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1

Synthesis of Aziridines with Multiple Chiral Substitutions by

Copper-catalyzed Diastereoselective Radical

Aminotrifluoromethylation of Alkenes

Shuanglin Qin,a, b, § Linbin Yao, c, § Yunhao Luo, a, § Tongtong Liu, a, § Jiayuan Xu, c Yue Sun, a Ning Wang, a Jun Yan, d Bencan Tang, c, * Guang Yang, a, * Guang Yang a, *

a The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University,

Tianjin, 300350, China.

b School of pharmacy, Hubei University of Science and Technology, Xianning, 437100, China.

c Department of Chemical and Environmental Engineering, Faculty of Science and Engineering, The

University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo, 315100, China.

d School of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China.

§ These authors contributed equally to this work.

Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers.This journal is © the Partner Organisations 2020

2

Contents of information 1 General Information .................................................................................................... 3

2 Synthesis of Substrates C. ........................................................................................... 4

3 Synthesis of Substrates G. ......................................................................................... 15

4 Asymmetric alkylation of Cyclic Sulfinimines ......................................................... 17

5 Transformations of the substrate 3 ............................................................................ 33

5 Crystal data of Compounds 7 and 26 ........................................................................ 36

6 Computational Studies .............................................................................................. 38

7 NMR Spectrums of Compounds ............................................................................... 46

8 Reference ................................................................................................................ 180

3

1 General Information

All reactions were carried out under an argon atmosphere with dry, freshly distilled

solvents under anhydrous conditions, unless otherwise noted. Yields refer to

chromatographically and spectroscopically (1H NMR) homogeneous materials, unless

otherwise stated. The used solvents were purified and dried according to common

procedures. Other chemicals and solvents were commercially available. High-

resolution mass spectra (HRMS) were obtained with a FTICR-MS (Ion spec 7.0T)

spectrometer. Enantio ratio (er) was determined using different columns, Daicel

Chiralpak AD-H Column (250 x 4.6 mm), Chiralpak ID Column (250 x 4.6 mm),

Chiralpak IE Column (250 x 4.6 mm) on Agilent HPLC 1260 and Shimadzu HPLC LC-

20AT. 1H NMR spectra were obtained by using a Bruker AV 400 or AV 600. Chemical

shifts are reported in parts per million (ppm) relative to either a tetramethylsilane

internal standard or solvent signals. Data are reported as follows: chemical shift,

multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet),

coupling constants and integration. 13C NMR spectra were recorded using a Bruker AV

400 spectrometer (100 MHz) using CDCl3 as the solvent. Chemical shifts (δ) are

reported in parts per million measured relative to the solvent peak. IR spectra were

recorded with a Bio-Rad FTS 6000 Fourier infrared spectrometer.

4

2 Synthesis of Substrates C.

General procedure:

To a solution of aldehyde A (1.0 equiv.) and (R)-2-methylpropane-2-sulfinamide (1.2

equiv.) in tetrahydrofuran (0.2 M) was added tetraethoxytitanium (1.5 equiv.). The

mixture was stirred at 60 oC for 12 h. When complete, the mixture was slowly poured

into water (1 L) and then filtered, the filtrate was concentrated in vacuo. The resulting

residue was extracted with ethyl acetate, the organic layer was washed with water, dried

over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by

chromatography on silica gel to give the compounds B with high yield.

To a solution of B in CH2Cl2 at -78 °C was added Grignard reagent in Et2O. The

mixture was stirred at -78 °C for 3-7 h and then was warmed to rt with stirring overnight.

On completion, the reaction mixture was quenched by the addition of sat'd aq. NH4Cl

and extracted with EtOAc. The combined organic layers were dried over Na2SO4,

filtered and concentrated in vacuo. Then the crude product was chromatographed to

give the product C.

C1

(R)-2-methyl-N-((S)-1-phenylallyl) propane-2-sulfinamide C1:

70%, pale yellow oil. [α]20 D = - 71.70 (c 1.4, CHCl3). IR (KBr) νmax: 3063, 3029, 2978,

2958, 2925, 2867, 2360, 2342, 1493, 1474, 1454, 1363, 1260, 1062, 921, 700 cm-1.1H

NMR (400 MHz, CDCl3) δ 7.36 – 7.31 (m, 4H), 7.31 – 7.27 (m, 1H), 6.04 (ddd, J =

17.1, 10.2, 7.0 Hz, 1H), 5.34 – 5.17 (m, 2H), 4.97 (dd, J = 6.9, 3.6 Hz, 1H), 3.49 (d, J

= 3.0 Hz, 1H), 1.21 (s, 9H).13C NMR (101 MHz, CDCl3) δ 140.5, 139.4, 128.7, 128.0,

127.9, 116.8, 61.7, 55.9, 22.7. HRMS (ESI) calculated for C13H19NNaOS+ [M+Na]+:

260.1080, found 260.1081.

C2

(R)-2-methyl-N-((S)-1-(p-tolyl)allyl)propane-2-sulfinamide C2:

5

68%, white solid. [α]19 D = - 71.27 (c 1.4, CHCl3). m. p. 83-84 oC. IR (KBr) νmax: 3192,

29733, 2952, 2921, 2360, 1646, 1510, 1362, 1058, 912, 814. cm-1.1H NMR (400 MHz,

CDCl3) δ 7.22 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.02 (ddd, J = 17.1, 10.2,

7.0 Hz, 1H), 5.23 (dd, J = 43.1, 13.6 Hz, 2H), 4.93 (dd, J = 6.9, 3.4 Hz, 1H), 3.47 (d, J

= 3.1 Hz, 1H), 2.34 (s, 3H), 1.21 (s, 9H).13C NMR (101 MHz, CDCl3) δ 139.6, 137.7,

137.4, 129.5, 127.8, 116.5, 61.4, 55.8, 22.7, 21.3. HRMS (ESI) calculated for

C14H21NNaOS+ [M+Na]+: 274.1236, found 274.1235.

HNS

O

t-Bu

F C3

(R)-N-((S)-1-(4-fluorophenyl)allyl)-2-methylpropane-2-sulfinamide C3:

71%, colourless oil. [α]18 D = - 86.72 (c 2.1, CHCl3). IR (KBr) νmax: 2980, 2964, 2360,

1513, 1341, 1147, 1090, 841, 712. cm-1.1H NMR (400 MHz, CDCl3) δ 7.35 – 7.29 (m,

2H), 7.08 – 7.00 (m, 2H), 6.01 (ddd, J = 17.1, 10.2, 6.9 Hz, 1H), 5.24 (dd, J = 29.6,

13.2 Hz, 2H), 4.97 (dd, J = 6.8, 3.1 Hz, 1H), 3.50 (d, J = 2.7 Hz, 1H), 1.21 (s, 9H).13C

NMR (101 MHz, CDCl3) δ 163.6, 161.2, 139.2, 136.1, 136.1, 129.6, 129.5, 116.9, 115.7,

115.5, 60.8, 55.8, 22.7.19F NMR (376 MHz, CDCl3) δ -114.40 (tt, J = 8.7, 5.4 Hz).

HRMS (ESI) calculated for C13H18FNNaOS+ [M+Na]+: 278.0985, found 278.0987.

C4

(R)-N-((S)-1-(4-chlorophenyl)allyl)-2-methylpropane-2-sulfinamide C4:


2973, 2901, 2359, 1716, 1540, 1058, 1012, 884, 600. cm-1.1H NMR (400 MHz, CDCl3)

δ 7.34 – 7.27 (m, 4H), 6.00 (ddd, J = 17.1, 10.2, 6.9 Hz, 1H), 5.25 (dd, J = 28.5, 13.6

Hz, 2H), 4.96 (dd, J = 6.9, 3.1 Hz, 1H), 3.48 (d, J = 2.7 Hz, 1H), 1.22 (s, 9H).13C NMR

(101 MHz, CDCl3) δ 138.8, 133.7, 129.2, 128.8, 117.1, 60.8, 55.8, 22.6. HRMS (ESI)

calculated for C13H18ClNNaOS+ [M+Na]+: 294.0690, found 294.0692.

C5

(R)-2-methyl-N-((S)-1-(4-(trifluoromethyl)phenyl)allyl)propane-2-sulfinamide C5:

65%, white solid. [α]22 D = - 56.70 (c 1.4, CHCl3). m. p. 73-74 oC.IR (KBr) νmax: 3216,

2994, 2963, 2927, 2360, 1617, 1418, 1327, 1163, 1056, 1015, 925, 599. cm-1.1H NMR

6

(400 MHz, CDCl3) δ 7.61 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.2 Hz, 2H), 6.00 (ddd, J =

17.1, 10.1, 7.0 Hz, 1H), 5.27 (dd, J = 25.7, 13.6 Hz, 2H), 5.04 (dd, J = 6.9, 2.9 Hz, 1H),

3.52 (d, J = 2.7 Hz, 1H), 1.22 (s, 9H).13C NMR (101 MHz, CDCl3) δ 138.6, 130.3,

130.0, 128.3, 125.8, 125.8, 125.7, 125.7, 125.5, 122.8, 117.7, 61.2, 56.1, 22.7. 19F NMR

(376 MHz, CDCl3) δ -62.51 (s). HRMS (ESI) calculated for C14H18F3NNaOS+ [M+Na]+:

328.0953, found 328.0955.

C6

(R)-2-methyl-N-((S)-1-(o-tolyl)allyl)propane-2-sulfinamide C6:


2958, 2360, 1463, 1363, 1061, 923, 759. cm-1.1H NMR (400 MHz, CDCl3) δ 7.37 –

7.31 (m, 1H), 7.24 – 7.14 (m, 3H), 6.03 (ddd, J = 17.0, 10.2, 6.9 Hz, 1H), 5.27 – 5.14

(m, 3H), 3.48 (d, J = 3.3 Hz, 1H), 2.38 (s, 3H), 1.21 (s, 9H).13C NMR (101 MHz, CDCl3)

δ 138.7, 138.3, 136.3, 130.7, 127.6, 127.4, 126.3, 116.8, 57.6, 55.8, 22.7, 19.5. HRMS

(ESI) calculated for C14H21NNaOS+ [M+Na]+: 274.1236, found 274.1237.

C7

(R)-N-((S)-1-(4-ethylphenyl)allyl)-2-methylpropane-2-sulfinamide C7:


2360, 1471, 1415, 1057, 830. cm-1.1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 8.2 Hz,

2H), 7.18 (d, J = 8.0 Hz, 2H), 6.04 (ddd, J = 17.1, 10.1, 7.1 Hz, 1H), 5.29 (d, J = 17.0

Hz, 1H), 5.18 (d, J = 10.2 Hz, 1H), 4.94 (dd, J = 6.8, 3.6 Hz, 1H), 3.47 (d, J = 3.2 Hz,

1H), 2.65 (q, J = 7.6 Hz, 2H), 1.28 – 1.19 (m, 12H).13C NMR (101 MHz, CDCl3) δ

144.0, 139.6, 137.7, 128.2, 127.8, 116.5, 61.5, 55.9, 28.6, 22.7, 15.5. HRMS (ESI)

calculated for C15H23NNaOS+ [M+Na]+: 288.1393, found 288.1395.

C8

(R)-2-methyl-N-((S)-1-(4-(trifluoromethoxy)phenyl)allyl)propane-2-sulfinamide C8:


2980, 2958, 2360, 1506, 1417, 1262, 1162, 1056, 1015, 9441, 599. cm-1.1H NMR (400

MHz, CDCl3) δ 7.36 (d, J = 7.5 Hz, 2H), 7.18 (d, J = 7.2 Hz, 2H), 5.98 (dd, J = 16.6,

7

8.5 Hz, 1H), 5.24 (dd, J = 27.8, 13.5 Hz, 2H), 4.98 (s, 1H), 3.50 (s, 1H), 1.20 (s, 9H).13C

NMR (101 MHz, CDCl3) δ 148.8, 139.2, 138.9, 129.3, 124.4, 121.8, 121.1, 119.3, 117.3,

60.9, 56.0, 22.7. 19F NMR (376 MHz, CDCl3) δ -57.85 (s). HRMS (ESI) calculated for

C14H18F3NNaO2S+ [M+Na]+: 344.0903, found 344.0902.

C9

(R)-2-methyl-N-((S)-1-(3-(trifluoromethoxy)phenyl)allyl)propane-2-sulfinamide C9:


2360, 1610, 1488, 1262, 1251, 1164, 1063, 704. cm-1.1H NMR (400 MHz, CDCl3) δ

7.37 (t, J = 7.9 Hz, 1H), 7.30 – 7.25 (m, 1H), 7.22 (s, 1H), 7.14 (dd, J = 8.1, 1.0 Hz,

1H), 6.00 (ddd, J = 17.1, 10.2, 7.0 Hz, 1H), 5.27 (dd, J = 25.5, 13.6 Hz, 2H), 5.01 (dd,

J = 6.9, 3.2 Hz, 1H), 3.50 (d, J = 2.8 Hz, 1H), 1.22 (s, 9H).13C NMR (101 MHz, CDCl3)

δ 149.7, 143.0, 138.7, 130.1, 126.4, 124.4, 121.9, 120.4, 120.2, 119.3, 117.6, 116.7,

61.0, 56.0, 22.6.19F NMR (376 MHz, CDCl3) δ -57.79 (s). HRMS (ESI) calculated for


C10

(R)-N-((S)-1-(3,4-dichlorophenyl)allyl)-2-methylpropane-2-sulfinamide C10:


2987, 2955, 2360, 1469, 1388, 1057, 1027, 926, 878, 669. cm-1.1H NMR (400 MHz,

CDCl3) δ 7.42 (d, J = 8.1 Hz, 2H), 7.18 (dd, J = 8.3, 2.0 Hz, 1H), 5.95 (ddd, J = 17.1,

10.1, 7.0 Hz, 1H), 5.26 (dd, J = 23.6, 13.6 Hz, 2H), 4.93 (dd, J = 6.8, 2.7 Hz, 1H), 3.48

(d, J = 2.4 Hz, 1H), 1.22 (s, 9H).13C NMR (101 MHz, CDCl3) δ 140.8, 138.4, 132.9,


C13H17Cl2NNaOS+ [M+Na]+: 328.0300, found 328.0301.

C11

(R)-N-((S)-1-(3,4-difluorophenyl)allyl)-2-methylpropane-2-sulfinamide C11:

8


2360, 1610, 1517, 1457, 1282, 1208, 1062, 821. cm-1.1H NMR (400 MHz, CDCl3) δ

7.19 – 7.03 (m, 3H), 6.02 – 5.90 (m, 1H), 5.25 (dd, J = 22.7, 13.5 Hz, 2H), 4.93 (d, J =

6.2 Hz, 1H), 3.47 (s, 1H), 1.21 (s, 9H).13C NMR (101 MHz, CDCl3) δ 151.8, 151.7,

151.3, 151.2, 149.4, 149.3, 148.8, 148.7, 138.6, 137.5, 124.1, 124.1, 124.0, 124.0, 117.6,

117.5, 117.4, 116.9, 116.7, 60.5, 56.0, 22.7.19F NMR (376 MHz, CDCl3) δ -136.82 – -

137.00 (m), -138.67 – -138.86 (m). HRMS (ESI) calculated for C13H17F2NNaOS+

[M+Na]+: 296.0891, found 296.0892.

C12

(R)-2-methyl-N-((S)-1-(naphthalen-2-yl)allyl)propane-2-sulfinamide C12:


2951, 2856, 2360, 1261, 1057, 1019, 865, 830.cm-1.1H NMR (400 MHz, CDCl3) δ 7.88

– 7.74 (m, 4H), 7.52 – 7.39 (m, 3H), 6.13 (ddd, J = 17.0, 10.2, 6.8 Hz, 1H), 5.29 (dd, J

= 43.6, 13.6 Hz, 2H), 5.15 (dd, J = 6.7, 3.3 Hz, 1H), 3.56 (d, J = 3.0 Hz, 1H), 1.22 (s,

9H).13C NMR (101 MHz, CDCl3) δ 139.3, 137.8, 133.5, 133.2, 128.6, 128.1, 127.8,



C13

(R)-N-((S)-1-(4-fluoro-3-methylphenyl)allyl)-2-methylpropane-2-sulfinamide C13:


2925, 2360, 1499, 1473, 1117, 1059, 1020, 823. cm-1.1H NMR (400 MHz, CDCl3) δ

7.13 (s, 2H), 6.97 (t, J = 8.4 Hz, 1H), 6.01 (dd, J = 15.4, 6.9 Hz, 1H), 5.23 (dd, J = 34.8,

13.5 Hz, 2H), 4.91 (s, 1H), 3.45 (s, 1H), 2.26 (s, 3H), 1.21 (s, 9H).13C NMR (101 MHz,

CDCl3) δ 162.2, 159.8, 139.4, 135.9, 135.8, 131.2, 131.1, 126.8, 126.7, 125.2, 125.1,

116.7, 115.4, 115.2, 60.9, 55.9, 22.7, 14.7. 19F NMR (376 MHz, CDCl3) δ -118.70 (s).

HRMS (ESI) calculated for C14H20FNNaOS+ [M+Na]+: 292.1142, found 292.1143.

C14

9

(R)-N-((S)-1-([1,1'-biphenyl]-4-yl)allyl)-2-methylpropane-2-sulfinamide C14:


2953, 2924, 2854, 2360, 1485, 1261, 1057, 1013, 803, 728. cm-1.1H NMR (400 MHz,

CDCl3) δ 7.62 – 7.54 (m, 4H), 7.48 – 7.38 (m, 4H), 7.35 (t, J = 7.3 Hz, 1H), 6.08 (ddd,

J = 17.1, 10.2, 7.0 Hz, 1H), 5.34 (d, J = 17.0 Hz, 1H), 5.23 (d, J = 10.2 Hz, 1H), 5.03

(dd, J = 6.9, 3.5 Hz, 1H), 3.51 (d, J = 3.3 Hz, 1H), 1.24 (s, 9H).13C NMR (101 MHz,

CDCl3) δ 140.9, 140.8, 139.5, 139.4, 128.9, 128.3, 127.5, 127.2, 116.9, 61.5, 56.0, 22.8.

HRMS (ESI) calculated for C19H23NNaOS+ [M+Na]+: 336.1393, found 336.1395.

C15

(R)-2-methyl-N-((S)-1-(thiophen-3-yl)allyl)propane-2-sulfinamide C15:


1474, 1456, 1363, 1062, 923, 788. cm-1.1H NMR (400 MHz, CDCl3) δ 7.30 (dd, J = 5.0,

3.0 Hz, 1H), 7.20 (d, J = 2.6 Hz, 1H), 7.02 (dd, J = 5.0, 0.9 Hz, 1H), 6.05 (ddd, J = 17.1,

10.1, 7.1 Hz, 1H), 5.26 (dd, J = 35.8, 13.6 Hz, 2H), 5.09 – 5.01 (m, 1H), 3.46 (d, J =

4.3 Hz, 1H), 1.21 (s, 9H).13C NMR (101 MHz, CDCl3) δ 141.6, 138.8, 126.8, 126.4,

122.8, 117.0, 57.9, 55.9, 22.7. HRMS (ESI) calculated for C11H17NNaOS2+ [M+Na]+:

266.0644, found 266.0644.

C16

(R)-2-methyl-N-((R)-5-methylhex-1-en-3-yl)propane-2-sulfinamide C16:


2360, 2341, 1469, 1418, 1385, 1364, 1058, 916, 799 cm-1.1H NMR (400 MHz, CDCl3)

δ 5.81 (dt, J = 17.3, 8.7 Hz, 1H), 5.32 – 5.08 (m, 2H), 3.77 (p, J = 7.0 Hz, 1H), 3.02 (d,

J = 6.5 Hz, 1H), 1.68 (td, J = 13.2, 6.6 Hz, 1H), 1.58 – 1.43 (m, 1H), 1.32 (dt, J = 13.8,

6.8 Hz, 1H), 1.19 (s, 9H), 0.89 (d, J = 6.5 Hz, 6H).13C NMR (101 MHz, CDCl3) δ 140.5,



C17

(R)-N-((R)-hept-1-en-3-yl)-2-methylpropane-2-sulfinamide C17:

10


2360, 2341, 1457, 1417, 1387, 1362, 1058, 1221, 915, 668 cm-1.1H NMR (400 MHz,

CDCl3) δ 5.81 (ddd, J = 17.3, 10.3, 7.2 Hz, 1H), 5.30 – 5.13 (m, 2H), 3.78 – 3.66 (m,

1H), 3.07 (d, J = 6.1 Hz, 1H), 1.70 – 1.59 (m, 1H), 1.56 – 1.44 (m, 1H), 1.36 – 1.26 (m,

4H), 1.21 (s, 9H), 0.89 (t, J = 6.9 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 140.1, 116.6,

58.9, 55.9, 35.1, 27.8, 22.7, 22.6, 14.2. HRMS (ESI) calculated for C11H23NNaOS+

[M+Na]+: 240.1393, found 240.1394.

C18

(R)-2-methyl-N-((R)-5-phenylpent-1-en-3-yl)propane-2-sulfinamide C18:


2360, 2341, 1455, 1362, 1261, 1056, 919, 699 cm-1.1H NMR (400 MHz, CDCl3) δ 7.28

(dd, J = 12.6, 5.2 Hz, 2H), 7.19 (t, J = 8.9 Hz, 3H), 5.88 (ddd, J = 17.3, 10.3, 7.1 Hz,

1H), 5.26 (dd, J = 29.2, 13.8 Hz, 2H), 3.81 (p, J = 6.6 Hz, 1H), 3.15 (d, J = 6.1 Hz, 1H),

2.73 – 2.59 (m, 2H), 2.08 – 1.93 (m, 1H), 1.91 – 1.77 (m, 1H), 1.23 (s, 9H).13C NMR

(101 MHz, CDCl3) δ 141.7, 139.6, 128.6, 128.5, 126.1, 117.1, 58.4, 55.9, 37.2, 31.9,

22.8. HRMS (ESI) calculated for C15H23NNaOS+ [M+Na]+: 288.1393, found 288.1395.

C19

(R)-2-methyl-N-((R)-oct-1-en-3-yl)propane-2-sulfinamide C19:


2360, 1457, 1418, 1362, 1058, 914, 597. cm-1.1H NMR (400 MHz, CDCl3) δ 5.81 (ddd,

J = 17.3, 10.3, 7.2 Hz, 1H), 5.20 (dd, J = 36.5, 13.7 Hz, 2H), 3.77 – 3.66 (m, 1H), 3.07

(d, J = 6.2 Hz, 1H), 1.69 – 1.58 (m, 1H), 1.49 (ddd, J = 20.9, 14.1, 6.7 Hz, 1H), 1.34 –

1.24 (m, 6H), 1.21 (s, 9H), 0.87 (t, J = 6.8 Hz, 3H).13C NMR (101 MHz, CDCl3) δ

140.1, 116.5, 58.9, 55.8, 35.3, 31.7, 25.3, 22.7, 22.7, 14.1. HRMS (ESI) calculated for


C20

(R)-N-((R)-dec-1-en-3-yl)-2-methylpropane-2-sulfinamide C20:


2360, 1458, 1362, 1059, 914. cm-1.1H NMR (400 MHz, CDCl3) δ 5.80 (ddd, J = 17.3,

10.3, 7.2 Hz, 1H), 5.19 (dd, J = 36.6, 13.7 Hz, 2H), 3.71 (p, J = 6.7 Hz, 1H), 3.07 (d, J

11

= 6.2 Hz, 1H), 1.62 (dt, J = 8.9, 6.0 Hz, 1H), 1.56 – 1.41 (m, 1H), 1.32 – 1.22 (m, 10H),

1.20 (s, 9H), 0.86 (t, J = 6.8 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 140.1, 116.5, 58.9,

55.8, 35.4, 31.9, 29.5, 29.3, 25.6, 22.8, 22.7, 14.2. HRMS (ESI) calculated for


C21

(R)-N-((S)-1-cyclohexylallyl)-2-methylpropane-2-sulfinamide C21:


2359, 2341, 1450, 1362, 1059, 914, 596 cm-1.1H NMR (400 MHz, CDCl3) δ 5.80 (ddd,

J = 17.5, 10.3, 7.5 Hz, 1H), 5.20 (dd, J = 20.2, 13.7 Hz, 2H), 3.53 (dd, J = 13.2, 7.1 Hz,

1H), 3.05 (d, J = 7.4 Hz, 1H), 1.77 – 1.63 (m, 5H), 1.56 – 1.44 (m, 1H), 1.21 (s, 9H),

1.19 – 0.87 (m, 5H).13C NMR (101 MHz, CDCl3) δ 138.4, 117.2, 64.3, 56.1, 42.5, 29.3,

28.8, 26.6, 26.3, 26.2, 22.8. HRMS (ESI) calculated for C13H25NNaOS+ [M+Na]+:

266.1549, found 266.1550.

C22

(R)-2-methyl-N-((R)-1-phenylbut-3-en-2-yl)propane-2-sulfinamide C22:


2955, 2924, 2866, 2360, 2342, 1496, 1474, 1455, 1363, 1055, 921, 700 cm-1.1H NMR

(400 MHz, CDCl3) δ 7.32 – 7.26 (m, 2H), 7.24 – 7.16 (m, 3H), 5.91 (ddd, J = 17.1,

10.4, 6.6 Hz, 1H), 5.21 (dd, J = 34.0, 13.8 Hz, 2H), 4.04 (p, J = 6.8 Hz, 1H), 3.20 (d, J

= 6.7 Hz, 1H), 2.96 – 2.83 (m, 2H), 1.10 (s, 9H).13C NMR (101 MHz, CDCl3) δ 139.2,



C23

(R)-2-methyl-N-((S)-2-methyl-1-(naphthalen-2-yl)allyl)propane-2-sulfinamide C23:


2922, 2360, 1507, 1473, 1456, 1364, 1123, 1056, 898, 747. cm-1.1H NMR (400 MHz,

CDCl3) δ 7.81 (d, J = 9.3 Hz, 4H), 7.52 – 7.40 (m, 3H), 5.26 (s, 1H), 5.01 (s, 2H), 3.65

(d, J = 1.8 Hz, 1H), 1.69 (s, 3H), 1.23 (s, 9H).13C NMR (101 MHz, CDCl3) δ 146.2,

136.9, 133.3, 133.2, 128.4, 128.1, 127.8, 127.8, 126.3, 126.2, 125.6, 111.7, 63.5, 55.9,

12

22.8, 20.3. HRMS (ESI) calculated for C18H23NNaOS+ [M+Na]+: 324.1393, found

324.1392.

C24

(R)-2-methyl-N-((S)-2-methyl-1-phenylallyl)propane-2-sulfinamide C24:


2867, 2360, 1648, 1474, 1064, 900, 700. cm-1.1H NMR (400 MHz, CDCl3) δ 7.36 –

7.27 (m, 5H), 5.18 (s, 1H), 4.95 (s, 1H), 4.85 (d, J = 3.1 Hz, 1H), 3.55 (d, J = 2.7 Hz,

1H), 1.65 (s, 3H), 1.22 (s, 9H).13C NMR (101 MHz, CDCl3) δ 146.3, 139.6, 128.5,

128.2, 127.9, 111.7, 63.5, 55.9, 22.7, 20.0. HRMS (ESI) calculated for C14H21NNaOS+

[M+Na]+: 274.1236, found 274.1237.

C25

(R)-N-((S)-1-(4-fluorophenyl)-2-methylallyl)-2-methylpropane-2-sulfinamide C25:


1603, 1508, 1465, 1223, 1157, 1062, 1015, 903, 833, 599. cm-1.1H NMR (400 MHz,

CDCl3) δ 7.36 – 7.28 (m, 2H), 7.06 – 6.97 (m, 2H), 5.16 (s, 1H), 4.95 (s, 1H), 4.83 (d,

J = 2.7 Hz, 1H), 3.54 (d, J = 2.3 Hz, 1H), 1.64 (s, 3H), 1.21 (s, 9H).19F NMR (376 MHz,

CDCl3) δ -114.45 (ddd, J = 8.5, 5.3, 3.2 Hz). HRMS (ESI) calculated for

C14H20FNNaOS+ [M+Na]+: 292.1142, found 292.1145.

C26

(R)-2-methyl-N-((S)-2-methyl-1-(4-(trifluoromethyl) phenyl) allyl) propane-2-

sulfinamide C26:


1640, 1495, 1474, 1390, 1263, 1219, 1146, 1084, 931, 795, 770, 703 cm-1. 1H NMR

(400 MHz, CDCl3) δ 7.58 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 5.17 (d, J = 0.8

Hz, 1H), 5.02 – 4.88 (m, 2H), 3.57 (d, J = 2.8 Hz, 1H), 1.65 (s, 3H), 1.22 (s, 9H). 13C

NMR (100 MHz, CDCl3) δ 145.5, 143.9, 130.7, 130.4, 130.0, 129.7, 128.6, 125.6, 125.5,

125.5, 125.5, 122.9, 112.7, 63.1, 56.1, 22.7, 19.8.19F NMR (376 MHz, CDCl3) δ -62.54

(s).HRMS (ESI) calculated for C15H20F3NNaOS+ [M+Na]+: 342.1110, found 342.1111.

13

C27

(R)-N-((S)-1-(4-fluoro-3-methylphenyl)-2-methylallyl)-2-methylpropane-2-

sulfinamide C27:

72%, colourless oil. [α]20 D = - 153.28 (c 1.0, CHCl3) . IR (KBr) νmax: 3205, 2960, 2925,

2360, 1650, 1502, 1474, 1248, 1118, 1065, 900, 819, 602. cm-1.1H NMR (400 MHz,

CDCl3) δ 7.13 (d, J = 6.6 Hz, 2H), 6.95 (t, J = 8.8 Hz, 1H), 5.16 (s, 1H), 4.95 (s, 1H),

4.78 (s, 1H), 3.52 (s, 1H), 2.26 (s, 3H), 1.64 (s, 3H), 1.21 (s, 9H).13C NMR (101 MHz,

CDCl3) δ 162.3, 159.8, 146.3, 135.0, 134.9, 131.5, 131.4, 127.1, 127.0, 125.0, 124.8,

115.2, 115.0, 111.5, 100.1, 62.7, 55.9, 22.8, 20.0, 14.8, 14.7. 19F NMR (376 MHz,

CDCl3) δ -118.76 (d, J = 2.4 Hz). HRMS (ESI) calculated for C15H22FNNaOS+

[M+Na]+: 306.1298, found 306.1298.

C28

(R)-N-((S)-1-(4-chlorophenyl)-2-methylallyl)-2-methylpropane-2-sulfinamide C28:


2360, 1650, 1489, 1407, 1065, 1014, 903. cm-1.1H NMR (400 MHz, CDCl3) δ 7.34 –

7.26 (m, 4H), 5.16 (s, 1H), 4.96 (s, 1H), 4.82 (d, J = 2.7 Hz, 1H), 3.53 (d, J = 2.5 Hz,

1H), 1.64 (s, 3H), 1.21 (s, 9H).13C NMR (101 MHz, CDCl3) δ 145.9, 138.2, 133.8,

129.6, 128.8, 112.0, 62.8, 55.9, 22.7, 19.9. HRMS (ESI) calculated for

C14H20ClNNaOS+ [M+Na]+: 308.0846, found 308.0846.

C29

(R)-2-methyl-N-((S)-2-methyl-1-(p-tolyl)allyl) propane-2-sulfinamide C29:


1513, 1473, 1363, 1065, 1019, 898, 814. cm-1.1H NMR (400 MHz, CDCl3) δ 7.22 (d, J

= 8.0 Hz, 2H), 7.14 (d, J = 7.9 Hz, 2H), 5.17 (s, 1H), 4.94 (s, 1H), 4.81 (d, J = 2.9 Hz,

1H), 3.53 (d, J = 2.6 Hz, 1H), 2.34 (s, 3H), 1.65 (s, 3H), 1.22 (s, 9H).13C NMR (101

MHz, CDCl3) δ 146.5, 137.7, 136.6, 129.3, 128.2, 111.4, 63.3, 55.8, 22.8, 21.3, 20.0.


14

C30

(R)-N-((S)-1-(4-ethylphenyl)-2-methylallyl)-2-methylpropane-2-sulfinamide C30:


1510, 1472, 1353, 1065, 1034, 890, 814, 747. cm-1.1H NMR (400 MHz, CDCl3) δ 7.24

(d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 5.17 (s, 1H), 4.94 (s, 1H), 4.83 (d, J = 3.1

Hz, 1H), 3.53 (d, J = 2.9 Hz, 1H), 2.64 (q, J = 7.6 Hz, 2H), 1.65 (s, 3H), 1.25 – 1.21

(m, 12H).13C NMR (101 MHz, CDCl3) δ 146.5, 143.9, 136.8, 128.1, 128.0, 111.5,

63.4, 55.8, 28.6, 22.8, 19.9, 15.5. HRMS (ESI) calculated for C16H25NNaOS+ [M+Na]+:

302.1549, found 302.1550.

C31

(R)-2-methyl-N-((S)-2-methylpent-1-en-3-yl) propane-2-sulfinamide C31:

67%, white solid. [α]26 D = -102.23 (c 3.0, CHCl3). m. p. 86-87 oC. IR (KBr) νmax: 3162,

3071, 2959, 2871, 1644, 1454, 1048, 890, 570. cm-1. 1H NMR (400 MHz, CDCl3) δ

4.90 (d, J = 13.2 Hz, 2H), 3.60 (s, 1H), 3.11 (s, 1H), 1.69 (s, 4H), 1.52 (s, 1H), 1.18 (s,

9H), 0.82 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 145.2, 113.6, 62.7, 55.7, 26.0, 22.7,

18.0, 10.1. HRMS (ESI) calculated for C10H21NNaOS+ [M+Na]+: 226.1236, found

226.1231.

C32

(R)-N-((S)-1-cyclohexyl-2-methylallyl)-2-methylpropane-2-sulfinamide C32:

65%, colourless oil. [α]26 D = -27.29 (c 3.3, CHCl3). IR (KBr) νmax: 3198, 3075, 2932,

2855, 1473, 1389, 1049, 887. cm-1. 1H NMR (400 MHz, CDCl3) δ 4.90 (s, 2H), 3.29 (d,

J = 4.6 Hz, 1H), 3.06 (s, 1H), 1.93 (d, J = 12.0 Hz, 1H), 1.74 – 1.50 (m, 7H), 1.36 (d, J

= 3.6 Hz, 1H), 1.19 (s, 12H), 0.89 (d, J = 6.5 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ

145.0, 114.0, 68.5, 56.3, 40.6, 30.3, 29.9, 26.5, 26.2, 26.2, 22.7, 18.2. HRMS (ESI)

calculated for C14H27NNaOS+ [M+Na]+: 280.1706, found 280.1701.

15

3 Synthesis of Substrates G.

General procedure:

To a mixture of aqueous formaldehyde solution (37% formaldehyde in water) and

aldehyde in i-PrOH was added propionic acid and pyrrolidine. The reaction mixture

was stirred at 45 oC overnight. NaHCO3 was added and the mixture was extracted with

CH2Cl2. The combined extracts were washed with brine, dried with Na2SO4, and

concentrated in vacuo to give the crude product α,β-unsaturated aldehyde E which was

used directly in the next step.

To a solution of α,β-unsaturated aldehyde E (1.0 equiv.) and (R)-2-methylpropane-

2-sulfinamide (1.2 equiv.) in THF (0.2 M) was added Ti(OEt)4 (1.5 equiv.). The mixture

was stirred at 60 oC for 4-10 h. When complete, the mixture was slowly poured into

water (1 L) and then filtered, the filtrate was concentrated in vacuo. The resulting

residue was extracted with ethyl acetate, the organic layer was washed with water, dried

over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by

chromatography on silica gel to give the compounds F with high yield.

To a solution of F in THF, NaBH4 was added. The mixture was stirred at room

temperature for additional 2 h. When the reaction was complete, methanol was added

dropwise until there was no bubble. The mixture was poured to 10 mL of brine, stirred

for a while and filtered. The filtrate was extracted with ethyl acetate, dried over

anhydrous Na2SO4, and concentrated under reduced pressure. Purification by flash

column chromatography gave the products G in high yield.

G1

(R)-2-methyl-N-(3-methyl-2-methylenebutyl)propane-2-sulfinamide G1:


1649, 1466, 1389, 1364, 1056, 898, 841. cm-1. 1H NMR (400 MHz, Chloroform-d) δ

4.98 (s, 1H), 4.90 (s, 1H), 3.79 (dd, J = 14.7, 4.1 Hz, 1H), 3.65 (dd, J = 15.0, 7.5 Hz,

1H), 3.25 (d, J = 7.1 Hz, 1H), 2.32 (m, 1H), 1.23 (s, 9H), 1.05 (t, J = 5.7 Hz, 6H). 13C

16

NMR (100 MHz, Chloroform-d) δ 152.8, 109.4, 56.0, 49.2, 31.7, 29.8, 22.8, 21.8, 21.7.


G2

(R)-N-(2-benzylallyl)-2-methylpropane-2-sulfinamide G2:


2924, 1494, 1454, 1060, 1021, 902, 701. cm-1. 1H NMR (400 MHz, CDCl3) δ 7.31 –

7.27 (m, 2H), 7.23 – 7.16 (m, 3H), 5.11 (s, 1H), 4.94 (s, 1H), 3.70 (d, J = 14.4 Hz, 1H),

3.57 (dd, J = 14.6, 5.0 Hz, 1H), 3.41 (s, 2H), 3.21 (s, 1H), 1.21 (s, 9H). 13C NMR (100

MHz, CDCl3) δ 145.9, 138.9, 129.0, 128.6, 126.5, 114.1, 55.9, 49.7, 40.8, 22.8. HRMS

(ESI) calculated for C14H21NNaOS+ [M+Na]+: 274.1236, found 274.1231.

G3

(R)-2-methyl-N-(2-methylenehexyl)propane-2-sulfinamide G3:


2871, 1466, 1391, 1174, 1057, 897. cm-1. 1H NMR (400 MHz, CDCl3) δ 4.98 (s, 1H),

4.87 (s, 1H), 3.74 (dd, J = 14.6, 4.9 Hz, 1H), 3.60 (dd, J = 14.6, 8.0 Hz, 1H), 3.29 –

3.19 (m, 1H), 2.05 (dd, J = 13.4, 5.6 Hz, 2H), 1.41 (dd, J = 10.8, 5.2 Hz, 2H), 1.33 –

1.28 (m, 2H), 1.21 (d, J = 6.3 Hz, 9H), 0.89 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz,

CDCl3) δ 146.8, 111.6, 55.9, 50.2, 33.7, 29.8, 22.8, 22.5, 14.0. HRMS (ESI) calculated

for C11H23NNaOS+ [M+Na]+: 240.1393, found 240.1395.

G4

(R)-N-(2-(4-chlorobenzyl)allyl)-2-methylpropane-2-sulfinamide G4:


1493, 1477, 1460, 1393, 1363, 1300, 1260, 1171, 1114, 912, 806, 676. cm-1. 1H NMR

(400 MHz, CDCl3) δ 7.28 – 7.25 (m, 2H), 7.12 (s, 2H), 5.13 (s, 1H), 4.92 (s, 1H), 3.69

(dd, J = 14.6, 5.1 Hz, 1H), 3.56 (dd, J = 14.6, 7.3 Hz, 1H), 3.39 (s, 2H), 3.19 (s, 1H),

1.22 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 145.6, 137.4, 132.4, 130.4, 128.8, 114.6,

56.0, 49.7, 40.1, 22.8. HRMS (ESI) calculated for C14H20ClNNaOS+ [M+Na]+:

308.0846, found 308.0848.

17

G5

(R)-2-methyl-N-(2-((5-methylfuran-2-yl)methyl)allyl)propane-2-sulfinamide G5:


2869, 1565, 1453, 1363, 1219, 1057, 1020, 783.cm-1.1H NMR (400 MHz, CDCl3) δ

5.92 (d, J = 2.9 Hz, 1H), 5.86 (d, J = 2.0 Hz, 1H), 5.11 (s, 1H), 4.99 (s, 1H), 3.77 (dd,

J = 14.7, 5.2 Hz, 1H), 3.63 (dd, J = 14.7, 7.7 Hz, 1H), 3.37 (s, 2H), 3.27 – 3.21 (m, 1H),

2.24 (s, 3H), 1.22 (d, J = 2.7 Hz, 9H). 13C NMR (101 MHz, CDCl3) δ 151.2, 150.9,


C13H21NNaO2S+ [M+Na]+: 278.1185, found 278.1183.

4 Asymmetric alkylation of Cyclic Sulfinimines

General procedure:

In a flask, the corresponding substrate (C1-C32，G1-G5，1 mmol), CuI (0.08 mmol,

0.08 equiv), L-proline (0.16 mmol, 0.16 equiv) were dissolved in t-BuOH (5 mL). Then,

1-TrifluoroMethyl-1,2-benziodoxol-3(1H)-one (Togni reagent, 1.5 mmol, 1.5 equiv)

and NaHCO3 (1 mmol, 1 equiv) were added. The mixture was stirred at 60 oC overnight.

The reaction mixture was then washed with saturated aqueous NaHCO3 solution (50

mL). The aqueous layer was separated and extracted with ethyl acetate (50 mL X 3).

The combined organic layers were concentrated in vacuo. The residue was purified by

silica gel flash column chromatography (EtOAc/hexanes) to afford the products 3-41.

3

(2R,3R)-1-(tert-butylsulfinyl)-2-phenyl-3-(2,2,2-trifluoroethyl)aziridine 3:

0.25g, 82%, as a pale yellow solid. [α]19 D = - 189.29 (c 2.0, CHCl3). m. p. 101-102 oC.

IR (KBr) νmax: 3069, 3033, 2962, 2870, 2360, 1604, 1392, 1253, 1200, 1152, 1038, 855,

794, 754, 700. cm-1.1H NMR (400 MHz, CDCl3) δ 7.38 – 7.25 (m, 5H), 3.46 (d, J = 3.3

Hz, 1H), 3.18 – 3.02 (m, 1H), 2.94 – 2.83 (m, 1H), 2.77 (dt, J = 10.7, 3.1 Hz, 1H), 1.30

(s, 9H).13C NMR (101 MHz, CDCl3) δ 135.9, 130.0, 128.9, 128.4, 127.2, 126.4, 124.5,

121.7, 57.7, 44.4, 43.8, 43.7, 43.7, 43.7, 34.3, 34.0, 33.7, 33.5, 22.7.19F NMR (376 MHz,

CDCl3) δ -65.41 (t, J = 10.1 Hz). HRMS (ESI) calculated for C14H18F3NNaOS+

[M+Na]+: 328.0953, found 328.0953.

18

4

(2R,3R)-1-(tert-butylsulfinyl)-2-(p-tolyl)-3-(2,2,2-trifluoroethyl)aziridine 4:

0.25g, 80%, as a colourless oil. [α]19 D = - 175.84 (c 2.0, CHCl3). IR (KBr) νmax: 2982,

2961, 2900, 2871, 2363, 2349, 1730, 1716, 1612, 1559, 1508, 1456, 1403, 1369, 1237,

1101, 937, 822, 796, cm-1.1H NMR (400 MHz, CDCl3) δ 7.16 (s, 4H), 3.41 (d, J = 3.4

Hz, 1H), 3.15 – 3.00 (m, 1H), 2.92 – 2.72 (m, 2H), 2.34 (s, 3H), 1.29 (s, 9H).13C NMR

(101 MHz, CDCl3) δ 138.3, 132.8, 129.5, 127.3, 126.3, 124.5, 57.6, 44.5, 43.4, 43.4,

34.1, 33.8, 22.6, 21.3. 19F NMR (376 MHz, CDCl3) δ -65.36 (t, J = 10.0 Hz). HRMS

(ESI) calculated for C15H20F3NNaOS+ [M+Na]+: 342.1110, found 342.1112.

5

(2R,3R)-1-(tert-butylsulfinyl)-2-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)aziridine 5:


2964, 2931, 2907, 2870, 2360, 2341, 1778, 1732, 1716, 1659, 1610, 1558, 1513, 1458,

1405, 1368, 1237, 1106, 1075, 1036, 1017, 938, 915, 821, 793, 712, 650 cm-1.1H NMR

(400 MHz, CDCl3) δ 7.28 – 7.21 (m, 2H), 7.05 (t, J = 8.7 Hz, 2H), 3.45 (d, J = 3.4 Hz,

1H), 3.13 – 2.99 (m, 1H), 2.89 (dp, J = 14.8, 10.2 Hz, 1H), 2.74 (dt, J = 10.7, 3.2 Hz,

1H), 1.30 (s, 9H).13C NMR (101 MHz, CDCl3) δ 164.0, 161.6, 131.7, 131.6, 130.0,

128.1, 128.0, 127.2, 124.5, 116.0, 115.8, 57.7, 43.8, 43.8, 43.6, 34.3, 34.0, 33.7, 33.4,

22.7.19F NMR (376 MHz, CDCl3) δ -65.44 (t, J = 10.1 Hz), -113.53 (ddd, J = 10.3, 6.8,

4.3 Hz). HRMS (ESI) calculated for C14H17F4NNaOS+ [M+Na]+: 346.0859, found

346.0859.

6

(2R,3R)-1-(tert-butylsulfinyl)-2-(4-chlorophenyl)-3-(2,2,2-trifluoroethyl)aziridine 6:

0.27g, 80%, as a white solid. [α]19 D = -156.78 (c 1.2, CHCl3). m. p. 97-99 oC. IR (KBr)

νmax: 2960, 2923, 2361, 2339, 1451, 1410, 1361, 1342, 1312, 1279, 1257, 1102, 956,

863 cm-1.1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz,

19

2H), 3.42 (d, J = 3.3 Hz, 1H), 3.12 – 2.98 (m, 1H), 2.88 (dp, J = 14.8, 10.2 Hz, 1H),

2.72 (dt, J = 10.7, 3.2 Hz, 1H), 1.29 (s, 9H).13C NMR (101 MHz, CDCl3) δ 134.5, 134.3,

130.0, 129.1, 127.7, 127.2, 124.4, 121.7, 57.7, 43.9, 43.9, 43.5, 34.2, 33.9, 33.7, 33.4,

22.7.19F NMR (376 MHz, CDCl3) δ -65.44 (t, J = 10.1 Hz). HRMS (ESI) calculated for

C14H17ClF3NNaOS+ [M+Na]+: 362.0564, found 362.0565.

7

(2R,3R)-1-(tert-butylsulfinyl)-2-(2,2,2-trifluoroethyl)-3-(4-(trifluoromethyl)phenyl)

aziridine 7:

0.28g, 76%, as a white solid. m.p.=69.1-70.5 oC. [α]19 D = - 126.2 (c 1.4, CHCl3). IR (KBr)

νmax: 2965, 2928, 2360, 2341, 1475, 1458, 1438, 1412, 1363, 1343, 1326, 1282, 1255,

1173, 1154, 1127, 1115, 946, 862, 677, 636, 593 cm-1.1H NMR (400 MHz, CDCl3) δ

7.61 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 3.52 (d, J = 3.2 Hz, 1H), 3.15 – 3.00

(m, 1H), 3.00 – 2.86 (m, 1H), 2.76 (dt, J = 10.7, 3.2 Hz, 1H), 1.31 (s, 9H).13C NMR

(101 MHz, CDCl3) δ 140.1, 131.1, 130.8, 130.5, 130.1, 129.9, 128.1, 127.1, 126.7,

125.9, 125.9, 125.9, 125.8, 125.4, 124.4, 122.7, 121.6, 120.0, 57.9, 44.3, 44.3, 43.4,

34.2, 33.9, 33.6, 33.3, 22.7.19F NMR (376 MHz, CDCl3) δ -62.63 (s), -65.52 (t, J = 10.1

Hz). HRMS (ESI) calculated for C15H17F6NNaOS+ [M+Na]+: 396.0827, found

396.0827.

8

(2R,3R)-1-(tert-butylsulfinyl)-2-(o-tolyl)-3-(2,2,2-trifluoroethyl) aziridine 8:


2989, 2963, 2928, 2872, 2360, 2341, 1470, 1434, 1416, 1367, 1342, 1272, 1242, 1212,

1153, 1117, 1097, 1072, 1055, 937, 910, 868, 846, 820, 792, 758, 725, 638, 548 cm-

1.1H NMR (400 MHz, CDCl3) δ 7.25 – 7.12 (m, 4H), 3.62 (d, J = 3.5 Hz, 1H), 3.19 –

3.02 (m, 1H), 3.03 – 2.88 (m, 1H), 2.77 (dt, J = 10.7, 3.2 Hz, 1H), 2.45 (s, 3H), 1.32 (s,

9H).13C NMR (101 MHz, CDCl3) δ 137.2, 133.9, 130.4, 130.0, 128.1, 127.2, 126.4,

125.1, 124.4, 121.7, 57.8, 43.7, 43.7, 41.8, 34.5, 34.2, 33.9, 33.6, 22.8, 19.3.19F NMR

(376 MHz, CDCl3) δ -65.18 (t, J = 10.3 Hz). HRMS (ESI) calculated for

C15H20F3NNaOS+ [M+Na]+: 342.1110, found 342.1111.

20

9

(2R,3R)-1-(tert-butylsulfinyl)-2-(4-ethylphenyl)-3-(2,2,2-trifluoroethyl) aziridine 9:


2931, 2361, 2342, 1473, 1451, 1439, 1410, 1359, 1342, 1325, 1281, 1253, 1109, 1101,

947, 832 cm-1.1H NMR (400 MHz, CDCl3) δ 7.19 (s, 4H), 3.42 (s, 1H), 3.06 (dd, J =

22.2, 11.7 Hz, 1H), 2.85 (dd, J = 22.8, 11.9 Hz, 1H), 2.76 (d, J = 12.1 Hz, 1H), 2.64 (q,

J = 7.4 Hz, 2H), 1.29 (s, 9H), 1.23 (t, J = 7.8 Hz, 3H).13C NMR (101 MHz, CDCl3) δ

144.5, 132.9, 129.9, 128.2, 127.2, 126.3, 124.4, 121.7, 57.5, 44.3, 43.4, 43.4, 34.3, 34.0,

33.7, 33.4, 28.6, 22.5, 15.5. 19F NMR (376 MHz, CDCl3) δ -65.37 (t, J = 10.0 Hz).

HRMS (ESI) calculated for C16H22F3NNaOS+ [M+Na]+: 356.1266, found 356.1268.

10

(2R,3R)-1-(tert-butylsulfinyl)-2-(2,2,2-trifluoroethyl)-3-(4-(trifluoromethoxy) phenyl)

aziridine 10:

0.29g, 75%, as a colourless oil. [α]23 D = - 63.21 (c 1.8, CHCl3) . IR (KBr) νmax: 2961,

2937, 2880, 2361, 2344, 1616, 1519, 1451, 1365, 1355, 1300, 1253, 1236, 1091, 1036,

1017, 946, 843 cm-1.1H NMR (400 MHz, CDCl3) δ 7.34 – 7.27 (m, 2H), 7.20 (d, J =

8.1 Hz, 2H), 3.47 (d, J = 3.3 Hz, 1H), 3.16 – 2.99 (m, 1H), 2.99 – 2.83 (m, 1H), 2.74

(dt, J = 10.7, 3.3 Hz, 1H), 1.31 (s, 9H).13C NMR (101 MHz, CDCl3) δ 149.3, 134.8,

127.8, 127.2, 124.5, 121.8, 121.5, 119.3, 57.8, 44.2, 44.1, 43.3, 34.3, 34.0, 33.7, 33.4,

22.8.19F NMR (376 MHz, CDCl3) δ -57.88 (s), -65.48 (t, J = 10.1 Hz). HRMS (ESI)

calculated for C15H17F6NNaO2S+ [M+Na]+: 412.0776, found 412.0777.

11

(2R,3R)-1-(tert-butylsulfinyl)-2-(2,2,2-trifluoroethyl)-3-(3 (trifluoromethoxy)phenyl)

aziridine 11:

21

0.31, 79%, as a pale yellow oil. [α]23 D = - 231.87 (c 0.7, CHCl3). IR (KBr) νmax: 2969,

2926, 2360, 2342, 1507, 1457, 1436, 1262, 1217, 1107, 1069, 1051, 1039, 947, 845,

802, 696, 676 cm-1.1H NMR (400 MHz, CDCl3) δ 7.38 (t, J = 7.9 Hz, 1H), 7.25 – 7.07

(m, 3H), 3.48 (s, 1H), 3.11 – 2.85 (m, 2H), 2.74 (d, J = 10.4 Hz, 1H), 1.31 (s, 9H).13C

NMR (101 MHz, CDCl3) δ 149.8, 138.6, 130.4, 129.9, 127.2, 124.9, 124.4, 121.8, 120.7,

119.3, 118.5, 57.9, 44.3, 44.3, 43.2, 34.2, 33.9, 33.7, 33.4, 22.7.19F NMR (376 MHz,

CDCl3) δ -57.84 (s), -65.50 (t, J = 10.1 Hz). HRMS (ESI) calculated for


12

(2R,3R)-1-(tert-butylsulfinyl)-2-(3,4-dichlorophenyl)-3-(2,2,2-trifluoroethyl)aziridine

12:


2929, 2360, 2342, 1476, 1437, 1392, 1362, 1274, 1254, 1155, 1107, 1081, 1052, 1033,

944, 925, 839, 815, 674, 661, 645, 584 cm-1.1H NMR (400 MHz, CDCl3) δ 7.42 (d, J =

8.1 Hz, 1H), 7.33 (s, 1H), 7.11 (d, J = 8.2 Hz, 1H), 3.41 (s, 1H), 3.12 – 2.82 (m, 2H),

2.78 – 2.65 (m, 1H), 1.30 (s, 9H).13C NMR (101 MHz, CDCl3) δ 136.4, 133.2, 132.6,

130.9, 129.9, 128.2, 127.1, 125.8, 124.4, 121.6, 57.9, 44.3, 44.2, 42.7, 34.2, 33.9, 33.6,

33.3, 22.8. 19F NMR (376 MHz, CDCl3) δ -65.49 (t, J = 10.0 Hz). HRMS (ESI)

calculated for C14H16Cl2F3NNaOS+ [M+Na]+: 396.0174, found 396.0174.

13

(2R,3R)-1-(tert-butylsulfinyl)-2-(3,4-difluorophenyl)-3-(2,2,2-trifluoroethyl)aziridine

13:


2930, 2871, 2360, 2342, 1610, 1521, 1476, 1445, 1365, 1341, 1300, 1255, 1235, 1155,

1082, 1054, 1036, 942, 844, 815, 788, 675, 660, 595 cm-1. 1H NMR (400 MHz, CDCl3)

δ 7.14 (dd, J = 18.1, 8.5 Hz, 1H), 7.09 – 6.99 (m, 2H), 3.42 (d, J = 3.3 Hz, 1H), 3.10 –

2.85 (m, 2H), 2.70 (dt, J = 10.6, 3.3 Hz, 1H), 1.31 (s, 9H).13C NMR (101 MHz, CDCl3)

δ 152.1, 151.9, 151.7, 151.6, 149.6, 149.5, 149.3, 149.1, 133.2, 133.2, 133.2, 133.1,

129.9, 127.2, 124.4, 122.7, 122.7, 122.6, 122.6, 121.7, 117.9, 117.8, 115.2, 115.1, 57.8,

22

44.3, 44.3, 44.2, 44.2, 42.8, 34.2, 33.9, 33.6, 33.3, 22.8.19F NMR (376 MHz, CDCl3) δ

-65.53 (t, J = 10.4 Hz), -135.71 – -137.06 (m), -137.31 – -138.79 (m). HRMS (ESI)

calculated for C14H16F5NNaOS+ [M+Na]+: 364.0765, found 364.0766.

14

(2R,3R)-1-(tert-butylsulfinyl)-2-(naphthalen-2-yl)-3-(2,2,2-trifluoroethyl)aziridine 14:

0.19g, 55%, as a white solid. [α]19 D = - 159.63 (c 0.4, CHCl3). IR (KBr) νmax: 2984, 2958,

2925, 2855, 2360, 2342, 1510, 1475, 1456, 1393, 1364, 1260, 1151, 1108, 1069, 943,

869, 748, 594, 467 cm-1.1H NMR (400 MHz, CDCl3) δ 7.83 (dd, J = 8.5, 4.8 Hz, 3H),

7.76 (s, 1H), 7.54 – 7.44 (m, 2H), 7.34 (dd, J = 8.5, 1.6 Hz, 1H), 3.60 (d, J = 2.7 Hz,

1H), 3.22 – 3.05 (m, 1H), 3.00 – 2.83 (m, 2H), 1.32 (s, 9H).13C NMR (101 MHz, CDCl3)

δ 133.4, 133.4, 133.3, 128.9, 127.9, 126.7, 126.5, 125.9, 124.6, 123.6, 57.8, 44.8, 43.7,

43.7, 34.4, 34.1, 33.8, 33.6, 22.7.19F NMR (376 MHz, CDCl3) δ -65.33 (t, J = 9.9 Hz).


15

(2R,3R)-1-(tert-butylsulfinyl)-2-(4-fluoro-3-methylphenyl)-3-(2,2,2-trifluoroethyl)

aziridine 15:


2931, 2881, 2363, 2341, 1613, 1511, 1455, 1355, 1351, 1301, 1251, 1237, 1154, 1081,

1056, 1037, 943, 841, 816 cm-1.1H NMR (400 MHz, CDCl3) δ 7.09 – 7.01 (m, 2H),

7.01 – 6.92 (m, 1H), 3.39 (d, J = 3.4 Hz, 1H), 3.13 – 2.98 (m, 1H), 2.85 (ddd, J = 20.2,

14.8, 10.2 Hz, 1H), 2.72 (dt, J = 10.7, 3.2 Hz, 1H), 2.26 (d, J = 1.8 Hz, 3H), 1.29 (s,

9H).13C NMR (101 MHz, CDCl3) δ 162.6, 160.2, 131.3, 131.3, 130.0, 129.5, 129.4,

127.3, 125.6, 125.4, 125.3, 125.2, 124.5, 115.6, 115.4, 57.7, 43.8, 43.7, 43.6, 34.3, 34.0,

33.7, 33.5, 22.7, 14.8, 14.7.19F NMR (376 MHz, CDCl3) δ -65.41 (t, J = 10.4 Hz), -

116.86 – -118.74 (m). HRMS (ESI) calculated for C15H19F4NNaOS+ [M+Na]+:

360.1016, found 360.1018.

23

16

(2R,3R)-2-([1,1'-biphenyl]-4-yl)-1-(tert-butylsulfinyl)-3-(2,2,2-trifluoroethyl)aziridine

16:


2926, 2360, 2342, 1489, 1474, 1340, 1273, 1259, 1170, 1154, 1095, 1071, 1056, 1038,

939, 840, 808, 762, 673 cm-1.1H NMR (400 MHz, CDCl3) δ 7.61 – 7.54 (m, 4H), 7.45

(t, J = 7.5 Hz, 2H), 7.36 (t, J = 7.9 Hz, 3H), 3.50 (d, J = 3.3 Hz, 1H), 3.18 – 3.04 (m,

1H), 2.97 – 2.85 (m, 1H), 2.85 – 2.79 (m, 1H), 1.32 (s, 9H).13C NMR (101 MHz, CDCl3)

δ 141.5, 140.7, 134.9, 129.0, 127.6, 127.3, 127.2, 126.9, 124.5, 57.8, 44.2, 43.8, 43.8,

34.4, 34.1, 33.8, 33.5, 22.7.19F NMR (376 MHz, CDCl3) δ -65.35 (t, J = 10.0 Hz).


17

(2R,3R)-1-(tert-butylsulfinyl)-2-(thiophen-3-yl)-3-(2,2,2-trifluoroethyl)aziridine 17:

0.20g, 66%, as a pale yellow oil. [α]19 D = - 222.88 (c 0.1, CHCl3) . IR (KBr) νmax: 2960,

2925, 2856, 2360, 2342, 1476, 1437, 1409, 2394, 1276, 1260, 1162, 1100, 1069, 1057,

1034, 848, 838, 785, 670, 591 cm-1.1H NMR (400 MHz, CDCl3) δ 7.31 (dd, J = 4.9, 3.0

Hz, 1H), 7.23 (d, J = 2.3 Hz, 1H), 6.99 (d, J = 4.9 Hz, 1H), 3.51 (d, J = 3.3 Hz, 1H),

3.11 – 2.98 (m, 1H), 2.86 – 2.70 (m, 2H), 1.28 (s, 9H).13C NMR (101 MHz, CDCl3) δ

137.0, 127.2, 126.7, 126.0, 124.5, 123.0, 57.6, 42.7, 42.6, 41.3, 34.6, 34.3, 34.0, 33.7,


C12H16F3NNaOS2+ [M+Na]+: 334.0518, found 334.0519.

18

(2R,3R)-1-(tert-butylsulfinyl)-2-isobutyl-3-(2,2,2-trifluoroethyl)aziridine 18:


2901, 2360, 2342, 1508, 1261, 1065, 1048, 801 cm-1. 1H NMR (400 MHz, CDCl3) δ

2.84 – 2.68 (m, 1H), 2.62 – 2.43 (m, 3H), 1.81 – 1.66 (m, 2H), 1.51 (ddd, J = 13.8, 7.7,

24

6.2 Hz, 1H), 1.28 (s, 9H), 0.96 (dd, J = 6.5, 3.9 Hz, 6H). 13C NMR (101 MHz, CDCl3)

δ 57.1, 43.4, 39.8, 39.6, 39.5, 35.4, 35.1, 27.1, 22.9, 22.8, 22.6.19F NMR (376 MHz,


[M+Na]+: 308.1266, found 308.1267.

19

(2R,3R)-2-butyl-1-(tert-butylsulfinyl)-3-(2,2,2-trifluoroethyl)aziridine 19:


2873, 2360, 1458, 1444, 1274, 1256, 1151, 1085, 1019, 955, 802, 675. cm-1.1H NMR

(400 MHz, CDCl3) δ 2.87 – 2.68 (m, 1H), 2.55 – 2.36 (m, 3H), 1.92 – 1.79 (m, 1H),

1.66 – 1.52 (m, 1H), 1.47 – 1.31 (m, 4H), 1.25 (d, J = 11.0 Hz, 9H), 0.90 (t, J = 7.1 Hz,

3H).13C NMR (101 MHz, CDCl3) δ 130.1, 127.3, 124.6, 121.8, 57.1, 44.8, 39.0, 39.0,

35.8, 35.5, 35.2, 34.9, 30.3, 29.2, 22.7, 22.5, 14.0. 19F NMR (376 MHz, CDCl3) δ -

65.25 (t, J = 10.0 Hz). HRMS (ESI) calculated for C12H22F3NNaOS+ [M+Na]+:

308.1266, found 308.1267.

20

(2R,3R)-1-(tert-butylsulfinyl)-2-phenethyl-3-(2,2,2-trifluoroethyl)aziridine 20:


2960, 2928, 2867, 2360, 2342, 1497, 1476, 1455, 1374, 1363, 1341, 1275, 1253, 1153,

1078, 1027, 990, 966, 937, 835, 801, 749, 700, 674, 596 cm-1.1H NMR (400 MHz,

CDCl3) δ 7.32 – 7.17 (m, 5H), 2.85 – 2.62 (m, 3H), 2.60 – 2.36 (m, 3H), 2.18 (ddd, J =

20.0, 7.7, 4.7 Hz, 1H), 2.00 (td, J = 15.1, 7.5 Hz, 1H), 1.28 (s, 9H).13C NMR (101 MHz,

CDCl3) δ 140.8, 130.0, 128.6, 128.5, 127.3, 126.3, 124.5, 121.8, 57.2, 44.3, 39.0, 38.9,

35.8, 35.5, 35.2, 34.9, 33.3, 32.3, 22.8.19F NMR (376 MHz, CDCl3) δ -65.16 (t, J =


356.1265.

25

21

(2R,3R)-1-(tert-butylsulfinyl)-2-pentyl-3-(2,2,2-trifluoroethyl)aziridine 21:


2931, 2862, 1458, 1444, 1363, 1343, 1275, 1253, 1151, 1095, 935. 674 cm-1.1H NMR

(400 MHz, CDCl3) δ 2.86 – 2.67 (m, 1H), 2.54 – 2.36 (m, 3H), 1.92 – 1.76 (m, 1H),

1.57 (td, J = 14.9, 7.8 Hz, 1H), 1.48 – 1.36 (m, 2H), 1.35 – 1.27 (m, 4H), 1.24 (d, J =

21.3 Hz, 9H), 0.93 – 0.79 (m, 3H).13C NMR (101 MHz, CDCl3) δ 130.1, 127.3, 124.6,

121.8, 57.0, 44.8, 39.0, 35.8, 35.5, 35.2, 34.9, 31.5, 30.6, 26.7, 22.7, 22.6, 14.1.19F

NMR (376 MHz, CDCl3) δ -65.24 (t, J = 10.0 Hz). HRMS (ESI) calculated for


22

(2R,3R)-1-(tert-butylsulfinyl)-2-heptyl-3-(2,2,2-trifluoroethyl)aziridine 22:


2929, 2858, 2360, 2341, 1458, 1444, 1363, 1343, 1274, 1253, 1152, 1078, 1030, 947,

844, 805, 674, 596 cm-1.1H NMR (400 MHz, CDCl3) δ 2.84 – 2.67 (m, 1H), 2.53 – 2.38

(m, 3H), 1.90 – 1.78 (m, 1H), 1.57 (td, J = 14.9, 7.8 Hz, 1H), 1.49 – 1.37 (m, 2H), 1.36

– 1.17 (m, 17H), 0.86 (t, J = 6.9 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 130.1, 127.3,

124.6, 121.8, 57.0, 44.8, 39.0, 35.8, 35.5, 35.2, 34.9, 31.9, 30.6, 29.4, 29.2, 27.1, 22.7,



23

(2R,3R)-1-(tert-butylsulfinyl)-2-cyclohexyl-3-(2,2,2-trifluoroethyl)aziridine 23:


2931, 2360, 1652, 1507, 1362, 1159, 1096, 1067, 974, 846, 675. cm-1.1H NMR (400

MHz, CDCl3) δ 2.92 – 2.72 (m, 2H), 2.62 – 2.46 (m, 1H), 2.33 (dd, J = 7.4, 3.7 Hz,

1H), 1.88 (d, J = 12.4 Hz, 1H), 1.77 – 1.61 (m, 4H), 1.31 – 1.26 (m, 9H), 1.21 (ddd, J

26

= 15.5, 8.1, 4.1 Hz, 4H), 1.09 (ddd, J = 20.6, 10.9, 2.8 Hz, 2H).13C NMR (101 MHz,

CDCl3) δ 130.0, 127.3, 124.5, 121.8, 57.3, 47.1, 39.9, 39.8, 39.5, 34.8, 34.5, 34.2, 33.9,

30.4, 29.5, 26.3, 25.8, 25.7, 23.0. 19F NMR (376 MHz, CDCl3) δ -65.54 (t, J = 10.4

Hz).HRMS (ESI) calculated for C14H24F3NNaOS+ [M+Na]+: 334.1423, found

334.1425.

24

(2R,3R)-2-benzyl-1-(tert-butylsulfinyl)-3-(2,2,2-trifluoroethyl)aziridine 24:


3014, 2976, 2963, 2932, 2870, 2360, 2341, 1494, 1475, 1446, 1363, 1351, 1315, 1275,

1259, 1212, 1153, 1143, 1116, 1063, 1047, 1023, 968, 909, 840, 809, 750, 700, 676,

641, 592, 541 cm-1. 1H NMR (400 MHz, CDCl3) δ 7.31 (t, J = 7.2 Hz, 2H), 7.23 (dd, J

= 23.1, 6.9 Hz, 3H), 3.05 (ddd, J = 21.2, 14.3, 6.0 Hz, 2H), 2.76 – 2.65 (m, 2H), 2.66 –

2.53 (m, 2H), 1.29 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 137.4, 129.9, 129.1, 128.7,

127.2, 127.0, 124.4, 121.6, 57.3, 44.8, 39.0, 39.0, 36.9, 35.4, 35.1, 34.8, 34.5, 22.9.19F



25

(2R,3R)-1-(tert-butylsulfinyl)-2-methyl-3-(naphthalen-2-yl)-2-(2,2,2-trifluoroethyl)

aziridine 25:

0.26g, 72%, as a pale yellow oil. [α]18 D = - 22.03 (c 0.5, CHCl3). IR (KBr) νmax: 2962,

2926, 2360, 2342, 1699, 1683, 1653, 1558, 1541, 1521, 1507, 1473, 1262, 1147, 1100,

1026, 801 cm-1.1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 6.5 Hz, 3H), 7.76 (s, 1H),

7.47 (dd, J = 23.8, 6.1 Hz, 3H), 3.96 (d, J = 9.6 Hz, 1H), 3.45 – 3.27 (m, 1H), 2.92 –

2.73 (m, 1H), 1.39 (s, 9H), 1.19 (s, 3H).13C NMR (101 MHz, CDCl3) δ 133.2, 133.1,

132.1, 129.2, 128.3, 128.0, 127.9, 127.6, 126.6, 126.6, 126.3, 125.2, 124.8, 124.6, 57.3,

48.7, 48.6, 47.7, 39.3, 39.0, 38.7, 38.4, 23.1, 22.9, 19.9.19F NMR (376 MHz, CDCl3) δ

-61.66 (t, J = 10.5 Hz). HRMS (ESI) calculated for C19H22F3NNaOS+ [M+Na]+:

392.1266, found 392.1267.

27

26

(2R,3R)-1-(tert-butylsulfinyl)-2-methyl-3-phenyl-2-(2,2,2-trifluoroethyl)aziridine 26:

0.24g, 75%, as a pale yellow solid. [α]20 D = - 39.96 (c 1.4, CHCl3). m. p. 66-67 oC. IR

(KBr) νmax: 2967, 2926, 2360, 2341, 1456, 1394, 1361, 1262, 1236, 1147, 1102, 1079,

1060, 1023, 884, 801, 697, 687 cm-1.1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 10.6

Hz, 5H), 3.79 (s, 1H), 3.40 – 3.20 (m, 1H), 2.87 – 2.69 (m, 1H), 1.35 (s, 9H), 1.15 (s,

3H).13C NMR (101 MHz, CDCl3) δ 134.5, 128.5, 128.0, 127.5, 124.8, 57.2, 48.5, 48.5,

47.5, 39.3, 39.0, 38.7, 38.4, 23.0, 19.8.19F NMR (376 MHz, CDCl3) δ -61.74 (t, J =


342.1112.

27

(2R,3R)-1-(tert-butylsulfinyl)-3-(4-fluorophenyl)-2-methyl-2-(2,2,2-trifluoroethyl)

aziridine 27:


2926, 2359, 2342, 1512, 1456, 1262, 1152, 1085, 1064, 1026, 801 cm-1.1H NMR (400

MHz, CDCl3) δ 7.30 – 7.24 (m, 2H), 7.05 (t, J = 8.1 Hz, 2H), 3.77 (s, 1H), 3.42 – 3.26

(m, 1H), 2.76 (dq, J = 19.5, 9.9 Hz, 1H), 1.35 (s, 9H), 1.13 (s, 3H).13C NMR (101 MHz,

CDCl3) δ 163.9, 161.4, 130.3, 129.2, 129.1, 127.5, 115.7, 115.5, 100.1, 57.2, 48.6, 46.7,

39.1, 38.8, 38.5, 38.3, 23.1, 19.8.19F NMR (376 MHz, CDCl3) δ -61.77 (t, J = 11.6 Hz),

-114.15 (dd, J = 14.4, 6.3 Hz). HRMS (ESI) calculated for C15H19F4NNaOS+ [M+Na]+:

360.1016, found 360.1017.

28

(2R,3R)-1-(tert-butylsulfinyl)-2-methyl-2-(2,2,2-trifluoroethyl)-3-(4-(trifluoromethyl)

phenyl) aziridine 28:


2927, 2360, 2342, 1456, 1393, 1326, 1263, 1153, 1130, 1086, 1018, 831, 802 cm-1.1H

28

NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 8.1 Hz, 2H), 3.85 (s,

1H), 3.38 (dq, J = 15.0, 11.3 Hz, 1H), 2.78 (dq, J = 15.2, 9.8 Hz, 1H), 1.36 (s, 9H), 1.14

(s, 3H). 13C NMR (101 MHz, CDCl3) δ 138.7, 130.8, 130.5, 130.2, 129.9, 128.2, 127.9,

127.4, 125.6, 125.6, 125.5, 125.5, 124.7, 122.8, 120.1, 57.4, 48.9, 48.9, 46.7, 39.1, 38.8,

38.6, 38.3, 23.0, 19.9.19F NMR (376 MHz, CDCl3) δ -61.75 (t, J = 10.5 Hz), -62.58 (s).


29

(2R,3R)-1-(tert-butylsulfinyl)-3-(4-fluoro-3-methylphenyl)-2-methyl-2-(2,2,2-

trifluoroethyl) aziridine 29:


2934, 2874, 2360, 2342, 1507, 1477, 1460, 1425, 1361, 1340, 1273, 1252, 1232, 1160,

1102, 1068, 1033, 891, 849, 836, 794, 647, 598, 557 cm-1.1H NMR (400 MHz, CDCl3)

δ 7.10 (d, J = 7.2 Hz, 2H), 6.98 (t, J = 8.7 Hz, 1H), 3.72 (s, 1H), 3.41 – 3.22 (m, 1H),

2.76 (dq, J = 19.9, 10.1 Hz, 1H), 2.28 (s, 3H), 1.34 (s, 9H), 1.14 (s, 3H).13C NMR (101

MHz, CDCl3) δ 162.4, 159.9, 130.6, 130.5, 129.9, 129.9, 126.3, 126.2, 125.2, 125.1,

124.8, 115.2, 115.0, 57.2, 48.5, 46.8, 39.2, 38.9, 38.6, 38.3, 23.1, 19.8, 14.8, 14.8.19F

NMR (376 MHz, CDCl3) δ -61.74 (t, J = 11.7 Hz), -118.49 (s). HRMS (ESI) calculated

for C16H21F4NNaOS+ [M+Na]+: 374.1172, found 374.1171.

30

(2R,3R)-1-(tert-butylsulfinyl)-3-(4-chlorophenyl)-2-methyl-2-(2,2,2-trifluoroethyl)

aziridine 30:


2930, 2360, 2342, 1506, 1493, 1474, 1456, 1436, 1264, 1250, 1151, 1061, 1014, 888,

851, 822, 686 cm-1.1H NMR (400 MHz, CDCl3) δ 7.36 – 7.31 (m, 2H), 7.24 (d, J = 8.4

Hz, 2H), 3.76 (s, 1H), 3.33 (dq, J = 15.0, 11.3 Hz, 1H), 2.77 (dq, J = 15.1, 9.8 Hz, 1H),

1.34 (s, 9H), 1.13 (s, 3H).13C NMR (101 MHz, CDCl3) δ 133.8, 133.0, 130.1, 128.7,

128.7, 127.3, 124.6, 121.8, 57.1, 48.5, 48.5, 46.6, 39.0, 38.7, 38.4, 38.1, 22.9, 19.7.19F



29

31

(2R,3R)-1-(tert-butylsulfinyl)-2-methyl-3-(p-tolyl)-2-(2,2,2-trifluoroethyl)aziridine 31:


2929, 2870, 2360, 1516, 1456, 1362, 1265, 1252, 1150, 1102, 1085, 1061, 1019, 819,

687 cm-1.1H NMR (400 MHz, CDCl3) δ 7.18 (q, J = 8.1 Hz, 4H), 3.75 (s, 1H), 3.27 (dq,

J = 14.9, 11.3 Hz, 1H), 2.79 (dq, J = 15.1, 9.9 Hz, 1H), 2.35 (s, 3H), 1.34 (s, 9H), 1.15

(s, 3H).13C NMR (101 MHz, CDCl3) δ 137.8, 131.4, 129.2, 127.6, 127.4, 124.8, 122.0,

57.2, 48.3, 48.2, 47.6, 39.3, 39.0, 38.7, 38.4, 23.0, 21.3, 19.7.19F NMR (376 MHz,


[M+Na]+: 356.1266, found 356.1268.

32

(2R,3R)-1-(tert-butylsulfinyl)-3-(4-ethylphenyl)-2-methyl-2-(2,2,2-trifluoroethyl)

aziridine 32:


2933, 2873, 2361, 1516, 1456, 1390, 1362, 1265, 1265, 1214, 1149, 1103, 1061, 953,

891, 829, 686 cm-1.1H NMR (400 MHz, CDCl3) δ 7.21 (dd, J = 17.5, 7.4 Hz, 4H), 3.76

(s, 1H), 3.36 – 3.19 (m, 1H), 2.88 – 2.72 (m, 1H), 2.65 (q, J = 7.4 Hz, 2H), 1.34 (s, 9H),

1.24 (t, J = 7.5 Hz, 3H), 1.16 (s, 3H).13C NMR (101 MHz, CDCl3) δ 144.1, 131.6, 130.3,

128.0, 127.5, 127.5, 124.8, 57.1, 48.3, 48.3, 47.6, 39.0, 38.7, 28.7, 23.0, 19.7, 15.6.19F



33

(2R,3R)-1-((R)-tert-butylsulfinyl)-3-ethyl-2-methyl-2-(2,2,2-trifluoroethyl)aziridine

33:


2927, 1511, 1365, 1261, 1149, 1079, 1054, 686 cm-1.1H NMR (400 MHz, CDCl3) δ

30

3.04 (dq, J = 23.0, 11.5 Hz, 1H), 2.63 (dq, J = 15.2, 10.0 Hz, 1H), 2.52 (t, J = 6.7 Hz,

1H), 1.70 – 1.57 (m, 1H), 1.54 – 1.42 (m, 1H), 1.36 (s, 3H), 1.25 (s, 9H), 1.01 (t, J =

7.5 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 130.32 (s), 127.55 (s), 124.79 (s), 122.03

(s), 56.62 (s), 47.51 (s), 45.89 (s), 40.04 (s), 39.76 (s), 39.48 (s), 39.20 (s), 22.92 (s),

21.73 (s), 19.81 (s), 11.04 (s).19F NMR (376 MHz, CDCl3) δ -62.18 (t, J = 10.7 Hz).


34

(2R,3R)-1-((R)-tert-butylsulfinyl)-3-cyclohexyl-2-methyl-2-(2,2,2-trifluoroethyl)

aziridine 34:


2854, 1452, 1366, 1265, 1254, 1149, 1087, 949, 688 cm-1.1H NMR (400 MHz, CDCl3)

δ 3.39 (dq, J = 23.5, 11.7 Hz, 1H), 2.50 (dq, J = 15.3, 10.0 Hz, 1H), 2.40 (d, J = 6.4 Hz,

1H), 1.84 – 1.64 (m, 5H), 1.37 (s, 3H), 1.27 (s, 9H), 1.19 (dd, J = 18.1, 8.4 Hz, 6H). 13C

NMR (101 MHz, CDCl3) δ 130.20 (s), 127.45 (s), 124.68 (s), 121.95 (s), 56.68 (s),

49.17 (s), 48.14 (s), 39.47 (s), 39.19 (s), 38.92 (s), 38.64 (s), 37.70 (s), 30.78 (s), 30.03

(s), 26.28 (s), 25.72 (s), 25.63 (s), 23.41 (s), 20.52 (s).19F NMR (376 MHz, CDCl3) δ -

62.04 (t, J = 10.8 Hz). HRMS (ESI) calculated for C15H26F3NNaOS+ [M+Na]+:

348.1579, found 348.1575.

35

(R)-1-((R)-tert-butylsulfinyl)-2-(2,2,2-trifluoroethyl) aziridine 35:

0.35g, 86%, as a colourless oil. [α]19 D = - 89.23 (c 0.3, CHCl3). IR (KBr) νmax: 2969, 2902,

2360, 2341, 1507, 1262, 1065, 1046, 800 cm-1.1H NMR (400 MHz, CDCl3) δ 2.70 (d,

J = 6.3 Hz, 1H), 2.38 – 2.22 (m, 3H), 1.78 (d, J = 3.2 Hz, 1H), 1.22 (s, 9H). 13C NMR

(101 MHz, CDCl3) δ 130.1, 127.4, 124.6, 122.4, 57.4, 37.1(q, J = 28.6 Hz), 26.9 (q, J

= 4.0 Hz), 23.6, 22.8. 19F NMR (376 MHz, CDCl3) δ -65.02 (t, J = 10.3 Hz). HRMS

(ESI) calculated for C8H14F3NNaOS+ [M+Na]+: 252.0640, found 252.0641.

36

(2R)-1-(tert-butylsulfinyl)-2-methyl-2-(2,2,2-trifluoroethyl)aziridine 36:

0.15g, 62%, as a colourless oil. [α]25 D = -75.25 (c 0.5, CHCl3). IR (KBr) νmax: 2958, 2925,

2855, 1460, 1376, 1260, 1147, 1098, 1020, 802 cm-1.1H NMR (400 MHz, CDCl3) δ

31

2.49 (s, 1H), 2.28 (q, J = 10.7 Hz, 2H), 1.89 (s, 1H), 1.52 (s, 3H), 1.22 (s, 9H). 13C NMR

(101 MHz, CDCl3) δ 130.3, 127.5, 124.8, 121.0, 57.5, 43.9, 43.6, 43.3, 43.0, 36.6, 30.2,

22.6, 17.2. 19F NMR (376 MHz, CDCl3) δ -62.42 (t, J = 10.7 Hz). HRMS (ESI)

calculated for C9H16F3NNaOS+ [M+Na]+: 266.0797, found 266.0799.

NS

O

t-Bu CF3 37

(S)-1-((R)-tert-butylsulfinyl)-2-isopropyl-2-(2,2,2-trifluoroethyl)aziridine 37:


2926, 2855, 1739, 1673, 1621, 1464, 1377, 1263, 1115, 1083, 977, 802 cm-1.1H NMR

(400 MHz, CDCl3) δ 2.52 – 2.41 (m, 3H), 2.11 (s, 1H), 1.99 – 1.89 (m, 1H), 1.21 (s,

9H), 1.10 (d, J = 6.7 Hz, 3H), 1.02 (d, J = 6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ

58.0, 34.0, 33.8, 33.5, 33.2, 31.6, 30.0, 23.9, 22.4, 20.3, 17.8. 19F NMR (376 MHz,


[M+Na]+: 294.1110, found 294.1113.

38

(R)-2-benzyl-1-((R)-tert-butylsulfinyl)-2-(2,2,2-trifluoroethyl)aziridine 38:

0.20g, 63%, as a colourless oil. [α]25 D = - 68.10 (c 0.6, CHCl3). IR (KBr) νmax: 2987, 2955,

2925, 2826, 1455, 1392, 1364, 1256, 1141, 1076, 700, 676, 606 cm-1.1H NMR (400

MHz, CDCl3) δ 7.34 – 7.23 (m, 5H), 3.16 (d, J = 14.4 Hz, 1H), 2.67 (d, J = 14.4 Hz,

2H), 2.50 (q, J = 10.5 Hz, 2H), 1.93 (s, 1H), 1.25 (d, J = 5.7 Hz, 9H). 13C NMR (101

MHz, CDCl3) δ 137.3, 130.4, 129.5, 128.9, 127.6, 127.1, 124.9, 122.1, 58.1, 40.5, 40.5,

40.4, 40.4, 39.1, 38.9, 38.6, 38.3, 36.5, 30.5, 22.6. 19F NMR (376 MHz, CDCl3) δ -61.26

(t, J = 10.6 Hz).HRMS (ESI) calculated for C15H20F3NNaOS+ [M+Na]+: 342.1110,

found 342.1112.

39

(R)-1-((R)-tert-butylsulfinyl)-2-pentyl-2-(2,2,2-trifluoroethyl)aziridine 39:

0.20 g, 59%, as a colourless oil. [α]25 D = - 129.19 (c 0.5, CHCl3). IR (KBr) νmax: 2961,

2929, 2873, 1461, 1453, 1259, 1142, 1084, 831, 800 cm-1.1H NMR (400 MHz, CDCl3)

δ 2.46 (s, 1H), 2.43 – 2.17 (m, 2H), 1.92 – 1.80 (m, 2H), 1.74 – 1.23 (m, 7H), 1.21 (s,

9H), 0.91 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 130.3, 127.6, 124.8, 122.0,

57.8, 40.1, 40.1, 40.1, 40.0, 39.7, 39.4, 39.1, 30.3, 30.2, 28.8, 22.7, 22.6, 14.0. 19F NMR

32



40

(R)-1-((R)-tert-butylsulfinyl)-2-(4-chlorobenzyl)-2-(2,2,2-trifluoroethyl)aziridine 40:


2928, 1493, 1390, 1362, 1262, 1142, 1091, 982 cm-1.1H NMR (400 MHz, CDCl3) δ

7.30 (d, J = 8.3 Hz, 2H), 7.19 (d, J = 8.3 Hz, 2H), 3.17 (d, J = 14.6 Hz, 1H), 2.99 (d, J

= 14.6 Hz, 1H), 2.75 (s, 1H), 2.36 (dq, J = 15.3, 10.2 Hz, 1H), 2.02 – 1.90 (m, 2H), 1.26

(s, 9H). 13C NMR (101 MHz, CDCl3) δ 135.7, 133.1, 130.8, 130.3, 129.1, 127.6, 124.8,

122.0, 58.2, 40.2, 40.2, 40.2, 40.2, 39.2, 38.9, 38.6, 38.4, 35.9, 30.3, 22.6. 19F NMR



41

(R)-1-((R)-tert-butylsulfinyl)-2-((5-methylfuran-2-yl)methyl)-2-(2,2,2-trifluoroethyl)

aziridine 41:


2927, 2869, 1458, 1362, 1259, 1137, 1100, 1072, 791 cm-1.1H NMR (400 MHz, CDCl3)

δ 6.04 (d, J = 3.0 Hz, 1H), 5.91 – 5.86 (m, 1H), 3.17 – 3.12 (m, 1H), 3.01 (d, J = 15.5

Hz, 1H), 2.68 (s, 1H), 2.43 (dq, J = 15.3, 10.5 Hz, 1H), 2.26 (s, 3H), 2.25 – 2.15 (m,

1H), 1.96 (s, 1H), 1.23 (d, J = 5.5 Hz, 9H). 13C NMR (101 MHz, CDCl3) δ 151.7, 149.0,

130.2, 127.5, 124.7, 121.9, 108.9, 106.2, 57.9, 39.7, 39.5, 39.2, 39.0, 39.0, 39.0, 39.0,

38.9, 29.8, 29.7, 22.5, 13.6.19F NMR (376 MHz, CDCl3) δ -61.74 (t, J = 10.7 Hz).

HRMS (ESI) calculated for C14H20F3NNaO2S+ [M+Na]+: 346.1059.1423, found

346.1057.

33

5 Transformations of the substrate 3

42

(2R,3R)-1-(tert-butylsulfonyl)-2-phenyl-3-(2,2,2-trifluoroethyl) aziridine 42:

In a round bottom flask, 3 (305 mg, 1.00 mmol) and m-CPBA (258 mg, 1.50 mmol)

mixed with fresh distillated CH2Cl2 (3.0 mL) in a nitrogen atmosphere. The mixture

was kept stirring at room temperature for 2 h. Then, saturated NaHCO3 (20 mL) was

added, and the mixture was extracted by CH2Cl2 (3 x 20 mL). The combined organic

phase was dried over Na2SO4, and concentrated in vacuo. The residue was purified by

flash column chromatography on silica gel (petroleum ether: ethyl acetate = 10:1) to

furnish the desired compound 42 (304 mg, 95 % yield) as a white solid. [α]19 D = -59.29

(c 2.6, CHCl3); m. p. 88.5-88.7 oC; IR (KBr) νmax: 3066, 3036, 1437, 1280, 1133, 1114,

1078, 946, 807, 574 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.38 (d, J = 7.5 Hz,

3H), 7.28 – 7.25 (m, 2H), 3.72 (t, J = 2.9 Hz, 1H), 3.28 – 3.16 (m, 1H), 2.92 – 2.75 (m,

2H), 1.43 (s, 9H). 13C NMR (100 MHz, Chloroform-d) δ 134.6, 129.8, 129.1, 128.9,

127.0, 126.3, 124.2, 60.8, 48.8, 43.9, 43.8, 34.1, 33.8, 33.5, 33.2, 24.1. 19F NMR (376

MHz, Chloroform-d) δ -65.31 (t, J = 10.0 Hz). HRMS (ESI) calculated for


43

N-((1R,2S)-2-(benzylamino)-4,4,4-trifluoro-1-phenylbutyl)-2-methylpropane-2-

sulfonamide 43:

In a round bottom flask, 42 (100 mg, 0.31 mmol) dissolved in DMSO (1.0 mL) in a

nitrogen atmosphere. Then, Benzylamine (66 mg, 0.62 mmol) and Triethylamine (313

mg, 3.1 mmol) was added. The mixture was kept stirring at 80oC for 6 h. The mixture

was diluted with ethyl acetate and washed with water. The combined organic phase was

dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash

column chromatography on silica gel (petroleum ether: ethyl acetate = 10:1) to furnish

the desired compound 43 (106 mg, 80 % yield) as a colorless oil. [α]27 D = +24.89 (c 2.2,

CHCl3); IR (KBr) νmax: 3336, 3271, 3063, 3030, 2923, 2851, 1261, 1212, 1116, 929,

34

736, 631 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.43 (t, J = 7.4 Hz, 2H), 7.38 –

7.30 (m, 7H), 7.30 – 7.26 (m, 1H), 4.57 (d, J = 9.8 Hz, 1H), 4.28 (d, J = 3.1 Hz, 1H),

4.01 (dq, J = 12.2, 7.5, 5.6 Hz, 1H), 3.80 (dd, J = 12.7, 2.4 Hz, 1H), 3.69 (dd, J = 12.7,

2.5 Hz, 1H), 2.28 – 2.07 (m, 2H), 1.41 (s, 9H). 13C NMR (100 MHz, Chloroform-d) δ

139.8, 138.3, 129.3, 128.7, 128.5, 128.2, 127.5, 127.4, 127.3, 124.8, 65.7, 60.5, 54.4,

54.4, 52.5, 34.4, 34.1, 33.8, 33.6, 24.1. 19F NMR (376 MHz, Chloroform-d) δ -62.07 (t,

J = 10.7 Hz). HRMS (ESI) calculated for C21H27F3N2NaO2S+ [M+Na]+: 451.1638,

found 451.1631.

44

2-methyl-N-((1R,2S)-4,4,4-trifluoro-1-phenyl-2-(p-tolylthio)butyl)propane-2-

sulfonamide 44:

In a round bottom flask, 42 (100 mg, 0.31 mmol) dissolved in DMSO (1.0 mL) in a

nitrogen atmosphere. Then, p-Toluenethiol (77 mg, 0.62 mmol) and Triethylamine (313

mg, 3.1 mmol) was added. The mixture was kept stirring at room temperature for 20

min. The mixture was diluted with ethyl acetate and washed with water. The combined

organic phase was dried over Na2SO4, and concentrated in vacuo. The residue was

purified by flash column chromatography on silica gel (petroleum ether: ethyl acetate

= 10:1) to furnish the desired compound 44 (125 mg, 91 % yield) as a colorless oil.

[α]28 D = +103.91 (c 3.5, CHCl3); IR (KBr) νmax: 3294, 2980, 2924, 2393, 2235, 1520,

1315, 1271, 1156, 1076, 769 cm-1. 1H NMR (400 MHz, Chloroform-d) δ 7.60 – 7.50

(m, 2H), 7.38 – 7.24 (m, 5H), 7.02 (d, J = 7.8 Hz, 2H), 4.82 (d, J = 3.2 Hz, 1H), 4.62

(d, J = 10.9 Hz, 1H), 4.14 (tt, J = 10.1, 3.8 Hz, 1H), 2.44 – 2.27 (m, 2H), 2.24 (s, 3H),

1.45 (s, 9H). 13C NMR (100 MHz, Chloroform-d) δ 138.1, 137.9, 132.6, 130.1, 129.8,

129.1, 128.6, 128.2, 127.2, 124.4, 121.7, 62.8, 60.9, 55.5, 55.5, 34.6, 34.3, 34.0, 33.7,

23.9, 21.2. 19F NMR (376 MHz, Chloroform-d) δ -62.26. HRMS (ESI) calculated for

C21H26F3NNaO2S2+ [M+Na]+: 468.1249, found 468.1241.

46-M

N-((1S,2R)-1-(2-bromoethoxy)-4,4,4-trifluoro-1-phenylbutan-2-yl)-2-methylpropane-

2-sulfonamide 46-M:

35

In a round bottom flask, 42 (100 mg, 0.31 mmol) dissolved in 2-Bromoethanol (1.0 mL)

in a nitrogen atmosphere. Then, Cu(OTf)2 (11 mg, 0.03 mmol) was added. The mixture

was kept stirring at room temperature for 2 h. The mixture was diluted with ethyl acetate

and washed with water. The combined organic phase was dried over Na2SO4, and

concentrated in vacuo. The residue was purified by flash column chromatography on

silica gel (petroleum ether: ethyl acetate = 10:1) to furnish the desired compound 46-M

(125 mg, 91 % yield) as a colorless oil. [α]26 D = +43.81 (c 1.4, CHCl3); IR (KBr) νmax:

3296, 2961, 2928, 1422, 1198, 1037, 928, 709 cm-1. 1H NMR (400 MHz, Chloroform-

d) δ 7.42 – 7.30 (m, 5H), 4.96 (d, J = 2.7 Hz, 1H), 4.47 (d, J = 10.9 Hz, 1H), 3.99 –

3.90 (m, 2H), 3.79 (ddd, J = 11.1, 6.2, 4.5 Hz, 1H), 3.64 (ddd, J = 11.3, 6.9, 4.5 Hz,

1H), 3.56 (ddd, J = 10.8, 6.2, 4.7 Hz, 1H), 2.47 – 2.35 (m, 1H), 2.16 – 2.05 (m, 1H),

1.43 (s, 9H). 13C NMR (100 MHz, Chloroform-d) δ 137.2, 130.5, 129.1, 128.5, 127.7,

126.2, 125.0, 84.5, 70.1, 60.7, 55.6, 55.6, 32.2, 31.9, 31.6, 31.4, 31.3, 23.9. 19F NMR

(376 MHz, Chloroform-d) δ -62.26. HRMS (ESI) calculated for C16H23BrF3NNaO3S+

[M+Na]+: 468.0426, found 468.0427.

46

(2S,3R)-4-(tert-butylsulfonyl)-2-phenyl-3-(2,2,2-trifluoroethyl)morpholine 46:

In a round bottom flask, 50-M (125 mg, 0.28 mmol) dissolved in THF (3.0 mL) in a

nitrogen atmosphere. Then, KOH (31 mg, 0.56 mmol) was added. The mixture was kept

stirring at room temperature for 0.5 h. The mixture was diluted with ethyl acetate and

washed with water. The combined organic phase was dried over Na2SO4, and

concentrated in vacuo. The residue was purified by flash column chromatography on

silica gel (petroleum ether: ethyl acetate = 10:1) to furnish the desired compound 46

(94 mg, 92 % yield) as a colorless oil. [α]25 D = -28.03 (c 1.4, CHCl3); IR (KBr) νmax: 3031,

2962, 2930, 2871, 1264, 1204, 1161, 1118, 1063, 1037, 993, 758, 698 cm-1. 1H NMR

(400 MHz, Chloroform-d) δ 7.43 – 7.27 (m, 5H), 4.97 (d, J = 2.4 Hz, 1H), 4.37 (dt, J =

10.2, 3.1 Hz, 1H), 4.06 (qd, J = 6.2, 4.1, 3.0 Hz, 2H), 3.55 (dt, J = 15.7, 1.5 Hz, 1H),

3.49 – 3.36 (m, 1H), 2.71 (dp, J = 15.8, 10.5 Hz, 1H), 2.06 – 1.93 (m, 1H), 1.42 (s, 9H). 13C NMR (100 MHz, Chloroform-d) δ 137.8, 128.8, 127.8, 128.1, 125.1, 80.8, 68.4,

62.4, 54.5, 54.5, 42.6, 29.7, 29.4, 29.1, 28.8, 24.3. 19F NMR (376 MHz, Chloroform-d)

δ -62.55. HRMS (ESI) calculated for C16H22F3NNaO3S+ [M+Na]+: 388.1165, found

388.1168.

36

5 Crystal data of Compounds 7 and 26

Crystal data and structure refinement for 7.

Identification code 7

Empirical formula C15H17F6NOS

Formula weight 373.35

Temperature/K 150(2)

Crystal system orthorhombic

Space group P212121

a/Å 7.34650(10)

b/Å 13.64660(10)

c/Å 17.5192(2)

α/° 90

β/° 90

γ/° 90

Volume/Å3 1756.38(3)

Z 4

ρcalcg/cm3 1.412

μ/mm-1 2.231

F(000) 768.0

Crystal size/mm3 0.2 × 0.15 × 0.15

Radiation CuKα (λ = 1.54184)

2Θ range for data collection/° 8.212 to 148.492

Index ranges -8 ≤ h ≤ 8, -17 ≤ k ≤ 16, -21 ≤ l ≤ 21

Reflections collected 64477

Independent reflections 3543 [Rint = 0.0770, Rsigma = 0.0194]

Data/restraints/parameters 3543/0/220

Goodness-of-fit on F2 1.029

Final R indexes [I>=2σ (I)] R1 = 0.0421, wR2 = 0.1173

Final R indexes [all data] R1 = 0.0425, wR2 = 0.1177

Largest diff. peak/hole / e Å-3 0.48/-0.32

Flack parameter 0.007(6)

37

Crystal data and structure refinement for 26.

Identification code 26

Empirical formula C15H20F3NOS

Formula weight 319.38

Temperature/K 120.0(1)

Crystal system monoclinic

Space group P21

a/Å 6.2173(3)

b/Å 7.2888(4)

c/Å 17.6163(11)

α/° 90

β/° 96.159(5)

γ/° 90

Volume/Å3 793.70(8)

Z 2

ρcalcg/cm3 1.336

μ/mm-1 2.092

F(000) 336.0

Crystal size/mm3 0.15 × 0.1 × 0.1

Radiation CuKα (λ = 1.54184)

2Θ range for data collection/° 5.046 to 147.322

Index ranges -7 ≤ h ≤ 7, -8 ≤ k ≤ 8, -21 ≤ l ≤ 21

Reflections collected 7416

Independent reflections 2979 [Rint = 0.0251, Rsigma = 0.0273]

Data/restraints/parameters 2979/1/194

Goodness-of-fit on F2 1.073

Final R indexes [I>=2σ (I)] R1 = 0.0395, wR2 = 0.0999

Final R indexes [all data] R1 = 0.0406, wR2 = 0.1005

Largest diff. peak/hole / e Å-3 0.36/-0.25

Flack parameter 0.039(11)

38

6 Computational Studies

Density Functional theory (DFT) calculations were carried out using Gaussian09

program.[2] geometry optimizations were performed with dispersion-corrected density

functional method B3-LYP functional, SDD basis set [3] with effective core potential

(ECP) and associated double-valence basis set was used for Cu and I, and the 6-

31G(d,p) basis set was used for other atoms in the gas phase optimisation. Both local

minima and transition structures are confirmed by vibrational frequencies with 0 and 1

imaginary frequency, respectively. Single point energies using B3-LYP functional with

triple- valence polarized 6-311+G(d,p) basis set for other atoms and SDD ECP for Cu

and I in SMD continuum solvation model[4] with intrinsic atomic Coulomb radii were

evaluated to include the effect of 2-methyl-2-propanol (ε=12.47) on the computed

Gibbs energy profile. All transition structures are checked by intrinsic reaction

coordinate (IRC) calculation. Images were prepared using CYLview. [5]

Moreover, minimum energy crossing points (MECPs) between potential energy

surface (PES) of differen spin states were located with the code [6] developed by Harvey

and co-workers at the B3-LYP/6–31G(d) (SDD basis set for Cu and I) level of theory.

Our DFT studies started from the generation of CF3∙ radical using Togni’s reagent

under Cu(I) catalysis. This reaction was fully studed by Li [7] and Lan’s [8] groups

separatedly, using CuCl as the catalyst. We repeated this with CuI as the catalyst. Thus,

as shown in Figure 6.1, the Togni’s reagent and CuI were chosen as the relative zero

point for this energy profile. In the first step, CuI coordinated on the carbonyl group of

Togni’s reagent, insertion of copper into the I-O bond can then occur through TS1a,2a

with a free energy barrier of 9.6 kcal∙mol-1, leading to the formation of intermediate

Int2a. The subsequent hemolytic I-CF3 bond cleavage proceeds via minimum-energy

crossing point MECP(2a-3a) to generate a CF3∙ radical and cupric comound Int3a. And

the Gibbs free energy barrier for this process is 11.4 kcal∙mol-1, which agrees with the

Gibbs free energy barrier for the same step catalyzed by CuCl in Li’s paper, where 11.2

kcal∙mol-1 was reported. [7] Alternatively, silimilar to what has been reported by Lan

group[8], the direct hemolytic I-CF3 bond cleavage in intermediate Int1a via MECP(1a-

4a) could also afford free radical CF3∙ and cupric compound Int4a, but with a higer free

energy barrier.

39

Figure 6.1 Free Energy Profiles for the Generation of .CF3 Radical from Togni’s

Reageng with CuI Catalyst. Geometry optimized with (U)B3LYP/6-31G(d)-SDD(for

Cu and I) in gas phase. Free energy calculated with SMD(tBuOH)-(U)B3LYP/6-

311+G(d,p)-SDD(for Cu and I) // (U)B3LYP/6-31G(d)-SDD(for Cu and I). Bond

distance in Å and shown in red italic. The relative Gibbs free energies are given in

kcal∙mol-1.

After finishing the “test” calculation above, we set off to understand the reaction

mechanism of this diastereoselective radical aminotrifluoromethylation reaction

catalyzed by CuI and with L-proline as chiral ligand. To save computational cost, the

R1 group in alkenyl sulfinamide Int1 was simplified to methyl group (see Int1 in Figure

6.2). Different from what has been discussed above, in this reaction, a base (such as

Na2CO3) and a chiral ligand L-proline were used. Therefore, the deprotonated L-proline

replaces the Iodide in CuI, which can form a complex with Togn’s reagent and the

substrate alkenyl sulfinamide Int1, which leads to two complexes Int2_trans and Int2_cis

at a Gibbs free energies lower by 25.5 kcal∙mol-1 and 24.0 kcal∙mol-1 respectively than

the free energy sum of the starting materials. Int2_trans and Int2_cis are two conformers

which could interconvert to each other by rotating the single bond in C-C=C moiety in

the sulfinamide Int1 part of the complex. And in both structures, there are two sets of

hydrogen bonds: one is between the proline NH and the O on sulfonamide, and the

other is between the O on proline and the N-H on sulfonamide, with bond distances ca

2.00 Å (Figure 6.3). Whereas interactions between the Cu and the double doesn't exist,

40

due to the high number of coordination on Cu. Insertion of copper into the I-O bond in

Int2_trans and Int2_cis can then occur through TS2,3_trans and TS2,3_cis (Figure 6.4)

respectively with free energies 11.3 and 12.6 kcal∙mol-1, leading to the formation of

Int3_trans and Int3_cis respectively (Figure 6.2). Both Int3_trans and Int3_cis can have

similar CF3∙ radical generation process, through MECP(3-4)_trans and MECP(3-4)_cis

respectively, with Gibbs free energy barriers of 8.1 and 7.3 kcal∙mol-1 separatly. The

Gibbes free energy difference between MECP(3-4)_trans and MECP(3-4)_cis is only 1.5

kcal/mol. And the difference in the resulting cupric compound Int4_trans and Int4_cis lies

in that that the Cu is interacting with different faces of the double in alkenyl sulfinamide

Int1, and with a stronger interaction between the Cu and C=C bond in Int4_trans. The

bond distances for the two C-Cu bond are 3.11 Å and 2.80 Å repestively in Int4_trans.

Therefore, in the following step, while CF3∙ radical attacks the terminal carbon in the

double bond, the rest part of the molecule is fixed, this reaction happends via transition

state TS6,7_trans, which is 10.0 kcal∙mol-1 higer in Gibbs free energy, comparing to the

energy sum of Int4_trans and CF3∙ radical, and the resulting Int7_trans is with 16.9

kcal∙mol-1 lower in free energy than the energy sum of Int4_trans and CF3∙ radical.

Therefore, this is a no-barrier exogonic process. In Int7_trans, the Cu-C bond is already

formed with a 2.07 Å bond distance. On the other hand, similar radical reaction process

in Int4_cis happens in the same way but with higher energy. Int7_trans is the precursor for

the formation of the experimentally observed major aziridine product, after

deprotonation and reductive elimination steps (Figure 6.8). Whereas, Int7_cis would

serve as the precursor for the minor aziridine formed in the reaction, following similar

steps.

41

Gib

bs

Fre

e E

ne

rgy

(kca

l mo

l-1)

2.01 2

.05

2.55

2.41

2.02 2

.01

2.48

2.55

2.01

3.29

1.98

2.04

3.2

2 2.86

2.43

3.2

1 3.06

2 .07

1.96 2

.05

3.07

2.76

2.76

2.00 1

.90

4.20

3.85

1.85

1.97 2

.00

4.02

3.8

7

1.89

1.95 2

.142.

73

5.01

4.45

1.95 2

.09

4.37

4.04

1.88

4.50

4.28

Figure 6.2 Free Energy Profiles for Free Radical Initiation and Reaction with

Sulfinamide. Geometry optimized with (U)B3LYP/6-31G(d)-SDD(for Cu and I) in gas

phase. Free energy calculated with SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-SDD (Cu

and I) // (U)B3LYP/6-31G(d)-SDD(Cu and I). Bond distance in Å and shown in red

italic. The relative Gibbs free energies are given in kcal mol-1.

1.89

3.071.85

2.00 1

.90

2.29

1.89

3.07

1.85

Figure 6.3 Geometry for Int2_trans and Int2_cis. Geometry optimized with (U)B3LYP/6-

31G(d)-SDD(for Cu and I) in gas phase. Free energy calculated with SMD(tBuOH)-

(U)B3LYP/6-311+G(d,p)-SDD(Cu and I) // (U)B3LYP/6-31G(d)-SDD(Cu and I).

Bond distance in Å and shown in red italic. The relative Gibbs free energies are given

in kcal mol-1.

42

Figure 6.4 TS-energy Crossing Point MECP(3-4) and MECP(2-5). Minimum

energy crossing points (MECPs) were located with the code[5] developed by Harvey

and co-workers at the B3-LYP/6–31G(d) (SDD basis set for Cu and I) level of theory.

Free energy calculated with SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-SDD(Cu and I) //

(U)B3LYP/6-31G(d)-SDD(Cu and I). Bond distance in Å and shown in red italic. The

relative Gibbs free energies are given in kcal mol-1.

Figure 6.5 Transition State Geometry for the Insertion of Copper into the I-O

Bond in Int2_trans and Int2_cis. Geometry optimized with (U)B3LYP/6-31G(d)-SDD(for

Cu and I) in gas phase. Free energy calculated with SMD(tBuOH)-(U)B3LYP/6-

311+G(d,p)-SDD(Cu and I) // (U)B3LYP/6-31G(d)-SDD(Cu and I). Bond distance in

Å and shown in red italic. The relative Gibbs free energies are given in kcal mol-1.

Figure 6.6 Structures for Int4_trans and Int4_cis. Geometry optimized with

43

(U)B3LYP/6-31G(d)-SDD(for Cu and I) in gas phase. Free energy calculated with

SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-SDD(Cu and I) // (U)B3LYP/6-31G(d)-

SDD(Cu and I). Bond distance in Å and shown in red italic. The relative Gibbs free

energies are given in kcal mol-1.

Figure 6.7 Transition State Geometry for the CF3∙ Radical Attack and Cu-C Bond

Formation Steps. Geometry optimized with (U)B3LYP/6-31G(d)-SDD(for Cu and I)

in gas phase. Free energy calculated with SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-

SDD(Cu and I) // (U)B3LYP/6-31G(d)-SDD(Cu and I). Bond distance in Å and shown

in red italic. The relative Gibbs free energies are given in kcal mol-1.

The next part of the reaction involves three steps: the formation of the 4-membered

ring which doesn't involve a transition state, followed by deprotonation of NH

iodophenyl carboxylate, via TS8,9, leading to Int9, which, after the expelling of the

IPhCOOH, becomes Int10 in an exogonic process, Int10 is then transformed into Int11,

via TS10,11 in a reductive elimination process. Alternatively, the deprotonation and the

following reductive elimination can be done by deprotonated L-proline as shown in

purple in Figure 3, but with slightly higer energy.

44

-54.4-54.6

-57.1

Int8TS8,9

Int9-68.8

Int10

-54.2

-53.4

-51.8Int12

TS12,13

Int13

-70.7

Int14

L-proline

rCu-N 1.99rO-H 1.61rN-H 1.08

rCu-N 1.96rO-H 1.28rN-H 1.23

rCu-N 1.93rO-H 1.01rN-H 1.76

rCu-N 1.89rCu-C 1.96rC-N 2.23

rCu-N 1.96rO-H 1.76rN-H 1.05

rCu-N 1.91rO-H 1.01rN-H 1.79

rCu-N 1.89rCu-C 1.96rC-N 2.23O

S NtBu

CuIII

H3C HH CF3

OH O PHI

O O

NH

OS N

tBu

CuIII

H3C HH CF3

OH O PHI

O O

NH

OS N

tBu

CuIII

H3C HH CF3

OH O PHI

O O

NH

IPhCOOH

OS N

tBu

CuIII

H3C HH CF3

O O

NH

-49.3

Int7_trans

OS

N

tBu

CuIIN O

O

HH

H3C H CF3

O

PhI

-67.8

TS10,11-87.4

Int11

-66.8

-83.8

TS14,15

Int15

rCu-N 1.87rCu-C 2.26rC-N 1.95

rCu-N 1.92rCu-C 2.91rC-N 1.52

rCu-N 1.92rCu-C 2.23rC-N 1.84

rCu-N 1.93rCu-C 2.91rC-N 1.51

O

rCu-N 1.94rO-H 1.24rN-H 1.28

OS N

tBu

CuIII

H3C HH

H

OO

NH

OPhI

O

CF3OS N

tBu

CuIII

H3C HH

H

OO

NH

OPhI

O

CF3

OS N

tBu

CuIII

H3C HH

HO

O

NH

OPhI

O

CF3

OS N

tBu

CuIII

H3C HH

OPhI

O

CF3

OS N

tBu

CuIII

H3C HH CF3

O O

NH

O

S NtBu

CuI

H3C HH CF3

O O

NH

OS N

tBu

CuIII

H3C HH

OPhI

O

CF3

O

SNtBu

CuI

H3C HH

OPhI

O

CF3

4-membered ring formation and deprotonation Reduction elemination

Int8

TS8,9

Int9

Int10

TS10,11

Int11

Figure 6.8 Reaction Coordinate for the Reduction Elimination. Geometry

optimized with (U)B3LYP/6-31G(d)-SDD(for Cu and I) in gas phase. Free energy

calculated with SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-SDD(Cu and I) //

(U)B3LYP/6-31G(d)-SDD(Cu and I). Bond distance in Å. The relative Gibbs free

energies are given in kcal mol-1. 2.231.84

Figure 6.9 Transition State Geometry for the Deprotonation and Reduction

Eliminaton Steps, Using Iodo-phenyl Carboxylate as the Base. Geometry optimized

with (U)B3LYP/6-31G(d)-SDD(for Cu and I) in gas phase. Free energy calculated with

SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-SDD(Cu and I) // (U)B3LYP/6-31G(d)-

SDD(Cu and I). Bond distance in Å and shown in red italic. The relative Gibbs free

energies are given in kcal mol-1.

45

2.26

1.95

Figure 6.10 Transition State Geometry for the Deprotonation and Reduction

Eliminaton Steps, Using L-proline as the Base. Geometry optimized with

(U)B3LYP/6-31G(d)-SDD (for Cu and I) in gas phase. Free energy calculated with

SMD(tBuOH)-(U)B3LYP/6-311+G(d,p)-SDD(Cu and I) // (U)B3LYP/6-31G(d)-SDD

(Cu and I). Bond distance in Å and shown in red italic. The relative Gibbs free energies

are given in kcal mol-1.

46

7 NMR Spectrums of Compounds

C1

47

C2

48

C3

49

C3

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