Supporting Information

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Supporting Information

Polysulfuration via a Bilateral Thiamine Disulfurating Reagent

Jiahui Xue, Xuefeng Jiang*

Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai

200062, P. R. China [email protected]

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multiplicity (br = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants in Hertz (Hz), integration. Unless otherwise noted, commercially available reagents purchased from Adamas-beta, TCI, or Energy Chemical were used as received. Mass spectra were in general recorded on a Shimadzu GCMS-QP2010 Ultra and a HP 5989A mass selective detector. Column chromatography was performed with silica gel (300-400 mesh ASTM). Infrared spectrum was recorded on IRtracer-100 Series FT-IR Spectrometers.

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Synthesis and spectra data of disulfurating reagents

To a solution of (N,N’-ditosyl)-o-Phenylenediamine (5.2 g, 12.5 mmol) was added NaH (1.2 g, 30 mmol) in 250 mL of anhydrous THF under N2 in 0 °C. The solution was allowed to stirred

at rt for 30 min, then was cooled to -20 °C. A solution of S2Cl2 (1 mL, 12.5 mmol) in 100 mL

of anhydrous THF was added dropwise over 1 h. The reaction mixture was allowed to stir for a further 5 min at -20 °C. The reaction mixture was quenched with 50 mL of saturated NH4Cl

andallowed to warm to room temperature. The organic phase was washed with 3 × 20 mL of H2O. The organic phase was dried over Na2SO4. This mixture was vacuum filtered, and the

solvent was removed under vacuum. Purification of the residue by flash column chromatography (silica gel, petroleum ether /CH2Cl2 = 2:1→CH2Cl2) yielded the 1d (4.6 g,

77%) as white solid. Rf (10% EtOAc/hexanes) = 0.5.1H NMR (400 MHz, CDCl3) δ 7.94 – 7.89

(m, 2H), 7.36 – 7.29 (m, 2H), 7.15 (d, J = 8.4 Hz, 4H), 7.08 (d, J = 8.1 Hz, 4H), 2.32 (s, 6H).

13_{C NMR (101 MHz, CDCl}

3) δ 145.7, 132.0, 129.8, 129.2, 128.9, 128.8, 126.7, 21.7. IR (film)

3061, 2924, 1595, 1470, 1364, 1168, 1085, 850, 758, 667, 559. HRMS (EI) Calcd for C20H18N2O4S4 478.0149, found 478.0152.

General Procedure and spectra data of aza-trisulfides

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(20.0 mg, 0.1 mmol) in CH2Cl2 (1 mL) was added 1-adamantylthiol (16.8 mg, 0.1 mmol) in

CH2Cl2 (1 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 5 min before it was

concentrated under vacuum. Purification of the residue by column chromatography (silica gel, PE/CH2Cl2 = 4:1→2:1) afforded the desired product 2a (20.2 mg, 55%) as colorless oil. 1H

NMR (400 MHz, CDCl3) δ 7.36 (d, J = 7.5 Hz, 1H), 7.29 (dd, J = 6.7, 4.9 Hz, 2H), 7.25 – 7.20

(m, 1H), 4.94 (s, 2H), 4.66 (s, 2H), 2.01 (s, 3H), 1.83 (s, 6H), 1.60 (q, J = 12.1 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 140.0, 134.4, 130.6, 129.4, 129.0, 128.0, 63.0, 50.6, 42.8, 36.0,

29.9.IR (film) 3691, 2964, 2904, 2848, 1294, 1242, 1180, 1039, 906, 729, 684. HRMS (EI) Calcd for C18H24O2S3 368.0938, found 368.0939. The NMR data are in agreement with those

in the literature2_.

Compound 2a was prepared according to a modified literature procedure2_{: To a solution of}_1c

(37.0 mg, 0.1 mmol) in CH2Cl2 (1 mL) was added 1-adamantylthiol (16.8 mg, 0.1 mmol) in

CH2Cl2 (1 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 5 min before it was

concentrated under vacuum. Purification of the residue by column chromatography (silica gel, petroleum ether /ethyl acetate = 10:1) afforded the desired product 2c (50.5 mg, 94%) as colorless oil. Rf (10% EA/hexane) = 0.4. 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 8.0 Hz,

1H), 7.21 – 7.14 (m, 2H), 7.01 – 6.90 (m, 1H), 6.59 (s, 1H), 2.01 (s, 3H), 1.79 (d, J = 2.4 Hz, 6H), 1.65 – 1.54 (m, 6H), 1.44 (s, 9H), 1.40 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 154.7,

152.6, 134.4, 133.6, 128.5, 128.3, 123.2, 120.7, 83.6, 80.6, 50.7, 42.4, 36.0, 29.8, 28.3, 27.9. HRMS (EI) Calcd for C26H38N2O4S3 538.1994, found 538.1992.

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To a solution of 1d (47.8 mg, 0.1 mmol) in CH2Cl2 (1 mL) was added 1-adamantylthiol (20.2

mmol) in CH2Cl2 (1 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 5 min before it

was concentrated under vacuum. Purification of the residue by column chromatography (silica gel, petroleum ether /ethyl acetate = 10:1→5:1) afforded the desired product 2d (61.4 mg, 95%) as white foam. Rf (20% EA/hexane) = 0.4. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.3 Hz,

2H), 7.68 (d, J = 8.3 Hz, 2H), 7.64 (dd, J = 8.3, 1.3 Hz, 1H), 7.40 (s, 1H), 7.34 – 7.24 (m, 5H), 6.94 (td, J = 7.7, 1.4 Hz, 1H), 6.87 (dd, J = 8.0, 1.5 Hz, 1H), 2.47 (s, 3H), 2.38 (s, 3H), 2.10 (s, 3H), 1.76 (d, J = 2.4 Hz, 6H), 1.68 (dd, J = 27.6, 12.3 Hz, 6H).13_{C NMR (101 MHz, CDCl}

3) δ

145.4, 143.8, 136.8, 134.8, 134.4, 132.3, 130.1, 129.8, 129.8, 129.7, 129.0, 127.6, 124.4, 121.1, 51.0, 42.4, 35.9, 29.8, 21.8, 21.6. IR (film) 3290, 2850, 1599, 1493, 1450, 1344, 1271, 1163, 1091, 889, 846, 756, 673. HRMS (EI) Calcd for C30H34N2O4S5 646.1122, found 646.1124.

General Procedure and spectra data of unsymmetrical tetrasulfides

To a solution of 1d (57.4 mg, 0.12 mmol) in CH2Cl2 (1 mL) was added thiol (0.12 mmol) in

CH2Cl2 (1 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 5 min, then Li2CO3 (7.4

mg, 0.1 mmol) and another thiol (0.1 mmol) were added in order. The solution was allowed to warm to rt and stirred for 1 h before it was concentrated under vacuum. Purification by column chromatography afforded the desired product 3.

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The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg, 0.12

mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg, 0.1 mmol)

and p-toluenethiol (12.4 mg, 0.1 mmol) at rt for 1 h afforded compound 3a in 92% yield as a white solid by chromatography on silica gel eluting with PE. Rf (hexane)

= 0.9. 1H NMR (300 MHz, CDCl3) δ 7.55 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 2.39

(s, 3H), 2.14 (s, 3H), 1.95 (d, J = 2.9 Hz, 6H), 1.77 – 1.67 (m, 6H).13C NMR (126 MHz, CDCl3)

δ 138.6, 133.3, 130.7, 129.9, 51.0, 42.8, 36.1, 30.0, 21.3. IR (film) 2903, 2849, 1487, 1402, 1342, 1180, 1105, 1037, 970, 804, 687. HRMS (EI) Calcd for C17H22S4 354.0604, found

354.0605.

The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4

mg, 0.1 mmol) and 4-chlorothiophenol (14.5 mg, 0.1 mmol) at rt for 1 h afforded compound 3b in 85% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.8. 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.7 Hz, 2H), 7.35 (d, J

= 8.6 Hz, 2H), 2.13 (s, 3H), 1.93 (d, J = 2.8 Hz, 6H), 1.77 – 1.68 (m, 6H).13C NMR (101 MHz, CDCl3) δ 135.2, 134.4, 131.3, 129.2, 51.2, 42.8, 36.0, 30.0. IR (film) 2902, 2849, 1470, 1444,

1344, 1259, 1292, 1092, 1178, 1009, 814, 748, 684. HRMS (EI) Calcd for C16H19ClS4

374.0058, found 374.0060.

mg, 0.1 mmol) and 2-naphthalenethiol (16.0 mg, 0.1 mmol) at rt for 1 h afforded compound 3c in 89% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) =

0.8. 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.89 – 7.81 (m, 3H), 7.74 (dd, J = 8.6, 1.8 Hz,

1H), 7.57 – 7.48 (m, 2H), 2.13 (s, 3H), 1.96 (d, J = 2.5 Hz, 6H), 1.79 – 1.67 (m, 6H).13_{C NMR}

(101 MHz, CDCl3) δ 133.8, 133.4, 132.9, 129.0, 129.0, 127.8, 127.7, 127.2, 126.8, 126.6, 51.0,

42.8, 36.0, 30.0. IR (film) 3051, 2903, 2849, 1498, 1446, 1344, 1296, 1038, 851, 810, 744, 684, 638. HRMS (EI) Calcd for C20H22S4 390.0604, found 390.0604.

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The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg, 0.1

mmol) and 2-mercaptopyrimidine (11.2 mg, 0.1 mmol) t rt for 1 h afforded compound 3d in 85% yield as a pale yellow oil by chromatography on silica gel eluting with PE/EA (10:1). Rf (20% EA/hexane) = 0.3. 1H NMR (300 MHz, CDCl3) δ 8.68 (d, J = 4.8 Hz,

2H), 7.15 (t, J = 4.8 Hz, 1H), 2.12 (s, 3H), 1.95 (s, 6H), 1.77 – 1.65 (m, 6H).13C NMR (101 MHz, CDCl3) δ 170.4, 158.0, 118.3, 51.1, 42.8, 36.0, 30.0. IR (film) 2904, 2848, 1556, 1377,

1296, 1167, 769, 742. HRMS (EI) Calcd for C14H18N2S4 342.0353, found 342.0356. The NMR

data are in agreement with those in the literature2_.

mmol) and 1-Phenyl-1H-tetrazole-5-thiol (178.0 mg, 0.1 mmol) at rt for 1 h afforded compound 3f in 72% yield as a colorless gum by chromatography on silica gel eluting with PE/EA (10:1). Rf (20% EA in hexane) = 0.4.1H NMR (400 MHz, Acetone) δ 7.75

– 7.65 (m, 5H), 2.06 (s, 3H), 1.81 (d, J = 2.6 Hz, 6H), 1.74 – 1.66 (m, 6H). 13_{C NMR (101}

MHz, Acetone) δ 153.26, 133.85, 130.78, 129.86, 125.49, 51.46, 42.46, 41.99, 35.53. IR (film) 2905, 2849, 1707, 1595, 1496, 1386, 1225, 1099, 1040, 974, 760, 690. HRMS (EI) Calcd for C17H20N4S4 408.0571, found 408.0575.

mg, 0.1 mmol) and p-tert-butylbenzyl mercaptan (18.0 mg, 0.1 mmol) at rt for 1 h afforded compound 3f in 93% yield as a pale yellow oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.8. 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.3

Hz, 2H), 4.20 (s, 2H), 2.14 (s, 3H), 1.94 (d, J = 2.8 Hz, 6H), 1.79 – 1.67 (m, 6H), 1.35 (s, 9H).

13_{C NMR (101 MHz, CDCl}

3) δ 150.7, 133.4, 129.2, 125.6, 50.8, 43.6, 42.8, 36.1, 34.6, 31.4,

30.0. IR (film) 2959, 2909, 2853, 1452, 1267, 1105, 1038, 756, 684. HRMS (EI) Calcd for C H S 410.1230, found 410.1231.

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The reaction of 1d (57.4 mg, 0.12 mmol) and cyclopentanthiol (12.2 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4

mg, 0.1 mmol) and 1-propanethoil (7.6 mg, 0.1 mmol) at rt for 1 h afforded compound 3g in 85% yield as a pale yellow oil by chromatography on silica gel eluting with PE. Rf (hexane) =

0.8. 1_{H NMR (400 MHz, CDCl}

3) δ 3.68 – 3.39 (m, 1H), 2.89 – 2.83 (m, 2H), 2.05 – 1.93 (m,

2H), 1.80 – 1.65 (m, 6H), 1.62 – 1.52 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 51.1, 41.4, 33.2, 24.8, 22.4, 13.1. IR (film) 2955, 2864, 1448, 1416, 1286, 1232, 1084,

931, 895, 779, 737, 638. HRMS (EI) Calcd for C8H16S4 240.0135, found 240.0138.

The reaction of 1d (57.4 mg, 0.12 mmol) and 3-(triethoxysilyl)propane-1-thiol (28.5 mg, 0.12 mmol) in CH2Cl2 (2

mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg, 0.1 mmol) and 1-adamantylthiol (16.8 mg, 0.1

mmol) at rt for 1 h afforded compound 3h in 79% yield as a pale yellow oil by chromatography on silica gel eluting with PE/EA (50:1). Rf (2% EA/hexane) = 0.6. 1H NMR (400 MHz, CDCl3)

δ 3.76 (q, J = 7.0 Hz, 6H), 2.91 (t, J = 7.2 Hz, 2H), 2.04 (s, 3H), 1.86 (d, J = 2.6 Hz, 6H), 1.84

– 1.79 (m, 2H), 1.63 (d, J = 1.8 Hz, 6H), 1.16 (t, J = 7.0 Hz, 9H), 0.73 – 0.65 (m, 2H).13_C

NMR (101 MHz, CDCl3) δ 57.4, 49.8, 41.8, 41.3, 35.0, 29.0, 21.6, 17.3, 8.6. IR (film) 2972,

2905, 2849, 1452, 1389, 1298, 1167, 1103, 1078, 1040, 959, 790. HRMS (EI) Calcd for C19H36O3S4Si 468.1317, found 468.1322.

The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg,

0.1 mmol) and ethyl mercaptoacetate (12.0 mg, 0.1 mmol) at rt for 1 h afforded compound 3i in 83% yield as a pale yellow oil by chromatography on silica gel eluting with PE/EA (50:1→20:1). Rf (hexane) = 0.3. 1H NMR (400 MHz, CDCl3) δ 4.16 (q, J = 7.1

Hz, 2H), 3.66 (s, 2H), 2.05 (s, 3H), 1.86 (d, J = 2.8 Hz, 6H), 1.69 – 1.58 (m, 6H), 1.24 (t, J = 7.2 Hz, 3H).13C NMR (101 MHz, CDCl3) δ 167.8, 60.8, 50.1, 41.7, 40.3, 35.0, 28.9, 13.2. IR

(film) 2909, 2851, 1734, 1447, 1267, 1152, 1121, 1032, 756. HRMS (EI) Calcd for C14H22O2S4

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The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg,

0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg, 0.1

mmol) and 1-dodecanethiol (20.2 mg, 0.1 mmol) at rt for 1 h afforded compound 3j in 88% yield as a pale yellow oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.9. 1H NMR (400 MHz, CDCl3) δ 2.94 – 2.82 (m, 2H), 2.04 (s, 3H), 1.86

(d, J = 2.8 Hz, 6H), 1.70 (dt, J = 14.8, 7.2 Hz, 2H), 1.64 (d, J = 2.0 Hz, 6H), 1.39 – 1.30 (m, 2H), 1.20 (s, 16H), 0.81 (t, J = 6.8 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 50.8, 42.8, 39.5,

36.1, 31.9, 30.0, 29.7, 29.6 29.6, 29.5, 29.4, 29.2, 29.1, 28.5, 22.7, 14.1. IR (film) 2914, 2851, 1454, 1344, 1296, 1101, 1040, 972, 721, 684. HRMS (EI) Calcd for C22H40S4 432.2013, found

432.2018.

The reaction of 1d (57.4 mg, 0.12 mmol) and o-toluenethiol (14.9 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then

Li2CO3 (7.4 mg, 0.1 mmol) and 3,4-dimethoxylbenzenethiol

(17.0 mg, 0.1 mmol) at rt for 1 h afforded compound 3k in 80% yield as a pale yellow oil by chromatography on silica gel eluting with PE/EA (10:1). Rf (5% EA/hexane) = 0.4. 1H NMR

(400 MHz, CDCl3) δ 7.29 (d, J = 8.7 Hz, 2H), 7.13 (t, J = 7.6 Hz, 1H), 7.08 – 7.05 (m, 2H),

7.02 (d, J = 7.6 Hz, 1H), 6.75 – 6.68 (m, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 2.26 (s, 3H).13C NMR (101 MHz, CDCl3) δ 150.2, 149.3, 139.1, 136.0, 130.7, 129.2, 129.0, 127.2, 127.2, 125.1, 115.0,

111.4, 56.1, 56.0, 21.3. IR (film) 2953, 2837, 1582, 1398, 1255, 1136, 1024, 846, 770, 685, 600. HRMS (EI) Calcd for C15H16O2S4 356.0033, found 356.0035.

The reaction of 1d (57.4 mg, 0.12 mmol) and o-toluenethiol (14.9 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg,

0.1 mmol) and p-toluenethiol (12.4 mg, 0.1 mmol) at rt for 1 h afforded compound 3l in 80% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.8. 1H NMR (400 MHz, CDCl3) δ 7.71 (dd, J = 6.4, 3.1 Hz, 1H), 7.50

– 7.45 (m, 2H), 7.27 – 7.19 (m, 3H), 7.16 (d, J = 7.9 Hz, 2H), 2.45 (s, 3H), 2.38 (s, 3H).13C NMR (101 MHz, CDCl3) δ 139.2, 139.0, 135.0, 132.8, 132.1, 131.3, 130.6, 129.9, 128.8, 126.8,

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The reaction of 1d (57.4 mg, 0.12 mmol) and 2,5-dimethylbenzenethiol (16.6 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3

(7.4 mg, 0.1 mmol) and 1-adamantylthiol (16.8 mg, 0.1 mmol) at rt for 1 h afforded compound 3m in 89% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.9. 1H NMR (400 MHz, CDCl3) δ 7.64 (s, 1H), 7.11 (d, J = 7.7

Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 2.45 (s, 3H), 2.38 (s, 3H), 2.14 (s, 3H), 1.96 (d, J = 2.3 Hz, 6H), 1.80 – 1.69 (m, 6H).13C NMR (101 MHz, CDCl3) δ 136.4, 135.5, 134.9, 132.1, 130.3,

129.3, 50.9, 42.8, 36.1, 36.1, 30.0, 20.9, 20.1. IR (film) 2902, 2849, 1602, 1483, 1445, 1292, 1038, 974, 810, 752, 690. HRMS (EI) Calcd for C18H24S4 368.0761, found 368.0760.

The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg, 0.12

mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg, 0.1 mmol)

and 3,4-dimethylbenzenethiol (13.8 mg, 0.1 mmol) at rt for 1 h afforded compound 3n in 85% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.9. 1H NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 7.39 (dd, J = 7.8, 1.9 Hz, 1H),

7.14 (d, J = 7.9 Hz, 1H), 2.30 (s, 3H), 2.29 (s, 3H), 2.14 (s, 3H), 1.96 (d, J = 2.8 Hz, 6H), 1.77 – 1.67 (m, 6H). 13_{C NMR (101 MHz, CDCl}

3) δ 137.6, 137.3, 133.4, 131.7, 130.3, 128.0, 50.9,

42.8, 36.1, 30.0, 19.8, 19.5. IR (film) 2906, 2851, 1483, 1446, 1296,1182, 1036, 810, 756, 690. HRMS (EI) Calcd for C18H24S4 368.0761, found 368.0764.

The reaction of 1d (57.4 mg, 0.12 mmol) and p-toluenethiol (14.9 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg,

0.1 mmol) and cyclopentylthiol (10.2 mg, 0.1 mmol) at rt for 1 h afforded compound 3o in 83% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.9. 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.2 Hz, 2H), 7.09 (d, J

= 7.9 Hz, 2H), 3.33 (tt, J = 7.3, 5.4 Hz, 1H), 2.28 (s, 3H), 1.99 – 1.88 (m, 2H), 1.73 – 1.60 (m, 4H), 1.57 – 1.49 (m, 2H).13_{C NMR (101 MHz, CDCl}

3) δ 138.7, 133.3, 130.7, 129.9, 51.3, 33.2,

24.7, 21.2. IR (film) 3022, 2953, 2862, 1487, 1445, 1236, 1182, 1018, 935, 804, 756, 698. HRMS (EI) Calcd for C H S 288.0135, found 288.0137.

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The reaction of 1d (57.4 mg, 0.12 mmol) and 1-adamantylthiol (20.2 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then

Li2CO3 (7.4 mg, 0.1 mmol) and 1,3-propyldimercaptan (5.4 mg, 0.05 mmol) at rt for 1 h

afforded compound 3p in 73% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.5.1H NMR (400 MHz, CDCl3) δ 3.02 (t, J = 6.9 Hz, 4H), 2.25 (p, J =

6.9 Hz, 2H), 2.05 (s, 6H), 1.86 (d, J = 2.7 Hz, 12H), 1.69 – 1.57 (m, 12H).13C NMR (101 MHz, CDCl3) δ 51.0, 42.8, 37.4, 36.0, 30.0, 28.1. IR (film) 2901, 2846, 1450, 1342, 1296, 1180, 1038,

821, 684. HRMS (EI) Calcd for C23H36S8 568.0583, found 568.0590.

The reaction of 1d (57.4 mg, 0.12 mmol) and 1-propanethiol (9.1 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg,

0.1 mmol) and allyl mercaptan (7.4 mg, 0.1 mmol) at rt for 1 h afforded compound 3q in 75% yield as a colorless oil by chromatography on silica gel eluting with PE. Rf (hexane) = 0.8. 1H

NMR (400 MHz, CDCl3) δ 5.91 – 5.67 (m, 1H), 5.18 (dd, J = 21.3, 5.5 Hz, 2H), 3.52 (d, J =

7.3 Hz, 2H), 2.86 (t, J = 7.2 Hz, 2H), 1.83 – 1.63 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H).13_{C NMR}

(101 MHz, CDCl3) δ 132.6, 119.5, 42.1, 41.4, 22.4, 13.1 IR (film) 3082, 2961, 2928, 2871,

1634, 1454, 1377, 1288, 1074, 1034, 984, 918, 858, 781, 719, 578. HRMS (EI) Calcd for C6H12S4 211.9822, found 211.9822. The NMR data are in agreement with those in the

literature2

The reaction of 1d (57.4 mg, 0.12 mmol) and methyl 2-acetamido-3-mercapto-3-methylbutanoate (24.0 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3 (7.4

mg, 0.1 mmol) and methyl acetylcysteinate (17.8 mg, 0.1 mmol) at rt for 1 h afforded compound 3r in 87% yield as a white soid by chromatography on silica gel eluting with PE/EA (2:1). Rf (30% EA in hexane) = 0.3. H NMR (400 MHz, CDCl3) δ 6.52 (dd, J = 15.2, 8.0 Hz,

2H), 4.88 (dd, J = 12.4, 5.3 Hz, 1H), 4.73 (d, J = 8.7 Hz, 1H), 3.72 (s, 3H), 3.69 (s, 3H), 3.40 (ddd, J = 42.6, 14.3, 5.3 Hz, 2H), 2.01 (s, 3H), 2.01 (s, 3H), 1.42 (s, 3H), 1.38 (s, 3H). 13C NMR

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23.1, 23.1. IR (film) 3294, 2949, 1740, 1645, 1529, 1435, 1371, 1215, 1126, 1032, 982, 659, 584. HRMS (ESI) Calcd for C14H25N2O6S4 (M+H+) 445.0590, found 445.0594. The NMR data

are in agreement with those in the literature2

0.1 mmol) and glucosinolate (36.4 mg, 0.1 mmol) at rt for 1 h afforded compound 3t in 82% yield as a viscous gel by chromatography on silica gel eluting with PE/EA (2:1). Rf (30% EA in hexane) = 0.3. 1H NMR (400 MHz, CDCl3) δ 5.27 – 5.04 (m, 3H), 4.73

(d, J = 9.5 Hz, 1H), 4.23 (dd, J = 12.4, 4.7 Hz, 1H), 4.13 (dd, J = 12.4, 2.2 Hz, 1H), 3.73 (ddd,

J = 9.9, 4.5, 2.3 Hz, 1H), 2.06 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H), 1.97 (s, 3H), 1.95 (s, 3H), 1.85 (d, J = 2.3 Hz, 6H), 1.69 – 1.59 (m, 6H). 13_{C NMR (100 MHz, CDCl}

3) δ 170.6, 170.2,

169.3, 169.2, 88.2, 76.3, 73.9, 69.7, 68.0, 62.0, 51.1, 42.7, 36.0, 29.9, 20.8, 20.8, 20.7, 20.7, 20.6, 20.6. IR (film) 2906, 2851, 1747, 1452, 1365, 1298, 1211, 1035, 912, 737, 684, 598. HRMS (ESI) Calcd for C24H34O9S4Na (M+Na+) 617.0978, found 617.0970. The NMR data are

in agreement with those in the literature2

The reaction of 1d (57.4 mg, 0.12 mmol) and p-toluenethiol (14.9 mg, 0.12 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then Li2CO3

(7.4 mg, 0.1 mmol) and glucosinolate (36.4 mg, 0.1 mmol) at rt for 1 h afforded compound 3t in 77% yield as a viscous gel by chromatography on silica gel eluting with PE/EA (2:1). Rf (30% EA in hexane) = 0.3.1H NMR (500 MHz, CDCl3) δ 7.55 (d,

J = 7.8 Hz, 2H), 7.23 (d, J = 7.5 Hz, 2H), 5.23 (d, J = 9.2 Hz, 1H), 5.17 (dd, J = 19.0, 9.5 Hz, 2H), 4.70 (d, J = 9.8 Hz, 1H), 4.32 (dd, J = 12.3, 4.5 Hz, 1H), 4.18 (dd, J = 25.8, 9.6 Hz, 1H), 3.77 (d, J = 8.2 Hz, 1H), 2.41 (s, 3H), 2.12 (s, 3H), 2.09 – 2.03 (m, 9H).13C NMR (126 MHz, CDCl3) δ 170.7, 170.2, 169.4, 169.2, 139.3, 132.8, 131.1, 130.2, 88.2, 76.3, 73.7, 69.7, 68.0,

61.9, 21.2, 20.8, 20.7, 20.6, 20.6. IR (film) 2949, 1749, 1371, 1219, 1045, 908, 808, 557. HRMS (ESI) Calcd for C H O S Na 573.0352, found 573.0358.

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Scale-up reaction:

To a solution of 1d (2.64 g, 5.5 mmol) in CH2Cl2 (50 mL) was added 1-adamantylthiol (924

mg, 5 mmol) in CH2Cl2 (50 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 10 min,

then Li2CO3 (370 mg, 5 mmol) and p-toluenethiol (620 mg, 5 mmol) were added in order. The

solution was allowed to warm to rt and stirred for 2 h before it was concentrated under vacuum. Purification by column chromatography afforded the desired product 3a (1.59 g, 90%) as white solid.

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General Procedure and spectra data of unsymmetrical trisulfides

CH2Cl2 (1 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 5 min, then DMAP (12.2

mg, 0.1 mmol) and β-keto esters (0.1 mmol) were added in order. The solution was allowed to warm to rt and stirred for 1 h before it was concentrated under vacuum. Purification by column chromatography afforded the desired product 4.

The reaction of 1d (47.8 mg, 0.1 mmol) and 1-adamantylthiol (16.8 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then DMAP (12.2 mg, 0.1

mmol) and β-keto esters (19.0 mg, 0.1 mmol) at rt for 1 h afforded compound 4a in 89% yield as a pale yellow oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.4. 1H NMR (500 MHz, CDCl3) δ 7.86 (d, J

= 7.7 Hz, 1H), 7.70 (td, J = 7.6, 1.0 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 4.09 (d, J = 18.0 Hz, 1H), 3.84 (s, 3H), 3.80 (d, J = 18.0 Hz, 1H), 2.11 (s, 3H), 1.89 (d, J = 2.6 Hz, 6H), 1.74 – 1.64 (m, 6H). 13C NMR (126 MHz, CDCl3) δ 196.7, 168.4, 151.8, 135.9, 128.1,

126.2, 125.4, 65.3, 53.7, 51.2, 42.4, 38.8, 36.0, 29.8. IR (film) 2905, 2849, 1715, 1601, 1452, 1432, 1242, 1177, 1090, 1032, 960, 744, 692. HRMS (EI) Calcd for C21H24O3S3 420.0888,

(16)

The reaction of 1d (47.8 mg, 0.1 mmol) and 1-adamantylthiol (16.8 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then DMAP (12.2

mg, 0.1 mmol) and β-keto esters (22.0 mg, 0.1 mmol) at rt for 1 h afforded compound 4b in 90% yield as a pale yellow oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.3. 1H NMR (500 MHz, CDCl3)

δ 7.42 (dd, J = 8.1, 0.6 Hz, 1H), 7.31 – 7.29 (m, 1H), 7.28 (q, J = 2.5 Hz, 1H), 3.99 (d, J = 17.8 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.72 (d, J = 17.8 Hz, 1H), 2.11 (s, 3H), 1.90 (d, J = 2.6 Hz, 6H), 1.75 – 1.65 (m, 6H).13_{C NMR (126 MHz, CDCl}

3) δ 196.7, 168.5, 159.9, 144.8, 135.9,

126.8, 125.5, 106.2, 66.0, 55.7, 53.7, 51.2, 42.4, 38.3, 36.0, 29.8. IR (film) 2907, 2849, 1712, 1616, 1491, 1433, 1269, 1230, 1167, 1028, 966, 732, 586. HRMS (EI) Calcd for C22H26O4S3

450.0993, found 450.0997.

The reaction of 1d (47.8 mg, 0.1 mmol) and 1-adamantylthiol (16.8 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then DMAP

(12.2 mg, 0.1 mmol) and β-keto esters (20.4 mg, 0.1 mmol) at rt for 1 h afforded compound 4c in 90% yield as a colorless oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.3. 1H NMR (500 MHz, CDCl3)

δ 7.65 (s, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.42 (d, J = 7.8 Hz, 1H), 4.02 (d, J = 17.9 Hz, 1H), 3.83 (s, 3H), 3.75 (d, J = 17.9 Hz, 1H), 2.45 (s, 3H), 2.11 (s, 3H), 1.90 (d, J = 2.5 Hz, 6H), 1.75 – 1.65 (m, 6H). 13_{C NMR (126 MHz, CDCl}

3) δ 196.8, 168.5, 149.2, 138.2, 137.2, 134.9, 125.8,

125.2, 65.7, 53.6, 51.2, 42.4, 38.6, 36.0, 29.8, 21.1. IR (film) 2906, 2849, 1713, 1610, 1465, 1220, 1168, 1031, 965, 722, 680. HRMS (EI) Calcd for C22H26O3S3 434.1044, found 434.1042.

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The reaction of 1d (47.8 mg, 0.1 mmol) and cyclopentylthiol (10.2 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then DMAP

(12.2 mg, 0.1 mmol) and β-keto esters (20.4 mg, 0.1 mmol) at rt for 1 h afforded compound 4d in 85% yield as a colorless oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.3. 1_{H NMR (400 MHz, CDCl}

3) δ 7.54 (s, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H),

3.92 (d, J = 17.8 Hz, 1H), 3.73 (s, 3H), 3.63 (d, J = 17.9 Hz, 1H), 3.40 – 3.31 (m, 1H), 2.34 (s, 3H), 1.95 – 1.85 (m, 2H), 1.68 – 1.56 (m, 4H), 1.52 – 1.46 (m, 2H).13_{C NMR (101 MHz,}

CDCl3) δ 196.5, 168.5, 149.1, 138.2, 137.2, 134.8, 125.8, 125.2, 65.4, 53.6, 51.2, 38.4, 32.9,

32.8, 24.7, 24.6, 21.1. IR (film) 2953, 1737, 1717, 1431, 1279, 1244, 1174, 1031, 817, 686. HRMS (EI) Calcd for C17H20O3S3 368.0575, found 368.0580.

The reaction of 1d (47.8 mg, 0.1 mmol) and 1-dodecanethiol (20.2 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then

DMAP (12.2 mg, 0.1 mmol) and β-keto esters (20.4 mg, 0.1 mmol) at rt for 1 h afforded compound 4e in 73% yield as a colorless oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.3. 1H NMR (400

MHz, CDCl3) δ 7.55 (s, 1H), 7.41 (d, J = 7.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 1H), 3.92 (d, J =

17.9 Hz, 1H), 3.73 (s, 3H), 3.61 (d, J = 18.0 Hz, 1H), 2.83 – 2.69 (m, 2H), 2.35 (s, 3H), 1.58 (dt, J = 14.8, 7.2 Hz, 2H), 1.22 – 1.16 (m, 18H), 0.81 (t, J = 6.8 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 196.4, 168.4, 149.0, 138.3, 137.2, 134.7, 125.8, 125.2, 65.2, 53.6, 39.4, 38.4, 31.9,

29.6, 29.6, 29.5, 29.3, 29.1, 28.7, 28.4, 22.7, 21.1, 14.1. IR (film) 2924, 2853, 1719, 1458, 1248, 1178, 966, 819, 754. HRMS (EI) Calcd for C24H36O3S3 468.1827, found 468.1835.

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The reaction of 1d (47.8 mg, 0.1 mmol) and 2-naphthyl thiol (16.0 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then

DMAP (12.2 mg, 0.1 mmol) and β-keto esters (20.4 mg, 0.1 mmol) at rt for 1 h afforded compound 4f in 82% yield as a colorless oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.3. 1H NMR (400

MHz, CDCl3) δ 7.88 (d, J = 1.4 Hz, 1H), 7.71 (ddd, J = 12.8, 6.7, 2.4 Hz, 3H), 7.49 (dd, J =

8.6, 1.9 Hz, 1H), 7.46 (s, 1H), 7.44 – 7.39 (m, 2H), 7.31 (dd, J = 7.8, 1.1 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 3.85 (d, J = 17.9 Hz, 1H), 3.70 (s, 3H), 3.52 (d, J = 17.9 Hz, 1H), 2.30 (d, J = 8.9 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 196.3, 168.3, 148.8, 138.3, 137.2, 134.5, 133.5, 133.4,

133.0, 130.3, 129.1, 127.9, 127.9, 127.8, 126.9, 126.8, 125.7, 125.2, 65.5, 53.7, 38.6, 21.1. IR (film) 3051, 2953, 1713, 1584, 1493, 1429, 1246, 1180, 1024, 966, 816, 746, 689. HRMS (EI) Calcd for C22H18O3S3 426.0418, found 426.0422.

The reaction of 1d (47.8 mg, 0.1 mmol) and p-toluenethiol (12.4 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then DMAP

(12.2 mg, 0.1 mmol) and β-keto esters (20.4 mg, 0.1 mmol) at rt for 1 h afforded compound 4g in 80% yield as a colorless oil by chromatography on silica gel eluting with PE/CH2Cl2 (1:1). Rf (50% CH2Cl2 in hexane) = 0.3. 1H NMR (400 MHz, CDCl3)

δ 7.54 (s, 1H), 7.40 (dd, J = 7.8, 1.2 Hz, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 7.8 Hz, 1H), 7.05 (d, J = 8.0 Hz, 2H), 3.88 (d, J = 18.0 Hz, 1H), 3.73 (s, 3H), 3.56 (d, J = 17.9 Hz, 1H), 2.35 (s, 3H), 2.27 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 191.13, 163.1, 143.8, 134.0, 133.1, 132.0,

129.4, 127.7, 126.4, 124.8, 120.6, 120.1, 60.2, 48.5, 33.4, 16.0, 15.9. IR (film) 2951, 2922, 1711, 1616, 1583, 1489, 1427, 1244, 1176, 1078, 1020, 964, 808, 731, 690. HRMS (EI) Calcd for C19H18O3S3 390.0418, found 390.0422.

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The reaction of 1d (47.8 mg, 0.1 mmol) and methyl 2-acetamido-3-mercapto-3-methylbutanoate (20.0 mg, 0.1 mmol) in CH2Cl2 (2 mL) at 0 °C for 5 min, then DMAP (12.2 mg, 0.1

mmol) and β-keto esters (20.4 mg, 0.1 mmol) at rt for 1 h afforded compound 4h in 74% yield as a white solid by chromatography on silica gel eluting with PE/EA (2:1). Rf (50% EA in

hexane) = 0.3. diastereomeric ratio = 1:1. Isomer A: 1H NMR (500 MHz, CDCl3) δ 7.66 (s,

1H), 7.53 (d, J = 5.6 Hz, 1H), 7.43 (d, J = 3.8 Hz, 1H), 6.38 (d, J = 8.2 Hz, 1H), 4.71 (d, J = 8.8 Hz, 1H), 4.03 (d, J = 6.8 Hz, 1H), 3.84 (s, 3H), 3.76 (s, 3H), 3.67 (d, J = 3.3 Hz, 1H), 2.46 (s, 3H), 2.13 (s, 3H), 1.44 (s, 6H). 13C NMR (126 MHz, CDCl3) δ 196.9, 170.4, 170.3, 168.4,

149.2, 138.5, 137.4, 134.7, 125.9, 125.3, 65.5, 58.9, 53.8, 53.8, 52.4, 38.6, 26.4, 25.1, 23.2, 21.2. Isomer B: 1H NMR (501 MHz, CDCl3) δ 7.64 (s, 1H), 7.52 (d, J = 5.6 Hz, 1H), 7.41 (d,

J = 3.9 Hz, 1H), 6.33 (d, J = 8.7 Hz, 1H), 4.69 (d, J = 8.3 Hz, 1H), 3.99 (d, J = 6.8 Hz, 1H), 3.82 (s, 3H), 3.76 (s, 3H), 3.64 (d, J = 3.3 Hz, 1H), 2.46 (s, 3H), 2.05 (s, 3H), 1.44 (s, 6H). 13C NMR (126 MHz, CDCl3) δ 196.2, 170.4, 170.0, 168.3, 148.9, 138.4, 137.3, 134.6, 125.8, 125.3,

65.2, 58.7, 53.8, 53.7, 52.3, 38.5, 26.3, 25.0, 23.2, 21.1. IR (film) 3302, 2957, 1736, 1663, 1524, 1433, 1369, 1248, 1166, 1118, 1020, 914, 731, 688, 642, 586. HRMS (EI) Calcd for C20H25NO6S3 471.0844, found 471.0850.

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General Procedure and spectra data of unsymmetrical aza-trisulfides

CH2Cl2 (1 mL) dropwise at 0 °C. The mixture was stirred at 0 °C for 5 min, then Li2CO3 (7.4

mg, 0.1 mmol), B(C6F5)3 (2.5 mg, 5 mol%) and amine (0.1 mmol) were added in order. The

solution was allowed to warm to rt and stirred for 8 h before it was concentrated under vacuum. Purification by column chromatography afforded the desired product 5.

0.1 mmol), B(C6F5)3 (2.5 mg, 5 mol%) and 4-chloro-aniline (12.8 mg, 0.1 mmol) at rt for 8 h

afforded compound 5a in 85% yield as a white solid by chromatography on silica gel eluting with PE/CH2Cl2 (5:1). Rf (5% EA in hexane) = 0.3. 1H NMR (400 MHz, CD3CN) δ 7.32 – 7.24

(m, 2H), 7.19 – 7.09 (m, 2H), 6.71 (s, 1H), 2.08 (s, 3H), 1.88 (d, J = 2.6 Hz, 6H), 1.70 (q, J = 12.3 Hz, 6H). 13_{C NMR (101 MHz, CD}

3CN) δ 144.9, 129.6, 126.2, 118.5, 50.3, 43.1, 36.2,

30.5. IR (film) 2906, 1591, 1487, 1228, 1093, 891, 819, 659. HRMS (EI) Calcd for C16H20ClNS3 357.0446, found 357.0437. The NMR data are in agreement with those in the

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mmol), B(C6F5)3 (2.5 mg, 5 mol%) and 2,2-diphenylethylamine (19.7 mg, 0.1 mmol) at rt for

8 h afforded compound 5b in 78% yield as a colorless oil by chromatography on silica gel eluting with PE/EA (20:1). Rf (5% EA in hexane) = 0.4. 1H NMR (400 MHz, Acetone-d6) δ

7.36 – 7.27 (m, 8H), 7.22 – 7.16 (m, 2H), 4.46 (t, J = 7.8 Hz, 1H), 3.72 (dd, J = 7.8, 5.3 Hz, 2H), 2.07 (s, 3H), 1.88 (d, J = 2.8 Hz, 6H), 1.71 (p, J = 12.6 Hz, 6H). 13C NMR (101 MHz, Acetone-d6) δ 142.8, 128.4, 128.2, 126.4, 55.4, 50.4, 49.3, 42.6, 35.8, 29.9. IR (film) 3321,

2906, 2848, 1595, 1448, 736, 1257, 1186, 1070, 1034, 736, 696. HRMS (EI) Calcd for C24H29NS3 427.1462, found 427.1465.

mg, 0.1 mmol), B(C6F5)3 (2.5 mg, 5 mol%) and methyl L

-tryptophanate (21.8 mg, 0.1 mmol) at rt for 24 h afforded compound 5c in 90% yield as a white solid by chromatography on silica gel eluting with PE/EA (5:1). Rf (20% EA in hexane) = 0.3. 1_{H NMR (400 MHz, Acetone-d}

6) δ 10.06 (s, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.42 – 7.35 (m, 1H),

7.18 (d, J = 2.2 Hz, 1H), 7.12 – 7.07 (m, 1H), 7.05 – 7.01 (m, 1H), 4.14 – 4.07 (m, 1H), 3.62 (s, 3H), 3.25 (ddd, J = 6.5, 3.8, 0.5 Hz, 2H), 2.07 – 2.04 (m, 3H), 1.86 (d, J = 2.8 Hz, 6H), 1.76 – 1.63 (m, 6H). 13_{C NMR (101 MHz, Acetone-d}

6) δ 172.8, 136.7, 127.7, 123.6, 121.3, 118.7,

118.4, 111.3, 109.8, 64.8, 64.7, 51.3, 49.4, 42.6, 35.8, 29.9. IR (film) 3406, 2907, 2849, 1732, 1447, 1340, 1207, 1178, 1095, 816, 735, 696, 586. HRMS (EI) Calcd for C22H28N2O2S3

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Li2CO3 (7.4 mg, 0.1 mmol), B(C6F5)3 (2.5 mg, 5 mol%) and

methyl L-alanyl-L-leucinate (21.6 mg, 0.1 mmol) at rt for 24 h afforded compound 5d in 82% yield as a colorless gum by chromatography on silica gel eluting with PE/EA (5:1). Rf (20% EA in hexane) = 0.3.1H NMR (400 MHz, Acetone-d6) δ 7.44 (s,

1H), 4.84 (s, 1H), 4.59 – 4.42 (m, 1H), 3.84 – 3.78 (m, 1H), 3.68 (s, 3H), 2.08 (s, 3H), 1.88 (d,

J = 2.8 Hz, 6H), 1.80 – 1.75 (m, 1H), 1.72 (s, 6H), 1.66 – 1.58 (m, 2H), 1.38 (d, J = 6.9 Hz, 3H), 0.93 (dd, J = 6.6, 2.1 Hz, 6H).13_{C NMR (101 MHz, Acetone-d}

6) δ 178.0, 177.8, 65.2,

56.6, 55.7, 54.4, 47.8, 45.9, 41.0, 35.1, 29.8, 27.6, 26.3, 24.1. IR (film) 3302, 2907, 2851, 1742, 1657, 1522, 1445, 1250, 1151, 1037, 972, 738, 692, 634. HRMS (EI) Calcd for C20H34N2O3S3

446.1732, found 446.1735.

Li2CO3 (7.4 mg, 0.1 mmol), B(C6F5)3 (2.5 mg, 5 mol%) and

cinacalcet3 (42.9 mg, 0.1 mmol) at rt for 8 h afforded compound 5e in 90% yield as a colorless gum by chromatography on silica gel eluting with PE/EA (20:1). Rf (5% EA in hexane) = 0.5. 1H NMR (400 MHz, Acetone-d6) δ 8.20 (d, J = 8.5 Hz, 1H), 7.97

– 7.90 (m, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.57 – 7.53 (m, 1H), 7.48 (ddd, J = 16.3, 11.8, 4.8 Hz, 3H), 7.39 (d, J = 7.7 Hz, 1H), 7.36 (s, 1H), 7.25 – 7.16 (m, 1H), 5.14 (d, J = 4.6 Hz, 1H), 3.07 (s, 2H), 2.41 (s, 2H), 2.07 (s, 2H), 2.02 – 1.95 (m, 2H), 1.89 (d, J = 2.7 Hz, 6H), 1.79 (d, J = 6.8 Hz, 3H), 1.75 – 1.66 (m, 6H).19F NMR (376 MHz, Acetone) δ -57.73. 13_{C NMR (101 MHz, Acetone-d}

6) δ 148.7, 143.3, 139.4, 137.3, 136.9, 135.1 (q, 2JCF

= 31.5 Hz), 134.2, 134.0, 133.4, 131.2, 130.7, 130.4, 130.0, 129.9 (q, 3_J

CF = 3.7 Hz), 129.7 (q,

1_J

CF = 271.6 Hz), 129.1, 127.6 (q, 3JCF = 3.8 Hz), 55.0, 47.7, 41.0, 37.4, 36.1, 36.0, 35.1, 33.9,

31.8. IR (film) 3375, 2911, 2851, 1703, 1601, 1448, 1327, 1253, 1165, 1123, 787, 736, 698. HRMS (EI) Calcd for C32H36F3NS3 587.1962, found 587.1970.

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The reaction of 1d (57.4 mg, 0.1 mmol) and 4-ethylbenzenethiol (13.8 mg, 0.1 mmol) in CH2Cl2

(2 mL) at 0 °C for 5 min, then Li2CO3 (7.4 mg, 0.1

mmol), B(C6F5)3 (2.5 mg, 5 mol%) and peptide (36.3 mg, 0.1 mmol) at rt for 24 h afforded

compound 5f in 68% yield as a white solid by chromatography on silica gel eluting with CH2Cl2/MeOH (50:1). Rf (1% MeOH in CH2Cl2) = 0.3. 1H NMR (300 MHz, Acetone-d6) δ

7.57 – 7.45 (m, 4H), 7.33 – 7.19 (m, 7H), 4.53 (dq, J = 12.3, 7.4 Hz, 2H), 4.00 – 3.93 (m, 1H), 3.69 (s, 3H), 3.01 (ddd, J = 21.8, 13.9, 6.6 Hz, 2H), 2.66 (q, J = 7.6 Hz, 2H), 1.73 (tt, J = 12.8, 6.5 Hz, 1H), 1.61 (t, J = 7.2 Hz, 2H), 1.32 (d, J = 7.0 Hz, 4H), 1.21 (t, J = 7.6 Hz, 3H), 0.92 (dd, J = 6.4, 4.2 Hz, 6H). 13_{C NMR (101 MHz, Acetone-d}

6) δ 172.7, 171.8, 171.0, 144.9, 137.3,

134.0, 130.7, 129.5, 128.8, 128.2, 126.5, 66.4, 51.4, 50.6, 48.4, 40.6, 39.2, 28.2, 24.5, 22.4, 21.0, 17.8, 15.0. IR (film) 3300, 2958,1741, 1637, 1442, 1205, 1161, 930, 750, 700, 655. HRMS (EI) Calcd for C27H37N3O4S3 563.1946, found 563.1952.

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Comparison of ring tension release between different reagents with DFT

DFT (RB3LYP):

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ΔE = -2447.432518 – (-1820.185579 – 627.197289) = -0.04965 Hatree = -31.2 kcal

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X-ray Crystallography Analysis

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Reference

[1] Fieser, L. F. & Fieser, M. Reagents for organic synthesis; John Wiley and Sons, Inc.: New York, 1967; Vol. 1; p. 1122.

[2] Xue, J.; Jiang, X. Nature. Commun. 2020, 11, 4170. [3] Kramer, S. Org. Lett.2019, 21, 65.

Supporting Information