(OAc)2 or Ni(acac)2, proved to be less effective (entries 11 and 12). Furthermore, lowering the quantity of 2-aminophenol (2a) from 5 equiv. to 3 equiv. led to a diminished yield (entry 13). Thus, the best result for the reaction was obtained with NiCl2 (10 mol%) and 2-aminophenol (5 equiv.) in anhydrous toluene (3.0 ml) with Cs2CO3 (1.3 equiv.) as base at 135 °C for 40 h.

With the optimized conditions in hand, a diverse set of iodobenzenes 1 were utilized to test the scope of the reaction. The results are summarized in Table 2. 2a was efficiently reacted with different iodobenzenes bearing ortho, meta, and para substituents on the phenyl ring to afford the desired products 3a-3l in moderate to high yields (entries 1-12). In most cases, iodobenzenes bearing electron-withdrawing groups (entries 2-6) gave higher yields than those bearing electron-donating groups (entries 7-12). Furthermore, in accordance with steric hindrance effects, the yield for the reaction was lower when a methyl group was in the ortho position compared to the meta and para positions (entries 8-10). This reaction was not limited to an aryl moiety; the heterocycle-containing substrates such as 2-iodothiophene (1m) and 2-iodopyridine (1n) also underwent smooth reactions to afford the corresponding products 2-(thiophen-2-yl)benzo[d]oxazole (3m) and 2-(pyridin-2-yl)benzo[d]oxazole (3n) in good yields (entries 13 and 14).

Next, 2-aminoethanol derivatives 2b-2f were used as substrates to afford oxazolines (Table 3). As established in Table 3, oxazoline products were formed in moderate yields (entries 1-5). Compared to aryl substituted substrates, aliphatic ones led to the desired product in lower yields and generally required a longer reaction time.

A proposed reaction mechanism is outlined in Scheme 2. Oxidative addition of 1 leads to nickel complex A. Then it undergoes an insertion process with tert-butyl isocyanide B to afford C, followed by addition of 2 to give amidine intermediate D and regeneration of NiLn. Then, the intermediate D allows the formation of desired product 3 via cyclization.

In conclusion, we have developed an efficient coupling method for the synthesis of benzoxazoles and oxazolines from easily accessible substrates via tert-butyl isocyanide insertion. The process reported here was characterized by a ligand-free nickel catalyzed reaction demonstrating that nickel is also a highly efficient transition-metal catalyst for isocyanide insertion. This approach was tolerant of a wide range of substrates and applicable to library synthesis. Further studies on nickel-catalyzed reactions are currently underway in our laboratory.

EXPERIMENTAL
General
Reagents and chemicals were purchased from commercial suppliers and used without further purification. Flash chromatography (FC): silica gel (SiO2; 200-300 mesh) from Qingdao Ocean Chemicals, P. R. China. TLC: Silica-gel GF254 plates. Melting points were determined with a XT5 digital melting-point apparatus from Beijing Keyi Elec-opti Instrument Factory. 1H NMR and 13C NMR spectra were obtained from a solution in CDCl3 with TMS as internal standard using a 400/101 MHz (1H/13C) spectrometer, δ in parts per million (ppm), and J in hertz (Hz). IR measurements were recorded in KBr pellets, and wavenumbers are reported as cm-1. LRMS or HRMS were measured with an electrospray ionization (ESI) mass spectrometry.
General procedure for the synthesis of Benzoxazoles and Oxazolines (3):
Reactions were carried out under Ar. To an oven-dried, sealed tube (15 mL) containing 1 (0.5 mmol) in anhydrous toluene (3.0 mL), 2 (2.5 mmol), tert-butyl isocyanide (0.75 mmol, 85μL), NiCl2 (6.5 mg, 0.05 mmol), Cs2CO3 (212 mg, 1.3 mmol) were added, and the contents were stirred at 135 °C. After completion of the reaction, the mixture was filtered, and the residue was purified by column chromatography on silica gel using petroleum ether/EtOAc as eluent to afford pure target products 3.
2-Phenylbenzo[d]oxazole (3a):22 white solid (petroleum ether/EtOAc), mp 102-104 °C. 1H NMR (400 MHz, CDCl3): δ 8.26 (d, J = 3.6 Hz, 2H), 7.78 (d, J = 4.5 Hz, 1H), 7.57 (d, J = 5.2 Hz, 1H), 7.52 (s, 3H), 7.35 (d, J = 3.7 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 162.9, 150.7, 142.0, 131.4, 128.8, 127.5, 127.1, 125.0, 124.5, 119.9, 110.5. IR (KBr): 3060, 1617, 1552, 1455, 1447, 1242, 1197, 1053, 1022, 808, 745, 703, 687. LRMS (ESI): calcd. for C13H9NO [M+H]+ 196.1, found: 196.0.
2-(4-Chlorophenyl)benzo[d]oxazole (3b):23 white solid (petroleum ether/EtOAc), mp 147-149 °C. 1H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.1 Hz, 2H), 7.75 (s, 1H), 7.53 (s, 1H), 7.46 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 2.9 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 162.1, 150.8, 142.1, 137.8, 129.3, 128.9, 125.7, 125.4, 124.8, 120.2, 110.7. IR (KBr): 3060, 1618, 1578, 1484, 1453, 1405, 1092, 1056, 739. LRMS (ESI): calcd. for C13H8ClNO [M+H]+ 230.0, found: 230.0.
2-(4-Fluorophenyl)benzo[d]oxazole (3c):22 white solid (petroleum ether/EtOAc), mp 104-105 °C. 1H NMR (400 MHz, CDCl3): δ 8.32 – 8.17 (m, 2H), 7.75 (d, J = 4.6 Hz, 1H), 7.56 (d, J = 4.2 Hz, 1H), 7.42 – 7.29 (m, 2H), 7.19 (t, J = 8.1 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 165.0 (d, J = 252.6 Hz), 162.3, 150.9, 142.1, 130.0 (d, J = 9.0 Hz), 125.2, 124.8, 123.6, 120.1, 116.3 (d, J = 22.4 Hz), 110.7. IR (KBr): 3060, 1622, 1499, 1453, 1414, 1246, 1232, 1156, 1055, 835, 743, 628. LRMS (ESI): calcd. for C13H8FNO [M+H]+ 214.1, found: 214.0.
2-(3,5-Difluorophenyl)benzo[d]oxazole (3d):24 white solid (petroleum ether/EtOAc), mp149-151 °C. 1H NMR (400 MHz, CDCl3): δ 7.75 (dd, J = 10.9, 6.1 Hz, 3H), 7.60 – 7.50 (m, 1H), 7.42 – 7.29 (m, 2H), 6.94 (t, J = 8.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 163,3 (dd, J = 12.4, 250.0 Hz), 160.7 (t, J = 3.9 Hz), 150.8, 141.8, 130.1 (t, J = 10.5 Hz), 126.0, 125.1, 120.5, 110.9, 110.5 – 110.8 (m), 106.9 (t, J = 25.2 Hz). IR (KBr): 3074, 1632, 1601, 1558, 1471, 1441, 1350, 1244, 1130, 1074, 993, 948, 876, 864, 760, 740, 665. LRMS (ESI): calcd. for C13H7F2NO [M+H]+ 232.1, found: 232.1.
2-(4-(Trifluoromethyl)phenyl)benzo[d]oxazole (3e):6 white solid (petroleum ether/EtOAc), mp 141-143 °C. 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 8.2 Hz, 2H), 7.76 (dd, J = 14.1, 6.4 Hz, 3H), 7.60 – 7.53 (m, 1H), 7.41 – 7.32 (m, 2H). 13C NMR (101 MHz, CDCl3): δ 161.5, 150.9, 142.0, 133.0 (q, J = 33.5 Hz), 130.5, 127.9, 126.0 (d, J = 3.8 Hz), 125.9, 125.0, 123.9 (d, J = 274.0 Hz), 120.5, 110.9. IR (KBr): 3243, 1618, 1559, 1454, 1415, 1322, 1169, 1118, 1070, 1014, 847, 751, 744, 697. LRMS (ESI): calcd. for C14H8F3NO [M+H]+ 264.1, found: 264.0.
4-(Benzo[d]oxazol-2-yl)benzonitrile (3f):23 white solid (petroleum ether/EtOAc), mp 206-207 °C. 1H NMR (400 MHz, CDCl3): δ 8.30 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 7.1 Hz, 3H), 7.57 (d, J = 5.4 Hz, 1H), 7.38 (d, J = 3.2 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 160.9, 150.9, 141.9, 132.7, 131.1, 127.9, 126.2, 125.2, 120.6, 118.2, 114.7, 110.9. IR (KBr): 3097, 2229, 1615, 1548, 1494, 1452, 1411, 1242, 1056, 1013, 843, 762, 752, 548. LRMS (ESI): calcd. for C14H8N2O [M+H]+ 221.1, found: 221.0.
2-(4-Methoxyphenyl)benzo[d]oxazole (3g):22 white solid (petroleum ether/EtOAc), mp 97-98 °C. 1H NMR (400 MHz, CDCl3): δ 8.17 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 6.7 Hz, 1H), 7.52 (d, J = 6.9 Hz, 1H), 7.30 (d, J = 3.2 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 3.84 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 163.2, 162.4, 150.7, 142.3, 129.4, 124.6, 124.5, 119.7, 114.4, 110.4, 109.9, 55.5. IR (KBr): 3049, 2922, 1618, 1605, 1504, 1454, 1256, 1244, 1170, 1019, 832, 742, 730. LRMS (ESI): calcd. for C14H11NO2 [M+H]+ 226.1, found: 226.0.
2-p-Tolylbenzo[d]oxazole (3h):25 white solid (petroleum ether/EtOAc), mp 115-116 °C. 1H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 7.7 Hz, 2H), 7.81 – 7.72 (m, 1H), 7.59 – 7.52 (m, 1H), 7.33 (t, J = 6.6 Hz, 4H), 2.43 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 163.4, 150.8, 142.3, 142.2, 129.8, 127.7, 125.0, 124.6, 124.5, 119.9, 110.6, 21.8. IR (KBr): 3057, 2919, 2851, 1622, 1502, 1451, 1409, 1244, 1173, 1055, 821, 746, 727. LRMS (ESI): calcd. for C14H11NO [M+H]+ 210.1, found: 210.0.
2-m-Tolylbenzo[d]oxazole (3i):6 white solid (petroleum ether/EtOAc), mp 82-84 °C. 1H NMR (400 MHz, CDCl3): δ 8.09 (s, 1H), 8.05 (d, J = 7.5 Hz, 1H), 7.77 (d, J = 4.6 Hz, 1H), 7.57 (d, J = 4.9 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.34 (s, 3H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 163.3, 150.8, 142.2, 138.8, 132.4, 128.9, 128.3, 127.1, 125.1, 124.8, 124.6, 120.0, 110.6, 29.8. IR (KBr): 3070, 2921, 1637, 1552, 1454, 1246, 1058, 761, 745, 687. LRMS (ESI): calcd. for C14H11NO [M+H]+ 210.1, found: 210.0.
2-(o-Tolyl)benzo[d]oxazole (3j):25 white solid (petroleum ether/EtOAc), mp 62-64 °C. 1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 7.7 Hz, 1H), 7.86 – 7.76 (m, 1H), 7.60 (dd, J = 5.1, 3.3 Hz, 1H), 7.45 – 7.40 (m, 1H), 7.36 (d, J = 5.7 Hz, 4H), 2.83 (s, 3H). 13C NMR (101MHz, CDCl3): δ 163.5, 150.4, 142.3, 139.0, 131.9, 131.0, 130.1, 126.4, 126.2, 125.1, 124.5, 120.3, 110.6, 22.4. IR (KBr): 2958, 2921, 1616, 1549, 1453, 1241, 1029, 748, 724. LRMS (ESI): calcd. for C14H11NO [M+H]+ 210.1, found: 210.0.
2-([1,1'-Biphenyl]-4-yl)benzo[d]oxazole (3k):26 white solid (petroleum ether/EtOAc), mp 140-141 °C. 1H NMR (400 MHz, CDCl3): δ 8.32 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 8.4 Hz, 1H), 7.47 (t, J = 7.4 Hz, 2H), 7.41 (d, J = 7.4 Hz, 1H), 7.35 (dd, J = 9.6, 5.6 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 162.9, 150.8, 144.1, 142.2, 139.9, 129.0, 128.1, 127.5, 127.2, 125.9, 125.1, 124.6, 120.0, 110.6. IR (KBr): 3239, 1618, 1571, 1485, 1453, 1407, 1298, 1246, 1060, 845, 738, 623. LRMS (ESI): calcd. for C19H13NO [M+H]+ 272.1, found: 272.0.
2-(Naphthalen-1-yl)benzo[d]oxazole (3l):6 white solid (petroleum ether/EtOAc), mp 103-104 °C. 1H NMR (400 MHz, CDCl3): δ 9.52 (d, J = 8.5 Hz, 1H), 8.44 (d, J = 7.3 Hz, 1H), 8.03 (d, J = 8.1 Hz, 1H), 7.93 (t, J = 8.4 Hz, 2H), 7.73 (t, J = 7.8 Hz, 1H), 7.67 – 7.63 (m, 1H), 7.60 (t, J = 7.7 Hz, 2H), 7.42 (dd, J = 6.4, 2.7 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 162.9, 150.2, 142.4, 134.0, 132.4, 130.8, 129.4, 128.8, 128.0, 126.5, 126.4, 125.4, 125.0, 124.6, 123.7, 120.4, 110.6. IR (KBr): 3050, 1576, 1539, 1509, 1452, 1395, 1243, 1178, 1121, 1003, 971, 805, 777, 734. LRMS (ESI): calcd. for C17H11NO [M+H]+ 246.1, found: 246.1.
2-(Thiophen-2-yl)benzo[d]oxazole (3m):23 white solid (petroleum ether/EtOAc), mp 103-104 °C. 1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 3.1 Hz, 1H), 7.74 – 7.69 (m, 1H), 7.55 – 7.48 (m, 2H), 7.35 – 7.27 (m, 2H), 7.18 – 7.12 (m, 1H). 13C NMR (101 MHz, CDCl3): δ 159.1, 150.4, 142.0, 130.3, 130.0, 129.7, 128.3, 125.1, 124.8, 119.8, 110.5. IR (KBr): 3085, 1616, 1570, 1494, 1451, 1419, 1245, 1227, 1049, 1007, 852, 743. LRMS (ESI): calcd. for C11H7NOS [M+H]+ 202.0, found: 201.9.
2-(Pyridin-2-yl)benzo[d]oxazole (3n):27 white solid (petroleum ether/EtOAc), mp 108-109 °C. 1H NMR (400 MHz, CDCl3): δ 8.83 (s, 1H), 8.37 (d, J = 7.5 Hz, 1H), 7.91 (t, J = 7.1 Hz, 1H), 7.83 (d, J = 6.0 Hz, 1H), 7.67 (d, J = 6.4 Hz, 1H), 7.50 – 7.34 (m, 3H). 13C NMR (101 MHz, CDCl3): δ 161.4, 151.2, 150.3, 146.1, 141.9, 137.4, 126.2, 125.8, 125.1, 123.6, 120.8, 111.4. IR (KBr): 3059, 2924, 1584, 1554, 1453, 1243, 1077, 741. LRMS (ESI): calcd. for C12H8N2O [M+H]+ 197.1, found: 197.0.
2-Phenyl-4,5-dihydrooxazole (3o):28 colorless liquid (petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 7.5 Hz, 2H), 7.49 – 7.43 (m, 1H), 7.40 (t, J = 7.2 Hz, 2H), 4.42 (t, J = 9.4 Hz, 2H), 4.05 (t, J = 9.4 Hz, 2H). 13C NMR (101 MHz, CDCl3): δ 164.7, 131.4, 128.4, 128.2, 127.8, 67.7, 55.0. IR (KBr): 2961, 2925, 1639, 1541, 1490, 1451, 1364, 1270, 1177, 1069, 1026, 943, 711, 694, 616. LRMS (ESI): calcd. for C9H9NO [M+H]+ 148.1, found: 148.0.
4-Methyl-2-phenyl-4,5-dihydrooxazole (3p):29 colorless liquid (petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.7 Hz, 2H), 7.48 – 7.41 (m, 1H), 7.38 (t, J = 7.2 Hz, 2H), 4.50 (t, J = 8.6 Hz, 1H), 4.36 (dd, J = 15.0, 7.4 Hz, 1H), 3.93 (t, J = 7.8 Hz, 1H), 1.34 (d, J = 6.4 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 163.5, 131.3, 128.4, 128.3, 127.8, 74.1, 62.0, 21.5. IR (KBr): 2967, 2927, 1647, 1450, 1356, 1258, 1056, 969, 781, 693. LRMS (ESI): calcd. for C10H11NO [M+H]+ 162.1, found: 162.0.
4-Isopropyl-2-phenyl-4,5-dihydrooxazole (3q):30 colorless liquid (petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 7.6 Hz, 2H), 7.48 – 7.42 (m, 1H), 7.39 (t, J = 7.4 Hz, 2H), 4.43 – 4.33 (m, 1H), 4.16 – 4.03 (m, 2H), 1.86 (dq, J = 12.8, 6.3 Hz, 1H), 1.02 (d, J = 6.7 Hz, 3H), 0.92 (d, J = 6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3): δ 163.4, 131.3, 128.3, 128.3, 128.0, 72.6, 70.2, 32.9, 19.1, 18.2. IR (KBr): 2958, 2898, 1650, 1450, 1353, 1080, 1065, 965, 779, 693. LRMS (ESI): calcd. for C12H15NO [M+H]+ 190.1, found: 190.0.
2,4-Diphenyl-4,5-dihydrooxazole (3r):31 colorless liquid (petroleum ether/EtOAc). 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J = 7.1 Hz, 2H), 7.38 (d, J = 6.8 Hz, 1H), 7.33 (d, J = 7.0 Hz, 2H), 7.23 (d, J = 6.8 Hz, 2H), 7.20 (d, J = 4.8 Hz, 3H), 5.26 (t, J = 8.9 Hz, 1H), 4.67 (t, J = 9.1 Hz, 1H), 4.16 (t, J = 8.1 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 164.8, 142.4, 131.6, 128.8, 128.5, 128.4, 127.7, 127.5, 126.8, 74.9, 70.1. IR (KBr): 3030, 2899, 1644, 1533, 1450, 1317, 1273, 1066, 1025, 759, 693. LRMS (ESI): calcd. for C15H13NO [M+H]+ 224.1, found: 224.1.
2-Phenyl-4,8b-dihydro-3aH-indeno[2,1-d]oxazole (3s): yellow solid (petroleum ether/EtOAc), mp 104-106 °C. 1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.0 Hz, 2H), 7.58 (d, J = 4.3 Hz, 1H), 7.42 (d, J = 6.6 Hz, 1H), 7.37 (d, J = 6.9 Hz, 2H), 7.26 (s, 3H), 5.74 (d, J = 7.5 Hz, 1H), 5.48 (d, J = 6.9 Hz, 1H), 3.50 (dd, J = 17.9, 6.2 Hz, 1H), 3.36 (d, J = 17.8 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 164.1, 142.1, 139.8, 131.4, 128.5, 128.4, 128.3, 128.0, 127.6, 125.7, 125.4, 83.2, 76.8, 39.9. IR (KBr): 3032, 2964, 2928, 1641, 1494, 1450, 1300, 1249, 1082, 1065, 1024, 856, 753, 691. HRMS (ESI): calcd. for C16H13NO [M+H]+ 236.1078, found: 236.1077.

ACKNOWLEDGEMENTS
We gratefully acknowledge financial support by the PAPD (A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions) and NSFC (National Nature Science Foundation of China, No.21172162).

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