Enantioselective Organocatalyzed Direct α-thiocyanation of. Cyclic β-ketoesters by N-Thiocyanatophthalimide

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1 Supporting Information Enantioselective rganocatalyzed Direct α-thiocyanation of Cyclic β-ketoesters by N-Thiocyanatophthalimide Jiashen Qiu, Di Wu, Pran Gopal Karmaker, Hongquan Yin, and Fu-Xue Chen* School of Chemistry & Chemical Engineering, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian district, Beijing , China fuxue.chen@bit.edu.cn Contents 1. General Information... S2 2. Preparation of the Catalysts.... S3 3. Preparation of the Substrates and Reagents... S5 4. Asymmetric Reactions and Copies of HPLC Chromatograms... S6 4.1 General Procedure for the Synthesis of 4... S6 4.2 Scale-up reaction of 4d S26 5. X-Ray Structure of 4e (CCDC )... S28 6. References... S35 7. Copies of 1 H and 13 C NMR Spectra... S36 S1

2 1. General information All reactions were carried out with oven dried glassware under argon atmosphere, unless otherwise stated. All chemicals were purchased from Acros, Alfa, Aladdin, or InnoChem and used as it comes unless otherwise stated. TLC was performed on silica gel F254 TLC glass plates and visualized with UV light. All the HPLC columns were purchased from Daicel Chemical Industries. Solvent of petroleum ether (PE) and ethyl acetate (EA) were used directly in column chromatography. Toluene, THF were dried over sodium (diphenyl ketone) and distilled; CH2Cl2 were distilled over CaH2 before use. 1 H NMR spectra were recorded on a Brucker Avance400 (400 MHz) spectrometer in chloroform-d, all signals are reported in ppm with the internal chloroform signal at 7.26 ppm as the standard. 13 C{ 1 H} NMR spectra were recorded with 1 H-decoupling on a Brucker Avance400/700 (100/146 MHz) spectrometer in chloroform-d, all signals are reported in ppm with the internal chloroform signal at 77.0 ppm as the standard. The data is reported as (s = singlet, d = doublet, t = triplet, m = multiplet or unresolved, coupling constant(s) in Hz, integration, assignment). ther analyses were carried out on the following instruments. Infrared spectrometer: Bruker ALPHA FT-IR-Spektrometer. High resolution mass spectrum: AGILENT 7890A/5975C. Rotation polarity: Krüss P8000. High Performance Liquid Chromatography: Shimadzu LC-20A. Melting point detector:binocular microscope XT4A melting point apparatus (without correct). S2

3 Scheme S1. Lewis Acid-Catalyzed α-thiocyanation 2. Preparation of Catalysts. Catalysts 3a-3d were purchased from Sigma Aldrich and used without further purification. Catalysts 3e-k and QN-1 were prepared according to known literature procedures. 1 Figure S1. Structure of Catalysts Evaluated in This Study General Procedure for the Preparation of 3e-k (by using Quinidine as the starting material) and QN-1 (by using Quinine as the starting material): S3

4 3j was obtained as a yellowish powder with two steps (302.5 mg, 72% yield). TLC: eluent EA/MeH/Et3N (10/1/0.01, v/v/v), Rf = [α] 20 D = (c 0.30, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ (br, 1H), 8.70 (s, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.94 (s, 1H), 7.48 (br, 1H), 7.30 (d, J = 8.8 Hz, 1H), 6.80 (s, 2H), (m, 1H), 5.60 (br, 1H), (m, 2H), (m, 2H), 3.45 (br, 1H), (m, 4H), (m, 10H), 1.72 (br, 1H), (m, 2H), (m, 2H); 13 C NMR (100 MHz, CDCl3) δ 156.8, 146.4, 144.6, 143.7, 139.7, 137.8, 137.7, 131.3, 131.1, 128.9, 128.1, 123.2, 114.8, 106.8, 66.1, 59.6, 49.7, 48.7, 39.6, 31.6, 28.1, 26.1, 22.1, 21.0, 19.7 ppm. IR (KBr) (br.), 2935, 2872, 1616, 1508, 1458, 1242, 1051, 732 cm -1. HRMS (ESI): calc. for C29H35N22 [M+H] + : found: k was obtained as a yellowish powder with two steps (350.3 mg, 67% yield). TLC: eluent EA/MeH/Et3N (10/1/0.01, v/v/v), Rf = [α] 20 D = (c 0.45, CH2Cl2). [lit. [2] [ ] 25 D = (c 0.11, CHCl3)]. 1 H NMR (400 MHz, CDCl3) δ 9.68 (br, 1H), 8.71 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), (m, 1H), 7.50 (br, 1H), 7.32 (d, J = 8.8 Hz, 1H), 6.99 (s, 2H), (m, 1H), 5.70 (br, 1H), (m, 2H), (m, 2H), 3.53 (br, 1H), 3.25 (br, 2H), (m, 5H), (m, 2H), 1.72 (s, 2H), (m, 2H), (m, 19H); 13 C NMR (100 MHz, CDCl3) δ 156.8, 149.0, 148.5, 146.4, 144.4, 143.9, 139.5, S4

5 131.4, 128.6, 128.1, 123.1, 114.8, 106.8, 64.4, 59.5, 49.7, 48.6, 39.4, 34.4, 31.6, 29.3, 28.1, 27.0, 26.0, 25.2, 24.1 ppm. IR (KBr): (br.), 2958, 2868, 1616, 1508, 1458, 1242, 1050, 854 cm -1. HRMS (ESI): calc. for C35H47N22 [M+H] + : found: QN-1 was obtained as a yellowish powder with two steps (274.2 mg, 62% yield). TLC: eluent EA/MeH/Et3N (10/1/0.01, v/v/v), Rf = [α] 20 D = (c 0.60, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 8.70 (s, 1H), 8.01 (br, 1H), (m, 1H), 7.94 (s, 1H), 7.45 (br, 1H), 7.09 (d, J = 8.8 Hz, 1H), 6.80 (s, 2H), (m, 1H), 5.69 (br, 1H), (m, 2H), (m, 2H), 3.50 (br, 1H), (m, 2H), (m, 2H), (m, 10H), 1.83 (br, 1H), (m, 2H), (m, 2H); 13 C NMR (100 MHz, CDCl3) δ 157.7, 146.4, 145.6, 144.7, 140.8, 139.6, 137.8, 131.3, 131.0, 128.1, 122.9, 120.0, 115.5, 115.0, 106.9, 65.9, 61.5, 48.9, 48.5, 39.8, 39.3, 31.6, 27.8, 27.6, 26.3, 22.7, 21.0, 19.7 ppm. IR (KBr) (br.), 2914, 2852, 1616, 1051, 754 cm -1. HRMS (ESI): calc. for C29H35N22 [M+H] + : found: Preparation of the Substrates and Reagents Substrates 2a-b, 2k-m were prepared according to known literature procedures. 3 Substrates 2c-j, 2n-p were prepared according to known literature procedures. 4 Experimental procedure for synthesis of 1c: To a solution of N-chlorophthalimide (1.82 g, 10 mmol. 1.0 equiv) in 40 ml of dry acetonitrile under Ar was added cuprous thiocyanate (1.46 g, 12 mmol, 1.2 equiv) in S5

6 one portion. The dark brown reaction mixture was stirred at rt for 1-2 h. The resulting suspension was concentrated in vacuum directly. The resulting residues were dissolved and washed with DCM/PE (3:1, 40 ml x 2, v/v) and filtered through a layer of Celite, Filtrate was concentrated in vacuum to provide the title compound as a white solid (1.77 g, 87% yield) including 7% of a phthalimide product, which was used for the asymmetric reaction without further purification. The reagent 1c was stored in the dark at -15 o C under Ar. MP: o C. TLC: eluent PE/EA (5/1, v/v), Rf = H NMR (400 MHz, CDCl3) δ (m, 2H, Ar-H), (m, 2H, Ar- H) ppm. 13 C NMR (100 MHz, CDCl3) δ 164.6, 135.7, 131.5, 124.9, (SCN) ppm. IR (KBr): 2981, 2160 (SCN), 1751, 1273, 866 cm -1. MS (DART): Calc. for C9H8N32S [M+NH4] + : found: Calc. for [SCN] + : found: Calc. for C8H4N2 [M-SCN] + : found: Asymmetric reactions and copies of HPLC chromatograms 4.1 General procedure for the synthesis of 4 General procedure: In a screw-capped reaction tube, substrate 2a (0.05 mmol, 1.0 equiv) and catalyst 3j (2.2 mg, 10 mol %) were dissolved in a solvent (1.0 ml) for 5 min, then the reaction mixture was cooled to 78 o C. The N-thiocyanatophthalimide (1c, mmol, 1.5 equiv) was added in one portion at 78 o C. The resulting solution was stirred at the same temperature until the reaction was completed (monitored by TLC). The crude reaction mixture was directly charged on silica gel and purified by column chromatography (EtAc/PE = 1:10, v/v) to afford the desired product 4a. 1-Adamantanyl (R)-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (4a) was synthesized following the General procedure, using 3j (2.2 mg, mmol, 10 mol%), 1c (15.5 mg, mmol, 1.5 equiv), and 2a (15.5 mg, 0.05 mmol) in 1,1- dichloroethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The S6

7 crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (18.2 mg, 99% yield, 94% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.15, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 (dt, J = 7.6, 1.2 Hz, 1H, Ar-H), (m, 2H, Ar-H), 4.04 (Jab = 18.0 Hz, 1H, CH2), 3.62 (Jab = 18.0 Hz, 1H, CH2), 2.16 (s, 3H, Ad-H), 2.05 (s, 6H, Ad-H), 1.62 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 195.1, 164.8, 151.1, 136.7, 133.2, 128.8, 126.2, 125.8, (SCN), 86.2, 64.4, 40.9, 40.5, 35.8, 31.0 ppm. IR (KBr): 2912, 2850, 2156 (SCN), 1732, 1716, 1450 cm -1. HRMS (ESI): calc. for C21H25N23S [M+NH4] + : Found HPLC: on D-H column (n-hexane/iso-propanol 95:5, v/v, 1.0 ml min 1, 254 nm), tr(major) = 11.0 min, t S(minor) = 12.4 min. Peak time area area/% total Peak time area area/% total S7

8 Ethyl (R)-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (4b) was synthesized following the General procedure, using 3j (4.4 mg, 0.01 mmol), 1c (30.5 mg, 0.15 mmol), and 2b (20.4 mg, 0.10 mmol) in 1,1-dichloroethane (2.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 5 : 1 to 3 : 1, v/v) to provide the title compound as a white solid (22.7 mg, 87% yield, 75% ee). MP: o C. TLC: eluent PE/EA (5/1, v/v), Rf = [α] 20 D = (c 0.70, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 (t, J = 7.6 Hz, 1H, Ar-H), (m, 2H, Ar-H), 4.28 (dd, J = 14.0, 7.2 Hz, 2H, CH2), 4.10 (Jab = 18.0 Hz, 1H, CH2), 3.64 (Jab = 18.0 Hz, 1H, CH2), 1.26 (t, J = 7.2 Hz, 3H, CH3). 13 C NMR (100 MHz, CDCl3) δ 194.5, 166.3, 150.9, 137.0, 133.0, 129.0, 126.3, 126.0, 109.3(SCN), 64.2, 63.5, 40.4, 13.9 ppm. IR (KBr) 2983, 2158 (SCN), 1747, 1714, 1604 cm -1. HRMS (ESI): calc. for C13H15N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol 95:5, v/v, 1.0 ml min 1, 254 nm), tr(major) = 16.6 min, ts(minor) = 18.0 min. Peak time area area/% total S8

9 Peak time area area/% total tert-butyl (R)-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (4c) was synthesized following the General procedure, using 3j (4.4 mg, 0.01 mmol), 1c (30.5 mg, 0.15 mmol), and 2c (23.2 mg, 0.10 mmol) in 1,1-dichloroethane (2.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (28.6 mg, 99% yield, 93% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.50, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 7.6 Hz, 1H, Ar-H), 7.72 (t, J = 7.6 Hz, 1H, Ar-H), (m, 2H, Ar-H), 4.04 (Jab = 18.0 Hz, 1H, CH2), 3.61 (Jab = 18.0 Hz, 1H, CH2), 1.44 (s, 9H, tbu-h). 13 C NMR (100 MHz, CDCl3) δ 195.0, 165.1, 151.0, 136.8, 133.1, 128.8, 126.2, 125.8, (SCN), 86.1, 64.2, 40.4, 27.7 ppm. IR (KBr) 2985, 2150 (SCN), 1705, 1149 cm -1. HRMS (ESI): calc. for C15H19N23S [M+NH4] + : found: HPLC: on AD-H column (n-hexane/iso-propanol 98:2, v/v, 1.0 ml min 1, 254 nm), tr(major) = 11.9 min, ts(minor) = 12.9 min. S9

10 Peak time area area/% total Peak time area area/% total Adamantanyl (R)-5-fluoro-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4d) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2d (16.4 mg, 0.05 mmol) in 1,1- dichloroethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (18.8 mg, 98% yield, 90% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.75, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ (m, 1H, Ar-H), (m, 2H, Ar- H), 4.04 (Jab = 18.4 Hz, 1H, CH2), 3.60 (Jab = 18.0 Hz, 1H, CH2), 2.17 (s, 3H, Ad-H), 2.05 (s, 6H, Ad-H), 1.63 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 193.2, (d, 1 JC-F = Hz), 164.4, (d, 3 JC-F = 10.6 Hz), 129.6, (d, 3 JC-F = 10.7 Hz), (d, 2 JC-F = 23.8 Hz), (d, 2 JC-F = 23.0 Hz), (SCN), 86.5, 64.6, 40.9, 40.3 (d, 4 JC- F = 2.1 Hz), 35.8, 31.0 ppm. IR (KBr): 2914, 2854, 2156 (SCN), 1716, 1614, 1251 cm -1. HRMS (ESI): calc. for C21H24FN23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol, 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.2 min, ts(minor) = 8.6 min. S10

11 Peak time area area/% total Peak time area area/% total Adamantanyl (R)-5-chloro--1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4e) was synthesized following the General procedure, using 3j (3.3 mg, mmol), 1c (15.5 mg, mmol), and 2e (17.2 mg, 0.05 mmol) in 1,1- dichloroethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (19.6 mg, 98% yield, 90% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.30, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz, 1H, Ar-H), 7.51 (s, 1H, Ar- H), 7.46 (dd, J = 8.0, 1.2 Hz, 1H, Ar-H), 4.02 (Jab = 18.0 Hz, 1H, CH2), 3.59 (Jab = 18.0 Hz, 1H, CH2), 2.17 (s, 3H, Ad-H), 2.05 (s, 6H, Ad-H), 1.62 (s, 6H, Ad-H). S11

12 13 C NMR (100 MHz, CDCl3) δ 193.7, 164.4, 152.4, 143.6, 131.7, 129.7, 126.8, 126.5, 109.6(SCN), 86.5, 64.5, 40.9, 40.1, 35.8, 31.0 ppm. IR (KBr) 2914, 2852, 2156 (SCN), 1739, 1597, 1456 cm -1. HRMS (ESI): calc. for C21H24ClN23S [M+NH4] + : Found HPLC: on D-H column (n-hexane/iso-propanol, 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.0 min, ts(minor) = 8.5 min. Peak time area area/% total Peak time area area/% total Adamantan-yl (R)-5-bromo-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4f) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2f (19.4 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (20.5 mg, 92% yield, 84% ee). S12

13 MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.75, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ (m, 1H, Ar-H), 7.63 (d, J = 8.4 Hz, 1H, Ar-H), 4.02 (Jab = 18.0 Hz, 1H, CH2), 3.59 (Jab = 18.0 Hz, 1H, CH2), 2.17 (s, 3H, Ad-H), 2.05 (s, 6H, Ad-H), 1.63 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 194.0, 164.3, 152.4, , , 132.1, 129.5, 126.8, (SCN), 86.6, 64.4, 40.9, 40.1, 35.8, 31.0 ppm. IR (KBr): 2916, 2850, 2156 (SCN), 1732 cm -1. HRMS (ESI): calc. for C21H24Br 79 N23S [M+NH4] + : found: calc. for C21H24Br 81 N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.5 min, ts(minor) = 9.5 min. Peak time area area/% total Peak time area area/% total Adamantanyl (R)-6-bromo-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- S13

14 carboxylate (4g) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2g (19.4 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (18.2 mg, 82% yield, 80% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.80, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 8.00 (s, 1H, Ar-H), 7.81 (d, J = 8.0 Hz, 1H, Ar- H), 7.41 (t, J = 8.4 Hz, 1H, Ar-H), 3.98 (Jab = 18.4 Hz, 1H, CH2), 3.56 (Jab = 18.0 Hz, 1H, CH2), 2.17 (s, 3H, Ad-H), 2.05 (s, 6H, Ad-H), 1.63 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 193.8, 164.3, 149.6, 139.5, 135.0, 128.6, 127.7, 123.0, 109.6(SCN), 86.6, 64.6, 40.9, 40.2, 35.8, 31.0 ppm. IR (KBr) 2914, 2852, 2158 (SCN), 1732, 1257 cm -1. HRMS (ESI): calc. for C21H24Br 79 N23S [M+NH4] + : found: calc. for C21H24Br 81 N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.9 min, ts(minor) = 8.9 min. Peak time area area/% total Peak time area area/% total S14

15 1-Adamantanyl (R)-4-bromo-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4h) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2h (19.4 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (22.2 mg, 99% yield, 92% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 1.00, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.0 Hz, 1H, Ar-H), 7.82 (d, J = 7.6 Hz, 1H, Ar-H), 7.88 (t, J = 8.0 Hz, 1H, Ar-H), 3.96 (Jab = 18.4 Hz, 1H, CH2), 3.52 (Jab = 18.4 Hz, 1H, CH2), 2.17 (s, 3H, Ad-H), 2.06 (s, 6H, Ad-H), 1.63 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 194.5, 164.3, 150.7, 139.4, 135.2, 130.5, 124.6, 121.4, 109.4(SCN), 86.6, 64.1, 41.5, 40.9, 35.8, 31.0 ppm. IR (KBr): 2914, 2852, 2158 (SCN), 1747, 1714, 1597 cm -1. HRMS (ESI): calc. for C21H24Br 79 N23S [M+NH4] + : found: calc. for C21H24Br 81 N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol, 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 9.5 min, ts(minor) = 10.5 min. Peak time area area/% total S15

16 Peak time area area/% total Adamantanyl (R)-6-methyl-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4i) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1 (15.5 mg, mmol), and 2i (16.2 mg, 0.05 mmol) in 1,1- dichloroethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (19.0 mg, 99% yield, 84% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.90, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H, Ar-H), 7.52 (d, J = 8.0 Hz, 1H, Ar- H), 7.39 (t, J = 7.6 Hz, 1H, Ar-H), 3.98 (Jab = 17.6 Hz, 1H, CH2), 3.56 (Jab = 18.0 Hz, 1H, CH2), 2.43 (s, 3H, Me), 2.16 (s, 3H, Ad-H), 2.05 (s, 6H, Ad-H), 1.62 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 195.1, 164.9, 148.5, 139.0, 138.1, 133.4, 125.8, 125.7, 109.9(SCN), 86.0, 64.7, 40.9, 40.3, 35.9, 31.0, 21.2 ppm. IR (KBr) 2912, 2852, 2156 (SCN), 1732, 1253, 1045 cm -1. HRMS (ESI): calc. for C22H27N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.3 min, ts(minor) = 8.3 min. S16

17 Peak time area area/% total Peak time area area/% total Adamantanyl (R)-1,1-dimethyl-3-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4j) was synthesized following the General procedure, using 3j (4.4 mg, 0.01 mmol), 1c (15.5 mg, mmol), and 2j (16.9 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a colorless oil (18.5 mg, 95% yield, 87% ee). TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.60, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 1H, Ar-H), 7.70 (t, J = 7.6 Hz, 1H, Ar-H), (m, 2H, Ar-H), 2.13 (s, 3H, Ad-H), 1.99 (s, 6H, Ad- H), 1.59 (s, 6H, Me), 1.58 (s, 6H, Ad-H). 13 C NMR (100 MHz, CDCl3) δ 194.2, 164.8, 159.9, 136.3, 132.6, 128.6, 125.0, 123.0, 110.0(SCN), 86.1, 75.9, 48.3, 41.0, 35.8, 30.9, 30.0, 25.1 ppm. IR (KBr) 2156 (SCN), 1730, 1704, 1452 cm -1. HRMS (ESI): calc. for C23H23N23S [M+NH4] + : found: HPLC: on AD-H column (n-hexane / iso-propanol 90:10, 1.0 ml min 1, 254 nm), ts(minor) = 7.3 min, tr(major) = 7.9 min. S17

18 Peak time area area/% total Peak time area area/% total tert-butyl (R)-6-chloro-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (4k) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2k (13.3 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (15.0 mg, 93% yield, 83% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.50, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H, Ar-H), 7.68 (d, J = 8.4 Hz, 1H, Ar- H), 7.47 (d, J = 8.4 Hz, 1H, Ar-H), 4.01 (d, J = 18.4 Hz, 1H, CH2), 3.58 (d, J = 18.0 Hz, 1H, CH2), 1.45 (s, 9H, tbu-h). S18

19 13 C NMR (175 MHz, CDCl3) δ 193.9, 164.7, 149.1, 136.8, 135.3, 134.6, 127.4, 125.4, 109.5(SCN), 86.5, 64.5, 40.0, 27.7 ppm. IR (KBr) 2922, 2156 (SCN), 1716, 1147 cm -1. HRMS (ESI): calc. for C15H18ClN23S [M+NH4] + : found: HPLC: on AS-H column (n-hexane/iso-propanol 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 8.7 min, ts(minor) = 9.7 min. Peak time area area/% total Peak time area area/% total tert-butyl (R)-1-oxo-5-phenyl-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate (4l) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2l (15.4 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (17.3 mg, 95% yield, 74% ee). MP: o C. S19

20 TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.50, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.6 Hz, 1H, Ar-H), (m, 2H, Ar-H), 7.64 (d, J = 7.6 Hz, 1H, Ar-H), (m, 3H, Ar-H), 4.09 (Jab = 18.0 Hz, 1H, CH2), 3.67 (Jab = 18.0 Hz, 1H, CH2), 1.45 (s, 9H, tbu-h). 13 C NMR (100 MHz, CDCl3) δ 194.5, 165.2, 151.7, 149.9, 139.5, 131.9, 129.1, 129.0, 128.2, 127.6, 126.2, 124.5, 109.8(SCN), 86.2, 64.6, 40.5, 27.7 ppm. IR (KBr) 2918, 2850, 2156 (SCN), 1707, 1145 cm -1. HRMS (ESI): calc. for C21H23N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol 90:10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 10.5 min, ts(minor) = 13.6 min. Peak time area area/% total Peak time area area/% total tert-butyl (R)-1-oxo-6-(phenylethynyl)-2-thiocyanato-2,3-dihydro-1H-indene-2- carboxylate (4m) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2m (16.6 mg, 0.05 mmol) in S20

21 dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (19.3 mg, 98% yield, 87% ee). MP: o C. TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.35, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 8.01 (s, 1H, Ar-H), 7.85 (d, J = 8.0 Hz, 1H, Ar- H), (m, 3H, Ar-H), (m, 3H, Ar-H), 4.05 (Jab = 18.4 Hz, 1H, CH2), 3.62 (Jab = 18.4 Hz, 1H, CH2), 1.45 (s, 9H, tbu-h). 13 C NMR (100 MHz, CDCl3) δ 194.3, 164.9, 150.4, 139.5, 133.4, 131.8, 128.9, 128.6, 128.5, 126.2, 124.5, 122.5, 109.6(SCN), 91.4, 87.4, 86.3, 64.4, 40.4, 27.7 ppm. IR (KBr) 2980, 2926, 2156 (SCN), 1718, 1496, 1147 cm -1. HRMS (ESI): calc. for C23H23N23S [M+NH4] + : found: HPLC: on D-H column (n-hexane/iso-propanol 90:10, v/v, 1.0 ml min 1, 254 nm), ts(minor) = 9.1 min, tr(major) = 10.7 min. Peak time area area/% total Peak time area area/% total S21

22 1-Adamantanyl (R)-7-bromo-1-oxo-2-thiocyanato-1,2,3,4-tetrahydronaphthalene -2-carboxylate (4n) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2n (20.1 mg, 0.05 mmol) in 1,1- dichloroethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a white solid (17.8 mg, 78% yield, 65% ee). After recrystallization, 50% yield, 90% ee. MP: o C TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.50, CH2Cl2, 90% ee). 1 H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 2.2 Hz, 1H, Ar-H), 7.66 (dd, J = 8.2, 2.2 Hz, 1H, Ar-H), 7.17 (d, J = 8.2 Hz, 1H, Ar-H), (m, 3H), (m, 1H), 2.16 (s, 3H), 2.06 (s, 6H), 1.62 (s, 6H) ppm. 13 C NMR (100 MHz, CDCl3) δ 188.4, 164.8, 141.3, 137.6, 132.1, 130.8, 130.7, 121.5, (SCN), 85.9, 65.9, 40.9, 35.9, 33.9, 30.9, 26.7 ppm. IR (KBr) 2912, 2852, 2156 (SCN), 1728, 1693, 1589 cm -1. HRMS (ESI): calc. for C22H23BrN3S [M + H] + : ; Found HPLC: on AD-H column (n-hexane/iso-propanol, 98 : 2, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.5 min, ts(minor) = 8.4 min. Peak time area area/% total S22

23 After recrystallization Peak time area area/% total Peak time area area/% total Adamantanyl (R)-5-oxo-6-thiocyanato-6,7,8,9-tetrahydro-5Hbenzo[7]annulene-6-carboxylate (4o) was synthesized following the General procedure, using 3j (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2o (16.9 mg, 0.05 mmol) in 1,1-dichloroethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title compound as a colorless oil (18.5 mg, 94% yield, 36% ee). TLC: eluent PE/EA (10/1, v/v), Rf = [α] 20 D = (c 0.70, CH2Cl2). 1 H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 7.6, 0.8 Hz, 1H, Ar-H), (m, 1H), 7.31 (t, J = 7.6 Hz, 1H, Ar-H), 7.18 (d, J = 7.2 Hz, 1H, Ar-H), (m, 2H), (m, 1H), (m, 1H), (m, 5H), 1.89 (m, 6H), 1.57 (s, 6H). 13 C NMR (100 MHz, CDCl3) δ 197.6, 164.7, 139.7, 136.7, 132.5, 130.7, 129.9, 126.6, (SCN), 84.9, 72.2, 40.6, 35.9, 33.9, 30.8, 26.9, 24.9 ppm. IR (KBr) 2912, 2852, 2154 (SCN), 1737, 1682, 1597 cm -1. HRMS (ESI): calc. for C23H26N3S [M + H] + : found: HPLC: on D-H column (n-hexane/iso-propanol, 90 : 10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.1 min, ts(minor) = 7.6 min. S23

24 Peak time area area/% total Peak time area area/% total Adamantanyl (R)-2-chloro-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (5a) was synthesized following the General procedure, using 3j (3.3 mg, mmol), N- chlorophthalimide (14.5 mg, mmol), and 2a (15.5 mg, 0.05 mmol) in dichloromethane (1.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 15 : 1, v/v) to provide the title compound as a yellow oil (17.4 mg, 99% yield, 86% ee). TLC: eluent PE/EA (15/1, v/v), Rf = S24

25 [α] 20 D = (c 0.85, CH2Cl2). [lit. [5] [α] 20 D = (c 1.01, CHCl3) for 90% ee for R structure]. 1 H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.0 Hz, 1H, Ar-H), 7.68 (t, J = 7.2 Hz, 1H, Ar-H), (m, 1H, Ar-H), 7.18 (d, J = 7.2 Hz, 1H, Ar-H), 4.02 (Jab = 17.6 Hz, 1H), 3.53 (Jab = 18.0 Hz, 1H), 2.14 (s, 3H), 2.05 (s, 6H), 1.62 (s, 6H). The 1 H NMR data was accorded with the literature. 4 HPLC: on D-H column (n-hexane/iso-propanol, 90 : 10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 6.5 min, ts(minor) = 7.8 min. Peak time area area/% total Peak time area area/% total Adamantanyl (S)-1-oxo-2-thiocyanato-2,3-dihydro-1H-indene-2-carboxylate ((S)-4a) was synthesized following General procedure, using QN-1 (2.2 mg, mmol), 1c (15.5 mg, mmol), and 2a (15.5 mg, 0.05 mmol) in CH2Cl2 (1.5 ml), and the reaction mixture was stirred for 1 h at -78 o C. The crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide the title S25

26 compound as a white solid (18.2 mg, 99% yield, 85% ee). TLC: eluent PE/EA (10/1, v/v), Rf = ptical value: [α] 20 D = (c 0.15, CH2Cl2). HPLC: on D-H column (n-hexane/iso-propanol, 90 : 10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 8.9 min, t S(minor) = 10.0 min. Peak time area area/% total Scale-up reaction of 4d Peak time area area/% total The scale-up reaction was carried out on 1.17 mmol scale following the General procedure, using 3j (44.1 mg, 0.1 mmol, 8.5 mol %), 1c (384 mg, 1.17 mmol), and 2d (320 mg, 1.57 mmol, 1.3 equiv) in CH2Cl2 (20.0 ml), and the reaction mixture was stirred for 1 h at -78 o C. After removing solvent under reduced pressure the crude product was purified by flash column chromatography (PE : EtAc = 10 : 1, v/v) to provide 4d as a white solid (446 mg, 99% yield, 88% ee). HPLC: D-H column (n-hexane/iso-propanol, 90 : 10, v/v, 1.0 ml min 1, 254 nm), tr(major) = 7.97 min, ts(minor) = 9.76 min. S26

27 Peak time area area/% total Peak time area area/% total S27

28 5. X-Ray Structure of 4e (CCDC ) Table S1. Crystal data and structure refinement for 4e. Identification code data_1 Empirical formula C21 H20 Cl N 3 S Formula weight Temperature 296(2) K Wavelength Crystal system orthorhombic Space group P and P 2ac 2ab Unit cell dimensions a = 6.313(2) Å α = 90 b = (4) Å β = 90 c = (8) Å γ = 90 Volume (11) Å 3 Z 4 Density (calculated) g/cm 3 Absorption coefficient mm -1 F(000) 840 Crystal size mm 3 Theta range for data collection to Index ranges -9<=h<=9, -19<=k<=18, -34<=l<=34 Reflections collected Independent reflections 6149 [R int = ] Completeness to theta = % Max. and min. transmission and Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 6149 / 0 / 244 Goodness-of-fit on F Final R indices [I>2σ(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = S28

29 Table S2. Atomic coordinates and equivalent isotropic displacement parameters (Å 2 ) for 4e. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x y z U(eq) S1 S (14) (5) (3) (2) Cl1 Cl (2) (10) (4) (4) (3) (14) (7) (4) (4) (17) (8) (7) (4) (18) (12) (7) C12 C (3) (16) (8) (4) C17 C (4) (19) (11) (5) H17A H C3 C (4) (17) (9) (5) C11 C (4) (2) (10) (5) C4 C (4) (17) (10) (5) C18 C (3) (17) (9) (4) H18A H H18B H C9 C (4) (19) (10) (5) H9A H H9B H C8 C (4) (17) (9) (5) C19 C (5) (19) (11) (6) H19A H H19B H C20 C (4) (2) (11) (6) H20A H C21 C (4) (2) (10) (6) H21A H H21B H C7 C (4) (18) (11) (5) C2 C (5) (2) (11) (6) H2A H C13 C (4) (2) (10) (5) H13A H H13B H C14 C (4) (2) (12) (7) H14A H C16 C (5) (2) (14) (7) H16A H H16B H S29

30 C5 C (5) (2) (13) (7) H5A H C15 C (4) (3) (12) (8) H15A H H15B H C6 C (6) (2) (13) (9) H6A H C10 C (7) (2) (12) (9) C1 C (6) (2) (12) (7) N1 N (9) (3) (13) (17) Table S3. Bond lengths [Å] and angles [ o ] for 4e. S1 C (3) S1 C (2) Cl1 C (3) 3 C (3) 3 C (3) 2 C (3) 1 C (3) C12 C (3) C12 C (3) C12 C (3) C17 C (4) C17 C (4) C17 C (3) C17 H17A C3 C (4) C3 C (3) C3 C (3) C11 C (3) C4 C (4) C4 C (4) C18 H18A C18 H18B C9 C (3) C9 H9A C9 H9B C8 C (4) C19 C (4) C19 H19A C19 H19B S30

31 C20 C (4) C20 C (4) C20 H20A C21 H21A C21 H21B C2 C (4) C2 H2A C13 C (4) C13 H13A C13 H13B C14 C (4) C14 C (5) C14 H14A C16 H16A C16 H16B C5 C (5) C5 H5A C15 H15A C15 H15B C6 C (5) C6 H6A C10 N (4) C10 S1 C (12) C11 3 C (17) 3 C12 C (17) 3 C12 C (16) C18 C12 C (18) 3 C12 C (18) C18 C12 C (18) C13 C12 C (2) C21 C17 C (2) C21 C17 C (2) C16 C17 C (2) C21 C17 H17A C16 C17 H17A C18 C17 H17A C4 C3 C (2) C4 C3 C (2) C2 C3 C (2) 2 C (2) 2 C11 C (2) 3 C11 C (19) S31

32 C3 C4 C (2) C3 C4 C (2) C5 C4 C (3) C12 C18 C (17) C12 C18 H18A C17 C18 H18A C12 C18 H18B C17 C18 H18B H18A C18 H18B C3 C9 C (2) C3 C9 H9A C8 C9 H9A C3 C9 H9B C8 C9 H9B H9A C9 H9B C11 C8 C (2) C11 C8 C (2) C9 C8 C (19) C11 C8 S (15) C9 C8 S (16) C7 C8 S (17) C12 C19 C (2) C12 C19 H19A C20 C19 H19A C12 C19 H19B C20 C19 H19B H19A C19 H19B C15 C20 C (2) C15 C20 C (2) C21 C20 C (2) C15 C20 H20A C21 C20 H20A C19 C20 H20A C17 C21 C (2) C17 C21 H21A C20 C21 H21A C17 C21 H21B C20 C21 H21B H21A C21 H21B C7 C (3) 1 C7 C (3) C4 C7 C (2) C1 C2 C (3) C1 C2 H2A S32

33 C3 C2 H2A C12 C13 C (18) C12 C13 H13A C14 C13 H13A C12 C13 H13B C14 C13 H13B H13A C13 H13B C16 C14 C (2) C16 C14 C (2) C15 C14 C (2) C16 C14 H14A C15 C14 H14A C13 C14 H14A C17 C16 C (2) C17 C16 H16A C14 C16 H16A C17 C16 H16B C14 C16 H16B H16A C16 H16B C6 C5 C (3) C6 C5 H5A C4 C5 H5A C20 C15 C (2) C20 C15 H15A C14 C15 H15A C20 C15 H15B C14 C15 H15B H15A C15 H15B C1 C6 C (3) C1 C6 H6A C5 C6 H6A N1 C10 S (3) C6 C1 C (3) C6 C1 Cl (2) C2 C1 Cl (3) S33

34 Table S4. Anisotropic displacement parameters (Å 2 ) for 4e. U11 U22 U33 U23 U13 U12 S (5) (3) (3) (2) (3) (3) Cl (9) (9) (6) (6) (6) (8) (9) (10) (8) (7) (7) (8) (17) (14) (9) (9) (10) (13) (13) (14) (17) (12) (12) (11) C (9) (10) (9) (8) (8) (8) C (10) (12) (13) (10) (9) (9) C (12) (10) (10) (8) (9) (9) C (13) (13) (10) (9) (10) (11) C (13) (10) (11) (9) (10) (10) C (9)0.0427(11) (11) (9) (8) (8) C (13) (12) (10) (9) (10) (10) C (11) (10) (9) (8) (9) (9) C (14) (11) (13) (10) (11) (11) C (13) (16) (12) (11) (10) (12) C (11) (17) (11) (11) (9) (11) C (13) (11) (12) (9) (11) (10) C (15) (14) (12) (10) (12) (13) C (10) (13) (12) (10) (9) (11) C (11) (16) (15) (13) (10) (11) C (15) (14) (19) (13) (14) (12) C (17) (13) (15) (12) (14) (13) C (11) 0.111(3) (14) (15) (11) (14) C (3) (15) (15) (12) (16) (16) C (3) (16) (13) (12) (16) (18) C (19) (15) (13) (11) (13) (15) N (4) 0.119(3) (14) (16) (2) (3) S34

35 6. References [1] Y. Wang, X. F. Liu, and L. Deng, J. Am. Chem. Soc. 2006, 128, [2] T. Sekikawa, H. Kitaura, T. Kitaguchi, T. Minami, Y. Hatanaka, Tetrahedron Lett. 2016, 57, [3] J. S. Qiu, Y. F. Wang, G.R. Qi, P. G. Karmaker, H. Q. Yin, and F. X. Chen, Chem. Eur. J. 2017, 23, [4] X. Gu, Y. Zhang, Z. J. Xu, and C. M. Che. Chem. Commun., 2014, 50, [5] J. Li, W. Pan, Z. Wang, X. M. Zhang and K. L. Ding. Adv. Synth. Catal. 2012, 354, S35

36 7. Copies of 1 H and 13 C NMR spectra a CAd SCN ppm (t1) S36

37 a CAd SCN 200 ppm (t1) S37

38 b CEt SCN ppm (t1) S38

39 b CEt SCN 200 ppm (t1) S

40 CtBu 4c SCN ppm (t1) 5.0 S40 0.0

41 c CtBu SCN 200 ppm (t1) S

42 F 4d CAd SCN ppm (t1) 5.0 S42 0.0

43 F 4d CAd SCN 200 ppm (t1) S

44 Cl 4e CAd SCN ppm (t1) 5.0 S44 0.0

45 Cl CAd SCN 4e 200 ppm (t1) S

46 Br 4f CAd SCN ppm (t1) 5.0 S46 0.0

47 Br 4f CAd SCN 200 ppm (t1) S

48 Br 4g CAd SCN ppm (t1) 5.0 S48 0.0

49 Br 4g CAd SCN 200 ppm (t1) S

50 Br 4h CAd SCN ppm (t1) 5.0 S50 0.0

51 Br 4h CAd SCN 200 ppm (t1) S

52 i CAd SCN ppm (t1) 5.0 S52 0.0

53 Me 4i CAd SCN 200 ppm (t1) S

54 CAd SCN 4j ppm (t1) 5.0 S54 0.0

55 CAd SCN 4j 200 ppm (t1) S

56 Cl C t Bu 4k SCN ppm (t1) 5.0 S56 0.0

57 Cl 4k C t Bu SCN 200 ppm (f1) S

58 Ph 4l C t Bu SCN ppm (t1) 5.0 S58 0.0

59 Ph 4l C t Bu SCN 200 ppm (t1) S

60 Ph 4m C t Bu SCN ppm (t1) 5.0 S60 0.0

61 Ph 4m C t Bu SCN 200 ppm (t1) S

62 Br CAd SCN 4n ppm (t1) 5.0 S62 0.0

63 Br 4n CAd SCN 200 ppm (t1) S

64 S64 ppm (t1) CAd SCN 4o

65 CAd SCN 4o 200 ppm (t1) S

66 S66 ppm (t1) N H N H 9 6 QD-6, 3j

67 H N 9 H N QD-6, 3j 200 ppm (t1) S

68 S68 ppm (t1) N H N H 9 6 i Pr i Pr i Pr QD-7, 3k

69 i Pr i Pr H 6 i Pr N 9 H QD-7, 3k N 200 ppm (t1) S

70 S70 ppm (f1) H N N 6 9 QN-1

71 N 9 QN-1 H N 6 ppm (f1) S

72 1c N SCN ppm (t1) ppm (t1) 5.0 S72 0.0

73 1c N SCN 200 ppm (t1) S

74 5c Cl Ad ppm (t1) 5.0 S74 0.0