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Page 1: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

Supporting Information

Diastereoselective synthesis of CF3-oxazinoquinolines in waterVasiliy M. Muzalevskiya, Kseniya V. Belyaevab, Boris A. Trofimov*b, Valentine G. Nenajdenko*a

a M. V. Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory 1, Moscow, 119991 Russian Federation

bA. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., Irkutsk, 664033

Russian Federation; Fax: (395-2)41-93-46

Table of contents

General remarks S2

Reaction of CF3-ynones and quinolines in water (general procedure) S2

Characterization data of CF3-oxazinoquinolines 3 S2-S8

Epimerization of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a) S8

(3R*,4aR*)-3-Ethoxy-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinoline (4) S8

Reaction of oxazine (3a) with methyl 2-mercaptoacetate S9

Transformation of oxazine (3a) into 2-phenylquinoline (6) S9

Transformation of oxazine (3a) into 2,2,2-trifluoro-1-(2-phenylquinolin-3-yl)ethanone (7) S10

Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a) to form 8 and 9

S11

Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a)

to form 11 S11

Copies of all NMR spectra S13-S83

S1

Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2019

Page 2: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

General remarks. 1H, 13C and 19F NMR spectra were recorded on Bruker AVANCE 400 MHz spectrometer

in CD3CN and CDCl3 at 400, 100 and 376 MHz respectively. Chemical shifts (δ) in ppm are reported with

the use of the residual CHD2CN and chloroform signals (1.94 and 7.25 for 1H and 77.0 for 13C) as internal

reference. The 19F chemical shifts were referenced to C6F6, (-162.9 ppm). HRMS (ESI-TOF) spectra were

measured with an Orbitrap Elite instrument. TLC analysis was performed on “Merck 60 F254” plates. All

reagents were of reagent grade and were used as such or distilled prior to use. CF3-ynones 2 were prepared as

reported previously1. Melting points were determined on an Electrothermal 9100 apparatus. The NMR and

m.p. data of compounds 3 (with the exception of 3i,j,k,n, which is a new compound) are in agreement with

those in the literature2.

Reaction of CF3-ynones and quinolines in water (general procedure): A 4 mL vial with a screw cap was

charged with water (0.5 mL), quinoline 1 (0.475 mmol, 0.95 equiv.) and then CF3-ynone 2 (0.5 mmol, 1

equiv.) was added at vigorous stirring. The reaction mixture was stirred at room temperature for 1-2 h (TLC

or 19F NMR control; 24 h for quinoline 1c and for ketone 2i). Excess water was decanted; the residue was

dissolved in ethyl acetate (0.5 mL) and dried over Na2SO4 (directly in the reaction vial). The solution was

transferred into a round bottomed flask and the product crystallized by addition of appropriate amount of

heptane (2-3 mL). The mother liquor was decanted, the crude product was dried under reduced pressure to

give pure (3R*,4aR*)-isomer of 3.

(3R*,4aR*)-1-Phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]-quinolin-3-ol (3a). Obtained from

quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5 mmol). White

powder, m.p. 154-156 C (heptane), yield 0.153 g (93%). For multi gram scale

reaction (60 equivalents of water): compound 3a was obtained from quinoline 1a

(0.613 g, 4.75 mmol), water (5 mL) and acetylene 2a (0.995 g, 5 mmol). Ethyl acetate

(2.5 mL) and heptane (8 mL) were used for isolation of 3a. White powder, m.p. 154-

156 C (heptane), yield 1.480 g (90%). Calculation of E-factor for multi gram scale reaction (60 equiv.):

E=[m(EtOAc)+m(heptane)+m(water)+m(Na2SO4)+m(1a)+m(2a)]/m(3a)=(2.25+5.44+5+0.30+0.613+0.995)/

1.480=9.86. For multi gram scale reaction (3 equivalents of water): compound 3a was obtained from

quinoline 1a (1.612 g, 12.5 mmol), water (0.675 mL) and acetylene 2a (2.612 g, 13.1 mmol). Ethyl acetate (6

mL) and heptane (20 mL) were used for first crystallization. For purification of material obtained from the

mother liquor ethyl acetate (2.5 mL) and heptane (8 mL) were used. White powder, m.p. 154-156 C

(heptane), yield 3.878 g (90%). Calculation of E-factor for multi gram scale reaction (3 equiv.):

1 V. M. Muzalevskiy, A. Yu. Rulev, A. R. Romanov, E. V. Kondrashov, I. A. Ushakov, V. A. Chertkov and V. G. Nenajdenko, J. Org. Chem., 2017, 82, 7200.2 B. A. Trofimov, K. V. Belyaeva, L. P. Nikitina, A. V. Afonin, A. V. Vashchenko, V. M. Muzalevskiy and V. G. Nenajdenko, Chem. Commun., 2018, 54, 2268.

S2

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

io

p

m

4aH

Page 3: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

E=[m(EtOAc)+m(heptane)+m(water)+m(Na2SO4)+m(1a)+m(2a)]/m(3a)=(7.667+19.152+0.675+0.70+1.613

+2.612)/3.878=8.36. Calculation of E-factor (approximate value) for the reaction in MeCN2:

E=[m(MeCN)+m(water)+m(1a)+m(2a)+m(Sicagel)+m(eluents)]/m(3a)=(2.37+0.009+0.061+0.099+25.0+26

6…399 (~200-300 mL of eluents was used))/0.148=1983…2867~ 2000-3000.1H NMR (400.13 MHz, CD3CN): δ 7.56-7.54 (m, 2H, Ho from Ph), 7.47-7.39 (m, 3H, Hm,p from Ph), 7.25

(dd, 3J = 7.1 Hz, 4J = 1.9 Hz, 1H, H-7), 7.01 (d, 3J5,6 = 9.8 Hz, 1H, H-6), 6.90 (td, 3J = 7.4 Hz, 4J = 1.8 Hz,

1H, H-9), 6.85 (td, 3J = 7.3 Hz, 4J = 1.2 Hz, 1H, H-8), 6.31 (d, 3J = 7.8 Hz, 1H, H-10), 6.12 (dd, 3J5,6 = 9.8

Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.03 (s, 1H, H-2), 5.66 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.55 (s, 1H, OH) ppm.19F NMR (376.50 MHz, CD3CN): δ -82.0 (CF3) ppm. 1H NMR (400.13 MHz, CDCl3): δ 7.54-7.52 (m, 2H, Ho from Ph), 7.43-7.35 (m, 3H, Hm,p from Ph), 7.18 (dd, 3J = 7.2 Hz, 4J = 0.8 Hz, 1H, H-7), 6.95 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.90 (td, 3J = 7.7 Hz, 4J = 1.1 Hz, 1H, H-

9), 6.84 (t, 3J = 7.2 Hz, 1H, H-8), 6.33 (d, 3J = 8.1 Hz, 1H, H-10), 6.04 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8 Hz, 1H,

H-5), 5.97 (s, 1H, H-2), 5.68 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 3.19 (s, 1H, OH) ppm.

(3R*,4aR*)-1-(4-Methylphenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3b)

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2b (0.106 g, 0.5

mmol). Light-brown powder, m.p. 132-134 C (heptane), RF(CH2Cl2-MeOH

100:1) = 0.27, yield 0.163 g (96%).1H NMR (400.1 MHz, CD3CN): δ 7.43 (d, 3J = 8.1 Hz, 2H, H-2’,6’), 7.24 (dd, 3J =

7.1 Hz, 4J = 1.6 Hz, 1H, H-7), 7.22 (d, 3J = 8.1 Hz, 2H, H-3’,5’), 6.99 (d, 3J5,6 = 9.7

Hz, 1H, H-6), 6.91-6.83 (m, 2H, H-9, H-8), 6.33 (d, 3J = 8.0 Hz, 1H, H-10), 6.11 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 =

4.8 Hz, 1H, H-5), 5.97 (s, 1H, H-2), 5.63 (d, 3J = 4.7 Hz, 1H, H-4a), 5.54 (br s, 1H, OH), 2.35 (s, 3H, Me)

ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.

(3R*,4aR*)-1-(3,4-Dimethylphenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3c).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2c (0.113 g, 0.5

mmol). Light-brown powder, m.p. 95-97 C (heptane), RF(CH2Cl2-MeOH 100:1) =

0.30, yield 0.169 g (95%).1H NMR (400.1 MHz, CD3CN): δ 7.34 (s, 1H, H-2’), 7.24-7.22 (m, 2H, H-7, H-

6’), 7.16 (d, 3J = 7.8 Hz, 1H, H-5’), 6.99 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.92-6.83 (m,

2H, H-9, H-8), 6.34 (d, 3J = 7.9 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.5 Hz, 3J4a,5 = 4.6 Hz, 1H, H-5), 5.93 (s, 1H,

H-2), 5.61 (d, 3J4a,5 = 4.5 Hz, 1H, H-4a), 5.47 (br s, 1H, OH), 2.27 (s, 3H, Me), 2.24 (s, 3H, Me) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.

S3

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4a

Me

1'2'3'

4' 5'6'

H

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4a

Me

1'2'3'

4' 5'6'

H

Me

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(3R*,4aR*)-1-(4-(tert-Butyl)phenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3d).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2d (0.127 g, 0.5

mmol). Light-brown powder, m.p. 104-106 C (heptane), RF(CH2Cl2-MeOH

100:1) = 0.27, yield 0.182 g (96%). 1H NMR (400.1 MHz, CD3CN): δ 7.42-7.48

(m, 4H, H-2’,3’,5’,6’), 7.24 (dd, 3J = 7.2 Hz, 4J = 1.6 Hz, 1H, H-7), 7.00 (d, 3J5,6 =

9.7 Hz, 1H, H-6), 6.90-6.83 (m, 2H, H-9, H-8), 6.32 (d, 3J = 7.8 Hz, 1H, H-10),

6.10 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 5.98 (s, 1H, H-2), 5.63 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.51

(s, 1H, OH), 1.31 (s, 9H, 3Me from t-Bu) ppm.19F NMR (376.3 Hz, CD3CN): δ -82.0 (CF3) ppm.

(3R*,4aR*)-1-(4-Methoxyphenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3e).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2e (0.114 g, 0.5

mmol). Light-brown powder, m.p. 95-97 C (heptane), RF(CH2Cl2-MeOH 100:1)

= 0.43, yield 0.176 g (99%).1H NMR (400.1 MHz, CD3CN): δ 7.46 (d, 3J = 8.9 Hz, 2H, H-2’,6’), 7.24 (dd, 3J =

7.3 Hz, 4J = 1.5 Hz, 1H, H-7), 7.00 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.93 (d, 3J = 8.9

Hz, 2H, H-3’,5’), 6.90-6.83 (m, 2H, H-9, H-8), 6.35 (d, 3J = 8.0 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.8 Hz, 3J4a,5

= 4.9 Hz, 1H, H-5), 5.92 (s, 1H, H-2), 5.63 (d, 3J4a,5 = 4.7 Hz, 1H, H-4a), 5.58 (br s, 1H, OH), 3.79 (s, 3H,

OMe) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.

(3R*,4aR*)-1-[4-(Methylthio)phenyl]-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3f).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2f (0.122 g, 0.5

mmol). Light-brown powder, m.p. 98-100 C (heptane), RF(CH2Cl2-MeOH 100:1)

= 0.20, yield 0.178 g (96%).1H NMR (400.1 MHz, CD3CN): δ 7.45 (d, 3J = 8.4 Hz, 2H, H-2’,6’), 7.26-7.21 (m,

3H, H-7, H-3’,5’), 6.99 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.94-6.84 (m, 2H, H-9, H-8),

6.33 (d, 3J = 8.1 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.6 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 5.98 (s, 1H, H-2), 5.61 (d, 3J4a,5 = 4.3 Hz, 1H, H-4a), 5.54 (br s, 1H, OH), 2.47 (s, 3H, MeS) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.

(3R*,4aR*)-1-(4-Chlorophenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3g).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2g (0.116 g, 0.5

mmol). Light-brown powder, m.p. 91-93 C (heptane), RF(CH2Cl2-MeOH 100:1) =

0.70, yield 0.159 g (88%).

S4

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

t-Bu

1'2'3'

4' 5'6'

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

O

1'2'3'

4' 5'6'

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

Cl

1'2'3'

4' 5'6'

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

S

1'2'3'

4' 5'6'

Page 5: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

1H NMR (400.1 MHz, CD3CN): δ 7.53 (d, 3J = 8.7 Hz, 2H, H-2’,6’), 7.42 (d, 3J = 8.7 Hz, 2H, H-3’,5’), 7.25

(dd, 3J = 7.4 Hz, 4J = 1.4 Hz, 1H, H-7), 6.99 (d, 3J5,6 = 9.8 Hz, 1H, H-6), 6.95-6.85 (m, 2H, H-9, H-8), 6.27

(d, 3J = 8.0 Hz, 1H, H-10), 6.11 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.03 (s, 1H, H-2), 5.62 (d, 3J =

4.8 Hz, 1H, H-4a), 5.55 (br s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.

(3R*,4aR*)-1-(4-Bromophenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3h).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2h (0.138 g, 0.5

mmol). Light-brown powder, m.p. 128-130 C (heptane), RF(CH2Cl2-MeOH 100:1)

= 0.73, yield 0.192 g (95%).1H NMR (400.1 MHz, CD3CN): δ 7.57 (d, 3J = 8.6 Hz, 2H, H-3’,5’), 7.45 (d, 3J =

8.6 Hz, 2H, H-2’,6’), 7.25 (dd, 3J = 7.3 Hz, 4J = 1.2 Hz, 1H, H-7), 7.00 (d, 3J5,6 =

9.7 Hz, 1H, H-6), 6.95-6.85 (m, 2H, H-9, H-8), 6.27 (d, 3J = 8.0 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.7 Hz, 3J4a,5

= 4.8 Hz, 1H, H-5), 6.04 (s, 1H, H-2), 5.61 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.56 (s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -81.9 (CF3) ppm.

(3R*,4aR*)-1-(2-Chlorophenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3i).

Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2i (0.116 g, 0.5

mmol). Light-brown powder, m.p. 100-102 C (heptane), yield 0.165 g (91%).1H NMR (400.1 MHz, CD3CN): δ 7.54-7.49 (m, 2H), 7.41 (td, 3J = 7.7 Hz, 4J = 1.8

Hz, 1H), 7.35 (td, 3J = 7.4 Hz, 4J = 1.4 Hz, 1H), 7.23 (dd, 3J = 7.4 Hz, 4J = 1.2 Hz,

1H, H-7), 6.97 (d, 3J5,6 = 9.8 Hz, 1H, H-6), 6.94-6.90 (m, 1H, H-9), 6.86-6.81 (m, 1H,

H-8), 6.36 (d, 3J = 8.1 Hz, 1H, H-10), 6.09 (dd, 3J5,6 = 9.8 Hz, 3J4a,5 = 4.6 Hz, 1H, H-5), 5.94 (s, 1H, H-2),

5.71 (d, 3J = 4.3 Hz, 1H, H-4a), 5.53 (br s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -81.8 (CF3) ppm.13C NMR (100.6 Hz, CD3CN): δ 145.0 (C-1), 137.4, 134.4, 133.0, 131.79, 131.77, 131.5, 130.2, 129.9,

129.1, 128.6, 123.6 (q, 1JCF = 285.3 Hz, CF3), 122.1, 121.9, 121.6, 119.1, 116.4, 116.0, 92.7 (q, 2JCF = 32.8

Hz, C-3), 78.8 (C-4a) ppm.

HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C19H12ClF3NO+: 362.0554; found: 362.0554; m/z [M+H]+ Calcd

for C19H14ClF3NO2+: 380.066; found: 380.0658.

(3R*,4aR*)-1-(2,3-Dihydrobenzo[b][1,4]dioxin-7-yl)-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-

a]quinolin-3-ol (3j). Obtained from quinoline 1a (0.061 g, 0.475 mmol) and

acetylene 2j (0.114 g, 0.5 mmol). Yellow-brown powder, m.p. 114-116 C

(heptane), yield 0.190 g (99%).

S5

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

Br

1'2'3'

4'5'

6'

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

1'6'5'

4'3'

2' Cl

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

4aH

1'2'3'

4' 5'6'

O

O

Page 6: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

1H NMR (400.1 MHz, CD3CN): δ 7.24 (dd, 3J = 7.5 Hz, 4J = 1.5 Hz, 1H, H-7), 7.03-6.92 (m, 4H, H-6, H-9,

H-5’,6’), 6.88-6.84 (m, 2H, H-8, H-2’), 6.36 (d, 3J = 8.2 Hz, 1H, H-10), 6.08 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8

Hz, 1H, H-5), 5.89 (s, 1H, H-2), 5.58 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.34 (br s, 1H, OH), 4.27-4.21 (m, 4H,

OCH2CH2O) ppm.13C NMR (100.6 Hz, CD3CN): δ 148.0, 146.2, 144.9 (C-1), 138.3, 130.4, 129.5, 128.8, 128.7, 123.5 (q, 1JCF

= 285.5 Hz, CF3), 122.5, 121.4, 120.3, 119.2, 118.6, 118.0, 116.0, 111.2, 93.0 (q, 2JCF = 32.8 Hz, C-3), 78.3

(C-4a), 65.3 (CH2), 65.0 (CH2) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.2 (CF3) ppm.

HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C21H15F3NO3+: 386.0999; found: 386.0999; m/z [M+H]+ Calcd

for C21H17F3NO4+: 404.1104; found: 404.1108.

(3R*,4aR*)-9-Chloro-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3k).

Obtained from quinoline 1b (0.078 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5

mmol). Pale yellow powder, m.p. 146-148 oC (heptane), yield 0.169 g (94%). 1H

NMR (400.13 MHz, CD3CN): δ 7.59-7.54 (m, 2H, Ho from Ph), 7.49-7.41 (m, 3H,

Hm,p from Ph), 7.22 (d, 3J7,8 = 8.1 Hz, 1H, H-7), 6.99 (d, 3J5,6 = 9.8 Hz, 1H, H-6),

6.85 (dd, 3J7,8 = 8.1 Hz, 4J8,10 = 1.9 Hz, 1H, H-8), 6.28 (d, 4J8,10 = 1.5 Hz, 1H, H-

10), 6.13 (dd, 3J5,6 = 9.8 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.07 (s, 1H, H-2), 5.67 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a),

5.49 (s, 1H, OH) ppm.13C NMR (100.6 Hz, CD3CN): δ 148.0 (C-1), 139.2, 135.0, 134.2, 131.1, 130.2, 130.1, 129.5, 127.3, 123.5

(q, 1JCF = 285.1 Hz, CF3), 121.4, 121.3, 119.7, 117.6, 113.3, 93.0 (q, 2JCF = 33.0 Hz, C-3), 78.2 (C-4a) ppm.19F NMR (376.50 MHz, CD3CN): δ -82.0 (CF3) ppm.

HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C19H12ClF3NO+: 362.0554; found: 362.0555; m/z [M+H]+ Calcd

for C19H14ClF3NO2+: 380.066; found: 380.0655.

(3R*,4aR*)-8-Chloro-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3l).

Obtained from quinoline 1c (0.078 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5

mmol). White powder, m.p. 138-140 oC (heptane), yield 0.175 g (97%). 1H NMR

(400.13 MHz, CDCl3): δ 7.53-7.50 (m, 2H, Ho from Ph), 7.44-7.36 (m, 3H, Hm,p

from Ph), 7.16 (d, 4J7,9 = 2.4 Hz, 1H, H-7), 6.86 (d, 3J5,6 = 8.9 Hz, 1H, H-6), 6.85

(d, 3J9,10 = 8.8 Hz, 1H, H-9), 6.28 (d, 3J9,10 = 8.8 Hz, 1H, H-10), 6.08 (dd, 3J5,6 =

9.8 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.00 (s, 1H, H-2), 5.67 (d, 3J4a,5 = 4.5 Hz, 1H, H-4a), 3.22 (s, 1H, OH) ppm. 19F NMR (376.3 MHz, CDCl3): δ -84.2 (CF3) ppm.

(3R*,4aR*)-3-Hydroxy-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-

a]quinoline-6-carbonitrile (3m). Obtained from quinoline 1f (0.073 g, 0.475 mmol)

S6

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

io

p

m

4aH

Cl

N O

CF3

OH1

23

4

567

8

9 10 10a11

6a

io

p

m

4aH

Cl

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

io

p

m

4a

CN

H

Page 7: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

and acetylene 2a (0.099 g, 0.5 mmol). Light-brown powder, m.p. 107-110 C (heptane), RF(CH2Cl2-MeOH

100:1) = 0.30, yield 0.170 g (97%).1H NMR (400.1 MHz, CD3CN): δ 7.56-7.52 (m, 2H, Ho from Ph), 7.46-7.39 (m, 3H, Hm,p from Ph), 7.31 (d, 3J5,6 = 10.0 Hz, 1H, H-6), 7.21 (dd, 3J = 7.7 Hz, 4J = 1.0 Hz, 1H, H-8), 7.00 (pseudo-t, 3J ~ 8 Hz, 1H, H-9),

6.59 (pseudo-d, 3J ~ 8 Hz, 1H, H-10), 6.38 (dd, 3J5,6 = 9.9 Hz, 3J4a,5 = 4.8 Hz, 1H, Н-5), 6.10 (s, 1H, H-2),

5.72 (d, 3J4a,5 = 5.0 Hz, 1H, H-4a), 5.72 (br. s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.2 (CF3) ppm.

(3R*,4aR*)-8-Bromo-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3n).

Obtained from quinoline 1d (0.098 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5

mmol). White powder, m.p. 136-138 oC (heptane), yield 0.195 g (97%).1H NMR (400.1 MHz, CD3CN): δ 7.55-7.53 (m, 2H, Ho from Ph), 7.45-7.39 (m,

4H, Hm,p from Ph, H-7), 7.00 (dd, 3J9,10 = 8.8 Hz, 4J = 2.4 Hz, 1H, H-9), 6.95 (d, 3J5,6 = 9.9 Hz, 1H, H-6), 6.21 (d, 3J9,10 = 8.8 Hz, 1H, H-10), 6.16 (dd, 3J5,6 = 9.8

Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.02 (s, 1H, H-2), 5.64 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.59 (s, 1H, OH) ppm. 13C NMR (100.16 Hz, CD3CN): δ 148.2 (C-1), 137.3 (C-10a), 135.1 (Ci from Ph), 131.9 (C-6), 131.00 and

130.98 (Cp from Ph, C-6), 130.1 (Cm from Ph), 129.3 (C-9), 127.3 (Co from Ph), 127.3 (C-7), 124.5 (C-8),

123.5 (q, 1JCF = 284.9 Hz, CF3), 120.8 (C-5), 119.7 (C-10), 113.3 (C-6a), 113.0 (C-2), 93.0 (q, 2JCF = 33.2

Hz, C-3), 78.2 (C-4a) ppm.19F NMR (376.50 Hz, CD3CN): δ -82.1 (CF3) ppm.

HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C19H12BrF3NO+: 406.0049; found: 406.0052; m/z [M+H]+ Calcd

for C19H14BrF3NO2+: 424.0155; found: 424.0157.

(3R*,4aR*)-6-Bromo-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3o).

Obtained from quinoline 1e (0.099 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5

mmol). Light-brown powder, m.p. 115-117 C (heptane), RF(CH2Cl2-MeOH 100:1) =

0.71, yield 0.199 g (99%).1H NMR (400.1 MHz, CD3CN): δ 7.55-7.53 (m, 2H, Ho from Ph), 7.45-7.36 (m, 4H,

H-6, Hm,p from Ph), 7.10 (d, 3J = 8.1 Hz, 1H, H-8), 6.77 (t, 3J = 8.1 Hz, 1H, H-9), 6.33

(d, 3J = 8.1 Hz, 1H, H-10), 6.25 (dd, 3J5,6 = 9.8 Hz, 3J4a,5 = 4.7 Hz, 1H, Н-5), 6.08 (s,

1H, H-2), 5.65 (d, 3J = 4.7 Hz, 1H, H-4a), 5.61 (br. s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.1 (CF3) ppm.

(3R*,4aR*)-5-Bromo-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-

a]quinolin-3-ol (3p). Obtained from quinoline 1g (0.099 g, 0.475 mmol) and acetylene

S7

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

io

p

m

4aH

Br

N O

CF3

OH1

23

4

567

8

910 10a

11

6a

io

p

m

4a

Br

H

N O

CF3

OH1

23

4

5678

910 10a

11

6a

io

p

m

4a

BrH

Page 8: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

2a (0.099 g, 0.5 mmol). Light-yellow powder, m.p. 68-70 oC (heptane), yield 0.186 g (92%). 1H NMR (400.1 MHz, CD3CN): δ 7.58-7.55 (m, 2H, Ho from Ph), 7.48-7.38 (m, 4H, Hm and Hp from Ph, H-

6), 7.22 (dd, 3J = 7.2 Hz, 4J = 1.7 Hz, 1H, H-7), 6.96-6.86 (m, 2H, H-9, H-8), 6.32 (d, 3J9,10 = 8.1 Hz, 1H, H-

10), 6.06 (s, 1H, H-2), 5.74 (s, 1H, H-4a), 5.67 (br. s, 1H, OH) ppm. 13C NMR (100.16 Hz, CD3CN): δ 148.0 (C-2), 136.9 (C-11a), 135.1 (Ci from Ph), 132.6 (C-6), 131.1 (Cp

from Ph), 130.1 (Cm from Ph), 130.0 (C-9), 128.4 (C-7), 127.4 (Co from Ph), 123.3 (q, 1JCF = 282.9 Hz, CF3),

122.1 (C-6a), 122.0 (C-8), 118.9 (C-10), 113.0 (C-5), 112.4 (C-2), 93.4 (q, 2JCF = 33.2 Hz, C-3), 83.3 (C-4a)

ppm.19F NMR (376.5 MHz, CD3CN): δ -82.0 (CF3) ppm.

(6aR*,8R*)-10-Phenyl-8-(trifluoromethyl)-6aH,8H-[1,3]oxazino[3,2-a][1,8]naphthyridin-8-ol (3q).

Obtained from 1,8-naphthyridine 1h (0.062 g, 0.475 mmol) and acetylene 2a (0.099 g,

0.5 mmol). Pale brown crystals, m.p. 145-147 C (heptane), yield 0.155 g (94%). 1H NMR (400.1 MHz, CD3CN): δ 7.73 (dd, 3J = 4.8 Hz, 4J = 1.6 Hz, 1H), 7.55 (dd, 3J =

7.4 Hz, 4J = 1.5 Hz, 1H), 7.49-7.45 (m, 2H, Ho from Ph), 7.37-7.32 (m, 3H, Hm,p from Ph), 7.00 (d, 3J = 9.7

Hz, 1H), 6.82 (dd, 3J = 7.4 Hz, 3J = 5.0 Hz, 1H), 6.16 (dd, 3J = 9.7 Hz, 3J = 4.7 Hz, 1H), 5.96 (s, 1H), 5.81 (d, 3J = 4.6 Hz, 1H), 5.65 (s, 1H, OH) ppm.

19F NMR (376.5 MHz, CD3CN): δ -82.0 (CF3) ppm.

Epimerization of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a).

Oxazine 3a (0.050 g, 0.145 mmol) was dissolved in t-BuOH (1 mL) and H2O (0.5

mL) was added. The solution formed was left overnight. The volatiles were

evaporated in vacuo to give mixture of 3a ((3R*,4aR)-isomer) and 3a’ ((3S*,4aR)-

isomer) (0.050 g, ~100%) as light brown powder, m.p. 142-144 oC. (3R*,

4aR*):(3S*, 4aR*)-isomers ratio is 87:13. 1H NMR (400.13 MHz, CDCl3): δ 7.54-7.52 (m, 2H, Ho from Ph), 7.43-7.35 (m, 3H, Hm,p from Ph), 7.0 (d, 3J

= 7.2 Hz, 1H, H-7), 6.97-6.81 (m, 3H, H-6, H-9, H-8), 6.33 (d, 3J = 7.8 Hz, 1H, H-10), 6.04 (dd, 3J5,6 = 9.3

Hz, 3J4a,5 = 4.4 Hz, 1H, H-5), 5.97 (s, 1H, H-2), 5.68 (br s, 1H, H-4a), 3.19 (s, 1H, OH) ppm.19F NMR (376.50 Hz, CDCl3): δ -84.3 (CF3) ppm;

(4S*, 5aR*)-3a’: 1H NMR (400.13 MHz, CDCl3): 6.09 (dd, 3J5a,6 = 4.7 Hz, 3J6,7 = 9.8 Hz, 1H, H-6), 5.62 (d, 3J5a,6 = 4.7 Hz, 1H, H-5a) ppm. The other signals are identical to those of major isomer.19F NMR (376.50 Hz, CDCl3): δ -81.1 (CF3) ppm.

(3R*,4aR*)-3-Ethoxy-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinoline (4).

Oxazine 3a (0.100 g, 0.29 mmol) was dissolved in absolute EtOH (1 mL) and the

solution formed was left for 1 day. The volatiles were evaporated in vacuo to give 4

(0.106 g, 98%) as light yellow powder, m.p. 130-132 oC. S8

N N O

Ph CF3

OH

H

N O

CF3

OH

3a

11

1

2 3

4

567

89 10a10

6a

io

p

m

4a

N O

CF3

OEt

1

1

2 3

4

567

8

911a10

6a

io

p

m

4a

Page 9: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

1H NMR (400.13 MHz, CD3CN): δ 7.56-7.54 (m, 2H, Ho from Ph), 7.47-7.38 (m, 3H, Hm,p from Ph), 7.25

(dd, 3J = 7.1 Hz, 4J = 1.8 Hz, 1H, H-7), 7.01 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.91-6.83 (m, 2H, H-9, H-8), 6.32

(d, 3J = 7.8 Hz, 1H, H-10), 6.20 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.7 Hz, 1H, H-5), 6.07 (s, 1H, H-2), 5.69 (d, 3J4a,5

= 4.8 Hz, 1H, H-4a), 3.91-3.78 (m, 2H, CH2), 1.24 (t, 3H, 3J = 7.0 Hz, CH3) ppm.19F NMR (376.50 MHz, CD3CN): δ -80.1 (CF3) ppm. 13C NMR (100.6 Hz, CD3CN): δ 150.5, 138.1, 135.4, 131.1, 130.4, 130.1, 129.6, 128.9, 127.42, 127.36,

123.2 (q, 1JCF = 286.2 Hz, CF3), 121.6, 119.0, 117.9, 112.8, 95.6 (q, 2JCF = 31.7 Hz), 80.3, 60.0, 15.8 ppm.

HRMS (ESI-TOF): m/z [M+H]+ Calcd for C21H18F3NO2+: 374.1362; found: 374.1369.

Reaction of oxazine (3a) with methyl 2-mercaptoacetate. A 4 mL vial with a screw cup was charged with

with oxazine 3a (0.071 g, 0.2 mmol), solution of methyl 2-mercaptoacetate in

MeOH (1 mL, 0.5 M, 0.5 mmol) and left at room temperature for 72 h. MeOH was

evaporated to give 0.093 g of light brown oil, consisting of quinoline, methyl 2-

((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (85:15 mixture of

isomers) and dimethyl 2,2'-disulfanediyldiacetate (MeCO2-CH2-S-S-CH2CO2Me

appeared due to oxidation of methyl 2-mercaptoacetate by oxygen) in molar ratio 1:1:0.22. Compound 5,

major isomer: 1H NMR (400.13 MHz, CDCl3): δ 7.40-7.42 (m, 2H, Ar), 7.21-7.25 (m, 3H, Ar), 6.57 (s, 1H,

C=CH), 3.52 (s, 3H, OCH3), 3.31 (s, 2H, SCH2). 13C NMR (100.6 MHz, CDCl3): δ 177.3 (q, С-CF3, J =

35.0), 171.3, 168.3, 136.7, 129.9, 128.8, 127.6, 116.1 (q, CF3, J = 290.4), 114.8, 52.5, 35.0. 19F NMR (376.50

Hz, CDCl3): δ -78.7. Minor isomer: 1H NMR (400.13 MHz, CDCl3): δ 7.41-7.44 (m, 2H, Ar), 7.30-7.32 (m,

3H, Ar), 6.47 (s, 1H, C=CH), 3.78 (s, 3H, OCH3), 3.66 (s, 2H, SCH2). 13C NMR (100.6 MHz, CDCl3): δ

130.2, 128.4, 127.9, 109.3, 52.9, other signals are identical to those of major isomer. 19F NMR (376.50 Hz,

CDCl3): δ -79.6. Quinoline: 1H NMR (400.13 MHz, CDCl3): δ 8.88 (dd, 3J = 4.3 Hz, 4J = 1.7 Hz, 1H), 8.14

(dd, 3J = 8.3 Hz, 4J = 1.1 Hz, 1H), 8.09 (d, 3J = 8.5 Hz, 1H), 7.78 (dd, 3J = 8.1 Hz, 4J = 0.7 Hz, 1H), 7.70-

7.66 (m, 1H), 7.53-7.49 (m, 1H), 7.38-7.34 (m, 1H). 13C NMR (100.6 MHz, CDCl3): δ 150.0, 147.7, 136.3,

129.5, 128.9, 128.2, 127.7, 126.6, 121.0. The NMR data of 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-

yl)thio)acetate 53 and quinoline4 are in agreement with those in the literature.

Transformation of oxazine (3a) into 2-phenylquinoline (6). A 4 mL vial with a screw cap was charged

with oxazine 3a (0.030 g, 0.087 mmol), water (0.5 mL) and NaOH (0.0104 g, 0.261 mmol). The reaction

mixture was heated at 80 C at stirring for 2 h. After cooling down to room temperature, the reaction mixture

was extracted with EtOAc (2x0.5 mL), combined organic phase was passed through a short silica gel pad

3 V. M. Muzalevskiy, A. A. Iskandarov, V. G. Nenajdenko, J. Fluorine Chem. 2018, 214, 13-16.4 T. Kaiya, N. Shiraiy, Y. Kawazoe, Chem. Pharm. Bull., 1986, 34, 881-885.

S9

MeO2C S O

Ph CF3

N

+

Page 10: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

using heptane followed by heptane-EtOAc (15:1) as an eluents. Evaporation of volatiles afforded 6 as light

brown powder, m.p. 81-83 C (Lit. data: 82-84 C5), yield 0.016 g (90%).1H NMR (400.1 MHz, CDCl3): δ 8.22 (d, 3J = 8.6 Hz, 1H), 8.19-8.15 (m, 3H), 7.87 (d, 3J = 8.6 Hz, 1H), 7.83 (dd, 3J = 8.1 Hz, 4J = 0.7 Hz, 1H), 7.75-7.70 (m, 1H), 7.54-7.51

(m, 3H), 7.48-7.44 (m, 1H) ppm.13C NMR (100.6 MHz, CDCl3): δ 157.3, 148.2, 139.6, 136.7, 129.63, 129.61, 129.3,

128.8, 127.5, 127.4, 127.1, 126.2, 119.0 ppm. The NMR data are in agreement with those in the literature4.

Transformation of oxazine (3a) into 2,2,2-trifluoro-1-(2-phenylquinolin-3-yl)ethanone (7). A 4 mL vial

with a screw cap was charged with oxazine 3a (0.030 g, 0.087 mmol), MeCN (0.5

mL) and morpholine (0.0075 g, 0.087 mmol). The reaction mixture was heated at 80

C for 6 h and then volatiles were evaporated in vacuo. The residue was passed

through a short silica gel pad using heptane followed by heptane-EtOAc (10:1) as an

eluents. Evaporation of volatiles afforded 7 as a pale yellow powder, m.p. 86-87 C,

yield 0.023 g (88%).1H NMR (400.1 MHz, CD3CN): δ 8.77 (s, 1H, H-4), 8.09 (m, 1H, H-8), 8.07 (m, 1H, H-5), 7.91 (m, 1H, H-

7), 7.68 (m, 1H, H-6), 7.56 (m, 2H, Ho from Ph), 7.49 (m, 3H, Hm,p from Ph) ppm.13C NMR (100.6 MHz, CD3CN): δ 185.4 (q, 2JCF = 36.0 Hz, C=O), 158.4 (C-2), 149.6 (C-8a), 140.8 (Ci from

Ph), 140.7 (q, 4JCF = 3.0 Hz, C-4), 134.3 (C-8), 130.3 (C-6), 130.2 (Cp from Ph, C-7), 130.1 (Co from Ph),

129.6 (Cm from Ph), 129.1 (C-5), 126.4 (C-4a), 126.0 (C-3), 117.1 (q, 1JCF = 291.7 Hz, CF3) ppm.19F NMR (376.5 MHz, CD3CN): δ -72.4 (CF3) ppm.1H NMR (400.1 MHz, CDCl3): δ 8.59 (s, 1H, H-4), 8.21 (d, 3J = 8.5 Hz, 1H, H-8), 7.97 (d, 3J = 8.1 Hz, 1H,

H-5), 7.91 (ptd, 3J ~ 8 Hz, 4J ~ 1 Hz, 1H, H-7), 7.68 (ptd, 3J ~ 8 Hz, 4J ~ 1 Hz, 1H, H-6), 7.59-7.57 (m, 2H,

Ho from Ph), 7.52-7.48 (m, 3H, Hm,p from Ph) ppm.13C NMR (100.6 MHz, CDCl3): δ 184.6 (q, 2JCF = 36.0 Hz, C=O), 157.7 (C-2), 148.7 (C-8a), 139.3 (Ci from

Ph), 139.0 (q, 4JCF = 3.0 Hz, C-4), 133.0 (C-8), 129.3 (C-6), 128.9 (Co from Ph), 128.8 (Cm from Ph), 128.7

(Cp from Ph, C-7), 127.9 (C-5), 125.9 (C-4a), 124.9 (C-3), 115.9 (q, 1JCF = 292.1 Hz, CF3) ppm.19F NMR (376.5 MHz, CDCl3): δ -73.7 (CF3) ppm.

HRMS (ESI-TOF): m/z [M+H]+ Calcd for C17H11F3NO+: 302.0793; found: 302.0790.

5 N. Sudhapriya, A. Nandakumar, P. T. Perumal, RSC Advances, 2014, 4, 58476-58480.S10

N

O

CF3

12

345

6

78

4a

8a io p

m

N

Page 11: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a)

to form 8 and 9. Three-necked round bottomed flask was charged with oxazine 3a

(0.105 g, 0.304 mmol), 10% Pd on carbon (0.032 g, 0.03 mmol, 10 mol%) and THF

(5 mL). The flask was evacuated and flushed with H2 from a balloon. The solution

formed was stirred 36 h and filtered off. The filter cake was washed with EtOAc

(3*3 mL), the volatiles were evaporated in vacuo. The residue was passed through a

short silica gel pad using heptane followed by heptane-EtOAc (10:1) as an eluents. Evaporation of the

volatiles afforded a mixture 8 and 9 (75:25) as a colorless oil, yield 0.077 g (72%).

(3R*,4aR*)-1-Phenyl-3-(trifluoromethyl)-2,3,4a,5-tetrahydro-1H,6H-[1,3]oxazino[3,2-a]quinolin-3-ol

(8). 1H NMR (400.13 MHz, CDCl3): δ 7.44-7.29 (m, 5H, Ph), 7.08 (d, 3J = 7.3 Hz, 1H, H-7), 7.01 (pseudo-t, 3J ~ 8 Hz, 1H, H-9), 6.76 (pseudo-t, 3J ~ 7 Hz, 1H, H-8), 6.40 (d, 3J = 8.1 Hz, 1H, H-10), 5.53 (br s, 1H, H-

4a), 4.98 (dd, 3J = 11.8 Hz, 3J = 7.0 Hz, 1H, H-1), 3.10-2.93 (m, 1H), 2.79-2.67 (m, 3H), 2.37-2.30 (m, 1H),

2.33 (dd, 3J = 14.4 Hz, 3J = 11.8 Hz, 1H, H-2), 2.11-2.02 (m, 1H) ppm.19F NMR (376.50 Hz, CDCl3): δ -88.0 (CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 143.4 (Cq), 142.2 (Cq), 129.1 (Cm from Ph), 128.5, 128.3, 127.5, 127.4,

127.0, 125.1 (Co from Ph), 123.2 (Cq), 122.3 (q, 1JCF = 285.5 Hz, CF3), 118.5, 112.9, 94.4 (q, 2JCF = 31.5 Hz,

C-3), 79.2 (C-4a), 55.5 (C-1), 33.4 (CH2), 25.9 (CH2), 21.6 (CH2) ppm.

HRMS (ESI-TOF): m/z [M+H]+ Calcd for C19H18F3NO2+: 350.1362; found: 350.1351.

4-(3,4-diHydroquinolin-1(2H)-yl)-1,1,1-trifluoro-4-phenylbutan-2-ol (9). 1H NMR (400.13 MHz, CDCl3):

δ 7.44-7.29 (m, 5H, Ph), 6.64 (pseudo-t, 3J ~ 7 Hz, 1H, H-8), 6.47 (d, 3J = 8.1 Hz, 1H,

H-10), 5.61-5.37 (m, 1H), 4.14-4.10 (m, 1H), 3.10-2.93 (m, 2H), 2.79-2.67 (m, 1H),

2.50-2.43 (m, 1H), 2.37-2.30 (m, 2H), 2.29-2.22 (m, 1H), 1.87-1.84 (m, 2H) ppm.19F NMR (376.50 Hz, CDCl3): δ -80.8 (d, 3JHF = 6.8 Hz CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 145.8 (Cq), 140.0 (Cq), 129.7 (Cm from Ph), 129.0,

127.4, 127.3, 125.5 (Co from Ph), 122.8 (Cq), 125.4 (q, 1JCF = 281.7 Hz, CF3), 116.2, 111.0, 67.7 (q, 2JCF =

31.5 Hz, C-3), 54.3 (C-1), 42.1, 29.9 (CH2), 28.5 (CH2), 21.7 (CH2) ppm.

HRMS (ESI-TOF): m/z [M+H]+ Calcd for C19H20F3NO+: 336.1570; found: 336.1560.

Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a)

to form 11. Three-necked round bottomed flask was charged with oxazine 3a

(0.105 g, 0.304 mmol), 10% Pd on carbon (0.034 g, 0.03 mmol, 10 mol%) and

MeOH (5 mL). The flask was evacuated and flushed with H2 from a balloon. The

solution formed was stirred 36 h and filtered off. The filter cake was washed with

EtOAc (3*3 mL), the volatiles were evaporated in vacuo. The residue was passed

S11

N O

CF3

O

11

11

1

2 3

4

567

89 10a10

6a

io

p

m

4a

N O

CF3

OH

8

11

1

2 3

4

567

89 10a10

6a

io

p

m

H

N

CF3

OH

9

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through a short silica gel pad using heptane followed by heptane-EtOAc (10:1) as an eluents. Compounds 10

and 11 were isolated as a separate fractions.

3-Methoxy-1-phenyl-3-(trifluoromethyl)-4a,5-dihydro-3H,6H-[1,3]oxazino[3,2-a]quinoline (10).

Colorless oil, yield 0.011 g (10%).1H NMR (400.13 MHz, CDCl3): δ 7.39-7.27 (m, 5H, Ph), 7.11-7.09 (m, 1H), 6.84-6.78 (m, 2H), 6.22-6.20

(m, 1H), 5.60 (br s, 1H, H-4a), 5.33 (t, 3J = 7.7 Hz, 1H), 3.52 (s, 1H, MeO), 2.81-2.63 (m, 3H), 1.92-1.82 (m,

1H) ppm.19F NMR (376.50 Hz, CDCl3): δ -81.5 (CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 149.3, 138.8, 134.7, 130.3, 129.6 128.6, 127.1, 126.8, 122.4 (q, 1JCF = 286.9

Hz, CF3), 121.5, 120.2, 105.6, 95.7 (q, 2JCF = 31.8 Hz, C-3), 83.0 (C-4a), 50.8 (MeO), 29.4(CH2), 24.7 (CH2)

ppm.

HRMS (ESI-TOF): m/z [M+H]+ Calcd for C20H19F3NO2+: 362.1362; found: 362.1357.

3-Methoxy-1-phenyl-3-(trifluoromethyl)-2,3,4a,5-tetrahydro-1H,6H-[1,3]oxazino[3,2-a]quinoline (11).

A colorless oil solidifies at standing, m.p. 142-143 C, yield 0.093 g (84%). 1H NMR (400.13 MHz, CDCl3):

δ 7.41-7.29 (m, 5H, Ph), 7.05 (d, 3J = 7.3 Hz, 1H, H-7), 6.99 (pseudo-t, 3J ~ 8 Hz, 1H, H-9), 6.73 (pseudo-t, 3J ~ 7 Hz, 1H, H-8), 6.39 (d, 3J = 8.1 Hz, 1H, H-10), 5.52 (br s, 1H, H-4a), 4.90 (dd, 3J = 11.9 Hz, 3J = 7.0

Hz, 1H, H-1), 3.29 (s, 1H, MeO), 3.14-3.06 (m, 1H), 2.78-2.68 (m, 1H), 2.59 (dd, 3J = 14.3 Hz, 3J = 7.0 Hz,

1H, H-2), 2.45-2.39 (m, 1H), 2.33 (dd, 3J = 14.3 Hz, 3J = 11.9 Hz, 1H, H-2), 2.12-2.03 (m, 1H) ppm.19F NMR (376.50 Hz, CDCl3): δ -83.1 (CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 143.5 (Cq), 142.3 (Cq), 129.1 (Cm from Ph), 128.3, 127.5, 127.4, 125.2 (Co

from Ph), 122.8 (Cq), 122.7 (q, 1JCF = 289.3 Hz, CF3), 118.3, 112.8, 95.8 (q, 2JCF = 31.5 Hz, C-3), 79.0 (C-

4a), 55.8 (MeO), 50.5 (C-1), 34.6 (CH2), 26.3(CH2), 22.3 (CH2) ppm.

HRMS (ESI-TOF): m/z [M+H]+ Calcd for C20H21F3NO2+: 364.1519; found: 364.1522.

S12

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23 Feb 2019

FW 345.3152 Formula C19H14F3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 22 Feb 2019 23:06:50File Name C:\BM_DATA\DOCS\Manuscr_Ultra\BM_2018\bm190222\BM-1499_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.01 1.98 0.97 0.88

Acetonitrile-d3

5.41

5.66

6.03

6.32

6.84

6.85

6.87

6.99

7.02

7.39

7.41

7.43

7.55

7.56

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

3.012.01 1.981.00 0.99 0.970.970.96 0.95 0.88

7.57

7.57

7.56

7.55

7.54

7.47

7.45

7.44

7.43

7.43

7.41

7.39

7.39

7.26 7.

247.

24 7.02 6.99

6.92 6.91

6.90 6.

886.

876.

876.

856.

856.

846.

83

6.32

6.30

6.13 6.12

6.11 6.10

6.03

5.66

5.65

5.41

1H NMR spectrum of 3a (400.1 MHz, CD3CN)

S13

Page 14: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

12 Feb 2019

FW 345.3152 Formula C19H14F3NO2

Acquisition Time (sec) 1.9000 Date Oct 1 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM-1371_20181001_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 169643Points Count 262144 Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71Temperature (degree C) 22.000

OHN O

FF

F

H

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-81.

99

19F NMR spectrum of 3a (376.5 MHz, CD3CN)

S14

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24 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 24 Jul 2019 17:34:04File Name C:\DOCS\OUTPUT_301\2019\07.èþ ëü\190724\BM-1659-1_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent CHLOROFORM-D Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.14 1.041.03 1.01

Chloroform-d

Chloroform-d

3.19

5.68

5.69

5.97

6.34

6.846.94

6.96

7.17

7.25

7.39

7.52

7.54

7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6Chemical Shift (ppm)

3.142.07 1.041.03 1.03 1.001.00 1.001.000.98

Chloroform-d

5.685.69

5.97

6.03

6.046.05

6.07

6.326.34

6.82

6.84

6.86

6.886.

906.

926.

946.

96

7.17

7.19

7.25

7.357.

367.

377.

397.39

7.40

7.41

7.43

7.527.52

7.54

1H NMR spectrum of 3a in multi gram scale synthesis (400.1 MHz, CDCl3)

S15

Page 16: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

12 Feb 2019

FW 359.3418 Formula C20H16F3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 27 Sep 2018 19:18:46File Name C:\DOCS\OUTPUT_301\2018\09.ñåí òÿáðü\BM-1372\BM-1372_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

CH3

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.193.14 1.00 0.98

Acetonitrile-d3

2.35

5.62

5.63

5.97

6.85

6.98

7.00

7.21

7.23

7.42

7.44

7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

Inte

nsity

3.142.10 2.041.00 1.000.99 0.98 0.98 0.88

7.44

7.42

7.25

7.25

7.23

7.21

7.00 6.98

6.91

6.89

6.89

6.88

6.87 6.

876.

86 6.85

6.84

6.83

6.83

6.34

6.32

6.12 6.11

6.10

6.08

5.97

5.63

5.62

5.54

1H NMR spectrum of 3b (400.1 MHz, CD3CN)

S16

Page 17: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

12 Feb 2019

FW 359.3418 Formula C20H16F3NO2

Acquisition Time (sec) 1.0000 Date Sep 28 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.09.28\BM-1372_20180928_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000

OHN O

FF

F

H

CH3

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-82.

00

19F NMR spectrum of 3b (376.5 MHz, CD3CN)S17

Page 18: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 373.3684 Formula C21H18F3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 17 Oct 2018 23:19:18File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181017\BM-1397d_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

CH3

CH3

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.232.09 0.990.96 0.96

Acetonitrile-d3

7.34

7.24 7.22 7.17

7.15

7.00

6.98

6.90

6.85

6.35

6.33 5.

935.

615.

605.

47

2.27

2.24

7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)

0

0.05

0.10

Inte

nsity

2.092.09 1.06 1.00 0.99 0.990.96 0.960.95 0.86

5.47

5.60

5.61

5.93

6.086.096.10

6.11

6.336.35

6.83

6.85

6.886.

906.

92

6.98

7.00

7.15

7.17

7.22

7.24

7.34

1H NMR spectrum of 3c (400.1 MHz, CD3CN)

S18

Page 19: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 373.3684 Formula C21H18F3NO2

Acquisition Time (sec) 2.3069 Date Oct 18 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.18\BM-1397d-F_20181018_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

OHN O

FF

F

H

CH3

CH3

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-81.

95

19F NMR spectrum of 3c (376.5 MHz, CD3CN)

S19

Page 20: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 401.4215 Formula C23H22F3NO2

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 02 Oct 2018 15:32:08File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1377-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

OHN O

FF

F

H

CH3

CH3

CH3

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

9.584.27 1.94 0.950.940.94

Acetonitrile-d3

7.50 7.48

7.45

7.25

7.23

7.01

6.98

6.89 6.86

6.84

6.33

6.31

6.11 5.

985.

635.

62

1.31

7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Inte

nsity

4.27 1.941.05 0.98 0.950.94 0.940.94 0.81

5.515.

625.

63

5.98

6.08

6.10

6.11

6.126.316.33

6.836.

846.86

6.88

6.89

6.906.

987.

01

7.23

7.23

7.25

7.25

7.427.

437.

447.

457.

467.

48

1H NMR spectrum of 3d (400.1 MHz, CD3CN)

S20

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13 Feb 2019

FW 401.4215 Formula C23H22F3NO2

Acquisition Time (sec) 2.3069 Date Oct 4 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.04\BM-1377-F_20181004_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

OHN O

FF

F

H

CH3

CH3

CH3

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-81.

97

19F NMR spectrum of 3d (376.5 MHz, CD3CN)

S21

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13 Feb 2019

FW 375.3412 Formula C20H16F3NO3

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 29 Sep 2018 14:08:28File Name C:\DOCS\OUTPUT_301\2018\09.ñåí òÿáðü\BM-1373.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

OHN O

FF

F

H

OCH3

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.012.242.09 0.990.97

Acetonitrile-d37.47 7.45

7.00

6.97

6.94

6.92

6.86 6.84

6.36

6.34 5.

925.

635.

58

3.79

7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Inte

nsity

2.242.09 1.851.011.00 0.990.97 0.960.95 0.71

5.58

5.62

5.63

5.92

6.08

6.096.10

6.12

6.346.36

6.83

6.83

6.84

6.85

6.86

6.89

6.90

6.92

6.94

6.95

6.97

7.00

7.22

7.23

7.24

7.25

7.45

7.47

1H NMR spectrum of 3e (400.1 MHz, CD3CN)

S22

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13 Feb 2019

FW 375.3412 Formula C20H16F3NO3

Acquisition Time (sec) 1.9000 Date Oct 1 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM-1373_20181001_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 169643Points Count 262144 Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71Temperature (degree C) 22.000

OHN O

FF

F

H

OCH3

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-82.

02

19F NMR spectrum of 3e (376.5 MHz, CD3CN)

S23

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13 Feb 2019

FW 391.4078 Formula C20H16F3NO2S

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 02 Oct 2018 15:34:56File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1378.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

OHN O

FF

F

H

SCH3

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.203.02 2.00 0.95 0.95

Acetonitrile-d3

7.46 7.44 7.

267.

247.

006.

986.

926.

87 6.86

6.34

6.32

6.10

6.09 5.

985.

615.

54

2.47

7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Inte

nsity

3.022.00 2.001.00 0.95 0.950.920.91 0.81

5.54

5.60

5.61

5.98

6.08

6.09

6.10

6.116.

326.34

6.84

6.86

6.87

6.906.

926.

946.

987.

00

7.24

7.26

7.44

7.46

1H NMR spectrum of 3f (400.1 MHz, CD3CN)

S24

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13 Feb 2019

FW 391.4078 Formula C20H16F3NO2S

Acquisition Time (sec) 2.3069 Date Oct 4 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.04\BM-1378-F_20181004_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

OHN O

FF

F

H

SCH3

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-82.

02

19F NMR spectrum of 3f (376.5 MHz, CD3CN)

S25

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13 Feb 2019

FW 379.7600 Formula C19H13ClF3NO2

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 16 Oct 2018 16:12:24File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1399-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

H

OHN O

FF

F

Cl

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

2.13 1.99 0.96 0.96

Acetonitrile-d3

7.54

7.52

7.43

7.41

7.26

7.24 7.01

6.98

6.87

6.28

6.03

5.62

5.61

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

Inte

nsity

2.13 2.06 1.991.06 1.00 0.96 0.960.95 0.91 0.83

5.55

5.615.62

6.03

6.08

6.106.11

6.126.

266.28

6.85

6.87

6.89

6.89

6.916.916.

936.

936.98

7.01

7.24

7.24

7.26

7.26

7.41

7.43

7.52

7.54

1H NMR spectrum of 3g (400.1 MHz, CD3CN)

S26

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13 Feb 2019

FW 379.7600 Formula C19H13ClF3NO2

Acquisition Time (sec) 1.9000 Comment STANDARD FLUORINE PARAMETERS Date Oct 1 2018File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM1375_20181001_01\FLUORINE_01 Frequency (MHz) 376.31Nucleus 19F Number of Transients 16 Original Points Count 169643 Points Count 262144Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000

H

OHN O

FF

F

Cl

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-81.

95

19F NMR spectrum of 3g (376.5 MHz, CD3CN)

S27

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13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 16 Oct 2018 20:47:00File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181016\BM-1398-2_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

H

OHN O

FF

F

Br

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

2.12 2.05 0.99 0.98

Acetonitrile-d3

7.58

7.56

7.46

7.44

7.24 7.01 6.98

6.87

6.28

6.04

5.61

5.60

5.56

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

Inte

nsity

2.12 2.052.03 1.02 0.99 0.980.97 0.960.95 0.87

5.565.

605.

61

6.04

6.08

6.096.11

6.126.

266.28

6.85

6.87

6.89

6.91

6.91

6.95

6.98

7.01

7.24

7.24

7.26

7.44

7.46

7.56

7.58

1H NMR spectrum of 3h (400.1 MHz, CD3CN)

S28

Page 29: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 1.9000 Date Oct 1 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM1376_20181001_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 169643Points Count 262144 Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71Temperature (degree C) 22.000

H

OHN O

FF

F

Br

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-81.

90

19F NMR spectrum of 3h (376.5 MHz, CD3CN)

S29

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Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 18 Mar 2019 15:56:38File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1520-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

Cl

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Inte

nsity

2.20 1.03 1.000.98

Acetonitrile-d3

7.53

7.51

7.41 7.41

7.35

7.22

6.94

6.84

6.82 6.

105.

945.

715.

53

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

Inte

nsity

2.202.05 1.05 1.03 1.02 1.000.99 0.98 0.94 0.93 0.80

5.53

5.71

5.72

5.94

6.07

6.096.

106.

11

6.356.37

6.82

6.83

6.84

6.86

6.90

6.92

6.94

6.96

6.997.

227.

24

7.33

7.33

7.35

7.35

7.37

7.41

7.41

7.42

7.43

7.507.51

7.53

1H NMR spectrum of 3i (400.1 MHz, CD3CN)

S30

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4 Apr 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 16 Mar 2019 14:04:18File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1520.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 106 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

OHN O

FF

F

H

Cl

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Acetonitrile-d3

Acetonitrile-d314

5.02 13

7.38

134.

4313

2.98

131.

79

129.

0512

8.62

122.

1412

1.87 12

1.62

119.

0511

6.02

93.2

292

.89

92.5

692

.24

78.8

0

144 142 140 138 136 134 132 130 128 126 124 122 120 118 116Chemical Shift (ppm)

0.25

0.50

0.75

1.00

Inte

nsity

Acetonitrile-d3

116.

0211

6.43

119.

0511

9.3112

1.62

121.

8712

2.14

124.

98

127.

81

128.

6212

9.05

129.

9113

0.19

131.

53131.

7713

1.79

132.

98

134.

43

137.

38

145.

02

93.0 92.5 92.0Chemical Shift (ppm)

0.05

0.10

Inte

nsity

92.2

4

92.5

6

92.8

9

93.2

2

13C NMR spectrum of 3i (100.6 MHz, CD3CN)

S31

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4 Apr 2019

Acquisition Time (sec) 2.3069 Date Mar 14 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.03.14\BM-1511-A-F_20190314_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

Cl

OHN O

FF

F

H

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-81.

77

19F NMR spectrum of 3i (376.5 MHz, CD3CN)

S32

Page 33: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 18 Mar 2019 16:02:18File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1521-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

O

O

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Inte

nsity

4.324.01 0.96 0.93 0.68

Acetonitrile-d3

7.23 7.22

7.03

7.01

6.88 6.86

6.84 6.

376.

355.

895.

595.

585.

34 4.27

4.25 4.

234.

23

7.0 6.5 6.0 5.5 5.0 4.5Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

Inte

nsity

4.324.01 2.001.02 0.96 0.95 0.93 0.92 0.68

4.214.

224.

224.

234.

234.23

4.25

4.25

4.26

4.26

4.26

4.27

5.34

5.58

5.59

5.89

6.06

6.07

6.09

6.106.

356.37

6.84

6.84

6.86

6.88

6.92

6.97

6.99

7.01

7.03

7.037.

227.

237.

247.

25

1H NMR spectrum of 3j (400.1 MHz, CD3CN)

S33

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4 Apr 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 16 Mar 2019 21:35:50File Name C:\DOCS\BM\190316\BM-1521_002001r Frequency (MHz) 100.61 Nucleus 13C Number of Transients 128Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30 Solvent CHLOROFORM-DSweep Width (Hz) 24154.59 Temperature (degree C) 27.000

OHN O

FF

F

H

O

O

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Acetonitrile-d3 Acetonitrile-d314

7.96

146.

1514

4.92

138.

33

130.

3812

9.48

128.

8212

8.70

122.

4512

1.39

120.

3311

9.23 11

8.61

118.

0011

5.95

111.

23

93.4

493

.11

92.7

892

.46 78

.29

65.2

665

.05

148 146 144 142 140 138 136 134 132 130 128 126 124 122 120 118 116 114 112Chemical Shift (ppm)

0.25

0.50

0.75

1.00

Inte

nsity

Acetonitrile-d3

111.

23

115.

95

118.

0011

8.61

119.

23

120.

33

121.

3912

2.1212

2.45

124.

96

127.

58

128.

7012

8.82

129.

48

130.

38138.

33

144.

92

146.

15

147.

96

93.5 93.0 92.5Chemical Shift (ppm)

0.05

0.10

Inte

nsity

92.4

6

92.7

8

93.1

1

93.4

4

13C NMR spectrum of 3j (100.6 MHz, CD3CN)

S34

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4 Apr 2019

Acquisition Time (sec) 0.7340 Date Mar 19 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.03.19\bm1521-2-f_20190319_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 1000 Original Points Count 65536Points Count 65536 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000

OHN O

FF

F

H

O

O

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-82.

20

19F NMR spectrum of 3j (376.5 MHz, CD3CN)

S35

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4 Apr 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 12 Mar 2019 14:47:30File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1512-P.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

Cl

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

3.04 1.001.00 0.98

Acetonitrile-d3

7.55

7.45

7.43

7.23 7.

217.

00 6.98

6.29

6.07

5.67 5.

49

7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

3.042.09 1.03 1.001.00 1.00 0.980.980.97 0.93

5.49

5.665.67

6.07

6.12

6.136.14

6.16

6.28

6.29

6.84

6.856.

866.

876.98

7.00

7.21

7.23

7.417.

417.

437.45

7.46

7.47

7.49

7.55

7.55

7.57

1H NMR spectrum of 3k (400.1 MHz, CD3CN)

S36

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4 Apr 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 12 Mar 2019 15:31:56File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1512-P.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 1116 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

OHN O

FF

F

H

Cl

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Acetonitrile-d3

Acetonitrile-d3

148.

02

139.

2313

5.03

131.

1313

0.19

127.

3412

4.91

121.

3611

9.67

118.

2011

7.58

113.

34

93.4

993

.16

92.8

392

.50

78.2

0

135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117Chemical Shift (ppm)

0.25

0.50

0.75

1.00

Inte

nsity

Acetonitrile-d3

117.

58

118.

20

119.

24

119.

67

121.

2612

1.36

122.

07

124.

91

127.

34

127.

74

129.

49

130.

0813

0.19

131.

13

134.

17

135.

03

93.5 93.0 92.5Chemical Shift (ppm)

0.05

0.10

Inte

nsity

92.5

0

92.8

3

93.1

6

93.4

9

13C NMR spectrum of 3k (100.6 MHz, CD3CN)

S37

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4 Apr 2019

Acquisition Time (sec) 0.7340 Date Mar 12 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.03.12\bm1512-f_20190312_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 100 Original Points Count 65536Points Count 65536 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000

OHN O

FF

F

H

Cl

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-81.

98

19F NMR spectrum of 3k (376.5 MHz, CD3CN)

S38

Page 39: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 379.7600 Formula C19H13ClF3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 18 Oct 2018 22:21:32File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181018\BM-1404_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent Tol Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000

OHN O

FF

F

H

Cl

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.19 2.01 1.02 0.98 0.95

Chloroform-d

7.53

7.51

7.40

7.38

7.16

6.85

6.29

6.09

6.00

5.68

3.69

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

3.192.07 2.01 1.02 1.021.01 0.98 0.98

Chloroform-d

5.665.68

6.00

6.06

6.076.

096.

10

6.276.

29

6.84

6.85

6.87

7.16

7.16

7.367.

377.

387.

407.

417.

417.

427.

447.

447.

507.51

7.53

7.53

1H NMR spectrum of 3l (400.1 MHz, CDCl3)

S39

Page 40: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 379.7600 Formula C19H13ClF3NO2

Acquisition Time (sec) 1.0000 Date Oct 19 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.19\BM-1404_20181019_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 32 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 22.000

OHN O

FF

F

H

Cl

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

C6F6

-84.

16

19F NMR spectrum of 3l (376.5 MHz, CDCl3)

S40

Page 41: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 370.3247 Formula C20H13F3N2O2

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 03 Oct 2018 17:50:24File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1380.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent CHLOROFORM-D Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

OHN O

FF

F

H

N

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.04 1.911.02 1.00 0.99

Acetonitrile-d37.

567.

557.

53 7.43

7.41

7.32 7.29 7.20

7.00

6.98

6.60

6.10

5.72

5.71

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7Chemical Shift (ppm)

0

0.1

0.2

0.3

0.4

0.5

Inte

nsity

3.042.06 1.911.021.02 1.001.00 1.00 0.99

5.71

5.72

5.72

6.10

6.36

6.376.

386.

40

6.586.

60

6.98

7.00

7.02

7.20

7.20

7.22

7.22

7.29

7.32

7.397.

397.

417.

437.

447.

457.

46

7.537.

537.

557.

557.

56

1H NMR spectrum of 3m (400.1 MHz, CD3CN)

S41

Page 42: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 370.3247 Formula C20H13F3N2O2

Acquisition Time (sec) 2.3069 Date Oct 4 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.04\BM-1380-F_20181004_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

OHN O

FF

F

H

N

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-82.

17

19F NMR spectrum of 3m (376.5 MHz, CD3CN)

S42

Page 43: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 17 Oct 2018 23:22:50File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181017\BM-1402-2_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

Br

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

4.34 1.051.02 1.00

Acetonitrile-d3

7.55 7.53 7.

43 7.41

7.41

6.99 6.96

6.94 6.22

6.02

5.64

5.59

7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Inte

nsity

4.342.22 1.051.021.02 1.001.000.98 0.88

5.595.

635.64

6.02

6.15

6.166.

176.18

6.196.22

6.94

6.96

6.99

7.00

7.01

7.02

7.39

7.40

7.41

7.41

7.43

7.44

7.44

7.45

7.53

7.53

7.55

7.55

1H NMR spectrum of 3n (400.1 MHz, CD3CN)

S43

Page 44: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 0.4999 Comment Imported from UXNMR. Date 17 Oct 2018 17:16:02File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1402.C_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 128 Original Points Count 12076 Points Count 65536Pulse Sequence zgpg30 Solvent DMSO-D6 Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

OHN O

FF

F

H

Br

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Acetonitrile-d3

Acetonitrile-d3

148.

17

137.

34 135.

1113

1.86

130.

9813

0.11

127.

2912

4.45

120.

7611

9.73

119.

2511

3.25

113.

03

93.5

193

.18

92.8

592

.53

78.1

7

137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113Chemical Shift (ppm)

0.25

0.50

0.75

1.00

Inte

nsity

Acetonitrile-d3

113.

0311

3.25

119.

25

119.

73

120.

76

122.

08124.

45

124.

91

127.

2912

7.75

129.

29

130.

11

130.

9813

1.00

131.

86

135.

11

137.

34

93.5 93.0 92.5Chemical Shift (ppm)

0.025

0.050

Inte

nsity

92.5

3

92.8

5

93.1

8

93.5

1

13C NMR spectrum of 3n (100.6 MHz, CD3CN)

S44

Page 45: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 2.3069 Date Oct 18 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.18\BM-1402-2-F_20181018_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

OHN O

FF

F

H

Br

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-82.

06

19F NMR spectrum of 3n (376.5 MHz, CD3CN)

S45

Page 46: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 04 Oct 2018 08:19:12File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1381.H\BM-1381.H_001000fid Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 16384Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

OHN O

FF

F

H

Br

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

4.07 1.061.011.00

Acetonitrile-d37.

557.

53 7.41

7.39

7.38

7.36

7.11 7.

096.

796.

776.

75

6.34

6.25

6.08

5.64

5.61

7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

4.072.10 1.061.011.00 1.00 0.990.98 0.86

5.61

5.64

5.65

6.08

6.23

6.246.25

6.27

6.326.

34

6.75

6.77

6.79

7.09

7.117.36

7.38

7.39

7.41

7.44

7.45

7.53

7.55

1H NMR spectrum of 3o (400.1 MHz, CD3CN)

S46

Page 47: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 1.0000 Date Oct 5 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.05\BM-1381_20181005_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 32 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000

OHN O

FF

F

H

Br

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-82.

06

19F NMR spectrum of 3o (376.5 MHz, CD3CN)

S47

Page 48: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 27 Oct 2018 22:02:24File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181027-2\BM-1392-2f_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

OHN O

FF

F

H

Br

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

4.02 2.00 1.731.02

Acetonitrile-d3

7.56

7.43

7.38

7.23 7.

226.

956.

886.

866.

336.

06 5.74

5.67

7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4 5.3 5.2Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

4.02 2.001.99 1.731.02 1.021.00

5.67

5.74

6.06

6.316.33

6.86

6.86

6.88

6.88

6.90

6.90

6.926.93

6.94

6.95

6.96

7.22

7.22

7.23

7.24

7.38

7.41

7.43

7.44

7.44

7.46

7.48

7.557.56

7.57

7.58

1H NMR spectrum of 3p (400.1 MHz, CD3CN)

S48

Page 49: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 27 Oct 2018 22:12:02File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181027-2\BM-1392-2f_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 240 Original Points Count 16384 Points Count 131072Pulse Sequence zgpg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 24154.59Temperature (degree C) 27.000

OHN O

FF

F

H

Br

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Acetonitrile-d3Acetonitrile-d3

147.

96

136.

8613

5.13

132.

6313

0.07

127.

3712

4.78

121.

9711

9.11

118.

04

112.

9911

2.42

93.8

793

.54

93.2

192

.88

83.2

5

137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113Chemical Shift (ppm)

0.25

0.50

0.75

1.00

Inte

nsity

Acetonitrile-d3

112.

42

112.

99118.

04

119.

11

121.

9712

2.13

124.

78

127.

3712

7.62

128.

42

129.

9713

0.07

131.

06

132.

63

135.

13

136.

86

94.0 93.5 93.0 92.5Chemical Shift (ppm)

0.025

0.050

Inte

nsity

92.8

8

93.2

1

93.5

4

93.8

7

13C NMR spectrum of 3p (100.6 MHz, CD3CN)

S49

Page 50: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 424.2113 Formula C19H13BrF3NO2

Acquisition Time (sec) 2.0000 Date Oct 29 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.29\BM-1392-2f_20181029_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 178571Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000

OHN O

FF

F

H

Br

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

C6F6

-81.

95

19F NMR spectrum of 3p (376.5 MHz, CD3CN)

S50

Page 51: Supporting Information Diastereoselective synthesis of CF3 ... · Supporting Information Diastereoselective synthesis of CF3-oxazinoquinolines in water Vasiliy M. Muzalevskiya, Kseniya

13 Feb 2019

FW 346.3033 Formula C18H13F3N2O2

Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 17 Oct 2018 17:28:12File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1394.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 6 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000

OHN N O

FF

F

H

14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.141.02 1.011.00

Acetonitrile-d3

7.73

7.72 7.54

7.48 7.46

7.46

7.35

7.34

7.33

7.01 6.99

6.83 6.82 6.82

6.17

5.96

5.81 5.80

7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

3.142.181.131.02 1.01 1.001.000.99 0.97

5.80

5.81

5.96

6.14

6.156.17

6.186.

806.82

6.82

6.83

6.99

7.01

7.327.

337.

347.

357.

367.

37

7.46

7.46

7.48

7.48

7.54

7.557.567.72

7.727.73

6.0 5.5 5.0Chemical Shift (ppm)

0

0.025

0.050

Inte

nsity

1.01 1.000.97 0.51

5.80

5.81

5.96

6.14

6.15

6.17

6.18

1H NMR spectrum of 3q (400.1 MHz, CD3CN)

S51

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13 Feb 2019

FW 346.3033 Formula C18H13F3N2O2

Acquisition Time (sec) 2.3069 Date Oct 18 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.18\BM-1394-F_20181018_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000

OHN N O

FF

F

H

100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)

C6F6

-82.

04

19F NMR spectrum of 3q (376.5 MHz, CD3CN)

S52

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26 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 06 Jun 2019 19:17:06File Name I:\SPEC_2019_H,C\06.èþ í ü\BM-1604-a_001001r Frequency (MHz) 400.13 Nucleus 1H Number of Transients 8Original Points Count 32768 Points Count 131072 Pulse Sequence zg30 Solvent CHLOROFORM-DSweep Width (Hz) 8012.82 Temperature (degree C) 27.000

OHN O

FF

F

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.11 3.00 0.97 0.82

Chloroform-d

3.24

5.62

5.635.

685.

976.

846.

946.

977.17

7.19

7.36

7.37

7.39

7.52

7.54

7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

3.11 3.002.07 1.01 0.970.94 0.84 0.78 0.150.12

Chloroform-d

5.62

5.635.

68

5.97

6.03

6.04

6.05

6.07

6.08

6.10

6.116.

326.

34

6.816.

836.84

6.86

6.88

6.926.

946.

977.17

7.19

7.357.36

7.377.

397.

397.

407.

417.

427.

437.

527.52

7.54

1H NMR spectrum of diastereomeric mixture of 3a and 3a’ (400.1 MHz, CDCl3)

S53

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26 Aug 2019

Acquisition Time (sec) 1.0000 Date Jun 7 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.06.07\BM-1604-a_20190607_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 21.000

OHN O

FF

F

0 -8 -16 -24 -32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176 -184Chemical Shift (ppm)

87.16

C6F6

-81.

09-8

4.28

19F NMR spectrum of diastereomeric mixture of 3a and 3a’ (376.5 MHz, CDCl3)S54

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26 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 31 May 2019 15:12:08File Name C:\DOCS\OUTPUT_301\2019\05.ì àé\BM-1588.H_001001r Frequency (MHz) 400.13 Nucleus 1HNumber of Transients 4 Original Points Count 32768 Points Count 131072 Pulse Sequence zg30Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000

ON O

FF

F

CH3

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

2.93 1.971.95 1.310.94 0.90

3a

3a

3aEthanol

Acetonitrile-d3

Ethanol

7.56 7.

557.

437.

417.

02 7.00 6.

876.

856.

83

6.33

6.07

6.04

5.69

5.68

5.57 3.91 3.

883.

873.

853.

823.

80 3.58

3.56

3.54

1.95

1.94

1.93

1.26

1.24

1.22

1.14

1.12

7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

2.932.00 1.951.00 0.940.91 0.900.66 0.630.24 0.18 0.14

3a

3a

3a

7.56 7.

557.

547.

47

7.46

7.45 7.

447.

437.

437.

417.

397.

397.

387.

27 7.26 7.

257.

25

7.02 7.00

6.91

6.90 6.89 6.88

6.87

6.87

6.85

6.84

6.83

6.33

6.31

6.21 6.20

6.19

6.17

6.14

6.13

6.10

6.07

6.04

5.69 5.68

5.57

1H NMR spectrum of 4 (400.1 MHz, CD3CN). Signals of 3a are the result of hydrolysis of 4 during preparation and storing of the NMR sample.

S55

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26 Aug 2019

Acquisition Time (sec) 1.0000 Date Jun 3 2019 File Name I:\SPEC_F_2019\2019.06.03\BM-1588_20190603_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 21.000

ON O

FF

F

CH3

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)

3a

C6F6

-80.

10-8

1.93

19F NMR spectrum of 4 (376.5 MHz, CD3CN). Signals of 3a are the result of hydrolysis of 4 during preparation and storing of the NMR sample.

S56

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26 Aug 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 31 May 2019 15:20:20File Name C:\DOCS\OUTPUT_301\2019\05.ì àé\BM-1588.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 161 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

ON O

FF

F

CH3

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

3a

3a

3a

3a

3a

3a

3a

3a

3a EtOHEtOH

Acetonitrile-d315

0.50

138.

0813

5.36

131.

0513

0.11

127.

4212

7.36 12

1.57

118.

9611

7.91

112.

78

96.0

695

.74

95.4

395

.11

80.2

7

60.0

3 15.8

1

1.92

1.71

1.51

1.30

1.09

0.68

138 137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118Chemical Shift (ppm)

3a

3a

3a

3a

3a

3a3a

3a

138.

08

135.

36

131.

05

130.

4313

0.11

129.

60 128.

91

127.

5012

7.42

127.

36

124.

66

121.

8212

1.57

118.

96

117.

91

13C NMR spectrum of 4 (100.6 MHz, CD3CN). Signals of 3a are the result of hydrolysis of 4 during preparation and storing of the NMR sample.

S57

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27 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 05 Jun 2019 17:26:50File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

4.30 2.561.000.98 0.85

Chloroform-d

(MeCO2CH2S)2

(MeCO2CH2S)2

8.88

8.88

8.13 8.10

8.08

7.70 7.

687.

517.

417.

407.

38 7.23 6.

576.

42

3.78

3.71

3.52

3.31

7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5Chemical Shift (ppm)

4.30 2.562.16 1.781.200.85 0.14

Chloroform-d

(MeCO2CH2S)2

(MeCO2CH2S)2

7.42

7.41

7.41

7.40

7.38

7.36 7.23

7.23

7.22 6.

57

6.42

3.78

3.73

3.71

3.69 3.

633.

553.

52

3.31

N

S

OO

CH3

O

F

F

F

S

OO

CH3

O

F

F

F

1H NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (400.1 MHz, CDCl3). The region with signals of compound 5 are highlighted.

S58

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27 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 05 Jun 2019 17:26:50File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4Chemical Shift (ppm)

1.08 1.071.00 1.000.990.98 0.95

8.89 8.88

8.88

8.87

8.15 8.13

8.10 8.

08

7.79

7.78 7.77

7.70

7.68

7.68

7.68 7.

667.

66

7.53

7.51

7.49

7.49

7.42

7.41

7.41

7.40 7.

407.

387.

37 7.36

7.35

7.34

N S

OO

CH3

O

F

F

F

1H NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (400.1 MHz, CDCl3). The region with signals of quinoline are highlighted.

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27 Aug 2019

Acquisition Time (sec) 1.0000 Date Jun 3 2019 File Name I:\SPEC_F_2019\2019.06.03\BM-1591_20190603_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 8 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 21.000

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

85.00

C6F6

-78.

72-7

9.60

-78.5 -78.6 -78.7 -78.8 -78.9 -79.0 -79.1 -79.2 -79.3 -79.4 -79.5 -79.6 -79.7Chemical Shift (ppm)

85.00 14.90

-78.

72

-79.

60

N S

OO

CH3

O

F

F

F

19F NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (376.5 MHz, CDCl3)

S60

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27 Aug 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 05 Jun 2019 17:41:04File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 361 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

177.

8617

7.51

177.

1617

6.82

171.

2516

8.32

136.

68

130.

2312

9.93

128.

8012

7.58

120.

9611

7.52

114.

8111

4.63

111.

7410

9.26

77.3

277

.00

76.6

8

52.9

052

.53 34

.98

136 134 132 130 128 126 124 122 120 118 116 114 112 110Chemical Shift (ppm)

136.

68

130.

2312

9.93

128.

8012

8.37

127.

8912

7.58

120.

96

120.

41

117.

52

114.

8111

4.63

111.

74

109.

26

N S

OO

CH3

O

F

F

F

178 176 174 172 170 168Chemical Shift (ppm)

0.1

0.2Inte

nsity

168.

32

171.

25

176.

8217

7.16

177.

5117

7.86

13C NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (100.6 MHz, CDCl3). The signals of compound 5 are highlighted.

S61

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27 Aug 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 05 Jun 2019 17:41:04File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 361 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

150 148 146 144 142 140 138 136 134 132 130 128 126 124 122Chemical Shift (ppm)

149.

98

147.

67

136.

34

129.

52

128.

89

128.

1612

7.70

126.

55

120.

96

N S

OO

CH3

O

F

F

F

13C NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (100.6 MHz, CDCl3). The signals of quinoline are highlighted.

S62

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26 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 20 Jun 2019 19:27:10File Name C:\Users\BM-1\Downloads\BM-1607\BM-1607_001001r Frequency (MHz) 400.13 Nucleus 1HNumber of Transients 8 Original Points Count 32768 Points Count 131072 Pulse Sequence zg30Solvent CHLOROFORM-D Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000

N

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

3.042.84

Chloroform-d

8.23 8.

218.

178.

157.

887.

827.

547.

537.

517.

48 7.46

7.44

8.30 8.25 8.20 8.15 8.10 8.05 8.00 7.95 7.90 7.85 7.80 7.75 7.70 7.65 7.60 7.55 7.50 7.45Chemical Shift (ppm)

3.042.84 1.121.051.00 1.00 1.00

8.23 8.

21

8.19

8.17

8.17

8.15

7.88

7.86

7.84 7.

82

7.75

7.74

7.72

7.71

7.70

7.54

7.54

7.53

7.52

7.51

7.48

7.48 7.

46

7.44

1H NMR spectrum of 6 (400.1 MHz, CDCl3).

S63

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26 Aug 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 01 Jun 2019 14:15:34File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1595.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 146 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent ACETONITRILE-D3 Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

N

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

118.

96

126.

2212

7.52

128.

7912

9.61

136.

7413

9.60

148.

19

157.

30

129.5 129.0 128.5 128.0 127.5 127.0Chemical Shift (ppm)

127.

11

127.

41

127.

52

128.

79

129.

26

129.

6112

9.63

13C NMR spectrum of 6 (100.6 MHz, CDCl3)

S64

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26 Aug 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 08 Jul 2019 15:50:32File Name C:\DOCS\OUTPUT_301\2019\07.èþ ëü\BM-1623-1.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent DMSO-D6 Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000

N

O

FF

F

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

3.151.041.00

Chloroform-d

7.25

7.49

7.50

7.57

7.67

7.69

7.968.20

8.23

8.59

8.60 8.55 8.50 8.45 8.40 8.35 8.30 8.25 8.20 8.15 8.10 8.05 8.00 7.95 7.90 7.85 7.80 7.75 7.70 7.65 7.60 7.55 7.50 7.45 7.40Chemical Shift (ppm)

3.152.011.04 1.031.011.00 0.99

7.48

7.49

7.50

7.51

7.52

7.577.

577.

58

7.59

7.65

7.65

7.67

7.69

7.69

7.887.88

7.90

7.91

7.92

7.96

7.988.

208.

23

8.59

1H NMR spectrum of 7 (400.1 MHz, CDCl3)

S65

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26 Aug 2019

Acquisition Time (sec) 0.7340 Date Jul 5 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.07.05\BM-1623-R_20190705_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 65536Points Count 65536 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 25.000

N

O

FF

F

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

C6F6

-73.

72

19F NMR spectrum of 7 (376.5 MHz CDCl3)

S66

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26 Aug 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 08 Jul 2019 16:10:16File Name C:\DOCS\OUTPUT_301\2019\07.èþ ëü\BM-1623-1.C_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 505 Original Points Count 16384 Points Count 131072Pulse Sequence zgpg30 Solvent DMSO-D6 Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

N

O

FF

F

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

111.

5411

4.45

117.

3512

0.2612

4.94

125.

9112

7.94

128.

79

132.

9813

8.98

139.

0113

9.33

148.

73

157.

71

184.

0318

4.38

184.

7418

5.10

139 138 137 136 135 134 133 132 131 130 129 128 127 126 125Chemical Shift (ppm)

124.

94

125.

91

127.

94

128.

7212

8.79

128.

90

129.

34

129.

72

132.

98

138.

96138.

9813

9.01

139.

0313

9.33

120 118 116 114 112Chemical Shift (ppm)

0

0.05

Inte

nsity

120.

26 117.

35

114.

45

111.

54

185.0 184.5 184.0Chemical Shift (ppm)

0

0.025

Inte

nsity

185.

10

184.

74

184.

38

184.

03

13C NMR spectrum of 7 (100.6 MHz, CDCl3)

S67

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0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (мд)

1H.1.fid

3.11

2.10

1.05

1.02

2.05

1.00

0.07

1.94

1.95

2.19

7.50

7.50

7.51

7.52

7.56

7.57

7.58

7.68

7.70

7.72

7.91

7.93

7.95

8.08

8.10

8.12

8.78

7.57.67.77.87.98.08.18.28.38.48.58.68.78.88.9f1 (мд)

3.11

2.10

1.05

1.02

2.05

1.00

7.50

7.50

7.51

7.52

7.56

7.57

7.58

7.68

7.70

7.72

7.91

7.93

7.95

8.08

8.10

8.12

8.78

1H NMR spectrum of 7 (400.1 MHz, CD3CN)

S68

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-100-95-90-85-80-75-70-65-60-55-50-45-40-35-30-25-20-15-10-50f1 (мд)

19F_.1.fidF19 -7

2.47

19F NMR spectrum of 7 (376.5 MHz, CD3CN)

S69

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0102030405060708090100110120130140150160170180190200f1 (мд)

13C_.1.fid

0.70

0.91

1.11

1.32

1.53

1.73

1.94

112.

7411

5.64

118.

2411

8.54

121.

4412

5.98

126.

4212

9.08

129.

5612

9.82

130.

0713

0.16

130.

1913

0.25

134.

2614

0.67

140.

6914

0.77

149.

64

158.

39

184.

9218

5.27

185.

6318

5.98

112114116118120122124126128130f1 (мд)

112.

74

115.

64

118.

2411

8.54

121.

44

125.

9812

6.42

129.

0812

9.56

129.

8213

0.07

130.

1613

0.19

130.

25

13C NMR spectrum of 7 (100.6 MHz, CD3CN)

S70

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3 Oct 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 28 Sep 2019 10:32:32File Name I:\BM-1716-2\BM-1716-2_001001r Frequency (MHz) 400.13 Nucleus 1H Number of Transients 8Original Points Count 32768 Points Count 131072 Pulse Sequence zg30 Solvent CHLOROFORM-DSweep Width (Hz) 8012.82 Temperature (degree C) 27.000

N O

FF

F

OH

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

7.00 3.56 1.101.00 0.99 0.84 0.38

Chloroform-d

1.76

1.85

1.87

2.06

2.072.

302.332.34

2.37

2.47

2.67

2.692.

71

2.75

2.96

3.02

3.07

3.08

4.104.12

4.14

4.964.97

4.99

5.53

5.61

6.416.44

6.74

6.76

7.01

7.07

7.25

7.38

7.42

7.44

7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)

3.06 1.00 0.990.830.34 0.330.16

5.53

5.53

5.54

5.57

5.61

6.416.44

6.48

6.636.

646.

646.

666.

666.74

6.74

6.76

6.76

6.78

6.99

7.01

7.037.

077.

08

N OH

FF

F

3.0 2.5 2.0 1.5Chemical Shift (ppm)

0

0.25

0.50

0.75

1.00

Inte

nsity

3.56 1.961.91 1.10 0.730.440.40

3.09 3.08

3.07

3.06 3.

033.

022.

99 2.98

2.97 2.96

2.93 2.79

2.77

2.76

2.75

2.73 2.

712.

69 2.67

2.50

2.50 2.

472.

442.

37 2.34

2.33

2.33 2.

302.

262.

11 2.10 2.10

2.09 2.

07 2.06

2.06

2.05

2.04

1.86 1.85

1.84

1.84

1.76

1.76

1.75

1H NMR spectrum of 8 and 9 (400.1 MHz, CDCl3)

S71

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3 Oct 2019

Acquisition Time (sec) 2.0000 Date Sep 30 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.30\BM-1716-2_20190930_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 178571Points Count 262144 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

75.0029.26

C6F6

-87.

99

-80.

79

N O

FF

F

OH

N OH

FF

F

19F NMR spectrum of 8 and 9 (376.5 MHz CDCl3)

S72

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3 Oct 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 28 Sep 2019 11:10:38File Name I:\BM-1716-2\BM-1716-2_002001r Frequency (MHz) 100.61 Nucleus 13C Number of Transients 904Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30 Solvent CHLOROFORM-DSweep Width (Hz) 24154.59 Temperature (degree C) 27.000

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

21.6

1

25.9

228

.45

29.9

233

.39

42.0

6

54.3

255

.53

67.1

967

.50

67.8

168

.12

79.1

8

93.8

894.2

194

.53

94.8

6

111.

0211

2.87

116.

1511

8.49

122.

7612

3.18

125.

1312

7.38

129.

1412

9.68

139.

9914

2.18

143.

3514

5.83

132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113 112 111 110 109 108Chemical Shift (ppm)

111.

02

112.

87

116.

15

118.

0611

8.49

120.

90

122.

7612

3.18

123.

7412

4.02

125.

1312

5.48

126.

5812

6.82

126.

9712

7.30

127.

3812

7.54

128.

2512

8.49

129.

0312

9.14

129.

68

N O

FF

F

OH

N OH

FF

F

21.7 21.6Chemical Shift (...

0.25

0.50

0.75

1.00

Inte

nsity

21.7

0

21.6

1

13C NMR spectrum of 8 and 9 (100.6 MHz, CDCl3)

S73

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3 Oct 2019

Acquisition Time (sec) 1.3664 Comment Imported from UXNMR. Date 30 Sep 2019 16:01:36File Name I:\SPEC_2019_H,C\09.ñåí òÿáðü\BM-1716-2.APT_004001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 49 Original Points Count 32768 Points Count 131072 Pulse Sequence jmodSolvent ACETONITRILE-D3 Sweep Width (Hz) 23980.81 Temperature (degree C) 27.000

145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20Chemical Shift (ppm)

Chloroform-d

21.6221.71

25.93

28.4629.93

33.40

42.07

54.3

555

.54

67.2

067.5

167

.83

68.1

4

79.1

9

93.8994.2194.54

94.87

111.

0311

2.88

116.

16

118.

50

123.18

125.

1312

5.49

126.

9812

7.38

128.

2612

9.14

129.

68

140.00

142.19143.36

145.83

N O

FF

F

OH

N OH

FF

F

13C APT NMR spectrum of 8 and 9 (100.6 MHz, CDCl3)

S74

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3 Oct 2019

Acquisition Time (sec) 1.0000 Date Sep 20 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.20\BM-1709-R_20190920_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 8 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

9.60

C6F6

-85.

01-8

4.53

-82.

98-8

1.51

-81.5 -82.0 -82.5 -83.0 -83.5 -84.0 -84.5 -85.0Chemical Shift (ppm)

9.60 1.16 0.750.58

-85.

01-84.

53

-82.

98

-81.

51

N O

FF

F

O

CH3

N O

FF

F

O

CH3

19F NMR monitoring of hydrogenation of 3a in MeOH.Spectrum of the reaction mixture after first 14 h (376.5 MHz CDCl3)

S75

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3 Oct 2019

Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 28 Sep 2019 16:54:48File Name C:\DOCS\BM\BM-1709-f\BM-1709-f_001001r Frequency (MHz) 400.13 Nucleus 1H Number of Transients 8Original Points Count 32768 Points Count 131072 Pulse Sequence zg30 Solvent CHLOROFORM-DSweep Width (Hz) 8012.82 Temperature (degree C) 27.000

N O

FF

F

OCH3

19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)

5.09 3.10 3.011.99 1.021.000.99

Chloroform-d

1.86

1.871.89

2.642.68

2.692.

722.

732.

772.

773.

52

5.315.

335.

60

6.20

6.22

6.78

6.81

6.82

6.84

7.25

7.31

7.38

7.39

7.45 7.40 7.35 7.30 7.25 7.20 7.15 7.10 7.05 7.00 6.95 6.90 6.85 6.80 6.75Chemical Shift (ppm)

5.09 1.991.07

Chloroform-d

6.78

6.796.

806.81

6.82

6.82

6.847.

097.

097.

107.11

7.25

7.277.27

7.29

7.31

7.31

7.32

7.33

7.35

7.377.38

7.39

1H NMR spectrum of 10 (400.1 MHz, CDCl3)

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3 Oct 2019

Acquisition Time (sec) 2.0000 Date Sep 30 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.30\BM-1709-F_20190930_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 178571Points Count 262144 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000

N O

FF

F

OCH3

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

C6F6

-81.

52

19F NMR spectrum of 10 (376.5 MHz CDCl3)

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3 Oct 2019

Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 30 Sep 2019 15:45:06File Name I:\SPEC_2019_H,C\09.ñåí òÿáðü\BM-1709-F.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 161 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000

N O

FF

F

OCH3

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

24.6

5

29.4

3

50.8

182.9

9

95.2

795

.57

95.8

996

.20

105.

63

118.

5212

0.19

121.

4512

3.86

126.

76127.

0812

8.64

129.

5513

0.33

134.

6813

8.80

149.

27

132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117Chemical Shift (ppm)

118.

52

120.

19

121.

01

121.

45

123.

86

126.

7212

6.7612

7.08

128.

64

129.

55

130.

33

13C NMR spectrum of 10 (100.6 MHz, CDCl3)

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3 Oct 2019

Acquisition Time (sec) 1.3664 Comment Imported from UXNMR. Date 30 Sep 2019 15:49:36File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-F.APT_004001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 33 Original Points Count 32768 Points Count 131072Pulse Sequence jmod Solvent ACETONITRILE-D3 Sweep Width (Hz) 23980.81Temperature (degree C) 27.000

N O

FF

F

O

CH3

150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25Chemical Shift (ppm)

Chloroform-d

24.6529.43

50.8

1

82.9

9

105.

64120.

1912

1.45

126.

7612

7.08

128.

6412

9.55

130.33

134.68

138.80

149.26

13C APT NMR spectrum of 10 (100.6 MHz, CDCl3)

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Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 27 Sep 2019 15:28:36File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-K.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent CHLOROFORM-D Sweep Width (Hz) 8012.82Temperature (degree C) 27.000

CH3

N O

FF

F

O

16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)

5.00 2.72 1.070.930.910.89 0.87

Chloroform-d

7.41

7.39 7.37

7.35

7.33

7.31

7.04

6.99 6.

736.

406.

38 5.52

4.92

4.90

4.89

4.87

3.29

2.75 2.60 2.

582.

572.

36 2.33

2.29

2.08

7.05 7.00 6.95Chemical Shift (ppm)

0.90 0.89

7.06

7.04

7.01

6.99

6.97

6.7 6.6 6.5 6.4Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Inte

nsity

0.890.88

6.386.

40

6.71

6.73

6.75

3.00 2.75 2.50 2.25 2.00Chemical Shift (ppm)

0

0.05

0.10

0.15

0.20

0.25

Inte

nsity

1.07 0.97 0.93 0.920.920.91

2.04

2.072.08

2.08

2.11

2.11

2.12

2.29

2.322.

332.

362.

392.

412.

412.

432.44

2.45

2.45

2.572.

582.

602.

622.

682.

712.

722.752.

752.

762.

78

3.06

3.07

3.093.11

3.13

1H NMR spectrum of 11 (400.1 MHz, CDCl3)

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Acquisition Time (sec) 1.0000 Date Sep 27 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.27\BM-1709-K_20190927_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 4 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000

CH3

N O

FF

F

O

30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)

C6F6

-83.

05

19F NMR spectrum of 11 (376.5 MHz CDCl3)

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Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 27 Sep 2019 15:38:00File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-K.C_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 233 Original Points Count 16384 Points Count 131072Pulse Sequence zgpg30 Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59Temperature (degree C) 27.000

CH3

N O

FF

F

O

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

22.2

926

.30

34.6

0

50.4

5

55.8

3

79.0

4

95.3

095

.61

95.9

296

.23

112.

79

118.

3212

1.29

122.

8212

5.15

128.

3012

9.10

142.

3414

3.47

144 142 140 138 136 134 132 130 128 126 124 122 120 118 116 114 112Chemical Shift (ppm)

112.

79

118.

3211

8.42

121.

29

122.

82

124.

16

125.

15

127.

0412

7.35

127.

4712

8.30

129.

10

142.

34

143.

47

13C NMR spectrum of 11 (100.6 MHz, CDCl3)

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Acquisition Time (sec) 1.3664 Comment Imported from UXNMR. Date 30 Sep 2019 15:55:04File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-R.APT_004001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 34 Original Points Count 32768 Points Count 131072Pulse Sequence jmod Solvent ACETONITRILE-D3 Sweep Width (Hz) 23980.81Temperature (degree C) 27.000

CH3

N O

FF

F

O

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)

Chloroform-d

143.49142.36

129.

1012

7.36

125.

15

122.83

118.

33

112.

80

79.0

5

55.8

5

50.4

6

34.62

26.3222.30

129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113Chemical Shift (ppm)

129.

10

128.

30

127.

4712

7.36

125.

15

122.83

118.

33

112.

80

13C APT NMR spectrum of 11 (100.6 MHz, CDCl3)

S83