Supporting Information

Supporting Information
for
Copper-Catalyzed Divergent Trifluoromethylation/Cyclization of
Unactivated Alkenes

Jing Zhenga, Ziyang Denga, Yan Zhanga, and Sunliang Cuia*

a
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou,
Zhejiang 310058, China
Fax: (+ 86)-571-8998-1456; e-mail: slcui@zju.edu.cn

Contents

1. General Information S2

2. Typical Synthesis Procedure of Terminal Alkene 1aa S2- S3

3. Typical Synthesis Procedure of Internal Alkene 1pa S4

4. Characterization of 1 S4-S20

5. Characterization of 5 S20-S28

6. Typical Synthesis Procedure of 3aa S28-S29

7. Characterization of 3, 4 and 6 S29-S65

8. Kinetic Isotope Effect Study S65-S73

9. Radical Scavenger Test S73-S74

10. References S75

11. Copies of NMR Spectra S76-S198

S1
1. General Information:
Infrared spectra were obtained on a FTIR spectrometer. 1H NMR
13
and C NMR spectra were recorded on BRUKER AVANCE III 500 or

BRUKER AVANCE III 400 spectrometer. CDCl3 were used as solvent.

Chemical shifts were referenced relative to residual solvent. The

following abbreviations are used to describe peak patterns where

appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m

= multiplet, dq = double quartet, dt = double triplet. Coupling constants (J)

are reported in Hertz (Hz). HRMS were performed on Waters GCT

Premier Time of Flight Mass Spectrometer (EI). Melting points were

measured with micro melting point apparatus.

The Cu2O, 2,2’-bipyridine, cyanogen bromide, various acids, Togni’s

reagent were commercial available. All alkenes were prepared according

to the literature.1

2. Typical Synthesis Procedure of Terminal alkene 1aa:

S2
 To a 50 mL flask containing 2-methyl-2-propen-1-ol (0.8 g, 10

mmol), Et3N (1.2 g, 12 mmol) was added and the reaction was kept at 90
o
C for 2 h. Then the solvent was concentrated to afford the benzoyl

chloride to be used for next step. To a THF solution containing amine and

aqueous NaOH was added benzoyl chloride at 0 oC over 30 min, then the

solution was warmed to RT and kept for 5 h. Afterwards, the solution was

filtered and the filtrate was concentrated. Then it was extracted with

diethyl ether and dried over Na2SO4 to give the crude acylamide, which

was next purified in flash column chromatography on silica gel using

ethyl acetate/petroleum ether (v/v, 1:5) as eluent to get benzamide (1.52 g,

80% yield) .

A 25 mL two-necked flask with a stir-bar was charged with NaH

(640 mg, 60% wt, 16 mmol), which was then evacuated and backfilled

with Argon for three times. THF (8 mL) was added and the solution was

cooled to 0 oC. Then a THF solution (4 mL) of benzamide (760 mg, 4

mmol) was added over 10 min to the solution and the reaction was kept at

60 oC for 2 h. Then cyanogen bromide (1.7 g, 16 mmol) was added into

the reaction solution at 0 oC and the reaction was kept at RT for 12 h.

Afterwards, the solution was filtered and the filtrate was concentrated,

which was subject to flash column chromatography on silica gel using

ethyl acetate/petroleum ether (v/v, 1:10) as eluent to obtain product 1aa

(418 mg, 48% yield).

S3
3. Typical Synthesis Procedure of Internal alkene 1pa:

To a toluene solution of cyclopentanone (60 mmol), NH4OAc (5 mmol)

was added cyanoacetic acid (50 mmol). The mixture was heated under

reflux for 16 h, incorporating a Dean-Stark Apparatus to remove water.

Then the solvent was removed, and the residue was subject to distillation

under vacuum in 160 oC to afford the nitrile (3.2 g, 50% yield).2 And the

nitrile was reduced to amine in the presence of LiAlH4. The next steps for

access to 1pa followed the typical procedure of 1aa. The compound of 5

was followed the typical procedure of 1aa.

4. Characterization of 1:
N-Cyano-N-(3-methylbut-3-en-1-yl)benzamide (1aa)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.78-7.76 (m, 2H),

S4
7.59 (t, 1H), 7.50-7.46 (m, 2H), 4.92 (s, 1H), 4.88 (s, 1H), 3.90 (t, J = 7.2
13
Hz, 2H), 2.51 (t, J = 7.2 Hz, 2H), 1.82 (s, 3H); C NMR (CDCl3,

100MHz), δ: 166.56, 140.73, 133.19, 131.25, 128.71, 128.65, 114.06,

111.10, 45.67, 35.72, 22.13; IR (film) v: 3070, 2956, 2853, 2233, 1647,

1707, 1446, 1269, 1121, 1047, 904, 747, 698 cm-1.

N-(But-3-en-1-yl)-N-cyanobenzamide (1ab)

N
CN
1ab

Pale yellow liquid; 1H NMR(CDCl3, 500MHz), δ: 7.79-7.77 (m, 2H),

7.60-7.57 (m, 1H), 7.49-7.46 (m, 2H), 5.87-5.78 (m, 1H), 5.26-5.23 (m,

1H), 5.20-5.18 (m, 1H), 3.85 (t, J = 4.0 Hz, 2H), 2.59-2.55 (m, 2H); 13C

NMR (CDCl3, 100MHz), δ: 168.53, 133.19, 133.05, 131.17, 128.69,

128.61, 118.98, 111.13, 46.83, 32.05; IR (film) v: 3072, 2921, 2853, 2233,

1707, 1275, 701 cm-1.

N-Cyano-4-methyl-N-(3-methylbut-3-en-1-yl)benzamide (1ba)

N
CN
H3C
1ba

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.69 (d, J = 8.0 Hz,

2H), 7.27 (d, J = 7.8 Hz, 2H), 4.91 (s, 1H), 4.87 (s, 1H), 3.89 (t, J = 7.2

S5
 13
Hz, 2H), 2.50 (t, J = 7.2 Hz, 2H), 2.41 (s, 3H), 1.82 (s, 3H); C NMR

(CDCl3, 100MHz), δ: 166.49, 144.12, 140.80, 129.36, 128.80, 128.38,

113.98, 111.35, 45.68, 35,74, 22.16, 21.81; IR (film) v: 3054, 2982, 2305,

2233, 1706, 1267, 741 cm-1.

N-(But-3-en-1-yl)-N-cyano-4-methylbenzamide (1bb)

N
CN
H3C
1bb

Yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.70 (d, J = 8.0 Hz, 2H),

7.28 (d, J = 9.2 Hz, 2H), 5.86-5.79 (m, 1H), 5.27-5.21 (m, 1H), 5.20-5.17
13
(m, 1H), 3.83 (t, J = 6.8 Hz, 2H), 2.59-2.54 (m, 2H), 2.42 (s, 3H); C

NMR (CDCl3, 100MHz), δ: 168.46, 144.12, 133.11, 129.33, 128.75,

128.28, 118.90, 111.37, 46.82, 32.07, 21.78; IR (film) v: 3072, 2947,

2228, 1707, 1275, 749 cm-1.

N-Cyano-4-methoxy-N-(3-methylbut-3-en-1-yl)benzamide (1ca)

N
CN
H3CO
1ca

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.80 (d, J = 7.8 Hz,

2H), 6.95 (d, J = 7.8 Hz, 2H), 4.90 (s, 1H), 4.86 (s, 1H), 3.89-3.85 (m,

5H), 2.49 (t, J = 6.8 Hz, 2H), 1.81 (s, 3H); 13C NMR (CDCl3, 100MHz), δ:

S6
167.75, 163.53, 140.83, 131.08, 123.20, 113.93, 113.87, 111.58, 55.61,

45.70, 35.70, 22.13; IR (film) v: 3077, 2947, 2838, 2228, 1702, 1603,

1509, 1259, 756 cm-1.

N-(But-3-en-1-yl)-N-cyano-4-methoxybenzamide (1cb)

N
CN
H3CO
1cb

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.81 (d, J = 8.8 Hz,

2H), 6.95 (d, J = 8.8 Hz, 2H), 5.87-5.77 (m, 1H), 5.25-5.21 (m, 1H),

5.19-5.16 (m, 1H), 3.86 (s, 3H), 3.82 (t, J = 7.2 Hz, 2H), 2.58-2.53 (m,
13
2H); C NMR (CDCl3, 100MHz), δ: 167.79, 163.59, 133.19, 131.11,

123.19, 118.86, 113.97, 111.66, 55.64, 46.94, 32.11; IR (film) v: 3072,

2958, 2832, 2233, 1697, 1254, 763 cm-1.

N,4-Dicyano-N-(3-methylbut-3-en-1-yl)benzamide (1da)

N
CN
NC
1da

White solid; m.p. 36-37 oC; 1H NMR (CDCl3, 400MHz), δ: 7.87-7.85 (m,

2H), 7.80-7.77 (m, 2H), 4.94 (s, 1H), 4.87 (s, 1H), 3.92 (t, J = 7.2 Hz,

2H), 2.51 (t, J = 7.2 Hz, 2H), 1.82 (s, 3H); 13C NMR (CDCl3, 100MHz), δ:

168.98, 140.51, 135.07, 132.54, 129.20, 117.56, 116.68, 114.34, 110.32,

45.71, 35.63, 22.03; IR (KBr) v: 3077, 2916, 2228, 1712, 1442, 1306,

S7
1208, 1124, 1072, 858, 739, 551 cm-1.

N-(But-3-en-1-yl)-N,4-dicyanobenzamide (1db)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.85 (d, J = 6.8 Hz,

2H), 7.78 (d, J = 6.8 Hz, 2H), 5.84-5.76 (m, 1H), 5.26-5.22 (m, 1H),

5.21-5.18 (m, 1H), 3.85 (t, J = 6.8 Hz, 2H), 2.58-2.54 (m, 2H); 13C NMR

(CDCl3, 100MHz), δ: 166.95, 134.99, 132.76, 132.50, 129.14, 119.25,

117.50, 116.64, 110.30, 46.93, 31.91; IR (film) v: 3072, 2947, 2228, 1707,

1269, 749 cm-1.

N-Cyano-N-(3-methylbut-3-en-1-yl)-4-(trifluoromethyl)benzamide

(1ea)

white liquid; 1H NMR (CDCl3, 400MHz), δ: 7.88 (d, J = 8.0 Hz, 2H),

7.75 (d, J = 8.4 Hz, 2H), 4.94 (s, 1H), 4.88 (s, 1H), 3.93 (t, J = 7.2 Hz,

2H), 2.52 (t, J = 7.2 Hz, 2H), 1.83 (s, 3H); 13C NMR (CDCl3, 100MHz), δ:

167.42, 140.59, 134.65 (q, J = 33.0 Hz), 134.53, 129.08, 125.86 (q, J =

3.0 Hz), 123.42 (q, J = 271.0 Hz), 114.27, 110.56, 45.70, 35.68, 22.05;
19
F NMR (CDCl3, 376MHz), δ: -63.29; IR (film) v: 3080, 2951, 2238,

S8
1706, 1412, 1324, 1293, 1174, 849, 704 cm-1.

N-(But-3-en-1-yl)-N-cyano-4-(trifluoromethyl)benzamide (1eb)

N
CN
F3C
1eb

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.88 (d, J = 8.0 Hz,

2H), 7.76 (d, J = 8.0 Hz, 2H), 5.87-5.77 (m, 1H), 5.28-5.19 (m, 2H), 3.87
13
(t, J = 7.2 Hz, 2H), 2.61-2.55 (m, 2H); C NMR (CDCl3, 100MHz), δ:

167.33, 134.58 (q, J = 33.0 Hz), 134.37, 132.76, 129.03, 128.96, 125.75

(q, J = 4.0 Hz), 125.40, 123.30 (q, J = 271.0 Hz), 119.14, 110.51, 46.84,

31.92; 19F NMR (CDCl3, 376MHz), δ: -63.30; IR (film) v: 3083, 2958,

2233, 1707, 1321, 1129, 853 cm-1.

N-Cyano-4-fluoro-N-(3-methylbut-3-en-1-yl)benzamide (1fa)

N
CN
F
1fa

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.84-7.81 (m, 2H),

7.19-7.14 (m, 2H), 4.92 (s, 1H), 4.87 (s, 1H), 3.90 (t, J = 7.2 Hz, 2H),
13
2.51 (t, J = 7.2 Hz, 2H), 1.82 (s, 3H); C NMR (CDCl3, 100MHz), δ:

167.42, 166.86, 164.33, 140.72, 131.45 (d, J = 10.0 Hz), 119.23 (d, J =

163.0 Hz), 116.09 (d, J = 23.0 Hz), 114.13, 45.77, 35.72, 22.13; 19F NMR

S9
(CDCl3, 376MHz), δ: -105.89; IR (film) v: 3072, 2942, 2233, 1707, 1603,

1509, 1275, 754 cm-1.

4-Chloro-N-cyano-N-(3-methylbut-3-en-1-yl)benzamide (1ga)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 8.40 (d, J = 8.4 Hz,

2H), 7.46 (d, J = 8.4 Hz, 2H), 4.92 (s, 1H), 4.87 (s, 1H), 3.89 (t, J = 7.2
13
Hz, 2H), 2.50 (t, J = 7.2 Hz, 2H), 1.82 (s, 3H); C NMR (CDCl3,

100MHz), δ: 167.52, 140.66, 139.69, 130.14, 129.52, 129.11, 114.13,

110.89, 45.73, 35.67, 22.10; IR (film) v: 3077, 2963, 2228, 1702, 1592,

1275, 743 cm-1.

N-(But-3-en-1-yl)-4-chloro-N-cyanobenzamide (1gb)

N
CN
Cl
1gb

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.73 (d, J = 8.4 Hz,

2H), 7.46 (d, J = 8.4 Hz, 2H), 5.86-5.76 (m, 1H), 5.26-5.21 (m, 1H),

5.20-5.17 (m, 1H), 3.83 (t, J = 6.8 Hz, 2H), 2.58-2.53 (m, 2H); 13C NMR

(CDCl3, 100MHz), δ: 167.49, 139.68, 132.94, 130.11, 129.43, 129.09,

119.09, 110.93, 46.91, 32.01; IR (film) v: 3083, 2952, 2233, 1702, 1275,

S10
1087, 743 cm-1.

N-Cyano-N-(3-methylbut-3-en-1-yl)-4-nitrobenzamide (1ha)

Pale yellow solid; m.p. 61-62 oC; 1H NMR (CDCl3, 400MHz), δ: 8.33 (d,

J = 10.0 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 4.95 (s, 1H), 4.89 (s, 1H), 3.94
13
(t, J = 6.8 Hz, 2H), 2.53 (t, J = 6.8 Hz, 2H), 1.83 (s, 3H); C NMR

(CDCl3, 100MHz), δ: 166.84, 150.30, 140.53, 136.72, 129.80, 124.01,

114.41, 110.26, 44.75, 35.67, 22.05; IR (KBr) v: 3395, 3109, 3083, 2920,

2852, 2228, 1707, 1650, 1603, 1525, 1452, 1291, 1124, 1108, 915, 853,

712 cm-1.

N-(But-3-en-1-yl)-N-cyano-4-nitrobenzamide (1hb)

N
CN
O2N
1hb

Yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 8.35 (d, J = 8.8 Hz, 2H),

7.94 (d, J = 9.2 Hz, 2H), 5.88-5.78 (m, 1H), 5.30-5.22 (m, 2H), 3.90 (t, J

= 6.8 Hz, 2H), 2.62-2.57 (m, 2H); 13C NMR (CDCl3, 100MHz), δ: 166.74,

150.19, 136.55, 132.67, 129.69, 123.89, 119.29, 110.21, 46.89, 31.89; IR

(film) v: 3109, 2921, 2848, 2233, 1702, 1603, 1525, 1348, 1269, 749

S11
cm-1.

N-Cyano-2-methyl-N-(3-methylbut-3-en-1-yl)benzamide (1ia)

CH3 O

N
CN
1ia

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.43-7.39 (m, 2H),

7.28-7.25 (m, 2H), 4.94 (s, 1H), 4.90 (s, 1H), 3.90 (t, J = 7.2 Hz, 2H),
13
2.51 (t, J = 7.2 Hz, 2H), 2.39 (s, 3H), 1.83 (s, 3H); C NMR (CDCl3,

100MHz), δ: 169.57, 140.59, 136.24, 131.97, 131.65, 131.17, 127.28,

125.90, 114.26, 110.33, 44.66, 35.80, 22.02, 19.34; IR (film) v: 3072,

2947, 2853, 2233, 1712, 1259, 733 cm-1.

N-Cyano-3-methyl-N-(3-methylbut-3-en-1-yl)benzamide (1ja)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.58-7.55 (m, 2H),

7.40-7.33 (m, 2H), 4.92 (s, 1H), 4.87 (s, 1H), 3.89 (t, J = 7.2 Hz, 2H),
13
2.50 (t, J = 7.2 Hz, 2H), 2.40 (s, 3H), 1.82 (s, 3H); C NMR (CDCl3,

100MHz), δ: 168.72, 140.73, 138.71, 133.92, 131.19, 129.12, 128.50,

125.63, 113.97, 111.10, 45.61, 35.68, 22.11, 21.40; IR (film) v: 3070,

2922, 2858, 2223, 1707, 1658, 1593, 1441, 1283, 1200, 1126, 1052, 904,

S12
801, 732, 688 cm-1.

N-Cyano-1-methyl-N-(3-methylbut-3-en-1-yl)-1H-indole-3-carboxami

de (1ka)

Pale yellow solid; m.p. 55-56 oC; 1H NMR (CDCl3, 400MHz), δ:

8.25-8.23 (m, 1H), 8.19 (s, 1H), 7.37-7.32 (m, 3H), 4.88 (s, 1H), 4.86 (s,

1H), 3.92 (t, J = 7.2 Hz, 2H), 3.86 (s, 3H), 2.52 (t, J = 7.2 Hz, 2H), 1.83

(s, 3H); 13C NMR (CDCl3, 100MHz), δ: 161.80, 141.10, 136.75, 134.37,

127.97, 123.80, 122.85, 122.26, 113.65, 113.13, 109.99, 106.20, 45.31,

35.92, 33.90, 22.32; IR (KBr) v: 3111, 3054, 2951, 2223, 1675, 1525,

1464, 1375, 1226, 1074, 756 cm-1.

N-(But-3-en-1-yl)-N-cyano-1-methyl-1H-indole-3-carboxamide (1kb)

N
CN
N
1kb

Pale yellow solid; m.p. 62-63 oC; 1H NMR (CDCl3, 400MHz), δ:

8.25-8.23 (m, 1H), 8.20 (s, 1H), 7.37-7.32 (m, 3H), 5.90-5.80 (m, 1H),

5.25-5.20 (m, 1H), 5.17-5.14 (m, 1H), 3.88-3.84 (m, 5H), 2.58-2.56 (m,
13
2H); C NMR (CDCl3, 100MHz), δ: 161.82, 136.75, 134.36, 133.44,

S13
127.98, 123.82, 122.87, 122.27, 118.63, 113.19, 109.99, 106.19, 46.47,

33.90, 32.33; IR (KBr) v: 3013, 2936, 2948, 2223, 1670, 1520, 1469,

1236, 1081, 745 cm-1.

N-Cyano-1,3-dimethyl-N-(3-methylbut-3-en-1-yl)-1H-pyrazole-5-carb

oxamide (1la)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 6.89 (s, 1H), 4.89 (s,

1H), 4.83 (s, 1H), 4.02 (s, 3H), 3.87 (t, J = 6.8 Hz, 2H), 2.47 (t, J = 6.8
13
Hz, 2H), 2.28 (s, 3H), 1.80 (s, 3H); C NMR (CDCl3, 100MHz), δ:

158.81, 147.04, 140.40, 131.40, 114.05, 110.54, 110.40, 45.56, 39.40,

35.53, 22.04, 13.28; IR (film) v: 3077, 2952, 2233, 1697, 1442, 1243, 743

cm-1.

N-Cyano-N-(3-methylbut-3-en-1-yl)thiophene-2-carboxamide (1ma)

CN
N
S
O
1ma

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 8.10 (d, J = 3.6 Hz,

1H), 7.69 (dd, J1 = 4.8 Hz, J2 = 0.8 Hz, 1H), 7.14 (t, J = 5.2 Hz, 1H), 4.88

(s, 1H), 4.84 (s, 1H), 3.90 (t, J = 7.2 Hz, 2H), 2.49 (t, J = 7.2 Hz, 2H),
13
1.80 (s, 3H); C NMR (CDCl3, 100MHz), δ: 160.39, 140.57, 134.33,

S14
134.05, 133.57, 128.22, 114.00, 111.25, 46.40, 35.63, 22.20; IR (film) v:

3083, 3103, 2968, 2843, 2228, 1681, 1520, 1410, 1269, 1108, 727 cm-1.

N-Cyano-N-(pent-4-en-1-yl)benzamide (1na)

N
CN
1na

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.82-7.79 (m, 2H),

7.62-7.58 (m, 1H), 7.51-7.47 (m, 2H), 5.88-5.78 (m, 1H), 5.14-5.09 (m,

1H), 5.08-5.04 (m, 1H), 3.79 (t, J = 7.2 Hz, 2H), 2.24-2.19 (m, 2H),
13
1.97-1.89 (m, 2H); C NMR (CDCl3, 100MHz), δ: 168.56, 136.60,

133.26, 131.20, 128.74, 128.70, 116.34, 111.27, 47.42, 30.52, 26.79; IR

(film) v: 3077, 2926, 2858, 2233, 1707, 1447, 1269, 707 cm-1.

N-(2-Allyl-4-methylphenyl)-N-cyanobenzamide (1oa)

Pale yellow solid; m.p. 82-83 oC; 1H NMR (CDCl3, 400MHz), δ:

7.88-7.83 (m, 2H), 7.64-7.60 (m, 1H), 7.52-7.48 (m, 2H), 7.29-7.24 (m,

1H), 7.17-7.16 (m, 2H), 5.99-5.89 (m, 1H), 5.18-5.11 (m, 2H), 3.42 (d, J
13
= 6.4 Hz, 2H), 2.39 (s, 3H); C NMR (CDCl3, 100MHz), δ: 168.24,

140.78, 137.05, 135.03, 133.50, 131.92, 131.60, 130.67, 130.57, 129.24,

S15
129.12, 129.01, 128.80, 127.88, 125.49, 117.53, 110.51, 35.83, 21.36; IR

(KBr) v: 3416, 3067, 2895, 2228, 1712, 1488, 1442, 1285, 1181, 1035,

920, 816, 701 cm-1.

N-Cyano-N-(2-(cyclopent-1-en-1-yl)ethyl)benzamide (1pa)

N
CN
1pa

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.77-7.75 (m, 2H),

7.61-7.56 (m, 1H), 7.49-7.46 (m, 2H), 5.55 (m, 1H), 3.88 (t, J = 7.2 Hz,

2H), 2.59 (t, J = 6.8 Hz, 2H), 2.34-2.31 (m, 4H), 1.93-1.86 (m, 2H); 13C

NMR (CDCl3, 100MHz), δ: 168.52, 139.29, 133.13, 131.31, 128.70,

128.59, 127.73, 111.09, 45.94, 34.82, 32.69, 29.30, 23.56; IR (film) v:

2842, 2838, 2228, 1702, 1436, 1283, 1131, 713 cm-1.

N-Cyano-N-(2-(cyclopent-1-en-1-yl)ethyl)-4-methoxybenzamide (1qa)

N
H3CO CN

1qa

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.83-7.76 (m, 2H),

6.97-6.94 (m, 2H), 5.54-5.53 (m, 1H), 3.88-3.84 (m, 5H), 2.57 (t, J = 7.6
13
Hz, 2H), 2.34-2.29 (m, 3H), 1.92-1.87 (m, 2H); C NMR (CDCl3,

100MHz), δ: 167.80, 163.53, 139.42, 131.06, 127.57, 123.30, 113.97,

S16
111.62, 55.63, 46.03, 34.86, 32.69, 29.35, 23.56; IR (film) v: 2927, 2858,

2228, 1707, 1608, 1520, 1441, 1308, 1264, 1175, 1102, 1023, 841, 757

cm-1.

4-Chloro-N-cyano-N-(2-(cyclopent-1-en-1-yl)ethyl)benzamide (1ra)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.72-7.70 (m, 2H),

7.47-7.45 (m, 2H), 5.54 (s, 1H), 3.88 (t, J = 6.8 Hz, 2H), 2.58 (t, J = 6.8
13
Hz, 2H), 2.34-2.30 (m, 4H), 1.93-1.85 (m, 2H); C NMR (CDCl3,

100MHz), δ: 167.50, 139.65, 139.22, 130.10, 129.59, 129.12, 127.84,

110.91, 46.05, 34.82, 32.70, 29.28, 23.57; IR (film) v: 2942, 2838, 2223,

1712, 1598, 1490, 1441, 1402, 1283, 1116, 1091, 1013, 846, 742 cm-1.

N-Cyano-N-(2-(cyclohex-1-en-1-yl)ethyl)benzamide (1sa)

N
CN
1sa

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.76-7.74 (m, 2H),

7.59-7.56 (m, 1H), 7.48-7.45 (m, 2H), 5.60 (s, 1H), 3.85 (t, J = 7.0 Hz,

2H), 2.40 (t, J = 7.0 Hz, 2H), 2.01-1.99 (m, 4H), 1.67-1.62 (m, 2H),
13
1.58-1.53 (m, 2H); C NMR (CDCl3, 100MHz), δ: 168.47, 132.02,

132.87, 131.40, 128.65, 128.52, 125.55, 111.19, 45.87, 36.08, 27.88,

S17
25.42, 22.81, 22.20; IR (film) v: 3070, 2922, 2858, 2223, 1707, 1658,

1593, 1441, 1283, 1200, 1126, 1052, 904, 801, 731, 688 cm-1.

N-Cyano-N-(2-(cyclohex-1-en-1-yl)ethyl)-4-methylbenzamide (1ta)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.67 (d, J = 8.4 Hz,

2H), 7.27 (d, J = 8.0 Hz, 2H), 5.59 (s, 1H), 3.83 (t, J = 6.8 Hz, 2H),

2.41-2.38 (m, 5H), 2.01-1.98 (m, 4H), 1.65-1.61 (m, 2H), 1.57-1.54 (m,
13
2H); C NMR (CDCl3, 100MHz), δ: 168.47, 143.96, 132.94, 129.34,

128.70, 128.53, 125.53, 111.48, 45.89, 36.13, 27.92, 25.45, 22.85, 22.24,

21.79; IR (film) v: 3040, 2932, 2853, 2829, 2238, 1712, 1608, 1436, 1348,

1185, 1131, 1018, 826, 732 cm-1.

4-Chloro-N-cyano-N-(2-(cyclohex-1-en-1-yl)ethyl)benzamide (1ua)

White solid; m.p. 84-85 oC; 1H NMR (CDCl3, 400MHz), δ: 7.72-7.70 (m,

2H), 7.47-7.45 (m, 2H), 5.59 (s, 1H), 3.84 (t, J = 6.8 Hz, 2H), 2.40 (t, J =

6.8 Hz, 2H), 2.00-1.98 (m, 4H), 1.67-1.60 (m, 2H), 1.58-1.52 (m, 2H);
13
C NMR (CDCl3, 100MHz), δ: 167.50, 139.58, 132.86, 130.06, 129.68,

S18
129.12, 125.70, 111.07, 45.99, 36.11, 27.90, 25.47, 22.83, 22.22; IR (KBr)

v: 2927, 2838, 2233, 1697, 1589, 1490, 1367, 1297, 1225, 1008, 865, 831,

698 cm-1.

N-Cyano-N-(2-(cyclohept-1-en-1-yl)ethyl)benzamide (1va)

Pale yellow liquid (CDCl3, 400MHz), δ: 7.79-7.75 (m, 2H), 7.60-7.56 (m,

1H), 7.50-7.46 (m, 2H), 5.75 (t, J = 6.4 Hz, 1H), 3.83 (t, J = 7.2 Hz, 2H),

2.44 (t, J = 7.2 Hz, 2H), 2.19-2.17 (m, 2H), 2.13-2.09 (m, 2H), 1.75-1.70
13
(m, 2H), 1.55-1.47 (m, 4H); C NMR (CDCl3, 100MHz), δ: 167.54,

138.37, 132.11, 130.42, 129.61, 127.71, 127.60, 110.27, 45.11, 37.21,

31.61, 31.39, 27.54, 26.09, 25.80; IR (film) v: 2932, 2848, 2233, 1707,

1451, 1259, 1121, 1016, 743, 703 cm-1.

N-Cyano-N-(2-(cyclohept-1-en-1-yl)ethyl)-4-(trifluoromethyl)benzam

ide (1wa)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.87 (d, J = 8.0 Hz,

2H), 7.76 (d, J = 8.0 Hz, 2H), 5.75 (t, J = 6.4 Hz, 2H), 3.85 (t, J = 6.8 Hz,

S19
2H), 2.45 (t, J = 6.8 Hz, 2H), 2.20-2.17 (m, 2H), 2.13-2.09 (m, 2H),
13
1.75-1.71 (m, 2H), 1.55-1.45 (m, 4H); C NMR (CDCl3, 100MHz), δ:

167.42, 139.25, 134,69, 134.62 (q, J = 33.0 Hz), 130.85, 129.03, 125.88

(q, J = 4.0 Hz), 123.44 (q, J = 271.0 Hz), 110.77, 46.20, 38.18, 32.61,

32.36, 28.57, 27.10, 26.81; 19F NMR (CDCl3, 376MHz), δ: -63.28; IR

(film) v: 2942, 2838, 2233, 1707, 1524, 1446, 1357, 1254, 1106, 1023,

752 cm-1.

N-Cyano-N-(2-(cyclohept-1-en-1-yl)ethyl)-1,3-dimethyl-1H-pyrazole-

5-carboxamide (1xa)

O
N
N N
CN
1xa

Yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 6.86 (s, 1H), 5.68 (t, J =

6.4 Hz, 1H), 4.00 (s, 3H), 3.77 (t, J = 7.2 Hz, 2H), 2.26 (s, 3H), 2.15-2.12
13
(m, 2H), 2.08-2.03 (m, 2H), 1.72-1.68 (m, 2H), 1.51-1.42 (m, 4H); C

NMR (CDCl3, 100MHz), δ: 158.88, 147.05, 139.07, 131.59, 130.66,

115.44, 110.36, 46.15, 39.41, 38.08, 32.59, 32.32, 28.48, 26.98, 26.73,

13.33; IR (film) v: 2922, 2848, 2238, 1928, 1707, 1515, 1446, 1318, 1288,

850, 762, 713 cm-1.

N-allyl-N-cyanobenzamide (5a)

S20
 O

N
CN
5a

White solid; m.p. 52-53 oC; 1H NMR (CDCl3, 400MHz), δ: 7.83-7.81 (m,

2H), 7.62-7.58 (m, 1H), 7.51-7.47 (m, 2H), 6.01-5.91 (m, 1H), 5.50-5.42
13
(m, 2H), 4.34-4.33 (m, 2H); C NMR (CDCl3, 100MHz), δ: 168.14,

133.35, 130.91, 129.48, 128.75, 128.74, 121.76, 110.86, 50.11; IR (KBr)

v: 3065, 2982, 2238, 1712, 1495, 1448, 1319, 1267, 1112, 942cm-1.

N-allyl-N-cyano-4-methylbenzamide (5b)

White solid; m.p. 47-48 oC; 1H NMR (CDCl3, 400MHz), δ: 7.74 (d, J =

8.4 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 5.99-5.91 (m, 1H), 5.49-5.42 (m,
13
2H), 4.33-4.31 (m, 2H), 2.42 (s, 3H); C NMR (CDCl3, 100MHz), δ:

168.11, 144.34, 129.62, 129.41, 128.92, 128.06, 121.69, 111.13, 50.12,

21.83; IR (KBr) v: 2926, 2843, 2228, 1707, 1275, 1191, 983, 946, 822,

743cm-1.

N-allyl-N-cyano-[1,1'-biphenyl]-4-carboxamide (5c)

S21
 O

N
CN
Ph
5c

White solid; m.p. 138-139 oC; 1H NMR (CDCl3, 400MHz), δ: 7.93-7.91

(m, 2H), 7.72-7.70 (m, 1H), 7.63-7.61 (m, 2H), 7.50-7.40 (m, 3H),

6.04-5.94 (m, 1H), 5.52-5.45 (m, 2H), 4.36 (d, J = 6.4 Hz, 2H); 13C NMR

(CDCl3, 100MHz), δ: 167.89, 146.30, 139.65, 129.55, 129.48, 129.16,

128.58, 127.44, 127.41, 121.88 111.05, 50.24; IR (KBr) v: 3418, 2944,

2844, 2223, 1703, 1455, 1338, 1261, 1121, 849, 726cm-1.

N-allyl-N-cyano-4-methoxybenzamide (5d)

N
CN
MeO
5d

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.85 (d, J = 9.2 Hz,

2H), 6.96 (d, J = 8.8 Hz, 2H), 6.00-5.90 (m, 1H), 5.49-5.41 (m, 2H),

4.32-4.30 (m, 2H), 3.87 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 167.42,

163.72, 131.27, 129.74, 122.93, 121.62, 114.03, 111.41, 55.68, 50.20; IR

(film) v: 3075, 2941, 2228, 1701, 1603, 1510, 1257, 1174, 1102, 998,

736cm-1.

N-allyl-N-cyano-4-fluorobenzamide (5e)

S22
Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.89-7.84 (m, 2H),

7.20-7.14 (m, 1H), 5.99-5.89 (m, 1H), 5.49-5.42 (m, 2H), 4.33-4.31 (m,
13
2H); C NMR (CDCl3, 100MHz), δ: 166.92 (d, J = 6.0 Hz), 164.35,

131.55 (d, J = 9.0 Hz), 129.35, 127.02 (d, J = 4.0 Hz), 121.09, 116.06 (d,

J = 22.0 Hz), 110.79, 50.18; 19F NMR (CDCl3, 376MHz), δ: -106.95; IR

(film) v: 3433, 2238, 1726, 1641, 1610, 1517, 1346, 1253, 1129, 857, 764,

632cm-1.

N-allyl-4-chloro-N-cyanobenzamide (5f)

White solid; m.p. 51-52 oC; 1H NMR (CDCl3, 400MHz), δ: 7.78 (d, J =

8.4 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 5.98-5.89 (m, 1H), 5.46 (t, 2H),

4.32 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3, 100MHz), δ: 167.12, 139.90,

130.27, 129.28, 129.21, 129.17, 122.10, 110.68, 50.23; IR (KBr) v: 3072,

2999, 2228, 1712, 1582, 1405, 1321, 1269, 1139, 1108, 942, 837,

749cm-1.

N-allyl-4-bromo-N-cyanobenzamide (5g)

S23
 O

N
CN
Br
5g

White solid; m.p. 65-66 oC; 1H NMR (CDCl3, 400MHz), δ: 7.71-7.69 (m,

2H), 7.65-7.63 (m, 2H), 5.98-5.91 (m, 1H), 5.50-5.43 (m, 2H), 4.33-4.31

(m, 2H); 13C NMR (CDCl3, 100MHz), δ: 167.25, 132.14, 130.31, 129.66,

129.25, 128.46, 122.12, 110.64, 50.22; IR (KBr) v: 3090, 2992, 2930,

2223, 1706, 1582, 1324, 1272, 1112, 937, 834, 751cm-1.

N-allyl-N-cyano-4-(trifluoromethyl)benzamide (5h)

N
CN
F3C 5h

White liquid; 1H NMR (CDCl3, 400MHz), δ: 7.94 (d, J = 8.4 Hz, 2H),

7.77 (d, J = 8.4 Hz, 2H), 6.01-5.91 (m, 1H), 5.52-5.46 (m, 2H), 4.37-4.35

(m, 2H); 13C NMR (CDCl3, 100MHz), δ: 167.04, 134.82 (q, J = 33.0 Hz),

129.22, 129.07, 125.90 (q, J = 3.0 Hz), 123.40 (q, J = 271.0 Hz), 122.38,

110.35, 50.25; 19F NMR (CDCl3, 376MHz), δ: -63.30; IR (film) v: 3088,

2947, 2864, 2228, 1707, 1401, 1285, 1327, 1176, 1066, 858cm-1.

4-(Allyl(cyano)carbamoyl)phenyl acetate (5i)

S24
 O

N
CN
MeOOC
5i

Pale yellow solid; m.p. 76-77 oC; 1H NMR (CDCl3, 400MHz), δ: 8.15 (d,

J = 8.4 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 6.01-5.91 (m, 1H), 5.51-5.45
13
(m, 2H), 4.35 (d, J = 6.4 Hz, 2H), 3.95 (s, 3H); C NMR (CDCl3,

100MHz), δ: 167.53, 165.91, 134.70, 134.28, 129.95, 129.19, 128.76,

122.24, 110.43, 52.74, 50.22; IR (KBr) v: 3472, 2929, 2844, 2362, 2215,

1711, 1657, 1439, 1268, 1090, 950, 726cm-1.

N-allyl-N-cyano-2-methylbenzamide (5j)

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.46-7.40 (m, 2H),

7.30-7.28 (m, 2H), 5.98-5.90 (m, 1H), 5.46 (t, 2H), 4.33 (d, J = 6.4 Hz,

2H), 2.41 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 169.30, 136.36, 131.83,

131.69, 131.27, 129.5, 127.30, 126.01, 121.81, 110.19, 49.32, 19.41; IR

(film) v: 3077, 3025, 2238, 1707, 1265, 1095, 960, 746cm-1.

N-allyl-N-cyano-3,4,5-trimethoxybenzamide (5k)

S25
Pale yellow solid; m.p. 75-76 oC; 1H NMR (CDCl3, 400MHz), δ: 7.09 (s,

2H), 6.01-5.91 (m, 1H), 5.50-5.43 (m, 2H), 4.34-4.32 (m, 2H), 3.91 (s,
13
9H); C NMR (CDCl3, 100MHz), δ: 167.44, 153.10, 142.48, 129.51,

125.38, 121.87, 111.01, 106.54, 61.11, 56.46, 50.43; IR (KBr) v: 3433,

2944, 2859, 2231, 1703, 1594, 1416, 1369, 1152, 989, 786cm-1.

N-allyl-N-cyanobenzo[d][1,3]dioxole-5-carboxamide (5l)

O
O N
O CN
5l

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.46 (dd, J1 = 8.0 Hz,

J2 = 1.6 Hz, 1H), 7.27 (s, 1H), 6.87 (d, J1 = 8.0 Hz, 1H), 6.06 (s, 2H),
13
5.99-5.89 (m, 1H), 5.48-5.41 (m, 2H), 4.31-4.29 (m, 2H); C NMR

(CDCl3, 100MHz), δ: 167.11, 152.05, 148.02, 129.58, 124.76, 124.42,

121.68, 111.07, 109.17, 108.24, 102.22, 50.26; IR (KBr) v: 3464, 2921,

2238, 1687, 1509, 1447, 1338, 1238, 1113, 1020, 927cm-1.

N-allyl-N-cyano-1-methyl-1H-indole-3-carboxamide (5m)

S26
 O

N
CN
N
5m

Pale yellow solid; m.p. 53-54 oC; 1H NMR (CDCl3, 400MHz), δ:

8.27-8.23 (m, 2H), 7.40-7.31 (m, 3H), 6.03-5.93 (m, 1H), 5.49-5.39 (m,
13
2H), 4.37-4.35 (m, 2H), 3.87 (s, 3H); C NMR (CDCl3, 100MHz), δ:

161.47, 136.76, 134.50, 130.31, 127.99, 123.85, 122.92, 122.29, 120.99,

112.88, 110.01, 106.01, 49.46, 33.93; IR (KBr) v: 3456, 2913, 2215, 1680,

1532, 1462, 1369, 1238, 1075, 927, 593cm-1.

N-cyano-N-(2-methylallyl)benzamide (5n)

N
CN

5n

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.84-7.81 (m, 2H),

7.63-7.59 (m, 1H), 7.52-7.48 (m, 2H), 5.29 (s, 1H), 5.11 (m, 2H), 4.31 (s,

2H), 1.85 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 162.48, 147.07, 133.29,

128.04, 119.88, 117.04, 115.04, 114.79, 35.11, 17.73; IR (film) v: 3488,

2944, 2231, 1711, 1447, 1331, 1137, 1020, 889, 795cm-1.

N,4-dicyano-N-(2-methylallyl)benzamide (5o)

S27
 O

N
CN
NC
5o

White solid; m.p. 92-93 oC; 1H NMR (CDCl3, 400MHz), δ: 7.91-7.89 (m,

2H), 7.80-7.78 (m, 2H), 5.10 (d, 2H), 4.30 (s, 2H), 1.83 (s, 3H); 13C NMR

(CDCl3, 100MHz), δ: 166.71, 136.91, 134.74, 132.52, 129.18, 117.48,

116.86, 116.70, 110.09, 53.28, 19.96; IR (KBr) v: 3472, 2238, 1726, 1649,

1354, 1299, 1121, 919, 842, 756, 617cm-1.

N-cyano-N-(cyclopent-1-en-1-ylmethyl)benzamide (5p)

N
CN

5p

Pale yellow liquid; 1H NMR (CDCl3, 400MHz), δ: 7.83-7.80 (m, 2H),

7.61-7.57 (m, 1H), 7.50-7.46 (m, 2H), 5.83 (s, 1H), 4.41 (s, 2H),
13
2.43-2.36 (m, 4H), 2.01-1.93 (m, 2H); C NMR (CDCl3, 100MHz), δ:

168.34, 136.37, 133.21, 131.81, 131.05, 128.68, 128.65, 111.08, 47.94,

33.19, 32.54, 23.45; IR (film) v: 3464, 2937, 2851, 2238, 1711, 1641,

1462, 1276, 1121, 989, 710cm-1.

5. Typical Procedure for Synthesis of 3aa:

S28
 O Me O
Cu2O (20 mol %)
N 2,2'-bipyridine (40 mol %) N
Togni's reagent 2 (2 equiv)
N CF3
N CH3CN, 80 oC Me
1aa 3aa

A Schlenk tube containing copper(I) oxide (5.8 mg, 20 mol %),

2,2'-bipyridine (11.2 mg, 40 mol %), and Togni’s reagent 2 (126 mg, 0.4

mmol) were evacuated and purged with Argon three times. Afterwards,

a CH3CN (2 mL) solution of N-cyano-N-(3-methylbut-3-en-

1-yl)benzamide 1aa (43 mg, 0.2 mmol) was added via syringe. The

solution was kept at 80 oC for 10 h. Then the solution was diluted with

CH2Cl2 and transferred to a round bottom flask. Silica was added to the

flask and volatiles were evaporated under vacuum. The purification was

performed by flash column chromatography on silica gel using ethyl

acetate/petroleum ether (v/v, 1:5) as eluent to give 3aa as a pale yellow

solid (46mg, 82% yield).

6. Characterization of 3 and 4:
3-Methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin

-9(1H)-one (3aa)

N CF3
Me
3aa

S29
Pale yellow solid; m.p. 91-92 oC; 1H NMR (CDCl3, 400MHz), δ: 8.29 (dd,

J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.76-7.72 (m, 1H), 7.67 (dd, J1 = 8.4 Hz, J2

= 0.8 Hz, 1H), 7.46 (dq, J1 = 7.4 Hz, J2 = 1.2 Hz, 1H), 4.30 (dq, J1 = 11.2

Hz, J2 = 3.0 Hz, 1H), 4.03 (dq, J1 = 12.4 Hz, J2 = 1.6 Hz, 1H), 2.93 (dq,

J1 = 15.2 Hz, J2 = 11.2 Hz, 1H), 2.55 (dq, J1 = 15.2 Hz, J2 = 11.6 Hz, 1H),
13
2.43-2.35 (m, 1H), 2.30-2.24 (m, 1H), 1.48 (s, 3H); C NMR (CDCl3,

100MHz), δ: 162.56, 161.05, 149.33, 134.37, 126.60 (q, J = 276.0 Hz),

127.35, 126.70, 126.58, 121.01, 44.04 (q, J = 2.0 Hz), 43.51, 41.56 (q, J

= 27.0 Hz), 32.95, 24.04; 19F NMR (CDCl3, 470MHz), δ: -60.29; IR (KBr)

v: 2989, 2947, 2905, 1660, 1614, 1437, 1363, 1389, 1207, 1056, 1009,

775, 613 cm-1; HRMS (EI) (m/z): calcd for C14H13F3N2O (M+): 282.0980;

Found: 282.0983.

3-(2,2,2-Trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-o

ne (3ab)

N
CF3
3ab

Pale yellow solid; m.p. 117-118 oC; 1H NMR (CDCl3, 400MHz), δ: 8.30

(dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.74-7.32 (m, 1H), 7.67 (dd, J1 = 8.4

Hz, J2 = 0.8 Hz, 1H), 7.46 (dt, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 4.40 (dq, J1

= 9.0 Hz, J2 = 2.0 Hz, 1H), 3.95 (dq, J1 = 9.0 Hz, J2 = 2.0 Hz, 1H), 3.53

S30
(dq, J1 = 9.8 Hz, J2 = 2.8 Hz, 1H), 3.35-3.21 (m, 1H), 2.73-2.66 (m, 1H),
13
2.36-2.22 (m, 1H), 2.10-1.99 (m, 1H); C NMR (CDCl3, 100MHz), δ:

160.90, 158.66, 149.01, 134.46, 126.70 (q, J = 275.0 Hz), 127.21, 126.84,

126.62, 120.97, 44.85, 38.48 (q, J = 3.0 Hz), 36.11 (q, J = 29.0 Hz), 27.64;
19
F NMR (CDCl3, 470MHz), δ: -64.67; IR (KBr) v: 2987, 2951, 2889,

1675, 1624, 1474, 1391, 1334, 1262, 1123, 1035, 777, 684, 632 cm-1;

HRMS (EI) (m/z): calcd for C13H11F3N2O (M+): 268.0823; Found:

268.0827.

3,6-Dimethyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinaz

olin-9(1H)-one (3ba)

Me N CF3
Me
3ba

White solid; m.p. 109-110 oC; 1H NMR (CDCl3, 400MHz), δ: 8.16 (d, J

= 8.0 Hz, 1H), 7.46 (s, 1H), 7.27 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 4.27

(dq, J1 = 10.8 Hz, J2 = 2.8 Hz, 1H), 4.01 (dq, J1 = 12.4 Hz, J2 = 1.6 Hz,

1H), 2.90 (dq, J1 = 15.2 Hz, J2 = 11.2 Hz, 1H), 2.59-2.47 (m, 4H),
13
2.41-2.33 (m, 1H), 2.27-2.22 (m, 1H), 1.46 (s, 3H); C NMR (CDCl3,

100MHz), δ: 162.62, 160.97, 149.45, 145.35, 128.21, 127.10, 126.60 (q, J

= 277.0 Hz), 126.35, 118.56, 43.98 (q, J = 2.0 Hz), 43.39, 41.53 (q, J =

27.0 Hz), 32.92, 24.01, 21.95; 19F NMR (CDCl3, 470MHz), δ: -60.30; IR

S31
(KBr) v: 2987, 2956, 1660, 1629, 1469, 1371, 1267, 1205, 1148, 1097,

787, 689 cm-1; HRMS (EI) (m/z): calcd for C15H15F3N2O (M+): 296.1136;

Found: 296.1136.

6-Methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin

-9(1H)-one (3bb)

Pale yellow solid; m.p. 92-93 oC; 1H NMR (CDCl3, 400MHz), δ: 8.14 (d,

J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.28 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 4.36

(dq, J1 = 9.2 Hz, J2 = 1.6 Hz, 1H), 3.91 (dq, J1 = 8.0 Hz, J2 = 2.0 Hz, 1H),

3.49 (dq, J1 = 10.0 Hz, J2 = 2.4 Hz, 1H), 3.24 (dq, J1 = 13.4 Hz, J2 = 2.8

Hz, 1H), 2.69-2.62 (m, 1H), 2.48 (s, 3H), 2.31-2.22 (m, 1H), 2.07-1.98

(m, 1H); 13C NMR (CDCl3, 100MHz), δ: 160.81, 158.69, 149.12, 145.44,

128.35, 126.94, 126.71 (q, J = 275.0 Hz), 126.36, 111.85, 44.73, 38.42 (q,
19
J = 3.0 Hz), 36.07 (q, J = 29.0 Hz), 27.60, 21.97; F NMR (CDCl3,

470MHz), δ: -64.68; IR (KBr) v: 2984, 2952, 2911, 1676, 1614, 1473,

1379, 1265, 1129, 1040, 832, 761, 691 cm-1; HRMS (EI) (m/z): calcd for

C14H13F3N2O (M+): 282.0980; Found: 282.0982.

6-Methoxy-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b

]quinazolin-9(1H)-one (3ca)

S32
White solid; m.p. 109-110 oC; 1H NMR (CDCl3, 400MHz), δ: 8.17 (d, J

= 8.8 Hz, 1H), 7.06-7.05 (d, 1H), 7.03 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H),

4.27 (dq, J1 = 10.6 Hz, J2 = 3.2 Hz, 1H), 4.01 (dq, J1 = 8.4 Hz, J2 = 1.2

Hz, 1H), 3.91 (s, 3H), 2.90 (dq, J1 = 15.2 Hz, J2 = 11.2 Hz, 1H), 2.53

(dq, , J1 = 15.8 Hz, J2 = 11.6 Hz, 1H), 2.42-2.34 (m, 1H), 2.28-2.22 (m,

1H), 1.47 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 164.66, 163.32, 160.63,

151.69, 128.02, 126.58 (q, J = 276.0 Hz), 116.75, 114.50, 108.04, 55.81,
19
44.11 (q, J = 2.0 Hz), 43.41, 41.55 (q, J = 28.0 Hz), 32.97, 24.02; F

NMR (CDCl3, 470MHz), δ: -60.30; IR (KBr) v: 2982, 2941, 1665, 1613,

1484, 1391, 1262, 1205, 844, 777, 689 cm-1; HRMS (EI) (m/z): calcd for

C15H15F3N2O2 (M+): 312.1086; Found: 312.1083.

6-Methoxy-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinazol

in-9(1H)-one (3cb)

Pale yellow solid; m.p. 113-114 oC; 1H NMR (CDCl3, 400MHz), δ: 8.15

S33
(d, J = 9.6 Hz, 1H), 7.04-7.01 (m, 2H), 4.35 (dq, J1 = 9.2 Hz, J2 = 1.6 Hz,

1H), 3.94-3.87 (m, 4H), 3.54-3.45 (m, 1H), 3.23 (dq, J1 = 13.0 Hz, J2 =

2.8 Hz, 1H), 2.69-2.62 (m, 1H), 2.27 (dq, J1 = 15.2 Hz, J2 = 10.0 Hz, 1H),
13
2.05-1.99 (m, 1H); C NMR (CDCl3, 100MHz), δ: 164.66, 160.45,

159.40, 151.32, 128.03, 126.69 (q, J = 275.0 Hz), 116.70, 114.41, 107.97,
19
55.77, 44.74, 38.52 (q, J = 3.0 Hz), 36.09 (q, J = 28.0 Hz); 27.59; F

NMR (CDCl3, 470MHz), δ: -64.70; IR (KBr) v: 2956, 2905, 2822, 1665,

1613, 1480, 1391, 1267, 1138, 1024, 859, 787 cm-1; HRMS (EI) (m/z):

calcd for C14H13F3N2O2 (M+): 298.0929; Found: 298.0932.

3-Methyl-9-oxo-3-(2,2,2-trifluoroethyl)-1,2,3,9-tetrahydropyrrolo[2,1-

b]quinazoline-6-carbonitrile (3da)

NC N CF3
Me
3da

White solid; m.p. 173-174 oC; 1H NMR (CDCl3, 400MHz), δ: 8.37 (d, J

= 8.0 Hz, 1H), 7.99 (d, J = 1.2 Hz, 1H), 7.65 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz,

1H), 4.31 (dq, J1 = 12.0 Hz, J2 = 3.2 Hz, 1H), 4.06 (dq, J1 = 12.4 Hz, J2 =

1.2 Hz, 1H), 2.88 (dq, J1 = 15.6 Hz, J2 = 11.2 Hz, 1H), 2.58 (dq, , J1 =

15.2 Hz, J2 = 11.2 Hz, 1H), 2.47-2.39 (m, 1H), 2.32-2.26 (m, 1H), 1.49 (s,
13
3H); C NMR (CDCl3, 100MHz), δ: 164.57, 159.89, 149.27, 132.18,

128.53, 127.88, 126.37 (q, J = 276.0 Hz), 124.00, 117.84, 117.69, 44.31

S34
 19
(q, J = 2.0 Hz), 43.87, 41.46 (q, J = 28.0 Hz), 32.56, 24.36; F NMR

(CDCl3, 470MHz), δ: -60.33; IR (KBr) v: 2979, 2947, 2233, 1674, 1614,

1379, 1254, 1207, 1039, 686 cm-1; HRMS (EI) (m/z): calcd for

C15H12F3N3O (M+): 307.0932; Found: 307.0932.

9-Oxo-3-(2,2,2-trifluoroethyl)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinaz

oline-6-carbonitrile (3db)

White solid; m.p. 188-189 oC; 1H NMR (CDCl3, 400MHz), δ: 8.37 (d, J

= 8.4 Hz, 1H), 7.98 (d, J = 1.2 Hz, 1H), 7.66 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz,

1H), 4.41 (dq, J1 = 12.4 Hz, J2 = 1.6 Hz, 1H), 3.97 (dq, J1 = 10.6 Hz, J2 =

6.8 Hz, 1H), 3.60-3.52 (m, 1H), 3.31-3.16 (m, 1H), 2.76-2.69 (m, 1H),
13
2.37-2.23 (m, 1H), 2.13-2.02 (m, 1H); C NMR (CDCl3, 100MHz), δ:

160.71, 159.72, 148.93, 132.03, 128.71, 127.92, 126.60 (q, J = 276.0 Hz),

124.00, 117.80, 117.78, 45.21, 38.66 (q, J = 3.0 Hz), 35.87 (q, J = 30.0
19
Hz), 27.52; F NMR (CDCl3, 470MHz), δ: -64.66; IR (KBr) v: 3066,

2957, 2910, 2231, 1681, 1618, 1421, 1385, 1287, 1250, 1136, 1032, 796

cm-1; HRMS (EI) (m/z): calcd for C14H10F3N3O (M+): 293.0776; Found:

293.0777.

3-Methyl-3-(2,2,2-trifluoroethyl)-6-(trifluoromethyl)-2,3-dihydropyrr

S35
olo[2,1-b]quinazolin-9(1H)-one (3ea)

White solid; m.p. 104-105 oC; 1H NMR (CDCl3, 400MHz), δ: 8.38 (d, J

= 8.4 Hz, 1H), 7.80 (s, 1H), 7.65 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 4.31

(dq, J1 = 9.2 Hz, J2 = 3.2 Hz, 1H), 4.06 (dq, J1 = 12.8 Hz, J2 = 7.6 Hz,

1H), 2.89 (dq, J1 = 15.6 Hz, J2 = 11.2 Hz, 1H), 2.58 (dq, J1 = 15.2 Hz, J2

= 11.2 Hz, 1H), 2.47-2.39 (m, 1H), 2.32-2.26 (m, 1H), 1.49 (s, 3H); 13C

NMR (CDCl3, 100MHz), δ: 164.08, 160.18, 149.32, 135.93 (q, J = 330.0

Hz), 127.71, 126.45 (q, J = 274.0 Hz), 124.96 (q, J = 5.0 Hz), 123.55 (q,

J = 271.0 Hz), 123.33, 122.68 (q, J = 4.0 Hz), 44.22 (q, J = 2.0 Hz),

43.75, 41.50 (q, J = 270.0 Hz), 32.66, 24.27; 19F NMR (CDCl3, 470MHz),

δ: -60.37, -63.20; IR (KBr) v: 2937, 1676, 1618, 1447, 1327, 1265, 1139,

1066, 915 cm-1; HRMS (EI) (m/z): calcd for C15H12F6N2O (M+): 350.0854;

Found: 350.0848.

3-(2,2,2-Trifluoroethyl)-6-(trifluoromethyl)-2,3-dihydropyrrolo[2,1-b]

quinazolin-9(1H)-one (3eb)

F3C N
CF3
3eb

S36
White solid; m.p. 108-109 oC; 1H NMR (CDCl3, 400MHz), δ: 8.37 (d, J

= 8.4 Hz, 1H), 7.94 (s, 1H), 7.66 (dd, J1 = 8.4 Hz, J2 = 0.8 Hz, 1H), 4.41

(dq, J1 = 9.2 Hz, J2 = 1.2 Hz, 1H), 3.96 (dq, J1 = 10.8 Hz, J2 = 7.2 Hz,

1H), 3.55 (dq, J1 = 9.6 Hz, J2 = 2.4 Hz, 1H), 3.32-3.19 (m, 1H), 2.75-2.68
13
(m, 1H), 2.37-2.23 (m, 1H), 2.16-2.01 (m, 1H); C NMR (CDCl3,

100MHz), δ: 160.18, 160.01, 149.98, 135.99 (q, J = 330.0 Hz), 127.74,

126.59 (q, J = 275.0 Hz), 124.81 (q, J = 4.0 Hz), 123.51 (q, J = 272.0 Hz),

123.30, 122.85 (q, J = 3.0 Hz), 45.09 (q, J = 3.0 Hz), 35.93 (q, J = 290.0
19
Hz), 22.58; F NMR (CDCl3, 470MHz), δ: -63.21, -64.73; IR (KBr) v:

2966, 2905, 1681, 1624, 1443, 1386, 1257, 1138, 1045, 931, 777, 694,

653 cm-1; HRMS (EI) (m/z): calcd for C14H10F6N2O (M+): 336.0697;

Found: 336.0705.

6-Fluoro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]q

uinazolin-9(1H)-one (3fa)

White solid; m.p. 104-105 oC; 1H NMR (CDCl3, 400MHz), δ: 8.23 (dd, J1

= 9.2 Hz, J2 = 6.4 Hz, 1H), 7.31 (dd, J1 = 9.6 Hz, J2 = 2.4 Hz, 1H), 7.17

(dt, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 4.28 (dq, J1 = 11.0 Hz, J2 = 2.8 Hz, 1H),

4.02 (dq, J1 = 9.2 Hz, J2 = 7.6 Hz, 1H), 2.89 (dq, J1 = 15.2 Hz, J2 = 11.2

S37
Hz, 1H), 2.54 (dq, J1 = 15.6 Hz, J2 = 11.6 Hz, 1H), 2.43-2.36 (m, 1H),

2.29-2.24 (m, 1H), 1.47 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 165.55

(d, J = 253.0 Hz), 163.93, 160.31, 151.59 (d, J = 13.0 Hz), 129.16 (d, J =

11.0 Hz), 126.51 (q, J = 277.0 Hz), 117.73 (d, J = 2.0 Hz), 115.40 (d, J =

24.0 Hz), 112.76 (d, J = 22.0 Hz), 44.19 (q, J = 2.0 Hz), 43.56, 41.48 (q,
19
J = 28.0 Hz), 32.81, 24.13; F NMR (CDCl3, 470MHz), δ: -60.32,

-103.69; IR (KBr) v: 2997, 2899, 1676, 1648, 1562, 1489, 1448, 1381,

1267, 1159, 1097, 885 cm-1; HRMS (EI) (m/z): calcd for C14H12F4N2O

(M+): 300.0886; Found: 300.0887.

6-Chloro-3-methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]q

uinazolin-9(1H)-one (3ga)

White solid; m.p. 122-123 oC; 1H NMR (CDCl3, 400MHz), δ: 8.19 (d, J

= 8.8 Hz, 1H), 7.66 (d, J = 2.0 Hz, 1H), 7.40 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz,

1H), 4.28 (dq, J1 = 10.8 Hz, J2 = 3.2 Hz, 1H), 4.02 (dq, J1 = 12.4 Hz, J2 =

7.6 Hz, 1H), 2.88 (dq, J1 = 15.6 Hz, J2 = 11.2 Hz, 1H), 2.55 (dq, J1 = 15.6

Hz, J2 = 11.2 Hz, 1H), 2.43-2.36 (m, 1H), 2.29-2.23 (m, 1H), 1.47 (s, 3H);
13
C NMR (CDCl3, 100MHz), δ: 163.88, 160.40, 150.32, 140.55, 127.95,

127.27, 126.98, 126.48 (q, J = 276.0 Hz), 119.47, 44.18 (q, J = 2.0 Hz),

S38
43.60, 41.47 (q, J = 27.0 Hz), 32.77, 24.15; 19F NMR (CDCl3, 470MHz),

δ: -60.32; IR (KBr) v: 2984, 2911, 1666, 1603, 1431, 1269, 1145, 1108,

1056, 910, 780, 681, 639 cm-1; HRMS (EI) (m/z): calcd for

C14H12ClF3N2O (M+): 316.0590; Found: 316.0595.

6-Chloro-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin

-9(1H)-one (3gb)

Colorless crystal; m.p. 162-163 oC; 1H NMR (CDCl3, 400MHz), δ: 8.18

(d, J = 8.8 Hz, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.40 (dd, J1 = 8.8 Hz, J2 =

2.0 Hz, 1H), 4.37 (dq, J1 = 8.8 Hz, J2 = 1.2 Hz, 1H), 3.92 (dq, J1 = 10.4

Hz, J2 = 6.8 Hz, 1H), 3.51 (dq, J1 = 9.6 Hz, J2 = 2.4 Hz, 1H), 3.23 (dq, J1

= 13.0 Hz, J2 = 2.8 Hz, 1H), 2.72-2.65 (m, 1H), 2.34-2.16 (m, 1H),
13
2.09-1.98 (m, 1H); C NMR (CDCl3, 100MHz), δ: 160.20, 159.99,

149.96, 140.59, 127.95, 127.39, 126.81, 126.62 (q, J = 275.0 Hz), 119.42,
19
44.93, 38.56 (q, J = 3.0 Hz), 35.94 (q, J = 29.0 Hz), 27.56; F NMR

(CDCl3, 470MHz), δ: -64.68; IR (KBr) v: 3062, 2958, 1681, 1598, 1556,

1431, 1384, 1275, 1124, 1020, 910, 785 cm-1; HRMS (EI) (m/z): calcd for

C13H10ClF3N2O (M+): 302.0434; Found: 302.0436.

3-Methyl-6-nitro-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]qu

S39
inazolin-9(1H)-one (3ha)

Pale yellow solid; m.p. 144-145 oC; 1H NMR (CDCl3, 400MHz), δ: 8.52

(d, J = 2.4 Hz, 1H), 8.44 (d, J = 8.8 Hz, 1H), 8.21 (dd, J1 = 8.8 Hz, J2 =

2.4 Hz, 1H), 4.32 (dq, J1 = 10.8 Hz, J2 = 3.2 Hz, 1H), 4.08 (dq, J1 = 8.8

Hz, J2 = 7.6 Hz, 1H), 2.89 (dq, J1 = 15.6 Hz, J2 = 11.2 Hz, 1H), 2.61 (dq,

J1 = 15.6 Hz, J2 = 11.2 Hz, 1H), 2.49-2.42 (m, 1H), 2.34-2.28 (m, 1H),
13
1.51 (s, 3H); C NMR (CDCl3, 100MHz), δ: 164.80, 159.60, 151.45,

149.75, 128.28, 126.20 (q, J = 276.0 Hz), 124.99, 122.87, 120.21, 44.19
19
(q, J = 2.0 Hz), 43.75, 41.31 (q, J = 28.0 Hz), 32.40, 24.25; F NMR

(CDCl3, 470MHz), δ: -60.34; IR (KBr) v: 3109, 2994, 2369, 1681, 1618,

1535, 1358, 1265, 1092, 1066, 783 cm-1; HRMS (EI) (m/z): calcd for

C14H12F3N3O3 (M+): 327.0831; Found: 327.0835.

6-Nitro-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinazolin-9

(1H)-one (3hb)

Pale yellow solid; m.p. 148-149 oC; 1H NMR (CDCl3, 400MHz), δ: 8.49

S40
(d, J = 2.0 Hz, 1H), 8.43 (d, J = 8.8 Hz, 1H), 8.21 (dd, J1 = 8.8 Hz, J2 =

2.4 Hz, 1H), 4.42 (dq, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 3.98 (dq, J1 = 10.8

Hz, J2 = 7.2 Hz, 1H), 3.58 (dq, J1 = 9.8 Hz, J2 = 2.8 Hz, 1H), 3.26 (dq, J1

= 15.2 Hz, J2 = 11.6 Hz, 1H), 2.77-2.70 (m, 1H), 2.39-2.25 (m, 1H),
13
2.15-2.04 (m, 1H); C NMR (CDCl3, 100MHz), δ: 161.11, 159.57,

151.61, 149.55, 128.48, 126.51 (q, J = 275.0 Hz), 125.14, 122.88, 120.51,
19
45.24, 38.68 (q, J = 3.0 Hz), 35.85 (q, J = 29.0 Hz), 27.55; F NMR

(CDCl3, 470MHz), δ: -64.66; IR (KBr) v: 3062, 2952, 1692, 1608, 1530,

1348, 1275, 1134, 1045, 920, 811, 733 cm-1; HRMS (EI) (m/z): calcd for

C13H10F3N3O3 (M+): 313.0674; Found: 313.0675.

3,8-Dimethyl-3-(2,2,2-trifluoroethyl)-2,3-dihydropyrrolo[2,1-b]quinaz

olin-9(1H)-one (3ia)

Me O

N CF3
Me
3ia

White solid; m.p. 117-118 oC; 1H NMR (CDCl3, 400MHz), δ: 7.55 (t, 1H),

7.49 (d, 1H), 7.19 (d, J = 7.2 Hz, 1H), 4.24 (dq, J1 = 7.2 Hz, J2 = 3.2 Hz,

1H), 3.98 (dq, J1 = 9.2 Hz, J2 = 7.6 Hz, 1H), 2.90 (m, 4H), 2.58-2.46 (m,
13
1H), 2.39-2.32 (m, 1H), 2.27-2.21 (m, 1H), 1.46 (s, 3H); C NMR

(CDCl3, 100MHz), δ: 162.10, 161.78, 151.04, 141.18, 133.42, 129.30,

126.63 (q, J = 277.0 Hz), 125.55, 119.50, 43.96 (q, J = 2.0 Hz), 43.43,

S41
41.49 (q, J = 28.0 Hz), 32.87, 23.94, 23.12; 19F NMR (CDCl3, 470MHz),

δ: -60.30; IR (KBr) v: 2989, 2958, 1662, 1618, 1592, 1483, 1369, 1301,

1249, 1098, 1009, 816, 706 cm-1; HRMS (EI) (m/z): calcd for

C15H15F3N2O (M+): 296.1136; Found: 296.1135.

3,5-Dimethyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-pyrrolo[1',2':1,2

]pyrimido[4,5-b]indol-10(5H)-one (3ka)

N
N N CF3
Me Me
3ka

Pale yellow solid; m.p. 196-197 oC; 1H NMR (CDCl3, 400MHz), δ: 8.24

(d, J = 6.0 Hz, 1H), 7.43-7.37 (m, 2H), 7.33 (m, 1H), 4.38 (s, 1H), 4.12 (d,

J = 7.2 Hz, 1H), 3.85 (s, 3H), 2.96-2.85 (m, 1H), 2.63-2.51 (m, 1H), 2.44

(s, 1H), 2.31-2.29 (m, 1H), 1.49 (s, 3H); 13C NMR (CDCl3, 100MHz), δ:

164.92, 154.53, 137.48, 126.55 (q, J = 276.0 Hz), 124.41, 121.95, 121.92,

121.87, 109.29, 44.44 (q, J = 1.0 Hz), 43.49, 41.65 (q, J = 27.0 Hz),

33.24, 28.16, 24.12; 19F NMR (CDCl3, 470MHz), δ: -60.25; IR (KBr) v:

2982, 2941, 2905, 1660, 1588, 1515, 1464, 1371, 1257, 1148, 1097, 1061,

781, 741 cm-1; HRMS (EI) (m/z): calcd for C17H16F3N3O (M+): 335.1245;

Found: 335.1248.

5-Methyl-3-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-pyrrolo[1',2':1,2]py

rimido[4,5-b]indol-10(5H)-one (3kb)

S42
 O

N
N N
Me CF3
3kb

Pale yellow solid; m.p. 217-218 oC; 1H NMR (CDCl3, 400MHz), δ: 8.22

(d, J = 8.0 Hz, 1H), 7.43-7.41 (m, 3H), 4.45 (dq, J1 = 9.2 Hz, J2 = 1.6 Hz,

1H), 3.98 (dq, J1 = 10.4 Hz, J2 = 6.8 Hz, 1H), 3.81 (s, 3H), 3.63-3.52 (m,

1H), 3.30-3.17 (m, 1H), 2.73-2.66 (m, 1H), 2.34-2.25 (m, 1H), 2.10-2.02

(m, 1H); 13C NMR (CDCl3, 100MHz), δ: 161.02, 157.67, 154.07, 137.36,

124.97 (q, J = 276.0Hz), 124.40, 121.95, 121.82, 109.28, 44.80, 38.71 (q,
19
J = 3.0 Hz), 36.22 (q, J = 27.0 Hz), 28.04, 27.92; F NMR (CDCl3,

470MHz), δ: -64.63; IR (KBr) v: 3049, 2930, 2884, 1670, 1572, 1515,

1435, 1339, 1252, 1123, 1030, 834, 745, 627 cm-1; HRMS (EI) (m/z):

calcd for C16H14F3N3O (M+): 321.1089; Found: 321.1086.

1,3,5-Trimethyl-5-(2,2,2-trifluoroethyl)-6,7-dihydro-1H-pyrazolo[4,3-

d]pyrrolo[1,2-a]pyrimidin-9(5H)-one (3la)

Me O
N N
N
N CF3
Me Me
3la

Pale yellow solid; m.p. 217-218 oC; 1H NMR (CDCl3, 400MHz), δ:

4.26-4.20 (m, 1H), 4.21 (s, 3H), 3.95 (dq, J1 = 9.2 Hz, J2 = 7.6 Hz, 1H),

2.88 (dq, J1 = 15.2 Hz, J2 = 11.2 Hz, 1H), 2.54-2.47 (m, 1H), 2.45 (s, 3H),

S43
 13
2.42-2.34 (m, 1H), 2.29-2.24 (m, 1H), 1.43 (s, 3H); C NMR (CDCl3,

100MHz), δ: 160.37, 153.33, 141.57, 139.36, 126.60 (q, J = 277.0Hz),

124.93, 43.27 (q, J = 2.0 Hz), 42.81, 41.76 (q, J = 27.0 Hz), 38.27, 33.73,

24.12, 10.72; 19F NMR (CDCl3, 470MHz), δ: -60.37; IR (KBr) v: 2989,

2952, 1671, 1592, 1488, 1379, 1306, 1265, 1103, 1051, 853, 754 cm-1;

HRMS (EI) (m/z): calcd for C13H15F3N4O (M+): 300.1198; Found:

300.1199.

5-Methyl-5-(2,2,2-trifluoroethyl)-6,7-dihydropyrrolo[1,2-a]thieno[3,2-

d]pyrimidin-9(5H)-one (3ma)

Pale yellow solid; m.p. 123-124 oC; 1H NMR (CDCl3, 400MHz), δ: 7.78

(d, J = 5.2 Hz, 1H), 7.30 (d, J = 5.2 Hz, 1H), 4.31 (dq, J1 = 10.8 Hz, J2

= 3.2 Hz, 1H), 4.06 (dq, J1 = 12.4 Hz, J2 = 8.8 Hz, 1H), 2.87 (dq, J1 =

15.2 Hz, J2 = 11.2 Hz, 1H), 2.60-2.48 (m, 1H), 2.48-2.41 (m, 1H),

2.32-2.67 (m, 1H), 1.48 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 164.61,

158.43, 157.17, 134.42, 126.46 (q, J = 276.0 Hz), 124.94, 121.98, 43.91
19
(q, J = 1.0 Hz), 43.56, 41.68 (q, J = 27.0 Hz), 33.27, 24.27; F NMR

(CDCl3, 470MHz), δ: -60.33; IR (KBr) v: 3083, 2989, 2958, 1666, 1603,

1508, 1379, 1269, 1207, 1155, 1113, 790 cm-1; HRMS (EI) (m/z): calcd

S44
for C12H11F3N2O S (M+): 288.0544; Found: 288.0540.

6-(2,2,2-Trifluoroethyl)-8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7

H)-one (3na)

3na CF3

White solid; m.p. 142-143 oC; 1H NMR (CDCl3, 400MHz), δ: 8.26 (dd, J1

= 8.0 Hz, J2 = 1.2 Hz, 1H), 7.75-7.71 (m, 1H), 7.63 (d, 1H), 7.47-7.43 (m,

1H), 4.36-4.29 (m, 1H), 3.99-3.93 (m, 1H), 3.58-3.50 (m, 1H), 3.22-3.14
13
(m, 1H), 2.44-2.33 (m, 1H), 2.07-2.00 (m, 2H), 1.72-1.64 (m, 1H); C

NMR (CDCl3, 100MHz), δ: 162.08, 154.86, 147.00, 134.36, 127.12,

127.10 (q, J = 275.0 Hz), 126.81, 126.75, 120.37, 41.30, 36.23 (q, J =
19
28.0 Hz), 35.48 (q, J = 3.0 Hz), 25.24, 20.74; F NMR (CDCl3,

470MHz), δ: -63.22; IR (KBr) v: 2963, 1676, 1614, 1468, 1379, 1269,

1139, 1056, 775 cm-1; HRMS (EI) (m/z): calcd for C14H13F3N2O (M+):

282.0980; Found: 282.0981.

3-Methyl-6-(2,2,2-trifluoroethyl)-5H-quinolino[2,1-b]quinazolin-12(6

H)-one (3oa)

S45
 Me
O

3oa CF3

Pale yellow solid; m.p. 140-141 oC; 1H NMR (CDCl3, 400MHz), δ: 8.35

(dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 7.78-7.42 (m,

1H), 7.67 (d, 1H), 7.50 (t, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.12 (s, 1H),

3.33-3.22 (m, 2H), 3.17-3.13 (m, 1H), 2.87-2.81 (m, 1H), 2.39 (s, 3H),
13
2.32-2.23 (m, 1H); C NMR (CDCl3, 100MHz), δ: 160.91, 153.82,

145.85, 137.25, 134.53, 131.25, 129.42, 129.10 (q, J = 295.0 Hz), 128.68,

127.94, 127.46, 127.16, 127.09, 123.82, 121.84, 37.11 (q, J = 1.0 Hz),
19
34.25 (q, J = 23.0 Hz), 29.72, 21.01; F NMR (CDCl3, 470MHz), δ:

-63.25; IR (KBr) v: 3072, 2937, 2843, 2364, 2228, 1702, 1265, 701 cm-1;

HRMS (EI) (m/z): calcd for C19H15F3N2O (M+): 344.1136; Found:

344.1137.

2-(Trifluoromethyl)-1'H-spiro[cyclopentane-1,3'-pyrrolo[2,1-b]quinaz

olin]-9'(2'H)-one (4a)

N
CF3
N

4a

White solid; m.p. 74-75 oC; 1H NMR (CDCl3, 500MHz), δ: 8.28 (dd, J1 =

8.0 Hz, J2 = 1.0 Hz, 1H), 7.73-7.70 (m, 1H), 7.67-7.65 (m, 1H), 7.45-7.42

S46
(m, 1H), 4.27 (dq, J1 = 10.5 Hz, J2 = 3.0 Hz, 1H), 4.02-3.96 (m, 1H),

3.52-3.46 (m, 1H), 2.58-2.52 (m, 1H), 2.30-2.27 (m, 1H), 2.13-2.06 (m,

2H), 2.02-1.84 (m, 4H); 13C NMR (CDCl3, 125MHz), δ: 162.29, 161.08,

149.38, 134.21, 127.52 (q, J = 277.5 Hz), 127.34, 126.53, 126.46, 121.01,

54.46, 48.96 (q, J = 26.3 Hz), 43.84, 40.12, 29.36 (q, J = 2.5 Hz), 25.78

(q, J = 2.5 Hz), 22.92; 19F NMR (CDCl3, 470MHz), δ: -65.54; IR (KBr) v:

3049, 2966, 2873, 1677, 1608, 1407, 1382, 1264, 1160, 1116, 1082, 762,

693 cm-1; HRMS (EI) (m/z): calcd for C16H15F3N2O (M+): 308.1136;

Found: 308.1141.

6'-Methoxy-2-(trifluoromethyl)-1'H-spiro[cyclopentane-1,3'-pyrrolo[

2,1-b]quinazolin]-9'(2'H)-one (4b)

Pale yellow solid; m.p. 132-133 oC; 1H NMR (CDCl3, 500MHz), δ: 8.17

(d, J = 9.0 Hz, 1H), 7.05 (d, J = 2.5Hz, 1H), 7.01 (dd, J1 = 8.5 Hz, J2 = 2.0

Hz, 1H), 4.25 (dq, J1 = 10.5 Hz, J2 = 3.0 Hz, 1H), 3.80-3.94 (m, 1H), 3.91

(s, 3H), 3.49-3.43 (m, 1H), 2.57-2.51 (m, 1H), 2.31-2.25 (m, 1H),
13
2.11-2.05 (m, 2H), 2.00-1.86 (m, 4H); C NMR (CDCl3, 125MHz), δ:

164.47, 162.89, 160.60, 151.62, 127.88, 127.39 (q, J = 276.3 Hz), 116.42,

114.42, 107.97, 55.66, 54.46, 48.88 (q, J = 26.3 Hz), 43.64, 39.99, 29.21

S47
(q, J = 1.3 Hz), 25.61 (q, J = 2.5 Hz), 22.80; 19F NMR (CDCl3, 470MHz),

δ: -65.52; IR (KBr) v: 3463, 3365, 2971, 2878, 1672, 1618, 1490, 1441,

1392, 1313, 1279, 1234, 989, 954, 841, 721 cm-1; HRMS (EI) (m/z):

calcd for C17H17F3N2O2 (M+): 338.1242; Found: 338.1239.

6'-Chloro-2-(trifluoromethyl)-1'H-spiro[cyclopentane-1,3'-pyrrolo[2,

1-b]quinazolin]-9'(2'H)-one (4c)

N
CF3
Cl N

4c

White solid; m.p. 134-135 oC; 1H NMR (CDCl3, 500MHz), δ: 8.20 (d, J

= 8.5 Hz, 1H), 7.67 (d, J = 2.0 Hz, 1H), 7.39 (dd, J1 = 8.5 Hz, J2 = 2.0

Hz, 1H), 4.26 (dq, J1 = 10.3 Hz, J2 = 3.5 Hz, 1H), 4.01-3.95 (m, 1H),

3.50-3.40 (m, 1H), 2.58-2.52 (m, 1H), 2.32-2.26 (m, 1H), 2.12-2.07 (m,

2H), 2.02-1.86 (m, 4H); 13C NMR (CDCl3, 125MHz), δ: 163.72, 160.45,

150.39, 140.43, 127.96, 127.45 (q, J = 277.5Hz), 127.07, 126.99, 119.52,

54.60, 49.02 (q, J = 26.3 Hz), 43.97, 40.14, 29.32 (q, J = 2.5 Hz), 25.77

(q, J = 1.3 Hz), 22.93; 19F NMR (CDCl3, 470MHz), δ: -65.56; IR (KBr) v:

3493, 3424, 2956, 2878, 1667, 1593, 1455, 1387, 1318, 1259, 1156, 1106,

919, 875, 767, 678 cm-1; HRMS (EI) (m/z): calcd for C16H14ClF3N2O

(M+): 342.0747; Found: 342.0752.

2-(Trifluoromethyl)-1'H-spiro[cyclohexane-1,3'-pyrrolo[2,1-b]quinaz

S48
olin]-9'(2'H)-one (4d)

White solid; m.p. 105-106 oC; 1H NMR (CDCl3, 500MHz), δ: 8.28 (d, J =

8.0 Hz, 1H), 7.72-7.66 (m, 2H), 7.42 (t, J = 7.5 Hz, 1H), 4.15-4.11 (m,

2H), 2.94-2.86 (m, 1H), 2.53-2.48 (m, 1H), 2.14-2.04 (m, 2H), 1.99-1.90
13
(m, 2H), 1.81-1.71 (m, 2H), 1.58-1.37 (m, 3H); C NMR (CDCl3,

125MHz), δ: 163.07, 161.24, 149.68, 134.14, 127.32 (q, J = 277.8 Hz),

127.23, 126.48, 126.27, 120.94, 48.28, 46.77 (q, J = 23.8 Hz), 43.76,
19
38.08, 25.48, 24.36, 22.79 (q, J = 2.5 Hz), 21.81; F NMR (CDCl3,

470MHz), δ: -66.85; IR (KBr) v: 3449, 3345, 3070, 2937, 2858, 1677,

1608, 1466, 1392, 1283, 1170, 1077, 767, 683 cm-1; HRMS (EI) (m/z):

calcd for C17H17F3N2O (M+): 322.1293; Found: 322.1297.

6'-Methyl-2-(trifluoromethyl)-1'H-spiro[cyclohexane-1,3'-pyrrolo[2,1

-b]quinazolin]-9'(2'H)-one (4e)

Pale yellow solid; m.p. 82-83 oC; 1H NMR (CDCl3, 500MHz), δ: 8.16 (d,

J = 8.0 Hz, 1H), 7.47 (s, 1H), 7.24 (dd, J1 = 8.0 Hz, J2 = 1.0 Hz, 1H),

S49
4.13-4.08 (m, 2H), 2.91-2.86 (m, 1H), 2.52-2.47 (m, 4H), 2.13-2.04 (m,

2H), 1.97-1.89 (m, 2H), 1.80-1.70 (m, 2H), 1.55-1.39 (m, 3H); 13C NMR

(CDCl3, 125MHz), δ: 163.14, 161.20, 149.80, 145.11, 127.87, 127.32 (q,

J = 280.0Hz), 126.99, 126.30, 118.54, 48.25, 46.76 (q, J = 25.0 Hz),

43.67, 38.06, 25.48, 24.38, 22.80 (q, J = 2.5 Hz), 21.92, 21.82; 19F NMR

(CDCl3, 470MHz), δ: -66.86; IR (KBr) v: 3512, 3424, 2922, 2858, 1677,

1613, 1480, 1451, 1397, 1343, 1274, 1165, 4082, 993, 949, 796, 693 cm-1;

HRMS (EI) (m/z): calcd for C18H19F3N2O (M+): 336.1449; Found:

336.1454.

6'-Chloro-2-(trifluoromethyl)-1'H-spiro[cyclohexane-1,3'-pyrrolo[2,1

-b]quinazolin]-9'(2'H)-one (4f)

N
CF3
Cl N

4f

White solid; m.p. 127-128 oC; 1H NMR (CDCl3, 500MHz), δ: 8.23 (d, J =

8.5 Hz, 1H), 7.71 (d, J = 2.0 Hz, 1H), 7.41 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz,

1H), 4.15 (t, J = 7.0 Hz, 2H), 2.94-2.89 (m, 1H), 2.57-2.52 (m, 1H),

2.18-2.09 (m, 2H), 2.20-1.94 (m, 2H), 1.86-1.84 (m, 1H), 1.78-1.75 (m,

1H), 1.62-1.41 (m, 3H); 13C NMR (CDCl3, 100MHz), δ: 164.48, 160.63,

150.67, 140.37, 127.92, 127.28 (q, J = 280.0 Hz), 126.91, 126.87, 119.43,

48.44, 46.75 (q, J = 24.0 Hz), 43.89, 38.00, 25.43, 24.35, 22.76 (q, J =

S50
3.0 Hz), 21.78; 19F NMR (CDCl3, 376MHz), δ: -66.85; IR (KBr) v: 2947,

2863, 1682, 1604, 1455, 1397, 1254, 1156, 1067, 909, 772, 693 cm-1;

HRMS (EI) (m/z): calcd for C17H16ClF3N2O (M+): 356.0903; Found:

356.0903.

2-(Trifluoromethyl)-1'H-spiro[cycloheptane-1,3'-pyrrolo[2,1-b]quinaz

olin]-9'(2'H)-one (4g)

N
CF3
N

4g

Pale yellow solid; m.p. 89-90 oC; 1H NMR (CDCl3, 500MHz), δ: 8.28 (d,

J = 7.5 Hz, 1H), 7.72-7.70 (m, 2H), 7.43 (dt, J1 = 7.0 Hz, J2 = 2.0 Hz, 1H),

4.22 (dq, J1 = 10.8 Hz, J2 = 1.0 Hz, 1H), 4.06-4.00 (m, 1H), 3.37-3.29 (m,

1H), 2.58-2.52 (m, 1H), 2.17-2.12 (m, 1H), 2.06-1.99 (m, 3H), 1.96-1.89
13
(m, 2H), 1.74-1.67 (m, 1H), 1.64-1.56 (m, 3H), 1.42-1.35 (m, 1H); C

NMR (CDCl3, 125MHz), δ: 163.05, 161.26, 149.41, 133.96, 128.02 (q, J

= 277.8 Hz), 127.44, 126.33, 126.13, 120.92, 49.74, 48.90 (q, J = 23.8

Hz), 43.19, 40.15, 29.65, 29.32, 29.01, 23.89 (q, J = 2.5 Hz), 21.37; 19F

NMR (CDCl3, 470MHz), δ: -66.15; IR (KBr) v: 3094, 2996, 2356, 2341,

1672, 1618, 1466, 1274, 747 cm-1; HRMS (EI) (m/z): calcd for

C18H19F3N2O (M+): 336.1449; Found: 336.1452.

2,6'-Bis(trifluoromethyl)-1'H-spiro[cycloheptane-1,3'-pyrrolo[2,1-b]q

S51
uinazolin]-9'(2'H)-one (4h)

N
CF3
F3C N

4h

White solid; m.p. 119-120 oC; 1H NMR (CDCl3, 500MHz), δ: 8.39 (d, J

= 8.0 Hz, 1H), 8.01 (s, 1H), 7.64 (dd, J1 = 8.5 Hz, J2 = 1.0 Hz, 1H), 4.24

(dq, J1 = 11.3 Hz, J2 = 3.5 Hz, 1H), 4.09-4.04 (m, 1H), 3.36-3.28 (m, 1H),

2.62-2.56 (m, 1H), 2.20-2.15 (m, 1H), 2.08-2.02 (m, 3H), 1.97-1.89 (m,

2H), 1.80-1.71 (m, 1H), 1.68-1.55 (m, 3H), 1.43-1.34 (m, 1H); 13C NMR

(CDCl3, 125MHz), δ: 164.84, 160.48, 149.45, 135.70 (q, J = 32.5 Hz),

128.06 (q, J = 280.0 Hz), 127.61, 125.13 (q, J = 3.8 Hz), 123.66 (q, J =

271.3 Hz), 123.35, 122.27 (q, J = 3.8 Hz), 50.05, 49.08 (q, J = 22.5 Hz),

43.56, 40.33, 29.78, 29.44, 29.20, 23.97 (q, J = 2.5 Hz), 21.49; 19F NMR

(CDCl3, 470MHz), δ: -63.12, -66.23; IR (KBr) v: 3443, 2942, 2868, 1677,

1618, 1564, 1490, 1446, 1377, 1312, 1160, 1067, 919, 781, 688 cm-1;

HRMS (EI) (m/z): calcd for C19H18F6N2O (M+): 404.1323; Found:

404.1323.

1',3'-Dimethyl-2-(trifluoromethyl)-6',7'-dihydrospiro[cycloheptane-1,

5'-Pyrazolo[4,3-d]pyrrolo[1,2-a]pyrimidin]-9'(1'H)-one (4i)

S52
 Me O
N N
N CF3
N
Me
4i

Pale yellow solid; m.p. 133-134 oC; 1H NMR (CDCl3, 500MHz), δ: 4.21

(s, 3H), 4.14 (dq, J1 = 10.5 Hz, J2 = 4.0 Hz, 1H), 3.99-3.94 (m, 1H),

3.28-3.20 (m, 1H), 2.59-2.53 (m, 1H), 2.46 (s, 3H), 2.12-2.07 (m, 1H),

2.04-1.97 (m, 3H), 1.92-1.85 (m, 2H), 1.68-1.63 (m, 1H), 1.61-1.54 (m,

3H), 1.40-1.33 (m, 1H); 13C NMR (CDCl3, 100MHz), δ: 160.93, 153.51,

141.43, 139.46, 128.05 (q, J = 280.0 Hz), 124.85, 49.08 (q, J = 23.0 Hz),

48.83, 42.52, 40.27, 38.11, 30.06, 29.70, 29.11, 23.86 (q, J = 3.0 Hz),

21.29, 10.65; 19F NMR (CDCl3, 470MHz), δ: -66.22; IR (KBr) v: 3438,

3355, 2952, 2868, 1687, 1593, 1490, 1357, 1306, 1259, 1175, 1087, 781,

693 cm-1; HRMS (EI) (m/z): calcd for C17H21F3N4O (M+): 354.1667;

Found: 354.1667.

1-Oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H)-carboni

trile (6a)

CN
N O

F3C

6a

Pale yellow solid; m.p. 75-76 oC; 1H NMR (CDCl3, 400MHz), δ: 8.14 (dd,

S53
J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.65 (dt, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 7.50

(dt, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 4.25 (dd, J1 =

12.8 Hz, J2 = 3.6 Hz, 1H), 4.00 (dd, J1 = 12.8 Hz, J2 = 2.8 Hz, 1H), 3.45
13
(m, 1H), 2.73-2.57 (m, 1H), 2.51-2.38 (m, 1H); C NMR (CDCl3,

100MHz), δ: 162.62, 140.26, 135.21, 130.06, 129.19, 127.69, 125.77 (q, J

= 276.0 Hz), 125.18, 109.13, 51.39, 37.23 (q, J = 28.0 Hz), 32.24 (q, J =

3.0 Hz), 27.52; 19F NMR (CDCl3, 470MHz), δ: -63.82; IR (KBr) v: 3395,

2215, 1734, 1617, 1455, 1377, 1276, 1145, 1012, 943, 756cm-1; HRMS

(EI) (m/z): calcd for C12H9F3N2O (M+): 254.0667; Found: 254.0664.

6-Methyl-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H

)-carbonitrile (6b)

CN
N O

F3C

Me
6b

Pale yellow solid; m.p. 82-83 oC; 1H NMR (CDCl3, 400MHz), δ: 8.02 (d,

J = 8.0 Hz, 1H), 7.30 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.11 (s, 1H), 4.21

(dd, J1 = 12.4 Hz, J2 = 3.2 Hz, 1H), 3.98 (dd, J1 = 12.4 Hz, J2 = 2.4 Hz,
13
1H), 3.38 (m, 1H), 2.71-2.57 (m, 1H), 2.48-2.35 (m, 4H); C NMR

(CDCl3, 100MHz), δ: 162.63, 146.65, 140.34, 130.13, 130.06, 128.14,

125.81 (q, J = 276.0 Hz), 122.54, 109.29, 51.33, 37.21 (q, J = 28.0 Hz),

32.25 (q, J = 2.0 Hz), 22.01; 19F NMR (CDCl3, 470MHz), δ: -63.88; IR

S54
(KBr) v: 3464, 2231, 1711, 1617, 1455, 1393, 1323, 1253, 1168, 1075,

834, 694cm-1; HRMS (EI) (m/z): calcd for C13H11F3N2O (M+): 268.0823;

Found: 268.0820.

1-Oxo-6-phenyl-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H

)-carbonitrile (6c)

CN
N O

F3C

6c Ph

Pale yellow solid; m.p. 145-146 oC; 1H NMR (CDCl3, 400MHz), δ: 8.21

(d, J = 8.0 Hz, 1H), 7.71 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.62-7.59 (m,

2H), 7.52-7.43 (m, 4H), 4.28 (dd, J1 = 12.8 Hz, J2 = 3.6 Hz, 1H), 4.03 (dd,

J1 = 12.4 Hz, J2 = 2.4 Hz, 1H), 3.51 (m, 1H), 2.77-2.64 (m, 1H),
13
2.57-2.43 (m, 1H); C NMR (CDCl3, 100MHz), δ: 162.50, 148.18,

140.80, 138.90, 130.72, 129.34, 129.20, 127.85, 127.44, 126.18, 125.81

(q, J = 276.0 Hz), 123.75, 109.19, 51.45, 37.35 (q, J = 28.0 Hz), 32.51 (q,
19
J = 2.0 Hz); F NMR (CDCl3, 376MHz), δ: -63.73; IR (KBr) v: 3441,

2231, 1695, 1610, 1401, 1331, 1238, 1121, 1075, 772, 694cm-1; HRMS

(EI) (m/z): calcd for C18H13F3N2O (M+): 330.0980; Found: 330.0984.

6-Methoxy-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1

H)-carbonitrile (6d)

S55
 CN
N O

F3C

OMe
6d

Pale yellow solid; m.p. 80-81 oC; 1H NMR (CDCl3, 400MHz), δ: 8.09 (d,

J = 8.8 Hz, 1H), 6.97 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 6.75 (d, J = 2.4

Hz, 1H), 4.20 (dd, J1 = 12.4 Hz, J2 = 3.2 Hz, 1H), 3.96 (dd, J1 = 12.4 Hz,

J2 = 2.8 Hz, 1H), 3.90 (s, 3H), 3.39-3.34 (m, 1H), 2.72-2.58 (m, 1H),
13
2.48-2.36 (m, 1H); C NMR (CDCl3, 100MHz), δ: 164.88, 162.25,

142.66, 132.64, 125.81 (q, J = 276.0 Hz), 117.66, 114.66, 112.76, 109.43,
19
55.95, 51.30, 37.19 (q, J = 29.0 Hz), 32.60 (q, J = 3.0 Hz); F NMR

(CDCl3, 470MHz), δ: -63.82; IR (KBr) v: 3441, 2967, 2865, 2231, 1711,

1602, 1470, 1307, 1268, 1137, 1020, 966, 857, 772, 702, 617cm-1; HRMS

(EI) (m/z): calcd for C13H11F3N2O2(M+): 284.0773; Found: 284.0775.

6-Fluoro-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H)

-carbonitrile (6e)

CN
N O

F3C

6e F

Pale yellow solid; m.p. 80-81 oC; 1H NMR (CDCl3, 400MHz), δ: 8.18 (dd,

J1 = 8.4 Hz, J2 = 5.6 Hz, 1H), 7.19 (dt, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 7.04

S56
(dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 4.25 (dd, J1 = 12.8 Hz, J2 = 3.6 Hz,

1H), 3.99 (dd, J1 = 12.8 Hz, J2 = 2.4 Hz, 1H), 3.47-3.42 (m, 1H),
13
2.74-2.61 (m, 1H), 2.53-2.40 (m, 1H); C NMR (CDCl3, 100MHz), δ:

167.42, 165.04, 161.62, 143.17 (d, J = 9.0 Hz), 133.23 (d, J = 10.0 Hz),

125.54 (q, J = 276.0 Hz), 121.52 (d, J = 3.0 Hz), 116.79 (d, J = 22.0 Hz),

114.79 (d, J = 23.0 Hz), 51.25, 37.45 (q, J = 28.0 Hz), 32.24 (q, J = 2.0

Hz); 19F NMR (CDCl3, 470MHz), δ: -63.74, -100.21; IR (KBr) v: 3441,

2913, 1859, 2238, 1718, 1617, 1462, 1393, 1253, 1059, 966, 842, 772,

694cm-1; HRMS (EI) (m/z): calcd for C12H8F4N2O(M+): 272.0573; Found:

272.0577.

6-Chloro-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H)

-carbonitrile (6f)

CN
N O

F3C

6f Cl

Pale yellow solid; m.p. 67-68 oC; 1H NMR (CDCl3, 400MHz), δ: 8.09 (d,

J = 8.4 Hz, 1H), 7.48 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.33 (d, J = 2.0

Hz, 1H), 4.24 (dd, J1 = 12.8 Hz, J2 = 3.6 Hz, 1H), 4.00 (dd, J1 = 12.8 Hz,

J2 = 2.4 Hz, 1H), 3.45-3.40 (m, 1H), 2.73-2.60 (m, 1H), 2.52-2.39 (m,
13
1H); C NMR (CDCl3, 100MHz), δ: 161.73, 141.65, 131.57, 129.64,

S57
127.73, 125.50 (q, J = 276.0 Hz), 123.53, 114.66, 108.69, 51.17, 36.96 (q,
19
J = 29.0 Hz), 32.09 (q, J = 3.0 Hz); F NMR (CDCl3, 470MHz), δ:

-63.76; IR (KBr) v: 3433, 2238, 1703, 1594, 1393, 1299, 1238, 1160,

1067, 1098, 958, 842, 694cm-1; HRMS (EI) (m/z): calcd for

C12H8ClF3N2O(M+): 288.0277; Found: 288.0280.

6-Bromo-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H)

-carbonitrile (6g)

CN
N O

F3C

6g Br

Pale yellow solid; m.p. 109-110 oC; 1H NMR (CDCl3, 400MHz), δ: 7.50

(d, J = 8.4 Hz, 1H), 7.65 (dd, J1 = 8.4 Hz, J2 = 1.6 Hz, 1H), 7.50 (d, J =

2.0 Hz, 1H), 4.24 (dd, J1 = 12.8 Hz, J2 = 2.8 Hz, 1H), 4.00 (dd, J1 = 12.8

Hz, J2 = 2.8 Hz, 1H), 3.44-3.40 (m, 1H), 2.73-2.60 (m, 1H), 2.52-2.39 (m,
13
1H); C NMR (CDCl3, 100MHz), δ: 162.02, 141.78, 132.73, 131.61,

130.80, 130.45, 125.61 (q, J = 276.0 Hz), 124.07, 108.80, 51.26, 37.06 (q,
19
J = 28.0 Hz), 32.10 (q, J = 3.0 Hz); F NMR (CDCl3, 470MHz), δ:

-63.75; IR (KBr) v: 2999, 2947, 2244, 1712, 1598, 1478, 1405, 1249,

1165, 1061, 957, 915, 932, 686cm-1; HRMS (EI) (m/z): calcd for

C12H8BrF3N2O(M+): 331.9772; Found: 331.9774.

S58
1-Oxo-4-(2,2,2-trifluoroethyl)-6-(trifluoromethyl)-3,4-dihydroisoquin

oline-2(1H)-carbonitrile (6h)

CN
N O

F3C

6h CF3

Pale yellow solid; m.p. 121-122 oC; 1H NMR (CDCl3, 400MHz), δ: 8.29

(d, J = 8.0 Hz, 1H), 7.77 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.60 (s, 1H),

4.29 (dd, J1 = 12.8 Hz, J2 = 3.6 Hz, 1H), 4.05 (dd, J1 = 12.8 Hz, J2 = 2.8
13
Hz, 1H), 3.56-3.53 (m, 1H), 2.77-2.63 (m, 1H), 2.57-2.43 (m, 1H); C

NMR (CDCl3, 100MHz), δ: 161.52, 140.93, 136.49 (q, J = 33.0 Hz),

130.93, 128.24, 125.65 (q, J = 257.0 Hz), 126.10 (q, J = 4.0 Hz), 124.89

(q, J = 4.0 Hz), 122.91 (q, J = 253.0 Hz), 108.52, 51.30, 37.14 (q, J =

29.0 Hz), 32.33 (q, J = 3.0 Hz); 19F NMR (CDCl3, 470MHz), δ: -63.42,

-63.69; IR (KBr) v: 2961, 2254, 1706, 1258, 1500, 1464, 1417, 1329,

1257, 1009, 947, 699cm-1; HRMS (EI) (m/z): calcd for C13H8F6N2O(M+):

322.0541; Found: 322.0540.

Methyl-2-cyano-1-oxo-4-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoqu

inoline-6-carboxylate (6i)

S59
Pale yellow solid; m.p. 132-133 oC; 1H NMR (CDCl3, 400MHz), δ: 8.22

(d, J = 8.4 Hz, 1H), 8.13 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.99 (s, 1H),

4.26 (dd, J1 = 12.8 Hz, J2 = 3.6 Hz, 1H), 4.04 (dd, J1 = 12.8 Hz, J2 = 2.8

Hz, 1H), 3.97 (s, 3H), 3.55-3.51 (m, 1H), 2.71-2.60 (m, 1H), 2.55-2.45

(m, 1H); 13C NMR (CDCl3, 100MHz), δ: 165.38, 161.92, 140.33, 135.91,

130.38, 129.93, 128.79, 128.58, 125.64 (q, J = 275.0 Hz), 108.70, 53.03,

51.28, 37.07 (q, J = 28.0 Hz), 32.27 (q, J = 3.0 Hz); 19F NMR (CDCl3,

470MHz), δ: -63.71; IR (KBr) v: 3425, 2262, 1726, 1447, 1393, 1331,

1121, 1012, 943, 826, 741, 601cm-1; HRMS (EI) (m/z): calcd for

C14H11F3N2O3(M+): 312.0722; Found: 312.0724.

8-Methyl-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H

)-carbonitrile (6j)

CN
N O

F3C Me

6j

Yellow solid; m.p. 82-83 oC; 1H NMR (CDCl3, 400MHz), δ: 7.48 (t, J =

7.6 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.14 (d, J = 7.6 Hz, 1H), 4.17 (dd,

S60
J1 = 12.4 Hz, J2 = 3.2 Hz, 1H), 3.94 (dd, J1 = 12.4 Hz, J2 = 2.0 Hz, 1H),
13
3.41-3.36 (m, 1H), 2.70-2.58 (m, 4H), 2.46-2.38 (m, 1H); C NMR

(CDCl3, 100MHz), δ: 162.66, 143.94, 141.46, 134.17, 132.82, 125.82 (q,

J = 276.0 Hz), 125.74, 123.41, 109.44, 50.84, 37.15 (q, J = 28.0 Hz),

33.32 (q, J = 3.0 Hz), 22.61; 19F NMR (CDCl3, 470MHz), δ: -63.88; IR

(KBr) v: 3433, 2991, 2937, 2254, 1703, 1602, 1462, 1401, 1323, 1245,

1160, 958, 780, 671cm-1; HRMS (EI) (m/z): calcd for C13H11F3N2O(M+):

268.0823; Found: 268.0819.

5,6,7-Trimethoxy-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoli

ne-2(1H)-carbonitrile (6k)

CN
N O

F3C

MeO OMe
OMe
6k

Pale yellow solid; m.p. 146-147 oC; 1H NMR (CDCl3, 400MHz), δ: 7.39(s,

1H), 4.13 (dd, J1 = 12.8 Hz, J2 = 3.2 Hz, 1H), 4.02 (dd, J1 = 12.8 Hz, J2 =

3.2 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.90 (s, 3H), 3.63 (d, J = 10.4 Hz

1H), 2.62-2.48 (m, 1H), 2.31-2.18 (m, 1H); 13C NMR (CDCl3, 100MHz),

δ: 162.48, 154.03, 149.20, 147.50, 127.39, 125.87 (q, J = 276.0 Hz),

120.15, 109.39, 107.48, 61.40, 61.14, 56.42, 41.00, 35.74 (q, J = 29.0 Hz),

26.38 (q, J = 3.0 Hz); 19F NMR (CDCl3, 470MHz), δ: -64.37; IR (KBr) v:

3472, 2937, 284, 2246, 1695, 1594, 1470, 108, 1261, 1129, 1036, 935,

S61
747cm-1; HRMS (EI) (m/z): calcd for C15H15F3N2O4(M+): 344.0984;

Found: 344.0988.

5-Oxo-8-(2,2,2-trifluoroethyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]isoquino

line-6(5H)-carbonitrile

6-Oxo-9-(2,2,2-trifluoroethyl)-8,9-dihydro-[1,3]dioxolo[4,5-f]isoquinol

ine-7(6H)-carbonitrile (6l)

CN CN
N O N O

F3C F3C

O O
O O
6l

Pale yellow solid; m.p. 124-125 oC; IR (KBr) v: 3456, 2913,, 2238, 1703,

1602, 1478, 1385, 1253, 1129, 1036, 935cm-1; HRMS (EI) (m/z): calcd

for C13H9F3N2O3(M+): 298.0565; Found: 298.0565.

5-Methyl-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydro-1H-pyrido[4,3-b]i

ndole-2(5H)-carbonitrile (6m)

Pale yellow solid; m.p. 78-79 oC; 1H NMR (CDCl3, 400MHz), δ:

8.12-8.10 (m, 1H), 7.41-7.31 (m, 3H), 4.27 (dd, J1 = 12.8 Hz, J2 = 3.6 Hz,

S62
1H), 4.04 (dd, J1 = 12.8 Hz, J2 = 1.2 Hz, 1H), 3.79 (s, 3H), 3.58-3.56 (m,

1H), 2.84-2.70 (m, 1H), 2.43-2.30 (m, 1H); 13C NMR (CDCl3, 100MHz),

δ: 160.05, 145.57, 141.95, 137.80, 125.64 (q, J = 276.0 Hz), 124.70,

124.60, 123.75, 121.38, 110.22, 103.52, 52.16, 35.00 (q, J = 29.0 Hz),

30.37, 26.75 (q, J = 2.0 Hz); 19F NMR (CDCl3, 470MHz), δ: -64.50; IR

(KBr) v: 3472, 2929, 2851, 2246, 1680, 1625, 1447, 1276, 1137, 1075,

974, 865, 624cm-1; HRMS (EI) (m/z): calcd for C15H12F3N3O(M+):

307.0932; Found: 307.0929.

4-Methyl-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2(1H

)-carbonitrile (6n)

Pale yellow solid; m.p. 95-96 oC; 1H NMR (CDCl3, 400MHz), δ: 8.16 (dd,

J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.67 (dt, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H), 7.49

(dt, J1 = 7.6 Hz, J2 = 0.8 Hz, 1H), 7.41 (d, 1H), 3.95-3.88 (m, 2H),

2.63-2.42 (m, 2H), 1.63 (s, 3H); 13C NMR (CDCl3, 100MHz), δ: 162.75,

144.63, 135.23, 130.32, 128.78, 125.61 (q, J = 277.0 Hz), 125.00, 124.58,
19
56.43, 41.76 (q, J = 27.0 Hz), 35.35, 22.58 (q, J = 1.0 Hz); F NMR

(CDCl3, 470MHz), δ: -59.96; IR (KBr) v: 3449, 2937, 2246, 1711, 1610,

1476, 1393, 1323, 1230, 1145, 1059, 756. 694cm-1; HRMS (EI) (m/z):

S63
calcd for C13H11F3N2O(M+): 268.0823; Found: 268.0820.

4-Methyl-1-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-2,6(1

H)-dicarbonitrile (6o)

CN
N O

F3C
Me

CN
6o

White solid; m.p. 104-105 oC; 1H NMR (CDCl3, 400MHz), δ: 8.28 (d, J =

8.0 Hz, 1H), 7.79 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.72 (s, 1H), 3.96 (s,
13
2H), 2.63-2.51 (m, 2H), 1.67 (s, 3H); C NMR (CDCl3, 100MHz), δ:

161.32, 145.28, 132.16, 131.02, 129.30, 128.14, 125.33 (q, J = 277.0 Hz),

118.54, 117.24, 108.07, 56.40, 41.69 (q, J = 28.0 Hz), 35.58, 22.56; 19F

NMR (CDCl3, 470MHz), δ: -59.83; IR (KBr) v: 3449, 2929, 2254, 1726,

1602, 1478, 1369, 1331, 1253, 1121, 1067, 879, 857, 733cm-1; HRMS (EI)

(m/z): calcd for C14H10F3N3O(M+): 293.0776; Found: 293.0779.

1'-Oxo-2-(trifluoromethyl)-1'H-spiro[cyclopentane-1,4'-isoquinoline]-

2'(3'H)-carbonitrile (6p)

CN
F3C N O

6p

S64
Pale yellow solid; m.p. 73-74 oC; 1H NMR (CDCl3, 400MHz), δ: 8.17 (dd,

J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.66 (dt, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H),

7.47(dt, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 4.12 (d, J

= 12.8 Hz, 1H), 3.85 (d, J = 12.8 Hz, 1H), 3.15-3.04 (m, 1H), 2.31-2.25
13
(m, 1H), 2.20-1.92 (m, 5H); C NMR (CDCl3, 100MHz), δ: 162.86,

144.17, 135.01, 130.31, 128.40, 126.96 (q, J = 278.0 Hz), 125.38, 123.93,

109.19, 52.30 (q, J = 2.0 Hz), 49.75 (q, J = 27.0 Hz), 46.96, 38.61, 24.99,
19
21.72; F NMR (CDCl3, 470MHz), δ: -64.46; IR (KBr) v: 3464, 2944,

2246, 1711, 1602, 1462, 1401, 1261, 1121, 756, 687cm-1; HRMS (EI)

(m/z): calcd for C15H13F3N2O(M+): 294.0980; Found: 294.0981.

7. Kinetic Isotope Effect (KIE) Study:

Deuterated benzoic acid was synthesized following literature report, and

[D5]-1aa and [D5]-5a was prepared following the typical procedure of

1aa. [D4]-3aa and [D4]-6a was prepared following the typical procedure

of 3aa.

S65
 D O
D
N
CN
D D
D [D5]-1aa

D O
D
N
CN
D D
D [D5]-1aa

S66
 D O
D
N

D N CF3
D Me
[D]4-3aa

D O
D
N

D N CF3
D Me
[D]4-3aa

S67
 D O
D
N

D N CF3
D Me
[D]4-3aa

S68
 CN
N O

F3C D

D D
D
[D]4-6a

S69
 CN
N O

F3C D

D D
D
[D]4-6a

CN
N O

F3C D

D D
D
[D]4-6a

S70
 A schlenk reaction tube containing copper(I) oxide (2.9 mg, 20 mol %),

2,2'-bipyridine (5.6 mg, 40 mol %), and Togni’s reagent 2 (63 mg, 0.2

mmol) were evacuated and purged with Argon three times. Afterwards,

a CH3CN (1 mL) solution of N-cyano-N-(3-methylbut-3-en-

1-yl)benzamide 1aa (21 mg, 0.1 mmol) was added via syringe. The

solution was kept at 80 oC for 40 min. At the same time, another

schlenk reaction tube containing copper(I) oxide (2.9 mg, 20 mol %),

2,2'-bipyridine (5.6 mg, 40 mol %), and Togni’s reagent 2 (63 mg, 0.2

mmol) were evacuated and purged with Argon three times. Afterwards,

a CH3CN (1 mL) solution of N-cyano-N-(3-methylbut-3-en-

1-yl)benzamide [D]5-1aa (22 mg, 0.1 mmol) was added via syringe. The

solution was kept at 80 oC for 40 min. Then the two solutions were mixed

and then diluted with CH2Cl2 and transferred to a round bottom flask.

Silica was added to the flask and volatiles were evaporated under vacuum.

The purification was performed by flash column chromatography on

silica gel using ethyl acetate/petroleum ether (v/v, 1:5) as eluent to give

[D]4-3aa/3aa as a Pale yellow solid (13mg, 22% yield).

S71
 CN
O
N O
N Standard conditions
F3C
CN 90 min
H5/D5 H4/D4
KIE = 1.13
[D]5-5a/5a [D]4-6a/6a
(parallel experiments)

A schlenk reaction tube containing copper(I) oxide (2.9 mg, 20 mol %),

2,2'-bipyridine (5.6 mg, 40 mol %), and Togni’s reagent 2 (63 mg, 0.2

mmol) were evacuated and purged with Argon three times. Afterwards,

a CH3CN (1 mL) solution of N-allyl-N-cyanobenzamide 5a (18.6 mg, 0.1

mmol) was added via syringe. The solution was kept at 80 oC for 90 min.

At the same time, another schlenk reaction tube containing copper(I)

oxide (2.9 mg, 20 mol %), 2,2'-bipyridine (5.6 mg, 40 mol %), and

S72
Togni’s reagent 2 (63 mg, 0.2 mmol) were evacuated and purged with

Argon three times. Afterwards, a CH3CN (1 mL) solution of

N-allyl-N-cyanobenzamide [D]5-5a (19 mg, 0.1 mmol) was added via

syringe. The solution was kept at 80 oC for 90 min. Then the two

solutions were mixed and then diluted with CH2Cl2 and transferred to a

round bottom flask. Silica was added to the flask and volatiles were

evaporated under vacuum. The purification was performed by flash

column chromatography on silica gel using ethyl acetate/petroleum ether

(v/v, 1:5) as eluent to give [D]4-6a/6a as a Pale yellow solid (16mg, 30%

yield).

CN
N O

F3C
H4/D4

[D]4-6a/6a

S73
8. Radical Scavenger Test:

A schlenk reaction tube containing copper(I) oxide (2.9 mg, 20 mol %),

2,2'-bipyridine (5.6 mg, 40 mol %), and Togni’s reagent 2 (63 mg, 0.2

mmol), TEMPO (48 mg, 0.3 mmol) were evacuated and purged with

Argon three times. Afterwards, a CH3CN (1 mL) solution of

N-cyano-N-(3-methylbut-3-en- 1-yl)benzamide 1aa (21 mg, 0.1 mmol)

was added via syringe. The solution was kept at 80 oC for 10 h. The

conversion was very low (< 10%).

Replacing TEMPO with BHT gave the same result.

A schlenk reaction tube containing copper(I) oxide (2.9 mg, 20 mol %),

2,2'-bipyridine (5.6 mg, 40 mol %), and Togni’s reagent 2 (63 mg, 0.2

mmol), TEMPO (48 mg, 0.3 mmol) were evacuated and purged with

Argon three times. Afterwards, a CH3CN (1 mL) solution of

N-allyl-N-cyanobenzamide 5a (18.6 mg, 0.1 mmol) was added via

syringe. The solution was kept at 80 oC for 10 h. The conversion was very

low (< 10%). Replacing TEMPO with BHT gave the same result.

S74
9. Reference:
(1) (a) Michael, F. E.; Cochran, B. M. J. Am. Chem. Soc. 2006, 128,

4246. (b) Muñiz, K.; Hövelmann, C. H.; Streuff, J. J. Am. Chem. Soc.

2008, 130, 763.

(2) Marson, C. M.; Grabowska, U.; Fallah, A. J. Org. Chem. 1994, 59,

291.

S75
S76
O

N
CN
1ab

N
CN
1ab

S77
 O

N
CN
H3C
1ba

N
CN
H3C
1ba

S78
 O

N
CN
H3C
1bb

N
CN
H3C
1bb

S79
 O

N
CN
H3CO
1ca

N
CN
H3CO
1ca

S80
 O

N
CN
H3CO
1cb

N
CN
H3CO
1cb

S81
 O

N
CN
NC
1da

N
CN
NC
1da

S82
S83
S84
 O

N
CN
F3C
1eb

S85
 O

N
CN
F3C
1eb

N
CN
F3C
1eb

S86
 O

N
CN
F
1fa

N
CN
F
1fa

S87
 O

N
CN
F
1fa

S88
 O

N
CN
Cl
1gb

S89
 O

N
CN
Cl
1gb

S90
 O

N
CN
O2N
1hb

S91
 O

N
CN
O2N
1hb

CH3 O

N
CN
1ia

S92
CH3 O

N
CN
1ia

S93
S94
 O

N
CN
N
1kb

S95
 O

N
CN
N
1kb

S96
 CN
N
S
O
1ma

S97
 CN
N
S
O
1ma

N
CN
1na

S98
O

N
CN
1na

S99
O

N
CN
1pa

S100
 O

N
CN
1pa

N
H3CO CN

1qa

S101
 O

N
H3CO CN

1qa

S102
O

N
CN
1sa

S103
O

N
CN
1sa

S104
S105
S106
S107
S108
 O
N
N N
CN
1xa

O
N
N N
CN
1xa

S109
 O

N
CN
5a

N
CN
5a

S110
S111
 O

N
CN
Ph
5c

N
CN
Ph
5c

S112
 O

N
CN
MeO
5d

N
CN
MeO
5d

S113
S114
S115
 O

N
CN
Br
5g

S116
 O

N
CN
Br
5g

N
CN
F3C 5h

S117
 O

N
CN
F3C 5h

N
CN
F3C 5h

S118
 O

N
CN
MeOOC
5i

N
CN
MeOOC
5i

S119
S120
S121
 O
O N
O CN
5l

O
O N
O CN
5l

S122
 O

N
CN
N
5m

N
CN
N
5m

S123
O

N
CN

5n

N
CN

5n

S124
 O

N
CN
NC
5o

N
CN
NC
5o

S125
O

N
CN

5p

N
CN

5p

S126
O

N CF3
Me
3aa

N CF3
Me
3aa

S127
O

N CF3
Me
3aa

N
CF3
3ab

S128
O

N
CF3
3ab

N
CF3
3ab

S129
 O

Me N CF3
Me
3ba

Me N CF3
Me
3ba

S130
 O

Me N CF3
Me
3ba

S131
S132
S133
S134
S135
 O

NC N CF3
Me
3da

NC N CF3
Me
3da

S136
 O

NC N CF3
Me
3da

S137
S138
S139
 O

F3C N
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S140
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S141
S142
S143
S144
S145
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N CF3
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S149
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S150
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S152
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S153
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S154
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S155
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S156
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S158
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S159
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S160
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S161
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S162
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S164
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S165
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S169
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S170
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S171
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S175
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S176
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S178
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S179
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S181
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S183
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S184
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S186
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S187
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S189
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S191
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S195
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S196
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S197
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S198