Supporting information Diversity Oriented Asymmetric Catalysis (DOAC): Stereochemically Divergent Synthesis of Thiochromanes Using an Imidazoline-aminophenol aminophenol (IAP)-Ni Catalyzed Michael/Henry Reaction Takayoshi Arai, Yushi Yamamoto Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi, Inage, Chiba 263-8522, Japan S1
Contents 1. General S3 2. General procedure for tandem catalytic asymmetric thio Michael/Henry reaction and one pot reduction of nitro group S4 3. Optimization of catalytic Asymmetric thio Michael/Henry reaction S5 4. Reduction of the nitro group of the chiral thiochromanes S7 5. ESI MS analysis of IAP Ni thiolate complex S8 6. Plausible transition state model S9 7. Analytical data of (2S,3R,4R)- 2-aryl-3-nitrothiochroman-4-ols (6) S10 8. Analytical data of (2S,3R,4R)-3-amino-2-arylthiochroman-4-ols (7) S18 9. 1 H NMR and 13 C NMR spectra of (2S,3R,4R)-3-nitro-2-arylthiochroman-4-ols (6) S26 10. 1 H NMR and 13 C NMR spectra of (2S,3R,4R)-3-amino-2-arylthiochroman-4-ols (7) S42 S2
1. General Dry solvents were purchased from commercial suppliers and used without further purification. Analytical thin layer chromatography (TLC) was performed on glass plates coated with 0.25 mm 230 400 mesh silica gel containing a fluorescent indicator (Merck, #1.05715.0009). Silica gel column chromatography was performed on Kanto silica gel 60 (spherical, 100 210 µm). IR spectra were recorded on JASCO FT/IR 4100 using ATR. 1 H NMR spectra were recorded on JEOL ECS 400 (400MHz) or ECA 500 (500MHz) spectrometers. Chemical shifts of 1 H NMR spectra were reported relative to tetramethylsilane (δ 0) or Acetone d 6 (δ 2.05) or DMSO d 6 (δ 2.50). 13 C NMR spectra were recorded on JEOL ECA 400 (100MHz) or ECA 500 (125MHz) spectrometers. Chemical shifts of 13 C NMR spectra were reported relative to CDCl 3 (δ77.0) or Acetone d 6 (δ 29.8) or DMSO d 6 (δ 39.5). Splitting patterns were reported as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. General experimental details for synthesis of imidazoline aminophenol ligand (IAP) have been described. 1, 2 Mercaptobenzaldehydes (2-mercaptobenzaldehyde: ca. 75% purity, 5-(tert-butyl)-2-mercaptobenzaldehyde: ca. 86% purity, and 5-chloro-2-mercaptobenzaldehyde: ca. 93% purity) were synthesized according to known procedure. 3 [1] Arai, T.; Yokoyama, N.; Yanagisawa, A. Chem. Eur. J. 2008, 14, 2052. [2] Yokoyama, N.; Arai, T. Chem. Commun. 2009, 3285. [3] Toste, F. D.; Lough, A. J.; Still, W. J. Tetrahedron Lett. 1995, 36, 6619. S3
2. General procedure for tandem catalytic asymmetric thio Michael/Henry reaction and one pot reduction of nitro group IAP1 (0.0165 mmol) and Ni(OAc) 2 4H 2 O (0.015mmol) were added to a two necked round flask containing a stir bir under argon. Anhydrous MeOH (1 ml) was added to the flask and the mixture was stirred for 2 hours. After removal of the solvent under reduced pressure, anhydrous PhMe (1 ml) was added. To the resulting solution, nitroalkene (0.15 mmol) was added at room temperature and cooled to -40 C. Slow addition of 2-mercaptobenzaldehyde (0.225 mmol, ca. 75% purity) in anhydrous PhMe (5 ml) using syringe pump was conducted for 15 hours. After being stirred for appropriate time, the crude mixture was warmed to room temperature. (Procedure A for nitro compound) 0.6 ml of the crude reaction mixture was transferred into another flask via syringe and removed solvent under reduced pressure. Yield and diastereomeric ratio of the nitrothiochromane were determined by crude 1 H NMR. The crude mixture was purified by flash silica gel column chromatography to afford the 2 aryl 3 nitrothiochroman 4 ols. The enantiomeric excesses of the products were determined by chiral stationary phase HPLC using a Daicel Chiralpak AD H, OD H and IC 3 column. (Procedure B for aminoalcohol) After removal of the solvent of the resulting 5.4 ml of crude reaction mixture, dry MeOH (1.2 ml) was added at room temperature under argon. 2.7 mmol of Zn (nanopowder, purchased from Sigma Aldrich) was added. A mixture of 1N aq. HCl (810 µl) and AcOH (405 µl) was added to the heterogeneous solution and stirred for 30 minutes. Zn was filtered out and the filtrate was concentrated by rotary evaporator. CHCl 3 was added to the flask and neutralized by aq. NaHCO 3. The resulting mixture was extracted with CHCl 3 (10 ml x 3) and combined organic layer was dried over Na 2 SO 4. After removal of solvent under reduced pressure, diastereomeric ratio was determined by crude 1 H NMR. The crude mixture was purified by flash silica gel column chromatography to afford the 3 amino 2 arylthiochroman 4 ols. The enantiomeric excesses of the products were determined by chiral stationary phase HPLC using a Daicel Chiralpak AD H, AS H, IA, IC 3, Chiralcel OD H and OJ H column. S4
3. Optimization of reaction condition Table S1. Catalyst screening for thio Michael/Henry reaction. S5
Table S2. Solvent effect for thio Michael/Henry reaction. S6
4. Reduction of the nitro group of the chiral thiochromanes Table S3. Optimization of reduction of the nitro group S7
5. ESI MS analysis of IAP Ni thiolate complex H Ph Ph O Ni-IAP S Ts N N N Ni O S Br + H OHC IAP-Ni-thiolate Ph Br HRMScalcd.forC 45 H 40 Br 2 N 3 NiO 4 S 2 [M+H] + :966.0175 found: m/z = 966.0162 Figure S1. ESI MS analysis of IAP Ni thiolate complex [IAP1 Ni thiolate + H] + species was observed in ESI MS. An ion peak at m/z = 966.0162 corresponds to the [IAP1 (phenoxide) Ni thiolate + H] +. S8
6. Plausible transition state model The formyl group of thiosalicylaldehyde would coordinate to the nickel center because Michael reaction of benzenethiol having no formyl group gave racemic product as shown in Scheme S1. (1.5 eq) SH IAP1(11mol%) Ni(OAc) 2 4H 2 O(10mol%) PhMe(0.025 M) -40 C,20h S Ph 8 86% yield <5%ee NO 2 Ph 5a NO 2 CHO 4a(1.5eq) SH IAP1(11mol%) Ni(OAc) 2 4H 2 O(10mol%) OH NO 2 PhMe(0.025 M) -40 C,16h Scheme S1. Effect of formyl group S Ph 6a >99% yield >99/1 dr 95%ee Figure S2. Plausible transition state model In TS2 (for all trans product), the diheadral angle between C=N and carbonyl C=O is narrow due to a strained thiochromane ring. TS1 having Ni containing chair like six-membered ring is favorable. S9
7. Analytical data of (2S,3R,4R)-2-aryl-3-nitro-thiochroman-4-ols (6) (2S,3R,4R) 3 nitro 2 phenylthiochroman 4 ol (6a) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to 0:1) as a yellow solid. 1 H NMR (500 MHz, Acetone d 6 ) δ 7.61 7.59 (m, 2H), 7.50 7.48 (m, 1H), 7.42 7.39 (m, 2H), 7.37 7.33 (m, 1H), 7.30 (dt, 1H, J = 7.8, 1.5 Hz), 7.20 (dt, 1H, J = 7.5, 1.2 Hz), 7.15 (dd, 1H, J = 8.1, 0.9 Hz), 5.70 (dd, 1H, J = 11.5, 2.9 Hz), 5.46 5.40 (m, 2H), 5.31 (d, 1H, J = 11.8 Hz) ; 13 C NMR (100 MHz, Acetone d 6 ) δ 137.7, 134.6, 133.5, 132.0,129.9, 129.7, 129.3, 129.2, 125.7, 125.4, 90.2, 70.6, 41.4; HRMS calcd for C 15 H 13 NO 3 SNa [M+Na] + : 310.0508, found: m/z 310.0504; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor 19.2 enantiomer t r = 15.1 min, major enantiomer t r = 22.6 min; 95% ee; [α] D = -231.3 (c = 1.0, MeOH, 98/2 diastereomixture, 95% ee); IR (neat) 3417, 2957, 2925, 2854, 1550, 1315, 1034, 763, 698 cm -1. (2S,3R,4R) 2 (4 chlorophenyl) 3 nitrothiochroman 4 ol (6b) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow solid. 1 H NMR (500 MHz, Acetone d 6 ) δ 7.67 7.64 (m, 2H), 7.49 (dd, 1H, J = 7.7, 1.6 Hz), 7.47 7.43 (m, 2H), 7.31 (dt, 1H, J = 7.7, 1.6 Hz), 7.22 7.18 (m, 1H), 7.17 7.15 (m, 1H), 5.70 (dd, 1H, J = 11.6, 2.9 Hz), 5.50 (br, 1H), 5.42 (br, 1H), 5.31 (d, 1H, J = 11.6 Hz); 13 C NMR (125 MHz, Acetone d 6 ) δ 136.8, 134.6, 134.4, 133.3, 132.2, 131.1, 130.1, 139.8, 125.8, 125.4, 89.9, 70.7, 40.6; HRMS calcd for C 15 H 11 NO 3 SCl [M H] : 320.0154, found: m/z 320.0164; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 16.4 min, major enantiomer t r = 22.6 min; 25.8 94% ee; [α] D = -204.2 (c = 0.1, MeOH, 96/4 diastereomixture, 94% ee); IR (neat) 3190, 2920, 1550, 1491, 1369, 1348, 1090, 1034, 1014, 768 cm -1. S10
(2S,3R,4R) 2 (3 chlorophenyl) 3 nitrothiochroman 4 ol (6c) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow amorphous. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.71 (s, 1H), 7.59 (dd, 1H, J = 7.5, 1.1 Hz), 7.50 (d, 1H, J = 7.7 Hz), 7.47 7.43 (m, 1H), 7.41 7.39 (m, 1H), 7.21 (t, 1H, J = 7.5 Hz), 7.16 (d, 1H, J = 7.7 Hz), 5.78 5.74 (m, 1H), 5.51 (br, 1H), 5.43 (br, 1H), 5.32 (d, 1H, J = 11.3 Hz); 13 C NMR (125 MHz, Acetone d 6 ) δ 140.4, 134.9, 134.4, 133.2, 132.2, 131.4, 130.1, 129.4, 129.3, 128.0, 125.8, 125.4, 89.7, 70.7, 40.8; HRMS calcd for C 15 H 11 NO 3 SCl [M H] : 320.0154, found: m/z 320.0166; Enantiomeric excess was determined by HPLC with a Chiralpak OD H column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 19.0 min, major enantiomer t r = 25.8 15.8 min; 95% ee; [α] D = -222.4 (c = 0.1, MeOH, 95/5 diastereomixture, 95% ee); IR (neat) 3420, 2921, 1550, 1476, 1366, 1090, 1036, 760, 733 cm -1. (2S,3R,4R) 2 (4 bromophenyl) 3 nitrothiochroman 4 ol (6d) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow solid. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.59 (s, 4H), 7.49 (dd, 1H, J = 7.8, 1.4 Hz), 7.31 (dt, 1H, J = 7.8, 1.4 Hz), 7.20 (dt, 1H, J = 7.6, 1.2 Hz), 7.17 7.14 (m, 1H), 5.70 (dd, 1H, J = 11.7, 3.0 Hz), 5.50 (br, 1H), 5.42 (d, 1H, J = 2.5 Hz), 5.29 (d, 1H, J = 11.7 Hz); 13 C NMR (125 MHz, Acetone d 6 ) δ 137.3, 134.4, 133.2, 132.7, 132.2, 131.4, 130.0, 125.8, 125.3, 122.7, 89.8, 70.6, 40.6; HRMS calcd for C 15 H 11 NO 3 SBr [M H] : 363.9648, found: m/z 363.9662; Enantiomeric excess was determined by HPLC with a Chiralpak IC 3 column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor 24.4 enantiomer t r = 30.6 min, major enantiomer t r = 11.7 min; 93% ee; [α] D = -200.5 (c = 0.1, MeOH, 97/3 diastereomixture, 93% ee); IR (neat) 3734, 1547, 1475, 1072, 1034, 1011, 765 cm -1. S11
(2S,3R,4R) 2 (3 bromophenyl) 3 nitrothiochroman 4 ol (6e) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a brown solid. 1 H NMR (500 MHz, Acetone d 6 ) δ 7.86 7.85 (m, 1H), 7.64 (dt, 1H, J = 7.7, 1.2 Hz), 7.56 7.54 (m, 1H), 7.50 (dd, 1H, J = 7.5, 1.4 Hz), 7.38 (t, 1H, J = 7.9 Hz), 7.31 (dt, 1H, J = 7.7, 1.4 Hz), 7.21 (dt, 1H, J = 7.5, 1.4 Hz), 7.16 (dd, 1H, J = 7.7, 1.2 Hz), 5.77 5.74 (m, 1H), 5.49 (br, 1H), 5.43 (br, 1H), 5.30 (d, 1H, J = 11.5 Hz); 13 C NMR (125 MHz, CDCl 3 ) δ 137.7, 123.3, 132.1, 131.6, 131.4, 130.9 130.5 130.0 127.2 125.4 125.2 122.9, 89.6, 70.0, 40.4; HRMS calcd for C 15 H 11 NO 3 SBr [M H] :363.9648, found: m/z 363.9659; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 24.7 15.2 min, major enantiomer t r = 21.2 min; 94% ee; [α] D = -168.4 (c = 0.1, MeOH, 97/3 diastreomixture, 94% ee); IR (neat) 3335, 2958, 1555, 1523, 1474, 1331, 1075, 1037, 768 cm -1. (2S,3R,4R) 2 (4 fluorophenyl) 3 nitrothiochroman 4 ol (6f) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a pale yellow amorphous. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.70 7.65 (m, 2H), 7.49 (dd, 1H, J = 7.7, 1.4 Hz), 7.33 7.28 (m, 1H), 7.22 7.14 (m, 4H), 5.68 (dd, 1H, J = 11.6, 2.9 Hz), 5.48 (br, 1H), 5.41 (d, 1H, J = 2.5 Hz), 5.31 (d, 1H, J = 11.6 Hz); 13 C NMR (100 MHz, Acetone d 6 ) δ 163.4 (d, J = 246.1 Hz), 134.4, 133.9 (d, J = 2.9 Hz), 133.4, 132.1, 131.4 (d, J = 8.6 Hz), 130.0, 125.7, 125.4, 116.5 (d, J = 21.0 Hz), 90.1, 70.7, 40.5; HRMS calcd for C 15 H 11 NO 3 SF [M H] : 304.0449, found: m/z 304.0461; Enantiomeric excess was determined by HPLC with a Chiralpak IA column (95:5 hexane : 2 propanol, 1.0 ml/min, 254 nm); minor enantiomer t r = 31.0 min, major enantiomer 25.8 t r = 37.6 min; 90% ee; [α] D = -174.6 (c = 0.1, MeOH, 95/5 diastereomixture, 90% ee); IR (neat) 3734, 3419, 2924, 1552, 1508, 1315, 1227, 1035, 760 cm -1. S12
(2S,3R,4R) 3 nitro 2 (4 nitrophenyl)thiochroman 4 ol (6g) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to 0:1) as a yellow solid. 1 H NMR (500 MHz, Acetone d 6 ) δ 8.30 8.27 (m, 2H), 7.95 7.93 (m, 2H), 7.52 7.50 (m, 1H), 7.32 (dt, 1H, J = 7.5, 1.4 Hz), 7.23 (dt, 1H, J = 7.5, 1.2 Hz), 7.18 7.17 (m, 1H), 5.83 5.50 (m, 1H), 5.60 (d, 1H, J = 5.2 Hz), 5.49 5.45 (m, 2H); 13 C NMR (125 MHz, Acetone d 6 ) δ 148.8, 145.5, 134.4, 132.7, 132.3, 130.7, 130.2, 126.0, 125.3, 124.8, 89.5, 70.6, 40.6; HRMS calcd for C 15 H 11 NO 3 SCl [M+Cl] : 367.0161, found: m/z 367.0173; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (80:20 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 49.3 min, major enantiomer t r = 37.3 min; 26.9 91% ee; [α] D = -224.3 (c = 0.2, MeOH, 91% ee); IR (neat) 3149, 3029, 2811, 1556, 1524, 1349, 1046, 764 cm -1. (2S,3R,4R) 3 nitro 2 (3 nitrophenyl)thiochroman 4 ol (6h) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow solid. 1 H NMR (400 MHz, Acetone d 6 ) δ 8.55 (t, 1H, J = 2.0 Hz), 8.26 8.24 (m, 1H), 8.12 (d, 1H, J = 7.7 Hz), 7.77 7.73 (m, 1H), 7.53 7.50 (m, 1H), 7.33 (dt, 1H, J = 7.7, 1.4 Hz), 7.23 (dt, 1H, J = 7.5, 1.1 Hz), 7.19 (d, 1H, J = 7.7 Hz), 5.90 (dd, 1H, J = 11.6, 2.9 Hz), 5.59 (d, 1H, J = 5.0 Hz), 5.52 5.48 (m, 2H); 13 C NMR (100 MHz, Acetone d 6 ) δ149.4, 140.4, 135.9, 134.4, 133.7, 132.8, 132.3, 131.1, 130.2, 125.9, 125.3, 124.2, 89.5, 70.7, 40.6; HRMS calcd for C 15 H 12 N 2 O 5 SCl [M+Cl] :367.0161, found: m/z367.0171; Enantiomeric excess was determined by HPLC with a Chiralpak IA column (90:10 hexane : 2 propanol, 1.0 ml/min, 254 nm); minor enantiomer t r = 36.1 20.4 min, major enantiomer t r = 44.1 min; 92% ee; [α] D = -94.6 (c = 0.1, MeOH, 97/3 diastereomixture, 93% ee); IR (neat) 3734, 3649, 3361, 3195, 2921, 2851, 1554, 1527, 1350, 1037, 758, 686 cm -1. S13
(2S,3R,4R) 2 (4 methoxyphenyl) 3 nitrothiochroman 4 ol (6i) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to 0:1) as a yellow solid. 1 H NMR (500 MHz, Acetone d 6 ) δ 7.53 7.50 (m, 2H), 7.47 (dd, 1H, J = 7.8, 1.5 Hz), 7.29 (dt, 1H, J = 7.5, 1.4 Hz), 7.19 (dt, 1H, J = 7.5, 1.2 Hz), 7.14 (dd, 1H, J = 8.0, 1.2 Hz), 6.96 6.93 (m, 2H), 5.62 (dd, 1H, J = 11.5, 2.9 Hz), 5.44 5.37 (m, 2H), 5.25 (d, 1H J = 11.8 Hz), 3.79 (s, 3H); 13 C NMR (125 MHz, Acetone d 6 ) δ 160.7, 134.5, 133.9, 132.1, 130.5, 129.9, 129.2, 125.6, 125.4, 115.0, 90.4, 70.8, 55.5, 40.9; HRMS calcd for C 16 H 14 NO 4 S [M H] :316.0649, found: m/z 316.0659; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor 26.6 enantiomer t r = 22.5 min, major enantiomer t r = 35.4 min; 84% ee; [α] D = -223.5 (c = 0.2, MeOH, 95/5 diastereomixture, 84% ee); IR (neat) 2927, 1558, 1513, 1308, 1255, 1176, 1033, 757 cm -1. (2S,3R,4R) 2 (3 methoxyphenyl) 3 nitrothiochroman 4 ol (6j) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow solid. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.48 (dd, 1H, J = 7.7, 1.4 Hz), 7.33 7.28 (m, 2H), 7.20 (dd, 1H, J = 7.5, 1.4 Hz), 7.18 7.14 (m, 3H), 6.93 6.90 (m, 1H), 5.73 5.69 (m, 1H), 5.48 (br, 1H), 5.40 (br, d, 1H, J = 2.7 Hz), 5.25 (d, 1H, J = 11.6 Hz), 3.82 (s, 3H); 13 C NMR (100 MHz, Acetone d 6 ) δ 160.9, 139.3, 134.5, 133.7, 132.1, 130.7, 130.0, 125.7, 125.4, 121.4, 114.9, 114.7, 90.0, 70.7, 55.6, 41.4; HRMS calcd for C 16 H 14 NO 4 S [M H] :316.0649, found: m/z 316.0660; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (85:15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 22.0 19.6 min, major enantiomer t r = 39.3 min; 92% ee; [α] D = -149.3 (c = 1.0, MeOH, 98/2 diastereomixture, 94% ee); IR (neat) 2926, 1551, 1317, 1261, 1035, 756 cm -1. S14
(2S,3R,4R) 3 nitro 2 (p tolyl)thiochroman 4 ol (6k) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to 0:1) as a yellow solid. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.49 7.46 (m, 3H), 7.29 (dt, 1H, J = 7.5, 1.4 Hz), 7.22 7.17 (m, 3H), 7.14 (dd, 1H, J = 7.9, 1.1 Hz), 5.66 (dd, 1H, J = 11.6, 2.9 Hz), 5.44 5.39 (br, 2H), 5.24 (d, 1H, J = 11.6 Hz), 2.32 (s, 3H); 13 C NMR (100 MHz, Acetone d 6 ) δ139.1, 134.6, 134.5, 133.8, 132.1, 130.3, 130.0, 129.2, 125.6, 125.4, 90.3, 70.7, 41.1, 21.1; HRMS calcd for C 16 H 14 NO 3 S [M H] : 300.0700, found: m/z 300.0710; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (80:20 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r =11.3 min, 20.3 major enantiomer t r = 19.0 min; 84% ee; [α] D = -123.7 (c = 0.1, MeOH, 91/9 diastereomixture, 84% ee); IR (neat) 2919, 1552, 1474, 1369, 1035, 760 cm -1. (2S,3R,4R) 3 nitro 2 (m tolyl)thiochroman 4 ol (6l) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as an orange amorphous. 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 7.38 (m, 1H), 7.32 7.23 (m, 4H), 7.20 7.13 (m, 3H), 5.35 5.25 (m, 3H), 2.88 (br, 1H), 2.35 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.7, 135.2, 132.9, 131.7, 130.8, 129.7 (2C), 129.1, 128.8, 125.4, 125.5, 125.4, 89.9, 70.0, 41.0, 21.3; HRMS calcd for C 16 H 14 NO 3 S [M H] : 300.0700, found: m/z 300.0713; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (90:10 hexane : 2 propanol, 0.7 ml/min, 254 23.7 nm); minor enantiomer t r = 19.1 min, major enantiomer t r = 29.1 min; 94% ee; [α] D = -139.8 (c = 0.1, MeOH, 96/4 diastereomixture, 94% ee); IR (neat) 3158, 1557, 1520, 1317, 1038, 760 cm -1. S15
(2R,3R,4R) 3 nitro 2 (thiophen 2 yl)thiochroman 4 ol (6m) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow solid. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.50 7.48 (m, 2H), 7.34 7.32 (m, 1H), 7.32 7.29 (m, 1H), 7.21 (dt, 1H, J = 7.5, 1.4 Hz), 7.18 7.16 (m, 1H), 7.04 (dd, 1H, J = 5.2, 1.6 Hz), 5.61 (d, 1H, J = 11.4 Hz), 5.54 (dd, 1H, J = 11.2, 2.8 Hz), 5.48 (br, 1H), 5.38 (d, 1H, J = 2.8 Hz); 13 C NMR (100 MHz, Acetone d 6 ) δ 140.3, 134.4, 133.3, 131.8, 130.0, 128.6, 128.0, 127.2, 125.9, 125.4, 91.8, 70.8, 37.3; HRMS calcd for C 13 H 10 NO 3 S 2 [M H] : 292.0108, found: m/z 292.0121; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (85:15 hexane : 2 propanol, 1.0 ml/min, 254 nm); minor enantiomer t r = 12.1 min, major enantiomer t r = 15.4 min; 24.1 94% ee; [α] D = -171.9 (c = 0.1, MeOH, 91/9 diastereomixture, 94% ee); IR (neat) 2922, 1552, 1518, 1315, 1077, 1032, 757, 733 cm -1. (2S,3R,4R) 6 chloro 3 nitro 2 phenylthiochroman 4 ol (6n) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow solid. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.62 7.59 (m, 2H), 7.56 (d, 1H, J = 2.2 Hz), 7.44 7.33 (m, 4H), 7.21 (d, 1H, J = 8.7 Hz), 5.75 (dd, 1H, J = 11.2, 3.1 Hz), 5.65 (br, 1H), 5.43 (d, 1H, J = 2.5 Hz), 5.26 (d, 1H, J = 11.4 Hz); 13 C NMR (100 MHz, Acetone d 6 ) δ 137.5, 136.7, 132.7, 131.4, 130.7, 129.9, 129.8, 129.5, 129.3, 127.3, 90.1, 70.2, 42.0; HRMS calcd for C 15 H 11 NO 3 SCl [M H] : 320.0154, found: m/z 320.0166; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (85:15 hexane : 2 propanol, 0.5 ml/min, 254 nm); minor 25.0 enantiomer t r = 25.2 min, major enantiomer t r = 27.4 min; 80% ee; [α] D = -131.0 (c = 0.1, MeOH, 84/16 diastereomixture, 80% ee); IR (neat) 3734, 3649, 2923, 2852, 1556, 1456, 1362, 1102, 696 cm -1. S16
(2S,3R,4R) 6 (tert butyl) 3 nitro 2 phenylthiochroman 4 ol (6o) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to AcOEt) as a yellow amorphous. 1 H NMR (400 MHz, Acetone d 6 ) δ 7.61 7.59 (m, 2H), 7.55 (d, 1H, J = 2.0 Hz), 7.43 7.34 (m, 4H), 7.09 7.06 (m, 1H), 5.70 5.66 (m, 1H), 5.41 (br, 2H), 5.28 (d, 1H, J = 11.7 Hz), 1.32 (s, 9H); 13 C NMR (100 MHz, CDCl 3 ) δ 148.6, 135.4, 131.0, 129.4, 129.1, 129.0, 128.9, 128.5, 128.1, 127.7, 127.4, 125.0, 90.2, 70.5, 40.9, 34.4, 31.2; HRMS calcd for C 19 H 20 NO 3 S [M H] :342.1169, found: m/z 342.1179; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (90:10 hexane : 2 propanol, 0.7 ml/min, 254 25.8 nm); minor enantiomer t r = 18.4 min, major enantiomer t r = 14.2 min; 87% ee; [α] D = -150.5 (c = 0.1, MeOH, 91/9 diastereomixture, 87% ee); IR (neat) 3735, 3649, 2962, 2904, 1556, 1485, 1457, 1361, 697 cm -1. (2S,3R,4R) 3 nitro 2 pentylthiochroman 4 ol (6p) According to the general procedure A, the title compound was obtained by silica gel column chromatography (Hexane : CHCl 3 = 1:1 to 0:1) as a yellow oil. 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 7.36 (m, 1H), 7.27 7.14 (m, 3H), 5.14 (s, 1H), 4.86 (dd, 1H, J = 9.5, 2.6 Hz), 4.13 (dt, 1H, J = 9.5, 4.0 Hz), 2.98 (d, 1H, J = 4.9 Hz), 1.79 1.25 (m, 8H), 0.92 0.87 (m, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 129.6, 129.5, 128.5, 126.6, 125.3, 90.2, 69.7, 38.0, 32.6, 31.2, 25.7, 22.3, 13.9; HRMS calcd for C 14 H 18 NO 3 S [M H] : 280.1013, found: m/z 280.1025; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (95:5 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 20.0 min, major enantiomer t r = 32.9 min; 4% ee; IR (neat) 3734, 3649, 3393, 2955, 2927, 2857, 1556, 1456, 1375, 1079, 1038, 750, 696 cm -1. S17
8. Analytical data of (2S,3R,4R)-3-amino-2-arylthiochroman-4-ols (7) (2S,3R,4R) 3 amino 2 phenylthiochroman 4 ol (7a) According to the general procedure B, the title compound was obtained by silica gel column chromatography (AcOEt to CHCl 3 : MeOH = 10:1) as a white solid. 1 H NMR (500 MHz, DMSO d 6 ) δ 7.46 7.44 (m, 2H), 7.39 (t, 2H, J = 7.5 Hz), 7.34 7.31 (m, 2H), 7.18 (dt, 1H, J = 7.5, 1.4 Hz), 7.10 7.07 (m, 2H), 4.55 (d, 1H, J = 2.6 Hz), 4.43 (d, 1H, J = 10.0 Hz), 3.31 (dd, 1H, J = 10.0, 2.6 Hz); 13 C NMR (125 MHz, DMSO d 6 ) δ 139.0, 136.2, 133.1, 131.2, 129.2, 128.7, 128.1, 127.8, 124.4, 123.9, 69.7, 54.8, 46.0; HRMS calcd for C 15 H 16 NOS [M+H] + :258.0947, found: m/z 258.0945; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column and Chiralcel OD H column (90:10 hexane : 2 propanol, 0.7 ml/min, 254 29.2 nm); minor enantiomer t r = 50.9 min, major enantiomer t r = 43.9 min; 96% ee; [α] D = -178.9 (c = 1.0, MeOH, 96% ee); IR (neat) 3734, 3649, 3134, 2878, 1560, 1472, 1104, 1078, 872, 698 cm -1. (2S,3R,4R) 3 amino 2 (4 chlorophenyl)thiochroman 4 ol (7b) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a white solid. 1 H NMR (500 MHz, CDCl 3 ) δ 7.40 7.35 (m, 5H), 7.23 7.20(m, 1H), 7.15 7.11 (m, 2H), 4.69 (d, 1H, J = 2.6 Hz), 4.44 (d, 1H, J = 9.7 Hz), 3.50 (d, 1H, J = 8.6 Hz), 2.04 (br, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 136.6, 134.1, 134.0, 133.3, 131.2, 130.3, 129.2, 128.8, 125.2, 124.7, 70.0, 55.3, 46.1; HRMS calcd for C 15 H 15 NOSCl [M+H] + :292.0557, found: m/z 292.0553; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (97.5 : 2.5 hexane : 2 propanol, 1.0 ml/min, 254 nm); minor enantiomer t r = 62.4 min, major enantiomer t r = 38.8 min; 25.8 95% ee; [α] D = -166.9 (c = 0.5, MeOH, 95% ee); IR (neat) 3734, 3649, 3375, 3066, 2875, 1490, 1088, 1012, 849, 752 cm -1. S18
(2S,3R,4R) 3 amino 2 (3 chlorophenyl)thiochroman 4 ol (7c) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a pale yellow solid. 1 H NMR (400 MHz, DMSO d 6 ) δ 7.51 (s, 1H), 7.43 7.36 (m, 3H), 7.32 (d, 1H, J = 7.5 Hz), 7.19 (dt, 1H, J = 7.7, 1.4 Hz), 7.10 7.07 (m, 2H), 4.53 (d, 1H, J = 2.5 Hz), 4.45 (d, 1H, J = 10.2 Hz), 3.32 (dd, 1H, J = 10.2 H; 13 C NMR (100 MHz, DMSO d 6 ) δ 141.9, 136.2, 133.1, 132.7, 131.1, 130.4, 129.0, 128.2, 128.0, 127.7, 124.3, 124.0, 69.9, 54.6, 45.6; HRMS calcd for C 15 H 15 NOSCl [M+H] + :292.0557, found: m/z 292.0556; Enantiomeric excess was determined by HPLC with a Chiralpak AD H and AS H column (93 : 7 hexane : 2 propanol, 0.7 25.8 ml/min, 254 nm); minor enantiomer t r = 63.6 min, major enantiomer t r = 43.3 min; 98% ee; [α] D = -151.6 (c = 0.25, MeOH, 98% ee); IR (neat) 3734, 3649, 3374, 3055, 2920, 2850, 1568, 1106, 1076, 780, 754 cm -1. (2S,3R,4R) 3 amino 2 (4 bromophenyl)thiochroman 4 ol (7d) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a white crystalline solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.53 7.50 (m, 2H), 7.39 (d, 1H, J = 7.6 Hz), 7.35 7.32 (m, 2H), 7.24 7.20 (m, 1H), 7.15 7.10 (m, 2H), 4.69 (d, 1H, J = 2.9 Hz), 4.43 (d, 1H, J = 9.7 Hz), 3.50 (dd, 1H, J = 9.7, 2.7 Hz), 1.95 (br, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 137.2, 134.0, 133.3, 132.2, 131.1, 130.7, 128.8, 125.2, 124.7, 122.3, 70.0, 55.3, 46.2; HRMS calcd for C 15 H 15 NOSBr [M+H] + :336.0052, found: m/z 336.0050; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (90 : 10 hexane : 2 propanol, 0.7 ml/min, 25.5 254 nm); minor enantiomer t r = 19.5 min, major enantiomer t r = 14.8 min; 93% ee; [α] D = -136.9 (c = 0.25, MeOH, 93% ee); IR (neat) 3734, 3649, 3375, 3065, 2875, 1569, 1486, 1472, 1071, 1009, 793, 752, 728 cm -1. S19
(2S,3R,4R) 3 amino 2 (3 bromophenyl)thiochroman 4 ol (7e) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a white solid. 1 H NMR (500 MHz, DMSO d 6 ) δ 7.65 (t, 1H, J = 1.7 Hz), 7.53 7.50 (m, 1H), 7.47 (d, 1H, J = 8.0 Hz), 7.36 7.31 (m, 2H), 7.19 (dt, 1H, J = 7.7, 1.4 Hz), 7.11 7.07 (m, 2H), 5.56 (br, 1H), 4.53 (br, 1H), 4.44 (d, 1H, J = 10.0 Hz), 3.32 3.30 (m, 1H), 1.48 (br, 2H); 13 C NMR (125 MHz, DMSO d 6 ) δ 142.2, 136.2, 132.7, 131.8, 131.1, 130.7, 130.6, 128.3, 128.1, 124.3, 124.0, 121.7, 69.9, 54.6, 45.5; HRMS calcd for C 15 H 15 NOSBr [M+H] + :336.0052, found: m/z 336.0050; Enantiomeric excess was determined by HPLC with a Chiralpak AD H column (95 : 5 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 25.2 39.2 min, major enantiomer t r = 30.8 min; 98% ee; [α] D = -130.9 (c = 0.1, MeOH, 98% ee); IR (neat) 3734, 3649, 3369, 3053, 2894, 2841, 1566, 1471, 1324, 1073, 1011, 919, 779, 756, 687 cm -1 (2S,3R,4R) 3 amino 2 (4 fluorophenyl)thiochroman 4 ol (7f) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a yellow solid. 1 H NMR (500 MHz, CDCl 3 ) δ 7.45 7.42 (m, 2H), 7.40 (d, 1H, J = 7.7 Hz), 7.23 7.20 (m, 1H), 7.15 7.06 (m, 4H), 4.71 (d, 1H, J = 2.9 Hz), 4.46 (d, 1H, J = 9.7 H), 3.53 3.50 (m, 1H), 2.02 (br, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 134.0, 133.5, 131.2, 130.7, 130.6, 128.8, 125.3, 124.7, 116.1, 115.9, 70.1, 55.5, 46.0; HRMS calcd for C 15 H 15 N 2 OSF [M+H] + :276.0853, found: m/z 276.0848; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (97.5 : 2.5 hexane : 2 propanol, 1.0 ml/min, 254 nm); minor 25.8 enantiomer t r = 55.4 min, major enantiomer t r = 35.6 min; 92% ee; [α] D = -140.3 (c = 0. 5, MeOH, 92% ee); IR (neat) 3734, 3649, 3384, 2924, 2880, 2852, 1599, 1507, 1473, 1212, 1159, 1108, 856, 789, 757 cm -1 S20
(2S,3R,4R) 3 amino 2 (4 methoxyphenyl)thiochroman 4 ol (7g) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as pale a yellow solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.37 7.35 (m, 3H), 7.21 7.18 (m, 1H), 7.14 7.08 (m, 2H), 6.91 (d, 2H, J = 8.6 Hz), 4.72 (d, 1H, J = 2.0 Hz), 4.42 (d, 1H, J = 10.0 Hz), 3.82 (s, 3H), 3.49 (dd, 1H, J = 10.0, 2.5 Hz), 2.37 (br, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 159.5, 134.2, 133.9, 131.3, 130.1, 129.5, 128.6, 125.2, 124.4, 70.1, 55.3, 45.6, 29.7; HRMS calcd for C 16 H 18 NO 2 S [M+H] + : 288.1053, found: m/z 288.1039; Enantiomeric excess was determined by HPLC with a Chiralcel OJ H column (90 : 10 hexane : 2 propanol, 1.0 ml/min, 254 nm); minor enantiomer t r = 31.7 min, major enantiomer t r = 22.9 min; 25.8 83% ee; [α] D = -148.9 (c = 0.25, MeOH, 83% ee); IR (neat) 3734, 3649, 2901, 2834, 1608, 1509, 1249, 1175, 1028, 754, 731 cm -1 (2S,3R,4R) 3 amino 2 (3 methoxyphenyl)thiochroman 4 ol (7h) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a slightly yellow solid. 1 H NMR (500 MHz, DMSO d 6 ) δ 7.32 7.28 (m, 2H), 7.18 (dt, 1H, J = 7.5, 1.4 Hz), 7.10 7.06 (m, 2H), 6.90 6.88 (m, 2H), 4.54 (d, 1H, J = 2.3 Hz), 4.40 (d, 1H, J = 10.0 Hz), 3.76 (s, 3H), 3.32 (br, 3H), 3.31 3.28 (m, 1H); 13 C NMR (125 MHz, DMSO d 6 ) δ 159.4, 140.6, 136.1, 133.1, 131.2, 129.8, 128.1, 124.4, 123.9, 121.3, 114.7, 113.3, 69.7, 55.1, 54.8, 46.1; HRMS calcd for C 16 H 18 NO 2 S [M+H] + : 288.1053, found: m/z 288.1049; Enantiomeric excess was determined by HPLC with a Chiralcel AS H column (95 : 5 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 78.0 min, major enantiomer t r = 29.8 58.5 min; 99% ee; [α] D = -136.5 (c = 0.25, MeOH, 99% ee); IR (neat) 3739, 3649, 3370, 2955, 2917, 2851, 1596, 1490, 1469, 1265, 1161, 775, 755 cm -1 S21
(2S,3R,4R) 3 amino 2 (p tolyl)thiochroman 4 ol (7i) According to the general procedure B, the title compound was obtained by silica gel column chromatography (AcOEt to CHCl 3 : MeOH = 5:1) as a slightly yellow solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 (d, 1H, J = 7.4 Hz), 7.33 (d, 2H, J = 8.1 Hz), 7.19 (d, 3H, J = 7.4 Hz), 7.15 7.09 (m, 2H), 4.72 (d, 1H, J = 2.5 Hz), 4.43 (d, 1H, J = 10.1 Hz), 3.55 3.52 (m, 1H), 2.48 (br, 3H), 2.36 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.2, 134.8, 134.1, 133.9, 131.2, 129.7, 128.9, 128.7, 125.2, 124.5, 70.1, 55.4, 46.2, 21.1; HRMS calcd for C 16 H 18 NOS [M+H] + :272.1104, found: m/z 272.1097; Enantiomeric excess was determined by HPLC with a Chiralcel OJ H column (90 : 10 hexane : 2 propanol, 0.7 ml/min, 20.6 254 nm); minor enantiomer t r = 32.7 min, major enantiomer t r = 20.2 min; 91% ee; [α] D = -130.2 (c = 0.25, MeOH, 91% ee); IR (neat) 3734, 3649, 3377, 2918, 1510, 775, 754 cm -1 (2S,3R,4R) 3 amino 2 (m tolyl)thiochroman 4 ol (7j) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane : AcOEt = 2:1 to CHCl 3 : MeOH = 5:1) as a white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 38 (d, 1H, J = 7.5 Hz), 7.29 7.22 (m, 3H), 7.20 7.18 (m, 1H), 7.14 7.09 (m, 3H), 4.74 (s, 1H), 4.42 (d, 1H, J = 10.0 Hz), 3.55 (d, 1H, J = 9.7 Hz), 2.81 (br, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.7, 137.8, 134.1, 133.8, 131.2, 129.7, 129.1, 128.9, 128.7, 126.1, 125.2, 124.5, 70.2, 55.4, 46.5, 21.4; HRMS calcd for C 16 H 17 NOS [M+H] + :272.1104, found: m/z 272.1103; Enantiomeric excess was determined by HPLC with a Chiralcel IC 3 and AD H column (95 : 5 hexane : 2 propanol, 0.6 ml/min, 254 24.6 nm); minor enantiomer t r = 98.1 min, major enantiomer t r = 62.7 min; >99% ee; [α] D = -165.3 (c = 0.25, MeOH, >99% ee); IR (neat) 3734, 3649, 3375, 2987, 2891, 1568, 1470, 1075, 1013, 768, 753 cm -1 S22
(2R,3R,4R) 3 amino 2 (thiophen 2 yl)thiochroman 4 ol (7k) According to the general procedure B, the title compound was obtained by silica gel column chromatography (hexane : AcOEt = 2:1 to CHCl 3 : MeOH = 5:1) as a white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.38 (d, 1H, J = 7.7 Hz), 7.32 (dd, 1H, J = 5.2, 0.9 Hz), 7.23 7.19 (m, 1H), 7.14 7.09 (m, 3H), 7.01 6.99 (m, 1H), 4.77 (d, 1H, J = 9.5 Hz), 4.72 (d, 1H, J = 2.7 Hz), 3.45 (dd, 1H, J = 9.5, 2.7 Hz), 2.28 (br, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 141.8, 133.9, 133.2, 131.1, 128.7, 127.4, 127.0, 126.1, 125.1, 124.7, 70.0, 56.8, 42.5; HRMS calcd for C 13 H 14 NOS 2 [M+H] + :264.0511, found: m/z 264.0508; Enantiomeric excess was determined by HPLC with a Chiralcel OJ H column (85 : 15 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor 24.8 enantiomer t r = 21.4 min, major enantiomer t r = 15.4 min; 97% ee; [α] D = -145.7 (c = 0.25, MeOH, 95/5 dr, 97% ee); IR (neat) 3734, 3649, 3374, 3083, 2879, 1574, 1472, 1425, 1105, 754, 722, 700 cm -1 (2S,3R,4R) 3 amino 2 (4 aminophenyl)thiochroman 4 ol (7l) According to the general procedure B, the title compound was obtained by silica gel column chromatography (AcOEt to CHCl 3 : MeOH = 5:1) as a yellow solid. 1 H NMR (400 MHz, DMSO d 6 ) δ 7.30 7.28 (m, 1H), 7.16 (dt, 1H, J = 7.8, 1.6 Hz), 7.08 7.02 (m, 4H), 6.55 (d, 2H, J = 8.6 Hz), 5.13 (br, 2H), 4.55 (d, 1H, J = 2.5 Hz), 4.26 (d, 1H, J = 10.4 Hz), 3.50 (br, 1H), 3.42 (br, 2H), 3.19 (dd, 1H, J = 10.2, 2.5 Hz); 13 C NMR (100 MHz, DMSO d 6 ) δ 148.4, 136.1, 134.0, 131.3, 129.7, 128.0, 124.6, 124.3, 123.7, 114.0, 69.7, 55.1, 45.6; HRMS calcd for C 15 H 17 N 2 OS [M+H] + :273.1056, found: m/z 273.1056; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (70 : 30 hexane : 2 propanol, 0.7 ml/min, 25.7 254 nm); minor enantiomer t r = 43.2 min, major enantiomer t r = 18.4 min; 92% ee; [α] D = -156.1 (c = 0.125, MeOH, 92% ee); IR (neat) 3734, 3649, 2919, 1619, 1516, 1474, 1289, 1270, 1010, 759, 728 cm -1 S23
(2S,3R,4R) 3 amino 2 (3 aminophenyl)thiochroman 4 ol (7m) According to the general procedure B, the title compound was obtained by silica gel column chromatography (AcOEt to CHCl 3 : MeOH = 5:1) as a yellow solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.38(d, 1H, J = 7.4 Hz), 7.22 7.08 (m, 4H), 6.82 (d, 1H, J = 7.9 Hz), 6.77 6.75 (m, 1H), 6.65 6.63 (m, 1H), 4.73 (d, 1H, J = 2.7 Hz), 4.36 (d, 1H, J = 10.1 Hz), 3.51 (dd, 1H, J = 9.9, 2.7 Hz), 3.34 (br) 2.03 (br); 13 C NMR (100 MHz, CDCl 3 ) δ 147.0, 138.6, 134.0, 133.6, 131.4, 130.0, 128.6, 125.2, 124.5, 119.0, 115.4, 115.1, 69.5, 55.4, 45.9; HRMS calcd for C 15 H 17 N 2 OS [M+H] + :273.1056, found: m/z 273.1053; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (70 : 30 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 20.9 min, major enantiomer t r = 20.8 15.7 min; 87% ee; [α] D = -148.2 (c = 0.025, MeOH, 87% ee); IR (neat) 3734, 3649, 3348, 3214, 2923, 1604, 1458, 1297, 1262, 1074, 754, 731, 698 cm -1 (2S,3R,4R) 3 amino 6 (tert butyl) 2 phenylthiochroman 4 ol (7n) According to the general procedure B, the title compound was obtained by silica gel column chromatography ((hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 10:1) as a pale yellow solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.44 (d, 2H, J = 7.0 Hz), 7.40 7.31 (m, 4H), 7.27 7.24 (m, 1H), 7.07 (d, 1H, J = 8.3 Hz), 4.71 (d, 1H, J = 2.0 Hz), 4.44 (d, 1H, J = 9.9 Hz), 3.53 (d, 1H, J = 9.0 Hz), 2.30 (br, 3H), 1.31 (s, 9H); 13 C NMR (100 MHz, CDCl 3 ) δ 147.6, 138.0, 133.6, 130.2, 129.03, 128.96, 128.3, 128.1, 126.1, 124.9, 70.3, 55.6, 46.4, 34.3, 31.2; HRMS calcd for C 19 H 24 NOS [M+H] + :314.1573, found: m/z 314.1563; Enantiomeric excess was determined by HPLC with a Chiralpak AS H column (95 : 5 hexane : 2 propanol, 0.7 ml/min, 254 nm); minor enantiomer t r = 23.1 min, major enantiomer t r = 18.5 min; 25.8 92% ee; [α] D = -130.2 (c = 0.5, MeOH, 92% ee); IR (neat) 3734, 3649, 3289, 2960, 2901, 1576, 1484, 1455, 1013, 819, 741, 698 cm -1 S24
(2S,3R,4R) 3 amino 6 chloro 2 phenylthiochroman 4 ol (7o) According to the general procedure B, the title compound was obtained by silica gel column chromatography ((hexane: AcOEt = 2:1 to CHCl 3 : MeOH = 5:1) as an orange amorphous. 1 H NMR (500 MHz, CDCl 3 ) δ 7.43 7.42 (m, 3H), 7.39 7.37 (m, 2H), 7.35 7.32 (m, 1H), 7.18 (dd, 1H, J = 8.6, 2.3 Hz), 7.09 (d, 1H, J = 8.3 Hz), 4.63 (d, 1H, J = 2.6 Hz), 4.40 (d, 1H, J = 9.5 Hz), 3.56 3.54 (m, 1H), 2.18 (br, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 137.7, 135.9, 132.1, 130.7, 130.0, 129.1, 128.9, 128.6, 128.4, 126.6, 69.2, 55.3, 47.1; HRMS calcd for C 15 H 14 NOSCl [M+H] + : 292.0557, found: m/z 292.0556; Enantiomeric excess was determined by HPLC with a Chiralcel OD H column (80 : 20 hexane : 2 propanol, 0.7 ml/min, 25.9 254 nm); minor enantiomer t r = 9.0 min, major enantiomer t r = 7.9 min; 84% ee; [α] D = -110.4 (c = 0.25, MeOH, 90/10 dr, 84% ee); IR (neat) 3734, 3649, 3287, 2902, 1455, 1101, 1024, 810, 736, 698 cm -1 S25
9. 1 H NMR and 13 C NMR spectra of (2S,3R,4R)-3-nitro-2-arylthiochroman-4-ols (6) S26
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10. 1 H NMR and 13 C NMR spectra of (2S,3R,4R)-3-amino-2-arylthiochroman-4-ols (7) S42
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