On the Utility of S-Mesitylsulfinimines for the Stereoselective Synthesis of Chiral Amines and Aziridines

Transcription

1 n the Utility of S-Mesitylsulfinimines for the Stereoselective Synthesis of Chiral Amines and Aziridines Caroline Roe, a Toni Moragas Solá, a Leonid Sasraku-eequaye, b eather obbs, c Ian Churcher, c David MacPherson c and Robert A. Stockman *a,b Supplementary Information

2 General Information Experimental All reactions were carried out under an environment of nitrogen. Dry solvents were purchased from Sigma-Aldrich. Unless otherwise noted, all reagents and solvents were obtained commercially and used without further purification. All reactions were stirred with a magnetic stirrer bar. IR spectra were recorded on a Perkin Elmer FT-IR spectrometer: points of maximum absorption (ν max ) were recorded in cm MR and 13 C MR spectra were recorded at ambient temperature using Bruker 400 Mz spectrometers. Chemical shifts are quoted with the deuterated solvent as the reference. Data for 1 MR are recorded as follows: chemical shift (δ, ppm), multiplicity (integration, s = singlet, d = doublet, t = triplet, q = quartet, qn = quintet, oct = octet, m = multiplet or unresolved, coupling constant(s) in z). Melting points were measured using a Stuart SMP40 apparatus in open capillary tubes and are uncorrected. The (S)-mesitylsulfinimine starting materials were prepared by the reported method with enantiomeric excesses in the range of %. 1 Diastereomeric ratios (dr s) of the mesitylsulfinamides were determined by the crude 1 MR spectra in acetoned 6 (where possible) and confirmed by the purified 1 MR spectra in acetone-d 6 and in some cases by chiral PLC analysis in comparison with the authentic racemates. The absolute configuration of the asymmetric carbon atom of the major diastereomer of a range of the mesitylsulfinamides was determined by treatment of the mesitylsulfinamide with 2M aqueous hydrochloric acid in methanol (general procedure B) and comparison of the sign of specific rotation of the obtained free amine (or amine hydrochloride) with the reported data. 2-9 General Procedure A A Grignard solution was added dropwise to a solution of (S)-mesitylsulfinimine in dry 2- methyltetrahydrofuran (1 ml) at -78 C and stirred overnight (16-24 hr) whilst warming to room temperature. The cooled reaction mixture (0 C) was quenched with saturated sodium bicarbonate solution and extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the crude mesitylsulfinamide, which was purified by flash chromatography. General Procedure B To a solution of mesitylsulfinamide ( mmol) in methanol (1.5 ml), 2M aqueous hydrochloric acid (1.00 ml, mmol) was added and it was stirred at room temperature for 1-3 hr. Then, the solvent was evaporated, a 2M aqueous hydrochloric acid solution (5 ml) was added and the mixture was extracted with three times with DCM. The organic layers were discarded. The aqueous layer was basified with solid sodium hydroxide and extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and then, either the solvent was evaporated to give the amine or 2M hydrochloric acid in ether (0.5 ml) was added and then the solvent was evaporated to give the amine hydrochloride, as required. (S)-2,4,6-trimethyl--((S)-1-phenylbutyl)benzenesulfinamide 3a (Entry 5, Table 1)

3 The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (56 mg, 92.4:7.6 dr). Purification by flash chromatography on silica gel (elution with 0-50% ethyl acetate/cyclohexane) gave the title compound 3a (38 mg, mmol, 82%, 91.2:8.8 dr) as a colourless oil. Diastereomeric ratio: 90.7:9.3, determined by PLC [Chiralcel J (heptane/ethanol 98:2, flow rate: 1.0 ml/min, l=215 nm, retention time: (major), (minor)]; [α] D (c 1.0, CCl 3 )]; IR (ATR) 3215, 2958, 2929, 2871, 1602, 1454, 1379, 1070, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereoisomer (5, m), 6.81 (2, s), 5.70 (1, d, J 6.8), 4.38 (1, q, J 7.2), 2.50 (6, s), 2.23 (3, s), (1, m), (1, m), (2, m), 0.90 (3, t, J 7.4); minor diastereomer (5, m), 6.85 (2, s), 5.54 (1, d, J 4.3), (1, m), 2.41 (6, s), 2.25 (3, s), (1, m), (1, m), (2, m), (3, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereoisomer 144.9, 140.7, 139.6, 137.5, 131.4, 129.0, 127.8, 127.7, 60.3, 40.7, 21.0, 20.3, 19.7, 14.2; m/z (ES+) 338 ([M+a] +, 43%), 316 ([M+] +, 36), 299 (35), 149 (48); RMS: Found: C S Alternative procedure for 3a (Entry 1, Table 1) n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) was added dropwise to a solution of (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide (40 mg, mmol) in dry DCM (1 ml) at -78 C and stirred overnight (18 hr) whilst warming to room temperature. The cooled reaction mixture (0 C) was quenched with saturated sodium bicarbonate solution and extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the crude product (48 mg, 52.6:47.4 dr). Purification by flash chromatography on silica gel (elution with 0-50% ethyl acetate/cyclohexane) gave the title compound 3a (25 mg, mmol, 54%, 50.6:49.4 dr) as a colourless oil. Spectral properties identical to previous compound 3a. Alternative procedure for 3a (Entry 3, Table 1) n-propylmagnesium chloride (2M in diethyl ether) (0.14 ml, mmol) was added dropwise to a solution of (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide (19 mg, mmol) in dry TF (1 ml) at -78 C and stirred for 3 hr whilst warming to room temperature. The cooled reaction mixture (0 C) was quenched with saturated sodium bicarbonate solution and extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the crude product (25 mg, 85.8:14.2 dr). Purification by flash chromatography on silica gel (elution with 0-50% ethyl acetate/cyclohexane) gave the title compound 3a (20 mg, mmol, 90%, 84.7:15.3 dr) as a colourless oil. Spectral properties identical to previous compound 3a. (S)-2,4,6-trimethyl--((S)-2-methyl-1-phenylpropyl)benzenesulfinamide 3b (Entry 6, Table 1)

4 The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.15 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (56 mg, 98.3:1.7 dr). Purification by flash chromatography on silica gel (elution with 0-50% ethyl acetate/cyclohexane) gave the title compound 3b (32 mg, mmol, 69%, 98.2:1.8 dr) as a white solid. M.p C; diastereomeric ratio: 98.2:1.8, determined by PLC [Chiralcel J (heptane/ethanol 90:10, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3258, 2974, 2949, 2919, 2866, 1602, 1455, 1383, 1064, 1045; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.76 (2, s), 5.71 (1, d, J 8.1), 4.04 (1, t, J 7.9), 2.44 (6, s), 2.20 (3, s), (1, m), 0.96 (3, d, J 6.5), 0.75 (3, d, J 6.8); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 143.9, 140.7, 139.7, 137.5, 131.3, 128.8, 128.2, 127.6, 67.1, 35.1, 20.9, 20.0, 20.0, 19.7; m/z (ES+) 338 ([M+a] +, 50%), 316 ([M+] +, 40), 299 (50), 149 (29); RMS: Found: C S Alternative procedure for 3b (Entry 2, Table 1) Iso-propylmagnesium chloride (2M in diethyl ether) (0.15 ml, mmol) was added dropwise to a solution of (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide (40 mg, mmol) in dry DCM (1 ml) at -78 C and stirred overnight (23 hr) whilst warming to room temperature. The cooled reaction mixture (0 C) was quenched with saturated sodium bicarbonate solution and extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the crude product (46 mg, 69.0:31.0 dr). Purification by flash chromatography on silica gel (elution with 0-50% ethyl acetate/cyclohexane) gave the title compound 3b (24 mg, mmol, 52%, 67.5:32.5 dr) as a colourless oil. Spectral properties identical to previous compound 3b. Alternative procedure for 3b (Entry 4, Table 1) Trimethylaluminum (2M in toluene) (0.15 ml, mmol) was added dropwise to a solution of (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide (40 mg, mmol) in dry TF (2 ml) at -78 C and stirred for 17 min. Then, iso-propyllithium (0.7M in pentane) (0.84 ml, mmol) was added dropwise and the mixture was left to warm to room temperature overnight (16 hr). The cooled reaction mixture (0 C) was quenched with saturated sodium bicarbonate solution, filtered through a frit and extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the crude product (52 mg, 87.0:13.0 dr). Purification by flash chromatography on silica gel (elution with 0-50% ethyl acetate/cyclohexane) gave the title compound 3b (37 mg, mmol, 80%, 88.8:11.2 dr) as a pale yellow oil. Spectral properties identical to previous compound 3b. (S)-2,4,6-trimethyl--((S)-1-phenylpropyl)benzenesulfinamide 3c

5 The general procedure A was followed using ethylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (49 mg, 90.6:9.4 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3c (41 mg, mmol, 92%, 90.8:9.2 dr) as a colourless oil. Diastereomeric ratio: 90.1:9.9, determined by PLC [Chiralcel J (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 )]; IR (ATR) 3213, 2964, 2928, 1602, 1453, 1378, 1071, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereoisomer (5, m), 6.82 (2, s), 5.71 (1, d, J 6.6), 4.29 (1, q, J 7.1), 2.50 (6, s), 2.23 (3, s), (1, m), (1, m), 0.87 (3, t, J 7.5); minor diastereoisomer (5, m), 6.85 (2, s), 5.57 (1, d, J 4.3), (1, m), 2.42 (6, s), 2.25 (3, s), (1, m), (1, m), (3, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereoisomer 144.6, 140.7, 139.6, 137.5, 131.4, 129.0, 127.8, 127.8, 62.1, 31.3, 21.0, 19.7, 11.3; m/z (ES+) 324 ([M+a] +, 100%), 302 ([M+] +, 16), 237 (8), 167 (9); RMS: Found: C as (S)-2,4,6-trimethyl--((S)-3-methyl-1-phenylbutyl)benzenesulfinamide 3d The general procedure A was followed using iso-butylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (52 mg, 95.3:4.7 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3d (38 mg, mmol, 78%, 94.6:5.4 dr) as a colourless oil. Diastereomeric ratio: 93.6:6.4, determined by PLC [Chiralpak IA (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3212, 2955, 2926, 2868, 1602, 1454, 1382, 1070, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.80 (2, s), 5.74 (1, d, J 7.3), 4.46 (1, q, J 7.3), 2.50 (6, s), 2.22 (3, s), (1, m), (2, m), 0.94 (3, d, J 6.3), 0.90 (3, d, J 6.6); minor diastereomer (5, m), 6.84 (2, s), 5.55 (1, d, J 4.8), (1, m), 2.40 (6, s), 2.25 (3, s), (1, m), (2, m), (3, m), 0.87 (3, d, J 6.3); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 145.3, 140.7, 139.6, 137.5, 131.4, 129.0, 127.7, 127.6, 58.8, 48.1, 25.6, 23.0, 22.7, 21.0, 19.6; m/z (ES+) 352 ([M+a] +, 100%), 330 ([M+] +, 12), 313 (12), 167 (12), 164 (13); RMS: Found: C as (S)-2,4,6-trimethyl--((S)-1-phenylheptyl)benzenesulfinamide 3e The general procedure A was followed using n-hexylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (58 mg, 74.2:25.8 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3e (39 mg, mmol, 74%, 73.6:26.4 dr) as a colourless oil.

6 Diastereomeric ratio: 72.1:27.9, determined by PLC [Chiralpak IA (heptane/ethanol 98:2, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), (minor)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3209, 2926, 2856, 1602, 1454, 1378, 1071, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.81 (2, s), 5.79 (1, d, J 7.1), 4.36 (1, q, J 7.2), 2.50 (6, s), 2.23 (3, s), (1, m), (1, m), (8, m), 0.85 (3, t, J 6.8); minor diastereomer (5, m), 6.85 (2, s), 5.64 (1, d, J 4.5), (1, m), 2.41 (6, s), 2.25 (3, s), (1, m), (1, m), (8, m), (3, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 145.0, 140.6, 139.5, 137.4, 131.3, 129.0, 127.7, 127.7, 60.6, 38.5, 32.6, 29.8, 27.1, 23.3, 20.9, 19.7, 14.4; m/z (ES+) 380 ([M+a] +, 100%), 358 (15), 341 (22), 192 (13), 166 (6); RMS: Found: C as (S)--((S)-cyclohexyl(phenyl)methyl)-2,4,6-trimethylbenzenesulfinamide 3f The general procedure A was followed using cyclohexylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (61 mg, 98.9:1.1 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3f (46 mg, mmol, 88%, 99.3:0.7 dr) as a white solid. M.p C; diastereomeric ratio: 98.5:1.5, determined by PLC [Whelk-o 1 (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3272, 2934, 2853, 1600, 1448, 1421, 1070, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (4, m), (1, m), 6.79 (2, s), 5.82 (1, d, J 8.6), 4.06 (1, t, J 8.3), 2.46 (6, s), 2.22 (3, s), (1, m), (4, m), (1, m), (5, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 144.1, 140.5, 139.6, 137.3, 131.3, 128.8, 128.1, 127.5, 66.6, 44.7, 30.9, 30.8, 27.1, 26.8, 26.8, 20.9, 19.7; m/z (ES+) 378 ([M+a] +, 100%), 339 (15), 190 (7), 167 (6); RMS: Found: C as (S)--((S)-1,2-diphenylethyl)-2,4,6-trimethylbenzenesulfinamide 3g The general procedure A was followed using benzylmagnesium chloride (1M in diethyl ether) (044 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (74 mg, 70.0:30.0 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3g (50 mg, mmol, 93%, 69.9:30.1 dr) as a white solid. M.p C; diastereomeric ratio: 77.1:22.9, determined by PLC [Chiralcel D- (heptane/ethanol 98:2, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3257, 3028, 2926, 1602, 1495, 1454, 1066, 1045; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (10, m), 6.78 (2, s), 5.76 (1, d, J 7.3), 4.65 (1, ddd, J 8.2, 7.3, 6.6), 3.21 (1, dd, J 13.6, 8.2), 3.11 (1, dd, J 13.6, 6.6),

7 2.32 (6, s), 2.22 (3, s); minor diastereomer (10, m), 6.83 (2, s), 5.23 (1, d, J 3.5), 4.71 (1, ddd, J 8.3, 6.6, 3.5), 3.13 (1, dd, J 13.6, 6.6), 3.06 (1, dd, J 13.6, 8.3), 2.27 (6, s), 2.25 (3, s); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 144.3, 140.7, 139.7, 139.7, 137.5, 131.3, 130.4, 129.0, 129.0, 128.0, 127.9, 127.1, 62.8, 45.1, 21.0, 19.5; minor diastereomer 143.0, 141.2, 139.5, 138.8, 137.6, 131.4, 130.3, 129.4, 129.2, 128.7, 128.5, 127.5, 60.3, 45.5, 21.0, 19.1; m/z (ES+) 386 ([M+a] +, 100%), 364 ([M+] +, 19); RMS: Found: C S (S)-2,4,6-trimethyl--((R)-1-phenylbut-3-en-1-yl)benzenesulfinamide 3h The general procedure A was followed using allylmagnesium bromide (1M in diethyl ether) (044 ml, mmol) and (S,E)--benzylidene-2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) and gave the crude product (55 mg, 83.4:16.6 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3h (41 mg, mmol, 89%, 83.2:16.8 dr) as a colourless oil. Diastereomeric ratio: 84.0:16.0, determined by PLC [Chiralcel J (heptane/ethanol 98:2, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3212, 3029, 2922, 1601, 1454, 1380, 1071, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.87 (2, s), 5.77 (1, m), 5.41 (1, d, J 4.3), (2, m), 4.50 (1, td, J 7.1, 4.3), 2.59 (2, dd, J 7.1, 6.5), 2.43 (6, s), 2.26 (3, s); minor diastereomer (5, m), 6.82 (2, s), (2, m), (2, m), (1, m), (2, m), 2.50 (6, s), 2.23 (3, s); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 143.3, 141.1, 139.7, 137.6, 135.9, 131.4, 129.2, 128.5, 128.4, 118.5, 58.8, 43.5, 21.0, 19.4; m/z (ES+) 336 ([M+a] +, 93%), 314 ([M+] +, 100), 287 (53), 261 (39), 217 (27), 167 (17); RMS: Found: C S (S)-2,4,6-trimethyl--((R)-phenyl(p-tolyl)methyl)benzenesulfinamide 3i p-tolylmagnesium bromide (0.5M in diethyl ether) (1.77 ml, mmol) was added to copper(i) iodide (84 mg, mmol) in dry tetrahydrofuran (1 ml) at -30 C and stirred for 35 min. The reaction mixture was cooled to -60 C and a solution of (S,E)--benzylidene- 2,4,6-trimethylbenzenesulfinamide 2a (40 mg, mmol) in dry tetrahydrofuran (1 ml) was added slowly to the reaction mixture, and it was allowed to warm to room temperature overnight (16 hr). The cooled reaction mixture (0 C) was quenched with saturated sodium bicarbonate solution, filtered through a frit and flushed and extracted three times with DCM. The combined organic layers were dried using a hydrophobic frit and concentrated to give the crude mesitylsulfinamide (79 mg). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 3i (34 mg, mmol, 64%, 82.6:17.4 dr) as a cream solid. M.p C; diastereomeric ratio: 83.3:16.7, determined by PLC [Chiralpak AD- (heptane/isopropanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] 21 D +140 (c

8 1.0, CCl 3 ); IR (ATR) 3210, 3021, 2920, 1601, 1509, 1453, 1072, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.36 (4, d, J 7.8), 7.26 (3, t, J 7.4), 7.15 (2, d, J 7.8), 6.85 (2, s), 5.88 (1, d, J 4.5), 5.66 (1, d, J 4.8), 2.49 (6, s), 2.30 (3, s), 2.25 (3, s); minor diastereomer 7.48 (2, d, J 7.3), (5, m), 7.08 (2, d, J 7.8), 6.85 (2, s), (1, m), (1, m), 2.49 (6, s), 2.26 (3, s), 2.25 (3, s); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 144.2, 141.0, 140.3, 139.3, 137.9, 137.8, 131.5, 129.9, 129.2, 128.9, 128.3, 128.0, 63.0, 21.2, 21.0, 19.6; m/z (ES+) 386 ([M+a] +, 100%), 364 ([M+] +, 19); RMS: Found: C S (S)--((S)-1-(4-methoxyphenyl)butyl)-2,4,6-trimethylbenzenesulfinamide 4b The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(4-methoxybenzylidene)-2,4,6- trimethylbenzenesulfinamide 2b (45 mg, mmol) and gave the crude product (53 mg, 85.4:14.6 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4b (42 mg, mmol, 80%, 85.3:14.7 dr) as a white solid. M.p C; diastereomeric ratio: 84.5:15.5, determined by PLC [Chiralpak IA (heptane/ethanol 96:4, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] 21 D +169 (c 1.0, CCl 3 ); IR (ATR) 3214, 2959, 2934, 2872, 1613, 1516, 1459, 1254, 1179, 1024; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.23 (2, d, J 8.6), 6.82 (2, d, J 8.6), 6.82 (2, s), 5.54 (1, d, J 6.3), 4.33 (1, q, J 7.0), 3.76 (3, s), 2.50 (6, s), 2.23 (3, s), (1, m), (1, m), (2, m), 0.89 (3, t, J 7.3); minor diastereomer 7.32 (2, d, J 8.7), 6.90 (2, d, J 8.7), 6.84 (2, s), 5.43 (1, d, J 4.0), (1, m), 3.79 (3, s), 2.42 (6, s), 2.25 (3, s), (2, m), (2, m), 0.86 (3, t, J 7.4); 13 C MR (101 Mz, acetoned 6 ) major diastereomer 159.8, 140.7, 139.7, 137.5, 136.7, 131.4, 128.9, 114.4, 59.7, 55.5, 40.6, 21.0, 20.3, 19.7, 14.2; m/z (ES+) 368 ([M+a] +, 100%), 346 ([M+] +, 68), 329 (46), 217 (25); RMS: Found: C S (S)--((S)-1-mesitylbutyl)-2,4,6-trimethylbenzenesulfinamide 4c The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)-2,4,6-trimethyl--(2,4,6- trimethylbenzylidene]benzenesulfinamide 2c (47 mg, mmol) and gave the crude product (59 mg, 93.9:6.1 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4c (51 mg, mmol, 94%, 94.5:5.5 dr) as a white solid. M.p C; [α] D (c 1.0, CCl 3 ); IR (ATR) 3248, 2957, 2927, 2870, 1605, 1454, 1377, 1071, 1050; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.85 (2, s), 6.76 (2, s), 5.30 (1, d, J 5.1), 4.88 (1, td, J 7.6, 5.1), 2.51 (6, s), 2.44 (3, br. s.), 2.27 (3, br. s.), 2.24 (3, s), 2.18 (3, s), (1, m), (1, m), (1, m), (1, m), 0.91 (3, t, J 7.3); minor diastereomer 6.85 (2, s), 6.82 (2, s), 5.22 (1, d, J 2.5), 4.95 (1, td, J 7.6, 2.5), (18, m), 2.07-

9 2.17 (1, m), (1, m), (1, m), (1, m), 0.90 (3, t, J 7.3); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 140.8, 139.4, 137.6, 137.2, 137.1, 136.9, 136.6, 132.0, 131.5, 129.9, 55.7, 37.5, 21.5, 21.3, 21.0, 20.9, 20.8, 19.6, 14.5; m/z (ES+) 380 ([M+a] +, 68%), 358 ([M+] +, 82), 341 (19), 238 (19), 217 (24); RMS: Found: C S (S)--((S)-1-(4-chlorophenyl)butyl)-2,4,6-trimethylbenzenesulfinamide 4d The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(4-(chlorobenzylidene)-2,4,6- trimethylbenzenesulfinamide 2d (46 mg, mmol) and gave the crude product (57 mg, 88.4:11.6 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4d (48 mg, mmol, 92%, 86.7:13.3 dr) as a white solid. M.p C; diastereomeric ratio: 86.3:13.7, determined by PLC [Chiralpak IA (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] 21 D +164 (c 1.0, CCl 3 ); IR (ATR) 3204, 2959, 2929, 2872, 1601, 1460, 1408, 1065, 1032; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.32 (2, d, J 8.6), 7.26 (2, d, J 8.6), 6.79 (2, s), 5.81 (1, d, J 7.1), 4.41 (1, q, J 7.1), 2.49 (6, s), 2.22 (3, s), (1, m), (1, m), (2, m), 0.90 (3, t, J 7.4); minor diastereomer 7.43 (2, d, J 8.6), 7.37 (2, d, J 8.6), 6.85 (2, s), 5.62 (1, d, J 4.0), (1, m), 2.42 (6, s), 2.25 (3, s), (1, m), (1, m), (2, m), 0.88 (3, t, J 7.3); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 144.1, 140.8, 139.3, 137.6, 132.9, 131.4, 129.5, 129.0, 59.5, 40.7, 21.0, 20.2, 19.7, 14.1; m/z (ES+) 372 ([M+a] +, 69%), 350 ([M+] +, 100), 333 (21), 217 (36); RMS: Found: C SCl (S)-2,4,6-trimethyl--((S)-1-phenylhex-1-yn-3-yl)benzenesulfinamide 4e The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)-2,4,6-trimethyl--(3-phenylpropyn-2-yn-1- ylidene]benzenesulfinamide 2e (44 mg, mmol) and gave the crude product (50 mg, 88.0:12.0 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4e (41 mg, mmol, 81%, 88.0:12.0 dr) as a colourless oil. Diastereomeric ratio: 87.1:12.9, determined by PLC [Chiralpak IA (heptane/isopropanol 97:3, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] 21 D +115 (c 1.0, CCl 3 ); IR (ATR) 3200, 2959, 2927, 2871, 1600, 1490, 1443, 1379, 1070, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.87 (2, s), 5.77 (1, d, J 6.8), 4.33 (1, q, J 7.1), 2.58 (6, s), 2.25 (3, s), (2, m), (2, s), 0.97 (3, t, J 7.4); minor diastereomer (5, m), 6.87 (2, s), 5.65 (1, d, J 6.3), (1, m), 2.58 (6, s), 2.26 (3, s), (2, m), (2, s), 0.93 (3, t, J 7.6); 13 C MR (101 Mz, acetone-d 6 )

10 major diastereomer 141.0, 139.4, 137.7, 132.4, 131.5, 129.3, 129.1, 124.2, 90.9, 84.5, 48.3, 40.4, 21.0, 20.0, 19.6, 14.0; m/z (ES+) 362 ([M+a] +, 100%), 340 ([M+] +, 62), 217 (27); RMS: Found: C S (S)--((S)-1-(furan-2-yl)butyl)-2,4,6-trimethylbenzenesulfinamide 4f The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(furan-2-ylmethylene]-2,4,6- trimethylbenzenesulfinamide 2f (39 mg, mmol) and gave the crude product (50 mg, 86.8:13.2 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4f (42 mg, mmol, 92%, 87.6:12.4 dr) as a white solid. M.p C; diastereomeric ratio: 86.4:13.6, determined by PLC [Chiralpak IA (heptane/isopropanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3170, 2956, 2929, 2871, 1602, 1453, 1377, 1150, 1069, 1045; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.43 (1, dd, J 1.8, 0.8), 6.85 (2, s), 6.32 (1, dd, J 3.3, 1.8), 6.26 (1, dd, J 3.3, 0.8), 5.69 (1, d, J 7.3), 4.44 (1, q, J 7.1), 2.51 (6, s), 2.25 (3, s), (2, m), (2, m), 0.92 (3, t, J 7.4); minor diastereomer 7.47 (1, dd, J 1.8, 0.8), 6.85 (2, s), 6.36 (1, dd, J 3.1, 1.8), (1, m), 5.57 (1, d, J 6.3), (1, m), 2.47 (6, s), 2.25 (3, s), (2, m), (2, m), 0.88 (3, t, J 7.3); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 157.2, 142.6, 140.8, 139.8, 137.5, 131.4, 111.0, 107.3, 54.5, 38.2, 21.0, 20.0, 19.6, 14.1; m/z (ES+) 328 ([M+a] +, 100%), 306 ([M+] +, 29), 289 (25), 217 (12); RMS: Found: C S (S)-2,4,6-trimethyl--(nonan-4-yl)benzenesulfinamide 4g The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--hexylidene-2,4,6-trimethylbenzenesulfinamide 2g (40 mg, mmol) and gave the crude product (46 mg). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4g (25 mg, mmol, 54%) as a colourless oil. Diastereomeric ratio: 57.1:42.9, determined by PLC [Chiralpak AY- (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3211, 2956, 2928, 2859, 1602, 1458, 1378, 1069, 1047; 1 MR (400 Mz, acetoned 6 ) major and minor diastereomers 6.86 (2, s), (1, m), (1, m), 2.55 (6, s), 2.25 (3, s), (12, m), (6, m); 13 C MR (101 Mz, acetoned 6 ) major and minor diastereomers 140.5, 140.4, 137.2, 137.2, 131.4, 131.3, 57.3, 57.1, 39.5, 39.3, 37.2, 37.0, 32.7, 32.6, 26.5, 26.2, 23.4, 23.4, 21.0, 19.9, 19.7, 19.7, 19.7, 14.4; m/z (ES+) 332 ([M+a] +, 32%), 310 ([M+] +, 43), 293 (24); RMS: Found: C S (S)-2,4,6-trimethyl--((S,E)-1-phenylhex-1-en-3-yl)benzenesulfinamide 4h

11 The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)-2,4,6-trimethyl--((E)-3- phenylallylidene)benzenesulfinamide 2h (45 mg, mmol) and gave the crude product (51 mg, 91.2:8.8 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the impure product (45 mg) which was further purified by purification by flash chromatography on silica gel (elution with 0-13% ethyl acetate/dcm) to give the title compound 4h (37 mg, mmol, 72%, 91.8:8.2 dr) as a colourless oil. Diastereomeric ratio: 91.7:8.3, determined by PLC [Chiralpak IA (heptane/ethanol 97:3, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3209, 2958, 2929, 2870, 1601, 1450, 1379, 1071, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.36 (2, d, J 7.3), 7.30 (2, t, J 7.3), 7.21 (1, t, J 7.3), 6.85 (2, s), 6.52 (1, d, J 16.1), 6.26 (1, dd, J 16.1, 7.1), 5.45 (1, d, J 6.8), 4.01 (1, qn, J 7.0), 2.59 (6, s), 2.23 (3, s), (2, m), (2, m), 0.94 (3, t, J 7.4); minor diastereomer (5, m), 6.87 (2, s), 6.65 (1, d, J 15.9), (1, m), 5.35 (1, d, J 5.0), (1, m), 2.53 (6, s), 2.26 (3, s), (2, m), (2, m), (3, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 140.7, 139.8, 138.2, 137.5, 133.2, 131.4, 131.1, 129.4, 128.2, 127.3, 58.6, 39.1, 21.0, 19.9, 19.7, 14.2; m/z (ES+) 364 ([M+a] +, 98%), 342 ([M+] +, 100), 325 (20); RMS: Found: C S (S)--(1-cyclohexylbutyl)-2,4,6-trimethylbenzenesulfinamide 4i The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(cyclohexylmethylene)-2,4,6- trimethylbenzenesulfinamide 2i (42 mg, mmol) and gave the crude product (56 mg, 58.8:41.2 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4i (35 mg, mmol, 73%, 58.2:41.8 dr) as a white solid. M.p C; [α] D (c 1.0, CCl 3 ); IR (ATR) 3220, 2923, 2852, 1602, 1448, 1378, 1068, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.87 (2, s), 4.98 (1, d, J 8.1), (1, m), 2.55 (6, s), 2.25 (3, s), (15, m), 0.88 (3, t, J 6.8); minor diastereomer 6.87 (2, s), 5.13 (1, d, J 8.6), (1, m), 2.55 (6, s), 2.25 (3, s), (15, m), (3, m); 13 C MR (101 Mz, acetoned 6 ) major and minor diastereomers 140.9, 140.7, 140.6, 140.5, 137.2, 137.1, 131.4, 131.3, 62.5, 62.0, 44.0, 43.6, 35.9, 35.7, 29.8, 29.3, 27.5, 27.4, 27.3, 27.3, 27.2, 21.0, 20.3, 19.9, 19.8, 19.7, 14.4, 14.4; m/z (ES+) 344 ([M+a] +, 34%), 322 ([M+] +, 100), 305 (19); RMS: Found: C S (S)--((S)-1-(3,4-dimethoxyphenyl)butyl)-2,4,6-trimethylbenzenesulfinamide 4j

12 The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(3,4-dimethoxybenzylidene)-2,4,6- trimethylbenzenesulfinamide 2j (50 mg, mmol) and gave the crude product (64 mg, 79.4:20.6 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4j (50 mg, mmol, 89%, 82.0:18.0 dr) as a white solid. M.p C; [α] D (c 1.0, CCl 3 ); IR (ATR) 3247, 2955, 2915, 2871, 1595, 1516, 1456, 1260, 1023; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.94 (1, s), 6.82 (4, s), 5.60 (1, d, J 6.8), 4.32 (1, q, J 7.2), 3.76 (3, s), 3.76 (3, s), 2.51 (6, s), 2.23 (3, s), (1, m), (1, m), (2, m), 0.90 (3, t, J 7.3); minor diastereomer 7.03 (1, s), 6.90 (2, s), 6.85 (2, s), 5.42 (1, d, J 4.3), (1, m), 3.80 (3, s), 3.77 (3, s), 2.44 (6, s), 2.25 (3, s), (1, m), (1, m), (2, m), 0.87 (3, t, J 7.3); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 150.3, 149.5, 140.7, 139.7, 137.6, 137.5, 131.4, 119.8, 112.6, 112.0, 59.9, 56.2, 56.1, 40.8, 21.0, 20.4, 19.7, 14.2; m/z (ES+) 398 ([M+a] +, 100%), 376 ([M+] +, 97), 235 (18); RMS: Found: C S (S)--(1-(3,4-dimethoxyphenyl)butyl)-2,4,6-trimethylbenzenesulfonamide 3-Chloroperbenzoic acid (22 mg, mmol) (70% purity) was added to a solution of (S)-- ((S)-1-(3,4-dimethoxyphenyl)butyl)-2,4,6-trimethylbenzenesulfinamide 4j (30 mg, mmol) in DCM (1 ml) at room temperature and was stirred for 2.5 hr. A saturated sodium bicarbonate solution (3 ml) was added and the mixture was extracted three times with DCM. The combined organic phase was washed with a saturated sodium bicarbonate solution, dried using a hydrophobic frit and the solvent evaporated to give the title compound (29 mg, mmol, 94%) as a yellow oil. [α] D (c 1.1, CCl 3 ); IR (ATR) 3296, 2958, 2936, 2872, 1603, 1514, 1454, 1319, 1261, 1147; 1 MR (400 Mz, acetone-d 6 ) 6.81 (2, s), 6.68 (1, d, J 1.9 z), 6.64 (1, d, J 8.2), (1, m), 6.59 (1, dd, J 8.2, 1.9), 4.17 (1, q, J 7.8), 3.71 (3, s), 3.66 (3, s), 2.50 (6, s), 2.19 (3, s), (1, m), (1, m), (2, m), 0.83 (3, t, J 7.3); 13 C MR (101 Mz, acetone-d 6 ) 150.1, 149.5, 142.1, 139.3, 136.9, 135.5, 132.4, 119.6, 112.5, 111.1, 58.4, 56.3, 55.9, 40.5, 23.3, 20.8, 20.1, 13.9; m/z (ES+) 414 ([M+a] +, 14%), 392 ([M+] +, 12), 193 (18), 151 (100); RMS: Found: C S (S)-1-(3,4-dimethoxyphenyl)butan-1-amine Trifluoroacetic acid (0.01 ml, mmol) was added to a solution of (S)--((S)-1-(3,4- dimethoxyphenyl)butyl)-2,4,6-trimethylbenzenesulfinamide 4j (20 mg, mmol,

13 82.0:18.0 dr) in dry methanol (2 ml) and stirred for 3 hr. The solvent was evaporated to give the crude product, to which DCM (5 ml) and 2M hydrochloric acid (5 ml) were added. The organic phase was discarded. The acid phase was basified with solid sodium hydroxide and then extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the title compound (9.4 mg, mmol, 85%, 64% ee) as a colourless oil. [α] D 20-5 (c 0.8, CCl 3, 64% ee); IR (ATR) 3368, 3305, 2955, 2931, 1592, 1511, 1461, 1258, 1231, 1138; 1 MR (400 Mz, CDCl 3 ) 6.89 (1, s), 6.83 (2, s), 3.90 (3, s), 3.88 (3, s), 3.86 (1, t, J 7.0), (2, m), (2, m), 0.92 (3, t, J 7.3); 13 C MR (101 Mz, CDCl 3 ) 149.1, 147.9, 139.6, 118.4, 111.1, 109.6, 56.0, 55.9, 55.8, 42.0, 19.8, Alternative procedure for (S)-1-(3,4-dimethoxyphenyl)butan-1-amine Boron trifluoride diethyl etherate (0.014 ml, mmol) was added to a solution of (S)-- ((S)-1-(3,4-dimethoxyphenyl)butyl)-2,4,6-trimethylbenzenesulfinamide 4j (20 mg, mmol, 82.0:18.0 dr) in dry methanol (2 ml) and stirred for 3 hr. The solvent was evaporated to give the crude product, to which DCM (5 ml) and 2M hydrochloric acid (5 ml) were added. The organic phase was discarded. The acid phase was basified with solid sodium hydroxide and then extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the title compound (9.1 mg, mmol, 82%, 64% ee) as a colourless oil. Spectral properties identical to previous compound. Alternative procedure for (S)-1-(3,4-dimethoxyphenyl)butan-1-amine The general procedure B was followed using (S)--((S)-1-(3,4-dimethoxyphenyl)butyl)- 2,4,6-trimethylbenzenesulfinamide 4j (20 mg, mmol, 82.0:18.0 dr) and gave the title compound (8.6 mg, mmol, 77%, 64% ee) as a colourless oil. Spectral properties identical to previous compound. Alternative procedure for (S)-1-(3,4-dimethoxyphenyl)butan-1-amine Methylmagnesium bromide (3M in diethyl ether) (0.053 ml, mmol) was added dropwise to a solution of (S)--((S)-1-(3,4-dimethoxyphenyl)butyl)-2,4,6- trimethylbenzenesulfinamide 4j (20 mg, mmol, 82.0:18.0 dr) in dry TF (1 ml) at -78 C and stirred for 40 min and then the dry ice bath was removed and it was stirred for 1 hr whilst warming to room temperature. DCM (5 ml) and 2M hydrochloric acid (5 ml) were added to the mixture and the aqueous phase was further extracted two times with DCM. The organic phase was discarded. The acid phase was basified with solid sodium hydroxide and then extracted three times with DCM. The combined organic phase was dried using a hydrophobic frit and the solvent evaporated to give the title compound (9.0 mg, mmol, 81%, 64% ee) as a colourless oil. Spectral properties identical to previous compound. Determination of the enantiomeric excess of (S)-1-(3,4-dimethoxyphenyl)butan-1-amine (S)-1-(3,4-dimethoxyphenyl)butan-1-amine (8.8 mg, mmol), 2-formylphenylboronic acid (6.3 mg, mmol) and (S)-binol (13.3 mg, mmol) were dissolved in chloroform-d (4 ml) in the presence of 4Å molecular sieves and the 1 MR spectra of an aliquot was acquired after 5 min. The 1 MR spectrum (400 Mz) of the diastereoisomeric imino-boronate esters had characteristic peaks for the imine proton (8.36 (1, s) (R), 8.11 (1, s) (S)), the α-methine proton (4.84 (1, dd, J 10.5, 3.8) (S), 4.70 (1,

14 dd, J 10.8, 4.0) (R)) and the two methoxy groups (3.97 (3, s) (S), 3.90 (3, s) (S), 3.82 (3, s) (R), 3.48 (3, s) (R)) and the resonances were all well resolved. The relative intensities of these four sets of protons confirmed the enantiopurity of the amine, according to the reported procedure used for similar amines. 10 (S)--((S,E)-hept-2-en-4-yl)-2,4,6-trimethylbenzenesulfinamide 4k The general procedure A was followed using n-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--((E)-but-2-en-1-ylidene)-2,4,6- trimethylbenzenesulfinamide 2k (35 mg, mmol) and gave the crude product (49 mg, 76.9:23.1 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 4k (28 mg, mmol, 67%, 77.5:22.5 dr) as a colourless oil. [α] D (c 1.0, CCl 3 ); IR (ATR) 3208, 2958, 2929, 2871, 1602, 1451, 1378, 1071, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.86 (2, s), 5.59 (1, dd, J 15.7, 6.7), 5.47 (1, ddd, J 15.7, 6.5, 1.5), 5.16 (1, d, J 6.6), 3.76 (1, qn, J 6.8), 2.53 (6, s), 2.25 (3, s), 1.62 (3, d, J 6.5), (2, m), (2, m), 0.90 (3, t, J 7.3); minor diastereomer 6.86 (2, s), (1, m), (1, m), 5.10 (1, d, J 4.0), (1, m), 2.51 (6, s), 2.25 (3, s), 1.70 (3, dd, J 6.3, 1.5), (2, m), (2, m), 0.87 (3, t, J 7.3); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 140.6, 140.1, 137.3, 134.6, 131.4, 126.7, 58.6, 39.1, 21.0, 19.9, 19.7, 18.0, 14.2; m/z (ES+) 302 ([M+a] +, 71%), 280 ([M+] +, 82), 263 (29); RMS: Found: C S (S)--((S)-1-(4-methoxyphenyl)-2-methylpropyl)-2,4,6-trimethylbenzenesulfinamide 5b The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(4-methoxybenzylidene)-2,4,6- trimethylbenzenesulfinamide 2b (45 mg, mmol) and gave the crude product (53 mg, 99.1:0.9 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5b (41 mg, mmol, 79%, 99.2:0.8 dr) as a white solid. M.p C; diastereomeric ratio: 99.6:0.4, determined by PLC [Chiralpak (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] 20 D +197 (c 1.0, CCl 3 ); IR (ATR) 3236, 2949, 2917, 2866, 1614, 1517, 1460, 1383, 1064, 1024; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.20 (2, d, J 8.6), 6.81 (2, d, J 8.6), 6.80 (2, s), 5.64 (1, d, J 7.8), 4.02 (1, t, J 7.7), 3.76 (3, s), 2.47 (6, s), 2.23 (3, s), 2.05 (1, oct, J 6.8), 0.98 (3, d, J 6.6), 0.77 (3, d, J 6.8); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 159.6, 140.6, 139.8, 137.4, 135.8, 131.3, 129.2, 114.1, 66.6, 55.5, 35.0, 21.0, 20.1, 19.9, 19.7; m/z (ES+) 368 ([M+a] +, 100%), 346 ([M+] +, 8), 329 (13), 163 (15); RMS: Found: C as (S)--((S)-1-mesityl-2-methylpropyl)-2,4,6-trimethylbenzenesulfinamide 5c

15 The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)-2,4,6-trimethyl--(2,4,6- trimethylbenzylidene]benzenesulfinamide 2c (47 mg, mmol) and gave the crude product (53 mg, 99.0:1.0 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5c (44 mg, mmol, 82%, 99.2:0.8 dr) as a white solid. M.p C; diastereomeric ratio: 99.9:0.1, determined by PLC [Chiralpak IA (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3252, 2959, 2865, 1605, 1464, 1378, 1071, 1050; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.85 (2, s), 6.81 (1, s), 6.79 (1, s), 5.24 (1, d, J 7.8), 4.40 (1, dd, J 10.4, 7.8), 2.47 (6, s), 2.43 (3, s), 2.34 (3, s), 2.25 (3, s), (1, m), 2.20 (3, s), 1.18 (3, d, J 6.6), 0.67 (3, d, J 6.8); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 140.9, 140.5, 137.3, 137.2, 137.1, 136.7, 136.0, 131.9, 131.4, 130.0, 64.2, 33.8, 21.9, 21.8, 21.6, 21.0, 20.9, 20.1, 19.6; m/z (ES+) 380 ([M+a] +, 100%), 358 ([M+] +, 12), 341 (5); RMS: Found: C as (S)--((S)-1-(4-chlorophenyl)-2-methylpropyl)-2,4,6-trimethylbenzenesulfinamide 5d The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(4-(chlorobenzylidene)-2,4,6- trimethylbenzenesulfinamide 2d (46 mg, mmol) and gave the crude product (59 mg, 95.9:4.1 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5d (47 mg, mmol, 90%, 95.5:4.5 dr) as a white solid. M.p C; diastereomeric ratio: 95.0:5.0, determined by PLC [Chiralpak IA (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (major), min (minor)]; [α] 21 D +184 (c 1.0, CCl 3 ); IR (ATR) 3188, 2965, 2927, 2868, 1599, 1493, 1441, 1381, 1064, 1044; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (4, m), 6.77 (2, s), 5.84 (1, d, J 8.1), 4.10 (1, t, J 7.9), 2.46 (6, s), 2.22 (3, s), (1, m), 0.98 (3, d, J 6.8), 0.77 (3, d, J 6.8); minor diastereomer (4, m), 6.85 (2, s), 5.61 (1, d, J 4.8), 4.16 (1, dd, J 7.9, 4.8), 2.41 (6, s), 2.25 (3, s), (1, m), (3, m), (3, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 143.0, 140.8, 139.3, 137.5, 132.7, 131.4,

16 129.9, 128.7, 66.1, 35.1, 21.0, 20.0, 19.9, 19.7; m/z (ES+) 372 ([M+a] +, 100%), 350 ([M+] +, 10), 151 (12); RMS: Found: C ascl (S)-2,4,6-trimethyl--((S)-4-methyl-1-phenylpent-1-yn-3-yl)benzenesulfinamide 5e The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)-2,4,6-trimethyl--(3-phenylpropyn-2-yn-1- ylidene]benzenesulfinamide 2e (44 mg, mmol) and gave the crude product (53 mg, 82.9:17.1 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5e (31 mg, mmol, 61%, 82.4:17.6 dr) as a colourless oil. Diastereomeric ratio: 83.3:16.7, determined by PLC [Chiralpak AY- (heptane/ethanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3206, 2961, 2926, 2870, 1600, 1465, 1443, 1382, 1072, 1048; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.88 (2, s), 5.78 (1, d, J 7.2), 4.12 (1, dd, J 7.2, 6.3), 2.57 (6, s), 2.25 (3, s), 2.09 (1, qqd, J 6.8, 6.6, 6.3), 1.11 (3, d, J 6.8), 1.09 (3, d, J 6.6); minor diastereomer (5, m), 6.90 (2, s), 5.69 (1, d, J 6.6), 4.23 (1, dd, J 6.6, 5.3), 2.58 (6, s), 2.26 (3, s), (1, m), (6, m); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 141.0, 139.3, 137.7, 132.4, 131.5, 129.3, 129.1, 124.1, 89.5, 85.4, 54.7, 35.2, 21.0, 19.7, 19.7, 18.7; m/z (ES+) 362 ([M+a] +, 100%), 340 ([M+] +, 29); RMS: Found: C as (S)--((S)-1-(furan-2-yl)-2-methylpropyl)-2,4,6-trimethylbenzenesulfinamide 5f The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(furan-2-ylmethylene]-2,4,6- trimethylbenzenesulfinamide 2f (39 mg, mmol) and gave the crude product (53 mg, 96.8:3.2 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5f (43 mg, mmol, 93%, 97.8:2.2 dr) as a white solid. M.p C; diastereomeric ratio: 97.1:2.9, determined by PLC [Chiralpak AD (heptane/isopropanol 95:5, flow rate: 1.0 ml/min, l=215 nm, retention time: min (minor), min (major)]; [α] D (c 1.0, CCl 3 ); IR (ATR) 3198, 2952, 2925, 2865, 1602, 1441, 1380, 1068, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 7.43 (1, dd, J 1.8, 0.8), 6.85 (2, s), 6.32 (1, dd, J 3.3, 1.8), 6.23 (1, d, J 3.3), 5.61 (1, d, J 8.5), 4.19 (1, dd, J 8.5, 6.8), 2.51 (6, s), 2.25 (3, s), 2.19 (1, oct, J 6.8), 0.94 (3, d, J 6.8), 0.88 (3, d, J 6.8); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 156.6, 142.3, 140.8, 139.7, 137.4, 131.4, 110.9, 107.6, 60.9, 33.7, 21.0, 19.6, 19.2; m/z (ES+) 328 ([M+a] +, 100%), 306 ([M+] +, 38), 167 (16); RMS: Found: C as (S)-2,4,6-trimethyl--(2-methyloctan-3-yl)benzenesulfinamide 5g

17 The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--hexylidene-2,4,6-trimethylbenzenesulfinamide 2g (40 mg, mmol) and gave the crude product (49 mg). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the impure product (30 mg) which was further purified by mass directed autopreparation (Xbridge column using acetonitrile/water with an ammonium carbonate modifier) to give the title compound 5g (18 mg, mmol, 39%, 51.0:49.0 dr) as a colourless oil. [α] D (c 1.0, CCl 3 ); IR (ATR) 3217, 2956, 2928, 2870, 1602, 1462, 1379, 1069, 1046; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.87 (2, s), 5.13 (1, d, J 8.8), (1, m), 2.56 (6, s), 2.26 (3, s), (1, m), (8, m), (9, m); minor diastereomer 6.87 (2, s), 5.02 (1, d, J 7.8), (1, m), 2.56 (6, s), 2.26 (3, s), (1, m), (8, m), (9, m); 13 C MR (101 Mz, acetone-d 6 ) major and minor diastereomers 140.9, 140.9, 140.6, 140.5, 137.3, 137.2, 131.4, 131.4, 63.3, 62.4, 33.5, 33.4, 33.3, 33.1, 32.6, 32.6, 27.0, 26.4, 23.4, 23.4, 21.0, 19.8, 19.3, 18.8, 18.8, 18.3, 14.4, 14.4; m/z (ES+) 332 ([M+a] +, 31%), 310 ([M+] +, 83); RMS: Found: C S (S)-2,4,6-trimethyl--((E)-4-methyl-1-phenylpent-1-en-3-yl)benzenesulfinamide 5h The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.15 ml, mmol) and (S,E)-2,4,6-trimethyl--((E)-3- phenylallylidene)benzenesulfinamide 2h (45 mg, mmol) and gave the crude product (64 mg, 50.0:50.0 dr). Purification by flash chromatography on silica gel (elution with 0-13% ethyl acetate/dcm) gave the title compound 5h (18 mg, mmol, 34%, 51.5:48.5 dr) as a colourless oil. [α] D (c 1.0, CCl 3 ); IR (ATR) 3211, 2958, 2926, 2870, 1601, 1450, 1380, 1071, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereomer (5, m), 6.87 (2, s), 6.65 (1, d, J 15.9), 6.29 (1, dd, J 15.9, 8.1), 5.31 (1, d, J 5.6), (1, m), 2.54 (6, s), 2.26 (3, s), (1, m), 1.00 (3, d, J 6.8), 0.95 (3, d, J 6.8); minor diastereomer (5, m), 6.85 (2, s), 6.49 (1, d, J 15.9), 6.27 (1, dd, J 15.9, 7.6), 5.41 (1, d, J 7.1), (1, m), 2.56 (6, s), 2.23 (3, s), (1, m), 0.97 (6, d, J 6.8); 13 C MR (101 Mz, acetone-d 6 ) major and minor diastereomers 140.8, 140.7, 139.9, 139.8, 138.3, 138.1, 137.7, 137.5, 133.3, 132.2, 131.5, 131.4, 131.0, 130.1, 129.5, 129.4, 128.4, 128.2, 127.3, 127.3, 64.6, 64.2, 34.2, 21.0, 21.0, 19.8, 19.6, 19.6, 19.4, 19.1, 18.6; m/z (ES+) 364 ([M+a] +, 64%), 342 ([M+] +, 100); RMS: Found: C S (S)--((S)-1-cyclohexyl-2-methylpropyl)-2,4,6-trimethylbenzenesulfinamide 5i

18 The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.15 ml, mmol) and (S,E)--(cyclohexylmethylene)-2,4,6- trimethylbenzenesulfinamide 2i (42 mg, mmol) and gave the crude product (50 mg, 75.2:24.8 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5i (27 mg, mmol, 57%, 75.8:24.2 dr) as a white solid. M.p C; [α] D (c 1.0, CCl 3 ); IR (ATR) 3233, 2922, 2851, 1602, 1447, 1381, 1068, 1047; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.88 (2, s), 4.87 (1, d, J 8.8), (1, m), 2.59 (6, s), 2.26 (3, s), (12, m), 0.94 (3, d, J 6.6), 0.79 (3, d, J 6.8); minor diastereomer 6.88 (2, s), (1, m), (1, m), 2.59 (6, s), 2.26 (3, s), (12, m), 1.01 (3, d, J 6.8), 0.97 (3, d, J 6.8); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 142.0, 140.5, 136.7, 131.4, 68.9, 41.2, 32.0, 30.8, 30.0, 27.4, 27.4, 27.2, 21.4, 21.0, 19.9, 18.0; m/z (ES+) 344 ([M+a] +, 14%), 322 ([M+] +, 88), 318 (28); RMS: Found: C S (S)--((S)-1-(3,4-dimethoxyphenyl)-2-methylpropyl)-2,4,6-trimethylbenzenesulfinamide 5j The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.22 ml, mmol) and (S,E)--(3,4-dimethoxybenzylidene)-2,4,6- trimethylbenzenesulfinamide 2j (50 mg, mmol) and gave the crude product (58 mg, 98.9:1.1 dr). Purification by flash chromatography on silica gel (elution with 0-25% ethyl acetate/cyclohexane) gave the title compound 5j (52 mg, mmol, 92%, 99.5:0.5 dr) as a white solid. M.p C; [α] D (c 1.0, CCl 3 ); IR (ATR) 3241, 2949, 2918, 2866, 1593, 1521, 1466, 1261, 1022; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.93 (1, d, J 1.8), 6.81 (1, d, J 8.3), 6.80 (2, s), 6.77 (1, dd, J 8.3, 1.8), 5.66 (1, d, J 8.3), 4.00 (1, t, J 8.0), 3.77 (6, s), 2.48 (6, s), 2.23 (3, s), 2.04 (1, oct, J 6.8), 0.99 (3, d, J 6.6), 0.79 (3, d, J 6.6); 13 C MR (101 Mz, acetone-d 6 ) major diastereomer 150.1, 149.3, 140.6, 139.8, 137.5, 136.7, 131.4, 120.3, 112.4, 112.3, 66.9, 56.2, 56.1, 35.2, 21.0, 20.2, 20.0, 19.7; m/z (ES+) 398 ([M+a] +, 89%), 376 ([M+] +, 100), 359 (17), 193 (20); RMS: Found: C S (S)-2,4,6-trimethyl--((S,E)-2-methylhex-4-en-3-yl)benzenesulfinamide 5k The general procedure A was followed using iso-propylmagnesium chloride (2M in diethyl ether) (0.15 ml, mmol) and (S,E)--((E)-but-2-en-1-ylidene)-2,4,6- trimethylbenzenesulfinamide 2k (35 mg, mmol) and gave the crude product (50 mg, 92.1:7.9 dr). Purification by flash chromatography on silica gel (elution with 0-13% ethyl acetate/dcm) gave the title compound 5k (25 mg, mmol, 60%, 93.0:7.0 dr) as a white solid. M.p C; [α] D (c 1.0, CCl 3 ); IR (ATR) 3175, 2951, 2921, 2866, 1602, 1438, 1379, 1068, 1044; 1 MR (400 Mz, acetone-d 6 ) major diastereomer 6.86 (2, s), 5.58 (1, dq, J 15.3, 6.5), 5.47 (1, ddd, J 15.3, 7.1, 1.4), 5.12 (1, d, J 6.6), 3.57 (1, ddd, J 7.1, 6.8, 6.6), 2.54 (6, s), 2.25 (3, s), 1.86 (1, oct, J 6.8), 1.64 (3, d, J 6.5), 0.89 (6, d, J 6.8); minor diastereomer 6.86 (2, s), (2, m), (1, m), (1, m), 2.52 (6, s), 2.25 (3, s), (1, m), 1.72 (3, dd, J 6.4, 1.4),