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S1
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
210023, China.
‡ Department of Chemistry, The Scripps Research Institute, 10550 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 ................................................................................................... S12
2.3 Optimization Studies .................................................................................... S13
2.4 General procedure for Rh (III)-catalyzed meta-C-H Olefination ................... S20
2.5 meta-C–H Olefination of Indoline and N-Methylaniline…………………….S40
2.6 Kinetic Isotope Effect Studies………………………………………………..S40
2.7 The Procedure for the 10 mmol Reaction in Toluene………………………..S43
3. NMR Spectra for New Compounds ................................................................... S44
S2
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 CDCl3. High-resolution mass spectra
(HRMS) were obtained with a Q-TOF (ESI).
2. Experimental Section
2.1 Preparation and characterization of substrates
2.1.1 Procedure for the preparation of template (T3)1
Toa 100 mL round bottom flask was added 2-fluorobenzonitrile (20 mmol,
1.0 equiv), 2-fluoroaniline (20 mmol, 1.0 equiv) and tBuOK (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.
2-(2-fluorophenylamino)benzonitrile (T3): 1H NMR (400 MHz, CDCl3) 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), 7.20-7.07 (m, 4 H), 6.91 (td, J = 7.6, 1.2 Hz, 1 H), 6.25 (br, 1 H); 13
C NMR (100
MHz, CDCl3) δ 155.31 (d, JC-F = 195.4 Hz), 146.54, 133.57 (d, JC-F = 83.5 Hz),
S3
128.20 (d, JC-F = 9.5 Hz), 124.98 (d, JC-F = 5.9 Hz), 124.65 (d, JC-F = 2.7 Hz),
122.72, 120.111, 117.34, 116.47 (d, JC-F = 15.5 Hz), 114.78, 99.62; HRMS
(EI-TOF): m/zCalcd. for C13H10FN2 [M+H]+: 213.0823, found 213.0824.
2.1.2 General procedure for the preparation of substrates (1a-1).2
To an ice cooled solution of template (T3) (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 0oC 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 oC. The
reaction was stirred overnight, then quenched with water, and extracted with DCM
three times.The combined organic extractsweredried over MgSO4 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): 1H NMR
(400 MHz, CDCl3) δ 7.72 (dd, J = 8.0, 1.6 Hz, 1 H), 7.59 (td, J = 7.6, 1.2 Hz, 1 H),
7.46-7.31 (m, 4 H), 7.28-7.13 (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, CDCl3) δ 172.87, 158.25 (d, JC-F = 247.6 Hz), 144.80,
140.88, 133.85 (d, JC-F = 4.3 Hz), 130.82, 129.41, 128.99, 128.66, 128.59, 128.56,
127.92, 126.45, 126.31, 125.62, 117.31 (d, JC-F = 20.7 Hz), 117.01, 113.10, 36.15,
31.21; HRMS (EI-TOF): m/zCalcd. for C22H18FN2O [M+H]+: 345.1398, found
345.1401.
S4
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-phenylbutanamide (1b): 1H NMR (400
MHz, CDCl3) δ 7.71 (s, 1 H), 7.54 (t, J = 6.8 Hz, 1 H), 7.36 (m, 2 H), 7.29-7.12 (m,
9 H), 3.49-3.43 (m, 1 H), 2.65-2.49 (m, 2 H), 1.36 (d, J = 6.4 Hz, 3 H); 13
C NMR
(100 MHz, CDCl3) δ 172.34, 158.81 (d, JC-F = 245.3 Hz), 146.07, 144.64, 133.82 (d,
JC-F = 38.8 Hz), 130.84, 129.46 (d, JC-F = 13.2 Hz), 129.08, 128.55, 127.85, 126.96,
126.39, 125.50, 124.79, 117.25 (d, JC-F = 20.5 Hz), 116.85, 112.97, 42.72, 36.36,
21.43; HRMS (EI-TOF): m/zCalcd. for C23H20FN2O [M+H]+: 359.1554, found
359.1552.
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-o-tolylpropanamide (1c): 1H NMR
(400 MHz, CDCl3) δ 7.73 (dd, J = 7.8, 1.8 Hz, 1 H), 7.59 (td, J = 7.8, 1.8 Hz, 1 H),
7.48-7.33 (m, 4 H), 7.26-7.10 (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, CDCl3) δ 173.00, 157.75 (d, JC-F = 249.1
Hz), 144.82, 138.94, 136.18, 133.82 (d, JC-F = 47.6 Hz), 130.76, 130.37, 129.47,
129.01, 127.91, 126.50, 126.23, 125.65, 117.32 (d, JC-F = 20.7 Hz), 117.00, 113.09,
34.76, 28.80, 19.16; HRMS (EI-TOF): m/zCalcd. for C23H20FN2O [M+H]+:
359.1554, found 359.1556.
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(2-methoxyphenyl)propanamide (1d):
1H NMR (400 MHz, CDCl3) δ 7.72 (dd, J = 8.0, 1.2 Hz, 1 H), 7.58 (td, J = 8.0,
S5
1.6Hz, 1 H), 7.45-7.32 (m, 4 H), 7.18-7.14 (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, CDCl3) δ 173.45, 158.25 (d, JC-F = 247.0 Hz), 157.58, 144.84, 133.76 (d,
JC-F = 38.9 Hz), 130.90, 130.57, 130.38, 129.68, 129.02, 127.77, 127.64, 125.39,
120.51, 117.10 (d, JC-F = 24.0 Hz), 116.98, 113.03, 110.20, 55.05, 34.14, 26.66;
HRMS (EI-TOF): m/zCalcd. for C23H20FN2O2 [M+H]+: 375.1503, found 375.1504.
N-(2-cyanophenyl)-N,3-bis(2-fluorophenyl)propanamide (1e): 1H NMR (400
MHz, CDCl3) 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), 7.37-7.33 (m, 3 H), 7.23-7.14 (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,
CDCl3) δ 172.63, 161.22 (d, JC-F = 243.9 Hz), 158.22 (d, JC-F = 249.5 Hz),144.70,
133.81 (d, JC-F = 49.0 Hz), 130.92 (d, JC-F = 37.9 Hz), 130.89, 129.27, 128.93,
128.10 (d, JC-F = 7.7 Hz), 127.90, 127.55 (d, JC-F = 16.1 Hz), 125.63, 124.17 (d, JC-F
= 3.4 Hz), 117.29 (d, JC-F = 20.1 Hz),116.98, 115.27 (d, JC-F = 21.7 Hz), 112.99,
34.39, 24.91; HRMS (EI-TOF): m/zCalcd. for C22H17F2N2O [M+H]+: 363.1303,
found 363.1300.
3- (2-chlorophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1f):
1H NMR (400 MHz, CDCl3) 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), 7.36-7.31 (m, 3 H), 7.28-7.25 (m, 2 H), 7.22-7.12 (m,4 H),
3.15 (t, J = 7.6 Hz, 2 H), 2.64 (s, 2 H); 13
C NMR (100 MHz, CDCl3) δ 172.63,
158.20 (d, JC-F = 248.1 Hz), 144.66, 138.24, 133.96, 133.77 (d, JC-F = 50.8 Hz),
130.96, 130.83, 130.73, 129.48, 129.28, 128.86, 127.87, 127.03, 125.60, 124.87,
S6
117.26 (d, JC-F = 20.0 Hz), 116.95, 112.94, 33.92, 29.39; HRMS (EI-TOF):
m/zCalcd. for C22H17ClFN2O [M+H]+: 379.1008, found 379.1005.
3-(2-bromophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1g):
1H NMR (400MHz, CDCl3) δ 7.72 (d, J = 7.6,Hz, 1 H), 7.58 (t, J = 7.8 Hz, 1 H),
7.47-7.26 (m, 6H), 7.23-7.19 (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, CDCl3) δ 172.56, 158.24 (d, JC-F = 248.5
Hz), 144.68, 139.97, 133.77 (d, JC-F = 49.2 Hz), 132.82, 130.99, 130.77, 128.88,
128.12, 127.87, 127.71, 125.64, 124.37, 117.29 (d, JC-F = 20.3 Hz), 116.95, 112.98,
34.06, 31.86; HRMS (EI-TOF): m/zCalcd. for C22H16BrFN2NaO [M+Na]+:
445.0322, found 445.0323.
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(2-(trifluoromethyl)phenyl)propanam
ide (1h): 1H NMR (400 MHz, CDCl3) δ 7.73 (dd, J = 7.6, 1.2Hz, 1 H),7.61-7.56 (m,
2 H), 2.48-7.28 (m, 7 H), 7.22-7.16 (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, CDCl3) δ 172.48, 158.15 (d, JC-F = 249.5 Hz),
144.67, 139.55, 133.76 (d, JC-F = 52.4 Hz), 132.15, 131.61, 131.00, 130.69, 129.25,
128.93, 128.77, 128.47, 126.73 (q, JC-F = 233 Hz ), 126.50,126.04 (q, JC-F = 5.7 Hz),
125.90, 123.18, 120.46, 117.31 (d, JC-F = 20.4 Hz), 117.02, 113.05, 36.00, 28.15;
HRMS (EI-TOF): m/zCalcd. for C23H17F4N2O [M+H]+: 413.1272, found 413.1275.
S7
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-m-tolylpropanamide (1i): 1H NMR
(400 MHz, CDCl3) 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), 7.40-7.32 (m,3 H), 7.23-7.14 (m, 3 H), 7.01 (d, J = 7.2 Hz,
1 H), 6.96-6.93 (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, CDCl3) δ 172.91, 158.17 (d, JC-F = 249.0 Hz), 144.79,
140.78, 138.16, 133.84 (d, JC-F = 46.7 Hz), 130.80, 129.35, 128.96, 128.47, 127.88,
127.01, 125.50, 117.28 (d, JC-F = 20.9 Hz), 116.98, 113.05, 36.19, 31.13, 21.43;
HRMS (EI-TOF): m/zCalcd. for C23H19FN2NaO [M+Na]+: 381.1374, found
381.1373.
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-methoxyphenyl)propanamide (1j):
1H NMR (400 MHz, CDCl3) 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), 7.37-7.32 (m,3 H), 7.23-7.16 (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, CDCl3) δ 172.78, 159.77, 158.17 (d, JC-F =
248.5 Hz),144.78, 142.47, 133.82 (d, JC-F = 48.0 Hz), 130.80, 129.56, 128.95,
127.90, 125.60, 120.87, 117.32 (d, JC-F = 20.5 Hz), 117.00, 114.16, 113.05, 111.74,
55.26, 36.08, 31.28;HRMS (EI-TOF): m/zCalcd. for C23H19FN2NaO2 [M+Na]+:
397.1323, found 397.1327.
S8
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-fluorophenyl)propanamide (1k): 1H
NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.59 (t, J = 7.8 Hz, 1 H),
7.46-7.38 (m,3 H), 7.32 (d, J = 8.0 Hz, 1 H) 7.24-7.18 (m, 3 H), 6.93 (d, J = 7.6 Hz,
1 H), 6.89-6.81 (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, CDCl3) δ 172.51, 162.87 (d, JC-F = 244.1 Hz), 158.17 (d, JC-F =
246.1 Hz), 144.73, 143.39 (d, JC-F = 6.2 Hz), 133.84 (d, JC-F = 49.5 Hz), 131.00 (d,
JC-F = 6.8 Hz), 130.76,130.02 (d, JC-F = 8.3 Hz), 129.33, 128.96, 127.99, 125.69,
124.27, 117.34 (d, JC-F = 20.7 Hz), 116.99, 115.40 (d, JC-F = 20.9 Hz), 113.20 (d,
JC-F = 20.9 Hz), 35.70, 30.85; HRMS (EI-TOF): m/zCalcd. for C22H17F2N2O
[M+H]+: 363.1303, found 363.1307.
3-(3-chlorophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1l): 1H
NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 1 H),
7.44-7.38 (m,3 H), 7.32 (t, J = 8.0 Hz, 1 H), 7.26-7.17 (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, CDCl3) δ 172.42, 158.11 (d, JC-F = 249.2 Hz), 144.65, 142.84, 134.21,
133.70 (d, JC-F = 53.3 Hz), 131.00 (d, JC-F = 7.0 Hz), 130.69, 129.85, 129.29, 128.89,
128.61, 127.96, 126.82, 126.49, 125.68, 117.34 (d, JC-F = 20.1 Hz), 116.97, 112.97,
35.66, 30.76; HRMS (EI-TOF): m/zCalcd. for C22H17ClFN2O [M+H]+: 379.1008,
found 379.1002.
S9
3-(3-bromophenyl)-N-(2-cyanophenyl)-N-(2-fluorophenyl)propanamide (1m):
1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H),
7.44-7.38 (m,3 H), 7.31 (t, J = 7.6 Hz, 1 H),7.26-7.08 (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, CDCl3) δ 172.44, 158.11 (d,
JC-F = 248.4Hz), 144.72, 143.20, 133.86 (d, JC-F = 50.4Hz), 131.57, 131.03, 130.75,
130.10, 129.48, 128.96, 127.98, 127.36, 125.72, 122.58, 117.37 (d, JC-F = 19.0 Hz),
116.97, 113.06, 35.73, 30.80; HRMS (EI-TOF): m/zCalcd. for C22H16BrFN2NaO
[M+Na]+: 445.0322, found 445.0325.
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)propanam
ide (1n): 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 1 H), 7.58 (t, J = 7.2
Hz, 1 H), 7.45-7.36 (m,7 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.26-7.20 (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, CDCl3) δ 172.30,
158.15 (d, JC-F = 249.1 Hz), 144.60, 141.66, 133.81 (d, JC-F = 55.9 Hz), 132.10,
131.21, 130.98, 130.69, 130.60 (d, JC-F = 4 Hz), 130.26, 129.02, 128.84, 127.97,
125.67, 125.15 (q, JC-F = 4.0 Hz), 123.17 (d, JC-F = 3.0 Hz), 122.88, 120.17, 117.32
(d, JC-F = 19.8 Hz), 116.95, 112.94, 35.58, 30.84; HRMS (EI-TOF): m/zCalcd. for
C23H16F4N2NaO [M+Na]+: 435.1091, found 435.1095.
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N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(4-methoxyphenyl)propanamide (1o):
1H NMR (400 MHz, CDCl3) 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), 7.37-7.32 (m,3 H), 7.20-7.18 (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, CDCl3) δ 172.62, 158.00 (d, JC-F = 248.8 Hz),
157.91, 144.47, 133.59 (d, JC-F = 58.5 Hz), 132.60, 130.72 (d, JC-F = 7.2 Hz), 130.50,
129.22, 129.12, 128.63, 127.68, 125.41, 124.65, 117.15 (d, JC-F = 20.0 Hz), 116.83,
113.75, 112.71, 55.07, 36.18, 30.09; HRMS (EI-TOF): m/zCalcd. for C23H20FN2O2
[M+H]+: 375.1503, found 375.1503.
N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(4-fluorophenyl)propanamide (1p):1H
NMR (400 MHz, CDCl3) 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), 7.39-7.37 (m, 2 H), 7.32 (d, J = 8.0 Hz, 1 H), 7.23-7.20 (m,2 H),
7.11-7.08 (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, CDCl3) δ 172.62, 161.55 (d, JC-F = 242.4 Hz),
158.18 (d, JC-F = 248.5 Hz), 144.72, 136.46, 133.59 (d, JC-F = 51.0 Hz), 130.90,19.3
Hz), 117.00, 115.29 (d, JC-F = 21.0 Hz), 113.11, 36.10, 30.30; HRMS (EI-TOF):
m/zCalcd. for C22H16F2N2NaO [M+Na]+: 385.1123, found 385.1124.
N-(2-cyanophenyl)-N,3-diphenylpropanamide (1q): 1H NMR (400 MHz, CDCl3)
δ 7.71 (dd, J = 7.6, 1.6 Hz, 2 H), 7.58 (t, J = 7.6Hz, 1 H),7.38-7.31 (m, 4 H),
7.31-7.18 (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);
13C NMR (100 MHz, CDCl3) δ 172.90, 145.47, 141.58, 140.90, 133.98, 133.63,
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130.00, 129.09, 128.60, 128.52, 128.35, 127.65, 126.26, 117.06, 112.92, 36.57,
31.47; HRMS (EI-TOF): m/zCalcd. for C22H18N2O [M+H]+: 327.1497, found
327.1495.
N-(2-cyanophenyl)-3-phenyl-N-o-tolylpropanamide (1r): 1H NMR (400 MHz,
CDCl3) δ 7.72 (dd, J = 7.6, 1.6 Hz, 1 H), 7.48 (t, J = 7.6Hz, 1 H),7.31-7.12 (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),
2.68-2.49 (m, 2 H), 2.23(s, 3H); 13
C NMR (100 MHz, CDCl3) δ 172.90, 144.08,
140.97, 140.31, 133.59, 133.42, 132.19, 129.72, 129.13, 128.58, 128.49, 128.34,
127.54, 127.05, 126.62, 126.20, 117.28, 112.45, 37.14, 31.34, 18.25; HRMS
(EI-TOF): m/zCalcd. for C23H21N2O [M+H]+: 341.1654, found 341.1655.
1H NMR (400 MHz, CDCl3) δ 7.72 (dd, J = 7.6, 1.6 Hz, 1 H), 7.58 (td, J = 7.6,
1.6Hz, 1 H),7.46-7.31 (m, 4 H), 7.25-7.16 (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, CDCl3) δ172.89, 158.23 (d, JC-F = 248.1 Hz),
144.76, 140.66, 133.82 (d, JC-F = 46.8 Hz), 130.80,129.50, 129.38, 128.97,
128.34,128.30, 128.05, 127.89, 127.81, 125.62, 117.30 (d, JC-F = 20.4 Hz), 116.99,
113.05, 36.12, 31.07; HRMS (EI-TOF): m/zCalcd. for C22H13D5FN2O [M+H]+:
350.1717, found 350.1716.
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2.2 References
(1) Gorvin, J. H. J. Chem. Soc., Perkin Trans. 1988, 1, 1331.
(2) Wan, L.; Dastbaravardeh, N.; Li, G.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135,
18056.
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2.3 Optimization Studies
Table S1. Initial Screening Solventsa
Table S2. Screening of Temperaturea
S20
Table S9.Utilityof T3 with Palladium catalystsa
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*Cl2]2 (3.1 mg, 0.005 mmol), Cu
(CO2CF3)2·xH2O (28.9mg, 0.1 mmol), CF3CO2H (0.1 mmol), olefin (0.5 mmol) and
DCE (2.0 mL). The tube was evacuated then back-filled with O2 (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.
S21
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)phenyl)
acrylate (3amono): 1H NMR (400 MHz, CDCl3) 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), 7.44-7.35 (m, 4 H), 7.32-7.28(m, 3
H), 7.21-7.16(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, CDCl3) δ 172.59, 167.14, 158.21 (d, JC-F = 251.0 Hz), 144.62, 142.93, 141.57,
134.74, 133.86 (d, JC-F = 51.4 Hz), 130.95, 130.75, 130.61, 129.95, 129.16, 128.93,
128.28, 127.97,126.05, 125.67, 119.97, 118.39, 117.46 (d, JC-F = 19.7 Hz), 116.99,
113.02, 60.61, 35.87, 30.96, 14.44; HRMS (EI-TOF): m/zCalcd. for C27H24FN2O3
[M+H]+: 443.1765, found 443.1766.
(2E,2'E)-diethyl-3,3'-(5-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropy
l)-1,3-phenylene)diacrylate (3adi): 1H NMR (400 MHz, CDCl3) 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), 7.51-7.38 (m, 4 H),
7.31-7.27 (m, 3 H), 7.22-7.20 (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, CDCl3) δ 172.34, 166.87, 158.25 (d, JC-F = 166 Hz), 144.71, 143.75,
142.35, 135.497, 133.86 (d, JC-F = 52.2 Hz), 130.75, 130.61, 129.84, 128.92, 128.03,
125.69, 120.99, 119.97, 117.43 (d, JC-F = 13.1 Hz), 116.98, 113.06, 60.75, 35.67,
S22
30.84, 14.44; HRMS (EI-TOF): m/zCalcd. for C32H30FN2O5 [M+H]+: 541.2133,
found 541.2134.
(E)-ethyl-3-(3-(4-((2-cyanophenyl)(2-fluorophenyl)amino)-4-oxobutan-2-yl)phe
nyl)acrylate (3bmono): 1H NMR (400 MHz, CDCl3) 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), 7.38-7.36 (m, 3 H), 7.31-7.24 (m, 4
H), 7.20-7.17 (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), 2.65-2.49 (m, 2 H), 1.34 (m, 6 H); 13
C NMR (100 MHz, CDCl3) δ 172.04,
167.10, 158.15 (d, JC-F = 254.6 Hz), 146.84, 144.75, 142.95, 134.71, 133.82 (d, JC-F
= 43.4 Hz), 130.91, 129.15, 128.49, 128.36, 128.21, 127.91, 126.70, 126.14, 125.60,
119.87, 118.32, 117.43, 117.22, 112.98, 60.56, 42.47, 36.38, 21.50, 14.43; HRMS
(EI-TOF): m/zCalcd. for C28H26FN2O3 [M+H]+: 457.1922, found 457.1923.
(2E,2'E)-diethyl-3,3'-(5-(4-((2-cyanophenyl)(2-fluorophenyl)amino)-4-oxobutan
-2-yl)-1,3-phenylene)diacrylate (3bdi): 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J =
8.0 Hz, 1 H), 7.63 (d, J = 16.0 Hz, 2 H), 7.53-7.50 (m, 3 H), 7.40-7.35 (m, 2 H),
7.28-7.26 (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), 2.65-2.50 (m, 2 H), 1.33 (m, 9 H); 13
C NMR (100 MHz, CDCl3) δ
171.83, 166.86, 158.14 (d, JC-F = 251.1 Hz), 147.53, 144.56, 143.88, 135.44,
S23
133.85(d, JC-F = 49.5 Hz), 131.04, 129.00, 128.41, 127.98, 125.78, 119.32, 117.49,
117.30, 112.94, 60.72, 42.30, 36.39, 21.58, 14.42; HRMS (EI-TOF): m/zCalcd. for
C33H31FN2NaO5 [M+Na]+: 577.2109, found 577.2108.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-meth
ylphenyl)acrylate (3c): 1H NMR (400 MHz, CDCl3) 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), 7.45-7.39 (m, 3 H),
7.32 (d, J = 8.0 Hz, 1 H), 7.28 (d, J = 8.0 Hz, 1 H), 7.22-7.20 (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, CDCl3) δ 172.70, 167.27, 158.22 (d, JC-F = 246.8 Hz), 144.76, 144.56,
139.60, 139.00, 133.84 (d, JC-F = 51.5 Hz), 132.56, 131.00, 130.72, 129.54, 128.92,
128.81, 127.96, 126.10, 125.73, 119.08, 117.46 (d, JC-F = 19.1 Hz),116.98, 113.08,
60.50, 34.58, 28.67, 19.27, 14.46; HRMS (EI-TOF): m/zCalcd. for C28H26FN2O3
[M+H]+: 457.1922, found 457.1921.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-meth
oxyphenyl)acrylate (3d): 1H NMR (400 MHz, CDCl3) 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), 7.44-7.30 (m, 6 H),
S24
7.19-7.18(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, CDCl3) δ 173.16, 167.49, 159.42, 158.22 (d,
JC-F = 240.7 Hz), 144.79, 144.39, 133.81 (d, JC-F = 42.7 Hz), 130.85, 129.99, 129.64,
129.04, 128.38, 127.86, 127.01, 125.48, 117.29, 117.08, 115.83, 113.03, 110.44,
60.38, 55.35, 33.91, 26.58, 14.46; HRMS (EI-TOF): m/zCalcd. for C28H26FN2O4
[M+H]+: 473.1871, found 473.1871.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-fluor
ophenyl)acrylate (3e): 1H NMR (400 MHz, CDCl3) 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),
7.39-7.32(m, 5 H), 7.21-7.20 (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, CDCl3) 172.33, 167.00, 162.33 (d, JC-F = 249.2
Hz), 158.18 (d, JC-F = 247.4 Hz), 144.65, 143.45, 142.27 133.82 (d, JC-F = 52.6 Hz),
131.08, 131.03, 130.80 (d, JC-F = 3.6 Hz), 130.69, 129.28 (d, JC-F = 13.2 Hz), 128.89,
128.31(d, JC-F = 16.4 Hz), 127.94,125.68, 118.06, 117.33 (d, JC-F = 19.6 Hz),
116.94, 115.99 (d, JC-F = 22.7 Hz), 114.99 (d, JC-F = 22.4 Hz), 112.98, 60.58, 34.14,
24.82, 14.40; HRMS (EI-TOF): m/zCalcd. for C27H23F2N2O3 [M+H]+: 461.1671,
found 473.1670.
S25
(E)-ethyl-3-(4-chloro-3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropy
l)phenyl)acrylate (3f): 1H NMR (400 MHz, CDCl3) 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), 7.47-7.38 (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);
13C NMR (100 MHz, CDCl3) δ 172.38, 166.85, 158.24 (d, JC-F = 248.8 Hz), 144.70,
143.25,141.96,138.96, 135.88, 133.82 (d, JC-F = 50.3 Hz), 133.51,130.92, 130.76,
130.65, 130.08, 129.13, 128.91, 127.96, 127.17, 125.68, 119.05, 117.34 (d, JC-F =
19.5 Hz), 116.95, 113.05, 60.66, 33.78, 29.36, 14.41; HRMS (EI-TOF): m/zCalcd.
for C27H23ClFN2O3 [M+H]+: 477.1376, found 477.1379.
(E)-ethyl-3-(4-bromo-3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropy
l)phenyl)acrylate (3g): 1H NMR (400 MHz, CDCl3) 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), 7.47-7.40 (m, 3
H), 7.32 (d, J = 8.0 Hz, 1 H), 7.22-7.20 (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);
13C NMR (100 MHz, CDCl3) δ 172.18, 166.70, 158.24 (d, JC-F = 249.5 Hz), 144.51,
143.13, 141.82, 140.54, 133.66 (d, JC-F = 50.9 Hz), 133.26, 130.76, 130.60, 130.39,
129.91, 129.25,128.73, 127.80, 127.11, 126.15,125.55, 118.98, 117.19 (d, JC-F =
19.5 Hz), 116.78, 112.85, 60.53, 33.73, 31.62, 14.24;HRMS (EI-TOF): m/zCalcd.
S26
for C27H23BrFN2O3 [M+H]+: 521.0871, found 521.0870.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-4-(trifl
uoromethyl)phenyl)acrylate (3 H): 1H NMR (400 MHz, CDCl3) 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),7.48-7.34 (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, CDCl3) δ 172.19, 166.51, 158.16 (d, JC-F = 248.1 Hz), 144.65, 142.65, 140.29,
138.08, 135.89, 133.83 (d, JC-F = 56.8 Hz), 131.13, 130.63, 129.89, 129.59, 129.24,
128.84, 126.78 (q, JC-F = 248.1 Hz ), 126.42, 126.74 (q, JC-F = 5.6 Hz),
125.72,122.83, 121.02, 117.31 (d, JC-F = 19.8 Hz), 116.94, 112.99, 60.83, 35.84,
28.08, 14.36;HRMS (EI-TOF): m/zCalcd. for C28H23F4N2O3 [M+H]+: 511.1639,
found 511.1640.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-meth
ylphenyl)acrylate (3i): 1H NMR (400 MHz, CDCl3) 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), 7.45-7.38 (m, 3 H), 7.31
(d, J = 7.6 Hz, 1 H), 7.23-7.14 (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,
S27
2 H), 2.31 (s, 3 H), 1.33 (t, J = 7.2 Hz, 3 H); 13
C NMR (100 MHz, CDCl3) δ 172.69,
167.23, 158.23 (d, JC-F = 250.4 Hz), 144.79, 141.48, 138.88, 134.71, 133.85 (d, JC-F
= 49.1 Hz), 133.61, 131.55, 130.93 (d, JC-F = 7.7 Hz), 130.79, 128.96, 127.96,
126.78, 125.66, 125.45, 119.33, 118.18, 117.36 (d, JC-F = 20.2 Hz), 117.00, 113.05,
60.57, 35.94, 30.93, 21.34, 14.45; HRMS (EI-TOF): m/zCalcd. for C28H23F4N2O3
[M+H]+:457.1922, found 457.1923.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-meth
oxyphenyl)acrylate (3j): 1H NMR (400 MHz, CDCl3) 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), 7.46-7.38 (m, 3 H),
7.31(d,J = 8.0 Hz, 1 H), 7.23-7.15 (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, CDCl3) δ 172.55,
167.06, 160.15, 158.22 (d, JC-F = 249 Hz), 144.75, 144.57, 143.03, 135.97,133.85 (d,
JC-F = 49.4 Hz), 130.95, 130.78, 129.34, 128.94, 127.96, 125.72, 122.75,121.09,
118.71, 117.38 (d, JC-F = 19.8 Hz), 116.99, 116.48, 113.07, 110.89, 60.63, 55.45,
35.85, 31.13, 14.45; HRMS (EI-TOF): m/zCalcd. for C28H25FN2NaO4 [M+Na]+:
495.1691, found 495.1692.
S28
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3k): 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.2 Hz, 1 H),
7.59-7.55 (m, 2 H), 7.40-7.38 (m, 3 H), 7.32 (d, J = 8.0 Hz, 1 H), 7.26-7.21 (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, CDCl3) δ 172.26, 166.79, 163.14 (d, JC-F =
245.1 Hz), 158.20 (d, JC-F = 251.0 Hz), 144.66, 143.98(d, JC-F = 7.9 Hz), 143.36,
136.73 (d, JC-F = 8.2 Hz), 133.88 (d, JC-F = 54.8 Hz), 131.10 (d, JC-F = 9.3 Hz),
130.73, 129.26,128.92, 128.06, 125.79, 124.45 (d, JC-F = 2.1 Hz), 121.12, 119.75,
117.42 (d, JC-F = 20.8Hz), 117.32 (d, JC-F = 21.3 Hz), 116.99,113.05, 112.19 (d, JC-F
=22.0 Hz), 60.78, 35.47, 30.73, 14.43; HRMS (EI-TOF): m/zCalcd. for
C27H23F2N2O3 [M+H]+: 461.1671, found 461.1675.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3l): 1H NMR (400 MHz, CDCl3) 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), 7.47-7.38 (m, 3 H),
7.33-7.30 (m, 2 H), 7.23-7.21 (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
S29
H), 1.33 (t, J = 7.2 Hz, 3 H); 13
C NMR (100 MHz, CDCl3) δ 172.24, 166.74, 158.19
(d, JC-F = 247.9 Hz), 144.66, 143.42, 143.10, 136.43, 134.93, 133.88 (d, JC-F = 54.2
Hz), 131.14, 130.71, 130.28, 129.21, 128.90, 128.05, 126.74, 125.74, 120.95,
119.85, 117.43 (d, JC-F = 20.6 Hz), 116.99, 113.02, 60.79, 35.48, 30.66, 14.42;
HRMS (EI-TOF): m/zCalcd. for C27H23ClFN2O3 [M+H]+: 477.1376, found
477.1377.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3m): 1H NMR (400 MHz, CDCl3) 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), 7.49-7.38 (m, 4 H), 7.32 (d, J =
8.0 Hz, 1 H), 7.28 (s, 1 H), 7.23-7.21 (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, CDCl3) δ 172.18, 166.65, 158.18 (d, JC-F = 249.1 Hz),
144.66, 143.67, 142.94, 141.10, 136.71, 133.86 (d, JC-F = 53.7 Hz),133.13, 131.04,
130.71, 129.29 (d, JC-F = 13.7 Hz), 128.91,128.68, 128.02,127.17, 125.75, 123.08,
119.90, 117.41 (d, JC-F = 21.3 Hz), 116.95, 113.04, 60.76, 35.49, 30.64,
14.41;HRMS (EI-TOF): m/zCalcd. for C27H23BrFN2O3 [M+H]+: 521.0871, found
521.0870.
S30
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3n): 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 7.6 Hz, 1 H),
7.64 (d, J = 16.0 Hz, 1 H), 7.59-7.56 (m,2 H), 7.48-7.38 (m, 5 H), 7.29 (d, J = 8.0
Hz, 1 H), 7.22-7.21 (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, CDCl3) δ 172.11, 166.60, 158.21 (d, JC-F = 248.8 Hz), 144.66,
142.92, 142.69, 141.23, 135.63, 133.89 (d, JC-F = 55.2Hz), 132.17, 131.85, 131.56,
130.71, 128.90, 128.08, 126.77 (q, JC-F = 3.6 Hz), 125.80, 125.26, 122.64, 122.55,
120.38, 117.43 (d, JC-F = 20.5 Hz), 116.95, 113.06, 60.85, 35.43, 30.78, 14.42;
HRMS (EI-TOF): m/zCalcd. for C28H22F4N2NaO3 [M+Na]+: 533.1459, found
533.1460.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3o): 1H NMR (400 MHz, CDCl3) 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), 7.44-7.34 (m, 3 H), 7.31 (d,
J = 8.0 Hz, 1 H), 7.22-7.13 (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, CDCl3) δ 172.73,
167.66, 158.21 (d, JC-F = 253.5 Hz), 157.02, 144.74, 140.05, 138.67, 133.85 (d, JC-F
= 48.0 Hz),132.95, 131.63, 130.94, 130.80, 129.37, 128.92, 127.95, 125.65, 123.40,
120.35, 118.93, 117.36 (d, JC-F = 18.2 Hz), 116.99, 113.04, 111.39, 60.45, 55.69,
36.21, 30.22, 14.50; HRMS (EI-TOF): m/zCalcd. for C28H25FN2NaO4 [M+Na]+:
495.1691, found 495.1694.
S31
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3p): 1H NMR (400 MHz, CDCl3) 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), 7.47-7.38 (m, 3 H), 7.31 (d, J =
8.0 Hz, 1 H), 7.27 (dd, J = 6.8, 2.4 Hz, 1 H), 7.22-7.12 (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, CDCl3) δ
172.40, 166.96, 160.14 (d, JC-F = 251.0 Hz), 158.22 (d, JC-F = 251.4 Hz), 144.69,
137.35, 137.00, 135.42, 133.87 (d, JC-F = 53.4 Hz), 131.88 (d, JC-F = 8.5 Hz),131.07,
130.73, 129.98, 129.33, 129.02 (d, JC-F = 2.9 Hz), 128.91, 128.01, 125.72, 122.56,
122.40 (d, JC-F = 11.8 Hz), 120.95 (d, JC-F = 6.6 Hz), 117.38 (d, JC-F = 18.4 Hz),
116.99, 116.26 (d, JC-F = 21.9 Hz), 113.04, 60.70, 35.88, 30.24, 14.43; HRMS
(EI-TOF): m/zCalcd. for C27H23F2N2O3 [M+H]+: 461.1671, found 461.1670.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3q): 1H NMR (400 MHz, CDCl3) 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), 7.45-7.38 (m, 3 H), 7.32
(d, J = 8.4 Hz, 1 H), 7.24-7.20 (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, CDCl3) δ 172.55, 167.52, 160.12, 158.22 (d, JC-F =
S32
248.9 Hz), 144.88, 144.72, 143.05, 135.86, 133.85 (d, JC-F = 51.7 Hz), 130.96,
130.77, 129.31, 128.92, 127.98, 125.69, 121.07, 118.19, 117.38 (d, JC-F = 19.8 Hz),
117.00, 116.50, 113.03, 110.97, 55.46, 51.86, 35.84, 31.11; HRMS (EI-TOF):
m/zCalcd. for C27H24FN2O4 [M+H]+: 459.1715, found 459.1716.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3r): 1H NMR (400 MHz, CDCl3) 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), 7.46-7.38 (m, 3 H), 7.31 (d,
J = 8.0 Hz, 1 H), 7.23-7.14 (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),1.72-1.65 (m, 2 H), 1.48-1.41 (m, 2 H), 0.96 (t, J = 7.2 Hz, 3 H); 13
C
NMR (100 MHz, CDCl3) δ 172.58, 167.19, 160.12, 158.21 (d, JC-F = 248.5 Hz),
144.70, 144.55, 143.01, 135.96, 133.85 (d, JC-F = 50.9 Hz), 131.03, 130.77, 128.93,
128.37, 127.97, 125.68, 121.09, 118.69, 117.37 (d, JC-F = 19.6 Hz), 117.00, 116.49, ,
113.02, 110.86, 64.57, 55.45, 35.85, 31.12, 30.88, 19.32, 13.88; HRMS (EI-TOF):
m/zCalcd. for C30H30FN2O3 [M+H]+: 485.2235, found 485.2234.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
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ophenyl)acrylate (3s): 1H NMR (400 MHz, CDCl3) 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), 7.44-7.38 (m, 3 H), 7.31
(d, J = 7.6 Hz, 1 H), 7.23-7.18 (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, CDCl3) δ 172.58, 166.74, 160.06,
158.20 (d, JC-F = 249.1 Hz), 144.71, 142.85, 142.22, 137.81, 136.90, 133.82 (d,
JC-F= 53.5 Hz), 130.92, 130.73, 129.29, 128.87, 127.92, 125.65, 120.36, 117.93,
117.34 (d, JC-F = 19.8 Hz), 117.00, 115.38, 113.00, 111.40, 55.43, 37.57, 36.04,
35.94, 31.21;HRMS (EI-TOF): m/zCalcd. for C28H27FN3O3 [M+H]+: 472.2031,
found 472.2031.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3t): 1H NMR (400 MHz, CDCl3) 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), 7.43-7.38 (m, 3 H), 7.31
(d, J = 8.0 Hz, 1 H), 7.21-7.15 (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,
CDCl3) δ201.12, 172.57, 160.15, 158.29 (d, JC-F = 264.5 Hz), 144.72, 143.08,
142.27, 136.11, 133.87 (d, JC-F = 53.4 Hz), 131.04, 130.76, 129.30, 128.90, 128.00,
126.41, 125.72, 121.29, 117.48, 117.16 (d, JC-F = 26.1 Hz), 116.62, 113.02, 111.01,
55.47, 35.82, 34.14, 31.06, 8.35;HRMS (EI-TOF): m/zCalcd. for C28H26FN2O3
[M+H]+: 457.1922, found 457.1921.
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(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3u): 1H NMR (400 MHz, CDCl3) 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),
7.46-7.38 (m, 3 H), 7.32 (d, J = 8.0 Hz, 1 H), 7.24-7.20 (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, CDCl3) δ193.88, 172.45,
160.23, 158.21 (d, JC-F = 248.4 Hz), 152.94, 144.70, 143.35, 135.48, 133.87 (d, JC-F
= 54.9 Hz), 131.00, 130.75, 129.31, 128.91, 128.02, 125.73, 121.67, 117.50,117.39
(d, JC-F = 21.8 Hz), 113.04, 111.17, 55.51, 35.70, 30.96; HRMS (EI-TOF): m/zCalcd.
for C26H22FN2O3 [M+H]+: 429.1609, found 429.1608.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3v): 1H NMR (400 MHz, CDCl3) δ7.72 (dd, J = 7.6, 1.2 Hz, 1
H), 7.58 (td, J = 7.2, 1.6 Hz, 1 H), 7.47-7.33 (m, 3 H), 7.31 (d, J = 8.0 Hz, 1 H),
7.21-7.19 (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, CDCl3) δ 172.64, 167.37, 159.89, 158.08 (d, JC-F =
249.3 Hz), 155.89, 144.76, 143.90, 142.67, 133.87 (d, JC-F = 47.5 Hz), 130.95,
S35
130.81, 128.97, 128.88, 127.98, 125.69, 119.47, 119.10, 117.37 (d, JC-F = 20.6 Hz),
116.94, 114.95, 114.76, 113.10, 110.20, 55.49, 51.27, 36.06, 31.40, 21.71, 18.24;
HRMS (EI-TOF): m/zCalcd. for C29H27FN2NaO4 [M+Na]+: 509.1847, found
509.1840.
(E)-N-(2-cyanophenyl)-N-(2-fluorophenyl)-3-(3-methoxy-5-(4-oxopent-2-en-2-yl
)phenyl)propanamide (3w): 1H NMR (400 MHz, CDCl3) δ7.73 (dd, J = 7.6, 1.2
Hz, 1 H), 7.58 (t, J = 7.6, Hz, 1 H), 7.45-7.37 (m, 3 H), 7.33-7.29 (m, 2
H),7.14-7.26 (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, CDCl3) δ199.12,
172.65, 158.26 (d, JC-F = 250.0 Hz), 153.93, 144.76, 142.88, 141.25, 133.88 (d, JC-F
= 49.2 Hz), 131.00, 130.92, 130.81, 129.36, 128.95, 128.90, 128.84, 128.00, 126.75,
125.68, 124.66, 124.60, 117.36 (d, JC-F = 18.6 Hz), 116.97, 113.08, 36.08, 32.39,
31.41, 31.20, 18.50; HRMS (EI-TOF): m/zCalcd. for C28H25FN2NaO3 [M+Na]+:
479.1747, found 479.1748.
Dimethyl-2-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-meth
oxyphenyl)maleate (3x): 1H NMR (400 MHz, CDCl3) δ7.71 (d, J = 7.6Hz, 1 H),
7.57 (t, J = 7.6 Hz, 1 H), 7.46-7.32 (m, 4 H), 7.22-7.18 (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,
S36
3H),3.02 (t, J = 7.6 Hz, 2 H), 2.61 (t, J = 7.6 Hz, 2 H);13
C NMR (100 MHz, CDCl3)
δ172.64, 166.69, 165.58, 159.17,158.17 (d, JC-F = 249.2 Hz), 144.70, 143.66,
141.82,135.04, 133.75 (d, JC-F = 48.9 Hz), 130.80, 129.99, 129.30, 128.87,
127.85,125.60,124.85, 121.38, 119.37, 117.27 (d, JC-F = 20.3 Hz), 116.93, 114.44,
112.97,112.50, 55.29, 52.98, 51.91, 35.89, 31.19; HRMS (EI-TOF): m/zCalcd. for
C29H25FN2NaO6 [M+Na]+: 539.1594, found 539.1590.
Dimethyl-2-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-methox
yphenyl)fumarate (3y):1H NMR (400 MHz, CDCl3) δ7.71 (d, J = 7.6Hz, 1 H), 7.58
(t, J = 7.6 Hz, 1 H), 7.44-7.35 (m, 3 H),7.30 (d, J = 7.6Hz, 1 H), 7.26-7.19 (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, CDCl3) δ172.37,
168.27, 165.44, 160.12,158.12 (d, JC-F = 248.8 Hz), 148.91, 144.61,143.29, 134.32
(d, JC-F = 52.0 Hz), 133.51, 130.98 (d, JC-F = 6.7 Hz),130.67, 129.92, 129.26 (d, JC-F
= 12.4 Hz), 128.85, 127.91, 125.65, 124.89, 119.35, 117.41, 117.07 (d, JC-F = 29.0
Hz), 116.50, 112.92, 110.37, 55.45, 52.82, 52.13, 35.79, 31.15;HRMS (EI-TOF):
m/zCalcd. for C29H25FN2NaO6 [M+Na]+: 539.1594, found 539.1592.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
S37
ophenyl)acrylate (3z): 1H NMR (400 MHz, CDCl3) δ7.72 (d, J = 7.2 Hz, 1 H),
7.58 (t, J = 7.6 Hz, 1 H), 7.47-7.30 (m, 5 H), 7.23-7.19 (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, CDCl3) δ 172.56, 160.13, 158.20 (d, JC-F = 249.0 Hz), 148.70,
144.71, 143.02, 136.47, 136.23, 133.85 (d, JC-F = 53.2 Hz), 130.73, 129.40,
128.90,127.97, 125.72, 120.56, 117.39 (d, JC-F = 19.0 Hz), 117.00, 116.39, 115.26,
113.36, 113.00, 110.77, 62.03, 55.46, 35.82, 31.16, 16.56; HRMS (EI-TOF):
m/zCalcd. for C29H31FN2O5P [M+H]+: 537.1949, found 537.1950.
(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3α): 1H NMR (400 MHz, CDCl3) δ7.72 (dd, J = 7.6, 1.6 Hz, 1
H), 7.57 (td, J = 7.6, 1.6 Hz, 1 H), 7.48-7.31 (m, 6 H), 7.22-7.18 (m, 2 H), 7.07-7.00
(m, 3 H), 6.95-6.86 (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, CDCl3) δ 172.81, 162.51 (d, JC-F =
245.8 Hz),160.17, 158.23 (d, JC-F = 247.1 Hz), 144.81, 142.76, 138.79, 133.86 (d,
JC-F = 49.1 Hz), 133.56, 133.53,130.86, 129.59, 129.41, 128.99, 128.43, 128.15 (d,
JC-F = 7.9 Hz), 127.97, 125.63, 121.71, 119.52, 117.36 (d, JC-F = 18.9 Hz), 117.04,
115.77 (d, JC-F = 21.6 Hz), 113.70, 113.09, 109.76, 55.43, 36.09, 31.37;H HRMS
(EI-TOF): m/zCalcd. for C31H25F2N2O2 [M+H]+: 495.1879, found 495.1881.
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(E)-ethyl-3-(3-(3-((2-cyanophenyl)(2-fluorophenyl)amino)-3-oxopropyl)-5-fluor
ophenyl)acrylate (3β): 1H NMR (400 MHz, CDCl3) δ 7.96-7.93 (m, 2 H), 7.71 (d,
J = 7.6Hz, 1 H), 7.63-7.54 (m, 5 H), 7.44-7.38 (m, 3 H), 7.29 (d, J = 8.0 Hz, 1 H),
7.23-7.18 (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, CDCl3) δ 172.43, 160.21, 158.19 (d, JC-F = 248.4 Hz), 144.67, 143.36, 142.55,
140.79, 133.87 (d, JC-F = 56.8 Hz), 133.79, 133.53, 131.01, 130.73, 129.47, 129.25,
128.87, 128.02, 127.81, 127.73, 127.63, 125.74, 121.34, 117.46, 117.38 (d, JC-F =
17.0 Hz), 116.99, 113.00, 111.60, 55.52, 35.64, 30.97; HRMS (EI-TOF): m/zCalcd.
for C31H26FN2O4S [M+H]+: 541.1592, found 541.1593.
(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. 1H NMR (400 MHz, CDCl3) 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
S39
(s, 3 H), 2.92 (t, J = 8.4 Hz, 2 H), 2.17 (dd, J = 14.0, 6.0 Hz, 2 H), 1.72-1.67 (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, CDCl3) δ167.13, 161.20, 144.26, 142.68, 134.84, 134.21, 129.42,
126.70, 125.49, 124.36, 123.16, 118.70, 113.87, 111.60, 60.61, 55.81, 50.50, 46.99,
46.70, 27.92, 25.90, 23.58, 23.55, 14.44.
(E)-ethyl-3-(3-(3-(4-cyano-2,6-dimethylheptan-4-yl)-4-methoxy-N-methylpheny
lsulfonamido)phenyl)acrylate (7amono): 7 was olefinated following the general
procedure to provide 7amono and 7adi. 1H NMR (400 MHz, CDCl3) 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), 7.45-7.40(m, 1
H), 7.32 (t, J = 8.8 Hz, 1 H), 7.21-7.17 (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), 1.49-1.44 (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, CDCl3) δ 166.75, 160,85, 43.65, 142.25, 135.53, 129.98, 129.63, 129.34,
128.87, 128.72, 128.11, 126.78, 126.61, 126.05, 125.41, 123.16, 119.41, 111.35,
60.73, 55.83, 47.01, 46.84, 38.14, 25.99, 23.75, 23.72, 14.42.
S40
(2E,2'E)-diethyl-3,3'-(5-(3-(4-cyano-2,6-dimethylheptan-4-yl)-4-methoxy-N-met
hylphenylsulfonamido)-1,3-phenylene)diacrylate (7adi): 7 was olefinated
following the general procedure to provide 7amono and 7adi. 1H NMR (400 MHz,
CDCl3) 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), 1.49-1.44 (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, CDCl3) δ 166.52, 160.98, 142.91, 142.86, 136.17, 130.03, 129.26,
128.65, 126.78, 126.70, 126.08, 123.14, 120.38, 111.41, 60.88, 55.87, 47.07, 46.80,
38.08, 26.03, 23.70, 14.42.
2.5 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*Cl2]2 (3.1 mg, 0.005 mmol),
S41
Cu(CO2CF3)2•xH2O (28.9 mg, 0.1 mmol), CF3CO2H (0.1 mmol), olefin (0.5 mmol)
and DCE (2.0 mL). The tube was evacuated then back-filled with O2 (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 CH2Br2 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.
1 2 3 4 5
2
4
6
8
10
12
14
16
18
Yie
ld (
%)
Time (h)
Eq. 1
Eq. 2
S43
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*Cl2]2 (0.31 g, 0.5 mmol), Cu (CO2CF3)2·xH2O (2.89 g, 10 mmol),
CF3CO2H (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 O2 (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 MgSO4, 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).
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