Lewis acid-promoted cascade reaction for the synthesis of Michael acceptors and its application in a dimerization reaction.

An efficient Lewis acid-promoted cascade reaction with dimethyl sulfoxide as a methylene source for the synthesis of Michael acceptors is reported. The key to developing this procedure is the selection of a mild base to modulate the equilibrium of various intermediates in order to drive the reaction forward to the formation of Michael acceptor and dimeric compound products. Extensive studies were performed to gain insight into a possible reaction mechanism.

Introduction

Molecules containing various Michael acceptor scaffolds are common in pharmaceuticals, agrochemicals and natural products and have attracted considerable attention from organic chemists and medicinal chemists. Michael acceptors have been found to have various different biological activities, such as antibacterial, anticancer and antiviral activities. For example, the crystal structure of HCoV-NL63 MPro complexed with a Michael acceptor inhibitor was obtained, providing insight into the rational development of wide spectrum antiviral therapeutics to treat infections caused by human coronaviruses. Two Michael acceptors used as cysteine protease inhibitors, K-777 (CRA-3316) and rupintrivir (AG7088), and developed to treat Chagas disease and as an antirhinoviral agent, respectively, are already in clinical trials. On the other hand, as basic building blocks Michael acceptors have been extensively employed in the area of organic chemistry, such as in multicomponent cascade or Domino reactions, transition-metal catalyzed reactions, enantioselective organocatalysis and complex natural product synthesis.

In the textbook of graduate students, dimethyl sulfoxide (DMSO) is described as a high-boiling, protic and low-toxicity solvent, and a widely used oxidant in several named reactions, such as the Swern oxidation and Pftizner-Moffatt oxidation. In the past few decades, the nature of DMSO has been further exploited as a reagent that can act as an oxygen source, a carbon source and a sulfur source. However, the reaction scope of DMSO is still limited and needs to be expanded. To date, a cascade reaction with DMSO as both a solvent and one-carbon source for the preparation of Michael acceptors has not been reported.

Herein, we report a Lewis acid-promoted cascade reaction for the synthesis of α,β-unsaturated amides. The proper choice of base in the reaction results in the production of dimeric compounds. The Pummerer rearrangement with DMSO as a methylene source is believed to be an initial step for the reaction based on mechanistic studies.

Results and discussion

We are focused on C(sp)−H bond functionalization reactions. In this project, the C(sp)−H bond functionalization in amide substrate 1a was tested under the following reaction conditions: CoCl2 (1.5 equiv), KOAc (2.0 equiv) and AgOAc (2.0 equiv) dissolved in DMSO (2.0 mL) in a microwave and heated at 150 °C for 2 h. To our delight, functionalization at the benzylic position occurred as expected, affording α, β-unsaturated carboxylamide 2a in a 23% yield (Table 1 , entry 1). Control experiments showed that this reaction proceeded with similar results in the absence of AgOAc, while the reaction did not occur without KOAc (Table 1, entries 2–4). Then, various Lewis acids were screened in this reaction (Table 1, entries 5–9). When one equivalent of PbCl2 was used as the Lewis acid, the yield of product 2a increased to 55% along with some amount of sulfide product 3a (Table 1, entry 9). The effect of the base on the reaction was screened with various bases. The results of this screening indicated that potassium acetate and sodium acetate are the most favorable bases for this reaction (Table 1, entries 9–11 and details in supporting information). When the reaction was carried out in air or under O2 atmosphere, the yield of product decreased (Table 1, entries 12–13). In contrast, under N2, the reaction afforded product 2a in a 65% yield (Table 1, entries 14). This indicated that the oxidizing reagents hindered the reaction from proceeding. The effect of temperature on the reaction was subsequently investigated, which showed that temperatures either above 160 °C or below 150 °C were not suitable for this reaction (Table 1, entries 14–17). Finally, optimized reaction conditions of PbCl2 (1.5 equiv) and KOAc (1.5 equiv) in DMSO at 156 °C in a sealed tube under N2 for 13 h gave the product 2a in 77% yield and 3a in 12% yields, respectively (Table 1, entry 17). Interestingly, when Ac2O was used instead of PbCl2, sulfide product 3a was obtained in 50% yield (Table 1, entry 18). The combination of Ac2O/AcOH, or Ac2O/TsOH, or TFAA/TFA in DMSO, commonly used in the Pummerer rearrangement reaction, did not afford any product.

Table 1

Optimization of reaction conditions.a,b

Entry	Lewis acid	Base	Additive (equiv)	Temp (oC)	Product (%)
					2a	3a
1	CoCl2	KOAc	AgOAc/2	150	23	–
2	–	KOAc	AgOAc/2	150	12	8
3	CoCl2	–	AgOAc/2	150	trace	–
4	CoCl2	KOAc	–	150	24	–
5	CoF2	KOAc	–	150	26	6
6	CoBr2	KOAc	–	150	20	6
7	ZnCl2	KOAc	–	150	30	9
8	MnCl2	KOAc	–	150	23	7
9	PbCl2	KOAc	–	150	55	18
10	PbCl2	NaOAc	–	150	55	14
11	PbCl2	KHCO3	–	150	10	–
12c	PbCl2	KOAc	–	150	33	21
13d	PbCl2	KOAc	–	150	trace	–
14e	PbCl2	KOAc	–	150	65	18
15e	PbCl2	KOAc	–	160	48	26
16e	PbCl2	KOAc	–	156	66	14
17e	PbCl2	KOAc	–	156	77	12
18	Ac2O	KOAc	–	156	–	50

Entry 1–11 was conducted in microwave for 2 h, entry 12–18 was conducted in sealed tube for 13 h. Isolated yields.

Lewis acid (1.0 equiv) was used in entry 9–16.

The reaction was carried out in air.

The reaction was carried out under O2.

The reaction was carried out under N2.

The coexistence of products 2a and 3a throughout the process of optimizing the reaction conditions stimulated us to investigate the mechanism of this reaction. Several experiments concerning the study of the mechanism were conducted (eqs. (1)–(4)). Isolated sulfide 3a was subjected to the standard reaction conditions, affording product 2a in 75% yield with 22% recovery of 3a (eq. (1)). When purified 2a was put back under the standard conditions, it gave 17% yield of 3a with 74% recovery of 2a. These results indicated that there is an equilibrium between 2a and 3a in the reaction mixture. When the reaction was carried out in DMSO-d 6, it provided the corresponding deuterated products (d -2a and d -3a) in 73% and 9% yields, respectively, which provided precise evidence for the methylene group originating from the solvent dimethylsulfoxide (eq. (3)). When six equivalents of TMPO was added to a reaction run under the reaction conditions, 53% of 2a and 5% of 3a were still obtained, which suggested that this reaction probably did not involve any radical species (eq. (4)). Moreover, two control experiments showed that both Lewis acid PbCl2 and KOAc are necessary for the reaction to occur (see the supporting information).

Based on these preliminary results and some leading references on the Pummerer rearrangement reaction, a rational mechanism for this reaction is proposed in Scheme 1 . A sulfur-substituted carbocation is obtained through promotion by both the Lewis acid (PbCl2) and base (KOAc), and it then reacts with a carbon nucleophile to afford α-substituted sulfide 3a. There is an equilibrium between 3a and 2a in the reaction mixture. Michael acceptor product 2a is afforded by an elimination reaction of 3a affected by the base (KOAc). Meanwhile, 2a undergoes a Michael addition reaction to afford 3a. Furthermore, another Michael addition reaction proceeds with 2a through the attack of a carbon nucleophile to afford 4a.

Scheme 1

Possible mechanism.

With the optimized conditions in hand, we next explored the effect on the reaction of substitution on the phenyl ring. The results are summarized in Table 2 . Generally, electron-donating groups on the phenyl ring under our standard conditions led to good to excellent combined yields of products 2a-o and 3a-o (Table 2). This reaction tolerated mono-, di- or even tri-substituted patterns on the phenyl ring. Interestingly, a substrate with a heterocycle instead of a phenyl ring, such as thiofuran, afforded the corresponding product (2o) in a synthetically useful yield (Table 2). When substrates with electron-withdrawing groups on the phenyl rings were subjected to the standard reaction conditions, they gave low yields of the corresponding products. After an exploration of the types and amounts of bases, it was found that decreasing the amount of KOAc to 0.6 equivalent led to good yields of 2p-x and 3p-x with the concomitant production of dimeric compounds 4p-v (Table 3 ). The reaction tolerated many electron-withdrawing groups on the phenyl rings, such as F, Cl, Br, I, OCF3 and SCF3.

Table 2

Substrate scope with the electron-donating groups on the phenyl ring.a

Table 3

Substrate scope with the electron-withdrawing groups on the phenyl ring.a

The substrate scope with different phenyl amine groups was subsequently investigated (Table 4 ). In general, electron-withdrawing groups on the phenyl amine rings promoted the reaction, probably due to the easy formation of a carbon anion at the benzylic position of these substrates in the reaction mixture. In the case of substrates bearing alkylamines being used as the amide component, the reaction did not work at all.

Table 4

The effect on the reaction of substituents on the phenyl amine ring.a

After an extensive screening of many different bases, KHCO3 was identified to be the optimal one for producing a set of dimeric products (4a, 4l-m, 4o-x) in synthetically useful yields, probably because the mild basicity of KHCO3 modulates the equilibrium between the intermediates, such as the sulfur-substituted carbocation, carbon nucleophile, α-substituted sulfide 3a and Michael acceptor 2a, all of which exist in the reaction mixture, to directly push the reaction forward to the formation of dimeric compounds (Table 5 ). Unfortunately, in the case of substrates with electron-donating groups on the phenyl ring, the reaction was unable to afford any of the corresponding dimeric products, regardless of the kind of base used.

Table 5

The effect of base on the production of dimeric compounds 4.a

Conclusion

In conclusion, we have studied a Lewis acid-promoted cascade reaction with dimethyl sulfoxide as a methylene source for the synthesis of α,β-unsaturated amides. The reaction proceeds with a wide substrate scope under mild conditions and with inexpensive reagents. The identity of both the Lewis acid and base were found to be critical for this reaction to proceed well. Extensive studies provide insight into a possible mechanism, leading to the belief that the Pummerer rearrangement with dimethyl sulfoxide as a methylene source is an initial step.

Experimental section

General techniques

All melting points are uncorrected. Preparative chromatographic separations were performed on silica gel (300–400 mesh). Reactions were followed by TLC analysis using silica plates with a fluorescent indicator (254 nm) and visualized with a UV lamp. 1H and 13C NMR spectra were recorded in Fourier transform mode at the field strength specified on a 400, or 600 MHz spectrometer. Spectra were obtained on CDCl3 solution in 5 mm diameter tubes, and chemical shifts in ppm (part per million) are quoted relative to the residual signals of chloroform (δ H 7.26 ppm, or δ C 77.00 ppm). J values are given in hertz. IR spectra were measured for samples as KBr pellets in a FT-IR spectrophotometer. High resolution mass spectra (HRMS) were measured at 70 eV using a double focusing magnetic sector mass analyzer with an EI source or ESI source. 2-Phenyl-N-[2-(trifluoromethoxy) phenyl]acetamides (1a-1x, 1aa-1ae and 1ba-1bc) were prepared according to the literature procedure.13a Among them, substrates 1aa, 1ad and 1ae were known.

General procedure for the preparation of 2-phenyl-N-[2-(trifluoromethoxy) phenyl]

Acetamides (1a-1x, 1ab, 1ac and 1ba-1bc). To a solution of 2-phenylacetic acid (7.0 mmol), 2-(trifluoromethoxy)aniline (7.7 mmol) in anhydrous CH2Cl2 (25 mL) were added EDCI (1.745 g, 9.1 mmol) and DMAP (256.6 mg, 2.1 mmol). The reaction mixture was stirred at room temperature overnight, diluted with HCl (1 M) aqueous solution, and extracted with CH2Cl2 (3 × 25 mL). The combined organic phase was washed with saturated NaHCO3 aqueous solution and brine, dried over anhydrous Na2SO4, and concentrated under vacuum. Purification by flash chromatography (Silica gel, petroleum ether: ethyl acetate = 50: 1 as eluent) gave the corresponding 2-phenyl-N-[2-(trifluoromethoxy)phenyl]acetamide compound.

2-Phenyl White solid; mp 85–86 °C; 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.1 Hz, 1 H), 7.60–7.30 (m, 6 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.16 (d, J = 8.2 Hz, 1 H), 7.10–7.01 (m, 1 H), 3.79 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 169.0, 137.9, 133.7, 130.5, 129.6, 129.4, 128.0, 127.5, 124.2, 120.2 (q, J C-F = 257.8 Hz), 121.4, 120.5 (d, J C-F = 0.6 Hz), 45.1; 19F NMR (376 MHz, CDCl3) δ −58.11; HRMS (EI) Calculated for C15H12F3NO2 [M+]:295.0820, found 295.0819; IR (KBr) ν(cm−1): 3408, 3295, 1665, 1607, 1532, 1456,1264, 1168, 1104.

2-( White solid; mp 65–66 °C; 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.1 Hz, 1 H), 7.51 (br, 1 H), 7.31 (t, J = 7.5 Hz, 1 H), 7.29–7.23 (m, 1 H), 7.21–7.10 (m, 4 H), 7.08–7.03 (m, 1 H), 3.75 (s, 2 H), 2.37 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 169.2, 139.3, 137.8 (d, J C-F = 1.3 Hz), 133.6, 130.6, 130.2, 129.3, 128.7, 127.5, 126.6, 124.1, 121.4, 120.5 (d, J C-F = 0.8 Hz), 120.2 (q, J C-F = 257.8 Hz), 45.0, 21.2; 19F NMR (376 MHz, CDCl3) δ −58.22; HRMS (EI) Calculated for C16H14F3NO2 [M+]: 309.0977, found 309.0971; IR (KBr) ν(cm−1): 3405, 3301, 1697, 1677, 1610, 1531, 1490, 1453,1313, 1254, 1176, 1106.

2-(3-Methoxyphenyl): White solid; mp 91–92 °C; 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.2 Hz, 1 H), 7.54 (br s, 1 H), 7.34 (t, J = 7.9 Hz, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.16 (d, J = 8.2 Hz, 1 H), 7.09–7.03 (m, 1 H), 6.94–6.88 (m, 2 H), 6.86 (s, 1 H), 3.82 (s, 3 H), 3.76 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.9, 160.4, 137.9, 135.2, 130.6, 127.5, 124.2, 121.7, 121.4, 120.5 (d, JC-F = 0.7 Hz), 120.2 (q, JC-F = 257.9 Hz), 115.1, 113.5, 100.0, 55.2, 45.1; 19F NMR (376 MHz, CDCl3) δ −58.16; HRMS (EI) Calculated for C16H14F3NO3 [M+]: 325.0926, found 325.0947; IR (KBr) ν(cm-1): 3405, 3267, 1666, 1608, 1587, 1533, 1491, 1454, 1302, 1248.

2-( White solid; mp 91–92 °C;1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.0 Hz, 1 H), 7.49 (br s, 1 H), 7.29–7.18 (m, 5 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.08–7.01 (m, 1 H),3.74 (s, 2 H), 2.37 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 169.4, 137.84, 137.81, 130.62, 130.59, 130.1, 129.4, 127.5, 124.1, 121.3, 120.4 (d, J C-F = 1.0 Hz), 120.2 (q, J C-F = 257.9 Hz), 44.6, 21.0; 19F NMR (376 MHz, CDCl3) δ −58.19; HRMS (EI) Calculated for C16H14F3NO2 [M+]: 309.0977, found 309.0981; IR (KBr) ν(cm−1): 3405, 3268,1669,1609, 1536,1454,1265, 1210, 1188, 1166.

2-(4-Isopropylphenyl) White solid; mp 57–58 °C; 1H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 8.0 Hz, 1 H), 7.52 (br s, 1 H), 7.45–7.20 (m,5 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.08–7.02 (m, 1 H), 3.76 (s, 2 H), 2.99–2.87 (m, 1 H), 1.26 (d, J = 6.9 Hz, 6 H); 13C NMR (100 MHz, CDCl3) 169.4, 148.8, 137.78, 137.77, 130.9, 130.6, 129.5, 127.5, 124.0, 121.2, 120.5 (d, J C-F = 0.8 Hz), 120.2 (q, J C-F = 257.8 Hz), 44.6, 33.8, 23.8; 19F NMR (376 MHz, CDCl3) δ −58.12; HRMS (EI) Calculated for C18H18F3NO2 [M+]: 337.1290, found 337.1287; IR (KBr) ν(cm−1): 3406, 2963, 2931, 1698, 1680, 1610, 1530,1453,1253, 1176.

2-[4-( Yellow oil;1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 8.2 Hz, 1 H), 7.52 (br s, 1 H), 7.46 (d, J = 8.2 Hz, 2 H), 7.32–7.22 (m, 3 H), 7.19–7.12 (m, 1 H), 7.09–7.02 (m, 1 H), 3.77 (s, 2 H), 1.34 (s, 9 H); 13C NMR (100 MHz, CDCl3) 169.4, 151.1, 137.8, 130.63, 130.58, 129.3, 127.5, 126.4, 124.0, 121.2, 120.5 (d, J C-F = 1.0 Hz), 120.2 (q, J C-F = 258.1 Hz), 44.5, 34.5, 31.2; 19F NMR (376 MHz, CDCl3) δ −58.10; HRMS (EI) Calculated for C19H20F3NO2 [M+]: 351.1446, found 351.1450; IR (KBr) ν(cm−1): 3405, 3325, 3268,1686, 1668, 1610, 1532,1453,1254.

2-(4-Butoxyphenyl) Yellow solid; mp 86–88 °C; 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.1 Hz, 1 H), 7.51 (br s, 1 H), 7.28–7.20 (m, 3 H), 7.16 (d, J = 8.2 Hz, 1 H), 7.08–7.02 (m, 1 H), 6.94 (d, J = 8.5 Hz, 2 H), 3.98 (t, J = 6.5 Hz, 2 H), 3.72 (s, 2 H), 1.82–1.73 (m, 2 H), 1.57–1.45 (m, 2 H), 0.98 (t, J = 7.4 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 169.6, 159.0, 137.9 (d, J C-F = 1.1 Hz), 130.7, 130.6, 127.5, 125.4, 124.1, 121.3, 120.4, 120.3 (q, J C-F = 257.9 Hz), 115.5, 67.8, 44.2, 31.2, 19.2, 13.8; 19F NMR (376 MHz, CDCl3) δ −58.08; HRMS (EI) Calculated for C19H20F3NO3 [M+]: 367.1395, found 367.1390; IR (KBr) ν(cm−1): 3440, 3404, 3306,1667, 1609, 1529, 1514, 1455,1262, 1212, 1167.

2-(4-Phenoxyphenyl) White solid; mp 56–58 °C;1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.2 Hz, 1 H), 7.51 (br s, 1 H), 7.34 (t, J = 7.5 Hz, 2 H), 7.30–7.23 (m, 3 H), 7.17 (d, J = 7.7 Hz, 1 H), 7.11 (t, J = 7.4 Hz, 1 H), 7.08–6.99 (m, 4 H), 3.74 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 169.1, 157.3, 156.7, 137.9, 131.0, 130.5, 129.8, 128.2, 127.6, 124.2, 123.6, 121.4, 120.5, 120.3 (q, J C-F = 257.9 Hz), 119.4, 119.2, 44.2; 19F NMR (376 MHz, CDCl3) δ −57.95; HRMS (EI) Calculated for C21H15F4NO3 [M+]: 387.1082, found 387.1076; IR (KBr) ν(cm−1): 3312, 1672, 1609, 1592, 1531, 1507, 1489, 1453, 1433, 1356, 1249, 1196, 1165, 1106, 1073, 875, 845, 759, 692.

2-[(1,1′-Biphenyl)-4-yl] Yellow solid; mp 99–100 °C;1H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 8.2 Hz, 1 H), 7.64 (d, J = 8.0 Hz, 2 H), 7.59 (d, J = 7.5 Hz, 2 H), 7.54 (br, 1 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.42–7.34 (m, 3 H), 7.26 (t, J = 7.3 Hz, 1 H), 7.16 (d, J = 8.2 Hz, 1 H), 7.09–7.02 (m, 1 H), 3.83 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 169.0, 141.1, 140.5, 137.9, 132.7, 130.5, 130.0, 128.8, 128.2, 127.6, 127.5, 127.1, 124.2, 121.4, 120.5, 120.2 (q, J C-F = 257.9 Hz), 44.6; 19F NMR (376 MHz, CDCl3) δ −58.05; HRMS (EI) Calculated for C21H16F3NO2 [M+]: 371.1133, found 371.1131; IR (KBr) ν(cm−1): 3405, 3293, 3283, 3197, 1665, 1609, 1534, 1489, 1454, 1259, 1188, 1170.

2-(3,5-Dimethylphenyl) White solid; mp 97–98 °C;1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.2 Hz, 1 H), 7.53 (br s, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.08–7.02 (m, 1 H),7.00 (s, 1 H), 6.94 (s, 2 H), 3.71 (s, 2 H), 2.33 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 169.3, 139.2, 137.8, 133.5, 130.7, 129.5, 127.5, 127.3, 124.0, 121.3, 120.5, 120.2 (q, J C-F = 257.6 Hz), 45.0, 21.1; 19F NMR (376 MHz, CDCl3) δ −58.30; HRMS (EI) Calculated for C17H16F3NO2 [M+]: 323.1133, found 323.1140; IR (KBr) ν(cm−1): 3402, 3295, 1668, 1608, 1532, 1450, 1356, 1290, 1261, 1209, 1174.

2-(3,5-Dimethoxyphenyl) White solid; mp 114–116 °C;1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.0 Hz, 1 H), 7.61 (br s, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.16 (d, J = 8.2 Hz, 1 H), 7.09–7.01 (m, 1 H), 6.48–6.44 (m, 3 H), 3.80 (s, 6 H), 3.71 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.8, 161.7, 137.9, 135.8, 130.6, 127.6, 124.2, 121.3, 120.5, 120.3 (d, J C-F = 258.0 Hz), 107.5, 99.8, 55.3, 45.3; 19F NMR (376 MHz, CDCl3) δ −58.21; HRMS (EI) Calculated for C17H16F3NO4 [M+]: 355.1031, found 355.1036; IR (KBr) ν(cm−1): 3441, 3403, 3263, 1665, 1608, 1596, 1536, 1457, 1318, 1299, 1267, 1212, 1190, 1158.

2-(3-Fluoro-4-methoxyphenyl) White solid; mp 91–92 °C;1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.2 Hz, 1 H), 7.48 (br s, 1 H), 7.26 (t, J = 7.8 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H), 7.10–6.97 (m, 4 H), 3.90 (s, 3 H), 3.70 (s, 2 H);13C NMR (100 MHz, CDCl3) 168.7, 152.6 (d, J C-F = 246.5 Hz), 147.5 (d, J C-F = 10.5 Hz), 137.9, 130.4, 127.6, 126.5 (d, J C-F = 6.3 Hz), 125.4 (d, J C-F = 3.6 Hz), 124.3, 121.4, 120.5, 120.3 (q, J C-F = 257.9 Hz), 117.3 (d, J C-F = 18.5 Hz), 114.2 (d, J C-F = 2.3 Hz), 56.3, 43.9; 19F NMR (376 MHz, CDCl3) δ −58.09, −133.54; HRMS (EI) Calculated for C16H13F4NO3 [M+]: 343.0832, found 343.0836; IR (KBr) ν(cm−1): 3268, 1659, 1609, 1519, 1455, 1274, 1207, 1190, 1170.

White solid; mp 97-101 °C; 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.1 Hz, 1 H), 7.64 (br s, 1 H), 7.26 (t, J = 8.0 Hz, 1 H), 7.17 (d, J = 8.1 Hz, 1 H), 7.06 (t, J = 7.6 Hz, 1 H), 6.54 (s, 2 H), 3.86 (s, 6 H), 3.85 (s, 3 H), 3.72 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.9, 153.9, 137.7, 137.6, 130.5, 129.2, 127.5, 124.1, 121.3, 120.5, 120.2 (q, J C-F = 257.7 Hz), 106.3, 60.6, 55.9, 45.2; 19F NMR (376 MHz, CDCl3) δ −58.11; HRMS (EI) Calculated for C18H18F3NO5 [M+]: 385.1137, found 385.1141; IR (KBr) ν(cm−1): 3289, 1661, 1608, 1593, 1537, 1509, 1460, 1424, 1329, 1295, 1256, 1187, 1172, 1150, 1128.

2-(Naphthalen-2-yl) Yellow solid; mp 104–105 °C;1H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 8.2 Hz, 1 H), 7.91 (d, J = 8.4 Hz, 1 H), 7.89–7.80 (m, 3 H), 7.57–7.48 (m, 3 H), 7.43 (dd, J = 8.4 and 1.5 Hz, 1 H), 7.30–7.23 (m, 1 H), 7.12 (d, J = 8.2 Hz, 1 H), 7.09–7.01 (m, 1 H), 3.95 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 169.0, 137.9, 133.6, 132.7, 131.2, 130.5, 129.3, 128.5, 127.7, 127.6, 127.5, 127.0, 126.6, 126.3, 124.2, 121.5, 120.4120.1 (q, J C-F = 257.9 Hz), 45.1; 19F NMR (376 MHz, CDCl3) δ −58.24; HRMS (EI) Calculated for C19H14F3NO2 [M+]: 345.0977, found 345.0970; IR (KBr) ν(cm−1): 3263, 1664, 1606, 1533, 1494, 1454, 1407, 1341, 1302, 1265, 1190, 1172.

2-(Thiophen-3-yl) White solid; mp 50–51 °C; 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.1 Hz, 1 H), 7.62 (br s, 1 H), 7.43 (dd, J = 4.7 and 3.0 Hz, 1 H), 7.26 (t, J = 7.5 Hz, 2 H), 7.17 (d, J = 8.2 Hz, 1 H), 7.10–7.03 (m, 2 H), 3.82 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.6, 137.9, 133.7, 130.5, 128.2, 127.6, 127.5, 124.3, 124.2, 121.4, 120.4, 120.3 (q, J C-F = 257.9 Hz), 39.2; 19F NMR (376 MHz, CDCl3) δ −58.05; HRMS (EI) Calculated for C13H10F3NO2S [M+]: 301.0384, found 301.0381; IR (KBr) ν(cm−1): 3401, 3280, 1675, 1610, 1532, 1454, 1256, 1174.

2-(2-Bromophenyl) White solid; mp 141–142 °C;1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.2 Hz, 1 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.54 (br s, 1 H), 7.45–7.40 (m, 1 H), 7.37 (t, J = 7.4 Hz, 1 H), 7.31–7.21 (m, 2 H), 7.21–7.16 (m, 1 H), 7.10–7.04 (m, 1 H), 3.94 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 167.7, 137. 9, 133.9, 133.4, 131.7, 130.5, 129.6, 128.3, 127.5, 125.0, 124.2, 121.5, 120.3, 120.28 (q, J C-F = 257.9 Hz), 45.3; 19F NMR (376 MHz, CDCl3) δ −57.92; HRMS (EI) Calculated for C15H11BrF3NO2 [M+]: 372.9925, found 372.9932; IR (KBr) ν(cm−1): 3416, 3256, 1667, 1607, 1535, 1454, 1409, 1346, 1297, 1260, 1178.

2-(4-Chlorophenyl) White solid; mp 90–91 °C;1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.0 Hz, 1 H), 7.26 (br s, 1 H), 7.17 (d, J = 8.1 Hz, 2 H), 7.09–7.02 (m, 3 H), 6.97 (d, J = 7.9 Hz, 1 H), 6.86 (t, J = 7.6 Hz, 1 H), 3.54 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.4, 138.0, 134.0, 132.2, 130.8, 130.3, 129.4, 127.5, 124.4, 121.5, 120.4, 120.3 (q, J C-F = 258.0 Hz), 44.2; 19F NMR (376 MHz, CDCl3) δ −58.03; HRMS (EI) Calculated for C15H11ClF3NO2 [M+]: 329.0430, found 329.0437; IR (KBr) ν(cm−1): 3265, 1668, 1610, 1600, 1540, 1493, 1455, 1410, 1343, 1302, 1268, 1212, 1193.

2-(3-Bromophenyl) White solid; mp 111–112 °C;1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.1 Hz, 1 H), 7.54–7.31 (m, 3 H), 7.26–7.14 (m, 3 H), 7.10 (d, J = 8.2 Hz, 1 H), 6.99 (t, J = 7.4 Hz, 1 H), 3.66 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.2, 138.0, 136.0, 132.5, 131.0, 130.7, 130.3, 128.0, 127.5, 124.4, 123.3, 121.6, 120.5, 120.3 (q, J C-F = 258.0 Hz), 44.3; 19F NMR (376 MHz, CDCl3) δ −58.00; HRMS (EI) Calculated for C15H11BrF3NO2 [M+]: 372.9925, found 372.9926; IR (KBr) ν(cm−1): 3295, 3279, 1671, 1610, 1541, 1454, 1345, 1303, 1257, 1192, 1164.

2-(4-Iodophenyl) White solid; mp 134–135 °C;1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.1 Hz, 1 H), 7.72 (d, J = 8.2 Hz, 2 H), 7.51 (br s, 1 H), 7.24 (t, J = 7.8 Hz, 1 H), 7.17 (d, J = 8.2 Hz, 1 H), 7.07 (d, J = 8.1 Hz, 3 H),3.70 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.3, 138.3, 138.0, 133.4, 131.3, 130.3, 127.5, 124.4, 121.6, 120.4, 120.2 (q, J C-F = 257.9 Hz), 93.3, 44.2; 19F NMR (376 MHz, CDCl3) δ −57.98; HRMS (EI) Calculated for C15H11F3INO2 [M+]: 420.9787, found 420.9795; IR (KBr) ν(cm−1): 3261, 1675, 1662, 1609, 1535, 1487, 1455, 1257, 1214, 1194.

2-(3-Fluorophenyl) White solid; mp96-97 °C;1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.1 Hz, 1 H), 7.42 (br s, 1 H), 7.40–7.33 (m, 1 H), 7.25–7.21 (m, 1 H), 7.15 (d, J = 8.2 Hz, 1 H), 7.10 (d, J = 7.6 Hz, 1 H), 7.08–6.99 (m, 3 H), 3.75 (s, 2 H); 13C NMR (100 MHz, CDCl3) 168.2, 163.2 (d, J C-F = 246.6 Hz), 137.9, 136.1 (d, J C-F = 7.4 Hz), 131.0 (d, J C-F = 8.4 Hz), 130.4, 127.6, 125.2 (d, J C-F = 3.0 Hz), 124.4, 120.3 (q, J C-F = 257.9 Hz), 121.5, 120.5, 116.6 (d, J C-F = 21.5 Hz), 115.0 (d, J C-F = 20.9 Hz), 44.6; 19F NMR (376 MHz, CDCl3) δ −58.10, −111.71; HRMS (EI) Calculated for C15H11F4NO2 [M+]:313.0726, found 313.0732; IR (KBr) ν(cm−1): 3413, 3277, 1669, 1644, 1611, 1593, 1535, 1490, 1454, 1347, 1304, 1261, 1215, 1188, 1172, 1144, 1106, 763 cm−1.

2-(3-Bromophenyl) White solid; mp 111–112 °C;1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.1 Hz, 1 H), 7.54–7.31 (m, 3 H), 7.26–7.14 (m, 3 H), 7.10 (d, J = 8.2 Hz, 1 H), 6.99 (t, J = 7.4 Hz, 1 H), 3.66 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.2, 138.0, 136.0, 132.5, 131.0, 130.7, 130.3, 128.0, 127.5, 124.4, 123.3, 121.6, 120.5, 120.3 (q, J C-F = 258.0 Hz), 44.3; 19F NMR (376 MHz, CDCl3) δ −58.00; HRMS (EI) Calculated for C15H11BrF3NO2 [M+]: 372.9925, found 372.9926; IR (KBr) ν(cm−1): 3295, 3279, 1671, 1610, 1541, 1454, 1345, 1303, 1257, 1192, 1164.

White solid; mp 104–105 °C;1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.1 Hz, 1 H), 7.52 (br s, 1 H), 7.43 (t, J = 8.3 Hz, 1 H), 7.26 (t, J = 7.3 Hz, 2 H), 7.23–7.15 (m, 3 H), 7.06 (t, J = 7.3 Hz, 1 H), 3.78 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.1, 149.8 (d, J C-F = 1.8 Hz), 138.1, 136.0, 130.6, 130.3, 127.8, 127.5, 124.5, 122.0, 121.7, 120.5, 120.1, 120.38 (q, J C-F = 256.0 Hz), 120.27 (q, J C-F = 257.8 Hz), 44.4; 19F NMR (376 MHz, CDCl3) δ −57.89, −58.17; HRMS (EI) Calculated for C16H11F6NO3 [M+]: 379.0643, found 379.0634; IR (KBr) ν(cm−1): 3295, 3281, 1670, 1611, 1542, 1491, 1456, 1281.

White solid; mp 90–91 °C; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.1 Hz, 1 H), 7.74–7.58 (m, 2 H), 7.49 (d, J = 4.8 Hz, 2 H), 7.39 (br s, 1 H), 7.28 (t, J = 7.5 Hz, 1 H), 7.19 (d, J = 8.2 Hz, 1 H), 7.09 (t, J = 7.5 Hz, 1 H), 3.82 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 168.0, 137.2, 135.6, 135.4, 131.9, 130.3, 130.2, 129.4 (q, J C-F = 306.3 Hz), 127.6, 124.5, 121.6, 120.5, 120.3 (q, J C-F = 258.6 Hz), 44.4; 19F NMR (376 MHz, CDCl3) δ −42.55, −58.07; HRMS (EI) Calculated for C16H11F6NO2S [M+]: 395.0415, found 395.0404; IR (KBr) ν(cm−1): 3416, 3295, 1669, 1610, 1534, 1456, 1357, 1300, 1263, 1211, 1185, 1167, 1149.

White solid; mp 84–85 °C; 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.1 Hz, 1H), 7.56 (s, 1H), 7.44 (t, J = 8.3 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.24–7.15 (m, 3H), 7.09–7.01 (m, 2H), 6.33 (t, J = 73.3 Hz, 1H), 3.79 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 168.0, 149.7, 140.0, 136.2, 130.6, 129.8, 127.9, 126.3, 124.4, 122.1, 121.3, 120.4 (q, J C-F = 255.9 Hz), 120.1, 118.6, 116.1 (t, J C-F = 258.9 Hz), 44.5; 19F NMR (376 MHz, CDCl3) δ −57.81, −80.26; HRMS (EI) Calculated for C16H12F5NO3 [M+]: 361.0737, found 361.0742; IR (KBr) ν(cm−1): 3262, 1670, 1607, 1540, 1454, 1381, 1348, 1280, 1216, 1151, 1123.

White solid; mp 60–61 °C;1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 7.7 Hz, 1 H), 7.60 (br s, 1 H), 7.52–7.28 (m, 5 H), 7.22–7.16 (m, 1 H), 7.04 (d, J = 3.6 Hz, 2 H), 6.27 (t, J = 73.4 Hz, 1 H), 3.78 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ 169.1, 139.9, 134.0, 130.0, 129.6, 129.3, 127.8, 126.2, 124.2, 121.1, 118.7, 116.0 (t, J C-F = 259.9 Hz), 45.1; 19F NMR (376 MHz, CDCl3) δ −80.24; HRMS (EI) Calculated for C15H13F2NO2 [M+]: 277.0914, found 277.0906; IR (KBr) ν(cm−1): 3399, 3294, 1673, 1608, 1530, 1496, 1455, 1383, 1349, 1321, 1295, 1260, 1191, 1131, 1100, 1054, 1041, 757, 727, 706.

2-Phenyl- White solid; mp 136–138 °C; 1H NMR (400 MHz, CDCl3) δ 7.49–7.41 (m, 3H), 7.40–7.28 (m, 5H), 7.12 (d, J = 8.6 Hz, 2H), 3.72 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 169.3, 145.3, 136.2, 134.1, 129.4, 129.2, 127.8, 121.6, 121.0, 120.4 (q, J C-F = 255.2 Hz), 44.6; 19F NMR (376 MHz, CDCl3) δ −58.16; HRMS (EI) Calculated for C15H12F3NO2 [M+]: 295.0820, found 295.0821; IR (KBr) ν(cm−1): 3265, 1657, 1611, 1556, 1509, 1408, 1294, 1204, 1164.

2-( White solid; mp 112–113 °C; 1H NMR (400 MHz, CDCl3) 7.64 (s, 1 H), 7.53 (s, 1 H), 7.35–7.18 (m, 6 H), 6.97 (d, J = 6.9 Hz, 1 H), 3.70 (s, 2 H), 2.39 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 169.8, 149.4, 139.1, 137.5, 130.9, 129.9, 129.8, 129.3, 120.4 (q, J C-F = 255.9 Hz), 117.8, 116.4, 112.6, 44.2, 21.0; 19F NMR (376 MHz, CDCl3) δ −58.17; HRMS (EI) Calculated for C16H14F3NO2 [M+]: 309.0977, found 309.0973; IR (KBr) ν(cm−1): 3429, 1664, 1639, 1609, 1539, 1493, 1441, 1262, 1221, 1168.

White solid; mp 85–86 °C;1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 7.6 Hz, 2 H), 7.48–7.33 (m, 1 H), 7.29–7.17 (m, 5 H), 6.99 (t, J = 7.4 Hz, 1 H), 3.74 (s, 2 H), 2.35 (s, 3 H), 2.02 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 169.4, 138.4, 137.2, 133.3, 131.1, 129.8, 129.5, 129.0, 124.9, 124.1, 120.0, 44.8, 21.0, 18.5; HRMS (EI) Calculated for C16H17NOS [M+]: 271.1031, found 271.1025; IR (KBr) ν(cm−1): 3431, 3247, 1661, 1577, 1527, 1517, 1437, 1341, 1296, 1275, 1186.

White solid; mp 145–146 °C;1H NMR (400 MHz, CDCl3) 7.41 (d, J = 7.7 Hz, 2 H), 7.31–7.18 (m, 6 H), 7.08 (t, J = 7.3 Hz, 2 H), 3.70 (s, 2 H), 2.37 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 169.3, 137.6, 137.4, 131.3, 129.9, 129.4, 128.9, 124.4, 119.7, 44.4, 21.1; HRMS (EI) Calculated for C15H15NO [M+]: 225.1154, found 225.1148; IR (KBr) ν(cm−1): 3440, 3432, 3298, 1670, 1598, 1530, 1499, 1442, 1410, 1343, 1307, 1298, 1254, 1188.

General procedure for the synthesis of α,β-unsaturatal amide compounds 2 and sulfide compounds 3

A mixture of substrate 1 (0.1 mmol), PbCl2 (41.7 mg, 0.15 mmol) and KOAc (14.7 mg, 0.15 mmol) or (5.9 mg, 0.06 mmol) in DMSO (2.0 mL) was put into a 15 mL seal tube. The air in the seal tube was exchanged with N2. The reaction mixture was stirred at 156 °C for 13 h under N2, then cooled down to room temperature, diluted with H2O, and extracted with EtOAc (3 × 5 mL). The combined organic phase was washed with brine and dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by preparative TLC plate (petroleum ether: ethyl acetate = 10: 1 as eluent) to get the product 2 and 3.

2-Phenyl- Data of 2a: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 7.8 Hz, 1H), 7.83 (s, 1H), 7.51–7.38 (m, 5H), 7.34–7.28 (m, 1H), 7.24–7.16 (m, 1H), 7.13–7.06 (m, 1H), 6.43 (s, 1H), 5.75 (s, 1H).; 13C NMR (100 MHz, CDCl3) δ 164.4, 144.5, 138.1 (d, J = 1.3 Hz), 136.3, 130.5, 128.9, 128.8, 128.3, 127.5, 124.7, 124.3, 121.5, 120.2 (q, J C-F = 257.8 Hz), 120.3 (d, J = 1.0 Hz); 19F NMR (376 MHz, CDCl3) δ −57.99; HRMS (EI) Calcd for C16H12F3NO2 [M+]: 307.0820, found 307.0828; IR (KBr) ν(cm−1): 3416, 1691, 1611, 1528, 1452, 1257, 1216, 1180. Data of 3a: White solid; mp 74–75 °C; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.2 Hz, 1H), 7.54 (s, 1H), 7.44–7.32 (m, 5H), 7.29–7.23 (m, 1H), 7.20–7.15 (m, 1H), 7.10–7.04 (m, 1H), 3.82 (t, J = 7.4 Hz, 1H), 3.44 (dd, J = 13.3 and 7.1 Hz, 1H), 2.99 (dd, J = 13.3 and 7.7 Hz, 1H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 138.0, 137.6, 130.4, 129.3, 128.3, 128.0, 127.5, 121.6, 120.4 (d, J = 1.0 Hz), 120.3 (q, J C-F = 258.1 Hz), 54.7, 36.9, 16.3; 19F NMR (376 MHz, CDCl3) δ −57.92; HRMS (EI) Calcd for C17H16F3NO2S [M+]: 355.0854, found 355.0848; IR (KBr) ν(cm−1): 3420, 1692, 1670, 1610, 1528, 1452, 1258,1217, 1180.

2-( Data of 2b: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.1 Hz, 1H), 7.83 (s, 1H), 7.34–7.25 (m, 2H), 7.25–7.11 (m, 4H), 7.09–7.03 (m, 1H), 6.40 (s, 1H), 5.69 (d, J = 0.6 Hz, 1H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.5, 144.6, 138.9, 138.1 (d, J = 1.2 Hz), 136.3, 130.7, 129.7, 129.01, 128.95, 127.6, 125.5, 124.8, 124.3, 121. 6, 120.4 (d, J = 1.0 Hz), 120.3 (q, J C-F = 257.9 Hz), 21.3; 19F NMR (376 MHz, CDCl3) δ −58.07; HRMS (EI) Calcd for C17H14F3NO2 [M+]: 321.0977, found 321.0982; IR (KBr) ν(cm−1): 3414, 1691, 1611, 1527, 1452, 1255, 1216, 1178. Data of 3b: White solid; mp 81–82 °C; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 7.33–7.22 (m, 2H), 7.21–7.13 (m, 4H), 7.10–7.03 (m, 1H), 3.79 (t, J = 7.4 Hz, 1H), 3.43 (dd, J = 13.3 and 7.0 Hz, 1H), 2.98 (dd, J = 13.2 and 7.9 Hz, 1H), 2.36 (s, 3H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.4, 139.2, 137.9, 137.5, 130.5, 129.2, 129.1, 128.7, 127.5, 125.1, 124.2, 121.6, 120.4 (d, J = 0.9 Hz), 120.3 (q, J C-F = 258.7 Hz), 54.6, 36.8, 21.4, 16.3; 19F NMR (376 MHz, CDCl3) δ −58.00; HRMS (EI) Calcd for C18H18F3NO2S [M+]: 369.1010, found 369.1014; IR (KBr) ν(cm−1): 3409, 1692, 1609, 1528, 1257, 1217, 1180.

2-(3-Methoxyphenyl)- Data of 2c: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.1 Hz, 1H), 7.89 (s, 1H), 7.37 (t, J = 7.9 Hz, 1H), 7.34–7.28 (m, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.12–7.06 (m, 1H), 7.03–6.92 (m, 3H), 6.44 (s, 1H), 5.75 (d, J = 0.6 Hz, 1H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.3, 160.0, 144.4, 138.1 (d, J = 1.4 Hz), 137.7, 130.6, 130.2, 127.6, 125.0, 124.3, 121.5, 120.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.8 Hz), 114.5, 114.0, 55.2; 19F NMR (376 MHz, CDCl3) δ −58.03; HRMS (EI) Calcd for C17H14F3NO3 [M+]: 337.0926, found 337.0929; IR (KBr) ν(cm−1): 3411, 1691, 1606, 1527, 1453, 1255, 1217, 1180. Data of 3c: White solid; mp 81–82 °C; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.0 Hz, 1H), 7.57 (s, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.29–7.22 (m, 1H), 7.21–7.14 (m, 1H), 7.10–7.03 (m, 1H), 6.95 (d, J = 7.5 Hz, 1H), 6.92–6.84 (m, 2H), 3.83–3.77 (m, 4H), 3.42 (dd, J = 13.3 and 7.0 Hz, 1H), 2.98 (dd, J = 13.3 and 7.8 Hz, 1H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.2, 160.3, 139.1, 138.0, 130.44, 130.38, 127.5, 124.3, 121.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 258.3 Hz), 120.2, 113.7, 113.6, 55.2, 54.7, 36.7, 16.3; 19F NMR (376 MHz, CDCl3) δ −57.95; HRMS (EI) Calcd for C18H18F3NO3S [M+]: 385.0960, found 385.0959; IR (KBr) ν(cm−1): 3352, 1670, 1608, 1529, 1255, 1215, 1185.

2-( Data of 2d: White solid; mp 61–62 °C; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 8.1 Hz, 1H), 7.86 (s, 1H), 7.35–7.28 (m, 3H), 7.25 (d, J = 7.8 Hz, 2H), 7.22–7.16 (m, 1H), 7.12–7.06 (m, 1H), 6.38 (s, 1H), 5.72 (s, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.7, 144.5, 139.0, 138.2, 133.4, 130.6, 129.7, 128.3, 127.6, 124.29, 124.25, 121.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.4 Hz), 21.2; 19F NMR (376 MHz, CDCl3) δ −57.99; HRMS (EI) Calcd for C17H14F3NO2 [M+]: 321.0977, found 321.0968; IR (KBr) ν(cm−1): 3419, 1689, 1614, 1527, 1256, 1217, 1180. Data of 3d: White solid; mp 80–81 °C; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 7.31–7.14 (m, 6H), 7.10–7.02 (m, 1H), 3.79 (t, J = 7.4 Hz, 1H), 3.42 (dd, J = 13.2 and 6.8 Hz, 1H), 2.98 (dd, J = 13.2 and 8.1 Hz, 1H), 2.35 (s, 3H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.6, 138.2, 134.5, 130.5, 130.0, 128.7, 127.9, 127.5, 124.2, 121.5, 120.4, 120.3 (q, J C-F = 257.4 Hz), 54.2, 36.8, 21.1, 16.3; 19F NMR (376 MHz, CDCl3) δ −57.96; HRMS (EI) Calcd for C18H18F3NO2S [M+]: 369.1010, found 369.1020; IR (KBr) ν(cm−1): 3409, 1660, 1609, 1529, 1455, 1253,1216, 1186.

2-(4-Isopropylphenyl)- Data of 2e: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 7.6 Hz, 1H), 7.88 (s, 1H), 7.38–7.28 (m, 5H), 7.22–7.16 (m, 1H), 7.12–7.06 (m, 1H), 6.41 (d, J = 0.8 Hz, 1H), 5.72 (d, J = 0.9 Hz, 1H), 3.01–2.91 (m, 1H), 1.28 (d, J = 6.9 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 164.7, 149.9, 144.5, 138.1 (d, J = 1.5 Hz), 133.8, 130.7, 128. 5, 127.6, 127.1, 124.5, 124.2, 121.4, 120.4 (d, J = 1.0 Hz), 120.3 (q, J C-F = 257.9 Hz), 34.0, 23.8; 19F NMR (376 MHz, CDCl3) δ −57.96; HRMS (EI) Calcd for C19H18F3NO2 [M+]: 349.1290, found 349.1293; IR (KBr) ν(cm−1): 3401, 1699, 1609, 1531, 1455, 1255, 1217, 1180. Data of 3e: White solid; mp 85–86 °C; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.0 Hz, 1H), 7.53 (s, 1H), 7.31–7.22 (m, 5H), 7.20–7.13 (m, 1H), 7.10–7.02 (m, 1H), 3.80 (t, J = 7.4 Hz, 1H), 3.43 (dd, J = 13.2 and 6.9 Hz, 1H), 2.98 (dd, J = 13.2 and 7.9 Hz, 1H), 2.95–2.85 (m, 1H), 2.11 (s, 3H), 1.24 (d, J = 6.9 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 170.6, 149.0, 137.9, 134.7, 130.5, 128.0, 127.5, 127.4, 124.2, 121.5, 120.4, 120.2 (q, J C-F = 258.0 Hz), 54.2, 36.8, 33.8, 23.8, 23.8, 16.4. 19F NMR (376 MHz, CDCl3) δ −57.92;; HRMS (EI) Calcd for C20H22F3NO2S [M+]: 397.1323, found 397.1324; IR (KBr) ν(cm−1): 3432, 1681, 1634, 1528, 1252, 1215, 1175.

2-(4-( Data of 2f: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 7.9 Hz, 1H), 7.89 (s, 1H), 7.48 (d, J = 8.2 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.34–7.28 (m, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.14–7.05 (m, 1H), 6.42 (s, 1H), 5.73 (s, 1H), 1.35 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.6, 152.1, 144.4, 138.1 (d, J = 1.2 Hz), 133.4, 130.7, 128.2, 127.6, 126.0, 124.5, 124.2, 121.4, 120.3 (d, J = 1.0 Hz), 120.2 (q, J C-F = 258.0 Hz), 34.7, 31.2; 19F NMR (376 MHz, CDCl3) δ −57.94; HRMS (EI) Calcd for C20H20F3NO2 [M+]: 363.1446, found 363.1442; IR (KBr) ν(cm−1): 3411, 1695, 1610, 1529, 1454, 1255, 1216, 1179. Data of 3f: White solid; mp 84–85 °C; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 7.42 (d, J = 8.2 Hz, 2H), 7.31–7.23 (m, 3H), 7.20–7.13 (m, 1H), 7.10–7.01 (m, 1H), 3.81 (t, J = 7.4 Hz, 1H), 3.43 (dd, J = 13.2 and 6.9 Hz, 1H), 2.99 (dd, J = 13.2 and 7.9 Hz, 1H), 2.11 (s, 3H), 1.31 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 170.6, 151.3, 137.9, 134.4, 130.5, 127.7, 127.5, 126.3, 124.2, 121.5, 120.4, 120.2 (q, J C-F = 257.8 Hz), 54.2, 36.8, 34.6, 31.2, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.90; HRMS (EI) Calcd for C21H24F3NO2S [M+]: 411.1480, found 411.1479; IR (KBr) ν(cm−1): 3426, 1686, 1617, 1528, 1257, 1217, 1178.

2-(4-Butoxyphenyl)- Data of 2g: White solid; mp 64–66 °C; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 8.1 Hz, 1H), 7.89 (s, 1H), 7.38–7.28 (m, 3H), 7.21 (d, J = 8.1 Hz, 1H), 7.13–7.05 (m, 1H), 6.95 (d, J = 8.5 Hz, 2H), 6.32 (s, 1H), 5.69 (s, 1H), 4.00 (t, J = 6.5 Hz, 2H), 1.85–1.73 (m, 2H), 1.57–1.45 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.1, 159.7, 144.2, 138.2 (d, J = 1.3 Hz), 130.7, 129.6, 128.3, 127.6, 124.3, 123.5, 121.6, 120.4 (d, J = 1.0 Hz), 120.3 (q, J C-F = 257.8 Hz), 115.0, 67.8, 31.2, 19.2, 13.8; 19F NMR (376 MHz, CDCl3) δ −57.87; HRMS (EI) Calcd for C20H20F3NO3 [M+]: 379.1395, found 379.1401; IR (KBr) ν(cm−1): 3415, 1690, 1611, 1525, 1453, 1255, 1217, 1178. Data of 3g: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 7.29–7.23 (m, 3H), 7.22–7.14 (m, 1H), 7.10–7.02 (m, 1H), 6.92 (d, J = 8.6 Hz, 2H), 3.96 (t, J = 6.4 Hz, 2H), 3.76 (t, J = 7.4 Hz, 1H), 3.41 (dd, J = 13.2 and 6.8 Hz, 1H), 2.96 (dd, J = 13.2 and 8.2 Hz, 1H), 2.10 (s, 3H), 1.81–1.72 (m, 2H), 1.54–1.44 (m, 2H), 0.97 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 170.8, 159.1, 137.9, 130.5, 129.1, 128.9, 127.5, 124.2, 121.5, 120.4, 120.3 (q, J C-F = 257.9 Hz), 115.2, 67.7, 53.8, 37.0, 31.2, 19.2, 16.3, 13.8; 19F NMR (376 MHz, CDCl3) δ −57.89; HRMS (EI) Calcd for C21H24F3NO3S [M+]: 427.1429, found 427.1441; IR (KBr) ν(cm−1): 3426, 1688, 1614, 1521, 1255, 1217, 1180.

2-(4-Phenoxyphenyl)- Data of 2h: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 8.1 Hz, 1H), 7.88 (s, 1H), 7.44–7.35 (m, 4H), 7.35–7.29 (m, 1H), 7.25–7.20 (m, 1H), 7.17 (d, J = 7.4 Hz, 1H), 7.15–7.10 (m, 1H), 7.10–7.02 (m, 4H), 6.37 (s, 1H), 5.75 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.7, 158.2, 156.5, 144.0, 138.1 (d, J = 1.3 Hz), 130.9, 130.6, 129.90, 129.87, 127.7, 124.4, 124.1, 123.8, 121. 6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.9 Hz), 119.4, 118.8; 19F NMR (376 MHz, CDCl3) δ −57.82; HRMS (EI) Calcd for C22H16F3NO3 [M+]: 399.1082, found 399.1086; IR (KBr) ν(cm−1): 3415, 1692, 1610, 1526, 1490, 1454, 1250, 1217, 1172. Data of 3h: White solid; mp 83–84 °C; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.39–7.30 (m, 4H), 7.30–7.24 (m, 2H), 7.23–7.17 (m, 1H), 7.15–7.05 (m, 2H), 7.02 (d, J = 8.4 Hz, 3H), 3.80 (t, J = 7.4 Hz, 1H), 3.41 (dd, J = 13.3 and 7.1 Hz, 1H), 2.97 (dd, J = 13.2 and 7.7 Hz, 1H), 2.12 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.4, 158.6, 157.5, 156.6, 132.1, 130.4, 129.8, 129.4, 127.6, 124.3, 123.7, 121.7, 120.5, 120.4 (q, J C-F = 259.1 Hz), 119.3, 119.2, 54.0, 37.1, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.80; HRMS (EI) Calcd for C23H20F3NO3S [M+]: 447.1116, found 447.1115; IR (KBr) ν(cm−1): 3426, 1633, 1616, 1529, 1252, 1220, 1176.

2-([1,1′-Biphenyl]-4-yl)- Data of 2i: White solid; mp 116–118 °C; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 8.2 Hz, 1H), 7.91 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 7.5 Hz, 2H), 7.55–7.45 (m, 4H), 7.43–7.36 (m, 1H), 7.36–7.29 (m, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.15–7.08 (m, 1H), 6.44 (s, 1H), 5.82 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.6, 144.3, 141.9, 140.3, 138.2 (d, J = 1.4 Hz), 135.1, 130.6, 128.9, 128.8, 127.74, 127.69, 127.6, 127.1, 124.5, 124.4, 121.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.6 Hz); 19F NMR (376 MHz, CDCl3) δ −57.86; HRMS (EI) Calcd for C22H16F3NO2 [M+]: 383.1133 found 383.1138; IR (KBr) ν(cm−1): 3416, 1665, 1609, 1527, 1453, 1254, 1218, 1177. Data of 3i: White solid; mp 79–80 °C; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.1 Hz, 1H), 7.63 (d, J = 8.1 Hz, 2H), 7.58 (d, J = 7.4 Hz, 3H), 7.49–7.42 (m, 4H), 7.39–7.33 (m, 1H), 7.31–7.24 (m, 1H), 7.21–7.15 (m, 1H), 7.11–7.04 (m, 1H), 3.87 (t, J = 7.4 Hz, 1H), 3.47 (dd, J = 13.3 and 7.1 Hz, 1H), 3.04 (dd, J = 13.3 and 7.8 Hz, 1H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 140.4, 139.9, 136.5, 130.4, 128.8, 128.5, 128.0, 127.5, 127.1, 124.3, 121.7, 120.5 (q, J C-F = 259.0 Hz), 120.4, 117.7, 117.5, 54.3, 36.9, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.86; HRMS (EI) Calcd for C23H20F3NO2S [M+]: 431.1167 found 431.1154; IR (KBr) ν(cm−1): 3406, 1673, 1608, 1529, 1255, 1217, 1180.

2-(3,5-Dimethylphenyl)- Data of 2j: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 8.0 Hz, 1H), 7.89 (s, 1H), 7.35–7.27 (m, 1H), 7.25–7.15 (m, 1H), 7.14–7.04 (m, 2H), 7.02 (s, 2H), 6.42 (d, J = 0.6 Hz, 1H), 5.70 (d, J = 0.8 Hz, 1H), 2.35 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 164.6, 144.7, 138.8, 138.1 (d, J = 1.5 Hz), 136.3, 130.7, 130.5, 127.6, 126.2, 124.7, 124.2, 121.6, 120.4 (d, J = 1.0 Hz), 120.3 (q, J C-F = 257.7 Hz), 21.2; 19F NMR (376 MHz, CDCl3) δ −58.15; HRMS (EI) Calcd for C18H16F3NO2 [M+]: 335.1133, found 335.1138; IR (KBr) ν(cm−1): 3408, 1693, 1610, 1526, 1454, 1254, 1216, 1175. Data of 3j: White solid; mp 81–82 °C; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.2 Hz, 1H), 7.54 (s, 1H), 7.29–7.22 (m, 1H), 7.20–7.13 (m, 1H), 7.10–7.02 (m, 1H), 6.97 (d, J = 6.7 Hz, 3H), 3.75 (t, J = 7.4 Hz, 1H), 3.42 (dd, J = 13.2 and 6.9 Hz, 1H), 2.98 (dd, J = 13.2 and 8.0 Hz, 1H), 2.32 (s, 6H), 2.12 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.5, 139.1, 137.9, 137.3, 130.5, 130.0, 127.5, 125.7, 124.2, 121.5, 120.4, 120.3 (q, J C-F = 258.0 Hz), 54.4, 36.6, 21.2, 16.3; 19F NMR (376 MHz, CDCl3) δ −58.08; HRMS (EI) Calcd for C19H20F3NO2S [M+]: 383.1167, found 383.1161; IR (KBr) ν(cm−1): 3404, 1691, 1607, 1528, 1255, 1217, 1179.

2-(3,5-Dimethoxyphenyl)- Data of 2k: White solid; mp 57–59 °C; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 7.9 Hz, 1H), 7.95 (s, 1H), 7.33–7.27 (m, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.12–7.05 (m, 1H), 6.58–6.48 (m, 3H), 6.45 (d, J = 0.6 Hz, 1H), 5.73 (d, J = 0.8 Hz, 1H), 3.81 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 164.1, 161.2, 144.4, 138.3, 138.1 (d, J = 1.3 Hz), 130.6, 127.6, 125.1, 124.3, 121.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 258.0 Hz), 106.5, 100.7, 55.4; 19F NMR (376 MHz, CDCl3) δ −58.10; HRMS (EI) Calcd for C18H16F3NO4 [M+]: 367.1031, found 367.1025; IR (KBr) ν(cm−1): 3409, 1689, 1600, 1528, 1454, 1255, 1213, 1161. Data of 3k: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.1 Hz, 1H), 7.60 (s, 1H), 7.29–7.23 (m, 1H), 7.21–7.15 (m, 1H), 7.10–7.01 (m, 1H), 6.55–6.47 (m, 2H), 6.47–7.39 (m, 1H), 3.79 (s, 6H), 3.75 (t, J = 7.4 Hz, 1H), 3.40 (dd, J = 13.3 and 6.9 Hz, 1H), 2.97 (dd, J = 13.3 and 7.9 Hz, 1H), 2.12 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.0, 161.5, 142.9, 139.8, 130.5, 127.5, 124.2, 121.6, 120.45, 120.38 (q, J C-F = 256.6 Hz), 106.1, 99.9, 55.3, 54.9, 36.5, 16.4; 19F NMR (376 MHz, CDCl3) δ −58.00; HRMS (EI) Calcd for C19H20F3NO4S [M+]: 415.1065, found 415.1071; IR (KBr) ν(cm−1): 3404, 1696, 1608, 1527, 1255, 1215, 1184.

2-(3-Fluoro-4-methoxyphenyl)- Data of 2l: White solid; mp 69–70 °C; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.2 Hz, 1H), 7.84 (s, 1H), 7.35–7.29 (m, 1H), 7.25–7.15 (m, 3H), 7.14–7.08 (m, 1H), 7.05–6.98 (m, 1H), 6.30 (s, 1H), 5.73 (s, 1H), 3.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 164.6, 152.3 (d, J C-F = 246.5 Hz), 148.3 (d, J = 10.6 Hz), 143.4 (d, J = 15.7 Hz), 138.2 (d, J = 1.5 Hz), 130.5, 129.0 (d, J = 6.5 Hz), 127.7, 124.5, 124.4 (d, J = 3.6 Hz), 123.8, 121.6, 120.4 (d, J = 1.2 Hz), 120.3 (q, J C-F = 257.9 Hz), 116.2 (d, J = 19.1 Hz), 113.6 (d, J = 2.3 Hz), 56.3; 19F NMR (376 MHz, CDCl3) δ −58.09, −133.54; HRMS (EI) Calcd for C17H13F4NO3 [M+]: 355.0832 found 355.0848; IR (KBr) ν(cm−1): 3416, 1666, 1615, 1522, 1450, 1252, 1217, 1181. Data of 3l: White solid; mp 81–82 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.1 Hz, 1H), 7.54 (s, 1H), 7.30–7.25 (m, 1H), 7.23–7.16 (m, 1H), 7.16–7.05 (m, 3H), 7.02–6.94 (m, 1H), 3.89 (s, 3H), 3.74 (t, J = 7.4 Hz, 1H), 3.37 (dd, J = 13.3 and 7.0 Hz, 1H), 2.94 (dd, J = 13.3 and 7.9 Hz, 1H), 2.11 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.0, 152.6 (d, J C-F = 246.5 Hz), 147.6 (d, J C-F = 18.9 Hz), 138.1, 130.4 (d, J C-F = 5.9 Hz), 130.3, 127.6, 124.4, 124.0 (d, J C-F = 3.5 Hz), 121.7, 120.5, 120.3 (q, J C-F = 257.9 Hz), 115.7 (d, J C-F = 18.9 Hz), 113.9 (d, J C-F = 2.0 Hz), 56.3, 53.7, 37.0, 16.4; 19F NMR (376 MHz, CDCl3) δ −58.09, −133.54; HRMS (EI) Calcd for C18H17F4NO3S [M+]: 403.0865 found 403.0875; IR (KBr) ν(cm−1): 3435, 1632, 1522, 1259, 1219, 1177.

Data of 2m: White solid; mp 62–63 °C; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.0 Hz, 1H), 7.92 (s, 1H), 7.35–7.27 (m, 1H), 7.24–7.15 (m, 1H), 7.14–7.05 (m, 1H), 6.61 (s, 2H), 6.42 (s, 1H), 5.72 (d, J = 0.7 Hz, 1H), 3.87 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.3, 153.6, 144.5, 138.6, 138.0 (d, J = 1.1 Hz), 131.8, 130.6, 127.7, 124.7, 124.3, 121.4, 120.4, 120.3 (q, J C-F = 257.9 Hz), 105.6, 60.8, 56.1; 19F NMR (376 MHz, CDCl3) δ −58.00; HRMS (EI) Calcd for C19H18F3NO5 [M+]: 397.1137, found 397.1133; IR (KBr) ν(cm−1): 3411, 1690, 1611, 1585, 1528, 1454, 1254, 1219, 1180, 1127. Data of 3m: White solid; mp 95–96 °C; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.2 Hz, 1H), 7.59 (s, 1H), 7.28 (d, J = 7.6 Hz, 1H), 7.19 (d, J = 8.2 Hz, 1H), 7.12–7.05 (m, 1H), 6.57 (s, 2H), 3.87 (s, 6H), 3.84 (s, 3H), 3.74 (t, J = 7.3 Hz, 1H), 3.41 (dd, J = 13.3 and 7.0 Hz, 1H), 2.98 (dd, J = 13.3 and 7.7 Hz, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.2, 153.9, 137.9, 133.2, 130.4, 127.6, 124.3, 121.6, 120.5 (d, J = 1.0 Hz), 120.3 (q, J C-F = 258.9 Hz), 104.9, 100.0, 60.8, 56.1, 55.0, 36.8, 16.5; 19F NMR (376 MHz, CDCl3) δ −57.92; HRMS (EI) Calcd for C20H22F3NO5S [M+]: 445.1171, found 445.1190; IR (KBr) ν(cm−1): 3427, 1634, 1615, 1529, 1250, 1217, 1182.

2-(Naphthalen-2-yl)- Data of 2n: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 8.0 Hz, 1H), 7.96–7.82 (m, 5H), 7.58–7.49 (m, 3H), 7.36–7.29 (m, 1H), 7.22–7.15 (m, 1H), 7.14–7.07 (m, 1H), 6.47 (s, 1H), 5.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.8, 144.7, 138.3 (d, J = 1.4 Hz), 133.6, 133.2, 130.6, 128.9, 128.2, 127.8, 127.7, 127.6, 126.8, 126.7, 125.6, 124.7, 124.5, 121.8, 120.4 (d, J = 1.0 Hz), 120.2 (q, J C-F = 258.1 Hz); 19F NMR (376 MHz, CDCl3) δ −57.98; HRMS (EI) Calcd for C20H14F3NO2 [M+]: 357.0977 found 357.0986; IR (KBr) ν(cm−1): 3401, 1693, 1609, 1529, 1454, 1255, 1216, 1180. Data of 3n: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.1 Hz, 1H), 7.92–7.81 (m, 4H), 7.60 (s, 1H), 7.54–7.44 (m, 3H), 7.28–7.23 (m, 1H), 7.19–7.11 (m, 1H), 7.09–7.01 (m, 1H), 3.99 (t, J = 7.4 Hz, 1H), 3.52 (dd, J = 13.3 and 7.1 Hz, 1H), 3.09 (dd, J = 13.3 and 7.7 Hz, 1H), 2.12 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.3, 138.0, 135.0, 133.5, 133.0, 130.4, 129.3, 127.9, 127.7, 127.5, 127.4, 126.6, 126.4, 125.2, 124.3, 121.7, 120.4, 120.2 (q, J C-F = 258.3 Hz), 54.8, 36.9, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.99; HRMS (EI) Calcd for C21H18F3NO2S [M+]: 405.1010 found 405.1003; IR (KBr) ν(cm−1): 3406, 1688, 1608, 1528, 1256, 1217, 1180.

2-(Thiophen-3-yl)- Data of 2o: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.1 Hz, 1H), 7.99 (s, 1H), 7.50–7.45 (m, 1H), 7.45–7.39 (m, 1H), 7.35–7.29 (m, 1H), 7.25–7.19 (m, 2H), 7.15–7.09 (m, 1H), 6.27 (s, 1H), 5.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.7, 139.5, 138.2 (d, J = 1.4 Hz), 136.7, 130.5, 127.6, 127.04, 126.99, 124.6, 124.4, 123.0, 121.7, 120.38 (d, J = 1.0 Hz), 120.37 (q, J C-F = 257.7 Hz); 19F NMR (376 MHz, CDCl3) δ −57.78; HRMS (EI) Calcd for C14H10F3NO2S [M+]: 313.0384 found 313.0378; IR (KBr) ν(cm−1): 3397, 1688, 1610, 1529, 1453, 1258, 1216, 1181. Data of 3o: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.1 Hz, 1H), 7.65 (s, 1H), 7.45–7.39 (m, 1H), 7.36–7.27 (m, 2H), 7.23–7.17 (m, 1H), 7.13–7.04 (m, 2H), 4.00 (t, J = 7.2 Hz, 1H), 3.37 (dd, J = 13.3 and 6.7 Hz, 1H), 3.00 (dd, J = 13.3 and 7.8 Hz, 1H), 2.11 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.0, 137.9, 130.4, 127.6, 127.5, 127.4, 126.6, 124.4, 123.4, 121.6, 120.4, 120.3 (q, J C-F = 257.9 Hz), 50.0, 37.0, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.87; HRMS (EI) Calcd for C15H14F3NO2S2 [M+]: 361.0418 found 361.0412; IR (KBr) ν(cm−1): 3422, 1688, 1613, 1529, 1256, 1217, 1180.

2-(2-Bromophenyl)- Data of 2p: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.63–8.50 (m, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.46–7.36 (m, 2H), 7.35–7.27 (m, 2H), 7.20–7.13 (m, 1H), 7.11–7.04 (m, 1H), 6.64 (d, J = 0.9 Hz, 1H), 5.71 (d, J = 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 162.9, 143.9, 138.0 (d, J = 1.5 Hz), 137.5, 133.3, 131.4, 130.65, 130.59, 128.1, 127.6, 127.3, 124.2, 123.7, 121.3, 120.3 (d, J = 1.0 Hz), 120.2 (q, J C-F = 258.0 Hz); 19F NMR (376 MHz, CDCl3) δ −58.12; HRMS (EI) Calcd for C16H11BrF3NO2 [M+]: 384.9925 found 384.9922; IR (KBr) ν(cm−1): 3419, 1696, 1611, 1526, 1453, 1254, 1216, 1183. Data of 3p: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.49–7.42 (m, 1H), 7.35 (t, J = 7.3 Hz, 1H), 7.29–7.23 (m, 1H), 7.23–7.14 (m, 2H), 7.12–7.07 (m, 1H), 4.52–4.42 (m, 1H), 3.43 (dd, J = 13.5 and 8.1 Hz, 1H), 2.95 (dd, J = 13.5 and 6.6 Hz, 1H), 2.17 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.4, 138.0, 137.1, 133.2, 130.4, 129.5, 128.7, 128.4, 127.5, 124.7, 124.3, 121.7, 120.4 (q, J C-F = 257.8 Hz), 120.3, 52.3, 36.0, 16.3; 19F NMR (376 MHz, CDCl3) δ −57.70; HRMS (EI) Calcd for C17H15BrF3NO2S [M+]: 432.9959 found 432.9931; IR (KBr) ν(cm−1): 3420, 1699, 1611, 1527, 1259, 1217, 1182.

2-(4-Chlorophenyl)- Data of 2q: White solid; mp 88–89 °C; 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.45–7.36 (m, 4H), 7.35–7.28 (m, 1H), 7.25–7.19 (m, 1H), 7.15–7.08 (m, 1H), 6.35 (s, 1H), 5.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.4, 143.7, 138.2 (d, J = 1.4 Hz), 135.1, 134.7, 130.4, 129.6, 129.2, 127.6, 124.6, 124.5, 121.7, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.9 Hz); 19F NMR (376 MHz, CDCl3) δ −57.89; HRMS (EI) Calcd for C16H11ClF3NO2 [M+]: 341.0430 found 341.0439; IR (KBr) ν(cm−1): 3420, 1689, 1611, 1527, 1452, 1256, 1216, 1180.

Data of 3q: White solid; mp 88–89 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 7.9 Hz, 1H), 7.52 (s, 1H), 7.39–7.24 (m, 5H), 7.22–7.17 (m, 1H), 7.12–7.06 (m, 1H), 3.77 (t, J = 7.4 Hz, 1H), 3.38 (dd, J = 13.3 and 7.3 Hz, 1H), 2.94 (dd, J = 13.3 and 7.5 Hz, 1H), 2.11 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.8, 138.1, 136.1, 134.2, 129.4, 129.3, 129.0, 127.6, 124.5, 121.7, 120.6 (q, J C-F = 256.9 Hz), 120.5, 54.0, 37.0, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.85; HRMS (EI) Calcd for C17H15ClF3NO2S [M+]: 389.0464 found 389.0471; IR (KBr) ν(cm−1): 3426, 1634, 1529, 1255, 1217, 1179.

2-(4-Bromophenyl)- Data of 2r: White solid; mp 90–91 °C; 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.58 (d, J = 8.3 Hz, 2H), 7.37–7.28 (m, 3H), 7.22 (d, J = 8.2 Hz, 1H), 7.16–7.08 (m, 1H), 6.36 (s, 1H), 5.78 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.3, 143.8, 138.2 (d, J = 1.1 Hz), 135.1, 132.2, 130.4, 129.9, 127.7, 124.6, 124.5, 123.3, 121.7, 120.5 (d, J = 1.2 Hz), 120.3 (q, J C-F = 257.7 Hz); 19F NMR (376 MHz, CDCl3) δ −57.87; HRMS (EI) Calcd for C16H11BrF3NO2 [M+]: 384.9925, found 384.9921; IR (KBr) ν(cm−1): 3420, 1689, 1611, 1527, 1453, 1256, 1216, 1181. Data of 3r: White solid; mp 97–98 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 7.9 Hz, 1H), 7.57–7.47 (m, 3H), 7.30–7.24 (m, 3H), 7.23–7.17 (m, 1H), 7.13–7.05 (m, 1H), 3.76 (t, J = 7.4 Hz, 1H), 3.37 (dd, J = 13.3 and 7.4 Hz, 1H), 2.93 (dd, J = 13.3 and 7.4 Hz, 1H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 169.8, 138.2, 136.7, 132.1, 130.1, 129.5, 129.2, 127.4, 124.5, 122.0, 120.4, 120.2 (q, J C-F = 257.8 Hz), 53.7, 36.9, 16.2; 19F NMR (376 MHz, CDCl3) δ −57.79; HRMS (EI) Calcd for C17H15BrF3NO2S [M+]: 432.9959, found 432.9956; IR (KBr) ν(cm−1): 3274, 1666, 1608, 1528, 1267, 1216, 1171.

2-(4-Iodophenyl)- Data of 2s: White solid; mp 95–97 °C; 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.1 Hz, 1H), 7.97–7.67 (m, 3H), 7.35–7.28 (m, 1H), 7.25–7.20 (m, 1H), 7.18 (d, J = 8.3 Hz, 2H), 7.15–7.09 (m, 1H), 6.35 (s, 1H), 5.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.2, 143.9, 138.3 (d, J = 1.3 Hz), 138.1, 135.7, 130.4, 130.0, 127.7, 124.6, 124.4, 121.7, 120.5 (d, J = 1.0 Hz), 120.3 (q, J C-F = 257.9 Hz), 94.9; 19F NMR (376 MHz, CDCl3) δ −57.85; HRMS (EI) Calcd for C16H11IF3NO2 [M+]: 432.9787 found 432.9780; IR (KBr) ν(cm−1): 3418, 1664, 1610, 1525, 1452, 1258, 1215, 1161. Data of 3s: White solid; mp 114–115 °C; 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.2 Hz, 2H), 7.53 (s, 1H), 7.31–7.23 (m, 1H), 7.22–7.17 (m, 1H), 7.16–7.05 (m, 3H), 3.74 (t, J = 7.4 Hz, 1H), 3.37 (dd, J = 13.3 and 7.4 Hz, 1H), 2.93 (dd, J = 13.3 and 7.4 Hz, 1H), 2.11 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.7, 138.3, 137.3, 130.2, 129.8, 129.6, 127.6, 124.5, 121.7, 120.5, 120.3 (q, J C-F = 258.2 Hz), 93.9, 54.1, 36.9, 16.4.; 19F NMR (376 MHz, CDCl3) δ −57.80; HRMS (EI) Calcd for C17H15F3INO2S [M+]: 480.9820 found 480.9810; IR (KBr) ν(cm−1): 3428, 1634, 1528, 1254, 1216, 1178.

2-(3-Fluorophenyl)- Data of 2t: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.1 Hz, 1H), 7.80 (s, 1H), 7.48–7.38 (m, 1H), 7.35–7.29 (m, 1H), 7.25–7.19 (m, 2H), 7.19–7.08 (m, 3H), 6.41 (s, 1H), 5.79 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.1, 164.0, 161.7, 143.7, 138.3 (d, J = 22.0 Hz), 130.7 (d, J = 8.4 Hz), 130.4, 127.7, 125.1, 124.6, 124.0 (d, J = 3.1 Hz), 121.6, 120.5 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.8 Hz), 116.0 (d, J = 20.9 Hz), 115.5 (d, J = 22.1 Hz); 19F NMR (376 MHz, CDCl3) δ −58.10, −111.71; HRMS (EI) Calcd for C16H11F4NO2 [M+]: 325.0726 found 325.0724; IR (KBr) ν(cm−1): 3419, 1691, 1610, 1528, 1451, 1256, 1217, 1181. Data of 3t: White solid; mp 73–74 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.41–7.33 (m, 1H), 7.31–7.24 (m, 1H), 7.22–7.14 (m, 2H), 7.13–6.98 (m, 3H), 3.80 (t, J = 7.4 Hz, 1H), 3.39 (dd, J = 13.3 and 7.4 Hz, 1H), 2.95 (dd, J = 13.3 and 7.4 Hz, 1H), 2.12 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.6, 163.2 (d, J C-F = 246.3 Hz), 140.1 (d, J = 7.1 Hz), 138.1, 130.8 (d, J = 8.3 Hz), 130.3, 127.6, 124.5, 123.8 (d, J = 2.9 Hz), 121.8, 120.5, 120.3 (q, J C-F = 258.0 Hz), 115.3 (d, J = 20.9 Hz), 115.0 (d, J = 21.9 Hz), 54.3, 36.9, 16.4; 19F NMR (376 MHz, CDCl3) δ −58.10, −111.71; HRMS (EI) Calcd for C17H15F4NO2S [M+]: 373.0760 found 373.0766; IR (KBr) ν(cm−1): 3417, 1682, 1612, 1529, 1257, 1218, 1181.

2-(3-Bromophenyl)- Data of 2u: White solid; mp 66–67 °C; 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.63–7.54 (m, 2H), 7.38 (d, J = 7.7 Hz, 1H), 7.35–7.29 (m, 2H), 7.25–7.19 (m, 1H), 7.15–7.08 (m, 1H), 6.38 (s, 1H), 5.78 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.1, 143.5, 138.3, 138.2 (d, J = 1.5 Hz), 132.0, 131.4, 130.42, 130.37, 127.6, 126.8, 125.1, 124.6, 123.1, 121.7, 120.5 (d, J = 1.1 Hz), 120.3 (q, J C-F = 258.0 Hz); 19F NMR (376 MHz, CDCl3) δ −57.91; HRMS (EI) Calcd for C16H11BrF3NO2 [M+]: 384.9925 found 384.9926; IR (KBr) ν(cm−1): 3303, 1661, 1608, 1526, 1453, 1257, 1213, 1170. Data of 3u: White solid; mp 72–73 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 7.9 Hz, 1H), 7.54 (s, 2H), 7.51–7.44 (m, 1H), 7.35–7.24 (m, 3H), 7.23–7.18 (m, 1H), 7.14–7.05 (m, 1H), 3.75 (t, J = 7.4 Hz, 1H), 3.38 (dd, J = 13.3 and 7.6 Hz, 1H), 2.94 (dd, J = 13.3 and 7.2 Hz, 1H), 2.12 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.5, 139.9, 138.1, 131.4, 131.0, 130.8, 130.7, 130.2, 127.6, 126.6, 124.6, 123.3, 121.8, 120.5, 120.3 (q, J C-F = 258.1 Hz), 54.2, 37.0, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.83; HRMS (EI) Calcd for C17H15BrF3NO2S [M+]: 432.9959 found 432.9945; IR (KBr) ν(cm−1): 3423, 1668, 1634, 1529, 1256, 1217, 1179.

Data of 2v: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.1 Hz, 1H), 7.75 (s, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.38 (d, J = 7.7 Hz, 1H), 7.35–7.27 (m, 3H), 7.25–7.19 (m, 1H), 7.15–7.09 (m, 1H), 6.40 (s, 1H), 5.81 (s, 1H); 13C NMR (150 MHz, CDCl3) δ 164.0, 149.6, 143.5, 138.23, 138.17, 130.4, 130.3, 127.7, 126.6, 125.2, 124.6, 121.6, 121.2, 121.0, 120.5, 120.4 (q, J C-F = 255.7 Hz), 120.3 (q, J C-F = 257.8 Hz); 19F NMR (376 MHz, CDCl3) δ −57.90, −58.08; HRMS (EI) Calcd for C17H11F6NO3 [M+]: 391.0643 found 391.0638; IR (KBr) ν(cm−1): 3422, 1691, 1610, 1528, 1453, 1260, 1216, 1173. Data of 3v: White solid; mp 114–115 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 7.9 Hz, 1H), 7.54 (s, 1H), 7.43 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.31–7.25 (m, 2H), 7.24–7.16 (m, 2H), 7.13–7.06 (m, 1H), 3.81 (t, J = 7.3 Hz, 1H), 3.39 (dd, J = 13.4 and 7.6 Hz, 1H), 2.95 (dd, J = 13.4 and 7.1 Hz, 1H), 2.11 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.5, 149.7, 140.0, 138.1, 130.6, 130.2, 127.6, 126.3, 126.0, 124.6, 121.9, 120.7, 120.5, 120.4 (q, J C-F = 257.9 Hz), 120.3 (q, J C-F = 257.7 Hz), 54.4, 37.1, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.85, −57.98; HRMS (EI) Calcd for C18H15F6NO3S [M+]: 439.0677 found 439.0673; IR (KBr) ν(cm−1): 3423, 1662, 1612, 1529, 1263, 1218, 1176.

Data of 2w: White solid; mp 62–63 °C; 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J = 8.0 Hz, 1H), 7.82–7.68 (m, 3H), 7.60–7.55 (m, 1H), 7.51 (t, J = 7.7 Hz, 1H), 7.35–7.29 (m, 1H), 7.25–7.19 (m, 1H), 7.15–7.09 (m, 1H), 6.39 (s, 1H), 5.83 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.2, 143.6, 138.2 (d, J = 1.4 Hz), 137.8, 136.6, 136.0, 130.6, 130.3, 130.0, 129.4 (q, J C-F = 306.1 Hz), 127.7, 125.5 (d, J = 2.2 Hz), 125.0, 124.7, 121.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 258.5 Hz); 19F NMR (376 MHz, CDCl3) δ −42.52, −58.01; HRMS (EI) Calcd for C17H11F6NO2S [M+]: 407.0415 found 407.0422; IR (KBr) ν(cm−1): 3423, 1693, 1611, 1526, 1454, 1256, 1217, 1168, 1119. Data of 3w: White solid; mp 79–80 °C; 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 7.9 Hz, 1H), 7.68 (s, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 8.1 Hz, 2H), 7.46 (t, J = 7.7 Hz, 1H), 7.31–7.24 (m, 1H), 7.24–7.17 (m, 1H), 7.14–7.07 (m, 1H), 3.81 (t, J = 7.4 Hz, 1H), 3.40 (dd, J = 13.4 and 7.7 Hz, 1H), 2.95 (dd, J = 13.4 and 7.0 Hz, 1H), 2.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.5, 139.4, 138.1, 135.94, 135.86, 130.3, 130.2, 130.1, 129.4 (q, J C-F = 306.0 Hz), 127.6, 125.4, 124.6, 121.9, 120.5, 120.3 (q, J C-F = 257.8 Hz), 54.3, 37.2, 16.4; 19F NMR (376 MHz, CDCl3) δ −42.56, −57.92;; HRMS (EI) Calcd for C18H15F6NO2S2 [M+]: 455.0448 found 455.0445; IR (KBr) ν(cm−1): 3432, 1632, 1529, 1258, 1217, 1166.

Data of 2x: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.49 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.40 (d, J = 7.7 Hz, 1H), 7.33 (s, 1H), 7.31–7.22 (m, 2H), 7.20–7.04 (m, 2H), 6.38 (t, J = 73.3 Hz, 1H), 6.35 (s, 1H), 5.81 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.3, 149.5, 143.8, 140.3 (t, J = 2.4 Hz), 138.3, 130.3, 129.8, 126.6, 126.3, 124.6, 124.5, 121.4, 121.2, 120.9, 120.4 (q, J C-F = 260.0 Hz), 118.6, 116.1 (t, J C-F = 260.0 Hz); 19F NMR (376 MHz, CDCl3) δ −80.31; HRMS (EI) Calcd for C17H12F5NO3 [M+]: 373.0737 found 373.0741; IR (KBr) ν(cm−1): 3413, 1686, 1608, 1527, 1455, 1260, 1214, 1168. Data of 3x: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.2 Hz, 1H), 7.66 (s, 1H), 7.45–7.39 (m, 1H), 7.34 (d, J = 7.7 Hz, 1H), 7.28–7.25 (m, 1H), 7.24–7.16 (m, 2H), 7.07 (d, J = 4.1 Hz, 2H), 6.37 (t, J = 73.3 Hz, 1H), 3.79 (t, J = 7.4 Hz, 1H), 3.38 (dd, J = 13.3 and 7.9 Hz, 1H), 2.93 (dd, J = 13.3 and 6.9 Hz, 1H), 2.12 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 169.5, 149.7, 140.2, 130.9, 130.5, 129.7, 126.3, 126.2, 124.6, 121.5, 120.7, 120.40, 120.39 (q, J C-F = 255.8 Hz), 118.7, 116.3 (t, J C-F = 259.7 Hz), 54.4, 37.3, 16.4; 19F NMR (376 MHz, CDCl3) δ −57.78, −80.07; HRMS (EI) Calcd for C18H16F5NO3S [M+]: 421.0771 found 421.0776; IR (KBr) ν(cm−1): 3423, 1683, 1609, 1529, 1265, 1220, 1175.

2-Phenyl- Data of 2aa: White solid; mp 66–67 °C; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.3 Hz, 1H), 7.79 (s, 1H), 7.62–7.52 (m, 2H), 7.49–7.37 (m, 5H), 7.25–7.18 (m, 1H), 6.40 (s, 1H), 5.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 165.0, 144.7, 136.0, 135.2 (d, J = 1.4 Hz), 132.8 (d, J = 0.8 Hz), 128.96, 128.94, 128.5, 126.0 (q, J C-F = 5.3 Hz), 124.53, 124.46, 123.84, 123.8 (q, J C-F = 271.4 Hz), 119.9 (d, J C-F = 29.7 Hz); 19F NMR (376 MHz, CDCl3) δ −61.07; HRMS (EI) Calcd for C16H12F3NO [M+]: 291.0871 found 291.0869; IR (KBr) ν(cm−1): 3428, 1692, 1594, 1530, 1454, 1321, 1290, 1171, 1114. Data of 3aa: White solid; mp 85–86 °C; 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.0 Hz, 1H), 7.57–7.49 (m, 2H), 7.46 (s, 1H), 7.43–7.30 (m, 5H), 7.19 (t, J = 7.6 Hz, 1H), 3.80 (t, J = 7.4 Hz, 1H), 3.44 (dd, J = 13.3 and 7.1 Hz, 1H), 2.98 (dd, J = 13.3 and 7.8 Hz, 1H), 2.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.5, 137.4, 135.0, 132.8, 129.3, 128.3, 128.1, 126.0 (q, J C-F = 5.3 Hz), 124.5, 124.1, 123.7 (q, J C-F = 271.4 Hz), 54.7, 36.9, 16.4; 19F NMR (376 MHz, CDCl3) δ −60.93; HRMS (EI) Calcd for C17H16F3NOS [M+]: 339.0905 found 339.0915; IR (KBr) ν(cm−1): 3422, 1665, 1616, 1527, 1283, 1208, 1169.

Data of 2ab: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 8.2 Hz, 1H), 7.95 (s, 1H), 7.49–7.41 (m, 5H), 7.29–7.18 (m, 1H), 7.14–6.99 (m, 2H), 6.38 (s, 1H), 6.33 (t, J = 73.3 Hz, 1H), 5.75 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 164.7, 144.8, 140.2 (t, J = 2.3 Hz), 136.4, 130.0, 128.9, 128.8, 128.4, 126.3, 124.4, 124.2, 121.4, 118.6, 116.0 (t, J C-F = 260.6 Hz); 19F NMR (376 MHz, CDCl3) δ −80.28; HRMS (EI) Calcd for C16H13F2NO2 [M+]: 289.0914 found 289.0907; IR (KBr) ν(cm−1): 3406, 1684, 1608, 1527, 1453, 1128, 1055. Data of 3ab: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.2 Hz, 1H), 7.65 (s, 1H), 7.46–7.36 (m, 4H), 7.36–7.30 (m, 1H), 7.22–7.16 (m, 1H), 7.10–7.02 (m, 2H), 6.32 (t, J = 73.4 Hz, 1H), 3.80 (t, J = 7.4 Hz, 1H), 3.42 (dd, J = 13.3 and 7.5 Hz, 1H), 2.96 (dd, J = 13.3 and 7.3 Hz, 1H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.3, 140.1, 137.9, 129.9, 129.2, 128.1, 128.0, 126.3, 124.3, 121.3, 118.7, 116.2 (t, J C-F = 259.8 Hz) 54.8, 37.1, 16.4; 19F NMR (376 MHz, CDCl3) δ −80.28; HRMS (EI) Calcd for C17H17F2NO2S [M+]: 337.0948 found 337.0941; IR (KBr) ν(cm−1): 3420, 1686, 1608, 1528, 1256, 1196, 1127.

2-Phenyl- Data of 2ac: Brown oil; 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 9.0 Hz, 2H), 7.51–7.38 (m, 6H), 7.17 (d, J = 8.6 Hz, 2H), 6.31 (s, 1H), 5.75 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 165.2, 145.5 (t, J = 1.9 Hz), 144.7, 136.4, 136.3, 129.04, 129.00, 128.3, 123.9, 121.7, 121.1, 120.4 (q, J C-F = 257.8 Hz); 19F NMR (376 MHz, CDCl3) δ −58.13; HRMS (EI) Calcd for C16H12F3NO2 [M+]: 307.0820 found 307.0809; IR (KBr) ν(cm−1): 3294, 1657, 1610, 1554, 1507, 1408, 1297, 1208, 1165. Data of 3ac: Brown oil; 1H NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.9 Hz, 2H), 7.44 (s, 1H), 7.42–7.36 (m, 4H), 7.35–7.31 (m, 1H), 7.14 (d, J = 8.6 Hz, 2H), 3.73 (t, J = 7.3 Hz, 1H), 3.40 (dd, J = 13.2 and 8.0 Hz, 1H), 2.91 (dd, J = 13.2 and 6.6 Hz, 1H), 2.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.3, 145.3, 138.1, 136.2, 129.2, 128.1, 127.9, 121.7, 120.9, 120.4 (q, J C-F = 255.3 Hz), 54.6, 37.6, 16.5; 19F NMR (376 MHz, CDCl3) δ −58.17; HRMS (EI) Calcd for C17H16F3NO2S [M+]: 355.0854 found 355.0851; IR (KBr) ν(cm−1): 3421, 1662, 1610, 1511, 1411, 1267, 1223, 1167.

2-Phenyl- Data of 2ad: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J = 2.4 Hz, 1H), 8.34 (d, J = 4.5 Hz, 1H), 8.22 (d, J = 8.2 Hz, 1H), 7.62 (s, 1H), 7.51–7.38 (m, 5H), 7.30–7.25 (m, 1H), 6.31 (s, 1H), 5.77 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 165.7, 145.5, 144.5, 141.2, 136.3, 134.5, 129.1, 129.0, 128.2, 127.3, 124.1, 123.6; HRMS (EI) Calcd for C14H12N2O [M+]: 224.0950 found 224.0953; IR (KBr) ν(cm−1): 3430, 1677, 1592, 1537, 1482, 1422. Data of 3ad: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 2.2 Hz, 1H), 8.32 (d, J = 4.5 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H), 7.58 (s, 1H), 7.42–7.28 (m, 5H), 7.25–7.21 (m, 1H), 3.81–3.75 (m, 1H), 3.40 (dd, J = 13.2 and 8.2 Hz, 1H), 2.90 (dd, J = 13.3 and 6.4 Hz, 1H), 2.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.8, 145.3, 141.0, 138.0, 134.6, 129.2, 128.2, 127.9, 127.2, 123.7, 54.5, 37.6, 16.5; HRMS (EI) Calcd for C15H16N2OS [M+]: 272.0983 found 272.0980; IR (KBr) ν(cm−1): 3429, 1690, 1667, 1540, 1422, 1280, 1027.

2-Phenyl- and 3-(Methylthio)-2-phenyl- Data of 2ae: Brown oil; 1H NMR (400 MHz, CDCl3) δ 10.26 (s, 1H), 8.90 (d, J = 7.4 Hz, 1H), 8.64 (dd, J = 4.1 and 1.5 Hz, 1H), 8.13 (dd, J = 8.3 and 1.4 Hz, 1H), 7.60–7.49 (m, 4H), 7.49–7.42 (m, 3H), 7.39 (dd, J = 8.3 and 4.2 Hz, 1H), 6.33 (s, 1H), 5.84 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 165.8, 148.2, 145.8, 138.7, 136.7, 136.2, 134.4, 128.7, 128.6, 128.3, 127.8, 127.3, 122.3, 121.8, 121.5, 116.6; Data of 3ae: Brown oil; 1H NMR (400 MHz, CDCl3) δ 9.96 (s, 1H), 8.82–8.71 (m, 2H), 8.12 (dd, J = 8.2 and 1.3 Hz, 1H), 7.55–7.46 (m, 4H), 7.44–7.35 (m, 3H), 7.33–7.27 (m, 1H), 4.01–3.95 (m, 1H), 3.48 (dd, J = 13.2 and 8.3 Hz, 1H), 3.00 (dd, J = 13.2 and 6.6 Hz, 1H), 2.15 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.5, 148.2, 138.6, 138.3, 136.3, 134.3, 129.0, 127.9, 127.84, 127.79, 127.3, 121.7, 121.6, 116.5, 55.0, 37.6, 16.4; HRMS (EI) Calcd for C19H18N2OS [M+]: 322.1140 found 322.1124; IR (KBr) ν(cm−1): 3428, 1683, 1604, 1528, 1485, 1426.

2-( Data of 2ba: White solid; mp 84–85 °C; 1H NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.40 (s, 1H), 7.30–7.20 (m, 4H), 7.17 (d, J = 8.2 Hz, 2H), 6.90 (d, J = 7.5 Hz, 1H), 6.21 (s, 1H), 5.64 (s, 1H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.4, 149.6 (d, J = 1.7 Hz), 144.5, 139.1, 133.4, 130.0, 129.7, 128.2, 123.6, 121.7, 120.4 (q, J C-F = 255.9 Hz), 117.8, 116.6, 112.7, 21.2; 19F NMR (376 MHz, CDCl3) δ −57.75; HRMS (EI) Calcd for C17H14F3NO2 [M+]: 321.0977 found 321.0980; IR (KBr) ν(cm−1): 3412, 1657, 1605, 1537, 1439, 1266, 1211, 1159. Data of 3ba: White solid; mp 64–65 °C; 1H NMR (400 MHz, CDCl3) δ 7.52 (s, 1H), 7.30–7.23 (m, 5H), 7.22–7.17 (m, 2H), 6.94 (d, J = 3.5 Hz, 1H), 3.74–3.67 (m, 1H), 3.38 (dd, J = 13.2 and 7.7 Hz, 1H), 2.90 (dd, J = 13.2 and 7.0 Hz, 1H), 2.35 (s, 3H), 2.10 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.5, 149.5, 139.0, 138.0, 134.9, 129.93, 129.92, 127.9, 120.4 (q, J C-F = 255.8 Hz), 117.7, 116.4, 112.6, 54.2, 37.5, 21.1, 16.5; 19F NMR (376 MHz, CDCl3) δ −57.75; HRMS (EI) Calcd for C18H18F3NO2S [M+]: 369.1010 found 369.1018; IR (KBr) ν(cm−1): 3426, 1660, 1610, 1544, 1261, 1220, 1167.

Data of 2bb: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 8.49 (d, J = 8.2 Hz, 1H), 7.47–7.41 (m, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.24 (d, J = 7.9 Hz, 2H), 7.09–7.01 (m, 1H), 6.32 (s, 1H), 5.71 (s, 1H), 2.40 (s, 3H), 2.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.2, 145.2, 138.6, 138.5, 133.7, 133.2, 129.4, 129.0, 128.4, 125.5, 124.5, 123.1, 120.4, 21.3, 18.8; HRMS (EI) Calcd for C17H17NOS [M+]: 283.1031 found 237.1020; IR (KBr) ν(cm−1): 3423, 1682, 1616, 1579, 1513, 1435. Data of 3bb: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 8.32 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H), 7.33–7.27 (m, 3H), 7.19 (d, J = 7.8 Hz, 2H), 7.05–6.98 (m, 1H) 3.79 (t, J = 7.5 Hz, 1H), 3.42 (dd, J = 13.2 and 7.4 Hz, 1H), 2.96 (dd, J = 13.2 and 7.6 Hz, 1H), 2.34 (s, 3H), 2.12 (s, 3H), 2.06 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 170.5, 138.6, 137.8, 135.2, 133.7, 129.8, 129.3, 127.9, 124.9, 124.3, 120.2, 54.4, 37.0, 21.1, 18.8, 16.4; HRMS (EI) Calcd for C18H21NOS2 [M+]: 331.1065 found 331.1066; IR (KBr) ν(cm−1): 3437, 1638, 1582, 1516, 1435, 1298, 1161.

Data of 2bc: White solid; mp 132–134 °C; 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.9 Hz, 2H), 7.38 (s, 1H), 7.37–7.28 (m, 4H), 7.26–7.21 (m, 2H), 7.11 (t, J = 7.4 Hz, 1H), 6.27 (s, 1H), 5.69 (s, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 165.3, 144.9, 138.9, 137.7, 133.7, 129.6, 129.0, 128.2, 124.5, 123.0, 119.8, 21.2; HRMS (EI) Calcd for C16H15NO [M+]: 237.1154 found 237.1158; IR (KBr) ν(cm−1): 3423, 1652, 1598, 1533, 1441.

General procedure for the preparation of d2-2a and d5-3a

A mixture of substrate 1a (29.5 mg, 0.1 mmol), PbCl2 (41.7 mg, 0.15 mmol) and KOAc (14.7 mg, 0.15 mmol) in DMSO-d 6 (2.0 mL) was put into a 15 mL seal tube. The air in the seal tube was exchanged with N2. The reaction mixture was stirred at 156 °C for 13 h under N2, then cooled down to room temperature, diluted with H2O, and extracted with EtOAc (3 × 5 mL). The combined organic phase was washed with brine and dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by preparative TLC plate (petroleum ether: ethyl acetate = 10: 1 as eluent) to get the product d -2a (22.8 mg, 73% yield), d -3a (3.9 mg, 9% yield). Data of d -2a: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.1 Hz, 1H), 7.84 (s, 1H), 7.52–7.35 (m, 5H), 7.34–7.28 (m, 1H), 7.23–7.15 (m, 1H), 7.13–7.06 (m, 1H), 6.43 (s, 0.02H), 5.75 (s, 0.02H); 13C NMR (100 MHz, CDCl3) δ 164.5, 144.4, 138.2 (d, J = 1.3 Hz), 136.3, 130.6, 129.0, 128.9, 128.4, 127.6, 124.4, 121.6, 120.4 (d, J = 1.1 Hz), 120.3 (q, J C-F = 257.8 Hz); 19F NMR (376 MHz, CDCl3) δ −57.98; HRMS (EI) Calcd for C16H10D2F3NO [M+]: 309.0946 found 309.0942; IR (KBr) ν(cm−1): 3400, 1697, 1608, 1531, 1453, 1256, 1216, 1181. Data of d -3a: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.1 Hz, 1H), 7.53 (s, 1H), 7.44–7.33 (m, 5H), 7.29–7.24 (m, 1H), 7.21–7.15 (m, 1H), 7.10–7.04 (m, 1H), 3.80 (s, 1H); 13C NMR (150 MHz, CDCl3) δ 170.3, 137.9, 137.6, 130.4, 129.3, 128.3, 128.04, 127.5, 124.3, 121.6, 120.4, 120.3 (q, J C-F = 258.3 Hz), 62.12; 19F NMR (376 MHz, CDCl3) δ −57.92; HRMS (EI) Calcd for C16H11D5F3NO2S [M+]: 348.1168 found 348.1157; IR (KBr) ν(cm−1): 3403, 1692, 1608, 1529, 1453, 1255, 1218, 1180.

General procedure for the synthesis of the dimeric compounds 4

A mixture of substrate 1 (0.1 mmol), PbCl2 (41.7 mg, 0.15 mmol) and KHCO3 (x mmol) in DMSO (2.0 mL) was put into a 15 mL seal tube. The air in the seal tube was exchanged with N2. The reaction mixture was stirred at 156 °C for 13 h under N2, then cooled down to room temperature, diluted with H2O, and extracted with EtOAc (3 × 5 mL). The combined organic phase was washed with brine and dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by preparative TLC plate (dichloromethane: petroleum ether = 2: 1 as eluent) to get the product 2 and 4.

, -bis(2-(trifluoromethoxy)phenyl) pentanediamide ( , -bis(2-(trifluoromethoxy)phenyl)pentanedi amide (±)-4a. Data of (: White solid; mp 115–117 °C; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.1 Hz, 2H), 7.43 (s, 2H), 7.42–7.36 (m, 4H), 7.36–7.29 (m, 6H), 7.29–7.23 (m, 2H), 7.20–7.15 (m, 2H), 7.10–7.03 (m, 2H), 3.67 (t, J = 7.5 Hz, 2H), 3.25–3.15 (m, 1H), 2.42–2.32 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 171.2, 138.4, 138.0, 130.5, 129.4, 128.1, 127.5, 124.2, 121.6, 120.4, 120.2 (q, J C-F = 257.9 Hz), 51.5, 35.9; 19F NMR (376 MHz, CDCl3) δ −57.92; HRMS (EI) Calcd for C31H24F6N2O4 [M+]: 602.1640, found 602.1629; IR (KBr) ν(cm−1): 3412, 1674, 1608, 1531, 1452, 1260, 1216, 1177. Data of (±)-4a: White solid; mp 135–137 °C; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.1 Hz, 2H), 7.47 (s, 2H), 7.44–7.39 (m, 4H), 7.39–7.34 (m, 2H), 7.34–7.28 (m, 4H), 7.25–7.21 (m, 2H), 7.18–7.10 (m, 2H), 7.08–7.01 (m, 2H), 3.59 (t, J = 7.8 Hz, 2H), 2.88 (t, J = 7.8 Hz, 2H); 13C NMR (150 MHz, CDCl3) δ 171.3, 137.9, 137.6, 130.5, 129.6, 128.4, 128.3, 127.5, 124.1, 121.5, 120.5, 120.2 (q, J C-F = 258.1 Hz), 51.6, 35.0; 19F NMR (376 MHz, CDCl3) δ −58.08; HRMS (EI) Calcd for C31H24F6N2O4 [M+]: 602.1640, found 602.1636; IR (KBr) ν(cm−1): 3419, 1665, 1608, 1528, 1452, 1260, 1218, 1173.

2,4-Di([1,1'-biphenyl]-4-yl)- -bis(2-(trifluoromethoxy) phenyl)pentanediamide 4i. Data of 4i: White solid; mp 160–161 °C; 1H NMR (400 MHz, CDCl3) δ 8.39 (t, J = 7.4 Hz, 3.27H), 7.65 (d, J = 8.1 Hz, 3.55H), 7.63–7.52 (m, 12.80H), 7.51–7.39 (m, 16.12H), 7.39–7.31 (m, 3.64H), 7.30–7.21 (m, 4.59H), 7.20–7.10 (m, 3.44H), 7.10–7.00 (m, 3.59H), 3.78 (t, J = 7.5 Hz, 1.79H), 3.71 (t, J = 7.8 Hz, 2H), 3.34–3.21 (m, 1H), 2.94 (t, J = 7.8 Hz, 1.79H), 2.54–2.40 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 171.3, 171.2, 141.4, 141.1, 140.45, 140.42, 138.04, 137.96, 137.3, 136.5, 130.5, 128.9, 128.83, 128.81, 128.5, 128.3, 128.1, 127.52, 127.47, 127.09, 127.06, 124.24, 124.20, 121.7, 121.5, 120.5, 120.3 (q, J C-F = 258.2 Hz), 120.2 (q, J C-F = 257.4 Hz), 51.3, 35.9, 35.0; 19F NMR (376 MHz, CDCl3) δ −57.85, −57.99; HRMS (ESI) Calcd for C43H32F6N2O4 [M+]: 755.2345 found 755.2338; IR (KBr) ν(cm−1): 3414, 1671, 1608, 1528, 1451, 1257, 1217, 1178.

2,4-Di(naphthalen-2-yl)- -bis(2-(trifluoromethoxy) phenyl)pentanediamide 4n. Data of 4n: White solid; mp 128–129 °C; 1H NMR (400 MHz, CDCl3) δ 8.44–8.31 (m, 4H), 7.92 (d, J = 8.5 Hz, 2H), 7.90–7.77 (m, 12H), 7.75 (s, 2H), 7.59–7.40 (m, 16H), 7.30–7.18 (m, 4H), 7.17–6.97 (m, 8H), 3.91 (t, J = 6.8 Hz, 2H), 3.78 (t, J = 7.3 Hz, 2H), 3.46–3.33 (m, 1H), 3.07 (t, J = 7.4 Hz, 2H), 2.66–2.53 (m, 1H);13C NMR (100 MHz, CDCl3) δ 171.2, 138.1, 138.0, 135.9, 135.0, 133.61, 133.57, 133.1, 132.9, 130.5, 130.4, 129.6, 129.4, 127.84, 127.78, 127.74, 127.67, 127.4, 127.3, 126.6, 126.5, 126.4, 126.3, 125.5, 125.4, 124.25, 124.20, 121.8, 121.6, 121.4, 120.4, 120.3 (q, J C-F = 258.2 Hz), 120.2 (q, J C-F = 257.4 Hz), 51.7, 35.9, 34.8; 19F NMR (376 MHz, CDCl3) δ −58.03, −58.21; HRMS (ESI) Calcd for C39H28F6N2O4 [M+]: 703.2032 found 703.2028; IR (KBr) ν(cm−1): 3262, 1669, 1607, 1530, 1452, 1258, 1216, 1179.

2,4-Di(thiophen-3-yl)- -bis(2-(trifluoromethoxy) phenyl)pentanediamide 4o. Data of 4o: White solid; mp 118–119 °C; 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 8.2 Hz, 3.11H), 7.68 (s, 1.80H), 7.53 (s, 1.73H), 7.45 (dd, J = 4.8 and 3.0 Hz, 1.57H), 7.40 (dd, J = 4.8 and 3.0 Hz, 1.48H), 7.31–7.22 (m, 7.25H), 7.22–7.14 (m, 3.24H), 7.12 (d, J = 4.8 Hz, 1.70H), 7.10–7.01 (m, 5.10H), 3.90 (t, J = 7.5 Hz, 1.87H), 3.82 (t, J = 7.9 Hz, 2H), 3.21–3.08 (m, 1H), 2.82 (t, J = 7.9 Hz, 1.88H), 2.43–2.31 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 170.9, 170.8, 138.6, 137.9, 130.5, 130.4, 127.9, 127.6, 127.52, 127.50, 126.7, 126.6, 124.3, 123.6, 123.1, 121.6, 121.5, 120.50, 120.45, 120.29 (q, J C-F = 258.2 Hz), 120.26 (q, J C-F = 257.4 Hz), 46.9, 46.8, 35.7, 35.4; 19F NMR (376 MHz, CDCl3) δ −57.88, −57.99; HRMS (ESI) Calcd for C27H20F6N2O4S2 [M+]: 615.0847 found 615.0843; IR (KBr) ν(cm−1): 3408, 1671, 1609, 1529, 1452, 1258, 1217, 1181.

2,4-Bis(4-chlorophenyl)- -bis(2-(trifluoromethoxy) phenyl)pentanediamide 4q. Data of 4q: White solid; mp 132–134 °C; 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.1 Hz, 4.03H), 7.46 (s, 2.69H), 7.44–7.33 (m, 10.66H), 7.27 (d, J = 6.3 Hz, 14.29H), 7.22–7.14 (m, 4.54H), 7.13–7.03 (m, 4.67H), 3.62 (dd, J = 13.7 and 7.4 Hz, 4.72H), 3.16–3.04 (m, 1H), 2.75 (t, J = 7.7 Hz, 2.71H), 2.35–2.25 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.6, 170.5, 138.2 (d, J = 2.5 Hz), 138.1 (d, J = 1.3 Hz), 136.7, 136.2, 134.3, 134.1, 130.8, 130.2, 129.7, 129.53, 129.52, 129.3, 127.52, 127.50, 124.5, 123.6, 121.9, 121.7, 120.5, 120.3 (q, J C-F = 258.1 Hz), 120.2 (q, J C-F = 257.9 Hz), 50.9, 50.8, 36.4, 35.7; 19F NMR (376 MHz, CDCl3) δ −57.86, −58.01; HRMS (ESI) Calcd for C31H22Cl2F6N2O4 [M+]: 671.0939 found 671.0936; IR (KBr) ν(cm−1): 3424, 1636, 1616, 1529, 1493, 1257, 1217, 1180.

, -bis(2-(trifluoromethoxy)phenyl)pentanediamide ( , -bis(2-(trifluoromethoxy) phenyl)pentanediamide (±)-4r. Data of (: White solid; mp 167–171 °C; 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.1 Hz, 2H), 7.58–7.46 (m, 4H), 7.41 (s, 2H), 7.30–7.24 (m, 3H), 7.20 (d, J = 8.3 Hz, 5H), 7.14–7.05 (m, 2H), 3.60 (t, J = 7.5 Hz, 2H), 3.15–3.03 (m, 1H), 2.35–2.25 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.5, 138.2, 137.2136.8, 132.7, 132.5, 130.2, 129.9, 129.7, 127.5, 124.6, 122.3, 121.9, 120.5 (d, J = 1.0 Hz), 120.3 (q, J C-F = 258.2 Hz), 50.9, 36.4; 19F NMR (376 MHz, CDCl3) δ −57.84; HRMS (ESI) Calcd for C31H22Br2F6N2O4Na [M + Na+]: 780.9748 found 780.9740; IR (KBr) ν(cm−1): 3422, 1674, 1613, 1530, 1452, 1254, 1218, 1179. Data of (±)-4r: White solid; mp 152–155 °C; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.0 Hz, 2H), 7.60–7.49 (m, 4H), 7.45 (s, 2H), 7.32–7.24 (m, 3H), 7.23–7.16 (m, 5H), 7.13–7.04 (m, 2H), 3.62 (t, J = 7.7 Hz, 2H), 2.74 (t, J = 7.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 170.5, 138.2, 136.8, 132.6, 130.2, 129.8, 127.5, 124.6, 122.4, 121.7, 120.5, 120.2 (q, J C-F = 257.6 Hz), 51.0, 35.6; 19F NMR (376 MHz, CDCl3) δ −57.99; HRMS (EI) Calcd for C31H22Br2F6N2O4 [M+]: 757.9850 found 757.9849; IR (KBr) ν(cm−1): 3418, 1665, 1609, 1535, 1453, 1257, 1217, 1171.

2,4-Bis(4-iodophenyl)- -bis(2-(trifluoromethoxy) phenyl)pentanediamide 4s. Data of 4s: White solid; mp 164–165 °C; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.9 Hz, 3.79H), 7.79–7.66 (m, 7.81H), 7.44 (d, J = 9.1 Hz, 4.32H), 7.31–7.22 (m, 5.06H), 7.22–7.14 (m, 4.07H), 7.13–7.02 (m, 12.47H), 3.64–3.53 (m, 4.17H), 3.16–3.01 (m, 1H), 2.74 (t, J = 7.7 Hz, 2.16H), 2.33–2.24 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.43, 170.39, 138.6, 138.4, 138.2, 138.1, 137.9, 137.4, 130.2, 130.1, 129.9, 127.52, 127.50, 124.6, 121.9, 121.7, 120.5, 120.33 (q, J C-F = 258.9 Hz), 120.29 (q, J C-F = 258.4 Hz), 93.9, 93.7, 51.1, 51.0, 36.2, 35.5; 19F NMR (376 MHz, CDCl3) δ −57.81, −57.97; HRMS (ESI) Calcd for C31H22F6I2N2O4 [M+]: 854.9652 found 854.9644; IR (KBr) ν(cm−1): 3415, 1670, 1608, 1530, 1452, 1256, 1217, 1179.

2,4-Bis(3-fluorophenyl)- -bis(2-(trifluoromethoxy) phenyl) pentanediamide 4t. Data of 4t: White solid; mp 130–131 °C; 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 8.2 Hz, 2.53H), 7.49 (s, 1.40H), 7.45–7.32 (m, 4.46H), 7.31–7.23 (m, 5.42H), 7.22–7.15 (m, 2.64H), 7.14–6.99 (m, 10.61H), 3.74–3.62 (m, 3.02H), 3.18–3.08 (m, 1H), 2.77 (t, J = 7.7 Hz, 1.41H), 2.39–2.29 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.4, 170.3, 164.6, 164.5, 162.1, 162.0, 140.7, 140.6, 140.3, 140.2, 138.1, 131.15, 131.07, 131.0, 130.9, 130.3, 127.5, 124.5, 123.93, 123.90, 123.81, 123.78, 121.8, 121.7, 120.5, 120.3 (q, J C-F = 258.0 Hz), 120.2 (q, J C-F = 257.7 Hz), 115.4, 115.3, 115.2, 115.1, 114.9, 51.2, 36.1, 35.6; 19F NMR (376 MHz, CDCl3) δ −57.96, −58.08, −111.06, −111.25; HRMS (ESI) Calcd for C31H22F8N2O4 [M+]: 639.1530 found 639.1528; IR (KBr) ν(cm−1): 3421, 1668, 1611, 1530, 1451, 1261, 1217, 1173.

2,4-Bis(3-bromophenyl)- -bis(2-(trifluoromethoxy) phenyl)pentanediamide 4u. Data of 4u: Brown oil; 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 3.54H), 7.62–7.39 (m, 11.71H), 7.36–7.23 (m, 12.50H), 7.23–7.15 (m, 3.95H), 7.14–7.03 (m, 4.12H), 3.70 (t, J = 7.7 Hz, 2H), 3.62 (t, J = 7.4 Hz, 2.04H), 3.19–3.05 (m, 1H), 2.72 (t, J = 7.7 Hz, 2.04H), 2.39–2.28 (m, 1H);13C NMR (101 MHz, CDCl3) δ 170.34, 170.26, 140.4, 140.2, 138.2, 131.4, 131.3, 131.2, 131.0, 130.9, 130.8, 130.20, 130.16, 127.5, 126.7, 124.6, 123.5, 123.4, 121.9, 121.8, 120.5, 120.3 (q, J C-F = 258.1 Hz), 120.2 (q, J C-F = 258.0 Hz), 51.1, 36.2, 35.9; 19F NMR (376 MHz, CDCl3) δ −57.87, −57.99. HRMS (ESI) Calcd for C31H22F6Br2N2O4 [M+]: 758.9929 found 758.9924; IR (KBr) ν(cm−1): 3417, 1677, 1609, 1527, 1453, 1256, 1215, 1181.

-bis(2-(trifluoromethoxy)phenyl)-2,4-bis(3-(trifluoromethoxy)phenyl)pentanediamide 4v. Data of 4v: White solid; mp 100–101 °C; 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 8.2 Hz, 3.98H), 7.55–7.38 (m, 8.78H), 7.35–7.23 (m, 10.71H), 7.23–7.14 (m, 10.77H), 7.14–7.04 (m, 4.40H), 3.73 (t, J = 7.7 Hz, 2.36H), 3.67 (t, J = 7.4 Hz, 2H), 3.21–3.07 (m, 1H), 2.77 (t, J = 7.7 Hz, 2.36H), 2.42–2.30 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.2, 170.1, 149.9, 140.4, 140.2, 138.2, 130.9, 130.8, 130.1, 127.5, 126.4, 126.3, 124.7, 121.9, 121.8, 120.9, 120.6, 120.5, 120.36 (q, J C-F = 256.1 Hz), 120.35 (q, J C-F = 256.1 Hz), 120.3 (q, J C-F = 257.8 Hz), 120.2 (q, J C-F = 257.8 Hz), 51.2, 36.4, 36.0; 19F NMR (376 MHz, CDCl3) δ −57.90, −57.94, −58.08, −58.19; HRMS (ESI) Calcd for C33H22F12N2O6 [M+]: 771.1365 found 771.1369; IR (KBr) ν(cm−1): 3420, 1665, 1610, 1532, 1454, 1265, 1217, 1172.

-bis(2-(trifluoromethoxy)phenyl)-2,4-bis(3-((trifluoromethyl)thio)phenyl)pentanediamide 4w. Data of 4w: White solid; mp 90–91 °C; 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 7.8 Hz, 4.26H), 7.73–7.56 (m, 9.14H), 7.55–7.39 (m, 14.37H), 7.32–7.23 (m, 5.25H), 7.23–7.15 (m, 4.52H), 7.14–7.04 (m, 4.55H), 3.75 (t, J = 7.6 Hz, 2.58H), 3.68 (t, J = 7.4 Hz, 2H), 3.22–3.10 (m, 1H), 2.78 (t, J = 7.6 Hz, 2.54H), 2.44–2.32 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.2, 170.1, 139.8, 139.6, 138.2, 137.3, 136.0, 135.9, 135.7, 130.54, 130.50, 130.43, 130.37, 130.12, 130.08, 129.4 (q, J C-F = 306.0 Hz), 127.5, 125.8, 124.7, 122.0, 121.9, 120.5, 120.3 (q, J C-F = 258.2 Hz), 120.2 (q, J C-F = 257.9 Hz), 51.1, 36.7, 36.2; 19F NMR (376 MHz, CDCl3) δ −42.54, −42.63, −58.01, −58.13; HRMS (ESI) Calcd for C33H22F12N2O4S2 [M+]: 803.0908 found 803.0913; IR (KBr) ν(cm−1): 3272, 1672, 1611, 1534, 1454, 1257, 1220, 1168.

-bis(2-(difluoromethoxy)phenyl)-2,4-bis(3-(trifluoromethoxy)phenyl)pentanediamide 4x. Data of 4x: White solid; mp 86–87 °C; 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.2 Hz, 3.01H), 7.57 (s, 1.70H), 7.51 (s, 1.51H), 7.48–7.37 (m, 3.61H), 7.35–7.25 (m, 6.05H), 7.24–7.15 (m, 9.08H), 7.13–7.03 (m, 6.09H), 6.37 (t, J = 73.3 Hz, 1.78H), 6.30 (t, J = 73.2 Hz, 2H), 3.73 (t, J = 7.7 Hz, 2H), 3.62 (t, J = 7.5 Hz, 1.79H), 3.15–3.05 (m, 1H), 2.73 (t, J = 7.7 Hz, 1.78H), 2.42–2.31 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.2, 170.1, 149.8, 140.6, 140.5, 140.4, 130.74, 130.67, 129.6, 126.4, 126.3, 126.21, 126.19, 124.72, 124.67, 121.85, 121.7, 120.8, 120.58, 120.57 (q, JC-F = 257.3 Hz), 120.55 (q, JC-F = 257.8 Hz), 120.4, 119.1, 118.9, 118.8, 116.11 (t, JC-F = 260.0 Hz), 116.06 (t, J C-F = 260.1 Hz), 51.24, 51.18, 36.6, 36.5; 19F NMR (376 MHz, CDCl3) δ −57.80, −57.85, −80.27, −80.30, −80.32, −80.35; HRMS (ESI) Calcd for C33H24F10N2O6 [M+]: 735.1553 found 735.1552; IR (KBr) ν(cm−1): 3287, 1660, 1609, 1530, 1455, 1262, 1217, 1135.