Synthesis of CF3CH2-Containing Indolines by Transition Metal-Free

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Synthesis of CF3CH2-Containing Indolines by Transition Metal-Free Aryltrifluoromethylation of Unactivated Alkenes Deqiang Liang, Qishan Dong, Penghui Xu, Ying Dong, Weili Li, and Yinhai Ma J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01861 • Publication Date (Web): 10 Sep 2018 Downloaded from http://pubs.acs.org on September 10, 2018

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The Journal of Organic Chemistry

Synthesis of CF3CH2-Containing Indolines by Transition Metal-Free Aryltrifluoromethylation of Unactivated Alkenes Deqiang Liang,*,†,§ Qishan Dong,† Penghui Xu,† Ying Dong,‡ Weili Li,§ and Yinhai Ma† †

Department of Chemistry, Kunming University, Kunming 650214, China College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014, China § Yunnan Engineering Technology Research Center for Plastic Films, Kunming 650214, China ‡

ABSTRACT: With unactivated double bond as the radical acceptor, allyl amines underwent metal-free trifluoromethylation/cyclization cascade with CF3SO2Na (Langlois' reagent), affording CF3CH2-containing indolines and tetrahydroisoquinolines, whose practical syntheses are significant challenges. This protocol features mild conditions, low cost, and broad substrate scope.

INTRODUCTION The polyfluoroalkyl-containing compounds, which show improved biological, physical, and chemical properties compared to that of their C-H counterparts, are finding increasing applications in pharmaceuticals, agrochemicals and material science.1 Significant efforts have been directed toward the incorporation of a polyfluoroalkyl group into various organic systems.2 In this context, trifluoromethylative vicinal difunctionalization of activated alkenes has proven to be a powerful strategy to access molecule complexity,3-6 while trifluoromethylation of unactivated ones remains more rudimentary.7,8

conditions (Scheme 2).8,13 The reduction of oxindoles might afford related indolines as well, yet it suffers from severe functional group intolerance.14 Therefore, it is highly desirable to develop a general, practical, and cost-effective method for the synthesis of the title CF3CH2-containing indolines. Scheme 2. Previous Syntheses of 3-(2,2,2-Trifluoroethyl) Indolines

Scheme 1. Synthesis of CF3CH2-Containing Oxindoles from NArylacrylamides

Indolic motifs are core structures of many natural alkaloids and clinical drugs,9 and it is more challenging in indole chemistry to elaborate an indoline framework than to synthesize other indolic variants such as oxindole.10 For example, CF3CH2-containing oxindoles can be readily accessed either through trifluoromethylation/cyclization cascade of activated alkenes of N-arylacrylamides5 (Scheme 1) or acryl sulfonamides,6 or through derivatization reaction of their parent oxindoles,11 whereas the synthesis of 3-(2,2,2trifluoroethyl) indolines still remains a significant challenge, probably because unactivated alkenes are prone to polymerization and double bond transfer.12 Very few examples of 3-(2,2,2-trifluoroethyl) indoline synthesis have been disclosed, and they are associated with tedious procedures, narrow substrate scope, high cost, and/or harsh/toxic

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In connection with our continuous efforts in the synthesis of biologically active molecules,15 herein, we report a metal-free tandem trifluoromethylation/arylation of unactivated alkenes, which leads to CF3CH2-containing indolines and 1,2,3,4tetrahydroisoquinolines. A methodology for 4-(2,2,2trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline synthesis is also highly valuable, because there is only one report on such a synthesis, in which only one example was presented.16 The inexpensive and stable solid CF3SO2Na (Langlois' reagent) was used as the radical trifluoromethylating agent, and this protocol features mild conditions, easy operation, low cost, and broad substrate scope.

RESULTS AND DISCUSSION

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performing the reaction in other tested solvents, including tetrahydrofuran (THF, entry 3), MeNO2, MeCN, CH2Cl2, toluene and EtOH (entries 4-8). A comparison of a series of oxidants was also conducted. While tert-butyl hydroperoxide (TBHP, entry 10) is less active than K2S2O8 in this cyclization, use of Oxone (entry 9), di-tert-butyl peroxide (DTBP, entry 11), phenyliodine diacetate (PIDA, entry 12), or mchloroperbenzoic acid (mCPBA, entry 13) gave product 2a1 in 0-6% yields. At room temperature under otherwise identical conditions, this aryltrifluoromethylation did not proceed, and only the decomposition of substrate 1a1 was observed (entry 14). With reduced loading of K2S2O8 (entry 15) or CF3SO2Na (entry 16), indoline 2a1 was yielded in compromised yields. Table 2. Synthesis of 3-(2,2,2-Trifluoroethyl) Indolinesa

Table 1. Optimization of the Reaction Conditionsa

Entry

Oxidant

Solvent

Yield (%)

1

K2S2O8

DMSO

83

2

K2S2O8

DMF

68 (13)b

3

K2S2O8

THF

nr

4

K2S2O8

MeNO2

nr

5

K2S2O8

MeCN

nr

6

K2S2O8

CH2Cl2

0 (4)b (65)c

7

K2S2O8

toluene

0 (7)b (78)c

8

K2S2O8

EtOH

nr

9

Oxone

DMSO

0 (12)b (66)c

DMSO

72 (9)b

d

10

TBHP

11

DTBP

DMSO

6 (70)b

12

PIDA

DMSO

nr

13

mCPBA

DMSO

nr

14

e

K2S2O8

DMSO

0 (32)b (48)c

15f

K2S2O8

DMSO

66

16g

K2S2O8

DMSO

72

a

Reaction conditions: 1a1 (1.0 mmol), CF3SO2Na (2.0 mmol), oxidant (1.5 mmol), solvent (3.0 mL), 50 °C, 24 h. bIsolation of Nphenylacetamide. cRecovery of 1a1. d5.0−6.0 mol/L in decane. e The reaction was performed at ambient temperature. fThe reaction was performed with 1.1 equiv of K2S2O8. gThe reaction was performed with 1.5 equiv of CF3SO2Na.

We began our studies by investigating the aryltrifluoromethylation of N-(2-methylallyl) acetanilide 1a1 (Table 1). To our delight, exposure of 1a1 to 2 equiv of CF3SO2Na and 1.5 equiv of K2S2O8 in 50 °C dimethylsulfoxide (DMSO, entry 1) furnished 3-(2,2,2-trifluoroethyl) indoline 2a1 in 83% yield. Using N,N-dimethylformamide (DMF, entry 2) as the solvent, 2a1 was delivered in 68% yield, along with acetanilide, arising from the oxidative N-deprotection, formed in 13% yield. Indoline 2a1 could not be obtained by

a

Reaction conditions: 1 (1.0 mmol), CF3SO2Na (2.0 mmol), K2S2O8 (1.5 mmol), DMSO (3.0 mL), 50 °C, 24 h.

Under the optimized reaction conditions, a variety of trifluoromethylated indolines 2 were prepared from various allylated anilines 1 (Table 2). N-(2-methylallyl) acetanilides bearing a methyl, bromo, or phenyl group at the para position of the N-aryl group reacted with CF3SO2Na to afford 5-

2


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substituted indolines 2a2-4 in 64-86% yields. Propionyl- and octanoyl-protected indolines 2b1,2 were both furnished in high yields from corresponding anilides. Sulfonyl protecting groups (PGs) were also tolerated, and methylsulfonyl-, ethylsulfonyl-, phenylsulfonyl-, tosyl-, o-tolylsulfonyl-, (4bromophenyl)sulfonyl-, or N,N-dimethylsulfamoyl-protected allylated anilines having an electron-neutral, -rich, or -deficient N-aryl group all participated in this tandem reaction smoothly, affording the desired CF3CH2-containing indolines 2c-h in moderate to high yields. The structure of 2e1 was unambiguously confirmed by X-ray crystallography (Figure S1, see the Supporting Information). N-Allyl acetanilide with an ortho-substituent on the N-aryl ring proved to be a challenging substrate, providing corresponding 7-methyl indoline 2i in only a poor yield as a result of steric conflict. With anilines bearing a meta-substituted N-aryl group, poor regioselectivity was observed, and 4-substituted indolines 2j-l and regioisomeric 6-substituted counterparts 2j'-l' were simultaneously produced. Interestingly, more encumbered products 2j-l are major isomers. At this stage, the origin of such a selectivity remains unclear, yet it might be associated with intermediate stability. Unfortunately, we failed to isolate any pure product from the complex reaction mixture of 3chlorobenzoyl-protected N-allyl aniline, which is probably because both phenyl rings might serve as the radical acceptor during reaction. An electron-withdrawing N-PG is essential, for the use of N-methyl-N-(2-methylallyl)aniline also gave a complex mixture, probably due to overreaction as a result of the electron-rich nature of the substrate. Table 3. Synthesis Tetrahydroisoquinolinesa

of

CF3CH2-Containing

1,2,3,4-

Our initial studies focused on the trifluoromethylative cyclization of N-(2-methylallyl) substrates, in order to steer clear of potentially competing formal 6-endo-trig cyclization, which is also favoured according to Baldwin's rule.17 After we achieved excellent exo selectivity in all the above reactions, simple N-allyl aniline was also evaluated as the substrate. To our surprise, subjecting N-allyl-N-(4bromophenyl)methanesulfonamide 5 to our standard conditions delivered 5-exo-trig product 6 exclusively in 91% yield (Scheme 3). Scheme 4. Proposed Reaction Mechanism

To probe the radical nature of this transformation, radical trapping experiments were conducted (Scheme 4a). As might be expected, the model reaction under standard conditions was almost completely suppressed by adding 4 equiv of 2,2,6,6tetramethylpiperidine-1-oxyl (TEMPO), 2,6-di-tert-butyl-4methylphenol (BHT), or 1,1-diphenylethylene (DPE) as the radical scavenger, and DPE-CF3 adduct 7 was isolated in 32% yield in the DPE experiment. On the basis of the above results and previous reports,5g,h,18 a tentative mechanism is proposed (Scheme 4b). At the beginning, CF3SO2Na reacts with K2S2O8 to deliver sulfate dianion, sulfate radical anion, and trifluoromethanesulfonyl radical. The decomposition of the radical releases a molecule of SO2 to furnish trifluoromethyl radical, the addition of which to the unactivated double bond of 1a1 gives alkyl radical A.5a,7,8e,f,17a,b Ring closure ensues, through intramolecular radical tapping by the phenyl ring, producing dearomatizated aryl radical B.5,6,8e Subsequent hydrogen atom transfer from B to sulfate radical anion releases indoline 2a1 as well as the hydrogen sulfate anion.

a

CONCLUSIONS

This protocol could be extended to N-allylated benzylamines 3 (Table 3). For example, 4-(2,2,2trifluoroethyl)-1,2,3,4-tetrahydroisoquinolines 4a-d were obtained from N-allyl benzylamines protected by phenylsulfonyl, or o-tolylsulfonyl group, with yields ranging from 41-65%.

In conclusion, a metal-free trifluoromethylation/cyclization radical cascade of allyl amines using unactivated double bond as the radical acceptor has been developed. This reaction provides direct access to CF3CH2-containing indolines and 1,2,3,4-tetrahydroisoquinolines, and notable advantages include mild conditions, simple operation, low cost, and broad substrate scope.

Scheme 3. Trifluoromethylation/Cyclization of Simple N-Allyl Aniline

EXPERIMENTAL SECTION

Reaction conditions: 3 (1.0 mmol), CF3SO2Na (2.0 mmol), K2S2O8 (1.5 mmol), DMSO (3.0 mL), 50 °C, 24 h.

General. Chemicals were all purchased from commercial sources and used without treatment. Reactions were monitored by Thin Layer Chromatography (TLC) using silica gel F254 plates. Products were purified by column chromatography over 300-400 mesh silica gel under a positive pressure of air. 1H, 13C, DEPT, 19F and 2D NMR spectra were

3



recorded at 25 °C on a Bruker AscendTM 400 spectrometer using TMS as internal standard. High-resolution mass spectra (HRMS) were obtained using a Bruker microTOF II Focus spectrometer (ESI). Synthesis of CF3CH2-containing indolines and 1,2,3,4tetrahydroisoquinolines (2a1 as an example). A 35-mL Schlenk tube, equipped with a magnetic stirring bar, was charged with CF3SO2Na (312 mg, 2.0 mmol), K2S2O8 (405 mg, 1.5 mmol), and N-(2-methylallyl)-N-phenylacetamide 1a (189 mg, 1.0 mmol), followed by the addition of DMSO (3.0 mL). The mixture was stirred at 50 °C for 24 h, then it was quenched with saturated aqueous Na2S2O3 (2.0 mL) and water (15.0 mL), and extracted with CH2Cl2 (10.0 mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether– ethyl acetate = 30:1, v/v) to afford 1-(3-methyl-3-(2,2,2trifluoroethyl)indolin-1-yl)ethan-1-one 2a1 as a pale yellow oil (214 mg, 83% yield). 2a1, 1-(3-methyl-3-(2,2,2-trifluoroethyl)indolin-1-yl)ethan1-one, white solid: mp 73-74 °C. 1H NMR (400 MHz, DMSOd6) δ = 1.37 (s, 3H), 2.16 (s, 3H), 2.63-2.76 (m, 1H), 2.812.93 (m, 1H), 3.90 (d, J = 10.8 Hz, 1H), 4.14 (d, J = 10.8 Hz, 1H), 7.04 (ddd, J = 0.7, 7.4, 7.4 Hz, 1H), 7.20 (ddd, J = 0.9, 7.4, 7.4 Hz, 1H), 7.36 (d, J = 7.4 Hz, 1H), 8.03 (d, J = 7.4 Hz, 1H); 13C{1H} NMR (100 MHz, DMSO-d6) δ = 169.1, 141.8, 138.2, 128.4, 127.3 (q, 1J(C–F) = 277.1 Hz), 123.9, 123.6, 116.3, 60.7, 42.1 (q, 2J(C–F) = 25.4 Hz), 40.9 (q, 3J(C–F) = 1.3 Hz), 27.3, 24.4; 19F NMR (376 MHz, DMSO-d6) δ = -59.18 (t, J(H–F) = 11.9, 3F); HRMS (ESI-TOF) Calcd for C13H15F3NO+ ([M+H]+) 258.1100. Found 258.1103. 2a2, 1-(3,5-dimethyl-3-(2,2,2-trifluoroethyl)indolin-1yl)ethan-1-one, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.46 (s, 3H), 2.23 (s, 3H), 2.33 (s, 3H), 2.37-2.61 (m, 2H), 3.81 (d, J = 10.8 Hz, 1H), 4.09 (d, J = 10.8 Hz, 1H), 6.91 (s, 1H), 7.05 (dd, J = 1.0, 8.2 Hz, 1H), 8.07 (d, J = 8.2 Hz, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 168.4, 139.0, 137.7, 133.8, 129.2, 126.3 (q, 1J(C–F) = 276.9 Hz), 122.5, 117.0, 61.1 (q, 4J(C–F) = 2.0 Hz), 43.2 (q, 2J(C–F) = 26.7 Hz), 41.0 (q, 3J(C–F) = 1.4 Hz), 26.0 (q, 4J(C–F) = 0.9 Hz), 24.1, 21.1; 19F NMR (376 MHz, CDCl3) δ = -60.43 (t, J(H–F) = 10.9, 3F); HRMS (ESITOF) Calcd for C14H17F3NO+ ([M+H]+) 272.1257. Found 272.1272. 2a3, 1-(5-bromo-3-methyl-3-(2,2,2-trifluoroethyl)indolin-1yl)ethan-1-one, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.47 (s, 3H), 2.23 (s, 3H), 2.39-2.60 (m, 2H), 3.83 (d, J = 10.8 Hz, 1H), 4.13 (d, J = 10.8 Hz, 1H), 7.23 (d, J = 1.8 Hz, 1H), 7.35 (dd, J = 2.0, 8.6 Hz, 1H), 8.09 (d, J = 8.6 Hz, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 168.7, 140.5, 139.7, 131.6, 125.3, 126.1 (q, 1J(C–F) = 277.0 Hz), 118.7, 116.3, 61.0 (q, 4J(C–F) = 1.8 Hz), 42.9 (q, 2J(C–F) = 26.9 Hz), 41.1 (q, 3J(C–F) = 1.1 Hz), 26.1, 24.1; 19F NMR (376 MHz, CDCl3) δ = -60.41 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF) Calcd for C13H14BrF3NO+ ([M+H]+) 336.0205. Found 336.0209. 2a4, 1-(3-methyl-5-phenyl-3-(2,2,2-trifluoroethyl)indolin1-yl)ethan-1-one, white crystal: mp 165-166 °C. 1H NMR (400 MHz, CDCl3) δ = 1.53 (s, 3H), 2.27 (s, 3H), 2.47-2.68 (m, 2H), 3.87 (d, J = 10.8 Hz, 1H), 4.16 (d, J = 10.8 Hz, 1H),

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7.32-7.35 (m, 2H), 7.43 (dd, J = 7.8, 7.4 Hz, 2H), 7.49 (dd, J = 1.7, 8.4 Hz, 1H), 7.54-7.56 (m, 2H), 8.26 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 168.6, 140.7, 140.7, 138.2, 137.4, 128.8, 127.7, 127.2, 126.9, 126.3 (q, 1J(C–F) = 277.0 Hz), 120.7, 117.5, 61.3 (q, 4J(C–F) = 1.4 Hz), 43.3 (q, 2 J(C–F) = 26.7 Hz), 41.2, 26.1, 24.2; 19F NMR (376 MHz, CDCl3) δ = -60.35 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF) Calcd for C19H19F3NO+ ([M+H]+) 334.1413. Found 334.1413. 2b1, 1-(5-bromo-3-methyl-3-(2,2,2-trifluoroethyl)indolin1-yl)propan-1-one, white solid: mp 69-70 °C. 1H NMR (400 MHz, CDCl3) δ = 1.23 (t, J = 7.3 Hz, 3H), 1.46 (s, 3H), 2.382.59 (m, 4H), 3.82 (d, J = 10.8 Hz, 1H), 4.11 (d, J = 10.8 Hz, 1H), 7.22 (s, 1H), 7.36 (dd, J = 1.3, 8.6 Hz, 1H), 8.13 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 172.1, 140.7, 139.6, 131.7, 126.1 (q, 1J(C–F) = 277.1 Hz), 125.3, 118.7, 116.1, 60.1 (q, 4J(C–F) = 1.1 Hz), 43.1 (q, 2J(C–F) = 26.9 Hz), 41.1, 29.2, 26.1, 8.6; 19F NMR (376 MHz, CDCl3) δ = -60.40 (t, J(H–F) = 12.0, 3F); HRMS (ESI-TOF) Calcd for C14H16BrF3NO+ ([M+H]+) 350.0362. Found 350.0364. 2b2, 1-(5-bromo-3-methyl-3-(2,2,2-trifluoroethyl)indolin1-yl)octan-1-one, white crystal: mp 92-93 °C. 1H NMR (400 MHz, CDCl3) δ = 0.89 (t, J = 7.0 Hz, 3H), 1.25-1.42 (m, 8H), 1.46 (s, 3H), 1.72 (tt, J = 7.6, 7.4 Hz, 2H), 2.37-2.58 (m, 4H), 3.82 (d, J = 10.8 Hz, 1H), 4.12 (d, J = 10.8 Hz, 1H), 7.22 (d, J = 1.4 Hz, 1H), 7.36 (dd, J = 2.0, 8.6 Hz, 1H), 8.13 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 171.6, 140.7, 139.6, 131.7, 126.1 (q, 1J(C–F) = 277.0 Hz), 125.2, 118.8, 116.2, 60.3 (q, 4J(C–F) = 2.0 Hz), 43.1 (q, 2J(C–F) = 26.9 Hz), 41.1, 35.9, 31.7, 29.3, 29.1, 26.0, 24.5, 22.6, 14.1; 19F NMR (376 MHz, CDCl3) δ = -60.38 (t, J(H–F) = 10.9, 3F); HRMS (ESI-TOF) Calcd for C19H26BrF3NO+ ([M+H]+) 420.1144. Found 420.1143. 2c1, 3,5-dimethyl-1-(methylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.47 (d, J = 0.8 Hz, 3H), 2.33 (s, 3H), 2.39-2.62 (m, 2H), 2.90 (s, 3H), 3.74 (d, J = 10.4 Hz, 1H), 3.95 (d, J = 10.4 Hz, 1H), 6.95 (s, 1H), 7.05-7.07 (m, 1H), 7.29 (d, J = 8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 138.2, 137.4, 133.7, 129.6, 126.1 (q, 1J(C–F) = 277.0 Hz), 123.6, 113.3, 62.0 (q, 4J(C–F) = 2.1 Hz), 42.6 (q, 2J(C–F) = 27.0 Hz), 41.0 (q, 3J(C–F) = 1.7 Hz), 34.4, 25.6 (q, 4J(C–F) = 1.5 Hz), 21.0; 19F NMR (376 MHz, CDCl3) δ = -60.27 (t, J(H–F) = 11.2, 3F); HRMS (ESITOF) Calcd for C13H17F3NO2S+ ([M+H]+) 308.0927. Found 308.0923. 2c2, 5-bromo-3-methyl-1-(methylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.48 (s, 3H), 2.42-2.62 (m, 2H), 2.93 (s, 3H), 3.77 (d, J = 10.5 Hz, 1H), 3.99 (d, J = 10.5 Hz, 1H), 7.27 (d, J = 1.9 Hz, 1H), 7.29 (d, J = 8.6 Hz, 1H), 7.37 (dd, J = 2.0, 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.8, 139.4, 132.0, 126.4, 125.9 (q, 1J(C–F) = 276.9 Hz), 116.4, 115.0, 61.9 (q, 4J(C–F) = 2.1 Hz), 42.5 (q, 2J(C–F) = 27.2 Hz), 41.0 (q, 3J(C–F) = 1.7 Hz), 35.0, 25.8 (q, 4J(C–F) = 1.5 Hz); 19F NMR (376 MHz, CDCl3) δ = -60.21 (t, J(H–F) = 10.8, 3F); HRMS (ESI-TOF) Calcd for C12H14BrF3NO2S+ ([M+H]+) 371.9875. Found 371.9877.

4


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2c3, 3-methyl-1-(methylsulfonyl)-5-phenyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.53 (s, 3H), 2.46-2.69 (m, 2H), 2.95 (s, 3H), 3.81 (d, J = 10.5 Hz, 1H), 4.03 (d, J = 10.5 Hz, 1H), 7.32-7.36 (m, 2H), 7.41-7.45 (m, 2H), 7.47-7.48 (m, 2H), 7.51-7.54 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.3, 139.9, 137.9, 137.5, 128.9, 128.1, 127.4, 126.9, 126.1 (q, 1J(C–F) = 277.0 Hz), 121.9, 113.7, 62.2 (q, 4J(C–F) = 2.1 Hz), 42.7 (q, 2J(C– 3 4 F) = 27.0 Hz), 41.1 (q, J(C–F) = 1.7 Hz), 34.9, 25.8 (q, J(C–F) = 1.4 Hz); 19F NMR (376 MHz, CDCl3) δ = -60.14 (t, J(H–F) = 11.1, 3F); HRMS (ESI-TOF) Calcd for C18H19F3NO2S+ ([M+H]+) 370.1083. Found 370.1084. 2d1, 1-(ethylsulfonyl)-3-methyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.47 (d, J = 0.8 Hz, 3H), 2.41-2.62 (m, 2H), 3.15 (q, J = 7.4 Hz, 2H), 3.82 (d, J = 10.5 Hz, 1H), 4.05 (d, J = 10.5 Hz, 1H), 7.05 (ddd, J = 0.9, 7.5, 7.5 Hz, 1H), 7.14 (dd, J = 0.9, 7.5 Hz, 1H), 7.23 (ddd, J = 1.3, 7.4, 7.4 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.7, 137.0, 129.0, 126.1 (q, 1J(C–F) = 277.0 Hz), 123.5, 123.0, 113.4, 61.8 (q, 4J(C–F) = 2.1 Hz), 44.4, 42.7 (q, 2J(C–F) = 27.0 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz), 25.7 (q, 4J(C–F) = 1.5 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.28 (t, J(H– + F) = 11.2, 3F); HRMS (ESI-TOF) Calcd for C13H17F3NO2S + ([M+H] ) 308.0927. Found 308.0926. 2d2, 5-bromo-1-(ethylsulfonyl)-3-methyl-3-(2,2,2trifluoroethyl)indoline, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.47 (d, J = 0.6 Hz, 3H), 2.40-2.60 (m, 2H), 3.14 (q, J = 7.4 Hz, 2H), 3.82 (d, J = 10.6 Hz, 1H), 4.05 (d, J = 10.6 Hz, 1H), 7.24 (d, J = 1.9 Hz, 1H), 7.26 (d, J = 8.6 Hz, 1H), 7.34 (dd, J = 2.0, 8.6 Hz, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 140.1, 139.2, 131.9, 126.3, 125.9 (q, 1J(C–F) = 276.9 Hz), 115.9, 115.0, 61.9 (q, 4J(C–F) = 2.1 Hz), 44.7, 42.6 (q, 2J(C–F) = 27.2 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz), 25.8 (q, 4J(C–F) = 1.5 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.27 (t, J(H–F) = 11.1, 3F); HRMS (ESI-TOF) Calcd for C13H16BrF3NO2S+ ([M+H]+) 386.0032. Found 386.0032. 2d3, 1-(ethylsulfonyl)-3-methyl-3-(2,2,2trifluoroethyl)indoline-5-carbonitrile, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.44 (t, J = 7.4 Hz, 3H), 1.50 (s, 3H), 2.43-2.63 (m, 2H), 3.20 (q, J = 7.4 Hz, 2H), 3.90 (d, J = 10.3 Hz, 1H), 4.13 (d, J = 10.6 Hz, 1H), 7.40 (d, J = 1.5 Hz, 1H), 7.47 (dd, J = 0.3, 8.4 Hz, 1H), 7.55 (dd, J = 1.6, 8.5 Hz, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 144.8, 137.8, 133.9, 127.0, 125.7 (q, 1J(C–F) = 277.0 Hz), 118.6, 113.6, 106.5, 61.8 (q, 4J(C–F) = 2.1 Hz), 45.7, 42.7 (q, 2J(C–F) = 27.3 Hz), 40.9 (q, 3 J(C–F) = 1.7 Hz), 26.3 (q, 4J(C–F) = 1.3 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.24 (t, J(H–F) = 11.5, 3F); HRMS (ESITOF) Calcd for C14H16F3N2O2S+ ([M+H]+) 333.0879. Found 333.0882. 2d4, 1-(ethylsulfonyl)-3-methyl-5-phenyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.45 (t, J = 7.4 Hz, 3H), 1.52 (s, 3H), 2.46-2.68 (m, 2H), 3.18 (q, J = 7.4 Hz, 2H), 3.87 (d, J = 10.5 Hz, 1H), 4.10 (d, J = 10.5 Hz, 1H), 7.32-7.36 (m, 2H), 7.41-7.47 (m, 4H), 7.51-7.54 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ

= 140.4, 140.1, 137.7, 137.0, 128.9, 128.0, 127.3, 126.9, 126.1 (q, 1J(C–F) = 277.0 Hz), 121.8, 113.6, 62.1 (q, 4J(C–F) = 2.1 Hz), 44.5, 42.7 (q, 2J(C–F) = 27.0 Hz), 41.2 (q, 3J(C–F) = 1.6 Hz), 25.8 (q, 4J(C–F) = 1.4 Hz), 7.8; 19F NMR (376 MHz, CDCl3) δ = 60.20 (t, J(H–F) = 10.9, 3F); HRMS (ESI-TOF) Calcd for C19H21F3NO2S+ ([M+H]+) 384.1240. Found 384.1241. 2e1, 3-methyl-1-(phenylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, white solid: mp 121-122 °C. 1H NMR (400 MHz, CDCl3) δ = 1.22 (d, J = 0.8 Hz, 3H), 1.97-2.09 (m, 1H), 2.25-2.37 (m, 1H), 3.71 (d, J = 11.0 Hz, 1H), 3.96 (d, J = 11.0 Hz, 1H), 7.00-7.06 (m, 2H), 7.24-7.29 (m, 1H), 7.457.49 (m, 2H), 7.57 (dddd, J = 1.2, 1.2, 6.8, 6.6 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.82-7.85 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.3, 137.9, 136.9, 133.4, 129.2, 128.9, 127.2, 126.0 (q, 1J(C–F) = 277.1 Hz), 124.1, 122.7, 115.0, 61.3 (q, 4J(C–F) = 2.2 Hz), 42.7 (q, 2J(C–F) = 26.9 Hz), 41.0 (q, 3J(C–F) = 1.7 Hz), 25.2 (q, 4J(C–F) = 1.6 Hz); 19F NMR (376 MHz, CDCl3) δ = -60.38 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF) Calcd for C17H17F3NO2S+ ([M+H]+) 356.0927. Found 356.0928. 2e2, 5-bromo-3-methyl-1-(phenylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, white solid: mp 135-136 °C. 1H NMR (400 MHz, CDCl3) δ = 1.21 (d, J = 0.6 Hz, 3H), 1.96-2.08 (m, 1H), 2.22-2.34 (m, 1H), 3.70 (d, J = 11.1 Hz, 1H), 3.96 (d, J = 11.1 Hz, 1H), 7.13 (d, J = 2.0 Hz, 1H), 7.37 (dd, J = 2.0, 8.6 Hz, 1H), 7.48-7.51 (m, 2H), 7.57-7.62 (m, 2H), 7.80-7.83 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.1, 139.6, 136.6, 133.7, 131.9, 129.3, 127.2, 126.1, 125.8 (q, 1J(C–F) = 277.1 Hz), 116.7, 116.5, 61.4 (q, 4J(C–F) = 2.2 Hz), 42.6 (q, 2J(C– 3 4 F) = 27.1 Hz), 41.1 (q, J(C–F) = 1.7 Hz), 25.2 (q, J(C–F) = 1.5 19 Hz); F NMR (376 MHz, CDCl3) δ = -60.34 (t, J(H–F) = 10.8, 3F); HRMS (ESI-TOF) Calcd for C17H16BrF3NO2S+ ([M+H]+) 434.0032. Found 434.0035. 2f1, 3-methyl-1-tosyl-3-(2,2,2-trifluoroethyl)indoline, white crystal: mp 128-129 °C. 1H NMR (400 MHz, CDCl3) δ = 1.24 (d, J = 0.9 Hz, 3H), 1.96-2.09 (m, 1H), 2.22-2.34 (m, 1H), 2.38 (s, 3H), 3.69 (d, J = 11.0 Hz, 1H), 3.94 (d, J = 11.1 Hz, 1H), 7.00-7.05 (m, 2H), 7.24-7.28 (m, 3H), 7.68 (d, J = 8.1 Hz, 1H), 7.72 (ddd, J = 1.6, 1.6, 8.3 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 144.4, 140.4, 137.9, 133.8, 129.8, 128.9, 127.3, 126.0 (q, 1J(C–F) = 277.0 Hz), 124.0, 122.7, 115.0, 61.3 (q, 4J(C–F) = 2.1 Hz), 42.7 (q, 2J(C–F) = 26.9 Hz), 41.0 (q, 3 J(C–F) = 1.6 Hz), 25.1 (q, 4J(C–F) = 1.5 Hz), 21.5; 19F NMR (376 MHz, CDCl3) δ = -60.39 (t, J(H–F) = 10.9, 3F); HRMS (ESITOF) Calcd for C18H19F3NO2S+ ([M+H]+) 370.1083. Found 370.1082. 2f2, 1-((4-bromophenyl)sulfonyl)-3-methyl-3-(2,2,2trifluoroethyl)indoline, white crystal: mp 121-122 °C. 1H NMR (400 MHz, CDCl3) δ = 1.26 (d, J = 0.8 Hz, 3H), 2.062.18 (m, 1H), 2.32-2.44 (m, 1H), 3.69 (d, J = 10.9 Hz, 1H), 3.93 (d, J = 10.9 Hz, 1H), 7.03-7.08 (m, 2H), 7.24-7.29 (m, 1H), 7.60-7.66 (m, 3H), 7.70 (ddd, J = 2.2, 2.0, 8.7 Hz, 2H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 140.0, 137.8, 135.8, 132.5, 129.0, 128.7, 128.6, 126.0 (q, 1J(C–F) = 276.9 Hz), 124.3, 122.9, 114.7, 61.4 (q, 4J(C–F) = 2.2 Hz), 42.7 (q, 2J(C–F) = 26.9 Hz), 41.0 (q, 3J(C–F) = 1.6 Hz), 25.4 (q, 4J(C–F) = 1.6 Hz); 19F NMR (376 MHz, CDCl3) δ = -60.35 (t, J(H–F) = 11.1, 3F);

5



HRMS (ESI-TOF) Calcd for C17H16BrF3NO2S+ ([M+H]+) 434.0032. Found 434.0048. 2g1, 3-methyl-1-(o-tolylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, white solid: mp 114-115 °C. 1H NMR (400 MHz, CDCl3) δ = 1.34 (d, J = 0.7 Hz, 3H), 2.18-2.31 (m, 1H), 2.36-2.48 (m, 1H), 2.61 (s, 3H), 3.76 (d, J = 10.9 Hz, 1H), 4.01 (d, J = 10.9 Hz, 1H), 7.04 (ddd, J = 0.9, 7.6, 7.3 Hz, 1H), 7.09 (dd, J = 1.3, 7.5 Hz, 1H), 7.21 (ddd, J = 1.6, 7.3, 7.2 Hz, 1H), 7.33 (dd, J = 7.5, 8.2 Hz, 2H), 7.44 (d, J = 8.1 Hz, 1H), 7.48 (ddd, J = 1.2, 7.6, 7.5 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 141.0, 138.1, 137.6, 137.1, 133.3, 133.0, 129.4, 128.7, 126.4, 126.0 (q, 1J(C–F) = 277.0 Hz), 123.8, 122.7, 114.8, 61.1 (q, 4J(C–F) = 2.1 Hz), 42.6 (q, 2J(C–F) = 26.9 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz), 25.1 (q, 4 J(C–F) = 1.5 Hz), 20.8; 19F NMR (376 MHz, CDCl3) δ = -60.42 (t, J(H–F) = 11.3, 3F); HRMS (ESI-TOF) Calcd for C18H19F3NO2S+ ([M+H]+) 370.1083. Found 370.1081. 2g2, 5-chloro-3-methyl-1-(o-tolylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.32 (s, 3H), 2.17-2.29 (m, 1H), 2.32-2.44 (m, 1H), 2.60 (s, 3H), 3.73 (d, J = 10.9 Hz, 1H), 3.99 (d, J = 10.9 Hz, 1H), 7.04 (d, J = 2.1 Hz, 1H), 7.17 (dd, J = 2.1, 8.6 Hz, 1H), 7.33 (dd, J = 7.4, 7.2 Hz, 2H), 7.40 (d, J = 8.6 Hz, 1H), 7.48 (ddd, J = 1.2, 7.5, 7.5 Hz, 1H), 7.94-7.96 (m, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 139.7, 139.4, 138.1, 136.7, 133.5, 133.1, 129.5, 128.9, 128.8, 126.5, 125.8 (q, 1J(C–F) = 277.0 Hz), 123.2, 115.9, 61.2 (q, 4J(C–F) = 2.2 Hz), 42.5 (q, 2 J(C–F) = 27.2 Hz), 41.2 (q, 3J(C–F) = 1.7 Hz), 25.1 (q, 4J(C–F) = 1.4 Hz), 20.8; 19F NMR (376 MHz, CDCl3) δ = -60.41 (t, J(H–F) = 11.1, 3F); HRMS (ESI-TOF) Calcd for C18H18ClF3NO2S+ ([M+H]+) 404.0693. Found 404.0675. 2h1, N,N,3,5-tetramethyl-3-(2,2,2-trifluoroethyl)indoline1-sulfonamide, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.45 (d, J = 0.9 Hz, 3H), 2.31 (s, 3H), 2.38-2.60 (m, 2H), 2.90 (s, 6H), 3.74 (d, J = 10.4 Hz, 1H), 3.99 (d, J = 10.4 Hz, 1H), 6.91 (s, 1H), 7.00-7.03 (m, 1H), 7.24 (d, J = 8.2 Hz, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 139.2, 137.1, 132.8, 129.3, 126.3 (q, 1J(C–F) = 277.0 Hz), 123.2, 113.8, 62.2 (q, 4J(C–F) = 2.1 Hz), 42.7 (q, 2J(C–F) = 26.8 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz), 38.2, 25.4 (q, 4J(C–F) = 1.5 Hz), 20.9; 19F NMR (376 MHz, CDCl3) δ = -60.34 (t, J(H–F) = 11.0, 3F); HRMS (ESI-TOF) Calcd for C14H20F3N2O2S+ ([M+H]+) 337.1192. Found 337.1195. 2h2, 5-bromo-N,N,3-trimethyl-3-(2,2,2trifluoroethyl)indoline-1-sulfonamide, white solid: mp 8283 °C. 1H NMR (400 MHz, CDCl3) δ = 1.47 (d, J = 0.9 Hz, 3H), 2.39-2.58 (m, 2H), 2.91 (s, 6H), 3.75 (d, J = 10.4 Hz, 1H), 4.00 (d, J = 10.4 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.24 (d, J = 8.6 Hz, 1H), 7.33 (dd, J = 2.0, 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.9, 139.0, 131.7, 126.0 (q, 1 J(C–F) = 276.9 Hz), 125.9, 115.52, 115.48, 62.2 (q, 4J(C–F) = 2.1 Hz), 42.6 (q, 2J(C–F) = 27.1 Hz), 41.1 (q, 3J(C–F) = 1.7 Hz), 38.2, 25.5 (q, 4J(C–F) = 1.4 Hz); 19F NMR (376 MHz, CDCl3) δ = 60.33 (t, J(H–F) = 11.8, 3F); HRMS (ESI-TOF) Calcd for C13H17BrF3N2O2S+ ([M+H]+) 401.0141. Found 401.0144. 2h3, N,N,3-trimethyl-5-phenyl-3-(2,2,2trifluoroethyl)indoline-1-sulfonamide, white solid: mp 93-

Page 6 of 11

94 °C. 1H NMR (400 MHz, CDCl3) δ = 1.52 (s, 3H), 2.462.67 (m, 2H), 2.94 (s, 6H), 3.82 (d, J = 10.3 Hz, 1H), 4.06 (d, J = 10.3 Hz, 1H), 7.30 (d, J = 1.4 Hz, 1H), 7.33 (dddd, J = 1.2, 1.2, 7.3, 7.3 Hz, 1H), 7.41-7.47 (m, 4H), 7.52-7.54 (m, 2H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 141.0, 140.6, 137.5, 136.6, 128.8, 127.8, 127.2, 126.9, 126.2 (q, 1J(C–F) = 277.1 Hz), 121.4, 114.1, 62.4 (q, 4J(C–F) = 2.1 Hz), 42.8 (q, 2J(C–F) = 26.9 Hz), 41.1 (q, 3J(C–F) = 1.6 Hz), 38.3, 25.5 (q, 4J(C–F) = 1.3 Hz); 19 F NMR (376 MHz, CDCl3) δ = -60.27 (t, J(H–F) = 11.1, 3F); HRMS (ESI-TOF) Calcd for C19H22F3N2O2S+ ([M+H]+) 399.1349. Found 399.1368. 2i, 1-(3,7-dimethyl-3-(2,2,2-trifluoroethyl)indolin-1yl)ethan-1-one, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.41 (d, J = 0.8 Hz, 3H), 2.26-2.38 (m, 7H), 2.44-2.57 (m, 1H), 3.85 (brd, J = 9.8 Hz, 1H), 4.11 (d, J = 11.1 Hz, 1H), 6.94-6.98 (m, 1H), 7.07-7.12 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 168.9 (br), 141.0 (br), 140.3 (br), 130.8, 129.6 (br), 126.4 (q, 1J(C–F) = 276.9 Hz), 125.8, 119.0 (br), 62.4 (br), 42.2 (br), 41.6 (q, 2J(C–F) = 27.0 Hz), 23.6 (br), 23.4 (br), 20.4 (br); 19F NMR (376 MHz, CDCl3) δ = -60.41 (t, J(H– + F) = 11.1, 3F); HRMS (ESI-TOF) Calcd for C14H17F3NO ([M+H]+) 272.1257. Found 272.1260. 2j, 4-chloro-1-(ethylsulfonyl)-3-methyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.62 (s, 3H), 2.66-2.78 (m, 1H), 2.86-2.98 (m, 1H), 3.13-3.19 (m, 2H), 3.83 (d, J = 10.7 Hz, 1H), 4.16 (d, J = 10.7 Hz, 1H), 6.98 (dd, J = 0.8, 8.0 Hz, 1H), 7.17 (dd, J = 8.1, 8.1 Hz, 1H), 7.32 (dd, J = 0.8, 8.2 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 143.0, 131.9, 131.0, 130.3, 126.1 (q, 1J(C–F) = 277.0 Hz), 124.9, 111.9, 61.3 (q, 4J(C–F) = 2.3 Hz), 44.7, 42.4 (q, 3J(C–F) = 1.8 Hz), 40.4 (q, 2 J(C–F) = 26.7 Hz), 24.7 (q, 4J(C–F) = 1.3 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.35 (t, J(H–F) = 10.9, 3F); HRMS (ESITOF) Calcd for C13H16ClF3NO2S+ ([M+H]+) 342.0537. Found 342.0539. 2j', 6-chloro-1-(ethylsulfonyl)-3-methyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.44 (t, J = 7.4 Hz, 3H), 1.46 (s, 3H), 2.39-2.59 (m, 2H), 3.16 (q, J = 7.4 Hz, 2H), 3.84 (d, J = 10.5 Hz, 1H), 4.06 (d, J = 10.5 Hz, 1H), 7.01 (dd, J = 1.6, 8.1 Hz, 1H), 7.04 (d, J = 7.9 Hz, 1H), 7.39 (dd, J = 0.4, 1.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 141.9, 135.4, 134.8, 125.9 (q, 1 J(C–F) = 277.0 Hz), 123.9, 123.5, 113.8, 62.1 (q, 4J(C–F) = 2.1 Hz), 44.8, 42.6 (q, 2J(C–F) = 27.1 Hz), 40.8 (q, 3J(C–F) = 1.7 Hz), 25.9 (q, 4J(C–F) = 1.5 Hz), 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.29 (t, J(H–F) = 11.0, 3F); HRMS (ESI-TOF) Calcd for C13H16ClF3NO2S+ ([M+H]+) 342.0537. Found 342.0533. 2k, 5-bromo-1-(ethylsulfonyl)-3,4-dimethyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.42 (t, J = 7.4 Hz, 3H), 1.58 (s, 3H), 2.42 (s, 3H), 2.59 (q, J(H–F) = 11.2 Hz, 2H), 3.13 (q, J = 7.5 Hz, 2H), 3.72 (d, J = 10.6 Hz, 1H), 4.15 (d, J = 10.6 Hz, 1H), 7.14 (d, J = 8.6 Hz, 1H), 7.43 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.9, 135.0, 134.5, 133.1, 125.9 (q, 1J(C–F) = 277.2 Hz), 120.4, 112.5, 61.7 (q, 4J(C–F) = 2.2 Hz), 44.4, 42.3 (q, 3J(C–F) = 1.7 Hz), 41.1 (q, 2J(C–F) = 26.5 Hz), 24.9 (q, 4J(C–F) = 1.3 Hz), 19.2, 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.31 (t, J(H–F) =

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10.8, 3F); HRMS (ESI-TOF) Calcd for C14H18BrF3NO2S+ ([M+H]+) 400.0188. Found 400.0189. 2k', 5-bromo-1-(ethylsulfonyl)-3,6-dimethyl-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.43 (t, J = 7.4 Hz, 3H), 1.45 (d, J = 0.6 Hz, 3H), 2.37 (s, 3H), 2.41-2.59 (m, 2H), 3.14 (q, J = 7.4 Hz, 2H), 3.81 (d, J = 10.5 Hz, 1H), 4.04 (d, J = 10.5 Hz, 1H), 7.257 (s, 1H), 7.265 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.2, 138.7, 136.5, 126.7, 125.9 (q, 1J(C–F) = 276.9 Hz), 118.4, 115.4, 62.1 (q, 4J(C–F) = 2.1 Hz), 44.5, 42.7 (q, 2J(C–F) = 27.1 Hz), 40.8 (q, 3J(C–F) = 1.7 Hz), 25.9 (q, 4J(C–F) = 1.4 Hz), 23.4, 7.7; 19F NMR (376 MHz, CDCl3) δ = -60.31 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF) Calcd for C14H18BrF3NO2S+ ([M+H]+) 400.0188. Found 400.0189. 2l, 5-bromo-3,4-dimethyl-1-(methylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.59 (d, J = 0.8 Hz, 3H), 2.42 (s, 3H), 2.60 (q, J(H– F) = 11.0 Hz, 2H), 2.92 (s, 3H), 3.64 (d, J = 10.6 Hz, 1H), 4.10 (d, J = 10.6 Hz, 1H), 7.18 (d, J = 8.6 Hz, 1H), 7.46 (d, J = 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.7, 135.2, 134.7, 133.2, 125.9 (q, 1J(C–F) = 277.1 Hz), 120.9, 112.4, 61.7 (q, 4J(C–F) = 2.2 Hz), 42.2 (q, 3J(C–F) = 1.7 Hz), 41.1 (q, 2J(C–F) = 26.6 Hz), 34.7, 25.0 (q, 4J(C–F) = 1.3 Hz), 19.1; 19F NMR (376 MHz, CDCl3) δ = -60.28 (t, J(H–F) = 10.8, 3F); HRMS (ESITOF) Calcd for C13H16BrF3NO2S+ ([M+H]+) 386.0032. Found 386.0031. 2l', 5-bromo-3,6-dimethyl-1-(methylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.46 (s, 3H), 2.39 (s, 3H), 2.42-2.60 (m, 2H), 2.93 (s, 3H), 3.76 (d, J = 10.5 Hz, 1H), 3.97 (d, J = 10.5 Hz, 1H), 7.28 (s, 1H), 7.31 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.9, 138.9, 136.7, 126.9, 125.9 (q, 1J(C–F) = 277.0 Hz), 118.9, 115.5, 62.1 (q, 4J(C–F) = 2.0 Hz), 42.6 (q, 2J(C–F) = 27.1 Hz), 40.8 (q, 3J(C–F) = 1.7 Hz), 34.9, 25.9 (q, 4J(C–F) = 1.4 Hz), 23.4; 19F NMR (376 MHz, CDCl3) δ = -60.27 (t, J(H–F) = 11.2, 3F); HRMS (ESI-TOF) Calcd for C13H16BrF3NO2S+ ([M+H]+) 386.0032. Found 386.0030. 4a, 4-methyl-2-(phenylsulfonyl)-4-(2,2,2-trifluoroethyl)1,2,3,4-tetrahydroisoquinoline, white solid: mp 133-134 °C. 1 H NMR (400 MHz, CDCl3) δ = 1.47 (d, J = 1.0 Hz, 3H), 2.46-2.71 (m, 2H), 2.79 (d, J = 12.0 Hz, 1H), 3.62 (d, J = 12.0 Hz, 1H), 4.03 (d, J = 14.8 Hz, 1H), 4.46 (d, J = 14.8 Hz, 1H), 7.01-7.04 (m, 1H), 7.16-7.24 (m, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.56-7.66 (m, 3H), 7.86-7.89 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.8, 135.8, 133.1, 130.5, 129.3, 127.8, 127.4, 127.1, 126.5, 126.4, 126.3 (q, 1J(C–F) = 277.1 Hz), 53.6 (q, 4J(C–F) = 1.6 Hz), 48.3, 42.7 (q, 2J(C–F) = 26.6 Hz), 36.5 (q, 3J(C–F) = 1.4 Hz), 24.5 (q, 4J(C–F) = 1.2 Hz); 19F NMR (376 MHz, CDCl3) δ = -59.21 (t, J(H–F) = 11.6, 3F); HRMS (ESITOF) Calcd for C18H19F3NO2S+ ([M+H]+) 370.1083. Found 370.1086. 4b, 4-methyl-2-(o-tolylsulfonyl)-4-(2,2,2-trifluoroethyl)1,2,3,4-tetrahydroisoquinoline, white solid: mp 127-128 °C. 1 H NMR (400 MHz, CDCl3) δ = 1.41 (d, J = 1.1 Hz, 3H), 2.33-2.55 (m, 2H), 2.67 (s, 3H), 3.02 (d, J = 12.5 Hz, 1H), 3.63 (dd, J = 0.9, 12.5 Hz, 1H), 4.29 (d, J = 15.1 Hz, 1H), 4.56 (d, J = 15.0 Hz, 1H), 7.05-7.07 (m, 1H), 7.18-7.25 (m, 2H),

7.29-7.39 (m, 3H), 7.49 (ddd, J = 1.4, 7.5, 7.5 Hz, 1H), 7.98 (dd, J = 1.3, 7.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.0, 138.1, 135.3, 133.3, 133.0, 130.8, 130.4, 127.4, 127.1, 126.7, 126.4, 126.3, 126.1 (q, 1J(C–F) = 277.2 Hz), 53.1 (q, 4J(C–F) = 1.7 Hz), 47.4, 42.4 (q, 2J(C–F) = 26.6 Hz), 36.5 (q, 3J(C–F) = 1.4 Hz), 24.3 (q, 4J(C–F) = 1.3 Hz), 20.9; 19F NMR (376 MHz, CDCl3) δ = -59.50 (t, J(H–F) = 11.3, 3F); HRMS (ESI-TOF) Calcd for C19H21F3NO2S+ ([M+H]+) 384.1240. Found 384.1253. 4c, 4,6-dimethyl-2-(o-tolylsulfonyl)-4-(2,2,2trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.39 (d, J = 0.6 Hz, 3H), 2.31 (s, 3H), 2.35-2.51 (m, 2H), 2.66 (s, 3H), 3.00 (d, J = 12.5 Hz, 1H), 3.61 (d, J = 12.4 Hz, 1H), 4.24 (d, J = 14.8 Hz, 1H), 4.50 (d, J = 14.8 Hz, 1H), 6.94 (d, J = 7.9 Hz, 1H), 7.01 (dd, J = 0.8, 7.9 Hz, 1H), 7.09 (s, 1H), 7.31-7.37 (m, 2H), 7.48 (ddd, J = 1.2, 7.5, 7.5 Hz, 1H), 7.97 (dd, J = 1.1, 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.0, 138.1, 137.1, 135.4, 133.2, 133.0, 130.4, 128.0, 127.7, 126.7, 126.6, 126.3, 126.1 (q, 1J(C–F) = 277.3 Hz), 53.1 (q, 4J(C–F) = 1.7 Hz), 47.3, 42.4 (q, 2J(C–F) = 26.5 Hz), 36.4 (q, 3J(C–F) = 1.4 Hz), 24.3 (q, 4J(C–F) = 1.1 Hz), 21.3, 20.9; 19F NMR (376 MHz, CDCl3) δ = -59.48 (t, J(H–F) = 11.4, 3F); HRMS (ESI-TOF) Calcd for C20H23F3NO2S+ ([M+H]+) 398.1396. Found 398.1394. 4d, 6-chloro-4-methyl-2-(o-tolylsulfonyl)-4-(2,2,2trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.40 (d, J = 0.6 Hz, 3H), 2.312.54 (m, 2H), 2.66 (s, 3H), 3.00 (d, J = 12.6 Hz, 1H), 3.62 (d, J = 12.6 Hz, 1H), 4.24 (d, J = 15.2 Hz, 1H), 4.51 (d, J = 15.2 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 7.18 (dd, J = 2.1, 8.3 Hz, 1H), 7.28 (d, J = 2.0 Hz, 1H), 7.33-7.39 (m, 2H), 7.50 (ddd, J = 1.3, 7.5, 7.5 Hz, 1H), 7.97 (dd, J = 1.1, 7.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 142.0, 138.1, 135.2, 133.4, 133.2, 133.0, 130.4, 129.3, 128.1, 127.5, 126.6, 126.4, 125.9 (q, 1J(C–F) = 277.2 Hz), 52.8 (q, 4J(C–F) = 1.7 Hz), 47.1, 42.8 (q, 2J(C–F) = 26.8 Hz), 36.7 (q, 3J(C–F) = 1.4 Hz), 24.3 (q, 4J(C–F) = 1.2 Hz), 20.9; 19F NMR (376 MHz, CDCl3) δ = -59.45 (t, J(H–F) = 11.6, 3F); HRMS (ESI-TOF) Calcd for C19H20ClF3NO2S+ ([M+H]+) 418.0850. Found 418.0832. 6, 5-bromo-1-(methylsulfonyl)-3-(2,2,2trifluoroethyl)indoline, white solid: mp 100-101 °C. 1H NMR (400 MHz, CDCl3) δ = 2.31-2.45 (m, 1H), 2.56-2.69 (m, 1H), 2.91 (s, 3H), 3.67-3.74 (m, 1H), 3.77 (dd, J = 7.6, 10.5 Hz, 1H), 4.20 (dd, J = 9.1, 9.9 Hz, 1H), 7.31 (d, J = 8.6 Hz, 1H), 7.33 (s, 1H), 7.39 (ddd, J = 0.5, 1.9, 8.6 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.9, 134.1, 132.2, 127.7, 125.9 (q, 1J(C–F) = 275.8 Hz), 116.6, 115.3, 56.1 (q, 4J(C–F) = 1.4 Hz), 38.3 (q, 2J(C–F) = 28.3 Hz), 35.1, 34.5 (q, 3J(C–F) = 2.8 Hz); 19F NMR (376 MHz, CDCl3) δ = -64.64 (t, J(H–F) = 10.5, 3F); HRMS (ESI-TOF) Calcd for C11H12BrF3NO2S+ ([M+H]+) 357.9719. Found 357.9722. 7, (3,3,3-trifluoroprop-1-ene-1,1-diyl)dibenzene, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 6.13 (q, J(H–F) = 8.2 Hz, 1H), 7.23-7.26 (m, 4H), 7.30-7.41 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ = 152.5 (q, 3J(C–F) = 5.6 Hz), 140.1, 137.3, 129.4, 129.1 (q, 4J(C–F) = 1.8 Hz), 128.48, 128.47, 128.03, 127.96, 123.1 (q, 1J(C–F) = 269.0 Hz), 115.4 (q, 2J(C–F) = 33.6

7



Hz); 19F NMR (376 MHz, CDCl3) δ = -55.60 (d, J(H–F) = 8.3, 3F); HRMS (ESI-TOF) Calcd for C15H12F3+ ([M+H]+) 249.0886. Found 249.0887. Synthesis of allyl amines 1, 3 and 5. Allyl amines were prepared by the methods shown in Scheme S1 (see the Supporting Information). General procedure (1a2 as an example). A 100-mL flask, equipped with a magnetic stirring bar, was charged with ptoluidine (1.607 g, 15.0 mmol), CH2Cl2 (50.0 mL), and Et3N (4.170 mL, 30.0 mmol), followed by the addition of acetyl chloride (1.273 mL, 18.0 mmol). The reaction mixture was stirred at room temperature. After p-toluidine was consumed, as indicated by TLC, the reaction mixture was quenched with aqueous NaHCO3 (100 mL) and extracted with CH2Cl2 (100 mL) three times. The combined organic phase was washed with brine (50 mL) two times. After removal of solvents, the solid of the crude product was further purified by washing with petroleum ether/ethyl acetate mixture (5:1, v/v), affording N(p-tolyl)acetamide as a white crystal (2.104 g, 94% yield). To a stirred solution of N-(p-tolyl)acetamide (1.492 g, 10.0 mmol) and NaOH (600 mg, 15.0 mmol) in DMF (30.0 mL) was added 3-bromo-2-methylprop-1-ene (1.311 mL, 13.0 mmol), and the mixture was stirred at ambient temperature. After N(p-tolyl)acetamide was consumed, as indicated by TLC, the reaction mixture was quenched with brine (60 mL), and extracted with CH2Cl2 three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether–ethyl acetate = 20:1, v/v) to afford N-(2-methylallyl)-N-(p-tolyl)acetamide 1a2 as a colorless oil (1.830 g, 90% yield). 1a4, N-([1,1'-biphenyl]-4-yl)-N-(2-methylallyl)acetamide, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.78 (s, 3H), 1.96 (s, 3H), 4.32 (s, 2H), 4.75 (s, 1H), 4.85 (s, 1H), 7.23 (d, J = 8.2 Hz, 2H), 7.37 (dd, J = 7.3, 7.3 Hz, 1H), 7.45 (dd, J = 7.7, 7.4 Hz, 2H), 7.58-7.61 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ = 170.4, 142.3, 140.8, 140.6, 140.0, 128.9, 128.11, 128.05, 127.7, 127.1, 113.1, 55.0, 22.9, 20.4; HRMS (ESI-TOF) Calcd for C18H20NO+ ([M+H]+) 266.1539. Found 266.1538. 1c2, N-(4-bromophenyl)-N-(2methylallyl)methanesulfonamide, white crystal: mp 77-78 °C. 1 H NMR (400 MHz, CDCl3) δ = 1.74 (s, 3H), 2.90 (s, 3H), 4.22 (s, 2H), 4.80 (s, 1H), 4.83 (s, 1H), 7.22 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H), 7.51 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.5, 138.0, 132.5, 129.6, 121.7, 115.6, 56.6, 37.3, 19.8; HRMS (ESI-TOF) Calcd for C11H15BrNO2S+ ([M+H]+) 304.0001. Found 304.0004. 1d1, N-(2-methylallyl)-N-phenylethanesulfonamide, pale yellow solid: mp 78-79 °C. 1H NMR (400 MHz, CDCl3) δ = 1.39 (t, J = 7.4 Hz, 3H), 1.76 (s, 3H), 3.04 (q, J = 7.4 Hz, 2H), 4.29 (s, 2H), 4.79 (s, 2H), 7.27-7.32 (m, 1H), 7.34-7.39 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.2, 139.1, 129.2, 128.2, 127.6, 114.9, 57.3, 45.2, 19.8, 8.0; HRMS (ESITOF) Calcd for C12H18NO2S+ ([M+H]+) 240.1053. Found 240.1068. 1d3, N-(4-cyanophenyl)-N-(2methylallyl)ethanesulfonamide, colorless oil. 1H NMR (400

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MHz, CDCl3) δ = 1.38 (t, J = 7.4 Hz, 3H), 1.72 (s, 3H), 3.11 (q, J = 7.4 Hz, 2H), 4.37 (s, 2H), 4.84 (s, 1H), 4.86 (s, 1H), 7.51 (ddd, J = 2.2, 1.8, 8.7 Hz, 2H), 7.67 (ddd, J = 2.2, 2.0, 8.7 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 143.4, 139.3, 133.1, 127.0, 118.2, 115.4, 110.2, 56.1, 46.1, 19.7, 8.0; HRMS (ESI-TOF) Calcd for C13H17N2O2S+ ([M+H]+) 265.1005. Found 265.1003. 1d4, N-([1,1'-biphenyl]-4-yl)-N-(2methylallyl)ethanesulfonamide, white solid: mp 146-147 °C. 1 H NMR (400 MHz, CDCl3) δ = 1.41 (t, J = 7.4 Hz, 3H), 1.79 (s, 3H), 3.08 (q, J = 7.4 Hz, 2H), 4.33 (s, 2H), 4.84 (s, 2H), 7.35 (dddd, J = 1.2, 1.2, 7.4, 7.3 Hz, 1H), 7.40-7.46 (m, 4H), 7.55-7.60 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.4, 140.2, 140.0, 138.2, 128.9, 128.3, 127.9, 127.6, 127.1, 115.0, 57.2, 45.3, 19.9, 8.1; HRMS (ESI-TOF) Calcd for C18H22NO2S+ ([M+H]+) 316.1366. Found 316.1354. 1g1, 2-methyl-N-(2-methylallyl)-Nphenylbenzenesulfonamide, white solid: mp 56-57 °C. 1H NMR (400 MHz, CDCl3) δ = 1.75 (s, 3H), 2.30 (s, 3H), 4.20 (s, 2H), 4.73 (s, 1H), 4.76 (s, 1H), 7.08-7.13 (m, 2H), 7.207.29 (m, 5H), 7.41 (ddd, J = 1.3, 7.5, 7.5 Hz, 1H), 7.79 (dd, J = 1.2, 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.9, 138.6, 138.1, 136.8, 132.7, 132.6, 130.3, 128.8, 128.6, 127.6, 126.1, 115.3, 57.0, 20.8, 20.0; HRMS (ESI-TOF) Calcd for C17H20NO2S+ ([M+H]+) 302.1209. Found 302.1203. 1g2, N-(4-chlorophenyl)-2-methyl-N-(2methylallyl)benzenesulfonamide, white solid: mp 58-59 °C. 1H NMR (400 MHz, CDCl3) δ = 1.73 (s, 3H), 2.35 (s, 3H), 4.16 (s, 2H), 4.71 (s, 1H), 4.78 (s, 1H), 7.04 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H), 7.21-7.28 (m, 4H), 7.43 (ddd, J = 1.3, 7.6, 7.6 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.6, 138.0, 137.2, 136.5, 133.4, 133.0, 132.7, 130.4, 129.8, 129.1, 126.2, 115.8, 57.0, 20.8, 19.9; HRMS (ESI-TOF) Calcd for C17H19ClNO2S+ ([M+H]+) 336.0820. Found 336.0823. 1h1, N,N-dimethyl-N'-(2-methylallyl)-N'-(ptolyl)sulphamide, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.75 (s, 3H), 2.31 (s, 3H), 2.73 (s, 6H), 4.20 (s, 2H), 4.76 (s, 2H), 7.14 (d, J = 8.3 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 140.4, 137.5, 137.3, 129.7, 128.0, 114.7, 58.5, 38.3, 21.1, 20.0; HRMS (ESI-TOF) Calcd for C13H21N2O2S+ ([M+H]+) 269.1318. Found 269.1335. 1h2, N'-(4-bromophenyl)-N,N-dimethyl-N'-(2methylallyl)sulphamide, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.74 (s, 3H), 2.77 (s, 6H), 4.19 (s, 2H), 4.76 (s, 1H), 4.79 (s, 1H), 7.26 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H), 7.47 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.9, 139.3, 132.2, 129.6, 121.0, 115.3, 58.2, 38.3, 20.0; HRMS (ESI-TOF) Calcd for C12H18BrN2O2S+ ([M+H]+) 333.0267. Found 333.0262. 1i, N-(2-methylallyl)-N-(o-tolyl)acetamide, red oil. 1H NMR (400 MHz, CDCl3) δ = 1.79-1.80 (m, 6H), 2.23 (s, 3H), 3.48 (d, J = 14.5 Hz, 1H), 4.67-4.68 (m, 1H), 4.82-4.86 (m, 2H), 7.07 (dd, J = 1.4, 7.8 Hz, 1H), 7.18-7.26 (m, 2H), 7.27-7.30 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 170.6, 141.6, 140.7, 135.4, 131.4, 129.0, 128.3, 127.0, 113.8, 53.9, 22.3, 20.7,

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17.5; HRMS (ESI-TOF) Calcd for C13H18NO+ ([M+H]+) 204.1383. Found 204.1387. 1j, N-(3-chlorophenyl)-N-(2-methylallyl)ethanesulfonamide, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.39 (t, J = 7.4 Hz, 3H), 1.75 (s, 3H), 3.06 (q, J = 7.4 Hz, 2H), 4.28 (s, 2H), 4.81 (s, 1H), 4.83 (s, 1H), 7.25-7.33 (m, 3H), 7.35-7.36 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.3, 139.7, 134.6, 130.1, 128.0, 127.8, 126.2, 115.3, 57.1, 45.5, 19.8, 8.0; HRMS (ESI-TOF) Calcd for C12H17ClNO2S+ ([M+H]+) 274.0663. Found 274.0663. 1k, N-(4-bromo-3-methylphenyl)-N-(2methylallyl)ethanesulfonamide, pale yellow solid: mp 51-52 °C. 1 H NMR (400 MHz, CDCl3) δ = 1.38 (t, J = 7.4 Hz, 3H), 1.75 (s, 3H), 2.39 (s, 3H), 3.03 (q, J = 7.4 Hz, 2H), 4.25 (s, 2H), 4.79 (s, 1H), 4.82 (s, 1H), 7.03 (dd, J = 2.5, 8.5 Hz, 1H), 7.23 (d, J = 2.5 Hz, 1H), 7.51 (d, J = 8.5 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.9, 139.1, 138.2, 133.0, 130.5, 126.6, 123.9, 115.2, 57.2, 45.3, 23.1, 19.8, 8.0; HRMS (ESITOF) Calcd for C13H19BrNO2S+ ([M+H]+) 332.0314. Found 332.0316. 1l, N-(4-bromo-3-methylphenyl)-N-(2methylallyl)methanesulfonamide, pale yellow solid: mp 6667 °C. 1H NMR (400 MHz, CDCl3) δ = 1.75 (s, 3H), 2.39 (s, 3H), 2.90 (s, 3H), 4.21 (s, 2H), 4.81 (s, 1H), 4.83 (s, 1H), 7.02 (dd, J = 2.6, 8.5 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.52 (d, J = 8.5 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.7, 139.2, 138.1, 133.0, 130.5, 126.5, 124.2, 115.3, 56.7, 37.3, 23.1, 19.8; HRMS (ESI-TOF) Calcd for C12H17BrNO2S+ ([M+H]+) 318.0158. Found 318.0159. 1m, N-(4-bromophenyl)-3-chloro-N-(2methylallyl)benzamide, white solid: mp 104-105 °C. 1H NMR (400 MHz, CDCl3) δ = 1.80 (s, 3H), 4.46 (s, 2H), 4.87 (s, 1H), 4.92 (s, 1H), 6.91 (d, J = 8.4 Hz, 2H), 7.08-7.14 (m, 2H), 7.24-7.27 (m, 1H), 7.34 (d, J = 8.6 Hz, 2H), 7.40 (s, 1H); 13 C{1H} NMR (100 MHz, CDCl3) δ = 168.8, 142.3, 140.5, 137.4, 134.2, 132.3, 130.1, 129.2, 128.9, 128.5, 126.6, 120.4, 113.1, 55.7, 20.4; HRMS (ESI-TOF) Calcd for C17H16BrClNO+ ([M+H]+) 364.0098. Found 364.0094. 3a, N-benzyl-N-(2-methylallyl)benzenesulfonamide, pale yellow oil. 1H NMR (400 MHz, CDCl3) δ = 1.52 (s, 3H), 3.71 (s, 2H), 4.35 (s, 2H), 4.70 (s, 1H), 4.82 (s, 1H), 7.14-7.18 (s, 2H), 7.21-7.26 (m, 3H), 7.47-7.51 (m, 2H), 7.56 (dddd, J = 1.3, 1.3, 7.4, 7.3 Hz, 1H), 7.82-7.85 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 140.6, 139.9, 135.9, 132.5, 129.0, 128.7, 128.4, 127.7, 127.2, 114.9, 53.3, 50.6, 19.9; HRMS (ESI-TOF) Calcd for C17H20NO2S+ ([M+H]+) 302.1209. Found 302.1210. 3b, N-benzyl-2-methyl-N-(2methylallyl)benzenesulfonamide, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.55 (s, 3H), 2.58 (s, 3H), 3.73 (s, 2H), 4.38 (s, 2H), 4.79 (s, 1H), 4.93 (s, 1H), 7.03-7.05 (m, 2H), 7.22-7.25 (m, 3H), 7.30 (dd, J = 7.7, 7.6 Hz, 2H), 7.46 (ddd, J = 1.1, 7.6, 7.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.8, 138.6, 137.6, 135.6, 132.7, 132.6, 130.1, 128.9, 128.5, 127.8, 126.1, 115.3, 52.0, 49.4, 20.5, 19.8; HRMS (ESI-TOF) Calcd for C18H22NO2S+ ([M+H]+) 316.1366. Found 316.1369.

3c, 2-methyl-N-(2-methylallyl)-N-(4methylbenzyl)benzenesulfonamide, pale yellow solid: mp 4344 °C. 1H NMR (400 MHz, CDCl3) δ = 1.55 (s, 3H), 2.30 (s, 3H), 2.58 (s, 3H), 3.71 (s, 2H), 4.33 (s, 2H), 4.80 (s, 1H), 4.93 (s, 1H), 6.91 (d, J = 8.0 Hz, 2H), 7.04 (d, J = 7.8 Hz, 2H), 7.30 (dd, J = 7.9, 7.6 Hz, 2H), 7.45 (ddd, J = 1.1, 7.5, 7.5 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.8, 138.7, 137.6, 137.5, 132.7, 132.6, 132.5, 130.1, 129.1, 128.9, 126.1, 115.1, 51.7, 49.0, 21.1, 20.5, 19.8; HRMS (ESI-TOF) Calcd for C19H24NO2S+ ([M+H]+) 330.1522. Found 330.1538. 3d, N-(4-chlorobenzyl)-2-methyl-N-(2methylallyl)benzenesulfonamide, colorless oil. 1H NMR (400 MHz, CDCl3) δ = 1.51 (s, 3H), 2.58 (s, 3H), 3.69 (s, 2H), 4.35 (s, 2H), 4.77 (s, 1H), 4.91 (s, 1H), 7.02 (d, J = 8.4 Hz, 2H), 7.22 (ddd, J = 2.4, 1.8, 8.4 Hz, 2H), 7.31 (dd, J = 7.2, 7.4 Hz, 2H), 7.46 (ddd, J = 1.2, 7.6, 7.6 Hz, 1H), 7.97-7.99 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ = 139.6, 138.3, 137.6, 134.3, 133.6, 132.9, 132.7, 130.2, 130.1, 128.6, 126.2, 115.6, 52.2, 48.8, 20.5, 19.7; HRMS (ESI-TOF) Calcd for C18H21ClNO2S+ ([M+H]+) 350.0976. Found 350.0974. 5, N-allyl-N-(4-bromophenyl)methanesulfonamide, pale yellow semisolid. 1H NMR (400 MHz, CDCl3) δ = 2.91 (s, 3H), 4.27 (ddd, J = 1.2, 1.2, 6.4 Hz, 2H), 5.15-5.20 (m, 2H), 5.76-5.86 (m, 1H), 7.21 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H), 7.52 (ddd, J = 3.0, 2.1, 8.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ = 138.3, 132.6, 132.5, 130.0, 121.9, 119.6, 53.6, 38.2; HRMS (ESI-TOF) Calcd for C10H13BrNO2S+ ([M+H]+) 289.9845. Found 289.9831.

AUTHOR INFORMATION Corresponding Author *[email protected], [email protected]

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENT Financial support from the National Natural Science Foundation of China (No. 21702083) is gratefully acknowledged.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. X-ray crystallograpy data for 2e1 (CIF) Spectroscopic data (PDF)

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Synthesis of CF3CH2-Containing Indolines by Transition Metal-Free

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