Experimental Procedures for Chapter 2 - Experimental Procedures

Chapter 5: Experimental Procedures

5.3. Experimental Procedures for Chapter 2

Survey of Achiral Lewis Bases (Table 4)

General Procedure 1

An oven-dried, 5-mm NMR tube was charged with N-phenylthiophthalimide (56, 1.2 equiv) in a glovebox and capped with a septum. Outside of the glovebox, 5-phenyl-4-penten-1-ol (57a), the indicated amount of catalyst and 0.62 mL of CDCl3 was added and the mixture was shaken well. Subsequently, the corresponding amount of acid was added and the mixture was shaken again. Spectra were recorded at 3 h and 24 h time points. Conversion to product was measured by the appearance of the diagnostic 1H NMR resonance for the product at 4.14 ppm with respect to the substrate peaks at 6.23 ppm and 3.72 ppm. Generally, no other products were observed in the 1H NMR spectra. Formation of phthalimide byproduct was visually confirmed by the precipitation out of the solution.

Data for 58a: 1 H NMR: (500 MHz, CDCl3) 7.32 (m, 2 H, H(C-aryl)), 7.28 – 7.16 (m, 3 H, H(C-aryl)), 7.14 – 7.03 (m, 5 H, H(C-aryl)), 4.14 (d, J = 10.1 Hz, 1 H, HC(2)), 4.09 – 4.00 (m, 1 H, HC(6)), 3.53 (td, J = 11.9, 2.2 Hz, 1 H, HC(6)), 3.20 (ddd, J = 11.5, 10.2, 4.0 Hz, 1 H, HC(3)), 2.32 – 2.17 (m, 1 H, HC(4)), 1.93 – 1.73 (m, 1 H, HC(5)), 1.66 (m, 2 H, HC(4), HC(5)).

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (9.9 mg, 0.062 mmol), THT (Tetrahydrothiophene, 1.2 µL, 0.013 mmol, 0.22 equiv) and CDCl3 (0.62 mL). Trifluoroacetic acid (4.7 µL, 0.061 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 33% and 70% conversion after 3 h and 24 h respectively.

Sulfenocyclization with Tetrahydrothiophene and MsOH (Table 4 Entry 2) [DJK-3-34B]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (9.7 mg, 0.062 mmol), THT (1.2 µL, 0.013 mmol, 0.23 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.061 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 100% conversion after 3 h.

Background Sulfenofunctionalization with TFA (Table 4 Entry 3) [DJK-3-34D]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.2 mg, 0.063 mmol) and CDCl3 (0.62 mL). Trifluoroacetic acid (4.7 µL, 0.061 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed no conversion after 24 h.

Background Sulfenofunctionalization with MsOH (Table 4 Entry 4) [DJK-3-34E]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.0 mg, 0.062 mmol) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed trace and 10% conversion after 3 and 24 h respectively.

Sulfenofunctionalization with 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinthione (DMPU(S)) (Table 4 Entry 5) [DJK-3-25-M]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.2 mg, 0.063 mmol), 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)- pyrimidinethione (1.9 mg, 0.013 mmol, 0.21 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 7% and 55% conversion after 3 and 24 h respectively.

Sulfenofunctionalization with Triphenylphosphine sulfide (Table 4 Entry 6) [DJK-3-25-G]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.2 mg, 0.063 mmol), triphenylphosphine sulfide (3.63 mg, 0.012 mmol, 0.20 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 100% conversion after 3 h.

Sulfenofunctionalization with Tricyclohexylphosphine sulfide (Table 4 Entry 7) [DJK-3- 25-L]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.1 mg, 0.062 mmol), tricyclohexylphosphine sulfide (3.89 mg, 0.012 mmol, 0.20 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 100% conversion after 3 h.

Sulfenofunctionalization with Hexamethylphosphoramide (Table 4 Entry 8) [DJK-3-25-I]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.1 mg, 0.062 mmol), hexamethylphosphoramide (2.1 µL, 0.012 mmol, 0.20 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 0% conversion after 24 h.

Sulfenofunctionalization with Hexamethylsulfenophosphoramide (Table 4 Entry 9) [DJK- 3-25-H]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (9.8 mg, 0.061 mmol), hexamethylthiophosphoramide (2.42 mg, 0.012 mmol, 0.2 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 35% conversion after 24 h.

Sulfenofunctionalization with Hexamethylselenophosphoramide (Table 4 Entry 10) [DJK- 3-25-J]

Following General Procedure 1, an oven-dried NMR tube was charged with 56 (20 mg, 0.078 mmol 1.2 equiv), 57a (10.2 mg, 0.063 mmol), hexamethylselenophosphoramide (3.06 mg, 0.012 mmol, 0.2 equiv) and CDCl3 (0.62 mL). Methanesulfonic acid (4.0 µL, 0.062 mmol, 1.0 equiv) was added and the tube was shaken well. Spectral analysis revealed 31% and 100% conversion after 3 and 24 h respectively.

Survey of Chiral, Nonracemic Lewis Bases for Sulfenofunctionalization

Preparation of Catalysts for Table 5:

Preparation of (R)-4-(Azepan-1-yl)-3,5-dimethyl-4,5-dihydro-3H-dinaphtho[2,1-d:1',2'-

f][1,3,2]diazaphosphepine-4-selenide (62b) [DJK-2-27]

To a flame-dried, 50-mL Schlenk flask equipped with a magnetic stir bar and septum were added amine 65 (1.048 g, 3.35 mmol) and anhydrous toluene (10.0 mL) via syringe under argon. The solvent was removed under high vacuum (30 °C, 0.05 mm Hg) for 30 min. Anhydrous THF (30.0 mL) and Et3N (1.167 mL, 8.38 mmol, 2.5 equiv) were added via syringe and the homogeneous mixture was cooled to 0 °C. Phosphorus trichloride (880 µL, 10.0 mmol, 3.0 equiv) was added dropwise via syringe whereupon a colorless precipitate formed immediately. The reaction mixture was stirred at 0 °C for 1.5 h, then was allowed to warm to room temperature and was stirred for another 3 h. The volatiles were removed under high vacuum (30 °C, 0.05 mm Hg) and anhydrous Et2O (10.0 mL) was added via syringe and the mixture was stirred for 5 min. The supernatant was cannula filtered into a tared, flame-dried, argon filled, 50-mL Schlenk flask equipped with a rubber septum. The remaining precipitate in the reaction flask was washed with anhydrous Et2O (5.0 mL) and then was filtered into the receiver Schlenk flask. The volatiles were removed under high vacuum (30 °C, 0.05 mm Hg) to afford 1.262 g of a colorless foam. The solid was redissolved in anhydrous Et2O (10.0 mL) and the volatiles were again removed under high vacuum (30 °C, 0.05 mm Hg) to remove traces of HCl. The solid was then dried for 2.5 h at reduced pressure (23 oC, 0.05 mm Hg) to give a colorless foam. Anhydrous CH2Cl2 (30.0 mL) was added via syringe and the mixture was cooled to 0 °C. Triethylamine (560 µL, 4.0 mmol, 1.2 equiv) and hexahydro-1H-azepine (411 µL, 3.65 mmol, 1.1 equiv) were added via syringe and the reaction mixture was allowed to warm to room temperature and then was stirred for 24 h. Powdered selenium (796 mg, 10.1 mmol, 3.0 equiv)

was added and the mixture was stirred for 50 h, whereupon the mixture was filtered through a pad of Celite (5 g, 35 mm). The pad was washed with EtOAc (50 mL) and the filtrate was concentrated in vacuo (40 °C, 10 mm Hg) and the residue was purified by silica gel flash column chromatography (SiO2, 15 g, 20 mm Ø, hexanes/EtOAc, 60:1 to 40:1) to afford 1.233 g (71%) of 62b as an off-white solid.Data for (R)-62b:

mp: 252-253 °C (decomposition) 1 H NMR: (500 MHz, CDCl3) 8.06 (d, J = 8.8 Hz, 1 H, HC(4,4’)), 8.01 (d, J = 8.8 Hz, 1 H, HC(4,4’)), 7.96 (d, J = 8.1 Hz, 1 H, HC(6)), 7.93 (d, J = 8.2 Hz, 1 H, HC(6’)), 7.72 (d, J = 8.2 Hz, 1 H, HC(3,3’)), 7.71 (d, J = 8.4 Hz, 1 H, HC(3,3’)), 7.47 (t, J = 7.2 Hz, 1 H, HC(7)), 7.41 (t, J = 7.2 Hz, 1 H, HC(7’)), 7.34 (d, J = 8.4 Hz, 1 H, HC(9)), 7.27 (t, J = 7.4 Hz, 1 H, HC(8)), 7.18 (t, J = 7.4 Hz, 1 H, HC(8’)), 7.14 (d, J = 8.4 Hz, 1 H, HC(9’)), 3.46 - 3.36 (m, 2 H, H2C(12) and H2C(12’)), 3.33 (d, J = 12.3 Hz, 3 H, H3C(11,11’)), 3.17 - 3.02 (m, 2 H, H2C(12) and H2C(12’)), 2.95 (d, J = 13.4 Hz, 3 H, H3C(11,11’)), 1.72 (bs, 8 H, H2C(13), H2C(14)) 13 C NMR: (125 MHz, CDCl3) 142.9 (d, J = 11.3 Hz, C(2,2’)), 141.8 (C(2,2’)), 132.4 (C(aryl)), 132.2 (C(aryl)), 131.2 (C(aryl)), 130.9 (C(aryl)), 129.3 (C(4,4’)), 128.7 (C(6)), 128.5 (C(1,1’)), 128.0 (C(4,4’)), 2 × 127.8 (C(6’) and C(8’)), 127.4 (d, J = 2.5 Hz, C(1,1’)), 127.1 (C(9’)), 126.0 (C(9)), 125.7 (C(8’)), 125.1 (C(7)), 124.7 (C(7’)), 123.0 (C(3,3’)), 122.1 (C(3,3’)), 49.6 (C(12)), 37.9 (d, J = 11.3 Hz, C(11,11’)), 35.2 (d, J = 6.3 Hz, C(11,11’)), 30.3 (d, J = 3.8 Hz, C(13)), 26.7 (C(14)) 31 P NMR: (202 MHz, CDCl3) 91.64 IR: (KBr) 3046 (w), 2993 (w), 2929 (m), 2858 (w), 1618 (m), 1593 (s), 1506 (s), 1466 (s), 1329 (s), 1274 (s). 1147 (s), 1090 (s), 1052 (s), 934 (s), 815 (s), 753 (s) MS: (ESI) 522 (25), 521 (34), 520 (100, M+H+), 518 (57), 517 (24), 516 (21) HRMS: calcd for C28H31N3PSe+: 520.1415, found: 520.1422

Opt Rot. : [α]D24 -318.1 (c = 0.25, CHCl3)

SFC: (R)-3c, tR, 15.75 min (99.2%); (S)-3c, tR 19.42 min (0.8%) (Chiralpak AD, 15% MeOH in CO2, 2 mL/min, 220 nm.) Analysis: C28H30N3PSe (518.49) Calcd: C, 64.86; H, 5.83% N, 8.10% Found: C, 64.88; H, 5.83% N, 7.98% Preparation of (R)-4-(Azocin-1-yl)-3,5-dimethyl-4,5-dihydro-3H-dinaphtho[2,1-d:1',2'- f][1,3,2]diazaphosphepine-4-selenide (62c) [DJK-1-56]

To a flame-dried, 50-mL Schlenk flask equipped with a magnetic stir bar and septum were added amine 65 (161.2 mg, 0.5 mmol) and anhydrous toluene (10.0 mL) via syringe under argon. The solvent was removed under high vacuum (30 °C, 0.05 mm Hg) for 30 min. Anhydrous THF (30.0 mL) and Et3N (174 µL, 1.25 mmol, 2.5 equiv) were added via syringe and the homogeneous mixture was cooled to 0 °C. Phosphorus trichloride (131 µL, 1.5 mmol, 3.0 equiv) was added dropwise via syringe whereupon a colorless precipitate formed immediately. The reaction mixture was stirred at 0 °C for 1.5 h, then was allowed to warm to room temperature and was stirred for another 24 h. The volatiles were removed under high vacuum (30 °C, 0.05 mm Hg) and anhydrous Et2O (15.0 mL) was added via syringe and the mixture was stirred for 5 min. The supernatant was cannula filtered into a tared, flame-dried, argon filled, 50- mL Schlenk flask equipped with a rubber septum. The remaining precipitate in the reaction flask was washed with anhydrous Et2O (5.0 mL) and then was filtered into the receiver Schlenk flask. The volatiles were removed under high vacuum (30 °C, 0.05 mm Hg). The solid was redissolved in anhydrous Et2O (10.0 mL) and the volatiles were again removed under high vacuum (30 °C, 0.05 mm Hg) to remove traces of HCl. The solid was then dried for 2.5 h at reduced pressure (23 o

C, 0.05 mm Hg) to give 188.4 mg of a colorless foam. Anhydrous CH2Cl2 (10.0 mL) was added via syringe and the mixture was cooled to 0 °C. Triethylamine (90 µL, 0.63 mmol, 1.2 equiv)

and heptahydro-1H-azocine (80 mg, 0.58 mmol, 1.1 equiv) were added via syringe and the reaction mixture was allowed to warm to room temperature and then was stirred for 24 h. Powdered selenium (120 mg, 1.5 mmol, 3.0 equiv) was added and the mixture was stirred for 50 h, whereupon the mixture was filtered through a pad of Celite (5 g, 35 mm). The pad was washed with EtOAc (50 mL) and the filtrate was concentrated in vacuo (40 °C, 10 mm Hg) and the residue was purified by silica gel flash column chromatography (SiO2, 15 g, 20 mm Ø, hexanes/EtOAc, 60:1 to 40:1) to afford 223.1 mg (71%) of 62c as an off-white solid.Data for 62c: 1 H NMR: (500 MHz, CDCl3) δ 8.01 – 7.97 (d, J = 8.9 Hz, 1H, HC(4,4’)), 7.97 – 7.92 (d, J = 8.8 Hz, 1H, HC(4,4’)), 7.93 – 7.88 (d, J = 8.2 Hz, 1H, HC(6)), 7.89 – 7.85 (d, J = 8.1 Hz, 1H, HC(6’)), 7.70 – 7.65 (d, J = 9.0 Hz, 1H, HC(3,3’)), 7.65 – 7.61 (dd, J = 8.9, 1.3 Hz, 1H, HC(3,3’)), 7.46 – 7.40 (ddd, J = 8.1, 6.4, 1.5 Hz, 1H, HC(7)), 7.39 – 7.34 (t, J = 7.5 Hz, 1H, HC(7’)), 7.30 – 7.20 (m, 2H, HC(8,9)), 7.17 – 7.10 (ddd, J = 8.1, 6.7, 1.2 Hz, 1H, HC(8’)), 7.09 – 7.02 (d, J = 8.5 Hz, 1H, HC(9’)), 3.33 – 3.18 (d, J = 12.2 Hz, 4H, HC(11,11’,12)), 3.04 – 2.91 (tdd, J = 14.5, 8.1, 4.0 Hz, 2H, HC(12’)), 2.91 – 2.84 (d, J = 13.4 Hz, 3H, HC(11,11’)), 1.79 – 1.70 (m, 2H, HC(13,14,15), 1.70 – 1.63 (m, 6H, HC(13,14,15)), 1.62 – 1.55 (m, 2H, HC(13,14,15)). 31 P NMR: (202 MHz, CDCl3) 92.44

Sulfenofunctionalization with Chiral Nonracemic Lewis Bases (Table 5)

General Procedure

An oven-dried 5-mm NMR tube was charged with 56 in a glovebox. The tube was taken out of the box and the Lewis base, 57a, and 0.7 mL CDCl3 was added. If indicated, the tube was cooled to the appropriate temperature in a -20 oC freezer or cryocool unit. The acid was added at the indicated temperature and the mixture was shaken well. The reaction was quenched after the indicated time with excess Et3N, and the product was purified by silica gel flash column

chromatography prior to SFC analysis. Data for 58a:

1 H NMR: (500 MHz, CDCl3) 7.32 (m, 2 H, H(C-aryl)), 7.28 – 7.16 (m, 3 H, H(C-aryl)), 7.14 – 7.03 (m, 5 H, H(C-aryl)), 4.14 (d, J = 10.1 Hz, 1 H, HC(2)), 4.09 – 4.00 (m, 1 H, HC(6)), 3.53 (td, J = 11.9, 2.2 Hz, 1 H, HC(6)), 3.20 (ddd, J = 11.5, 10.2, 4.0 Hz, 1 H, HC(3)), 2.32 – 2.17 (m, 1 H, HC(4)), 1.93 – 1.73 (m, 1 H, HC(5)), 1.66 (m, 2 H, HC(4), HC(5)).

Sulfenofunctionalization with (R)-4-(1-Azepano)-3,5-dimethyl-4,5-dihydro-3H- dinaphtho[2,1-d:1’,2’-f][1,3,2]diazaphosphepine-4-selenide (62b) (Table 5 Entry 4) [DJK-1- 17]

Following General Procedure 2, an oven-dried NMR tube was charged with 56 (25.5 mg, 0.1 mmol, 1 equiv), and 57a (16.2 mg, 0.1 mmol). To this was added (R)-62b (5.2 mg, 0.01 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -20 oC in a freezer and MsOH (6.5 µL, 0.1 mmol, 1.0 equiv) was added. After 30 h, the reaction was quenched with Et3N (10 µL). Purification by flash chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 30:1) afforded 16 mg (59%) of 58a as a white solid.

Data for 58a:

SFC: (2R,3S)-58a, tR 4.29 min (90.6%); (2S,3R)-58a, tR 5.35 min (9.4%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Sulfenofunctionalization with (R)-4-(1-Azocano)-3,5-dimethyl-4,5-dihydro-3H- dinaphtho[2,1-d:1’,2’-f][1,3,2]diazaphosphepine-4-selenide (62c) (Table 5 Entry 5) [DJK-1- 66]

Following General Procedure 2, an oven-dried NMR tube was charged with 56 (30.6 mg, 0.12 mmol, 1.2 equiv), and 57a (16.2 mg, 0.1 mmol). To this was added (R)-62c (5.4 mg, 0.01 mmol, 0.1 equiv), CDCl3 (0.7 mL) and the reaction was cooled to -20 oC in a freezer. MsOH (6.6 µL, 0.1 mmol, 1.0 equiv) was added and the tube was shaken well. After 96 h, the reaction was quenched with Et3N (10 µL). Purification by silica gel flash column chromatography (SiO2, 20 g, 20 mm Ø, hexanes/EtOAc, 40:1) afforded 12 mg (44%) of 58a as a white solid.

Data for 58a:

SFC: (2R,3S)-58a, tR 4.29 min (90.7%); (2S,3R)-58a, tR 5.35 min (9.3%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Sulfenofunctionalization with (R)-4-(Diisobutylamino)-3,5-dimethyl-4,5-dihydro-3H- dinaphtho[2,1-d:1’,2’-f][1,3,2]diazaphosphepine-4-selenide (62d) (Table 5 Entry 6) [DJK-3- 75]

An oven-dried Schlenk flask was charged with 56 (64 mg, 0.25 mmol, 1 equiv), and 57a (40.6 mg, 0.25 mmol). To this was added (S)-62d (13.7 mg, 0.025 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -20 oC in an i-Pr bath with stirring and MsOH (17 µL, 0.25 mmol, 1.0 equiv) was added. After 48 h, the reaction was quenched with Et3N (50 µL). Purification by silica gel flash chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 40:1) afforded 25 mg (37%) of 58a as a white solid.

Data for 58a:

SFC: (2R,3S)-58a, tR 4.29 min (7.1%); (2S,3R)-58a, tR 5.35 min (92.9%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Sulfenofunctionalization with (R)-4-(Diisopropylamino)-3,5-dimethyl-4,5-dihydro-3H- dinaphtho[2,1-d:1’,2’-f][1,3,2]diazaphosphepine-4-selenide (62e) (Table 5 Entry 7) [DJK- 10-55]

An oven-dried Schlenk flask was charged with 56 (26 mg, 0.1 mmol, 1 equiv), and 57a (16.2 mg, 0.1 mmol). To this was added (S)-62e (5.2 mg, 0.01 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -20 oC in an i-Pr bath with stirring and MsOH (4.8 µL, 0.75 mmol, 0.75 equiv) was added. After 48 h, the reaction was quenched with Et3N (50 µL). Purification by flash chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 40:1) afforded 14 mg (52%) of 58a as a white solid.

Data for 58a:

SFC: (2R,3S)-58a, tR 4.29 min (5.3%); (2S,3R)-58a, tR 5.35 min (94.7%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Sulfenofunctionalization with Electrophilic Sulfenium Sources (Table 6)

General Procedure

An oven-dried NMR tube was charged with 56, 57a and catalyst. To this was added CDCl3, followed by MsOH. If necessary, the reaction was cooled to the appropriate reaction temperature. The reaction was monitored by 1H NMR spectroscopy. After the specified time, the reaction was quenched with excess Et3N, and purified by silica gel flash column chromatography.

An oven-dried NMR tube was charged with 56 (25.5 mg, 0.1 mmol, 1 equiv), and 57a (16.2 mg, 0.1 mmol). To this was added (R)-62b (5.2 mg, 0.01 mmol, 0.1 equiv) and CDCl3 (0.7 mL). The reaction was cooled to -20 oC in a freezer and MsOH (6.5 µL, 0.1 mmol, 1.0 equiv) was added. After 30 h, the reaction was quenched with Et3N (10 µL). Purification by silica gel flash column chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 30:1) afforded 6 mg (22%) of 58a as a white solid.

SFC: (2R,3S)-58a, tR 4.29 min (90.6%); (2S,3R)-58a, tR 5.35 min (9.4%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Sulfenofunctionalization with N-Phenylthiobismethanesulfonamide 69 (Table 6 Entry 4) [DJK-4-10]

An oven-dried NMR tube was charged with 69 (60 mg, 0.2 mmol, 2 equiv), and 57a (16.2 mg, 0.1 mmol). To this was added (R)-62b (10.3 mg, 0.02 mmol, 0.2 equiv) and CDCl3 (0.7 mL). The reaction was cooled to -20 oC in a freezer and 2,6-di-t-butyl-4-methylpyridine (44 mg, 0.2 mmol, 2 equiv) was added. After 18 h, the reaction was quenched with Et3N (50 µL). Purification by silica gel flash column chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 30:1) afforded 5 mg (19%) of 58a as a white solid.

SFC: (2R,3S)-58a, tR 4.29 min (68.3%); (2S,3R)-58a, tR 5.35 min (31.7%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Attempted Sulfenofunctionalization with Phenylsulfanyl ethanoate (Table 6 Entry 5) [DJK- 3-80]

An oven-dried Schlenk flask was charged with PhSCl (14.5 mg, 0.1 mmol, 1 equiv) and CH2Cl2 (0.7 mL). AgOAc (16.7 mg, 0.1 mmol, 1 equiv.) was added and the reaction was cooled to -20 oC and stirred 16 h. Afterwards, 57a (16.2 mg, 0.1 mmol) and (R)-62b (2.6 mg, 0.005 mmol, 0.05 equiv) were added. After 12 h, no change was visible by 1H NMR. No further manipulations were done.

Attempted Sulfenofunctionalization with 2-Nitrophenylsulfanyl ethanoate (Table 6 Entry 6) [DJK-3-79]

An oven-dried Schlenk flask was charged with 2-NO2-C6H4-SCl (19 mg, 0.1 mmol, 1 equiv) and CH2Cl2 (0.7 mL). AgOAc (16.7 mg, 0.1 mmol, 1 equiv.) was added and the reaction was cooled to -20 oC and stirred 16 h. Afterwards, 57a (16.2 mg, 0.1 mmol) and (R)-62b (2.6 mg, 0.005 mmol, 0.05 equiv) were added. After 16 h, no desired product was visible by 1H

NMR. No further manipulations were done.

Attempted Sulfenofunctionalization with 2,4-Dinitrophenylsulfanyl ethanoate (Table 6 Entry 7) [DJK-3-77]

An oven-dried NMR tube was charged with 2,4-NO2-C6H3-SOAc (10.4 mg, 0.04 mmol, 1 equiv) and CDCl3 (0.7 mL). 57a (16.2 mg, 0.1 mmol) was added and after 2h, (R)-62b (1 mg, 0.002 mmol, 0.05 equiv) were added. After 16 h, no desired product was visible by 1H NMR. No further manipulations were done.

Sulfenofunctionalization with N-methylthiophthalimide (Table 7 Entry 1) [DJK-4-14]

An oven-dried Schlenk flask was charged with 74 (19.3 mg, 0.1 mmol, 1 equiv) and CH2Cl2 (0.7 mL). 57a (16.2 mg, 0.1 mmol) was added and (R)-62b (5.1 mg, 0.01 mmol, 0.1 equiv) were added. The reaction was cooled to -20 oC and MsOH (6.4 µL, 0.1 mmol, 1 equiv) was added. After 48 h, the reaction was quenched with Et3N (50 µL Et3N). Purification by flash chromatography (SiO2, 8 g, 10 mm Ø, hexanes/EtOAc, 60:1) afforded 5 mg (24%) of pure 77. Data for 74a:

H NMR: (500 MHz, CDCl3)

7.45 – 7.39 (m, 2H), 7.39 – 7.26 (m, 83), 4.14 (m, 2H), 3.61 (td, J = 11.9, 2.4 Hz, 1H), 2.92 (s, 3H), 2.68 (ddd, J = 12.3, 10.2, 4.0 Hz, 1H), 2.01 (m, 1H), 1.89 (tdd, J = 17.1, 8.7, 4.2 Hz, 1H), 1.76 (dddd, J = 11.3, 9.5, 6.6, 4.6 Hz, 1H), 1.62 (m, 1H). SFC: (2R,3S)-74a, tR 3.43 min (76.3%); (2S,3R)-74a, tR 4.95 min (23.7%) (Chiralpak AD,

5% MeOH in CO2, 2 mL/min, 220 nm, 40 oC)

Entry 2) [DJK-4-21]

An oven-dried 5-mm NMR tube was charged with 75 (29.6 mg, 0.1 mmol, 1 equiv) and CDCl3 (0.7 mL). 57a (16.2 mg, 0.1 mmol), THT (1.8 µL, 0.02 mmol, 0.2 equiv) and MsOH (6.4 µL, 0.1 mmol, 1 equiv) were added. After 24 h, no reaction was observed. No further manipulations were made.

Attempted Sulfenofunctionalization with N-(4-Nitrophenyl)thiophthalimide (Table 7 Entry 3) [DJK-4-17]

An oven-dried 5-mm NMR tube was charged with 76 (29.9 mg, 0.1 mmol, 1 equiv) and CDCl3 (0.7 mL). 57a (16.2 mg, 0.1 mmol), THT (1.8 µL, 0.02 mmol, 0.2 equiv) and MsOH (6.4 µL, 0.1 mmol, 1 equiv) were added. After 2 h, substantial conversion was observed by 1H NMR. However, no product was isolated from the reaction.

Evaluation of Enantioselectivity as a Function of Temperature (Table 8)

General Procedure

An oven-dried 5-mm NMR tube was charged with 1 in a glovebox. The tube was taken out of the box and the Lewis base, 57a, and 0.7 mL CDCl3 was added. If indicated, the tube was cooled to the appropriate temperature in a cryocool unit. The acid was added at the indicated temperature and the mixture was shaken well. The reaction was quenched after the indicated time with excess Et3N, and the product was purified by silica gel column chromatography prior

to SFC analysis. Data for 58a: 1 H NMR: (500 MHz, CDCl3) 7.32 (m, 2 H, H(C-aryl)), 7.28 – 7.16 (m, 3 H, H(C-aryl)), 7.14 – 7.03 (m, 5 H, H(C-aryl)), 4.14 (d, J = 10.1 Hz, 1 H, HC(2)), 4.09 – 4.00 (m, 1 H, HC(6)), 3.53 (td, J = 11.9, 2.2 Hz, 1 H, HC(6)), 3.20 (ddd, J = 11.5, 10.2, 4.0 Hz, 1 H, HC(3)), 2.32 – 2.17 (m, 1 H, HC(4)), 1.93 – 1.73 (m, 1 H, HC(5)), 1.66 (m, 2 H, HC(4), HC(5)). Data for 59k: 1 H NMR: (500 MHz, CDCl3) 7.37 (d, J = 7.9 Hz, 2 H, HC(9)), 7.28 (t, J = 7.7 Hz, 2 H HC(10)), 7.17 (t, J = 7.4 Hz, 1 H, HC(11)), 4.11 – 4.00 (tt, J = 6, 7 Hz, 1 H, HC(2)), 3.91 (dd, J = 14.4, 7.3 Hz, 1 H, HC(5)), 3.77 (dd, J = 14.4, 7.8 Hz, 1 H, HC(5)), 3.16 (dd, J = 13.0, 5.8 Hz, 1 H, HC(6)), 2.97 (dd, J = 13.0, 6.8 Hz, 1 H, HC(6)), 2.06 (m, 1 H, HC(3)), 1.91 (m, 2 H, HC(4)), 1.66 (m, 1 H, HC(3)).

Evaluation of Enantioselectivity for the Sulfenofunctionalization of 57a at -10 oC (Table 8 Entry 2) [DJK-1-80]

Following General Procedure 4, an oven-dried NMR tube was charged with 56 (64 mg, 0.25 mmol, 1 equiv), and 57a (40.0 mg, 0.25 mmol). To this was added (R)-62b (13 mg, 0.025 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -10 oC in a cryocool. MsOH (17 µL, 0.25 mmol, 1.0 equiv) was added. After 24 h, the reaction was quenched with Et3N (50 µL). Purification by silica gel flash column chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 30:1) afforded 42 mg (63%) of 58a as a white solid.

Data for 58a:

SFC: (2R,3S)-58a, tR 4.29 min (89.4%); (2S,3R)-58a, tR 5.35 min (10.6%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Entry 3) [DJK-1-84]

Following General Procedure 4, an oven-dried NMR tube was charged with 56 (64 mg, 0.25 mmol, 1 equiv), and 57a (40.0 mg, 0.25 mmol). To this was added (R)-62b (13 mg, 0.025 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -20 oC in a cryocool. MsOH (17 µL, 0.25 mmol, 1.0 equiv) was added. After 48 h, the reaction was quenched with Et3N (50 µL). Purification by silica gel flash column chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 30:1) afforded 50 mg (74%) of 58a as a white solid.

Data for 58a:

SFC: (2R,3S)-58a, tR 4.29 min (91.1%); (2S,3R)-58a, tR 5.35 min (8.9%) (Chiralpak AD, 5% MeOH in CO2, 3 mL/min, 220 nm, 40 oC)

Evaluation of Enantioselectivity for for the Sulfenofunctionalization of 57k at 23 oC (Table 8 Entry 5) [DJK-1-21]

Following General Procedure 4, an oven-dried NMR tube was charged with 56 (28.4 mg, 0.11 mmol, 1.2 equiv), and 57k (8.2 mg, 0.09 mmol). To this was added (R)-62b (4.8 mg, 0.009 mmol, 0.1 equiv), CDCl3 (0.7 mL). MsOH (6 µL, 0.09 mmol, 1.0 equiv) was added. After 16 h the reaction was judged to be complete by 1H NMR. After 24 h, the reaction was quenched with Et3N (50 µL). Purification by silica gel flash column chromatography (SiO2, 20 g, 20 mm Ø, hexanes/EtOAc, 75:1) afforded 6 mg (34%) of 59k as a white solid.

Data for 59k:

SFC: (2S)-59k, tR 4.97 min (21.8%); (2R)-59k, tR 6.07 min (78.2%) (Chiralpak AD, 5 % MeOH in CO2, 2 mL/min, 220 nm, 40 oC)

Evaluation of Enantioselectivity for for the Sulfenofunctionalization of 57k at -10 oC (Table 8 Entry 6) [DJK-2-31]

Following General Procedure 4, an oven-dried Schlenk flask was charged with 56 (64 mg, 0.25 mmol, 1 equiv), and 57k (21.8 mg, 0.25 mmol). To this was added (R)-62b (13.1 mg,

0.025 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -10 oC in a cryocool. MsOH (17 µL, 0.25 mmol, 1.0 equiv) was added. After 48 h the reaction was quenched with Et3N (50 µL). Purification by silica gel flash column chromatography (SiO2, 20 g, 20 mm Ø, hexanes/EtOAc, 75:1) afforded 41 mg (85%) of 59k as a white solid.

Data for 59k:

SFC: (2S)-59k, tR 4.97 min (16.8%); (2R)-59k, tR 6.07 min (83.2%) (Chiralpak AD, 5 % MeOH in CO2, 2 mL/min, 220 nm, 40 oC)

Evaluation of Enantioselectivity for for the Sulfenofunctionalization of 57k at -20 oC (Table 8 Entry 7) [DJK-2-13]

Following General Procedure 4, an oven-dried Schlenk flask was charged with 56 (66 mg, 0.26 mmol, 1.04 equiv), and 57k (21.2 mg, 0.25 mmol). To this was added (R)-62b (13 mg, 0.025 mmol, 0.1 equiv), CDCl3 (0.7 mL). The reaction was cooled to -20 oC. MsOH (17 µL, 0.25 mmol, 1.0 equiv) was added. After 72 h, the reaction was quenched with Et3N (50 µL). Purification by flash chromatography (SiO2, 20 g,20 mm Ø, hexanes/EtOAc, 75:1) afforded 49 mg (98%) of 59k as a white solid.

Data for 59k:

SFC: (2S)-59k, tR 4.97 min (13.9%); (2R)-59k, tR 6.07 min (86.1%) (Chiralpak AD, 5 % MeOH in CO2, 2 mL/min, 220 nm, 40 oC)

Preparative Sulfenofunctionalization of Alkenes (Table 9)

General Procedure

In a glovebox, a 5-mL Schlenk flask equipped with a stirbar was charged with 1 (255 mg, 1.0 mmol, 1.0 equiv). The flask was transferred to a vacuum manifold and the corresponding alkene (1.0 mmol, 1.0 equiv), catalyst (R)-3c (52 mg, 0.1 mmol, 0.1 equiv), nucleophile (if indicated, 1.0 mmol, 1.0 equiv) and CH2Cl2 (2.5 mL) were added. The flask was placed into either a 1:1 ethylene glycol/water or isopropyl alcohol bath, and the bath was cooled to the appropriate temperature via a cryocool unit. The temperature of the mixture was monitored via a

thermocouple digital temperature probe. After the temperature stabilized, MsOH (65 µL, 1.0 mmol, 1.0 equiv) was added and the mixture was allowed to stir for the indicated time. The reaction was quenched while cold by the addition of 150 µL of Et3N. The resulting mixture was poured into 20 mL of 1 M HCl in a separatory funnel, 30 mL of CH2Cl2 was added and the layers were thoroughly mixed. The organic layer was poured into 20 mL of 1 M NaOH and the layers were thoroughly mixed and then separated. The acidic layer was back-extracted with 30 mL CH2Cl2, which was then poured into the basic layer and used to extract that layer as well. Both organic portions were combined, dried over MgSO4, filtered through glass wool and then concentrated on a rotavap (20-23 oC, 3 mm Hg). The product thioethers were purified by silica gel flash chromatography.

Preparation of (2R,3S)-Tetrahydro-2-phenyl-3-(phenylthio)-2H-pyran (58a) (Table 9 Entry 1) [DJK-3-67]

Following General Procedure 5, a 5-mL Schlenk flask was charged with 56 (255 mg, 1.0 mmol, 1.0 equiv), 57a (162 mg, 1.0 mmol), (R)-62b (52 mg, 0.1 mmol, 0.1 equiv) and CH2Cl2 (2.5 mL). The mixture was cooled to -20 oC in an i-PrOH bath. Methanesulfonic acid (65 µL, 1.0 mmol, 1.0 equiv) was added and the mixture was allowed to stir for 48 h. The reaction was worked up following the General Procedure. The product 58a was purified by flash chromatography (SiO2, 26 g, 20 mm Ø, hexanes/EtOAc, 80:1 to 40:1) to afford 216.1 mg, (80%) of a pale yellow oil. Kugelrohr distillation afforded 171 mg of analytically pure 58a which crystallized upon standing. The crystals were of suitable quality for single crystal X-ray diffraction, which unambiguously established relative and absolute configurations (see pp. 266)

bp: 100 oC (ABT), 2 x 10-4 mm Hg 1 H NMR: (500 MHz, CDCl3) 7.32 (m, 2 H, H(C-aryl)), 7.28 – 7.16 (m, 3 H, H(C-aryl)), 7.14 – 7.03 (m, 5 H, H(C-aryl)), 4.14 (d, J = 10.1 Hz, 1 H, HC(2)), 4.09 – 4.00 (m, 1 H, HC(6)), 3.53 (td, J = 11.9, 2.2 Hz, 1 H, HC(6)), 3.20 (ddd, J = 11.5, 10.2, 4.0 Hz, 1 H, HC(3)), 2.32 – 2.17 (m, 1 H, HC(4)), 1.93 – 1.73 (m, 1 H, HC(5)), 1.66 (m, 2 H, HC(4), HC(5)). 13 C NMR: (125 MHz, CDCl3)

139.9 (C(7)), 133.7 (C(12)), 133.0 (C-aryl), 128.5 (C-aryl), 128.2 (C-aryl), 128.1 (C-aryl), 127.7 (C-aryl), 127.0 (C-aryl), 85.1 (C(2)), 68.5 (C6)), 50.7 (C(3)), 32.3 (C(4)), 27.0 (C(5)) IR: 3033 (s), 2937 (s), 2850 (s), 2720 (m), 1951 (m), 1872 (m), 1809 (w), 1741 (w), 1583 (s), 1493 (s), 1473 (s), 1436 (s), 1369 (s), 1346 (m), 1325 (s), 1308 (m), 1256 (s), 1230 (m), 1213 (m), 1179 (s), 1077 (s), 1024 (s), 1002 (s), 968 (s), 941 (s), 909 (s), 883 (m), 851 (m), 819 (m), 780 (s), 755 (s), 696 (s), 636 (m) MS: (EI) 270 (65), 161 (35), 160 (40), 149 (24), 136 (100), 135 (43), 91 (52), 77 (19) TLC: Rf 0.27 (hexanes/EtOAc, 20:1) [CAM] Opt Rot. : [α]D24 -35.1 (c = 0.42, CHCl3)

SFC: (2R,3S)-58a, tR 5.53 min (91.1%); (2S,3R)-58a, tR 7.49 min (8.9%) (Chiralpak AD, 5% MeOH in CO2, 2 mL/min, 220 nm, 40 oC)

Analysis: C17H18OS (270.11)

Calcd: C, 75.51; H, 6.71% Found: C, 75.73; H, 6.55%

Preparation of (2R,3S)-Tetrahydro-3-(phenylthio)-2-(4-(trifluoromethyl)phenyl)-2H-pyran (58b) (Table 9 Entry 2) [DJK-3-43]

Following General Procedure 5, a 5-mL Schlenk flask was charged with 56 (255 mg, 1.0 mmol, 1.0 equiv), 57b (230 mg, 1.0 mmol), (R)-62b (52 mg, 0.1 mmol, 0.1 equiv) and CH2Cl2 (2.5 mL). The mixture was cooled to -10 oC in a glycol/water bath. Methanesulfonic acid (65 µL, 1.0 mmol, 1.0 equiv) was added and the mixture was allowed to stir for 48 h. The reaction was worked up following the General Procedure. The product 58b was purified by flash chromatography (SiO2, 27 g, 20 mm Ø, hexanes/dichloromethane, 9:1 to 4:1 to 0:100) to afford 120.1 mg (36%) of 58b along with 125.5 mg (55%) of unreacted 57b. Recrystallization from hot hexanes (5 mL) followed by sublimation (refluxing ethanol) yielded 30.2 mg (9%) of analytically pure 58b as a white solid.

Data for 58b :

mp: 86-88 oC (hexane) 1

H NMR: (500 MHz, CDCl3)

7.44 (m, 4 H, H(C-aryl)), 7.10 (m, 3 H, H(C-aryl)), 7.02 (m, 2 H, H(C-aryl)), 4.24 (d, 1 H, J = 10.2 Hz, HC(2)), 4.09 (m, 1 H, HC(6)), 3.57 (dt, 1 H, J = 2.3, 12 Hz, HC(6)), 3.18 (ddd, 1 H, J = 10.1, 4, 12 Hz, HC(3)), 2.34 (m, 1 H, HC(4)), 1.89 (m, 1H, HC(5)), 1.72 (m, 2 H, HC(4), HC(5)) 13 C NMR: (126 MHz, CDCl3) 143.77 (C(7)), 133.64 (C(13)), 132.65 (C-aryl), 130.17 (q, J = 32 Hz, C(10)), 128.58 (C-aryl), 128.15 (C-aryl), 127.12 (C-aryl), 124.96 (q, J = 3.8 Hz, C(9)), 124.06 (q, J = 272 Hz, C(11)), 85.02 (C(2)), 68.50 (C(6)), 50.98 (C(3)), 32.07 H(C(4)), 27.05 (HC(5)).

19 F NMR: (470 MHz, CDCl3) -63.04 IR: (KBr) 2975 (m), 2952 (m), 2925 (m), 2863 (m), 1618 (w), 1572 (w), 1481 (w), 1439 (m), 1425 (m), 1326 (s), 1261 (m), 1161 (s), 1134 (s), 1118 (s), 1095 (s), 1068 (s), 1018 (s), 943 (m), 844 (m), 824 (m), 782 (m), 739 (s), 688 (m), 666 (m), 604 (m) MS: (EI) 338 (81), 229 (27), 228 (28), 173 (20), 159 (29), 149 (40), 136 (100), 135 (40), 91 (19), 71 (17) TLC: Rf 0.31 (hexanes/EtOAc, 20:1) [CAM] Opt Rot. : [α]D24 -19.6 (c = 0.16, CHCl3)

SFC: (2R,3S)-58b, tR 4.77 min (88.1%); (2S,3R)-58b, tR 5.79 min (11.9%) (Chiralpak AD, 4% MeOH in CO2, 2 mL/min, 220 nm, 40 oC)

Analysis: C18H17F3OS (338.42)

Calcd: C, 63.89; H, 5.06% Found: C, 63.59; H, 4.91%

Preparation of (2R,3S)-Tetrahydro-2-(4-methoxyphenyl)-3-(phenylthio)-2H-pyran (57c) (Table 9 Entry 3) [DJK-3-41]

Following General Procedure 5, a 5-mL Schlenk flask was charged with 56 (255 mg, 1.0 mmol, 1.0 equiv), 57c (192 mg, 1.0 mmol, 1.0 equiv), (R)-62b (52 mg, 0.1 mmol, 0.1 equiv) and CH2Cl2 (2.5 mL). The mixture was cooled to -20 oC in a glycol/water bath. Methanesulfonic acid (65 µL, 1.0 mmol, 1.0 equiv) was added and the mixture was allowed to stir for 48 h. The reaction was worked up following the General Procedure. The product 58c was purified by flash

chromatography (SiO2, 27 g, 20 mm Ø, hexanes/dichloromethane, 9:1) to afford 250 mg (84%) of 58c as a white solid. Recrystallization from hot pentane provided 220 mg (73%) of analytically pure 58c as a white solid.

Data for 58c : mp: 71-73 oC (pentane) 1 H NMR: (500 MHz, CDCl3) 7.26 (d, 2 H, J = 8.6 Hz, HC(8)), 7.15 (m, 5 H, H(C-aryl)), 6.80 (d, 2 H, J = 8.7Hz, HC(9)), 4.14 (d, 1 H, J = 10.1Hz, HC(2)), 4.07 (m, 1 H, HC(6)), 3.78 (s, 3 H, HC(12)), 3.55 (dt, 1 H, J = 2.2Hz, J = 12.1Hz, HC(6)), 3.23 (ddd, 1 H, J = 4.0Hz, 10.2Hz, 12.0Hz, HC(3)), 2.26 (m, 1 H, HC(4)), 1.83 (m, 1 H, HC(5)), 1.67 (m, 2 H, HC(4), HC(5)) 13 C NMR: (125 MHz, CDCl3)

159.39 (C(10)), 133.67 (C(14)), 133.07 (C-aryl), 132.27 (C-aryl), 128.73 (C-aryl), 128.49 (C-aryl), 127.01 (C(7)), 113.56 (C(9)), 84.56 (C(2)), 68.57 (C(6)), 55.24 (C(12)). 51.76 (C(3)), 32.21 (C(4)), 27.04 (C(5)) IR: (KBr) 2955 (s), 2935 (m), 2914 (m), 2843 (s), 1612 (s), 1583 (m), 1560 (m), 1542 (w), 1518 (s), 1499 (m), 1491 (m), 1474 (s), 1459 (s), 1450 (m), 1440 (s), 1370 (m), 1330 (w), 1303 (m), 1267 (m), 1245 (s), 1176 (s), 1115 (m), 1092 (s), 1074 (s), 1030 (s), 962 (s), 949 (s), 940 (s), 922 (m), 829 (s), 817 (s), 778 (s), 748 (s), 693 (s) MS: (EI) 300 (40, M+), 191 (28), 190 (41), 136 (100), 135 (45), 121 (42), 91 (18) TLC: Rf 0.17 (hexanes/EtOAc, 10:1) [CAM] Opt Rot. : [α]D24 -45.5 (c = 0.2, CHCl3)

SFC: (2R,3S)-58c, tR 6.28 min (91.4%); (2S,3R)-58c, tR 9.88 min (8.6%) (Chiralpak AD, 5% MeOH in CO2, 2.5 mL/min, 220 nm, 40 oC)

Analysis: C18H20O2S (300.41)

Calcd: C, 71.96; H, 6.71% Found: C, 71.64; H, 6.90%

Attempted Sulfenofunctionalization of (E)-Methyl 6-hydroxyhex-2-enoate (57d) (Table 9 Entry 4) [DJK-1-98]

An oven-dried NMR tube was charged with 56 (25.6 mg, 0.1 mmol, 1 equiv), and 57d (14.6 mg, 0.1 mmol). To this was added (R)-62b (5.2 mg, 0.01 mmol, 0.1 equiv), CDCl3 (0.7 mL). MsOH (6.7 µL, 0.1 mmol, 1.0 equiv) was added. After 96 h, only 57d was detectable by 1H NMR. No further manipulations were done.

Preparation of (5S,6R)-Tetrahydro-2,2-dimethyl-6-phenyl-5-(phenylthio)-2H-pyran (58e) and (5S,8R)-Tetrahydro-2,2-dimethyl-5-(phenyl(phenylthio)methyl)furan (59e) (Table 9 Entry 5) [DJK-2-45]

Following General Procedure 5, a 5-mL Schlenk flask was charged with 56 (255 mg, 1.0 mmol, 1.0 equiv), 57e (190 mg, 1.0 mmol), (R)-62b (52 mg, 0.1 mmol, 0.1 equiv) and CH2Cl2 (2.5 mL). The mixture was cooled to -20 oC in a i-PrOH bath. Methanesulfonic acid (65 µL, 1.0 mmol, 1.0 equiv) was added and the mixture was allowed to stir for 48 h. The reaction was

In document Lewis base catalyzed enantioselective oxysulfenylation of alkenes (Page 125-174)