Construction of 1,3-Dithio-Substituted Tetralins by [1,5]-Alkylthio Group Transfer Mediated Skeletal Rearrangement

Transcript

1 Construction of 1,3-Dithio-Substituted Tetralins by [1,5]-Alkylthio Group Transfer Mediated Skeletal Rearrangement Naoya Hisano, Yuto Kamei, Yaoki Kansaku, and Keiji Mori * Masahiro Yamanaka, Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Nakacho, Koganei, Tokyo , Japan. Department of Chemistry and Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo , Japan k_mori@cc.tuat.ac.jp myamanak@rikkyo.ac.jp Supporting Information Table of contents General experimental procedures Procedure and spectral data DFT calculations Cartesian coordinates References S1 S2 S3 S32 S33 S1

2 General experimental procedures All reactions utilizing air- and moisture-sensitive reagents were performed in dried glassware under an atmosphere of dry nitrogen. Anhydrous ethereal solvents (THF, Et 2 O) were purchased from Kanto Chemical Co., INC., and used directly. Dichloromethane and 1,2-dichloroethane were distilled over CaH 2. Benzene and toluene were distilled over CaH 2, and stored over 4A molecular sieves. N,N-Dimethylformamide (DMF) was distilled over CaH 2, and stored over 4A molecular sieves. For thin-layer chromatography (TLC) analysis, Merck pre-coated plates (silica gel 60 F 254, Art 5715, 0.25 mm) were used. Column chromatography and preparative TLC (PTLC) were performed on Silica Gel 60N (spherical, neutral), Kanto Chemical Ltd. and Wakogel B-5F, Wako Pure Chemical Industries, respectively. 1 H NMR, 13 C NMR were measured on a AL-300 MR (JEOL Ltd., 300 MHz) and ECX-400 (JEOL Ltd., 400 MHz) spectrometers. Chemical shifts are expressed in parts per million (ppm) downfield from internal standard (tetramethylsilane for 1 H, 0.00 ppm), and coupling constants are reported as hertz (Hz). Splitting patterns are indicated as follows: br, broad; s, singlet; d, doublet; t, triplet; q, quartet; sep, septet; m, multiplet. Infrared (IR) spectra were recorded on a FTIR-8600PC instrument (Shimadzu Co.). Elemental analysis (EA) was carried out on Flash2000 instrument (Amco Inc.). S2

3 1. Preparation of starting materials. Scheme 1. Preparation of starting materials 3. Preparation of 3a was shown as a representative example. O Br KCN Br NaH, EtO Br O H 2 SO 4 Br O DMF/H 2 O THF H 2 O/ 1.4-dioxane Br CN CN s1 86% s2 s3 65% s4 TiCl 4, EtSH CH 2 Cl 2 Br i) n-buli ii) DMF THF 79% s5 93% O s6 MeO 2 C MeO 2 C AcOH, piperidine Benzene 91% 3a Br CN Synthesis of 2-(2-bromophenyl)acetonitrile (s2): To a solution of 2-bormobenzyl bromide (s1) (1.57 g, 6.26 mmol) in DMF (2.5 ml) and H 2 O (1.6 ml) was added KCN (612 mg, 9.39 mmol) at room temperature. After being stirred for 5 min, the reaction temperature was suddenly warmed up to room temperature. After being stirred for 2 h at room temperature, the reaction was stopped by adding H 2 O. The crude products were extracted with EtOAc (x3) and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexane/etoac = 10/1) to give s2 (1.05 g, 86%) as colorless oil. Br O Synthesis of 1-(2-bromophenyl)propan-2-one (s4): To a suspension of NaH (60% oil, 262 mg, 6.01 mmol) in THF (3.0 ml) was added a solution of s2 (1.00 g, 5.15 mmol) in THF (1.0 ml) at 0 C. After being stirred for 1.5 h, a solution of ethyl acetate (0.60 ml, 6.1 mmol) in THF (7.3 ml) was added to the reaction mixture, and then heated reflux. After being stirred for 40 h, the reaction was stopped by adding H 2 O. After separation of organic and aqueous layer, the aqueous layer acidified with 1 M HCl. The crude products were extracted with EtOAc (x3) S3

4 and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and concentrated in vacuo to give crude s3 as brown oil. This material was used next reaction without further purification. A solution of s3 in 1,4-dioxane (2.9 ml) and 60% H 2 SO 4 (8.7 ml) was heated at 105 C. After being stirred for 17 h at 105 C, the reaction was stopped by adding H 2 O at room tempersture. The crude products were extracted with EtOAc (x5) and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexane/etoac = 15/1) to give s4 (710 mg, 65%) as yellow oil. 1 H NMR (300 MHz, CDCl 3 ) δ 2.22 (s, 3H), 3.87 (s, 2H), (m, 3H), 7.58 (d, 1H, J = 8.1 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 30.1, 51.0, 125.2, 127.8, 129.1, 131.9, 133.1, 135.0, The 1 H and 13 C NMR was in complete agreement with those in the literature. 1 Br Synthesis of (1-(2-Bromophenyl)propane-2,2-diyl)bis(ethylsulfane) (s5): To a solution of s4 (217 mg, 1.02 mmol) in CH 2 Cl 2 (1.0 ml) were successively added EtSH (0.23 ml, 3.10 mmol) and TiCl 4 (1. 0 M in CH 2 Cl 2, 33 µl, 0.33 mmol) at 15 C. After being stirred for 5 min, the reaction temperature was suddenly warmed up to room temperature. After being stirred for 18 h at room temperature, the reaction was stopped by adding H 2 O at 0 C. The crude products were extracted with EtOAc (x3) and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexane/etoac = 15/1) to give s5 (256 mg, 79%) as colorless oil. IR (neat) 2967, 2926, 2868, 1469, 1440, 1372, 1262, 1072, 1060, 1046, 1023, 976, 752 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.25 (t, 6H, J = 7.5 Hz), 1.49 (s, 3H), (m, 4H, J = 3.9 Hz), 3.32 (s, 2H), 7.08 (t, 1H, J = 7.8 Hz), 7.24 (t, 1H, J = 7.8 Hz), 7.46 (d, 1H, J S4

5 = 7.8 Hz), 7.52 (d, 1H, J = 7.8 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.8, 26.6, 46.0, 60.6, 126.3, 126.7, 128.4, 132.8, 133.0, Anal. Calcd for C 13 H 19 BrS 2 : C, 48.90; H, Found: C, 48.67; H, O Synthesis of 2-(2,2-Bis(ethylthio)propyl)benzaldehyde (s6): To a solution of s5 (185 mg, mmol) in THF (2.9 ml) was added n-buli (1.55 M in hexane, 0.47 ml, mmol) at 78 C. After being stirred for 15 min, DMF (80 µl, 1.0 mmol) was added to the reaction mixture. After being stirred for 4 h at 78 C, the reaction was stopped by adding saturated aqueous NH 4 Cl at 0 C. The crude products were extracted with EtOAc (x3) and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexane/etoac = 8/1) to give s6 (144 mg, 93%) as colorless oil. IR (neat) 2967, 2927, 2868, 1694, 1599, 1449, 1217, 758 cm 1. 1 H NMR (300 MHz, CDCl 3,) δ 1.18 (t, 6H, J = 7.5 Hz), 1.43 (s, 3H), 2.53 (q, 4H, J = 7.5 Hz), 3.54 (s, 2H), (m, 2H), 7.50 (dt, 1H, J = 1.2, 7.8 Hz), 7.86 (d, 1H, J = 7.8 Hz, 1H), (s, 1H). 13 C NMR (75 MHz, CDCl 3,) δ 13.8, 23.9, 27.4, 42.4, 59.8, 127.5, 130.2, 132.7, 133.6, 135.5, 138.4, Anal. Calcd for C 14 H 20 OS 2 : C, 62.64; H, Found: C, 62.73; H, MeO 2 C Synthesis of Dimethyl 2-(2-(2,2-bis(ethylthio)propyl)benzylidene)malonate (3a): To a solution of s6 (90.9 mg, mmol) in Benzene (4.1 ml) were successively added dimethyl malonate (39 µl, mmol), piperidine (39 µl, mmol) and AcOH (19 µl, mmol), and then the reaction mixture was heated to reflux. After S5

6 being stirred for 15 h, the reaction was stopped by adding saturated aqueous NaHCO 3 at 0 C. The crude products were extracted with EtOAc (x3) and the combined organic extracts were washed with 1 M aqueous HCl (x6), brine, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexane/etoac = 8/1) to give 3a (118 mg, 91%) as yellow amorphous. IR (neat) 2967, 2928, 2870, 1730, 1626, 1436, 1371, 1262, 1220, 1070, 984, 766 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.21 (t, 6H, J = 7.5 Hz), 1.42 (s, 3H), (m, 4H), 3.17 (s, 2H), 3.67 (s, 3H), 3.84 (s, 3H), (m, 3H), 7.40 (d, 1H, J = 7.8 Hz), 8.18 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 23.9, 27.4, 44.7, 52.4, 52.7, 60.5, 127.2, 127.2, 128.0, 129.4, 132.7, 134.0, 136.2, 143.7, 164.3, Anal. Calcd for C 19 H 26 O 4 S 2 : C, 59.66; H, Found: C, 59.47; H, Me I (1-(2-iodo-4-methylphenyl)propane-2,2-diyl)bis(ethylsulfane) (s7). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 830 mg (94%, synthesized from 1-(bromomethyl)-2-iodo-4-methylbenzene 2 ). IR (neat) 2966, 2925, 2868, 1600, 1485, 1445, 1372, 1261, 1061, 1034, 819 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.24 (t, 6H, J = 7.5 Hz), 1.51 (s, 3H), 2.26 (s, 3H), (m, 4H), 3.29 (s, 2H), 7.08 (d, 1H, J = 7.8 Hz), 7.34 (d, 1H, J = 7.8 Hz), 7.67 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 20.3, 23.8, 26.7, 50.1, 60.8, 103.3, 128.5, 131.4, 136.4, 138.5, Anal. Calcd for C 14 H 21 IS 2 : C, 44.21; H, Found: C, 44.46; H, Me O 2-(2,2-Bis(ethylthio)propyl)-5-methylbenzaldehyde (s8). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 530 mg (88%, synthesized from s7). S6

7 IR (neat) 2967, 2926, 2868, 1686, 1609, 1498, 1448, 1398, 1373, 1261, 1246, 1161, 1072, 838 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.21 (t, 6H, J = 7.5 Hz), 1.45 (s, 3H), 2.40 (s, 3H), (m, 4H), 3.53 (s, 2H), 7.27 (d, 1H, J = 7.8 Hz), 7.34 (d, 1H, J = 7.8 Hz), 7.70 (s, 1H), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 20.9, 23.9, 27.4, 42.1, 59.9, 130.5, 133.6, 133.7, 135.2, 135.5, 137.4, Anal. Calcd for C 15 H 22 OS 2 : C, 63.78; H, Found: C, 63.49; H, MeO 2 C Me Dimethyl 2-(2-(2,2-bis(ethylthio)propyl)-5-methylbenzylidene)malonate (3b). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 333 mg (84%, synthesized from s8). IR (neat) 2967, 2927, 2870, 1733, 1626, 1608, 1494, 1436, 1372, 1269, 1230, 1204, 1167, 1070, 986, 837 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 6H, J = 7.5 Hz), 1.42 (s, 3H), 2.30 (s, 3H), (m, 4H), 3.14 (s, 2H), 3.70 (s, 3H), 3.85 (s, 3H), 7.12 (s, 1H), 7.15 (d, 1H, J = 8.1 Hz), 7.28 (d, 1H, J = 8.1 Hz), 8.16 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 21.0, 23.8, 27.3, 44.2, 52.4, 52.7, 60.6, 126.7, 128.4, 130.3, 132.6, 133.2, 133.7, 136.9, 143.7, 164.3, Anal. Calcd for C 20 H 28 O 4 S 2 : C, 60.57; H, Found: C, 60.71; H, MeO Br (1-(2-Bromo-4-methoxyphenyl)propane-2,2-diyl)bis(ethylsulfane) (s9). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 589 mg (72%, synthesized from 2-bromo-1-(bromomethyl)-4-methoxybenzene 1 ). IR (neat) 2966, 2926, 2869, 2834, 1604, 1565, 1493, 1440, 1372, 1319, 1284, 1253, 1240, 1206, 1071, 1060, 1038, 1028, 859, 839, 815, 784 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.19 (t, 6H, J = 7.5 Hz), 1.43 (s, 3H), (m, 4H), 3.20 (s, 2H), 3.72 (s, 3H), 6.76 (dd, 1H, J = 2.7, 8.4 Hz), 7.03 (d, 1H, J = 2.7 Hz), 7.30 S7

8 (d, 1H, J = 8.4 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.7, 26.5, 45.2, 55.4, 60.8, 112.9, 117.7, 126.3, 128.0, 133.2, Anal. Calcd for C 14 H 21 BrOS 2 : C, 48.13; H, Found: C, 48.32; H, MeO O 2-(2,2-Bis(ethylthio)propyl)-5-methoxybenzaldehyde (s10). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 312 mg (68%, synthesized from s9). IR (neat) 2966, 2928, 2869, 1686, 1606, 1572, 1497, 1454, 1421, 1398, 1329, 1285, 1260, 1193, 1164, 1072, 1037 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.20 (t, 6H, J = 7.5 Hz), 1.46 (s, 3H), 2.55 (q, 4H, J = 7.5 Hz), 3.46 (s, 2H), 3.85 (s, 3H), 7.08 (dd, 1H, J = 2.7, 8.4 Hz), 7.29 (d, 1H, J = 8.4 Hz), 7.42 (d, 1H, J = 2.7 Hz),, (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 23.9, 27.6, 41.9, 55.4, 60.0, 112.1, 120.1, 131.0, 134.7, 136.2, 158.9, Anal. Calcd for C 15 H 22 O 2 S 2 : C, 60.36; H, Found: C, 60.09; H, MeO 2 C MeO Dimethyl 2-(2-(2,2-bis(ethylthio)propyl)-5-methoxybenzylidene)malonate (3c). Brown oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 354 mg (63%, synthesized from s10). IR (neat) 2965, 2928, 1730, 1625, 1605, 1570, 1494, 1436, 1371, 1274, 1238, 1203, 1169, 1070, 1038 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 6H, J = 7.5 Hz), 1.42 (s, 3H), (m, 4H), 3.12 (s, 2H), 3.73 (s, 3H), 3.76 (s, 3H), 3.86 (s, 3H), (m, 2H), 7.31 (d, 1H, J = 8.7 Hz), 8.15 (s, 1H). 13 C NMR (75 MHz, CDCl 3,) δ 13.9, 23.8, 27.4, 43.9, 52.6, 52.7, 55.2, 60.7, 112.5, 115.7, 127.2, 128.4, 133.8, 134.7, 143.4, 158.4, 164.3, S8

9 Anal. Calcd for C 20 H 28 O 5 S 2 : C, 58.22; H, Found: C, 58.45; H, F Br (1-(2-Bromo-4-fluorophenyl)propane-2,2-diyl)bis(ethylsulfane) (s11). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 881 mg (74%, synthesized from 2-bromo-1-(bromomethyl)-4-fluorobenzene 3 ). IR (neat) 2968, 2927, 2969, 1599, 1486, 1446, 1373, 1264, 1231, 1179, 1072, 1059, 1032, 905, 857, 822, 785 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.27 (t, 6H, J = 7.5 Hz), 1.49 (s, 3H), (m, 4H), 3.29 (s, 2H), 7.00 (ddd, 1H, J = 3.0, 6.0, 8.4 Hz), 7.31 (dd, 1H, J = 3.0, 8.4 Hz), 7.46 (dd, 1H, J = 6.0, 8.4 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.8, 26.5, 45.1, 60.4 (d, J = 1.3 Hz), (d, J = 20.4 Hz), (d, J = 24.1 Hz), (d, J = 9.2 Hz), (d, J = 3.1 Hz), (d, J = 8.0 Hz), (d, J = Hz). Anal. Calcd for C 13 H 18 BrFS 2 : C, 46.29; H, Found: C, 46.45; H, F O 2-(2,2-Bis(ethylthio)propyl)-5-fluorobenzaldehyde (s12). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 677 mg (91%, synthesized from s11). IR (neat) 2968, 2929, 2890, 1608, 1586, 1493, 1455, 1417, 1397, 1374, 1249, 1150, 1072, 1055, 971, 885, 840 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.22 (t, 6H, J = 7.5 Hz), 1.47 (s, 3H), 2.54 (q, 4H, J = 7.5 Hz), 3.49 (s, 2H), 7.24 (ddd, 1H, J = 3.0, 8.4, 9.0 Hz), 7.38 (dd, 1H, J = 3.0, 8.4 Hz), 7.11 (dd, 1H, J = 3.0, 8.4 Hz), 10.3 (d, 1H, J = 2.4 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.7, 24.0, 27.7, 42.0, 59.6 (d, J C-F = 1.2 Hz), (d, J C-F = 22.2 Hz), (d, J C-F = 21.0 Hz), (d, J C-F = 3.8 Hz), (d, J C-F = 6.8 Hz), (d, J C-F = 6.2 Hz), (d, J C-F = Hz), (d, J C-F = 1.8 Hz). Anal. Calcd for C 14 H 19 FOS 2 : C, 58.71; H, Found: C, 58.53; H, S9

10 MeO 2 C F Dimethyl 2-(2-(2,2-bis(ethylthio)propyl)-5-fluorobenzylidene)malonate (3d). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 12/1). Yield: 592 mg (90%, synthesized from s12). IR (neat) 2967, 2928, 1731, 1581, 1489, 1436, 1371, 1272, 1231, 1179, 1163, 1069 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 6H, J = 7.5 Hz), 1.43 (s, 3H), 2.61 (q, 4H, J = 7.5 Hz), 3.14 (s, 2H), 3.74 (s, 3H), 3.87 (s, 3H), (m, 2H), (m, 1H), 8.11 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 23.8, 27.4, 43.9, 52.6, 52.8, 60.3, (d, J = 22.2 Hz), (d, J = 21.0 Hz), 128.1, (d, J = 3.7 Hz), (d, J = 8.0 Hz), (d, J = 8.0 Hz), 142.1, (d, J = Hz), 164.0, Anal. Calcd for C 19 H 25 FO 4 S 2 : C, 56.98; H, Found: C, 57.24; H, I Me (1-(2-Iodo-5-methylphenyl)propane-2,2-diyl)bis(ethylsulfane) (s13). Colorless solid (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 449 mg (93%, synthesized from 2-(bromomethyl)-1-iodo-4-methylbenzene 4 ). IR (neat) 2966, 2925, 2868, 1465, 1445, 1372, 1262, 1071, 1063, 1010, 806 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.24 (t, 6H, J = 7.5 Hz), 1.54 (s, 3H), 2.31 (s, 3H), (m, 4H), 3.31 (s, 2H), 6.76 (dd, 1H, J = 1.8, 8.1 Hz), 7.29 (d, 1H, J = 1.8 Hz), 7.70 (d, 1H, J = 8.1 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 21.0, 23.9, 26.8, 50.5, 60.7, 99.3, 129.7, 132.9, 137.4, 139.1, Anal. Calcd for C 14 H 21 IS 2 : C, 44.21; H, Found: C, 44.12; H, O Me 2-(2,2-Bis(ethylthio)propyl)-4-methylbenzaldehyde (s14). S10

11 Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 290 mg (84%, synthesized from s13). IR (neat) 2967, 2926, 2868, 1689, 1606, 1447, 1373, 1221, 1072, 822 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.20 (t, 6H, J = 7.5 Hz), 1.45 (s, 3H), 2.41 (s, 3H), (m, 4H), 3.53 (s, 2H), 7.17 (s, 1H), 7.22 (d, 1H, J = 7.8 Hz), 7.78 (d, 1H, J = 7.8 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 21.8, 23.9, 27.3, 42.4, 59.8, 128.3, 130.6, 133.1, 134.3, 138.4, 143.6, Anal. Calcd for C 15 H 22 OS 2 : C, 63.78; H, Found: C, 63.94; H, MeO 2 C Me Dimethyl 2-(2-(2,2-bis(ethylthio)propyl)-4-methylbenzylidene)malonate (3e). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 348 mg (85%, synthesized from s14). IR (neat) 2967, 2928, 2870, 1737, 1626, 1608, 1496, 1436, 1372, 1265, 1243, 1218, 1182, 1069, 986, 833 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 6H, J = 7.5 Hz), 1.44 (s, 3H), 2.36 (s, 3H), (m, 4H), 3.16 (s, 2H), 3.71 (s, 3H), 3.85 (s, 3H), 7.05 (d, 1H, J = 8.1 Hz), (m, 2H), 8.17 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 21.5, 23.8, 27.4, 44.7, 52.5, 52.6, 60.5, 126.0, 127.9, 128.1, 130.9, 133.6, 136.2, 139.7, 143.5, 164.5, Anal. Calcd for C 20 H 28 O 4 S 2 : C, 60.57; H, Found: C, 60.44; H, Br MeO (1-(2-Bromo-5-methoxyphenyl)propane-2,2-diyl)bis(ethylsulfane) (s15). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 732 mg (88%, synthesized from commercially available, 1-bromo-2-(bromomethyl)-4-methoxybenzene). IR (neat) 2966, 2927, 1595, 1570, 1470, 1414, 1372, 1299, 1278, 1256, 1239, 1163, 1134, 1065, 1051, 1014, 802 cm 1. S11

12 1 H NMR (300 MHz, CDCl 3 ) δ 1.24 (t, 6H, J = 7.5 Hz), 1.49 (s, 3H), (m, 4H), 3.27 (s, 2H), 3.77 (s, 3H), 6.66 (dd, 1H, J = 3.0, 9.0 Hz), 7.04 (d, 1H, J = 3.0 Hz), 7.40 (d, 1H, J = 9.0 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.8, 26.5, 46.1, 55.3, 60.5, 114.2, 116.8, 118.5, 133.1, 136.9, Anal. Calcd for C 14 H 21 BrOS 2 : C, 48.13; H, Found: C, 48.04; H, O MeO 2-(2,2-Bis(ethylthio)propyl)-4-methoxybenzaldehyde (s16). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 486 mg (96%, synthesized from s15). IR (neat) 2967, 2928, 2868, 1684, 1600, 1568, 1496, 1446, 1329, 1290, 1260, 1249, 1222, 1163, 1119, 1104, 1066, 1030, 812 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.22 (t, 6H, J = 7.5 Hz), 1.46 (s, 3H), 2.60 (q, 4H, J = 7.5 Hz), 3.57 (s, 2H), 3.88 (s, 3H), (m, 2H), 7.84 (d, 1H, J = 8.4 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 23.9, 27.2, 42.4, 55.5, 59.8, 112.7, 119.0, 128.9, 133.4, 140.9, 162.8, Anal. Calcd for C 15 H 22 O 2 S 2 : C, 60.36; H, Found: C, 60.52; H, MeO 2 C MeO Dimethyl 2-(2-(2,2-bis(ethylthio)propyl)-4-methoxybenzylidene)malonate (3f). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 265 mg (55%, synthesized from s16). IR (neat) 2966, 2929, 2870, 2840, 1733, 1602, 1567, 1496, 1436, 1373, 1308, 1255, 1216, 1107, 1069, 1034, 986, 942, 830 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 6H, J = 7.5 Hz), 1.44 (s, 3H), (m, 4H), 3.18 (s, 2H), 3.73 (s, 3H), 3.83 (s, 3H), 3.85 (s, 3H), 6.78 (dd, 1H, J = 2.7, 8.7 Hz), 6.95 (d, 1H, J = 2.7 Hz), 7.30 (d, 1H, J = 8.7 Hz), 8.13 (s, 1H). S12

13 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.9, 27.4, 44.8, 52.4, 52.5, 55.2, 60.3, 112.9, 118.2, 124.9, 126.2, 129.6, 138.5, 142.8, 160.4, 164.6, Anal. Calcd for C 20 H 28 O 5 S 2 : C, 58.22; H, Found: C, 58.02; H, I (1-(3-Iodonaphthalen-2-yl)propane-2,2-diyl)bis(ethylsulfane) (s17). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 674 mg (95%, synthesized from 2-bromomethyl-3-iode-naphthalene 5 ). IR (neat) 3051, 2965, 2925, 2867, 1579, 1489, 1444, 1371, 1261, 1217, 1128, 1070, 971, 879, 743 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.29 (t, 6H, J = 7.5 Hz), 1.56 (s, 3H), (m, 4H), 3.52 (s, 2H), (m, 2H), 7.69 (d, 1H, J = 7.2 Hz), 7.80 (d, 1H, J = 7.2 Hz), 7.95 (s, 1H), 8.41 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.9, 26.6, 50.2, 61.0, 101.3, 126.3, 126.5, 126.5, 127.8, 130.4, 132.4, 133.7, 135.5, Anal. Calcd for C 17 H 21 IS 2 : C, 49.04; H, Found: C, 44.29; H, O 3-(2,2-Bis(ethylthio)propyl)-2-naphthaldehyde (s18). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 629 mg (80%, synthesized from s17). IR (neat) 2967, 2926, 2868, 1695, 1628, 1591, 1445, 1372, 1262, 1174, 1071, 893, 748 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 6H, J = 7.5 Hz), 1.48 (s, 3H), (m, 4H), 3.78 (s, 2H), (m, 2H), 7.81 (s, 1H), 7.87 (d, 1H, J = 7.5 Hz), 7.97 (d, 1H, J = 7.5 Hz), 8.36 (s, 1H), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 23.9, 27.1, 42.4, 60.2, 126.8, 127.7, 129.1, 129.2, 131.6, 133.0, 133.6, 134.7, 134.9, Anal. Calcd for C 18 H 22 OS 2 : C, 67.88; H, Found: C, 67.63; H, S13

14 MeO 2 C Dimethyl 2-((3-(2,2-bis(ethylthio)propyl)naphthalen-2-yl)methylene)malonate (3g). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 562 mg (92%, synthesized from s18). IR (neat) 2967, 2927, 1732, 1620, 1436, 1371, 1265, 1227, 1214, 1182, 1070, 749 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.24 (t, 6H, J = 7.5 Hz), 1.49 (s, 3H), (m, 4H), 3.33 (s, 2H), 3.67 (s, 3H), 3.89 (s, 3H), (m, 2H), 7.80 (dd, 2H, J = 8.1, 8.1 Hz), 7.85 (s, 2H), 8.35 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 23.8, 27.4, 44.6, 52.5, 52.7, 60.6, 126.4, 127.2, 127.4, 127.5, 127.9, 128.0, 131.6, 131.9, 132.3, 132.5, 133.3, 143.7, 164.2, Anal. Calcd for C 23 H 28 O 4 S 2 : C, 63.86; H, Found: C, 63.95; H, Br (1-(2-Bromophenyl)butane-2,2-diyl)bis(ethylsulfane) (s19). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 464 mg (76%, synthesized from s2). IR (neat) 3062, 2968, 2927, 2870, 1469, 1438, 1376, 1261, 1048, 1024, 976, 936, 750 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.05 (t, 3H, J = 7.2 Hz), 1.22 (t, 6H, J = 7.5 Hz), 1.84 (q, 2H, J = 7.2 Hz), (m, 4H), 3.34 (s, 2H), 7.09 (dt, 1H, J = 1.5, 7.8 Hz), 7.26 (dt, 1H, J = 1.5, 7.8 Hz), 7.55 (dd, 1H, J = 1.5, 7.8 Hz), 7.60 (dd, 1H, J = 1.5, 7.8 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 9.5, 13.8, 23.4, 31.5, 43.1, 65.1, 126.4, 126.8, 128.3, 132.5, 132.9, Anal. Calcd for C 14 H 21 BrS 2 : C, 50.44; H, Found: C, 50.71; H, O 2-(2,2-Bis(ethylthio)butyl)benzaldehyde (s20). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). S14

15 Yield: 375 mg (89%, synthesized from s19). IR (neat) 2968, 2929, 2869, 1693, 1599, 1450, 1213, 758 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.04 (t, 6H, J = 7.5 Hz), 1.06 (t, 3H, J = 7.2 Hz), 1.75 (q, 2H, J = 7.2 Hz), (m, 4H), 3.43 (s, 2H), (m, 3H), 7.86 (d, 1H, J = 7.5 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 9.3, 13.5, 23.3, 32.4, 39.4, 64.6, 127.5, 129.2, 132.6, 133.1, 135.8, 139.0, Anal. Calcd for C 15 H 22 OS 2 : C, 63.78; H, Found: C, 63.88; H, MeO 2 C Dimethyl 2-(2-(2,2-bis(ethylthio)butyl)benzylidene)malonate (3h). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 411 mg (90%, synthesized from s20). IR (neat) 2969, 2930, 1730, 1626, 1436, 1374, 1260, 1218, 1068, 984, 944 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.06 (t, 3H, J = 7.2 Hz), 1.16 (t, 6H, J = 7.5 Hz), 1.81 (q, 2H, J = 7.2 Hz), (m, 4H), 3.15 (s, 2H), 3.69 (s, 3H), 3.86 (s, 3H), (m, 3H), 7.48 (d, 1H, J = 7.8 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 9.5, 13.7, 23.3, 32.1, 41.5, 52.4, 52.7, 64.8, 127.0, 127.1, 127.9, 129.3, 132.3, 134.1, 136.5, 144.1, 164.3, Anal. Calcd for C 20 H 28 O 4 S 2 : C, 60.57; H, Found: C, 60.73; H, Br (1-(2-Bromophenyl)pentane-2,2-diyl)bis(ethylsulfane) (s21). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 875 mg (62%, synthesized from s2). IR (neat) 2962, 2928, 2870, 2362, 1470, 1455, 1438, 1025, 748 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 0.88 (t, 3H, J = 7.2 Hz), 1.22 (t, 6H, J = 7.5 Hz), (m, 2H), (m, 2H), 2.60 (q, 4H, J = 7.5 Hz), 3.35 (s, 2H), 7.10 (dt, 1H, J = 1.5, 7.5 Hz), 7.25 (t, 1H, J = 7.5 Hz), 7.56 (t, 2H, 7.5 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 13.8, 14.2, 18.2, 23.4, 41.2, 43.6, 64.5, 126.4, 126.7, S15

16 128.3, 132.5, 132.9, Anal. Calcd for C 15 H 23 BrS 2 : C, 51.86; H, Found: C, 51.63; H, O 2-(2,2-Bis(ethylthio)pentyl)benzaldehyde (s22). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 699 mg (82%, synthesized from s21). IR (neat) 2962, 2929, 2871, 1694, 1599, 1452, 1213, 759 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 0.91 (t, 3H, J = 7.2 Hz), 1.08 (t, 6H, J = 7.5 Hz), (m, 4H), (m, 4H), 3.49 (s, 2H), (m, 2H), 7.89 (d, 1H, J = 7.5 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.5, 14.1, 18.0, 23.4, 39.9, 42.1, 64.1, 127.4, 129.2, 132.6, 133.1, 135.8, 139.0, Anal. Calcd for C 16 H 24 OS 2 : C, 64.82; H, Found: C, ; H, MeO 2 C Dimethyl 2-(2-(2,2-bis(ethylthio)pentyl)benzylidene)malonate (3i). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 558 mg (88%, synthesized from s22). IR (neat) 2959, 2931, 2871, 1729, 1625, 1435, 1373, 1261, 1217, 1067, 985, 767 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 0.89 (t, 3H, J = 7.2 Hz), 1.16 (t, 6H, J = 7.2 Hz), (m, 4H), (m, 4H), 3.16 (s, 2H), 3.69 (s, 3H), 3.86 (s, 3H), (m, 3H), 7.47 (d, 1H, J = 7.8 Hz), 8.34 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.7, 14.0, 18.0, 23.3, 41.6, 42.0, 52.3, 52.6, 64.2, 126.9, 127.0, 127.8, 129.3, 132.3, 134.0, 136.5, 143.9, 164.3, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.27; H, S16

17 MeO 2 C Ph Dimethyl 2-(2-(2,2-bis(ethylthio)-2-phenylethyl)benzylidene)malonate (3j). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 247 mg (79%, synthesized from s2). IR (neat) 2966, 2928, 1731, 1625, 1486, 1436, 1373, 1261, 1219, 1099, 1068, 985, 945, 833 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.23 (t, 3H, J = 7.5 Hz), (m, 4H), 3.43 (s, 2H), 3.63 (s, 3H), 3.83 (s, 3H), (m, 1H), (m, 6H), 7.46 (s, 1H), (m, 2H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.3, 24.5, 45.7, 52.2, 52.4, 68.9, 126.7, 126.9, 127.3, 127.4, 128.1, 128.8, 132.3, 133.9, 135.3, 140.8, 143.2, 164.1, Anal. Calcd for C 24 H 28 O 4 S 2 : C, 64.83; H, Found: C, 64.97; H, MeO 2 C H Dimethyl 2-(2-(2,2-bis(ethylthio)ethyl)benzylidene)malonate (3k). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 190 mg (58%, synthesized from s2). IR (neat) 2953, 2926, 1730, 1627, 1435, 1372, 1261, 1215, 1068, 984, 764 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.19 (t, 6H, J = 7.5 Hz), (m, 4H), 3.18 (d, 1H, J = 7.5 Hz), 3.69 (s, 3H), 3.86 (s, 3H), 3.88 (t, 1H, J = 7.5 Hz), (m, 4H), 8.09 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 14.3, 25.0, 41.2, 51.7, 52.4, 52.6, 127.2, 127.9, 128.0, 129.8, 131.2, 132.6, 138.1, 142.4, 164.0, Anal. Calcd for C 18 H 24 O 4 S 2 : C, 58.67; H, Found: C, 58.41; H, EtO 2 C CO 2 Et Diethyl 2-(2-(2,2-bis(ethylthio)propyl)benzylidene)malonate (3l). S17

18 Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 235 mg (75%, synthesized from s6). IR (neat) 2975, 2929, 2871, 1731, 1627, 1446, 1375, 1349, 1293, 1257, 1217, 1094, 1068, 1023, 764 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.12 (t, 3H, J = 7.2 Hz), 1.23 (t, 6H, J = 7.2 Hz), 1.32 (t, 3H, J = 7.2 Hz), 1.45 (s, 3H), (m, 2H), 3.19 (s, 2H), 4.18 (q, 2H, J = 7.2 Hz), 4.32 (q, 2H, J = 7.2 Hz), (m, 2H), 7.33 (dd, 1H, J = 7.8, 7.8 Hz), 7.42 (d, 1H, J = 7.8 Hz), 8.18 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.7, 13.8, 14.1, 23.8, 27.4, 44.7, 60.4, 61.3, 61.5, 127.0, 128.1, 128.2, 129.1, 132.5, 134.1, 136.0, 143.0, 163.8, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.59; H, Br SPr SPr (1-(2-Bromophenyl)propane-2,2-diyl)bis(propylsulfane) (s23). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 458 mg (71%, synthesized from s4). IR (neat) 2961, 2927, 2871, 1468, 1438, 1372, 1059, 1046, 1023, 751 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.03 (t, 6H, J = 7.5 Hz), 1.50 (s, 3H), 1.64 (sext, 4H, J = 7.5 Hz), (m, 4H), 3.33 (s, 2H), 7.10 (dt, 1H, J = 1.5, 7.8 Hz), 7.26 (dt, 1H, J = 1.5, 7.8 Hz), 7.49 (dd, 1H, J = 1.5, 7.8 Hz), 7.55 (dd, 1H, J = 1.5, 7.8 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 14.0, 22.5, 26.6, 31.9, 45.9, 60.5, 126.3, 126.7, 128.4, 132.8, 133.1, Anal. Calcd for C 15 H 23 BrS 2 : C, 51.86; H, Found: C, 51.64; H, O SPr SPr 2-(2,2-Bis(propylthio)propyl)benzaldehyde (s24). Yellow oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 336 mg (90%, synthesized from s23). IR (neat) 2961, 2928, 2871, 1694, 1599, 1454, 1373, 1290, 1218, 1202, 1185, 1066, 757 cm 1. S18

19 1 H NMR (300 MHz, CDCl 3 ) δ 0.99 (t, 6H, J = 7.5 Hz), 1.45 (s, 3H), 1.58 (sext, 4H, J = 7.5 Hz), 2.54 (t, 4H, J = 7.5 Hz), 3.58 (s, 2H), (m, 2H), 7.54 (dt, 1H, J = 1.2, 7.5 Hz), 7.90 (dd, 1H, J = 1.2, 7.5 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.94, 22.4, 27.5, 31.9, 42.5, 59.8, 127.5, 130.1, 132.8, 133.6, 135.4, 138.5, Anal. Calcd for C 16 H 24 OS 2 : C, 64.82; H, Found: C, 64.57; H, MeO 2 C SPr SPr Dimethyl 2-(2-(2,2-bis(propylthio)propyl)benzylidene)malonate (3m). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 366 mg (57%, synthesized from s24). IR (neat) 2960, 2929, 2871, 1730, 1626, 1436, 1371, 1291, 1292, 1220, 1069, 767 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.00 (t, 6H, J = 7.2 Hz), 1.43 (s, 3H), 1.61 (sext, 4H, J = 7.2 Hz), (m, 4H), 3.19 (s, 2H), 3.70 (s, 3H), 3.86 (s, 3H), (m, 3H), 7.43 (d, 1H, J = 7.5 Hz), 8.21 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 13.9, 22.4, 27.4, 31.8, 44.6, 52.4, 52.6, 60.4, 127.1, 127.2, 127.9, 129.3, 132.7, 133.9, 136.1, 143.7, 164.2, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.53; H, Br Si-Pr Si-Pr (1-(2-Bromophenyl)propane-2,2-diyl)bis(isopropylsulfane) (s25). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 15/1). Yield: 734 mg (32%, synthesized from s4). IR (neat) 2956, 2925, 2862, 1438, 1365, 1241, 1154, 1043, 1023, 752 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.26 (d, 6H, J = 6.9 Hz), 1.31 (d, 6H, J = 6.9 Hz), 1.50 (s, 3H), 3.14 (sept, 2H, J = 6.9 Hz), 3.36 (s, 2H), 7.04 (dd, 1H, J = 7.5 Hz), 7.19 (dd, 1H, J = 7.5 Hz), 7.49 (dd, 2H, J = 7.5 Hz). 13 C NMR (75 MHz, CDCl 3 ) δ 25.6, 25.8, 27.5, 34.9, 48.0, 62.1, 126.3, 126.7, 128.4, 132.8, 133.1, Anal. Calcd for C 15 H 23 BrS 2 : C, 51.86; H, Found: C, 51.89; H, S19

20 O Si-Pr Si-Pr 2-(2,2-Bis(isopropylthio)propyl)benzaldehyde (s26). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 551 mg (84%, synthesized from s25). IR (neat) 2958, 2925, 2864, 1695, 1599, 1450, 1383, 1368, 1291, 1240, 1219, 1201, 1185, 1156, 1070, 1047, 809, 758 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.26 (d, 6H, J = 6.9 Hz), 1.34 (d, 6H, J = 6.9 Hz), 1.52 (s, 3H), (m, 2H), 3.67 (s, 2H), 7.23 (d, 2H, J = 7.5 Hz), (m, 1H), 7.88 (d, 1H, J = 7.5 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 25.5, 25.7, 28.1, 35.0, 44.2, 61.4, 127.5, 130.5, 132.8, 133.7, 135.3, 138.6, Anal. Calcd for C 16 H 24 OS 2 : C, 64.82; H, Found: C, 64.63; H, MeO 2 C Si-Pr Si-Pr Dimethyl 2-(2-(2,2-bis(isopropylthio)propyl)benzylidene)malonate (3l). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 486 mg (34%, synthesized from s26). IR (neat) 2956, 2925, 2864, 1732, 1627, 1436, 1366, 1263, 1221, 1184, 1156, 1070, 766 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.22 (d, 6H, J = 6.9 Hz), 1.27 (d, 6H, J = 6.9 Hz), 1.42 (s, 2H), 3.05 (septet, 2H, J = 6.9 Hz), 3.21 (s, 2H), 3.63 (s, 3H), 3.80 (s, 3H), (m, 3H), 7.44 (d, 1H, J = 7.5 Hz), 8.13 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 25.6, 25.6, 28.3, 35.0, 46.7, 52.4, 52.7, 62.0, 127.2, 127.2, 127.9, 129.4, 132.8, 133.8, 136.3, 143.8, 164.2, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.23; H, S20

21 Br S S 2-(2-Bromobenzyl)-2-methyl-1,3-dithiane (s27). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 20/1). Yield: 310 mg (94%, synthesized from s4). IR (neat) 2903, 1469, 1437, 1422, 1370, 1276, 1061, 1046, 1022, 906, 753 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.61 (s, 3H), (m, 2H), (m, 4H), 3.51 (s, 2H), 7.11 (ddd, 1H, J = 1.8, 7.5, 7.5 Hz), 7.26 (ddd, 1H, J = 1.8, 7.5, 7.5 Hz), 7.46 (dd, 1H, J = 1.8, 7.5 Hz), 7.57 (dd, 1H, J = 1.8, 7.5 Hz),. 13 C NMR (75 MHz, CDCl 3 ) δ 25.0, 26.9, 26.9, 45.5, 59.5, 126.3, 126.6, 128.5, 132.9, 133.0, Anal. Calcd for C 12 H 15 BrS 2 : C, 47.52; H, Found: C, 47.78; H, O S S 2-((2-Methyl-1,3-dithian-2-yl)methyl)benzaldehyde (s28). Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 275 mg (64%, synthesized from s27). IR (neat) 2905, 2862, 2829, 1693, 1598, 1574, 1448, 1421, 1370, 1290, 1277, 1220, 1202, 1186, 759 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.51 (s, 3H), (m, 2H), (m, 4H), 3.74 (s, 2H), (m, 2H), 7.54 (ddd, 1H, J = 1.5, 7.5, 7.5 Hz), 7.88 (dd, 1H, J = 1.5, 7.5 Hz), (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 24.8, 26.8, 27.7, 42.0, 49.4, 127.6, 130.6, 132.8, 133.8, 135.5, 138.0, Anal. Calcd for C 13 H 16 OS 2 : C, 61.86; H, Found: C, 61.75; H, O O MeO OMe S S Dimethyl 2-(2-((2-methyl-1,3-dithian-2-yl)methyl)benzylidene)malonate (3o). S21

22 Colorless oil (purified by silica gel column chromatography, Hexane/EtOAc = 10/1). Yield: 305 mg (74%, synthesized from s28). IR (neat) 2951, 1729, 1625, 1436, 1369, 1263, 1221, 1109, 1070, 984, 767 cm 1. 1 H NMR (300 MHz, CDCl 3 ) δ 1.49 (s, 3H), (m, 2H), (m, 4H), 3.36 (s, 2H), 3.70 (s, 3H), 3.86 (s, 3H), (m, 3H), 7.42 (d, 1H, J = 8.1 Hz), 8.19 (s, 1H). 13 C NMR (75 MHz, CDCl 3 ) δ 24.9, 26.8, 27.5, 44.0, 49.8, 52.5, 52.7, 127.2, 127.3, 128.0, 129.3, 132.8, 134.0, 135.8, 143.7, 164.3, Anal. Calcd for C 18 H 22 O 4 S 2 : C, 58.99; H, Found: C, 59.26; H, S22

23 2. Synthesis of 1,3-dithiotetralin derivatives. General Procedure of skeletal rearrangement involving [1,5]-alkylthio group transfer/cyclization sequence. To a solution of thio ketals 3 (0.10 mmol) in ClCH 2 CH 2 Cl (1.0 ml) was added Sc(OTf) 3 (0.010 mmol, 10 mol%) at room temperature. After completion of the reaction, the reaction was stopped by adding saturated aqueous NaHCO 3. The crude products were extracted with EtOAc (x3) and the combined organic extracts were washed with brine, dried (Na 2 SO 4 ), and concentrated in vacuo. The residue was purified by preparative TLC to give 1,3-dithiotetralin derivatives 4. CO2 Me Dimethyl 1,3-bis(ethylthio)-3-methyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4a). Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 37.0 mg (88%, d.r. = 1:1.5). * shows the peaks of minor diastereomer. IR (neat) 2951, 2928, 2870, 1762, 1736, 1494, 1451, 1433, 1377, 1266, 1219, 1121, 1107, 1046, 959, 914, 786 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6+6*H), 1.74* (s, 3H), 1.79 (s, 3H), (m, 5+5*H), 3.05 (d, 1H, J = 17.6 Hz), 3.35* (d, 1H, J = 17.6 Hz), 3.66* (s, 3H), 3.73 (s, 3H), 3.74 (s, 3H), 3.87* (s, 3H), 4.51 (s, 1H), 5.03* (s, 1H), (m, 3H+3H*), 7.66 (d, 1H, J = 8.0 Hz), 7.79* (d, 1H, J = 8.0 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 13.8, 14.5, 14.6, 22.8, 23.8, 24.9, 26.5, 29.4, 32.1, 42.0, 43.6, 47.5, 49.9, 50.5, 51.1, 52.0, 52.1, 52.5, 52.7, 68.8, 68.9, 126.4, 126.5, 126.6, 126.8, 128.0, 128.1, 128.5, 128.6, 132.2, 133.3, 136.7, 138.4, 168.2, 168.6, 169.6, Anal. Calcd for C 19 H 26 O 4 S 2 : C, 59.66; H, Found: C, 59.49; H, S23

24 Me CO2 Me Dimethyl 1,3-bis(ethylthio)-3,7-dimethyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4b). Colorless oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 30.1 mg (76%, d.r. = 1:1.5). * shows the peaks of minor diastereomer. IR (neat) 2951, 2927, 1762, 1735, 1505, 1433, 1377, 1267, 1217, 1047, 812 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6+6*H), 1.74* (s, 3H), 1.79 (s, 3H), 2.33 (s, 3H), 2.34* (s, 3H), (m, 6+5*H), 3.28* (d, 1H, J = 17.6 Hz), 3.67* (s, 3H), 3.73 (s, 3H), 3.75 (s, 3H), 3.84* (s, 3H), 4.48 (s, 1H), 5.00* (s, 1H), (m, 2H+2H*), 7.44 (s, 1H), 7.59* (s, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 13.9, 14.5, 14.6, 21.3, 21.4, 22.8, 23.8, 24.9, 26.4, 29.5, 32.3, 41.7, 43.3, 47.6, 50.1, 50.6, 51.2, 51.9, 52.1, 52.5, 52.7, 68.8, 68.9, 127.5, 127.7, 127.9, 128.0, 128.8, 129.0, 129.1, 130.2, 136.0, 136.2, 136.4, 138.2, 168.2, 168.6, 169.6, Anal. Calcd for C 20 H 28 O 4 S 2 : C, 60.57; H, Found: C, 60.51; H, MeO CO2 Me Dimethyl 1,3-bis(ethylthio)-7-methoxy-3-methyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4c). Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 31.1 mg (82%, d.r. = 1:1.6). * shows the peaks of minor diastereomer. IR (neat) 2951, 2928, 1734, 1611, 1504, 1433, 1377, 1242, 1037, 802 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6H+6H*), 1.74* (s, 3H), 1.79 (s, 3H), (m, 6+5*H), 3.25* (d, 1H, J = 16.8 Hz), 3.67* (s, 3H), 3.74 (s, 6H), 3.76 (s, 3H), 3.80 (s, 3H), 3.81* (s, 3H), 3.84* (s, 3H), 4.47 (s, 1H), 5.01* (s, 1H), (m, 1+1*H), 6.86 (d, 1H, J = 7.6 Hz), 6.89* (d, 1H, J = 7.6 Hz), 7.21 (d, 1H, J = 2.0 Hz), S24

25 7.38* (d, 1H, J = 2.0 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 14.7, 14.8, 22.8, 23.8, 24.8, 26.4, 29.4, 32.2, 41.3, 43.0, 47.8, 50.4, 50.8, 51.4, 52.0, 52.2, 52.5, 52.7, 55.1, 68.7, 68.9, 112.9, 113.0, 113.3, 113.5, 124.6, 125.5, 128.9, 129.0, 137.9, 139.5, 158.2, 158.2, 168.2, 168.6, 169.5, Anal. Calcd for C 20 H 28 O 5 S 2 : C, 58.22; H, Found: C, 58.47; H, F CO2 Me Dimethyl 1,3-bis(ethylthio)-7-fluoro-3-methyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4d). Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1).. Yield: 33.2 mg (92%, d.r. = 1:1.5). * shows the peaks of minor diastereomer. IR (neat) 2952, 2929, 1763, 1734, 1613, 1499, 1434, 1378, 1261, 1238, 1217, 1144, 1094, 1047, 735 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6H+6H*), 1.74* (s, 3H), 1.80 (s, 3H), (m, 6+5*H), 3.26* (d, 1H, J = 17.2 Hz), 3.67* (s, 3H), 3.75 (s, 3H), 3.75 (s, 3H), 3.85* (s, 3H), 4.45 (s, 1H), 5.00* (s, 1H), (m, 2+2*H), 7.36 (dd, 1H, J = 2.0, 10.4 Hz), 7.54* (dd, 1H, J = 2.0, 10.4 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 13.8, 14.5, 14.6, 22.8, 23.8, 24.8, 26.4, 29.5, 32.2, 41.2, 43.0, 47.5, 50.0, 50.7, 51.0, 52.0, 52.2, 52.6, 52.8, 68.5, 68.6, (d, J C-F = 25.7 Hz), (d, J C-F = 25.8 Hz), (d, J C-F = 22.9 Hz), (d, J C-F = 22.9 Hz), (d, J C-F = 3.0 Hz), (d, J C-F = 2.9 Hz), (d, J C-F = 8.5 Hz), (d, J C-F = 8.6 Hz), (d, J C-F = 7.6 Hz), (d, J C-F = 7.6 Hz), (d, J C-F = Hz), 168.0, 168.5, 169.4, Anal. Calcd for C 19 H 25 FO 4 S 2 : C, 56.98; H, Found: C, 56.73; H, CO2 Me Me S25

26 Dimethyl 1,3-bis(ethylthio)-3,6-dimethyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4e). Colorless oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 29.3 mg (74%, d.r. = 1:1.5). * shows the peaks of minor diastereomer. IR (neat) 2951, 2926, 1762, 1735, 1502, 1432, 1376, 1265, 1216, 1047, 959, 821 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6H+6H*), 1.73* (s, 3H), 1.78 (s, 3H), 2.26 (s, 3H), 2.28* (s, 3H), (m, 6+5*H), 3.32* (d, 1H, J = 17.2 Hz), 3.67* (s, 3H), 3.73 (s, 6H), 3.83* (s, 3H), 4.48 (s, 1H), 4.99* (s, 1H), 6.74 (s, 1H), 6.77* (s, 1H), 7.03 (d, 1H+1H*, J = 7.6 Hz), 7.53 (d, 1H, J = 7.6 Hz), 7.65* (d, 1H, J = 7.6 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 13.9, 14.6, 14.6, 20.9, 22.8, 23.8, 24.9, 26.4, 29.3, 29.7, 32.1, 42.1, 43.7, 47.6, 49.8, 50.4, 51.0, 51.9, 52.1, 52.5, 52.7, 68.8, 68.9, 127.5, 127.8, 128.3, 128.5, 128.5, 128.6, 131.9, 133.0, 133.5, 135.4, 136.0, 136.1, 168.2, 168.6, 169.6, Anal. Calcd for C 20 H 28 O 4 S 2 : C, 60.57; H, Found: C, 60.71; H, MeO Dimethyl 1,3-bis(ethylthio)-6-methoxy-3-methyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4f). CO2 Me Colorless oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 31.3 mg (79%, d.r. = 1:1.5). * shows the peaks of minor diastereomer. IR (neat) 2951, 2928, 1734, 1610, 1500, 1432, 1377, 1271, 1237, 1216, 1048, 819 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6H+6H*), 1.74* (s, 3H), 1.78 (s, 3H), (m, 6+5*H), 3.38* (d, 1H, J = 17.2 Hz), 3.67* (s, 3H), 3.74 (s, 6H), 3.76 (s, 3H), 3.78 (s, 3H), 3.81* (s, 3H), 3.84* (s, 3H), 4.48 (s, 1H), 4.99* (s, 1H), 6.47 (d, 1H, J = 2.4 Hz), 6.51* (d, 1H, J = 2.4 Hz), 6.81 (d, 1+1*H, J = 2.4, 8.4 Hz), 7.57 (d, 1H, J = 8.4 Hz), 7.70* (d, 1H, J = 8.4 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 13.9, 14.6, 22.8, 23.8, 24.9, 26.4, 29.2, 31.9, 42.4, 44.0, 47.5, 49.5, 50.4, 50.8, 52.0, 52.1, 52.5, 52.7, 55.2, 68.8, 68.8, 112.5, 112.5, 112.7, S26

27 113.3, 128.6, 129.7, 130.0, 130.4, 133.5, 134.5, 157.9, 158.0, 168.3, 168.6, 169.6, Anal. Calcd for C 20 H 28 O 5 S 2 : C, 58.22; H, Found: C, 58.29; H, CO2 Me Dimethyl 1,3-bis(ethylthio)-3-methyl-3,4-dihydroanthracene-2,2(1H)-dicarboxylate (4g). Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 45.0 mg (99%, d.r. = 1:1.6). * shows the peaks of minor diastereomer. IR (neat) 2951, 1760, 1733, 1506, 1432, 1376, 1254, 1220, 1047, 877 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6+6*H), 1.78* (s, 3H), 1.84 (s, 3H), (m, 6+6*H), 3.28* (d, 1H, J = 17.6 Hz), 3.64* (s, 3H), 3.75 (s, 3H), 3.76 (s, 3H), 3.88* (s, 3H), 4.73 (s, 1H), 5.24* (s, 1H), (m, 5H+5H*), 8.20 (s, 1H), 8.35* (s, 1H). 13 C NMR (100 MHz, CDCl 3 ) δ 13.7, 13.8, 14.6, 14.8, 22.8, 23.8, 24.8, 26.6, 29.5, 32.1, 41.9, 43.8, 47.9, 50.6, 51.1, 51.3, 52.0, 52.2, 52.6, 52.7, 69.1, 69.3, 125.3, 125.3, 125.7, 125.7, 126.3, 126.5, 126.7, 126.8, 127.3, 127.4, 127.7, 127.8, 131.1, 132.0, 132.4, 132.5, 132.6, 132.7, 135.6, 137.2, 168.2, 168.7, 169.4, Anal. Calcd for C 23 H 28 O 4 S 2 : C, 63.86; H, Found: C, 63.95; H, CO2 Me EtS Dimethyl 3-ethyl-1,3-bis(ethylthio)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4h). Colorless oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 30.2 mg (74%, d.r. = 1:1.9). * shows the peaks of minor diastereomer. IR (neat) 2954, 2928, 1761, 1734, 1451, 1433, 1262, 1232, 1214, 1157, 1051, 785 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 9H+9H*), * (m, 1H), 2.02 S27

28 2.10* (m, 1H), (m, 8H+6H*), 3.61* (s, 3H), 3.71 (s, 3H), 3.75 (s, 3H), 3.82* (s, 3H), 4.61 (s, 1H), 5.22* (s, 1H), (m, 3H+3H*), 7.58 (d, 1H, J = 7.6 Hz), 7.84* (d, 1H, J = 7.6 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 8.6, 8.8, 13.6, 13.7, 14.4, 14.7, 23.4, 24.5, 27.4, 29.4, 29.6, 31.9, 38.2, 38.6, 51.0, 51.4, 51.9, 52.1, 52.4, 52.4, 52.7, 56.2, 69.3, 69.9, 126.5, 126.5, 126.9, 128.1, 128.1, 128.2, 128.5, 131.8, 132.9, 137.0, 138.7, 168.2, 169.1, 169.7, Anal. Calcd for C 20 H 28 O 4 S 2 : C, 60.57; H, Found: C, 60.31; H, CO2 Me Dimethyl 1,3-bis(ethylthio)-3-propyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4i). Colorless oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 20.9 mg (52%, d.r. = 1:2.0). Two diastereomers (4ia and 4ib) could be separated. For 4ia. IR (neat) 2957, 2928, 2871, 1762, 1733, 1451, 1432, 1231, 1058, 975, 746 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ 0.95 (t, 3H, J = 7.6 Hz), 1.10 (t, 3H, J = 7.6 Hz), 1.28 (t, 3H, J = 7.6 Hz), (m, 1H), (m, 2H), (m, 1H), (m, 2H), (m, 2H), (m, 1H), 3.22 (d, 1H, J = 17.2 Hz), 3.72 (s, 3H), 3.76 (s, 3H), 4.61 (s, 1H), 6.94 (d, 1H, J = 7.6 Hz), 7.10 (dd, 1H, J = 7.6, 7.6 Hz), 7.22 (dd, 1H, J = 7.6 Hz), 7.59 (d, 1H, J = 7.6 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.6, 14.4, 14.5, 17.4, 24.5, 31.9, 37.1, 38.9, 51.0, 51.9, 52.0, 52.7, 70.0, 126.5, 126.8, 128.1, 128.5, 132.0, 138.7, 168.2, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.27; H, For 4ib. IR (neat) 2957, 2928, 2871, 1732, 1451, 1432, 1246, 1047, 747 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ 0.96 (t, 3H, J = 7.6 Hz), 1.07 (t, 3H, J = 7.6 Hz), 1.28 (t, 3H, J = 7.6 Hz), (m, 2H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), 2.94 (d, 1H, J = 17.2 Hz), 3.27 (d, 1H, S28

29 J = 17.2 Hz), 3.62 (s, 3H), 3.83 (s, 3H), 5.24 (s, 1H), 6.97 (d, 1H, J = 7.6 Hz), 7.14 (dd, 1H, J = 7.6, 7.6 Hz), 7.23 (dd, 1H, J = 7.6 Hz), 7.84 (d, 1H, J = 7.6 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.7, 14.5, 14.7, 17.6, 23.5, 29.6, 39.1, 39.2, 51.3, 52.1, 52.4, 55.8, 69.4, 126.5, 126.5, 128.1, 128.3, 133.0, 136.9, 169.1, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.19; H, Dimethyl (4j). 1,3-bis(ethylthio)-3-phenyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 47.1 mg (98%, d.r. = 1:1.4). * shows the peaks of minor diastereomer. IR (neat) 2951, 2927, 1735, 1625, 1491, 1435, 1373, 1258, 1219, 1098, 1067, 982, 767 cm 1. CO2 Me Ph 1 H NMR (400 MHz, CDCl 3 ) δ (m, 6+6*H), 2.34* (s, 3H), (m, 6+5*H), 3.24* (d, 1H, J = 17.6 Hz), 3.67* (s, 3H), 3.75 (s, 6H), 3.84* (s, 3H), 4.27 (s, 1H), 5.01* (s, 1H), (m, 9H+9H*). 13 C NMR (100 MHz, CDCl 3 ) δ 13.2, 13.3, 14.4, 14.8, 22.8, 23.6, 26.3, 26.6, 30.0, 30.5, 37.4, 41.2, 51.0, 51.9, 52.1, 52.6, 56.8, 57.4, 69.5, 70.6, 126.5, 126.8, 127.4, 127.4, 128.2, 128.3, 128.3, 128.5, 128.5, 129.8, 130.2, 132.1, 134.8, 137.9, 138.1, 140.0, 140.6, 141.8, 142.5, 142.7, 167.6, 168.4, 168.8, Anal. Calcd for C 24 H 28 O 4 S 2 : C, 64.83; H, Found: C, 64.63; H, CO2 Et CO 2 Et Diethyl 1,3-bis(ethylthio)-3-methyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4l). Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 33.3 mg (81%, d.r. = 1:1.2 with 20 mol% Sc(OTf) 3 ). * shows the peaks of minor diastereomer. IR (neat) 2975, 2928, 2870, 1758, 1732, 1451, 1376, 1365, 1297, 1264, 1234, 1216, S29

30 1190, 1095, 1044, 977, 864, 778 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 12+12*H), 1.77* (s, 3H), 1.83 (s, 3H), (m, 5+5*H), 3.04 (d, 1H, J = 17.6 Hz), 3.36* (d, 1H, J = 17.6 Hz), (m, 4+4*H), 4.52 (s, 1H), 5.04* (s, 1H), 6.93 (d, 1H, J = 8.0 Hz), 6.96* (d, 1H, J = 8.0 Hz) (m, 2H+2H*), 7.64 (d, 1H, J = 8.0 Hz), 7.82* (d, 1H, J = 8.0 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 13.8, 13.9, 14.0, 14.1, 14.4, 14.6, 22.8, 23.9, 25.1, 26.4, 29.6, 29.7, 32.5, 42.0, 43.7, 47.4, 50.3, 50.7, 51.2, 61.0, 61.2, 61.7, 61.8, 68.6, 68.7, 126.3, 126.4, 126.5, 126.8, 127.9, 128.0, 128.4, 128.5, 132.1, 133.3, 137.1, 138.9, 167.6, 168.0, 169.0, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.71; H, SPr CO2 Me SPr Dimethyl 3-methyl-1,3-bis(propylthio)-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4m). Colorless oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 34.2 mg (75%, d.r. = 1:1.4). * shows the peaks of minor diastereomer. IR (neat) 2959, 2931, 2871, 1763, 1736, 1454, 1432, 1378, 1354, 1266, 1235, 1218, 1043, 746 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 10H+10H*), 1.74* (s, 3H), 1.77 (s, 3H), (m, 5+5*H), 3.07 (d, 1H, J = 17.6 Hz), 3.36 (d, 1H, J = 17.6 Hz), 3.67* (s, 3H), 3.74 (s, 3H), 3.74 (s, 3H), 3.84* (s, 3H), 4.50 (s, 1H), 5.09* (s, 1H), 6.94 (d, 1H, J = 7.6 Hz), 6.96* (d, 1H, J = 7.6 Hz), 7.11 (d, 1+1*H, J = 7.6 Hz), 7.23 (d, 1+1*H, J = 7.6 Hz), 7.66 (d, 1H, J = 7.6 Hz), 7.89* (d, 1H, J = 7.6 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 13.7, 13.7, 13.8, 13.9, 22.5, 23.0, 24.8, 26.5, 30.7, 31.7, 37.6, 40.4, 42.1, 43.7, 47.4, 50.2, 50.2, 51.4, 51.9, 52.1, 52.5, 52.7, 68.8, 69.0, 126.4, 126.5, 126.6, 126.8, 127.9, 128.1, 128.5, 128.6, 132.4, 133.3, 136.7, 138.4, 168.2, 168.6, 169.5, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.62; H, S30

31 Si-Pr CO2 Me Si-Pr Dimethyl 1,3-bis(isopropylthio)-3-methyl-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate (4n). Yellow oil (purified by preparative TLC, Hexane/EtOAc = 5/1). Yield: 24.2 mg (58%, d.r. = 1:1.1). * shows the peaks of minor diastereomer. IR (neat) 2935, 2925, 2864, 1735, 1452, 1433, 1265, 1240, 1216, 1155, 1044 cm 1. 1 H NMR (400 MHz, CDCl 3 ) δ 1.15* (d, 1H, J = 6.8 Hz), (m, 12H+9H*), 1.81 (s, 3+3*H), * (m, 4+4*H), 3.63* (s, 3H), 3.68 (s, 3H), 3.77 (s, 3H), 3.84* (s, 3H), 4.49 (s, 1H), 5.11* (s, 1H), 6.95 (d, 1+1*H, J = 7.6 Hz), 7.81 (d, 1+1*H, J = 7.6 Hz), 7.22 (d, 1+1*H, J = 7.6 Hz), 7.80 (d, 1H, J = 7.6 Hz), 7.84* (d, 1H, J = 7.6 Hz). 13 C NMR (100 MHz, CDCl 3 ) δ 23.0, 24.2, 24.4, 24.6, 25.2, 25.9, 26.2, 26.3, 27.0, 29.7, 33.7, 34.4, 38.3, 39.3, 42.5, 44.8, 49.1, 49.3, 49.8, 52.0, 52.1, 52.2, 52.4, 52.6, 69.6, 69.7, 126.4, 126.6, 126.6, 128.0, 128.4, 128.6, 128.7, 133.2, 133.3, 137.2, 137.5, 168.8, 168.9, 169.5, Anal. Calcd for C 21 H 30 O 4 S 2 : C, 61.43; H, Found: C, 61.56; H, S31

32 3. DFT calculations All calculations were performed with the Gaussian 09 package. 6 The promising pathway was investigated using the Ti-catalyzed reaction model by M06/LANL2DZ for Ti, 6-31G* for the rest with the polarizable continuum model (PCM, ClCH2CH2Cl). 7,8 Frequency analyses were also carried out to identify the stationary points (RT, INT, PD: no imaginary frequency, TS: one imaginary frequency) and to estimate thermodynamic properties at K and 1atm and Gibbs free energies. The molecular structures were depicted by using the CYLview v β. 9 After ring opening of cyclic thionium (TS2), the sequential C 1 -C 2 /C2-C3/C 4 -C 5 bond rotation would occur with lower energy barrier. At the C-C bond formation process (TS3), it should be possible to exist various diastereomeric TSs (TS3t, TS3c) leading to trans and cis adducts, respectively (Figure S1). Figure S1. The 3D structures and the relative Gibbs free energies in the pathways leading to (a) trans and (b) cis adducts S32

33 RT SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z TS1 SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z INT1 SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S33

34 TS2 SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z INT2(INT2t) SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S34

35 TS3(TS3t) SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z PD(PDt) SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z INT2c SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S35

36 TS3c SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z PDc SCF Done: E(RM06) = a.u. Sum of electronic and thermal Free Energies= a.u. Center Atomic Atomic Coordinates (Angstroms) Number Number Type X Y Z S36