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May 16, 2019 - Described herein is a visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization reaction to synthesize...
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Cite This: J. Org. Chem. 2019, 84, 7509−7517

Visible-Light-Driven Chlorotrifluoromethylative and Chlorotrichloromethylative Cyclizations of Enynes Hong Hou,*,† Daliang Tang,† Hengxue Li,† Yue Xu,† Chaoguo Yan,† Yaocheng Shi,† Xiaoyun Chen,*,‡ and Shaoqun Zhu*,† †

School of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225005, China School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang 212005, China

‡

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S Supporting Information *

ABSTRACT: Described herein is a visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization reaction to synthesize chlorotrifluoromethylated and chlorotrichloromethylated cyclic compounds. Visible-light photochemistry was utilized to generate trifluoromethyl and trichloromethyl radicals and trigger radical addition/cyclization/chlorination sequences. The use of terminal alkenederived enynes enables the regioselective and stereoselective synthesis of chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines, and cyclopentanes.

T

which indicated that the transition metal was not essential for the present reaction system (Scheme 1).9,10

he radical addition and cyclization of substrates containing multiple unsaturated bonds represents a powerful and efficient synthetic strategy for the synthesis of complex organic compounds.1−3 Various radical precursors have been reported for radical generation to trigger the cascade reactions that result in cyclic structures.3,4 However, most of the reactions reported in the literature were ineffective, and only one atom or group was inserted into the final products.4 Visible-light photochemistry offers the unique ability of single electron transfer radical generation, which enables a redox-neutral radical addition and cyclization reaction without excess oxidant or reductant, leading to highly efficient and atom-economical organic synthesis.5 One example of this technique is the atom transfer radical cyclization (ATRC) reaction, which could provide final products with added chemical groups, with more than three new chemical bonds formed in one reaction step.6,7 Due to the high efficiency and atom economy of the visiblelight-promoted ATRC reaction, this reaction has attracted our attention. Recently, we reported a visible-light-mediated chlorosulfonylative cyclization reaction of enynes, in which the regioselective sulfonyl radical addition to the CC π-bond of the enyne yielded a choro-alkyl-substituted cyclic alkenyl sulfone product.8 To continue our research on heterocyclic compound synthesis, we report herein new visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization reactions to generate various chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines, and cyclopentane using the readily accessible enynes, CF3SO2Cl and CCl3SO2Cl. Compared with the previously reported electrocatalytic chlorotrifluoromethylative cyclization reaction, both Acr+-Mes·ClO4 (9-mesityl-10-methylacridinium perchlorate) and Ir(dtbbpy)(ppy)2PF6 could be used as the catalyst, © 2019 American Chemical Society

Scheme 1. Electrocatalytic Enyne Chlorotrifluoromethylative Cyclizations and Visible-LightDriven Chlorotrifluoromethylative and Chlorotrichloromethylative Cyclizations of Enynes

4-Methyl-N-(2-methylallyl)-N-(3-phenylprop-2-yn-1-yl)benzenesulfonamide (1a, 0.40 mmol, 1.0 equiv) and CF3SO2Cl (2, 0.8 mmol, 2.0 equiv) were reacted in MeCN as the solvent. Under irradiation with a 23 W fluorescent bulb, different catalysts including Ir(dtbbpy)(ppy)2PF6, Ir(bpy)(ppy)2PF6, and Ru(bpy)3Cl2 were tested, and all gave the desired product (Z)-4-(chloro(phenyl)methylene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine 3a in a moderate to good yield (61− 70%). When the organic dye Acr+-Mes·ClO4 (9-mesityl-10methylacridinium perchlorate) was used as s catalyst (5.0 mol % catalyst loading), 3a was isolated in 88% yield. Different Received: March 26, 2019 Published: May 16, 2019 7509

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

Note

The Journal of Organic Chemistry solvents were tested next, and acetone gave 3a in 70% isolated yield. When EtOAc was used, 3a was obtained in 68% yield. The background reactions were carefully investigated, and the reactions without a catalyst yielded trace amounts of 3a. When the reaction was performed in the dark, 3a was isolated in 18% yield (Table 1, entries 9 and 10). Notably, the E isomer of 3a was not observed in any of the reactions tested during the reaction condition screening process.

Table 2. Scope of Enynes for the Chlorotrifluoromethylative Cyclizationa

Table 1. Reaction Condition Screening for the Chlorotrifluoromethylative Cyclizationsa

entry

catalyst

loading (mol %)

solvent

yield (%)b

1 2 3 4 5 6 7 8 9c 10

Ir(dtbbpy)(ppy)2PF6 Ir(bpy)(ppy)2PF6 Ru(bpy)3Cl2 Acr+-Mes·ClO4 Acr+-Mes·ClO4 Acr+-Mes·ClO4 Acr+-Mes·ClO4 Acr+-Mes·ClO4 Acr+-Mes·ClO4

1.0 1.0 1.0 5.0 5.0 5.0 5.0 5.0 5.0

MeCN MeCN MeCN MeCN DCM DCE acetone EtOAc DCM DCM

61 65 70 80 88 78 70 68 18 trace

entry

R1

R

X

3

yield [%]b

1 2 3 4 5 6 7 8 9 10 11 12 13 14

C6H5 4-MeOC6H4 3-MeOC6H4 2-MeC6H4 4-ClC6H4 4-CO2MeC6H4 2-thienyl 1-naphthyl 3-pyridinyl C6H5 C6H5 Me C6H5 C6H5

Me Me Me Me Me Me Me Me Me H CO2Me Me Me Me

NTs NTs NTs NTs NTs NTs NTs NTs NTs NTs NTs NTs C(CO2Me)2 O

3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n

88 78 73 83 76 82 63 77 78 58 67 64 67 0

a

Reactions were carried out with 0.4 mmol of 1, 0.8 mmol of 2a, 2.0 mmol of K2HPO4, and 0.02 mmol of Acr+-Mes·ClO4 in dichloromethane (DCM) (2.0 mL) under an argon atmosphere. bYield of the isolated product.

radical intermediate generated from 1a before the 5-exo cyclization step. Replacement of the methyl group with an ester was also possible, and the ester-containing pyrrolidine 3k was formed in 67% yield. When the N-(but-2-yn-1-yl)-4-methylbenzenesulfonamide-derived substrate 1l was subjected to the abovementioned reaction conditions, (Z)-4-(1-chloroethylidene)-3methyl-1-tosyl-3-(2,2,2-trifluoroethyl)pyrrolidine 3l was obtained in 64% yield. Some byproduct or isomer was observed by thin-layer chromatography (TLC), but we failed to isolate any other isomer or byproduct via column chromatography. The all-carbon cyclic compound (E)-dimethyl 4-(chloro(phenyl)methylene)-3-methyl-3-(2,2,2-trifluoroethyl)cyclopentane-1,1-dicarboxylate 3m was obtained in 67% yield. The propargyl alcohol-derived 1,6-enyne decomposed under the reaction conditions, and the desired chlorotrifluoromethylated tetrahydrofuran product 3n failed to be obtained (entry 14, Table 2). The protective group was investigated next, and different sulfonylamide groups were tested and proved to be suitable for this cyclization reaction. Both aromatic and aliphatic sulfonylamide groups were introduced to the reaction and successfully generated the corresponding products 3o−3t in good yields (53−88%, Table 3). The relative configuration was confirmed to be Z by single-crystal X-ray diffraction of 3p.11 Chlorotrichloromethylative cyclizations also attracted our attention, and we next investigated trichloromethanesulfonyl chloride 4. To our great delight, the reaction without the optimized condition afforded the desired chlorotrichloromethylated pyrrolidine products 5a−5f in good isolated yields and 1.0 mol % of Ir(dtbbpy)(ppy)2PF6 was used as the catalyst (56−89%, Table 4). To further expand the substrate scope, N-(3-phenylprop-2yn-1-yl)-N-tosylmethacrylamide 1u was subjected to the

a Reactions were carried out with 0.4 mmol of 1a, 0.8 mmol of 2a, 2.0 mmol of K2HPO4, 1.0 mol % or 5.0 mol % catalyst, and 2.0 mL of solvent under an argon atmosphere. bYield of the isolated product. c The reaction was performed in the dark. Acr+-Mes·ClO4: 9-mesityl10-methylacridinium perchlorate

Under the best reaction conditions established above, the enyne substrate scope was further investigated. First, different enynes with different electronic and steric aryl groups on the alkyne were introduced to react with CF3SO2Cl, and all proved to be compatible, giving the corresponding products 3a−3f in good yields (73−88%, entries 1−6 in Table 2). Electrondonating groups such as MeO and Me at different positions were tested, and all gave the products 3b, 3c, and 3d in a good yield. 4-Methyl-N-(2-methylallyl)-N-(3-(o-tolyl)prop-2-yn-1yl)benzenesulfonamide 1d and 4-methyl-N-(2-methylallyl)-N(3-(naphthalen-1-yl)prop-2-yn-1-yl)benzenesulfonamide 1h also gave the desired products 3d and 3h in 83% and 77% isolated yields, respectively. The highly steric nature of the substrate also led to the product formation (entries 4 and 8, Table 2). Electron-withdrawing groups, such as Cl and CO2Me, were compatible as well, and the corresponding products 3e and 3f were obtained in 76% and 82% yields, respectively. Heterocyclic aromatic groups were also suitable, and 2-thienyl- and 3-pyridinyl-containing enynes gave their corresponding products 3g and 3i in 63% and 78% yields. respectively (entries 7 and 9, Table 2). N-Allyl-4-methylbenzenesulfonamide-derived enyne 1j was next subjected to the above reaction conditions, and the radical transformation successfully gave the desired product 3j in 58% yield (entry 10, Table 2). Compared to the reaction of 1a with 2, the reaction of 1j formed 3j in a lower yield, which could be explained by the lower stability of the secondary carbon radical intermediate generated from 1j than of the tertiary carbon 7510

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

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The Journal of Organic Chemistry

6 was introduced to the reaction. The major component, 7′, was isolated in 48% yield, upon addition of the trifluoromethane carbon radical to the CC π-bond (site b, Scheme 2), and the minor product, 7, obtained in 40% yield, was generated from the addition of the trifluoromethane carbon radical addition to the CC π-bond (site a, Scheme 2). Both 7 and 7′ were fully characterized, and the structure was defined by single-crystal X-ray single diffraction (see the Supporting Information for details).11 The reaction of 4.0 mmol 1u with 8.0 mmol of 2 at a concentration of 0.2 M was tested next, and 1.39 g of (Z)-4(chloro(phenyl)methylene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidin-2-one 3u was isolated (76% yield, Scheme 3)

Table 3. Scope of the Sulfonylamide Protected Group for the Chlorotrifluoromethylative Cyclizationa

entry

R2

R

3

yield [%]b

1 2 3 4 5 6

C6H5 4-PhC6H4 2-naphthyl benzyl n Bu 4-PhC6H4

Me Me Me Me Me H

3o 3p 3q 3r 3s 3t

61 73 88 85 71 53

Scheme 3. Large Scale Reaction

a

Reactions were carried out with 0.4 mmol of 1, 0.8 mmol of 2a, 2.0 mmol of K2HPO4, and 0.02 mmol of Acr+-Mes·ClO4 in dichloromethane (DCM) (2.0 mL) under an argon atmosphere. bYield of the isolated product.

Table 4. Scope of Enynes for the Chlorotrichloromethylative Cyclizationa Based on literature reports and our previous report on the radical cyclization reaction using sulfonyl chloride, a possible mechanism for this chlorotrifluoromethylative cyclization reaction is presented in Scheme 4. The generation of CF3 entry

Ar

X

5

yield [%]b

1 2 3 4 5 6

4-MeOC6H4 2-thienyl 4-ClC6H4 4-CO2Me C6H4 Me C6H5

NTs NTs NTs NTs NTs C(CO2Me)2

5a 5b 5c 5d 5e 5f

89 56 78 70 79 82

Scheme 4. Possible Mechanisms

a Reactions were carried out with 0.4 mmol of 1, 0.8 mmol of 4, 2.0 mmol of K2HPO4, and 0.02 mmol of Ir(dtbbpy)(ppy)2PF6 in dichloromethane (DCM) (2.0 mL) under an argon atmosphere. b Yield of the isolated product.

specified reaction conditions, and the desired product 5g was obtained in 81% yield (Scheme 2). The internal alkene-derived enynes were suitable, affording the chlorotrifluoromethylated piperidines. However, two different products resulting from the different radical addition steps were formed and isolated when

radical 9 from CF3SO2Cl 2 is a well-established process, and the single electron transfer process between the photoexcited catalyst species and the sulfonyl chloride leads to the formation of sulfonyl radicals and chlorine anions. Fragmentation of the trifluoromethyl sulfonyl radical leads to CF3 radical 9 formation.12 The addition of the CF3 radical to the CC πbond of enyne 1a gives tertiary carbon radical intermediate 10, and subsequent intramolecular 5-exo radical cyclization results in vinyl radical 11 formation. The direct chlorine atom transfer reaction between the vinyl carbon radical 11 and CF3SO2Cl 2 affords the desired chlorotrifluoromethylated pyrrolidine product 3a and results in sulfonyl radical 8 regeneration.13 The sulfonyl radical would returns to the reaction cycle. In all cases, 6-endoradical cyclization products were not observed, and the above reactions gave only Z-products. In conclusion, we have described a visible-light-driven chlorotrifluoromethylative and chlorotrichloromethylative cyclization approach, and a series of chlorotrifluoromethylated and chlorotrichloromethylated pyrrolidines, piperidines, and

Scheme 2. Reaction of N-(3-Phenylprop-2-yn-1-yl)-Ntosylmethacrylamide, Internal Alkene-Derived 1,6-Enynes with Sulfonyl Chloride

7511

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

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The Journal of Organic Chemistry

(d, J = 12.1 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 139.4, 131.6, 130.9, 128.8, 128.64, 128.60, 128.5, 122.0, 115.2, 85.8, 83.1, 58.3, 53.3, 36.1, 19.4; IR (neat) ν 3071, 2929, 1594, 1492, 1444, 1342, 1148, 1023, 760, 695 cm−1; HRMS (ESI) exact mass calcd for [C20H21SO2NNa]+ [M + Na]+ 362.1185, found 362.1185. N-(2-Methylallyl)-N-(3-phenylprop-2-yn-1-yl)butane-1-sulfonamide (1s): 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 6.1 Hz, 1H), 7.32 (s, 1H), 5.03 (d, J = 16.6 Hz, 1H), 4.21 (s, 2H), 3.90 (s, 2H), 3.24−3.01 (m, 2H), 1.84 (dt, J = 15.1, 7.5 Hz, 1H), 1.77 (s, 1H), 1.39 (dt, J = 31.8, 15.8 Hz, 1H), 0.89 (t, J = 7.2 Hz, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 139.4, 131.5, 128.7, 128.4, 122.0, 115.2, 85.5, 82.7, 52.8, 51.8, 35.8, 25.0, 21.7, 19.5, 13.5; IR (neat) ν 3062, 2951, 1589, 1455, 1334, 1145, 1023, 760, 698 cm−1; HRMS (ESI) exact mass calcd for [C17H23SO2NNa]+ [M + Na]+ 328.1342, found 328.1338. N-Allyl-N-(3-phenylprop-2-yn-1-yl)-[1,1′-biphenyl]-4-sulfonamide (1t): 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 7.9 Hz, 2H), 7.66 (d, J = 7.6 Hz, 2H), 7.44 (dd, J = 17.4, 8.9 Hz, 5H), 7.20 (t, J = 7.0 Hz, 1H), 7.10 (t, J = 7.5 Hz, 2H), 7.00 (d, J = 7.5 Hz, 2H), 5.83 (td, J = 16.1, 6.5 Hz, 1H), 5.32 (dd, J = 25.6, 13.5 Hz, 2H), 4.35 (s, 2H), 3.94 (d, J = 6.1 Hz, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 145.6, 139.3, 137.4, 131.9, 131.4, 128.9, 128.4, 128.3, 128.2, 127.5, 127.3, 122.0, 120.1, 85.9, 81.4, 49.3, 36.7; IR (neat) ν 1484, 1334, 1163, 893, 763, 674 cm−1; HRMS (ESI) exact mass calcd for [C24H21SO2NNa]+ [M + Na]+ 410.1185, found 410.0879. General Procedure for the Chlorotrifluoromethylative Cyclizations of Enynes. An oven-dried reaction tube with a stir bar was charged with enynes 1 (0.40 mmol, 1.0 equiv), trifluoromethanesulfonyl chloride 2 (134.8 mg, 0.80 mmol), K2HPO4·3H2O (456.4 mg, 2.00 mmol), and Acr+-Mes·ClO4 (6.2 mg, 0.02 mmol) and was sealed with a rubber stopper, evacuated, and backfilled with argon three times; then dry DCM (4.0 mL) as a solvent was added. The tube was then immersed sideways into a sand bath under room temperature and irradiated by a 23 W fluorescent bulb for 5−12 h with stirring. After the enynes 1 were completely consumed (monitored by TLC), the crude mixture was directly purified by flash column chromatography on silica gel (EtOAc/ petroleum ether 1:20) to give the desired products 3a−3u. (Z)-4-(Chloro(phenyl)methylene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine (3a): white solid (157.2 mg, 88%); mp 75− 77 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.1 Hz, 2H), 7.39 (dd, J = 7.3, 5.8 Hz, 5H), 7.22 (dd, J = 6.5, 2.8 Hz, 2H), 4.15 (d, J = 15.4 Hz, 1H), 3.91 (d, J = 15.4 Hz, 1H), 3.21 (s, 2H), 2.47 (s, 3H), 2.05 (dq, J = 15.2, 11.4 Hz, 1H), 1.86 (dq, J = 15.4, 11.3 Hz, 1H), 1.17 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.1, 140.4, 137.0, 131.7, 129.9, 129.5, 128.8, 128.7, 128.1, 127.0, 125.7 (d, J = 277.4 Hz, CF3), 59.9 (d, J = 2.4 Hz), 53.1, 43.4 (d, J = 5.7 Hz), 40.4 (q, J = 27.3 Hz, CCF3), 24.4 (d, J = 1.2 Hz), 21.6; 19F NMR (376 MHz, CDCl3) δ −60.3 (t, J = 7.14 Hz, 3F); IR (neat) ν 3009, 2885, 1663, 1592, 1483, 1355, 1240, 1168, 1098, 1025, 887, 812, 702 cm−1; HRMS (ESI) exact mass calcd for [C21H21SO2ClNF3H]+ [M + H]+ 444.1006, found 444.1012. (Z)-4-(Chloro(4-methoxyphenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3b): white solid (146.9 mg, 78%); mp 121−123 °C; 1H NMR (400 MHz, CDCl3) δ 7.77−7.72 (m, 2H), 7.42−7.37 (m, 2H), 7.17−7.14 (m, 1H), 7.14−7.12 (m, 1H), 6.91− 6.88 (m, 1H), 6.88−6.85 (m, 1H), 4.13 (d, J = 15.4 Hz, 1H), 3.87 (d, J = 15.4 Hz, 1H), 3.82 (s, 3H), 3.20 (s, 2H), 2.47 (s, 3H), 2.13−1.99 (m, 1H), 1.91 (dq, J = 15.3, 11.3 Hz, 1H), 1.18 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 160.2, 144.1, 140.4, 131.6, 130.2, 129.9, 129.2, 128.1, 127.2, 125.8 (d, J = 277.4 Hz, CF3) 114.0, 59.9 (d, J = 2.4 Hz), 55.3, 53.2, 43.4, 40.4 (q, J = 27.2 Hz, CCF3), 24.4, 21.6; 19F NMR (376 MHz, CDCl3) δ −60.3 (t, J = 7.52 Hz, 3F); IR (neat) ν 2960, 2836, 1606, 1509, 1464, 1375, 1293, 1163, 889, 810, 704 cm−1; HRMS (ESI) exact mass calcd for [C22H23SO3ClNF3H]+ [M + H]+ 474.1112, found 474.1120. (Z)-4-(Chloro(3-methoxyphenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3c): white solid (138.4 mg, 73%); mp 74−76 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 12.7, 4.7 Hz, 1H), 6.93−

cyclopentane in moderate to good yields. A further application of this ATRC reaction is still underway in our laboratory.

■

EXPERIMENTAL SECTION

General Methods. All experiments were conducted under an argon atmosphere. DCM, DCE, EtOAc, and acetonitrile were dried and distilled by the standard methods. Other commercially available reagents were purchased and used without further purification, unless otherwise stated. Flash chromatographic separations were carried out on 200−300 mesh silica gel. Reactions were monitored by TLC analysis of reaction aliquots. Melting points were measured on a Yanaco micro melting point apparatus. 1H NMR, 13C NMR, and 19F NMR were recorded on a Variance VNMR 400 or a Bruker AV-600 spectrometer. Chemical shifts (δ) are reported in ppm, and coupling constants (J) are reported in hertz (Hz). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, m = multiplet, br = broad. IR spectra were recorded on a PerkinElmer Spectrum 100 FTIR (KBr disc) and are reported in terms of frequency of absorption (cm−1). High-resolution mass spectra (HRMS) were obtained on AB 5800 MALDI-TOF/TOF and are recorded using electrospray ionization (ESI). X-ray crystallographic data were collected using a SMART APEX II X-ray diffractometer. For the light source in detail and the material of the irradiation vessel, see the Supporting Information. Compounds 1a−1n and 1u were prepared according to the previous reported procedures.9 Citations to the references containing characterization data for these compounds (1b,9 1c,4e 1d,9 1e,9 1f,4g 1g,4h 1h,4g 1i,4e 1j,9 1k,14 1l,9 1m,15 1n,9 1u,9 1o, and 6) were prepared according to the previous reported, procedures and the characterization data are consistent with the previous reports.16,17 General Procedure for the Preparation of 1p−1t. To a mixture of 3-phenylprop-2-yn-1-amine (11 mmol, 1.1 equiv) in DCM (20 mL) were sequentially added RSO2Cl (10 mmol, 1.0 equiv) and triethylamine (25 mmol, 2.5 equiv). The reaction mixture was stirred overnight at room temperature. The resulting mixture was then extracted with DCM (2 × 20 mL), washed with a saturated aqueous solution of brine, dried over Na2SO4, and evaporated under reduced pressure to give the corresponding crude alkynyl sulfonamides. Then acetone (25 mL) was added as a solvent, and K2CO3 (15 mmol) and allyl bromide (15 mmol) were added. The reaction mixture was stirred at room temperature for 24 h. The resulting mixture was extracted with ethyl ether (2 × 20 mL), washed with a saturated aqueous solution of brine, dried over Na2SO4, and evaporated under reduced pressure and purified by chromatography on silica gel to afford the corresponding compounds 1p−1t. N-(2-Methylallyl)-N-(3-phenylprop-2-yn-1-yl)-[1,1′-biphenyl]-4sulfonamide (1p): 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.1 Hz, 2H), 7.66 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 6.8 Hz, 6H), 7.41 (d, J = 8.6 Hz, 1H), 7.19 (d, J = 7.4 Hz, 1H), 7.09 (t, J = 7.5 Hz, 2H), 6.98 (d, J = 7.5 Hz, 2H), 5.02 (s, 1H), 4.30 (s, 1H), 3.86 (s, 1H), 1.84 (s, 2H); 13C{1H} NMR (CDCl3, 100 MHz) δ 145.6, 139.3, 139.1, 137.5, 131.4, 128.9, 128.4, 128.3, 128.1, 127.5, 127.3, 122.0, 115.7, 85.8, 81.4, 52.8, 36.4, 19.7; IR (neat) ν 3067, 2917, 1593, 1487, 1440, 1345, 1161, 1099, 904, 839, 760, 693 cm−1; HRMS (ESI) exact mass calcd for [C25H23SO2NNa]+ [M + Na]+ 424.1342, found 424.1341. N-(2-Methylallyl)-N-(3-phenylprop-2-yn-1-yl)naphthalene-2-sulfonamide (1q): 1H NMR (400 MHz, CDCl3) δ 8.49 (s, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.89 (s, 2H), 7.84 (d, J = 8.2 Hz, 1H), 7.58 (dt, J = 14.9, 7.0 Hz, 2H), 7.15 (t, J = 7.5 Hz, 1H), 7.01 (t, J = 7.4 Hz, 2H), 6.64 (d, J = 7.7 Hz, 2H), 5.01 (s, 2H), 4.32 (s, 2H), 3.87 (s, 2H), 1.83 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 139.2, 136.0, 134.9, 132.3, 131.2, 129.3, 129.1, 129.0, 128.6, 127.8, 127.3, 123.1, 121.8, 115.6, 85.7, 81.4, 52.8, 36.5, 19.8; IR (neat) ν 3061, 2921, 2855, 1443, 1343, 1158, 904, 757, 695 cm−1; HRMS (ESI) exact mass calcd for [C23H21SO2NNa]+ [M + Na]+ 398.1185, found 398.1186. N-(2-Methylallyl)-1-phenyl-N-(3-phenylprop-2-yn-1-yl)methanesulfonamide (1r): 1H NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 17.9, 15.1 Hz, 5H), 7.36 (d, J = 8.3 Hz, 5H), 4.98 (s, 2H), 4.37 (d, J = 27.1 Hz, 2H), 4.31−4.19 (m, 2H), 3.58 (d, J = 20.9 Hz, 2H), 1.70 7512

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

Note

The Journal of Organic Chemistry

(Z)-4-(Chloro(naphthalen-1-yl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3h): white solid (152.7 mg, 77%); mp 170−172 °C; 1H NMR (400 MHz, CDCl3) δ 7.78−7.72 (m, 2H), 7.42−7.32 (m, 5H), 7.28−7.23 (m, 2H), 4.09 (dd, J = 15.6, 1.7 Hz, 1H), 3.90 (d, J = 15.6 Hz, 1H), 3.40 (dd, J = 10.1, 3.2 Hz, 1H), 3.30 (dd, J = 10.1, 6.3 Hz, 1H), 3.18 (d, J = 8.1 Hz, 1H), 2.46 (s, 3H), 2.17−1.97 (m, 1H), 1.90−1.75 (m, 1H). 13C{1H} NMR (CDCl3, 100 MHz) δ 144.2, 136.4, 135.9, 131.9, 129.9, 129.4, 128.8, 128.0, 127.9, 127.2, 125.6 (d, J = 274.3 Hz, CF3), 53.6, 52.4, 36.1 (d, J = 2.7 Hz), 35.8 (d, J = 28.0 Hz, CCF3), 21.6; 19F NMR (376 MHz, CDCl3) δ −65.2; IR (neat) ν 2989, 2894, 1662, 1594, 1363, 1261, 1163, 1094 cm−1; HRMS (ESI) exact mass calcd for [C25H23SO2ClNF3H]+ [M + H]+ 494.1163, found 494.1173. (Z)-3-(Chloro(4-methyl-1-tosyl-4-(2,2,2-trifluoroethyl)pyrrolidin3-ylidene)methyl)pyridine (3i): white solid (139.4 mg, 78%); mp 124−126 °C; 1H NMR (400 MHz, CDCl3) δ 8.63 (dd, J = 4.9, 1.7 Hz, 1H), 8.49 (dd, J = 2.2, 0.7 Hz, 1H), 7.77−7.71 (m, 2H), 7.60− 7.52 (m, 1H), 7.39 (d, J = 7.9 Hz, 2H), 7.36−7.33 (m, 1H), 4.13 (d, J = 15.7 Hz, 1H), 3.97 (d, J = 15.7 Hz, 1H), 3.30 (d, J = 9.7 Hz, 1H), 3.15 (d, J = 9.7 Hz, 1H), 2.47 (s, 3H), 2.13 (dq, J = 15.2, 11.2 Hz, 1H), 1.87 (dq, J = 15.3, 11.0 Hz, 1H), 1.13 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 150.5, 149.4, 144.3, 142.9, 136.8, 133.2, 131.6, 129.9, 128.0, 125.4 (d, J = 277.4 Hz, CF3), 123.6, 123.4, 59.7 (q, J = 2.3 Hz), 53.3, 43.6 (q, J = 1.7 Hz), 40.8 (q, J = 27.5 Hz, CCF3), 24.4 (d, J = 1.3 Hz), 21.6; 19F NMR (376 MHz, CDCl3) δ −60.2 (t, J = 7.52 Hz, 3F); IR (neat) ν 2979, 1669, 1595, 1352, 1258, 1161, 1090, 787, 711, 663 cm −1 ; HRMS (ESI) exact mass calcd for [C20H20SO2ClN2F3H]+ [M + H]+ 445.0959, found 445.0975. (Z)-3-(Chloro(phenyl)methylene)-1-tosyl-4-(2,2,2-trifluoroethyl)pyrrolidine (3j): colorless gum (99.3 mg, 58%); 1H NMR (400 MHz, CDCl3) δ 7.78−7.72 (m, 2H), 7.42−7.32 (m, 5H), 7.28−7.23 (m, 2H), 4.09 (dd, J = 15.6, 1.7 Hz, 1H), 3.90 (d, J = 15.6 Hz, 1H), 3.40 (dd, J = 10.1, 3.2 Hz, 1H), 3.30 (dd, J = 10.1, 6.3 Hz, 1H), 3.18 (d, J = 8.1 Hz, 1H), 2.46 (s, 3H), 2.17−1.97 (m, 1H), 1.90−1.75 (m, 1H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 144.2, 136.4, 135.9, 131.9, 129.9, 129.4, 128.8, 128.0, 127.9, 127.2, 125.6 (d, J = 274.3 Hz, CF3), 53.6, 52.4, 36.1 (d, J = 2.7 Hz), 35.8 (d, J = 28.0 Hz, CCF3), 21.6; 19F NMR (376 MHz, CDCl3) δ −65.2 (t, J = 6.77 Hz, 3F); IR (neat) ν 2945, 1596, 1568, 1453, 1324, 1136, 804, 763 cm−1; HRMS (ESI) exact mass calcd for [C20H19SO2ClNF3H]+ [M + H]+ 430.0850, found 430.0867. (Z)-Methyl 4-(Chloro(phenyl)methylene)-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine-3-carboxylate (3k): white solid (130.1 mg, 67%); mp 153−155 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.43−7.32 (m, 5H), 7.20−7.12 (m, 2H), 4.14 (q, J = 15.1 Hz, 2H), 3.78 (d, J = 10.1 Hz, 1H), 3.55 (d, J = 10.1 Hz, 1H), 3.47 (s, 3H), 2.55 (dq, J = 15.6, 10.7 Hz, 1H), 2.47 (s, 3H), 2.24 (dq, J = 15.5, 10.6 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 170.3, 144.2, 136.0, 135.1, 129.9, 129.7, 129.5, 128.61, 128.59, 128.0, 127.9, 125.0 (d, J = 277.1 Hz, CF3), 56.2 (d, J = 2.0 Hz), 53.12, 53.05, 52.4 (d, J = 2.1 Hz), 37.7 (q, J = 28.8 Hz, CCF3), 21.6; 19F NMR (376 MHz, CDCl3) δ − 59.9 (t, J = 6.77 Hz, 3F); IR (neat) ν 2923, 1736, 1592, 1447, 1352, 1261, 1162, 1052, 826, 763 cm−1; HRMS (ESI) exact mass calcd for [C22H21SO4ClNF3H]+ [M + H]+ 488.0905, found 488.0922. (Z)-4-(1-Chloroethylidene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine (3l): colorless gum (98.1 mg, 64%); 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 3.88 (dd, J = 14.7, 1.9 Hz, 1H), 3.77 (dd, J = 14.7, 1.9 Hz, 1H), 3.42 (d, J = 9.7 Hz, 1H), 2.92 (d, J = 9.7 Hz, 1H), 2.45 (s, 3H), 2.40 (d, J = 11.2 Hz, 2H), 2.13 (t, J = 1.9 Hz, 3H), 1.36 (s, 3H); 13 C{1H} (CDCl3, 100 MHz) δ 144.1, 137.1, 131.3, 129.8, 128.1, 126.1, 125.8 (d, J = 277.4 Hz, CF3), 60.6 (d, J = 2.1 Hz), 53.3, 42.7 (d, J = 1.6 Hz), 40.2 (q, J = 26.9 Hz, CH2CF3), 22.8, 22.4 (d, J = 1.4 Hz), 21.5; 19F NMR (376 MHz, CDCl3) δ −60.5 (t, J = 7.52 Hz, 3F); IR (neat) ν 2925, 2869, 1664, 1591, 1353, 1259, 1165, 1092, 799, 706 cm−1; HRMS (ESI) exact mass calcd for [C16H19SO2ClNF3H]+ [M + H]+ 382.0850, found 382.0861. (Z)-Dimethyl (E)-4-(Chloro(phenyl)methylene)-3-methyl-3-(2,2,2trichloroethyl)cyclopentane-1,1-dicarboxylate (3m): colorless gum

6.90 (m, J = 8.4, 2.6, 0.8 Hz, 1H), 6.82−6.78 (m, 1H), 6.74 (dd, J = 2.4, 1.6 Hz, 1H), 4.14 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 15.4 Hz, 1H), 3.79 (s, 3H), 3.22 (s, 2H), 2.47 (s, 3H), 2.08 (dq, J = 15.2, 11.4 Hz, 1H), 1.93 (dq, J = 15.3, 11.3 Hz, 1H), 1.20 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 159.5, 144.1, 140.3, 138.1, 131.6, 129.9, 129.8, 128.0, 126.7, 125.8 (d, J = 277.4 Hz, CF3), 121.1, 115.0, 114.5, 59.9 (q, J = 2.3 Hz), 55.3, 53.1, 43.4 (q, J = 1.7 Hz), 40.3 (q, J = 27.3 Hz, CCF3), 24.4 (d, J = 1.3 Hz), 21.6; 19F NMR (376 MHz, CDCl3) δ −60.2 (t, J = 7.52 Hz, 3F); IR (neat) ν 2943, 2840, 1599, 1486, 1430, 1352, 1164, 1044, 879, 814, 707 cm−1; HRMS (ESI) exact mass calcd for [C22H23SO3ClNF3H]+ [M + H]+ 474.1112, found 474.1124. (Z)-4-(Chloro(o-tolyl)methylene)-3-methyl-1-tosyl-3-(2,2,2trifluoroethyl)pyrrolidine (3d): white solid (151.7 mg, 83%); mp 89− 91 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.28 (dd, J = 12.7, 4.7 Hz, 1H), 6.92 (m, J = 8.4, 2.6, 0.8 Hz, 1H), 6.82−6.78 (m, 1H), 6.74 (dd, J = 2.4, 1.6 Hz, 1H), 4.14 (d, J = 15.4 Hz, 1H), 3.89 (d, J = 15.4 Hz, 1H), 3.79 (s, 3H), 3.22 (s, 2H), 2.47 (s, 3H), 2.08 (dq, J = 15.2, 11.4 Hz, 1H), 1.93 (dq, J = 15.3, 11.3 Hz, 1H), 1.20 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 159.5, 144.1, 140.3, 138.1, 131.6, 129.9, 129.8, 128.0, 126.7, 125.8 (d, J = 277.4 Hz, CF3), 121.1, 115.0, 114.5, 59.9 (q, J = 2.3 Hz), 55.3, 53.1, 43.4 (q, J = 1.7 Hz), 40.3 (q, J = 27.3 Hz, CCF3), 24.4 (d, J = 1.3 Hz), 21.6; 19F NMR (376 MHz, CDCl3) δ −60.2; IR (neat) ν 2981, 2894, 1624, 1548, 1453, 1341, 1243, 1013, 981, 782, 679 cm−1; HRMS (ESI) exact mass calcd for [C22H23SO2ClNF3H]+ [M + H]+ 458.1163, found 458.1151. (Z)-4-(Chloro(4-chlorophenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3e): white solid (146.2 mg, 76%); mp 103−105 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.40 (s, 1H), 7.37 (t, J = 2.4 Hz, 2H), 7.36−7.33 (m, 1H), 7.19−7.16 (m, 1H), 7.16−7.14 (m, 1H), 4.12 (d, J = 15.5 Hz, 1H), 3.91 (d, J = 15.6 Hz, 1H), 3.26 (d, J = 9.7 Hz, 1H), 3.17 (d, J = 9.7 Hz, 1H), 2.47 (s, 3H), 2.09 (dq, J = 15.2, 11.3 Hz, 1H), 1.90 (dq, J = 15.3, 11.1 Hz, 1H), 1.15 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.2, 141.3, 135.6, 135.4, 131.7, 130.2, 129.9, 129.1, 128.0, 125.8, 125.6 (d, J = 277.4 Hz, CF3), 59.8 (d, J = 2.3 Hz), 55.2, 43.5 (q, J = 1.7 Hz), 40.5 (q, J = 27.4 Hz, CCF3), 24.4 (d, J = 1.4 Hz), 21.6; 19F NMR (376 MHz, CDCl3) δ −60.2 (t, J = 7.14 Hz, 3F); IR (neat) ν 2925, 2869, 1594, 1487, 1348, 1314, 1161, 1043, 895, 832, 664 cm−1; HRMS (ESI) exact mass calcd for [C21H20SO2Cl2NF3H]+ [M + H]+ 478.0617, found 478.0621. (Z)-Methyl 4-(Chloro(4-methyl-1-tosyl-4-(2,2,2-trifluoroethyl)pyrrolidin-3-ylidene)methyl)benzoate (3f): white solid (165.0 mg, 82%); mp 125−127 °C; 1H NMR (400 MHz, CDCl3) δ 8.09−7.99 (m, 2H), 7.77−7.71 (m, 2H), 7.39 (d, J = 7.9 Hz, 2H), 7.34−7.27 (m, 2H), 4.13 (d, J = 15.6 Hz, 1H), 3.96−3.89 (m, 4H), 3.25 (d, J = 9.6 Hz, 1H), 3.17 (d, J = 9.7 Hz, 1H), 2.47 (s, 3H), 2.08 (dq, J = 15.3, 11.3 Hz, 1H), 1.86 (dq, J = 15.3, 11.1 Hz, 1H), 1.14 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 166.0, 144.2, 141.3, 141.2, 131.6, 131.0, 129.9, 129.8, 129.0, 128.0, 125.6, 125.5 (d, J = 277.5 Hz, CF3), 59.8 (d, J = 2.3 Hz), 53.2, 52.4, 43.5 (d, J = 1.7 Hz), 40.5 (q, J = 27.3 Hz, CCF3), 24.3 (d, J = 1.2 Hz), 21.6; 19F NMR (376 MHz, CDCl3) δ −60.2 (t, J = 7.52 Hz, 3F); IR (neat) ν 2957, 2849, 1722, 1603, 1440, 1375, 1261, 1184, 1137, 1042, 897, 808, 704, 667 cm−1; HRMS (ESI) exact mass calcd for [C23H23SO4ClNF3H]+ [M + H]+ 502.1061, found 502.1067. (Z)-4-(Chloro(thiophen-2-yl)methylene)-3-methyl-1-tosyl-3(2,2,2-trifluoroethyl)pyrrolidine (3g): white solid (112.9 mg, 63%); mp 107−109 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.9 Hz, 3H), 7.12−6.93 (m, 2H), 4.14 (d, J = 16.0 Hz, 1H), 3.88 (d, J = 16.0 Hz, 1H), 3.23 (s, 2H), 2.47 (s, 3H), 2.24− 1.97 (m, 2H), 1.27 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.6, 144.2, 137.3, 131.6, 129.9, 129.3, 128.3, 128.0, 126.8, 125.8 (d, J = 277.3 Hz, CF3), 119.9, 59.9 (d, J = 2.3 Hz), 53.6, 43.8 (d, J = 1.7 Hz), 39.7 (d, J = 27.5 Hz, CCF3), 24.0, 21.6; 19F NMR (376 MHz, CDCl3) δ −60.2 (t, J = 7.52 Hz, 3F); IR (neat) ν 2964, 1651, 1540, 1454, 1261, 1093, 1021, 800, 703 cm−1; HRMS (ESI) exact mass calcd for [C19H19S2O2ClNF3H]+ [M + H]+ 450.0571, found 450.0576. 7513

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

Note

The Journal of Organic Chemistry (108.5 mg, 67%); 1H NMR (400 MHz, CDCl3) δ 7.29 (s, 3H), 7.18 (d, J = 6.3 Hz, 2H), 3.72 (s, 3H), 3.69 (s, 3H), 3.50 (d, J = 18.5 Hz, 1H), 3.17 (d, J = 18.5 Hz, 1H), 2.66 (d, J = 14.1 Hz, 1H), 2.45 (d, J = 14.1 Hz, 1H), 2.05−1.86 (m, 1H), 1.90−1.67 (m, 1H), 0.98 (s, 3H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 179.94, 179.93, 144.2, 137.9, 131.5, 129.2, 129.0, 128.5, 126.1 (d, J = 277.6 Hz, CF3), 56.6, 53.1, 53.0, 52.7, 41.7, 42.6 (q, J = 26.3 Hz, CCF3), 41.6, 27.0; 19F NMR (565 MHz, CDCl3) δ −59.8 (t, J = 7.52 Hz, 3F); IR (neat) ν 2964, 1739, 1576, 1432, 1262, 1075, 949, 819, 781 cm−1; HRMS (ESI) exact mass calcd for [C19H20O4ClF3Na]+ [M + Na]+ 427.0894, found 427.0881. (Z)-4-(Chloro(phenyl)methylene)-3-methyl-1-(phenylsulfonyl)-3(2,2,2-trifluoroethyl)pyrrolidine (3o): white solid (104.3 mg, 61%); mp 65−67 °C; 1H NMR (400 MHz, CDCl3) δ 7.90−7.85 (m, 2H), 7.71−7.65 (m, 1H), 7.64−7.58 (m, 2H), 7.42−7.34 (m, 3H), 7.25− 7.19 (m, 2H), 4.18 (d, J = 15.5 Hz, 1H), 3.93 (d, J = 15.5 Hz, 1H), 3.24 (s, 2H), 2.05 (dq, J = 15.3, 11.4 Hz, 1H), 1.86 (dq, J = 15.3, 11.2 Hz, 1H), 1.17 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 140.3, 136.9, 134.9, 133.2, 129.5, 129.2, 128.8, 128.7, 128.0, 127.1, 124.3 (d, J = 277.5 Hz, CF3), 59.8 (q, J = 2.4 Hz), 53.1, 43.5 (q, J = 1.7 Hz), 40.4 (q, J = 27.3 Hz), 24.3 (d, J = 1.4 Hz); 19F NMR (376 MHz, CDCl3) δ −60.3 (t, J = 7.52 Hz, 3F); IR (neat) ν 3069, 2924, 2854, 1654, 1446, 1351, 1262, 1165, 1124, 1043, 893, 753 cm−1; HRMS (ESI) exact mass calcd for [C20H19SO2ClNF3H]+ [M + H]+ 430.0850, found 430.0862. (Z)-1-([1,1′-Biphenyl]-4-ylsulfonyl)-4-(chloro(phenyl)methylene)3-methyl-3-(2,2,2-trifluoroethyl)pyrrolidine (3p): white solid (148.0 mg, 73%); mp 108−110 °C; 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.60−7.54 (m, 2H), 7.43 (t, J = 7.4 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 7.33−7.26 (m, 3H), 7.19− 7.11 (m, 2H), 4.13 (d, J = 15.5 Hz, 1H), 3.90 (d, J = 15.5 Hz, 1H), 3.20 (s, 2H), 2.01 (dq, J = 15.1, 11.4 Hz, 1H), 1.80 (dq, J = 15.3, 11.3 Hz, 1H), 1.11 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 146.1, 140.4, 139.1, 136.9, 133.2, 129.5, 129.1, 128.8, 128.73, 128.65, 128.5, 127.8, 127.3, 127.1, 125.7 (d, J = 277.0 Hz, CF3), 59.9 (d, J = 2.5 Hz), 53.2, 43.5 (d, J = 1.7 Hz), 40.4 (q, J = 27.2 Hz, CCF3), 24.4 (d, J = 1.2 Hz); 19F NMR (376 MHz, CDCl3) δ −60.3 (t, J = 6.77 Hz, 3F); IR (neat) ν 3062, 2925, 2854, 1594, 1960, 1480, 1350, 1260, 1162, 1128, 1002, 827, 719 cm −1; HRMS (ESI) exact mass calcd for [C26H23SO2ClNF3H]+ [M + H]+ 506.1163, found 506.1171. (Z)-4-(Chloro(phenyl)methylene)-3-methyl-1-(naphthalen-2-ylsulfonyl)-3-(2,2,2-trifluoroethyl)pyrrolidine (3q): white solid (168.5 mg, 88%); mp 97−98 °C; 1H NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 8.05 (d, J = 8.3 Hz, 2H), 7.97 (d, J = 7.9 Hz, 1H), 7.87 (dd, J = 8.6, 1.7 Hz, 1H), 7.75−7.62 (m, 2H), 7.40−7.33 (m, 3H), 7.20 (dt, J = 7.5, 3.7 Hz, 2H), 4.23 (d, J = 15.5 Hz, 1H), 4.02 (d, J = 15.5 Hz, 1H), 3.32 (q, J = 9.7 Hz, 2H), 2.07 (dq, J = 15.7, 11.4 Hz, 1H), 1.87 (dq, J = 15.3, 11.3 Hz, 1H), 1.17 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 140.2, 136.8, 135.0, 132.2, 131.8, 129.43, 129.42, 129.34, 129.33, 129.0, 128.7, 128.6, 127.9, 127.7, 127.0, 125.7 (d, J = 277.3 Hz, CF3), 123.1, 59.9 (q, J = 2.3 Hz), 53.2, 43.5 (q, J = 1.7 Hz), 40.4 (q, J = 27.3 Hz, CCF3), 24.2 (d, J = 1.2 Hz); 19F NMR (376 MHz, CDCl3) δ −60.3 (t, J = 7.14 Hz, 3F); IR (neat) ν 3056, 2925, 2830, 1627, 1591, 1485, 1373, 1314, 1190, 1042, 894, 750 cm−1; HRMS (ESI) exact mass calcd for [C24H21SO2ClNF3H]+ [M + H]+ 480.1006, found 480.1007. (Z)-1-(Benzylsulfonyl)-4-(chloro(phenyl)methylene)-3-methyl-3(2,2,2-trifluoroethyl)pyrrolidine (3r): white solid (161.2 mg, 85%); mp 123−125 °C; 1H NMR (400 MHz, CDCl3) δ 7.51−7.35 (m, 8H), 7.24 (dd, J = 6.6, 2.7 Hz, 2H), 4.33 (s, 2H), 4.29−4.16 (m, 1H), 4.02 (d, J = 15.8 Hz, 1H), 3.31 (d, J = 10.3 Hz, 1H), 3.22 (d, J = 10.3 Hz, 1H), 2.00 (dq, J = 15.2, 11.4 Hz, 1H), 1.83 (dq, J = 15.4, 11.2 Hz, 1H), 1.10 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 140.5, 137.0, 130.6, 129.5, 128.93, 128.87, 128.8, 128.7, 128.6, 126.7,125.7 (d, J = 277.5 Hz, CF3), 59.9 (q, J = 2.4 Hz), 57.7, 53.2, 43.6 (q, J = 1.7 Hz), 40.3 (q, J = 27.5 Hz), 24.3 (d, J = 1.3 Hz); 19F NMR (376 MHz, CDCl3) δ −60.2 (t, J = 7.14 Hz, 3F); IR (neat) ν 2924, 2854, 1493, 1457, 1341, 1261, 1045, 891, 779 cm−1; HRMS (ESI) exact mass calcd for [C21H21SO2ClNF3H]+ [M + H]+ 444.1006, found 444.1020.

(Z)-1-(Butylsulfonyl)-3-(chloro(phenyl)methylene)-4-(2,2,2trifluoroethyl)pyrrolidine (3s): colorless gum (116.2 mg, 71%); 1H NMR (400 MHz, CDCl3) δ 7.49−7.39 (m, 3H), 7.36−7.22 (m, 2H), 4.37 (d, J = 15.7 Hz, 1H), 4.22 (d, J = 15.7 Hz, 1H), 3.53 (d, J = 10.1 Hz, 1H), 3.41 (d, J = 10.1 Hz, 1H), 3.10−3.01 (m, 2H), 2.24−2.09 (m, 1H), 1.95 (dt, J = 11.3, 9.2 Hz, 1H), 1.90−1.81 (m, 2H), 1.49 (dd, J = 14.9, 7.4 Hz, 2H), 1.20 (s, 3H), 0.98 (t, J = 7.4 Hz, 3H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 140.6, 137.0, 129.5, 128.9, 128.7, 127.0, 125.8 (d, J = 277.3 Hz, CF3), 59.5 (d, J = 2.3 Hz), 53.0, 50.2, 43.7 (q, J = 1.7 Hz), 40.5 (q, J = 27.3 Hz, CCF3), 25.1, 24.4 (d, J = 1.1 Hz), 21.6, 13.6; 19F NMR (565 MHz, CDCl3) δ −60.3 (t, J = 7.52 Hz, 3F); IR (neat) ν 2962, 2928, 2875, 1630, 1597, 1489, 1462, 1370, 1260, 1145, 1046, 893, 754 cm−1; HRMS (ESI) exact mass calcd for [C18H23SO2ClNF3H]+ [M + H]+ 410.1163, found 410.1168. (Z)-1-([1,1′-Biphenyl]-4-ylsulfonyl)-3-(chloro(phenyl)methylene)4-(2,2,2-trifluoroethyl)pyrrolidine (3t): white solid (105.1 mg, 53%); mp 112−114 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.4 Hz, 2H), 7.84−7.76 (m, 2H), 7.63 (dd, J = 5.2, 3.3 Hz, 2H), 7.53−7.46 (m, 2H), 7.46−7.40 (m, 1H), 7.38−7.31 (m, 3H), 7.30−7.22 (m, 2H), 4.15 (dd, J = 15.6, 1.6 Hz, 1H), 3.99 (d, J = 15.6 Hz, 1H), 3.49− 3.45 (m, 1H), 3.41−3.36 (m, 1H), 3.20 (s, 1H), 2.15−2.01 (m, 1H), 1.97−1.75 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 146.2, 139.0, 136.3, 135.8, 133.5, 129.5, 129.1, 128.8, 128.7, 128.5, 127.93, 127.89, 127.3, 125.7 (d, J = 276.2 Hz, CF3), 53.7, 52.4, 36.1 (q, J = 2.7 Hz), 35.8 (d, J = 27.7 Hz, CCF3); 19F NMR (376 MHz, CDCl3) δ −65.2 (t, J = 7.14 Hz, 3F); IR (neat) ν 3060, 1479, 1443, 1390, 1316, 1159, 1131, 830, 763 cm−1; HRMS (ESI) exact mass calcd for [C25H21SO2ClNF3H]+ [M + H]+ 492.1006, found 492.1003. Procedure for the Large Scale Reaction of N-(3-Phenylprop-2yn-1-yl)-N-tosylmethacrylamide 1u with Trifluoromethanesulfonyl Chloride 2. An oven-dried flask with a stir bar was charged with enynes 1u (4.0 mmol, 1.41 g), trifluoromethanesulfonyl chloride 2 (1.35 mg, 8.0 mmol), K2HPO4·H2O (4.56 g, 20.0 mmol), Acr+-Mes· ClO4 (62.0 mg, 0.02 mmol) and was sealed with a rubber stopper, evacuated, and backfilled with argon three times; then dry DCM (20.0 mL) as asolvent was added. The tube was then irradiated by a 23 W fluorescent bulb for 12 h under room temperature and with stirring. After the enyne 1u was completely consumed (monitored by TLC), the reaction mixture was evaporated under reduced pressure and then purified by flash column chromatography on silica gel (EtOAc/ petroleum ether 1:20) to give 1.39 g (76% yield) of (Z)-4(chloro(phenyl)methylene)-3-methyl-1-tosyl-3-(2,2,2-trifluoroethyl)pyrrolidin-2-one (3u): white solid; mp 108−110 °C; 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 8.3 Hz, 2H), 7.44−7.38 (m, 3H), 7.36 (d, J = 8.2 Hz, 2H), 7.28 (dd, J = 6.6, 2.9 Hz, 2H), 4.82 (d, J = 15.4 Hz, 1H), 4.46 (d, J = 15.4 Hz, 1H), 2.45 (s, 3H), 2.41−2.26 (m, 1H), 2.06−1.89 (m, 1H), 1.10 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 173.8, 145.7, 136.4, 133.9, 130.8, 130.0, 129.7, 129.6, 128.9, 128.7, 128.3, 124.9 (d, J = 277.0 Hz, CF3), 50.3, 46.5 (d, J = 2.3 Hz), 41.2 (d, J = 27.3 Hz, CH2CF3), 25.7, 21.7; 19F NMR (376 MHz, CDCl3) δ −62.3 (t, J = 6.34 Hz, 3F); IR (neat) ν 2963, 1745, 1651, 1558, 1507, 1457, 1261, 1090, 1022, 802, 704 cm−1; HRMS (ESI) exact mass calcd for [C21H19SO3ClNF3H]+ [M + H]+ 458.0799, found 458.0798. General Procedure for the Chlorotrichloromethylative Cyclizations of Enynes. An oven-dried reaction tube with a stir bar was charged with enynes 1 (0.40 mmol, 1.0 equiv), trichloromethanesulfonyl chloride 4 (174.3 mg, 0.80 mmol), K2HPO4·3H2O (456.4 mg, 2.00 mmol), and Ir(dtbbpy)(ppy)2PF6 (3.7 mg, 0.004 mmol) and was sealed with a rubber stopper, evacuated, and backfilled with argon three times; then dry DCM (4.0 mL) as a solvent was added. The tube was then immersed sideways into a sand bath under room temperature and irradiated by a 23 W fluorescent bulb for 5−12 h with stirring. After enynes 1 were completely consumed (monitored by TLC), the crude mixture was directly purified by flash column chromatography on silica gel (EtOAc/petroleum ether 1:20) to give the desired products 5a−5f. (Z)-4-(Chloro(4-methoxyphenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trichloroethyl)pyrrolidine (5a): colorless gum (186.1 mg, 89%); 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 6.81 (d, J = 7.7 Hz, 7514

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

Note

The Journal of Organic Chemistry

(CDCl3, 100 MHz) δ 173.3, 145.8, 136.8, 133.6, 130.4, 130.2, 129.7, 129.6, 128.8, 128.7, 128.6, 95.4, 60.8, 51.2, 50.0, 26.3, 21.8; IR (neat) ν 1742, 1596, 1459, 1372, 1296, 1235, 1176, 1115, 849, 791, 760 cm−1; HRMS (ESI) exact mass calcd for [C21H19SO3Cl4NH]+ [M + H]+ 507.9883, found 507.9896. Procedure for the Chlorotrifluormethylative Cyclizations of 4Methyl-N-(3-methylbut-2-en-1-yl)-N-(3-phenylprop-2-yn-1-yl)benzenesulfonamide. An oven-dried reaction tube with a stir bar was charged with 4-methyl-N-(3-methylbut-2-en-1-yl)-N-(3-phenylprop2-yn-1-yl)benzenesulfonamide 6 (0.40 mmol, 1.0 equiv), trifluoromethanesulfonyl chloride 2 (134.8 mg, 0.80 mmol), K2HPO4·3H2O (456.4 mg, 2.00 mmol), and Acr+-Mes·ClO4 (6.2 mg, 0.02 mmol) and was sealed with a rubber stopper, evacuated, and backfilled with argon three times; then dry DCM (4.0 mL) as a solvent was added. The tube was then immersed sideways into a sand bath under room temperature and irradiated by 23 W fluorescent bulb for 12 h with stirring. After the enyne 6 was completely consumed (monitored by TLC), the crude mixture was directly purified by flash column chromatography on silica gel (EtOAc/petroleum ether 1:20) to give the desired products 7 and 7′. 3-(2-Chloropropan-2-yl)-4-phenyl-1-tosyl-5-(trifluoromethyl)1,2,3,6-tetrahydropyridine (7): white solid (62.3 mg, 34%); mp 155− 157 °C; 1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 7.9 Hz, 2H), 7.30 (s, 3H), 7.13 (s, 2H), 4.48 (d, J = 12.2 Hz, 1H), 4.24 (d, J = 17.1 Hz, 1H), 3.31 (d, J = 17.1 Hz, 1H), 3.03 (s, 1H), 2.55 (dd, J = 12.3, 3.5 Hz, 1H), 2.44 (s, 3H), 1.68 (s, 3H), 1.42 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.3, 143.8 (d, J = 3.1 Hz), 139.4, 131.6, 129.9, 128.3, 128.0, 127.9, 124.9 (q, J = 27.3 Hz, CH2CF3), 122.6 (q, J = 274.7 Hz, CF3), 72.3, 53.2, 45.9, 44.2 (q, J = 4.5 Hz), 33.6, 31.4, 21.5; 19F NMR (376 MHz, CDCl3) δ − 57.8 (s, 3F); IR (neat) ν 2924, 2851, 1660, 1594, 1455, 1336, 1177, 1105, 944, 826, 672 cm −1 ; HRMS (ESI) exact mass calcd for [C22H23SO2ClNF3H]+ [M + H]+ 458.1163, found 458.1184. (Z)-3-(Chloro(phenyl)methylene)-4,4-dimethyl-1-tosyl-5(trifluoromethyl)piperidine (7′): white solid (99.2 mg, 54%); mp 161−163 °C; 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.32 (dd, J = 6.1, 2.8 Hz, 3H), 7.18 (s, 2H), 4.55 (dt, J = 14.6, 3.3 Hz, 1H), 3.90 (dd, J = 14.6, 6.8 Hz, 1H), 3.67−3.54 (m, 1H), 3.36 (dd, J = 12.7, 4.5 Hz, 1H), 2.47 (s, 3H), 2.28−2.13 (m, 1H), 1.09 (s, 3H), 0.87 (d, J = 1.4 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.0, 140.3, 133.9, 133.2, 129.9, 129.8, 128.2, 128.48, 128.1, 127.7,126.2 (d, J = 281.8 Hz, CF3), 49.6 (q, J = 23.4 Hz, CH2CF3), 47.2, 41.8 (q, J = 4.4 Hz), 38.6, 29.7, 26.7, 21.5; 19 F NMR (376 MHz, CDCl3) δ − 61.7 (d, J = 3.76 Hz, 3F); IR (neat) ν 2942, 2862, 1643, 1548, 1440, 1261, 1021, 967, 843 cm−1; HRMS (ESI) exact mass calcd for [C22H23SO2ClNF 3H]+ [M + H]+ 458.1163, found 458.1162.

2H), 4.01 (d, J = 14.8 Hz, 1H), 3.81 (d, J = 15.3 Hz, 1H), 3.73 (s, 3H), 3.65 (d, J = 9.5 Hz, 1H), 3.14 (d, J = 9.5 Hz, 1H), 2.81 (d, J = 15.6 Hz, 1H), 2.66 (d, J = 15.7 Hz, 1H), 2.39 (s, 3H), 1.18 (s, 3H); 13 C{1H} NMR (CDCl3, 100 MHz) δ 160.0, 144.0, 140.5, 131.2, 130.2, 129.8, 129.1, 128.0, 126.9, 113.9, 96.6, 59.4, 59.0, 55.3, 53.4, 47.0, 25.6, 21.6; IR (neat) ν 2934, 1605, 1509, 1458, 1351, 1292, 1251, 1163, 1094, 1033, 834, 800 cm−1; HRMS (ESI) exact mass calcd for [C22H23SO3Cl4NH]+ [M + H]+ 524.0196, found 524.0205. (Z)-4-(Chloro(thiophen-2-yl)methylene)-3-methyl-1-tosyl-3(2,2,2-trichloroethyl)pyrrolidine (5b): colorless gum (111.3 mg, 56%); 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.5 Hz, 2H), 7.45−7.31 (m, 3H), 7.10−6.93 (m, 2H), 4.12 (d, J = 15.8 Hz, 1H), 3.87 (d, J = 15.8 Hz, 1H), 3.71 (d, J = 9.5 Hz, 1H), 3.30 (d, J = 9.5 Hz, 1H), 2.96 (d, J = 15.6 Hz, 1H), 2.86 (d, J = 15.8 Hz, 1H), 2.47 (s, 3H), 1.38 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.7, 144.2, 137.4, 131.2, 129.9, 129.4, 128.3, 128.1, 126.8, 119.7, 96.6, 59.7, 58.4, 53.8, 47.6, 25.4, 21.6; IR (neat) ν 1597, 1452, 1351, 1236, 1163, 1093, 1044, 908, 864, 814 cm−1; HRMS (ESI) exact mass calcd for [C19H19S2O2Cl4NH]+ [M + H]+ 499.9655, found 499.9679. (Z)-4-(Chloro(4-chlorophenyl)methylene)-3-methyl-1-tosyl-3(2,2,2-trichloroethyl)pyrrolidine (5c): colorless gum (164.1 mg, 78%); 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 7.7 Hz, 2H), 7.39 (t, J = 8.5 Hz, 4H), 7.22 (d, J = 7.7 Hz, 2H), 4.09 (d, J = 15.4 Hz, 1H), 3.92 (d, J = 15.4 Hz, 1H), 3.78 (d, J = 9.6 Hz, 1H), 3.19 (d, J = 9.6 Hz, 1H), 2.89 (d, J = 15.7 Hz, 1H), 2.72 (d, J = 15.7 Hz, 1H), 2.47 (s, 3H), 1.24 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.2, 141.4, 135.5, 135.4, 131.2, 129.8, 129.0, 128.1, 125.4, 96.3, 59.3, 59.1, 53.5, 47.1, 25.7, 21.6; IR (neat) ν 1593, 1488, 1351, 1163, 1092, 1047, 896, 798 cm−1; HRMS (ESI) exact mass calcd for [C21H20SO2Cl5NH]+ [M + H]+ 527.9701, found 527.9734. (Z)-Methyl 4-(Chloro(4-methyl-1-tosyl-4-(2,2,2-trichloroethyl)pyrrolidin-3-ylidene)methyl)benzoate (5d): colorless gum (151.6 mg, 70%); 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.8 Hz, 2H), 7.68 (d, J = 7.7 Hz, 2H), 7.31 (dd, J = 13.7, 7.9 Hz, 4H), 4.08−3.94 (m, 1H), 3.87 (d, J = 15.2 Hz, 4H), 3.70 (d, J = 9.7 Hz, 1H), 3.12 (d, J = 9.6 Hz, 1H), 2.80 (d, J = 15.7 Hz, 1H), 2.63 (d, J = 15.7 Hz, 1H), 2.40 (s, 3H), 1.17 (d, J = 7.0 Hz, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 166.0, 141.4, 135.5, 135.4, 131.2, 129.8, 129.0, 128.1, 125.4, 96.3, 59.3, 59.1, 53.5, 47.1, 25.7, 21.6; IR (neat) ν 2952, 1726, 1601, 1438, 1352, 1278, 1163, 1097, 1048, 815, 757 cm−1; HRMS (ESI) exact mass calcd for [C23H23SO4Cl4NH]+ [M + H]+ 550.0175, found 549.9541. (Z)-4-(1-Chloroethylidene)-3-methyl-1-tosyl-3-(2,2,2trichloroethyl)pyrrolidine (5e): colorless gum (134.2 mg, 79%); 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 2H), 7.38 (d, J = 7.5 Hz, 2H), 3.89 (d, J = 14.5 Hz, 1H), 3.83 (d, J = 9.7 Hz, 1H), 3.77 (d, J = 13.5 Hz, 1H), 3.11 (s, 2H), 3.00 (d, J = 9.8 Hz, 1H), 2.46 (s, 3H), 2.20 (s, 3H), 1.53 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.1, 138.0, 131.2, 129.8, 128.1, 126.3, 96.9, 61.4, 59.2, 53.3, 46.6, 23.0, 22.5, 21.6; IR (neat) ν 2927, 1597, 1455, 1351, 1164, 1094, 1049, 815, 706 cm −1; HRMS (ESI) exact mass calcd for [C16H19SO2Cl4NH]+ [M + H]+ 431.9934, found 431.9934 (Z)-Dimethyl (E)-4-(Chloro(phenyl)methylene)-3-methyl-3-(2,2,2trichloroethyl)cyclopentane-1,1-dicarboxylate (5f): colorless gum (149.0 mg, 82%); 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 6.2 Hz, 3H), 7.30 (d, J = 6.6 Hz, 2H), 3.78 (s, 3H), 3.76 (s, 3H), 3.65 (d, J = 18.2 Hz, 1H), 3.22 (d, J = 13.9 Hz, 1H), 3.13 (d, J = 18.2 Hz, 1H), 2.78 (d, J = 15.7 Hz, 1H), 2.68 (d, J = 15.7 Hz, 1H), 2.57 (d, J = 14.0 Hz, 1H), 1.16 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 172.1, 171.9, 144.3, 138.0, 129.3, 128.9, 128.5, 126.3, 97.2, 60.7, 56.9, 53.2, 53.0, 47.4, 47.0, 41.8, 28.1; IR (neat) ν 2954, 1738, 1573, 1437, 1262, 1203, 1071, 948, 879, 781 cm−1; HRMS (ESI) exact mass calcd for [C19H20O4Cl4H]+ [M + H]+ 455.0159, found 455.0142. (Z)-4-(Chloro(phenyl)methylene)-3-methyl-1-tosyl-3-(2,2,2trichloroethyl)pyrrolidin-2-one (5g): colorless gum (163.9 mg, 81%); 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.5 Hz, 2H), 7.31 (d, J = 7.7 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 6.81 (d, J = 7.7 Hz, 2H), 4.01 (d, J = 14.8 Hz, 1H), 3.81 (d, J = 15.3 Hz, 1H), 3.73 (s, 3H), 3.65 (d, J = 9.5 Hz, 1H), 3.14 (d, J = 9.5 Hz, 1H), 2.81 (d, J = 15.6 Hz, 1H), 2.66 (d, J = 15.7 Hz, 1H), 2.39 (s, 3H), 1.18 (s, 3H); 13C{1H} NMR

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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.9b00842. Experimental methods and preparation, NMR spectra, and X-ray data (PDF) Crystal data for 3p (CIF) Crystal data for 7 (CIF) Crystal data for 7′ (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. *E-mail: [email protected]. ORCID

Hong Hou: 0000-0002-9103-9888 Chaoguo Yan: 0000-0002-2777-9582 Shaoqun Zhu: 0000-0003-2639-4098 7515

DOI: 10.1021/acs.joc.9b00842 J. Org. Chem. 2019, 84, 7509−7517

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The Journal of Organic Chemistry Notes

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The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This project was supported by the National Natural Science Foundation of China (21602085 and 21702179), the National Natural Science Foundation of Jiangsu Province (BK20160551), and the Priority Academic Program Development of Jiangsu Higher Education Institutions and Project supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (17KJB150042). We also thank the Testing Centre of Yangzhou University for the sample analysis.

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