Supporting Information. Rh (III)-Catalyzed Meta-C H Olefination Directed by a Nitrile Template

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1 Supporting Information Rh (III)-Catalyzed Meta-C H Olefination Directed by a Nitrile Template Hua-Jin Xu, Yi Lu, *, Marcus E. Farmer, Huai-Wei Wang, Dan Zhao, Yan-Shang Kang, Wei-Yin Sun, *, Jin-Quan Yu *, Coordination Chemistry Institute, State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National Laboratory of Microstructures, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing , China. Department of Chemistry, The Scripps Research Institute, N. Torrey Pines Road, La Jolla, California 92037, USA. Table of Contents 1. General Information... S2 2. Experimental Section... S2 2.1 Preparation and characterization of substrates... S2 2.2 References... S Optimization Studies... S General procedure for Rh (III)-catalyzed meta-c-h Olefination... S meta-c H Olefination of Indoline and N-Methylaniline.S Kinetic Isotope Effect Studies..S The Procedure for the 10 mmol Reaction in Toluene..S43 3. NMR Spectra for New Compounds... S44 S1

2 1. General Information Anhydrous solvents were prepared according to standard methods. Commercially available chemicals were used as received without further purification. NMR spectra were recorded on 300 MHz, 400 MHz and 600 MHz spectrometers. Chemical shifts are quoted in ppm relative to CDCl 3. High-resolution mass spectra (HRMS) were obtained with a Q-TOF (ESI). 2. Experimental Section 2.1 Preparation and characterization of substrates Procedure for the preparation of template (T 3 ) 1 Toa 100 ml round bottom flask was added 2-fluorobenzonitrile (20 mmol, 1.0 equiv), 2-fluoroaniline (20 mmol, 1.0 equiv) and t BuOK (42 mmol, 2.1 equiv). Next, 60 ml dry DMSO was added and the reaction wasstirred overnight at room temperature.the reaction was poured into ice waterand the resulting precipitate was filtered and washed with water to provide a crude solid. The crude productwaspurified either by column chromatography (EtOAc/hexanes = 1:4) or recrystallization from methanol. S2 2-(2-fluorophenylamino)benzonitrile (T 3 ): 1 H NMR (400 MHz, CDCl 3 ) δ 7.54 (dd, J = 8.0, 1.6 Hz, 1 H), 7.41 (td, J = 8.8, 1.6 Hz, 1 H), 7.34 (td, J = 8.0, 2.4 Hz, 1 H), (m, 4 H), 6.91 (td, J = 7.6, 1.2 Hz, 1 H), 6.25 (br, 1 H); 13 C NMR (100 MHz, CDCl 3 ) δ (d, J C-F = Hz), , (d, J C-F = 83.5 Hz),

3 (d, J C-F = 9.5 Hz), (d, J C-F = 5.9 Hz), (d, J C-F = 2.7 Hz), , , , (d, J C-F = 15.5 Hz), , 99.62; HRMS (EI-TOF): m/zcalcd. for C 13 H 10 FN 2 [M+H] + : , found General procedure for the preparation of substrates (1a-1). 2 To an ice cooled solution of template (T 3 ) (1.0 mmol, 1.0 equiv) in dry THF (10 ml) was added NaH (60% in mineral oil, 1.2 mmol, 1.2 equiv) in two portions at 0 o C andthe solution was stirred for another 1h at this temperature. Next, the acid chloride (1.0 mmol, 1.0 equiv.), prepared from the corresponding carboxylic acid and oxalyl chloride, was added dropwise to the reaction mixture at 0 o C. The reaction was stirred overnight, then quenched with water, and extracted with DCM three times.the combined organic extractsweredried over MgSO 4 and concentrated in vacuo. The crude product was purified by column chromatography (EtOAc/hexanes = 3:1) to yield the pure product in moderate yield. N-(2-cyanophenyl)-N- (2-fluorophenyl)-3-phenylpropanamide (1a): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 8.0, 1.6 Hz, 1 H), 7.59 (td, J = 7.6, 1.2 Hz, 1 H), (m, 4 H), (m, 7 H), 3.05 (t, J = 8.0 Hz, 2 H), 2.62 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 4.3 Hz), , , , , , , , , , , (d, J C-F = 20.7 Hz), , , 36.15, 31.21; HRMS (EI-TOF): m/zcalcd. for C 22 H 18 FN 2 O [M+H] + : , found S3

4 N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-phenylbutanamide (1b): 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (s, 1 H), 7.54 (t, J = 6.8 Hz, 1 H), 7.36 (m, 2 H), (m, 9 H), (m, 1 H), (m, 2 H), 1.36 (d, J = 6.4 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 38.8 Hz), , (d, J C-F = 13.2 Hz), , , , , , , , (d, J C-F = 20.5 Hz), , , 42.72, 36.36, 21.43; HRMS (EI-TOF): m/zcalcd. for C 23 H 20 FN 2 O [M+H] + : , found N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-o-tolylpropanamide (1c): 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (dd, J = 7.8, 1.8 Hz, 1 H), 7.59 (td, J = 7.8, 1.8 Hz, 1 H), (m, 4 H), (m, 6 H), 3.05 (t, J = 7.8 Hz, 2 H), 2.57 (t, J = 7.8 Hz, 2 H), 2.20 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , , (d, J C-F = 47.6 Hz), , , , , , , , , (d, J C-F = 20.7 Hz), , , 34.76, 28.80, 19.16; HRMS (EI-TOF): m/zcalcd. for C 23 H 20 FN 2 O [M+H] + : , found S4 N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(2-methoxyphenyl)propanamide (1d): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 8.0, 1.2 Hz, 1 H), 7.58 (td, J = 8.0,

5 1.6Hz, 1 H), (m, 4 H), (m, 4 H), 6.87 (t, J = 7.2 Hz, 1 H), 6.78 (d, J = 8.0 Hz, 1 H), 3.70 (s, 3 H), 3.05 (t, J = 7.6 Hz, 2 H), 26.3 (s, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 38.9 Hz), , , , , , , , , , (d, J C-F = 24.0 Hz), , , , 55.05, 34.14, 26.66; HRMS (EI-TOF): m/zcalcd. for C 23 H 20 FN 2 O 2 [M+H] + : , found N-(2-cyanophenyl)-N,3-bis(2-fluorophenyl)propanamide (1e): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), 7.46 (d, J = 7.2 Hz, 1 H), (m, 3 H), (m, 4 H), 7.04 (t, J = 7.2 Hz, 1 H), 6.95 (td, J = 8.0, 1.2 Hz, 1 H), 3.07 (t, J = 7.6 Hz, 2 H), 2.62 (s, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), (d, J C-F = Hz),144.70, (d, J C-F = 49.0 Hz), (d, J C-F = 37.9 Hz), , , , (d, J C-F = 7.7 Hz), , (d, J C-F = 16.1 Hz), , (d, J C-F = 3.4 Hz), (d, J C-F = 20.1 Hz),116.98, (d, J C-F = 21.7 Hz), , 34.39, 24.91; HRMS (EI-TOF): m/zcalcd. for C 22 H 17 F 2 N 2 O [M+H] + : , found S5 3- (2-chlorophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1f): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 8.0 Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.45 (t, J = 7.2 Hz, 1 H), (m, 3 H), (m, 2 H), (m,4 H), 3.15 (t, J = 7.6 Hz, 2 H), 2.64 (s, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , , (d, J C-F = 50.8 Hz), , , , , , , , , , ,

6 (d, J C-F = 20.0 Hz), , , 33.92, 29.39; HRMS (EI-TOF): m/zcalcd. for C 22 H 17 ClFN 2 O [M+H] + : , found (2-bromophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1g): 1 H NMR (400MHz, CDCl 3 ) δ 7.72 (d, J = 7.6,Hz, 1 H), 7.58 (t, J = 7.8 Hz, 1 H), (m, 6H), (m, 3H), 7.05 (t, J = 7.2 Hz, 1 H), 3.15(t, J = 8.0 Hz, 2 H), 2.65 (s, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 49.2 Hz), , , , , , , , , , (d, J C-F = 20.3 Hz), , , 34.06, 31.86; HRMS (EI-TOF): m/zcalcd. for C 22 H 16 BrFN 2 NaO [M+Na] + : , found N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(2-(trifluoromethyl)phenyl)propanam ide (1h): 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (dd, J = 7.6, 1.2Hz, 1 H), (m, 2 H), (m, 7 H), (m, 2 H), 3.23 (t, J = 8.0Hz, 2 H), 2.62(t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 52.4 Hz), , , , , , , , , (q, J C-F = 233 Hz ), , (q, J C-F = 5.7 Hz), , , , (d, J C-F = 20.4 Hz), , , 36.00, 28.15; HRMS (EI-TOF): m/zcalcd. for C 23 H 17 F 4 N 2 O [M+H] + : , found S6

7 N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-m-tolylpropanamide (1i): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 7.6, 1.6 Hz, 1 H), 7.58 (td, J = 8.0, 1.6 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 1 H), (m,3 H), (m, 3 H), 7.01 (d, J = 7.2 Hz, 1 H), (m,2 H), 3.02 (t, J = 8.0 Hz, 2 H), 2.62 (t, J = 7.6 Hz, 2 H), 2.31 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , , (d, J C-F = 46.7 Hz), , , , , , , , (d, J C-F = 20.9 Hz), , , 36.19, 31.13, 21.43; HRMS (EI-TOF): m/zcalcd. for C 23 H 19 FN 2 NaO [M+Na] + : , found N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-methoxyphenyl)propanamide (1j): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 1 H), (m,3 H), (m, 3 H), 6.72 (d, J = 7.6 Hz, 2 H), 6.68 (d, J = 2.0 Hz, 1 H), 3.77 (s, 3 H), 3.03 (t, J = 8.0 Hz, 2 H), 2.62 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz),144.78, , (d, J C-F = 48.0 Hz), , , , , , , (d, J C-F = 20.5 Hz), , , , , 55.26, 36.08, 31.28;HRMS (EI-TOF): m/zcalcd. for C 23 H 19 FN 2 NaO 2 [M+Na] + : , found S7

8 N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-fluorophenyl)propanamide (1k): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H), (m,3 H), 7.32 (d, J = 8.0 Hz, 1 H) (m, 3 H), 6.93 (d, J = 7.6 Hz, 1 H), (m, 2 H), 3.04 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), (d, J C-F = Hz), , (d, J C-F = 6.2 Hz), (d, J C-F = 49.5 Hz), (d, J C-F = 6.8 Hz), , (d, J C-F = 8.3 Hz), , , , , , (d, J C-F = 20.7 Hz), , (d, J C-F = 20.9 Hz), (d, J C-F = 20.9 Hz), 35.70, 30.85; HRMS (EI-TOF): m/zcalcd. for C 22 H 17 F 2 N 2 O [M+H] + : , found (3-chlorophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1l): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 1 H), (m,3 H), 7.32 (t, J = 8.0 Hz, 1 H), (m, 4 H), 7.10 (s, 1 H), 7.04 (d, J = 6.8 Hz, 1 H), 3.02 (t, J = 7.6 Hz, 2 H), 2.60 (t, J = 7.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , , (d, J C-F = 53.3 Hz), (d, J C-F = 7.0 Hz), , , , , , , , , , (d, J C-F = 20.1 Hz), , , 35.66, 30.76; HRMS (EI-TOF): m/zcalcd. for C 22 H 17 ClFN 2 O [M+H] + : , found S8

9 3-(3-bromophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1m): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H), (m,3 H), 7.31 (t, J = 7.6 Hz, 1 H), (m, 6 H), 3.01 (t, J = 7.2 Hz, 2 H), 2.60 (t, J = 7.8 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = 248.4Hz), , , (d, J C-F = 50.4Hz), , , , , , , , , , , (d, J C-F = 19.0 Hz), , , 35.73, 30.80; HRMS (EI-TOF): m/zcalcd. for C 22 H 16 BrFN 2 NaO [M+Na] + : , found N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)propanam ide (1n): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 1 H), (m,7 H), 7.31 (d, J = 8.0 Hz, 1 H), (m, 2 H), 3.11 (t, J = 7.2 Hz, 2 H), 2.65 (t, J = 7.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 55.9 Hz), , , , , (d, J C-F = 4 Hz), , , , , , (q, J C-F = 4.0 Hz), (d, J C-F = 3.0 Hz), , , (d, J C-F = 19.8 Hz), , , 35.58, 30.84; HRMS (EI-TOF): m/zcalcd. for C 23 H 16 F 4 N 2 NaO [M+Na] + : , found S9

10 N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(4-methoxyphenyl)propanamide (1o): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 7.6,1.2Hz, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 1 H), (m,3 H), (m, 2 H), 7.05 (d, J = 8.4 Hz, 2 H), 6.81 (d, J = 8.0 Hz, 2 H), 3.77 (s, 3 H), 3.00 (t, J = 8.0 Hz, 2 H), 2.59 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), , , (d, J C-F = 58.5 Hz), , (d, J C-F = 7.2 Hz), , , , , , , , (d, J C-F = 20.0 Hz), , , , 55.07, 36.18, 30.09; HRMS (EI-TOF): m/zcalcd. for C 23 H 20 FN 2 O 2 [M+H] + : , found N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(4-fluorophenyl)propanamide (1p): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), 7.45 (t, J = 7.2 Hz, 1 H), (m, 2 H), 7.32 (d, J = 8.0 Hz, 1 H), (m,2 H), (m, 2 H), 6.93 (t, J = 8.0 Hz, 2 H), 3.02 (t, J = 7.6 Hz, 2 H), 2.60 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz), (d, J C-F = Hz), , , (d, J C-F = 51.0 Hz), ,19.3 Hz), , (d, J C-F = 21.0 Hz), , 36.10, 30.30; HRMS (EI-TOF): m/zcalcd. for C 22 H 16 F 2 N 2 NaO [M+Na] + : , found N-(2-cyanophenyl)-N,3-diphenylpropanamide (1q): 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (dd, J = 7.6, 1.6 Hz, 2 H), 7.58 (t, J = 7.6Hz, 1 H), (m, 4 H), (m, 6 H),7.13 (d, J = 7.2 Hz, 2 H), 3.04 (t, J = 7.6 Hz, 2 H), 2.64 (s, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , , , , S10

11 130.00, , , , , , , , , 36.57, 31.47; HRMS (EI-TOF): m/zcalcd. for C 22 H 18 N 2 O [M+H] + : , found N-(2-cyanophenyl)-3-phenyl-N-o-tolylpropanamide (1r): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 7.6, 1.6 Hz, 1 H), 7.48 (t, J = 7.6Hz, 1 H), (m, 8 H), 7.12 (d, J = 7.6 Hz, 2 H), 7.03 (d, J = 7.6Hz, 1 H), 3.06 (t, J = 7.6 Hz, 2 H), (m, 2 H), 2.23(s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , , , , , 37.14, 31.34, 18.25; HRMS (EI-TOF): m/zcalcd. for C 23 H 21 N 2 O [M+H] + : , found H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 7.6, 1.6 Hz, 1 H), 7.58 (td, J = 7.6, 1.6Hz, 1 H), (m, 4 H), (m, 2 H), 3.05 (t, J = 7.6 Hz, 2 H), 2.62 (t, J = 7.6 Hz,2 H); 13 C NMR (100 MHz, CDCl 3 ) δ172.89, (d, J C-F = Hz), , , (d, J C-F = 46.8 Hz), ,129.50, , , ,128.30, , , , , (d, J C-F = 20.4 Hz), , , 36.12, 31.07; HRMS (EI-TOF): m/zcalcd. for C 22 H 13 D 5 FN 2 O [M+H] + : , found S11

12 2.2 References (1) Gorvin, J. H. J. Chem. Soc., Perkin Trans. 1988, 1, (2) Wan, L.; Dastbaravardeh, N.; Li, G.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, S12

13 2.3 Optimization Studies Table S1. Initial Screening Solvents a Table S2. Screening of Temperature a S13

14 S14 Table S3. Screening of Oxidants a

15 Table S4. Screening Equivalents of Oxidants a S15

16 Table S5. Screening of Additives a S16

17 Table S6.Screening of Time a S17

18 Table S7.Screening of Templates a S18

19 Table S8.Screening of theequivalentsof ethyl acrylate a S19

20 Table S9.Utilityof T 3 with Palladium catalysts a 2.4 General procedure for Rh (III)-catalyzed meta-c-h olefination To a 25 ml Schlenk-type sealed tube equipped with a magnetic stirring bar was added the substrate (0.1 mmol), [RhCp*Cl 2 ] 2 (3.1 mg, mmol), Cu (CO 2 CF 3 ) 2 xh 2 O (28.9mg, 0.1 mmol), CF 3 CO 2 H (0.1 mmol), olefin (0.5 mmol) and DCE (2.0 ml). The tube was evacuated then back-filled with O 2 (3 times, balloon), capped, and heated to 100 C for 48 hours. After cooling to room temperature, the reaction mixture was filtered through a pad of silica gel. The silica gel was washed with an additional 10 ml of DCM. The filtrate was concentrated in vacuo to afford crude products, which was purified by flash column chromatography on silica gel using hexanes/etoac (3/1) as the eluent to give the pure product. S20

21 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)phenyl) acrylate (3a mono ): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.63 (d, J = 16.0 Hz, 1 H), 7.58 (td, J = 8.0, 1.6 Hz, 1 H), (m, 4 H), (m, 3 H), (m, 3 H), 6.39 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H) 3.05(t, J = 7.6 Hz, 2 H), 2.62 (t, J = 7.2 Hz, 2 H), 1.34 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 51.4 Hz), , , , , , , , ,126.05, , , , (d, J C-F = 19.7 Hz), , , 60.61, 35.87, 30.96, 14.44; HRMS (EI-TOF): m/zcalcd. for C 27 H 24 FN 2 O 3 [M+H] + : , found (2E,2'E)-diethyl-3,3'-(5-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropy l)-1,3-phenylene)diacrylate (3a di ): 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (d, J = 7.2 Hz, 1 H), 7.63 (d, J = 16.0 Hz, 2 H), 7.58 (t, J = 8.0 Hz, 1 H), (m, 4 H), (m, 3 H), (m, 2 H), 6.43 (d, J = 16.0 Hz, 2 H), 4.27 (q, J = 7.6 Hz, 2 H), 3.07 (t, J = 7.6 Hz, 2 H), 2.63 (s, 2 H), 1.35 (t, J = 7.2 Hz, 6 H); 13 C NMR (125 MHz, CDCl 3 ) δ , , (d, J C-F = 166 Hz), , , , , (d, J C-F = 52.2 Hz), , , , , , , , , (d, J C-F = 13.1 Hz), , , 60.75, 35.67, S21

22 30.84, 14.44; HRMS (EI-TOF): m/zcalcd. for C 32 H 30 FN 2 O 5 [M+H] + : , found (E)-ethyl-3-(3-(4-((2-cyanophenyl)(2-fluorophenyl)amino)-4-oxobutan-2-yl)phe nyl)acrylate (3b mono ): 1 H NMR (400 MHz, CDCl 3 ) δ 7.70 (d, J = 7.6 Hz, 1 H), 7.64 (d, J = 16.0 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 1 H), (m, 3 H), (m, 4 H), (m, 3 H), 6.39 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H)3.48 (m, 1 H), (m, 2 H), 1.34 (m, 6 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 43.4 Hz), , , , , , , , , , , , , , , 60.56, 42.47, 36.38, 21.50, 14.43; HRMS (EI-TOF): m/zcalcd. for C 28 H 26 FN 2 O 3 [M+H] + : , found (2E,2'E)-diethyl-3,3'-(5-(4-((2-cyanophenyl)(2-fluorophenyl)amino)-4-oxobutan -2-yl)-1,3-phenylene)diacrylate (3b di ): 1 H NMR (400 MHz, CDCl 3 ) δ 7.68 (d, J = 8.0 Hz, 1 H), 7.63 (d, J = 16.0 Hz, 2 H), (m, 3 H), (m, 2 H), (m, 2 H), 7.22 (m, 3 H), 6.42 (d, J = 16.0 Hz, 2 H), 4.27 (q, J = 7.2 Hz, 4 H) 3.50 (m, 1 H), (m, 2 H), 1.33 (m, 9 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , S22

23 133.85(d, J C-F = 49.5 Hz), , , , , , , , , , 60.72, 42.30, 36.39, 21.58, 14.42; HRMS (EI-TOF): m/zcalcd. for C 33 H 31 FN 2 NaO 5 [M+Na] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-meth ylphenyl)acrylate (3c): 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (dd, J = 7.6, 1.2 Hz, 1 H), 7.60 (d, J = 15.6 Hz, 1 H), 7.58 (td, J = 7.2, 1.2 Hz, 1 H), (m, 3 H), 7.32 (d, J = 8.0 Hz, 1 H), 7.28 (d, J = 8.0 Hz, 1 H), (m, 3 H), 7.12 (d, J = 7.6 Hz, 1 H),6.35 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.05 (t, J = 8.0 Hz, 2 H), 2.57 (t, J = 7.6 Hz, 2 H), 2.23 (s, 3 H), 1.34 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 51.5 Hz), , , , , , , , , , , (d, J C-F = 19.1 Hz),116.98, , 60.50, 34.58, 28.67, 19.27, 14.46; HRMS (EI-TOF): m/zcalcd. for C 28 H 26 FN 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-meth oxyphenyl)acrylate (3d): 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 16.0 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H), (m, 6 H), S23

24 (m, 2 H), 6.77 (d, J = 8.4 Hz, 1 H), 6.28 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2 Hz, 2 H), 3.73 (s, 3 H), 3.02 (t, J = 7.6 Hz, 2 H), 2.59 (t, J = 7.2 Hz, 2 H), 1.32 (t, J = 7.2Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , (d, J C-F = Hz), , , (d, J C-F = 42.7 Hz), , , , , , , , , , , , , , 60.38, 55.35, 33.91, 26.58, 14.46; HRMS (EI-TOF): m/zcalcd. for C 28 H 26 FN 2 O 4 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-fluor ophenyl)acrylate (3e): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72(d, J = 7.6 Hz, 1 H), 7.59 (d, J = 16.0 Hz, 1 H), 7.60(t, J = 7.2 Hz, 1 H), 7.48 (t, J = 8.4 Hz, 1 H), (m, 5 H), (m, 2 H), 6.98 (t, J = 7.2 Hz, 1 H), 6.33 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.07(t, J = 7.6 Hz, 2 H), 2.63 (s, 2 H), 1.33(t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) , , (d, J C-F = Hz), (d, J C-F = Hz), , , (d, J C-F = 52.6 Hz), , , (d, J C-F = 3.6 Hz), , (d, J C-F = 13.2 Hz), , (d, J C-F = 16.4 Hz), ,125.68, , (d, J C-F = 19.6 Hz), , (d, J C-F = 22.7 Hz), (d, J C-F = 22.4 Hz), , 60.58, 34.14, 24.82, 14.40; HRMS (EI-TOF): m/zcalcd. for C 27 H 23 F 2 N 2 O 3 [M+H] + : , found S24

25 (E)-ethyl-3-(4-chloro-3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropy l)phenyl)acrylate (3f): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.59 (d, J = 16.0 Hz, 1 H), 7.58(t, J = 7.2 Hz, 1 H), (m, 4 H), 7.32 (d, J = 8.4Hz, 1 H),7.30(s, 2 H),7.20 (m, 2 H), 6.39 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2 Hz, 2 H), 3.16 (t, J = 7.6 Hz, 2 H), 2.64 (t, J = 7.2 Hz, 2 H), 1.33 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , ,141.96,138.96, , (d, J C-F = 50.3 Hz), ,130.92, , , , , , , , , , (d, J C-F = 19.5 Hz), , , 60.66, 33.78, 29.36, 14.41; HRMS (EI-TOF): m/zcalcd. for C 27 H 23 ClFN 2 O 3 [M+H] + : , found (E)-ethyl-3-(4-bromo-3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropy l)phenyl)acrylate (3g): 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (d, J = 7.2 Hz, 1 H), 7.57 (d, J = 16.0 Hz, 1 H), 7.58 (s, 1 H), 7.48 (d, J = 8.4 Hz, 2 H), (m, 3 H), 7.32 (d, J = 8.0 Hz, 1 H), (m, 3 H), 6.40 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2 Hz, 2 H), 3.16 (t, J = 8.0 Hz, 2 H), 2.65 (s, 2 H), 1.33 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 50.9 Hz), , , , , , ,128.73, , , ,125.55, , (d, J C-F = 19.5 Hz), , , 60.53, 33.73, 31.62, 14.24;HRMS (EI-TOF): m/zcalcd. S25

26 for C 27 H 23 BrFN 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-(trifl uoromethyl)phenyl)acrylate (3 H): 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (dd, J = 8.0, 1.6 Hz, 1 H), 7.64(d, J = 16.4 Hz, 1 H), 7.58 (d, J = 8.0 Hz, 2 H), (m, 6 H), 7.20 (m, 2 H), 6.48 (d, J = 16.4 Hz, 1 H), 4.27 (q, J = 7.2 Hz, 2 H), 3.23 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 H), 1.35 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , , (d, J C-F = 56.8 Hz), , , , , , , (q, J C-F = Hz ), , (q, J C-F = 5.6 Hz), ,122.83, , (d, J C-F = 19.8 Hz), , , 60.83, 35.84, 28.08, 14.36;HRMS (EI-TOF): m/zcalcd. for C 28 H 23 F 4 N 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-meth ylphenyl)acrylate (3i): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 16.0 Hz, 1 H), 7.58 (td, J = 7.2, 1.6 Hz, 1 H), (m, 3 H), 7.31 (d, J = 7.6 Hz, 1 H), (m, 3 H), 7.06 (s, 1 H), 6.99 (s, 1 H), 6.38 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2 Hz, 2 H), 3.01 (t, J = 7.6 Hz, 2 H), 2.60 (t, J = 7.2 Hz, S26

27 2 H), 2.31 (s, 3 H), 1.33 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 49.1 Hz), , , (d, J C-F = 7.7 Hz), , , , , , , , , (d, J C-F = 20.2 Hz), , , 60.57, 35.94, 30.93, 21.34, 14.45; HRMS (EI-TOF): m/zcalcd. for C 28 H 23 F 4 N 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-meth oxyphenyl)acrylate (3j): 1 H NMR (400 MHz, CDCl 3 ) δ7.73 (d, J = 7.6 Hz, 1 H), 7.58 (d, J = 16.0 Hz, 1 H), 7.58 (td, J =8.0, 1.6 Hz, 1 H), (m, 3 H), 7.31(d,J = 8.0 Hz, 1 H), (m, 2 H), 6.87 (s, 2 H), 6.72 (s, 1 H), 6.37 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.79 (s, 3 H), 3.02 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 H), 1.34 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , (d, J C-F = 249 Hz), , , , , (d, J C-F = 49.4 Hz), , , , , , , ,121.09, , (d, J C-F = 19.8 Hz), , , , , 60.63, 55.45, 35.85, 31.13, 14.45; HRMS (EI-TOF): m/zcalcd. for C 28 H 25 FN 2 NaO 4 [M+Na] + : , found S27

28 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3k): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), (m, 2 H), (m, 3 H), 7.32 (d, J = 8.0 Hz, 1 H), (m, 2 H), 7.06 (s, 1 H), 7.03 (s, 1 H), 6.88 (d, J = 8.8 Hz, 1 H), 6.38 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.04 (t, J = 7.2 Hz, 2 H), 2.63 (t, J = 7.2 Hz, 2 H), 1.34 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), (d, J C-F = Hz), , (d, J C-F = 7.9 Hz), , (d, J C-F = 8.2 Hz), (d, J C-F = 54.8 Hz), (d, J C-F = 9.3 Hz), , ,128.92, , , (d, J C-F = 2.1 Hz), , , (d, J C-F = 20.8Hz), (d, J C-F = 21.3 Hz), ,113.05, (d, J C-F =22.0 Hz), 60.78, 35.47, 30.73, 14.43; HRMS (EI-TOF): m/zcalcd. for C 27 H 23 F 2 N 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3l): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.58 (td, J = 8.0, 1.2 Hz, 1 H), 7.55 (d, J = 16.0 Hz, 1 H), (m, 3 H), (m, 2 H), (m, 2 H), 7.16 (s, 1 H), 7.13 (s, 1 H), 6.39 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.03 (t, J = 7.2 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 S28

29 H), 1.33 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , , (d, J C-F = 54.2 Hz), , , , , , , , , , , (d, J C-F = 20.6 Hz), , , 60.79, 35.48, 30.66, 14.42; HRMS (EI-TOF): m/zcalcd. for C 27 H 23 ClFN 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3m): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.59 (d,j = 7.2 Hz, 1 H), 7.54 (d, J = 16.0 Hz, 1 H), (m, 4 H), 7.32 (d, J = 8.0 Hz, 1 H), 7.28 (s, 1 H), (m, 3 H), 6.39 (d, J = 15.6 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.02 (t, J = 7.2 Hz, 2 H), 2.62 (t, J = 7.2 Hz, 2 H), 1.33 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , , (d, J C-F = 53.7 Hz),133.13, , , (d, J C-F = 13.7 Hz), ,128.68, ,127.17, , , , (d, J C-F = 21.3 Hz), , , 60.76, 35.49, 30.64, 14.41;HRMS (EI-TOF): m/zcalcd. for C 27 H 23 BrFN 2 O 3 [M+H] + : , found S29

30 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3n): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.64 (d, J = 16.0 Hz, 1 H), (m,2 H), (m, 5 H), 7.29 (d, J = 8.0 Hz, 1 H), (m, 2 H), 6.46 (d, J = 16.4 Hz, 1 H), 4.27 (q, J = 7.2 Hz, 2 H), 3.11 (t, J = 7.2 Hz, 2 H), 2.64 (t, J = 7.2 Hz, 2 H), 1.34 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , , (d, J C-F = 55.2Hz), , , , , , , (q, J C-F = 3.6 Hz), , , , , , (d, J C-F = 20.5 Hz), , , 60.85, 35.43, 30.78, 14.42; HRMS (EI-TOF): m/zcalcd. for C 28 H 22 F 4 N 2 NaO 3 [M+Na] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3o): 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 16.0 Hz, 1 H), 7.72 (d, J = 6.8 Hz, 1 H), 7.58 (td, J = 8.0, 1.2 Hz, 1 H), (m, 3 H), 7.31 (d, J = 8.0 Hz, 1 H), (m, 4 H), 6.81 (d, J = 8.4 Hz, 1 H), 6.47 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.85 (s, 3 H), 2.98 (t, J = 7.2 Hz, 2 H), 2.58 (t, J = 7.6 Hz, 2 H), 1.34 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 48.0 Hz),132.95, , , , , , , , , , , (d, J C-F = 18.2 Hz), , , , 60.45, 55.69, 36.21, 30.22, 14.50; HRMS (EI-TOF): m/zcalcd. for C 28 H 25 FN 2 NaO 4 [M+Na] + : , found S30

31 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3p): 1 H NMR (400 MHz, CDCl 3 ) δ 7.74 (d, J = 16.0 Hz, 1 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 1 H), (m, 3 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.27 (dd, J = 6.8, 2.4 Hz, 1 H), (m, 3 H), 6.98 (d, J = 8.4 Hz, 1 H), 6.49 (d, J = 16.0 Hz, 1 H), 4.26 (q, J = 7.2 Hz, 2 H), 3.02 (t, J = 7.6 Hz, 2 H), 2.60 (t, J = 7.2 Hz, 2 H), 1.34 (t, J = 6.8 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), (d, J C-F = Hz), , , , , (d, J C-F = 53.4 Hz), (d, J C-F = 8.5 Hz),131.07, , , , (d, J C-F = 2.9 Hz), , , , , (d, J C-F = 11.8 Hz), (d, J C-F = 6.6 Hz), (d, J C-F = 18.4 Hz), , (d, J C-F = 21.9 Hz), , 60.70, 35.88, 30.24, 14.43; HRMS (EI-TOF): m/zcalcd. for C 27 H 23 F 2 N 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3q): 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 (d, J = 7.6 Hz, 1 H), 7.60 (d, J = 16.0 Hz, 1 H), 7.59 (td, J = 8.0, 1.6 Hz, 1 H), (m, 3 H), 7.32 (d, J = 8.4 Hz, 1 H), (m, 2 H), 6.87 (s, 2 H), 6.73 (s, 1 H), 6.38 (d, J = 16.0 Hz, 1 H), 3.81 (s, 3 H), 3.79 (s, 3 H), 3.03 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , (d, J C-F = S31

32 248.9 Hz), , , , , (d, J C-F = 51.7 Hz), , , , , , , , , (d, J C-F = 19.8 Hz), , , , , 55.46, 51.86, 35.84, 31.11; HRMS (EI-TOF): m/zcalcd. for C 27 H 24 FN 2 O 4 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3r): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.58 (d, J = 16.0 Hz, 1 H), 7.58 (d, J = 6.4, 1.2 Hz, 1 H), (m, 3 H), 7.31 (d, J = 8.0 Hz, 1 H), (m, 2 H), 6.87 (s, 2 H), 6.72 (s, 1 H), 6.38 (d, J = 16.0 Hz, 1 H), 4.20 (t,j = 6.8 Hz, 2 H), 3.79 (s, 3 H), 3.02 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 H), (m, 2 H), (m, 2 H), 0.96 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , (d, J C-F = Hz), , , , , (d, J C-F = 50.9 Hz), , , , , , , , , (d, J C-F = 19.6 Hz), , ,, , , 64.57, 55.45, 35.85, 31.12, 30.88, 19.32, 13.88; HRMS (EI-TOF): m/zcalcd. for C 30 H 30 FN 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor S32

33 ophenyl)acrylate (3s): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (td, J = 8.0, 1.6 Hz, 1 H), 7.56 (d, J = 15.6 Hz, 1 H), (m, 3 H), 7.31 (d, J = 7.6 Hz, 1 H), (m, 2 H), 6.90 (s, 1 H), 6.86 (s, 1 H), 6.82 (s, 1 H), 6.67 (s, 1 H), 3.79 (s, 3 H), 3.17 (s, 3 H), 3.07 (s, 3 H), 3.02 (t, J = 8.0 Hz, 2 H), 2.61 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , (d, J C-F = Hz), , , , , , (d, J C-F = 53.5 Hz), , , , , , , , , (d, J C-F = 19.8 Hz), , , , , 55.43, 37.57, 36.04, 35.94, 31.21;HRMS (EI-TOF): m/zcalcd. for C 28 H 27 FN 3 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3t): 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (td, J = 8.0, 1.2 Hz, 1 H), 7.56 (d, J = 16.4 Hz, 1 H), (m, 3 H), 7.31 (d, J = 8.0 Hz, 1 H), (m, 2 H), 6.91 (s, 1 H), 6.89 (s, 1 H), 6.72 (s, 1 H), 6.68 (d, J = 16.4Hz, 1 H), 3.79 (s, 3 H), 3.03 (t, J = 7.6 Hz, 2 H), 2.69 (q, J = 7.2 Hz, 2 H), 2.61 (t, J = 7.6 Hz, 2 H), 1.16 (t, J = 7.2 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ201.12, , , (d, J C-F = Hz), , , , , (d, J C-F = 53.4 Hz), , , , , , , , , , (d, J C-F = 26.1 Hz), , , , 55.47, 35.82, 34.14, 31.06, 8.35;HRMS (EI-TOF): m/zcalcd. for C 28 H 26 FN 2 O 3 [M+H] + : , found S33

34 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3u): 1 H NMR (400 MHz, CDCl 3 ) δ 9.68 (d, J = 8.0 Hz, 1 H), 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 1 H), 7.41 (d, J = 22.8 Hz, 1 H), (m, 3 H), 7.32 (d, J = 8.0 Hz, 1 H), (m, 2 H), 6.93 (s, 1 H), 6.91 (s, 1 H), 6.78 (s, 1 H),6.68 (dd, J = 16.0, 7.6Hz, 1 H), 3.80 (s, 3 H), 3.05 (t, J = 7.6 Hz, 2 H), 2.63 (t, J = 7.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ193.88, , , (d, J C-F = Hz), , , , , (d, J C-F = 54.9 Hz), , , , , , , , , (d, J C-F = 21.8 Hz), , , 55.51, 35.70, 30.96; HRMS (EI-TOF): m/zcalcd. for C 26 H 22 FN 2 O 3 [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3v): 1 H NMR (400 MHz, CDCl 3 ) δ7.72 (dd, J = 7.6, 1.2 Hz, 1 H), 7.58 (td, J = 7.2, 1.6 Hz, 1 H), (m, 3 H), 7.31 (d, J = 8.0 Hz, 1 H), (m, 2 H), 6.80 (s, 2 H), 6.69 (s, 1 H), 6.08 (q, J = 1.2 Hz, 1 H), 3.79 (s, 3 H), 3.76 (s, 3 H), 3.03 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.6 Hz, 2 H), 2.52 (t, J = 1.6 Hz, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , (d, J C-F = Hz), , , , , (d, J C-F = 47.5 Hz), , S34

35 130.81, , , , , , , (d, J C-F = 20.6 Hz), , , , , , 55.49, 51.27, 36.06, 31.40, 21.71, 18.24; HRMS (EI-TOF): m/zcalcd. for C 29 H 27 FN 2 NaO 4 [M+Na] + : , found (E)-N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-methoxy-5-(4-oxopent-2-en-2-yl )phenyl)propanamide (3w): 1 H NMR (400 MHz, CDCl 3 ) δ7.73 (dd, J = 7.6, 1.2 Hz, 1 H), 7.58 (t, J = 7.6, Hz, 1 H), (m, 3 H), (m, 2 H), (m, 4 H), 6.47 (s, 1 H), 3.07 (t, J = 7.6 Hz, 2 H), 2.63 (t, J = 7.6 Hz, 2 H), 2.49 (d, J = 1.2 Hz, 3 H), 2.29 (s, 3 H); 13 C NMR (100 MHz, CDCl 3 ) δ199.12, , (d, J C-F = Hz), , , , , (d, J C-F = 49.2 Hz), , , , , , , , , , , , , (d, J C-F = 18.6 Hz), , , 36.08, 32.39, 31.41, 31.20, 18.50; HRMS (EI-TOF): m/zcalcd. for C 28 H 25 FN 2 NaO 3 [M+Na] + : , found Dimethyl-2-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-meth oxyphenyl)maleate (3x): 1 H NMR (400 MHz, CDCl 3 ) δ7.71 (d, J = 7.6Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), (m, 4 H), (m, 2 H), 6.97 (s, 1 H), 6.65 (d, J = 1.2 Hz, 1 H), 6.62 (s, 1H), 6.58 (s, 1 H), 3.78 (s, 3H), 3.74 (s, 3H), 3.56 (s, S35

36 3H),3.02 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ172.64, , , , (d, J C-F = Hz), , , ,135.04, (d, J C-F = 48.9 Hz), , , , , ,125.60,124.85, , , (d, J C-F = 20.3 Hz), , , ,112.50, 55.29, 52.98, 51.91, 35.89, 31.19; HRMS (EI-TOF): m/zcalcd. for C 29 H 25 FN 2 NaO 6 [M+Na] + : , found Dimethyl-2-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-methox yphenyl)fumarate (3y): 1 H NMR (400 MHz, CDCl 3 ) δ7.71 (d, J = 7.6Hz, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), (m, 3 H),7.30 (d, J = 7.6Hz, 1 H), (m, 2 H), 6.81 (s, 2 H), 6.76 (s, 1H), 6.25 (s, 1 H), 3.91 (s, 3H), 3.77 (s, 3H), 3.77 (s, 3H),3.02 (t, J = 7.6 Hz, 2 H), 2.60 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ172.37, , , , (d, J C-F = Hz), , ,143.29, (d, J C-F = 52.0 Hz), , (d, J C-F = 6.7 Hz),130.67, , (d, J C-F = 12.4 Hz), , , , , , , (d, J C-F = 29.0 Hz), , , , 55.45, 52.82, 52.13, 35.79, 31.15;HRMS (EI-TOF): m/zcalcd. for C 29 H 25 FN 2 NaO 6 [M+Na] + : , found S36 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor

37 ophenyl)acrylate (3z): 1 H NMR (400 MHz, CDCl 3 ) δ7.72 (d, J = 7.2 Hz, 1 H), 7.58 (t, J = 7.6 Hz, 1 H), (m, 5 H), (m, 2 H), 6.85 (s, 2 H), 6.71(s, 1 H), 6.19 (t, J = 17.6 Hz, 1 H), 4.12(td, J = 7.6, 1.6 Hz, 4 H), 3.78 (s, 3 H), 3.01 (t, J = 7.6 Hz, 2 H), 2.60 (t, J = 7.6 Hz, 2 H), 1.35 (t, J = 7.2 Hz, 6 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , , (d, J C-F = 53.2 Hz), , , ,127.97, , , (d, J C-F = 19.0 Hz), , , , , , , 62.03, 55.46, 35.82, 31.16, 16.56; HRMS (EI-TOF): m/zcalcd. for C 29 H 31 FN 2 O 5 P [M+H] + : , found (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3α): 1 H NMR (400 MHz, CDCl 3 ) δ7.72 (dd, J = 7.6, 1.6 Hz, 1 H), 7.57 (td, J = 7.6, 1.6 Hz, 1 H), (m, 6 H), (m, 2 H), (m, 3 H), (m, 3 H), 6.59 (s, 1 H), 3.80 (s, 3 H), 3.04 (t, J = 7.6 Hz, 2 H), 2.63 (t, J = 7.6 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , (d, J C-F = Hz),160.17, (d, J C-F = Hz), , , , (d, J C-F = 49.1 Hz), , ,130.86, , , , , (d, J C-F = 7.9 Hz), , , , , (d, J C-F = 18.9 Hz), , (d, J C-F = 21.6 Hz), , , , 55.43, 36.09, 31.37;H HRMS (EI-TOF): m/zcalcd. for C 31 H 25 F 2 N 2 O 2 [M+H] + : , found S37

38 (E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor ophenyl)acrylate (3β): 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2 H), 7.71 (d, J = 7.6Hz, 1 H), (m, 5 H), (m, 3 H), 7.29 (d, J = 8.0 Hz, 1 H), (m, 2 H), 6.84 (s, 1 H), 6.81 (d, J = 15.6 Hz, 1 H), 6.81 (s, 1 H), 6.75 (s, 1 H), 3.77 (s, 3 H), 3.00 (t, J = 7.6 Hz, 2 H), 2.59 (t, J = 7.2 Hz, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , (d, J C-F = Hz), , , , , (d, J C-F = 56.8 Hz), , , , , , , , , , , , , , , (d, J C-F = 17.0 Hz), , , , 55.52, 35.64, 30.97; HRMS (EI-TOF): m/zcalcd. for C 31 H 26 FN 2 O 4 S [M+H] + : , found (E)-ethyl-3-(1-(3-(4-cyano-2,6-dimethylheptan-4-yl)-4-methoxyphenylsulfonyl)i ndolin-6-yl)acrylate (6a): 6 was olefinated following the general procedure in the absence of added TFA to provide 6a. 1 H NMR (400 MHz, CDCl 3 ) δ 8.05 (d, J = 2.4 Hz, 1 H), 7.79 (dd, J = 8.8, 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.65 (d, J = 16.0 Hz, 1 H), 7.12 (dd, J= 8.0, 1.2 Hz, 1 H), 7.06 (d, J = 7.6 Hz, 1 H), 6.90 (d, J = 8.8 Hz, 1 H), 6.45 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2Hz, 2 H), 3.98 (q, J = 8.4 Hz, 2 H), 3.85 S38

39 (s, 3 H), 2.92 (t, J = 8.4 Hz, 2 H), 2.17 (dd, J = 14.0, 6.0 Hz, 2 H), (m, 3 H), 1.33 (t, J = 7.2 Hz, 3 H), 0.81 (d, J = 6.8 Hz, 6 H), 0.47 (d, J = 6.4 Hz, 6 H); 13 C NMR (100 MHz, CDCl 3 ) δ167.13, , , , , , , , , , , , , , 60.61, 55.81, 50.50, 46.99, 46.70, 27.92, 25.90, 23.58, 23.55, (E)-ethyl-3-(3-(3-(4-cyano-2,6-dimethylheptan-4-yl)-4-methoxy-N-methylpheny lsulfonamido)phenyl)acrylate (7a mono ): 7 was olefinated following the general procedure to provide 7a mono and 7a di. 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (d, J = 2.4 Hz, 1 H), 7.57 (d, J = 16.0 Hz, 1 H), 7.50 (dd, J = 8.8, 2.4 Hz, 1 H), (m, 1 H), 7.32 (t, J = 8.8 Hz, 1 H), (m, 2 H), 6.88 (d, J = 8.4 Hz, 1 H), 6.32 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2Hz, 2 H), 3.90 (s, 3 H), 3.23 (s, 3 H), 2.25 (dd, J = 14.0, 6.0Hz, 2 H), 1.75 (dd, J = 7.6, 6.4 Hz, 2 H), (m, 2 H), 1.32 (t, J = 7.2 Hz, 3 H), 0.92 (d, J = 6.8 Hz, 6 H), 0.62 (d, J = 6.8 Hz, 6 H); 13 C NMR (100 MHz, CDCl 3 ) δ , 160,85, 43.65, , , , , , , , , , , , , , , , 60.73, 55.83, 47.01, 46.84, 38.14, 25.99, 23.75, 23.72, S39

40 (2E,2'E)-diethyl-3,3'-(5-(3-(4-cyano-2,6-dimethylheptan-4-yl)-4-methoxy-N-met hylphenylsulfonamido)-1,3-phenylene)diacrylate (7a di ): 7 was olefinated following the general procedure to provide 7a mono and 7a di. 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (d, J = 2.0 Hz, 1 H), 7.57 (d, J = 16.0 Hz, 2 H), 7.52 (s, 1 H), 7.49(dd, J = 8.4, 2.4 Hz, 1 H), 7.27 (d, J = 1.6 Hz, 1 H),7.26 (s, 1 H), 6.89 (d, J = 8.8 Hz, 1 H), 6.37 (d, J = 16.0 Hz, 1 H), 4.25 (q, J = 7.2 Hz, 4 H), 3.90 (s, 3 H), 3.24 (s, 3 H), 2.26 (dd, J = 14.4, 6.0Hz, 2 H), 1.76 (dd, J = 14.4, 6.8 Hz, 2 H), (m, 2 H), 1.33 (t, J = 7.2 Hz, 6 H), 0.92 (d, J = 6.4 Hz, 6 H), 0.62 (d, J = 6.8 Hz, 6 H); 13 C NMR (100 MHz, CDCl 3 ) δ , , , , , , , , , , , , , , 60.88, 55.87, 47.07, 46.80, 38.08, 26.03, 23.70, meta-c H Olefination of Indoline and N-Methylaniline 2.6 Kinetic Isotope Effect. Kinetic studies on the meta-olefination of 1a and 1a-D were conducted in separate vessels. To a 25 ml Schlenk-type sealed tube equipped with a magnetic stirring bar was added the substrate (0.1 mmol), [RhCp*Cl 2 ] 2 (3.1 mg, mmol), S40

41 Yield (%) Cu(CO 2 CF 3 ) 2 xh 2 O (28.9 mg, 0.1 mmol), CF 3 CO 2 H (0.1 mmol), olefin (0.5 mmol) and DCE (2.0 ml). The tube was evacuated then back-filled with O 2 (3 times, balloon), capped, and immersed into a pre-heated oil bath at 100 C. After the indicated time, the Schlenk-type tube was cooled by ice water. The reaction mixture was filtered through Celite and eluted with DCM (4 4 ml). The filtrate was concentrated in vacuo to afford crude products. The yield was determined by 1H NMR analysis of the crude product using CH 2 Br 2 as an internal standard. Each time point was repeated three times and the equations for the lines were determined by linear regression. The ratio of the slopes for these lines corresponds to the KIE Eq. 1 Eq Time (h) S41

42 Table S10. Data from the Kinetic Isotope experiments with 1a and 1a-D S42

43 2.7 The procedure for the 10 mmol reaction in Toluene To a 250 ml round-bottom flask was added a magnetic stir bar, substrate 1a (10 mmol), [RhCp*Cl 2 ] 2 (0.31 g, 0.5 mmol), Cu (CO 2 CF 3 ) 2 xh 2 O (2.89 g, 10 mmol), CF 3 CO 2 H (1.14 g, 10 mmol), dry toluene (150 ml) and Ethyl acrylate (5.00 g, 50 mmol). The system was equipped with a reflux condenser and was evacuated and then back-filled with O 2 (balloon, 3 times). Next, the reaction was refluxed for 48 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and water and the phases were separated. The aqueous layer was extracted with ethyl acetate three times. The combined organic extracts were dried over MgSO 4, filtered and concentrated in vacuo to afford crude products, which were purified by flash column chromatography on silica gel using hexanes/etoac (3/1) as the eluent to give the pure products in 75% combined yield (mono 55%, di 20% isolated). S43

44 3. NMR Spectra for New Compounds S44

45 S45

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96 S96

97 1 H NMR of 3e at room temperature used d 6 -DMSO as solvent 1 H NMR of 3e at 100 d 6 -DMSO as solvent S97