Asymmetric Synthesis of New Chiral β-amino Acid Derivatives by Mannich-type Reactions of Chiral N- Sulfinyl Imidates with N-Tosyl Aldimines

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Asymmetric Synthesis of New Chiral β-amino Acid Derivatives by Mannich-type Reactions of Chiral N- Sulfinyl Imidates with N-yl Aldimines Filip Colpaert, Sven Mangelinckx, and Norbert De Kimpe Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium norbert.dekimpe@ugent.be Supporting Information Table of Contents I. General methods... S-2 II. Synthetic procedures and spectral data... S-3 1. Synthesis of β-(sulfonylamino)sulfinylimidates 3... S-3 2. N-Deprotection of β-(sulfonylamino)sulfinylimidates 3 to the corresponding β- sulfonylamino imidate hydrochlorides 4... S-8 3. Synthesis of chiral β-sulfonylamino amides 5... S-11 4. Synthesis of chiral β-sulfonylamino esters 6... S-14 5. Synthesis of chiral γ-sulfonylamino alcohols 7... S-18 6. Synthesis of chiral N-tosylazetidines 8... S-20 III. Copies of 1 H NMR and 13 C NMR spectra of 3, 4, 5, 6, 7 and 8... S-22 S-1

I. General methods Tetrahydrofuran (THF) and diethyl ether (Et 2 O) were freshly distilled under a nitrogen atmosphere from sodium/benzophenone ketyl. All other chemicals were of commercial grade and used without further purification. Petroleum ether refers to the 40-60 C boiling fraction. 1 H NMR (300 MHz), 13 C NMR (75 MHz) spectra were recorded in deuterated solvents with tetramethylsilane (TMS, δ = 0 ppm) as internal standard unless specified otherwise. Mass spectra were recorded using a direct inlet system (ESI, 4000 V). IR spectra were obtained from samples in neat form with an ATR (Attenuated Total Reflectance) accessory. Elementary analyses were performed using a Perkin-Elmer 2400 (Series II, CHNS/O) elementary analyzer. The purification of the reaction mixtures was performed by column chromatography with silica gel (particle size 0.035-0.070 mm, pore diameter ca. 6 nm). S-2

II. Synthetic procedures and spectral data 1. Synthesis of β-(sulfonylamino)sulfinylimidates 3 Table S1. Optimization of the addition reaction of N-sulfinyl imidate 1 across aldimines 2 R N tbu S O 1 1) base 2) 1.0 equiv N X H 2a X = Cl X 2b X = H 2c X = R S (R S,S,R)-anti-3a-c tbu tbu N S O N S O + R S + R R R X (R S,R,S)-anti-3a-c X S S N tbu S O (R S,S,S)-syn-3a-c entry X 1 (equiv) reaction conditions (R S,S,R)-3/(R S,R,S)-3/ (R S,S,S)-3 a anti/syn a yield (%) 1 Cl 1.5 1) 5 mol% DBU, DMF, 0 C - - - 2) 0 C to rt, 72 h 2 Cl 1.0 1) 1.05 equiv LDA, THF, -78 C, 2 min - - - 2) -78 C to 0 C, 3 h 3 Cl 2.0 1) 2.0 equiv LiHMDS, THF, -78 C, 45 min 67/26/7 93/7-2) -78 C, 1 h 4 Cl 2.0 1) 2.0 equiv LiHMDS, THF, -78 C, 45 min 57/37/6 94/6-2) -78 C to rt, 1 h 5 Cl 2.0 1) 2.0 equiv KHMDS, THF, -78 C, 45 min 62/16/22 78/22-2) -78 C, 1 h 6 Cl 2.0 1) 2.0 equiv LiHMDS, THF, -78 C, 45 min 45/49/6 94/6 - + 2.0 equiv ZnCl 2, -78 C, 15 min 2) -78 C, 1 h 7 Cl 1.2 1) 1.2 equiv LiHMDS, THF, -78 C, 45 min 2) -78 C, 1 h 75/25/0 > 99/1 (R S,S,R)-3a (59), (R S,R,S)-3a (21) 8 H 1.2 1) 1.2 equiv LiHMDS, THF, -78 C, 45 min 2) -78 C, 1 h 67/26/7 93/7 (R S,S,R)-3b (58), (R S,R,S)-3b (24), (R S,S,S)-3b (5) 9 1.2 1) 1.2 equiv LiHMDS, THF, -78 C, 45 min 2) -78 C, 1 h 38/60/2 98/2 (R S,S,R)-3c (34), (R S,R,S)-3c (50) 10 Cl 1.2 1) 1.2 equiv KHMDS, THF, -78 C, 45 min 63/12/25 75/25-2) -78 C, 1 h 11 Cl 1.2 1) 1.2 equiv NaHMDS, THF, -78 C, 45 min 51/22/27 73/27-2) -78 C, 1 h 12 Cl 1.2 1) 1.2 equiv LiHMDS, Toluene, -78 C, 45 min 67/26/7 93/7-2) -78 C, 1 h 13 Cl 1.2 1) 1.2 equiv LiHMDS, THF, -97 C, 45 min 75/18/7 93/7-2) -97 C, 1 h 14 Cl 1.2 1) 1.2 equiv LiHMDS, THF, -78 C, 45 min - - - + 1.2 equiv HMPA, -78 C, 15 min 2) -78 C, 1 h 15 Cl 1.2 1) 1.2 equiv LiHMDS, THF, -78 C, 45 min 87/4/9 91/9 - + 1.2 equiv MgBr 2, -78 C, 15 min 2) -78 C, 1 h 16 Cl 1.2 1) 1.2 equiv LiHMDS, THF, -97 C, 45 min + 1.2 equiv MgBr 2, -97 C, 15 min 91/0/9 91/9 (R S,S,R)-3a (76), (R S,S,S)-3a (6) 2) -97 C, 1 h 17 Cl 1.2 1) 1.2 equiv KHMDS, THF, -97 C, 45 min 89/1/10 90/10 - + 1.2 equiv MgBr 2, -97 C, 15 min 2) -97 C, 1 h 18 H 1.2 1) 1.2 equiv LiHMDS, THF, -97 C, 45 min + 1.2 equiv MgBr 2, -97 C, 15 min 2) -97 C, 1 h 89/6/5 95/5 (R S,S,R)-3b (77), (R S,R,S)-3b (3), (R S,S,S)-3b (4) 19 1.2 1) 1.2 equiv LiHMDS, THF, -97 C, 45 min 67/30/3 b 97/3 - + 1.2 equiv MgBr 2, -97 C, 15 min 2) -97 C, 1 h 20 1.2 1) 1.2 equiv LiHMDS, THF, -78 C, 45 min + 1.2 equiv MgBr 2, -78 C, 15 min 2) -78 C, 1 h 93/1/6 94/6 (R S,S,R)-3c (73), (R S,S,S)-3c (5) a Determined via 1 H NMR analysis of the crude reaction mixture. b Only 31% conversion of N-sulfinyl imidate 1 into β- (sulfonylamino)sulfinylimidates 3c. S-3

The synthesis of β-(sulfonylamino)sulfinylimidates 3a is representative. A solution of R s - methyl N-tert-butanesulfinyl propanimidate (1.0 equiv, 2.73 g, 14.29 mmol) in THF (30 ml) was cooled to -97 C. A 1.0 M solution of LiHMDS (1.0 equiv, 14.29 ml, 14.29 mmol) in THF was slowly added and the resulting solution was stirred for 45 minutes at -97 C. After deprotonation a solution of MgBr 2 (1.0 equiv, 2.63 g, 14.29 mmol) in THF (25mL) was added dropwise and the reaction mixture was stirred for 15 minutes at -97 C. A solution of N-(4- chloro-benzylidene)-4-methylbenzenesulfonamide (0.83 equiv, 3.50 g, 11.93 mmol) in THF (15 ml) was then added dropwise and the reaction mixture was stirred at -97 C for 1.0 hours. To the reaction mixture was added a saturated solution of 4 Cl (5 ml), followed by a 1.0 N aqueous solution of NaOH (20 ml). The aqueous phase was extracted with Et 2 O (3 x 20 ml). The combined organic phases were dried (MgSO 4 ), filtered and evaporated in vacuo. The crude product was purified by flash chromatography to yield 4.40 g (9.06 mmol) of pure (R S,S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,S,R)-anti-3a and 0.35 g (0.72 mmol) of pure (R S,S,S)-methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)-N-tert-butanesulfinyl propanimidate (R S,S,S)-syn-3a. (R S,S,R)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,S,R)-anti-3a. R f = 0.14 (petroleum ether/ Et 2 O 3:7). White crystals, yield 76%. [α] D - 79.9 (c 0.4, CHCl 3 ). Mp 64.8-65.2 C. IR (cm -1 ): ν max 750, 1035, 1160, 1611, 1630. 1 H NMR (300 MHz, CDCl 3 ): δ 0.94 (3H, d, J = 7.2 Hz), 1.23 (9H, s), 2.31 (3H, s), 3.74 (3H, s), 3.82-3.93 (1H, m), 4.46 (1H, d x d, J = 9.6, 9.6 Hz), 6.39 (1H, d, J = 9.6 Hz), 6.88-7.06 (6H, m), 7.41 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 16.0, 21.5, 22.2, 43.2, 54.5, 56.8, 60.3, 127.0 (2C), 128.4 (2C), 128.5 (2C), 129.2 (2C), 133.4, S-4

137.1, 137.8, 143.0, 173.9. MS (ES, pos. mode) m/z (%): 485/487 (M + H +, 100). Anal. Calcd for C 22 H 29 ClN 2 O 4 S 2 : C 54.47; H 6.03; N 5.72. Found: C 54.57; H 5.95; N 5.41. (R S,R,S)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,R,S)-anti-3a. R f = 0.33 (petroleum ether/ Et 2 O 6:4). Colourless oil, yield 21%. [α] D - 111.0 (c 0.8, CHCl 3 ). IR (cm -1 ): ν max 751, 1160, 1286, 1611. 1 H NMR (300 MHz, CDCl 3 ): δ 0.84 (3H, d, J = 7.2 Hz), 1.26 (9H, s), 2.23 (3H, s), 3.36-3.46 (1H, m), 3.66 (3H, s), 4.19 (1H, d x d, J = 10.7, 8.3 Hz), 6.89 (2H, d, J = 8.3 Hz), 6.94 (4H, s), 7.22 (2H, d, J = 4.4 Hz), 7.32 (1H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 14.7, 21.4, 22.0, 44.5, 54.9, 57.3, 59.8, 126.8 (2C), 128.4 (2C), 129.0 (4C), 133.5, 137.7, 138.6, 142.3, 174.8. MS (ES, pos. mode) m/z (%): 485/487 (M + H +, 100). Anal. Calcd for C 22 H 29 ClN 2 O 4 S 2 : C 54.47; H 6.03; N 5.72. Found: C 54.78; H 5.98; N 5.66. (R S,S,S)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,S,S)-syn-3a. R f = 0.08 (petroleum ether/ Et 2 O 3:7). White crystals, yield 6%. [α] D - 152.2 (c 0.2, CHCl 3 ). Mp 147.7-148.2 C. IR (cm -1 ): ν max 1049, 1160, 1286, 1600. 1 H NMR (300 MHz, CDCl 3 ): δ 1.04 (9H, s), 1.37 (3H, d, J = 6.6 Hz), 2.33 (3H, s), 3.51 (3H, s), 3.75-3.87 (1H, m), 4.43 (1H, d x d, J = 9.6, 9.6 Hz), 6.39 (1H, d, J = 9.6 Hz), 6.97-7.07 (6H, m), 7.42 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 16.0, 21.5, 21.9, 43.9, 54.0, 56.2, 60.0, 127.0 (2C), 128.2 (2C), 128.6 (2C), 129.2 (2C), 133.4, 138.0, 138.1, 143.0, 175.2. MS (ES, pos. mode) m/z (%): 485/487 (M + H +, 100). Anal. Calcd for C 22 H 29 ClN 2 O 4 S 2 : C 54.47; H 6.03; N 5.72. Found: C 54.71; H 5.92; N 5.86. (R S,S,R)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)-N-tert-butanesulfinyl propanimidate (R S,S,R)-anti-3b. R f = 0.18 (petroleum ether/ Et 2 O 3:7). White crystals, yield S-5

77%. [α] D - 84.6 (c 0.4, CHCl 3 ). Mp 75.7-76.1 C. IR (cm -1 ): ν max 1038, 1161, 1614, 2951, 3169. 1 H NMR (300 MHz, CDCl 3 ): δ 0.97 (3H, d, J = 7.2 Hz), 1.18 (9H, s), 2.30 (3H, s), 3.73 (3H, s), 3.89-3.99 (1H, m), 4.43 (1H, d x d, J = 9.6, 9.6 Hz), 5.56 (1H, d, J = 9.6 Hz), 6.94-7.15 (7H, m), 7.45 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.6, 21.4, 22.0, 43.0, 54.3, 56.3, 60.7, 126.5 (2C), 126.9 (2C), 127.6, 128.5 (2 C), 129.1 (2C), 137.6, 138.6, 142.8, 174.4. MS (ES, pos. mode) m/z (%): 451 (M + H +, 100). Anal. Calcd for C 22 H 30 N 2 O 4 S 2 : C 58.64; H 6.71; N 6.22. Found: C 58.31; H 6.33; N 6.18. (R S,R,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)-N-tert-butanesulfinyl propanimidate (R S,R,S)-anti-3b. R f = 0.49 (petroleum ether/ Et 2 O 3:7). White crystals, yield 24%. [α] D - 138.6 (c 0.9, CHCl 3 ). Mp 120.5-120.9 C. IR (cm -1 ): ν max 1032, 1159, 1613, 2925, 3105. 1 H NMR (300 MHz, CDCl 3 ): δ 0.92 (3H, d, J = 6.6 Hz), 1.36 (9H, s), 2.26 (3H, s), 3.49-3.59 (1H, m), 3.75 (3H, s), 4.30 (1H, d x d, J = 10.5, 8.8 Hz), 6.91 (2H, d, J = 8.3 Hz), 7.03-7.13 (5H, m), 7.31 (3H, d, J = 8.8 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 14.7, 21.3, 22.0, 44.6, 54.7, 57.1, 60.3, 126.6 (3C), 127.4, 127.5 (3C), 128.2, 128.7, 138.6, 139.2, 141.8, 175.2. MS (ES, pos. mode) m/z (%): 451 (M + H +, 100). Anal. Calcd for C 22 H 30 N 2 O 4 S 2 : C 58.64; H 6.71; N 6.22. Found: C 58.37; H 6.45; N 6.21. (R S,S,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)-N-tert-butanesulfinyl propanimidate (R S,S,S)-syn-3b. R f = 0.10 (petroleum ether/ Et 2 O 3:7). White crystals, yield 5%. [α] D - 203.0 (c 0.3, CHCl 3 ). Mp 175.4-175.5 C. IR (cm -1 ): ν max 1057, 1160, 1291, 1601, 3190. 1 H NMR (300 MHz, CDCl 3 ): δ 1.00 (9H, s), 1.37 (3H, d, J = 7.2 Hz), 2.31 (3H, s), 3.50 (3H, s), 3.72-3.87 (1H, m), 4.47 (1H, d x d, J = 9.6, 9.6 Hz), 5.62 (1H, d, J = 9.6 Hz), 6.98-7.10 (7H, m), 7.45 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.6, 21.5, 21.8, 44.0, 54.0, 56.0, 60.5, 126.9 (2C), 127.1 (2C), 127.7, 128.3 (2C), 129.7 (2C), 137.8, 139.3, 142.8, S-6

175.3. MS (ES, pos. mode) m/z (%): 451 (M + H +, 100). Anal. Calcd for C 22 H 30 N 2 O 4 S 2 : C 58.64; H 6.71; N 6.22. Found: C 58.44; H 6.44; N 6.21. (R S,S,R)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,S,R)-anti-3c. R f = 0.13 (petroleum ether/ Et 2 O 3:7). White crystals, yield 73%. [α] D - 75.7 (c 0.5, CHCl 3 ). Mp 117.7-118.0 C. IR (cm -1 ): ν max 1159, 1610, 2946. 1 H NMR (300 MHz, CDCl 3 ): δ 0.95 (3H, d, J = 6.6 Hz), 1.20 (9H, s), 2.31 (3H, s), 3.72 (3H, s), 3.73 (3H, s), 3.84-3.97 (1H, m), 4.38 (1H, d x d, J = 9.6, 9.6 Hz), 5.53 (1H, d, J = 9.6 Hz), 6.60 (2H, d, J = 8.3 Hz), 6.87 (2H, d, J = 8.3 Hz), 7.04 (2H, d, J = 8.3 Hz), 7.44 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.7, 21.5, 22.2, 43.2, 54.4, 55.3, 56.5, 60.4, 113.9 (2C), 127.1 (2C), 127.8 (2C), 129.2 (2C), 130.9, 137.9, 142.8, 159.1, 174.6. MS (ES, pos. mode) m/z (%): 481 (M + H +, 100). Anal. Calcd for C 23 H 32 N 2 O 5 S 2 : C 57.47; H 6.71; N 5.83. Found: C 57.50; H 6.38; N 5.76. (R S,R,S)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,R,S)-anti-3c. R f = 0.42 (petroleum ether/ Et 2 O 3:7). White crystals, yield 50%. [α] D - 161.3 (c 0.5, CHCl 3 ). Mp 107.8-108.0 C. IR (cm -1 ): ν max 1028, 1160, 1296, 1593, 2953, 3107. 1 H NMR (300 MHz, CDCl 3 ): δ 0.92 (3H, d, J = 6.6 Hz), 1.33 (9H, s), 2.27 (3H, s), 3.45-3.56 (1H, m), 3.72 (3H, s), 3.75 (3H, s), 4.26 (1H, d x d, J = 10.7, 8.8 Hz), 6.59 (2H, d, J = 8.3 Hz), 6.94 (2H, d, J = 8.3 Hz), 7.00 (2H, d, J = 8.3 Hz), 7.25 (1H, d, J = 8.8 Hz), 7.31 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 14.8, 21.4, 22.1, 44.8, 54.8, 55.3, 57.2, 60.0, 113.7 (2C), 126.8 (2C), 128.6 (2C), 128.8 (2C), 131.3, 138.9, 141.8, 159.1, 175.4. MS (ES, pos. mode) m/z (%): 481 (M + H +, 100). Anal. Calcd for C 23 H 32 N 2 O 5 S 2 : C 57.47; H 6.71; N 5.83. Found: C 57.09; H 6.44; N 5.62. S-7

(R S,S,S)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,S,S)-syn-3c. R f = 0.07 (petroleum ether/ Et 2 O 3:7). White crystals, yield 5%. [α] D - 131.7 (c 0.2, CHCl 3 ). Mp 145.7-146.1 C. IR (cm -1 ): ν max 1047, 1159, 1249, 1605, 2948. 1 H NMR (300 MHz, CDCl 3 ): δ 1.02 (9H, s), 1.36 (3H, d, J = 6.6 Hz), 2.32 (3H, s), 3.50 (3H, s), 3.75-3.86 (1H, m), 4.41 (1H, d x d, J = 9.3, 9.3 Hz), 5.79 (1H, d, J = 9.3 Hz), 6.56-6.61 (2H, m), 6.86-7.10 (4H, m), 7.45 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.8, 21.5, 21.9, 44.1, 53.9, 55.3, 56.0, 60.0, 113.6 (2C), 127.1 (2C), 128.1 (2C), 129.2 (2C), 131.6, 138.0, 142.7, 159.0, 175.5. MS (ES, pos. mode) m/z (%): 481 (M + H +, 100). Anal. Calcd for C 23 H 32 N 2 O 5 S 2 : C 57.47; H 6.71; N 5.83. Found: C 57.29; H 6.49; N 5.71. 2. N-Deprotection of β-(sulfonylamino)sulfinylimidates 3 to the corresponding β- sulfonylamino imidate hydrochlorides 4 The synthesis of (S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(ptoluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4a is representative. To a solution of (R S,S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)-N-tertbutanesulfinyl propanimidate (R S,S,R)-anti-3a (2.31 g, 4.77 mmol) in ethanol (40 ml) was added dropwise a 4.0 M solution of dioxane.hcl (2.0 equiv, 2.38 ml, 9.53 mmol) at 0 C. The mixture was allowed to stir for 0.5 hour at 0 C. Then the reaction mixture was concentrated in vacuo. Precipitation in diethyl ether afforded 1.69 g (4.05 mmol) of pure (S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4a. (S,R)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4a. White crystals, yield 85%. [α] D + 32.0 (c 0.5, DMF). Mp 104.2-104.5 C. IR (cm -1 ): ν max 1090, 1159, 1655, 2873, 3040. 1 H NMR (300 MHz, CDCl 3 ): δ S-8

0.99 (3H, d, J = 7.2 Hz), 2.31 (3H, s), 3.71-3.81 (1H, m), 4.36 (1H, d x d, J = 10.5, 10.5 Hz), 4.46 (3H, s), 6.98 (2H, d, J = 8.3 Hz), 7.05 (2H, d, J = 8.3 Hz), 7.13 (2H, d, J = 8.3 Hz), 7.37 (2H, d, J = 8.3 Hz), 8.20 (1H, d, J = 10.5 Hz), 11.55 (1H, br s), 11.61 (1H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 14.1, 21.5, 44.7, 60.6, 61.4, 126.9 (2C), 128.8 (2C), 129.1 (2C), 129.2 (2C), 134.2, 135.3, 137.5, 143.1, 181.1. MS (ES, pos. mode) m/z (%): 381/383 (M + H + - HCl, 100). Anal. Calcd for C 18 H 22 Cl 2 N 2 O 3 S: C 51.80; H 5.31; N 6.71. Found: C 51.54; H 4.93; N 6.35. (R,S)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanimidate hydrochloride (R,S)-anti-4a. White crystals, yield 69%. [α] D - 39.3 (c 0.4, DMF). Mp 105.8-106.1 C. IR (cm -1 ): ν max 1089, 1158, 1657, 2878, 3040. 1 H NMR (300 MHz, CDCl 3 ): δ 0.99 (3H, d, J = 6.1 Hz), 2.31 (3H, s), 3.71-3.88 (1H, m), 4.36 (1H, d x d, J = 10.5, 10.5 Hz), 4.46 (3H, s), 6.97 (2H, d, J = 8.3 Hz), 7.04 (2H, d, J = 8.3 Hz), 7.12 (2H, d, J = 8.3 Hz), 7.37 (2H, d, J = 8.3 Hz), 8.21 (1H, d, J = 10.5 Hz), 11.60 (2H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 14.1, 21.5, 44.7, 60.6, 61.5, 126.9 (2C), 128.8 (2C), 129.1 (2C), 129.2 (2C), 134.2, 135.3, 137.5, 143.1, 181.2. MS (ES, pos. mode) m/z (%): 381/383 (M + H + - HCl, 100). Anal. Calcd for C 18 H 22 Cl 2 N 2 O 3 S: C 51.80; H 5.31; N 6.71. Found: C 51.63; H 5.13; N 6.56. (S,R)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4b. White crystals, yield 87%. [α] D + 47.5 (c 0.4, DMF). Mp 112.6-112.8 C. IR (cm -1 ): ν max 1090, 1160, 1330, 1654, 2876, 3062. 1 H NMR (300 MHz, CDCl 3 ): δ 0.97 (3H, d, J = 6.6 Hz), 2.27 (3H, s), 3.74-3.85 (1H, m), 4.36 (1H, d x d, J = 10.5, 10.5 Hz), 4.45 (3H, s), 6.95 (2H, d, J = 8.3 Hz), 7.06-7.21 (5H, m), 7.38 (2H, d, J = 8.3 Hz), 7.95 (1H, d, J = 10.5 Hz), 11.65 (1H, br s), 11.77 (1H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 14.0, 21.4, 44.9, 61.2, 61.3, 126.9 (2C), 127.7 (2C), 128.1, 128.7 (2C), 129.1 (2C), 136.9, S-9

137.7, 142.7, 181.3. MS (ES, pos. mode) m/z (%): 347 (M + H + - HCl, 100). Anal. Calcd for C 18 H 23 Cl 2 N 2 O 3 S: C 56.46; H 6.05; N 7.32. Found: C 56.11; H 6.31; N 7.24. (R,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanimidate hydrochloride (R,S)-anti-4b. White crystals, yield 83%. [α] D - 38.3 (c 0.3, DMF). Mp 115.2-115.4 C. IR (cm -1 ): ν max 1090, 1160, 1330, 1650, 2880, 3066. 1 H NMR (300 MHz, CDCl 3 ): δ 0.97 (3H, d, J = 6.6 Hz), 2.26 (3H, s), 3.72-3.90 (1H, m), 4.37 (1H, d x d, J = 10.5, 10.5 Hz), 4.44 (3H, s), 6.94 (2H, d, J = 8.3 Hz), 7.07-7.24 (5H, m), 7.38 (2H, d, J = 8.3 Hz), 7.98 (1H, d, J = 10.5 Hz), 11.69 (2H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 14.0, 21.4, 44.9, 61.2, 61.5, 126.9 (2C), 127.6 (2C), 128.1, 128.7 (2C), 129.1 (2C), 137.0, 137.7, 142.7, 181.3. MS (ES, pos. mode) m/z (%): 347 (M + H + - HCl, 100). Anal. Calcd for C 18 H 23 Cl 2 N 2 O 3 S: C 56.46; H 6.05; N 7.32. Found: C 56.80; H 6.09; N 7.40. (S,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,S)-syn-4b. White crystals, yield 63%. [α] D - 67.5 (c 0.2, DMF). Mp decomposition at 301.5-301.8 C. IR (cm -1 ): ν max 1158, 1667, 2872, 3361. 1 H NMR (300 MHz, CDCl 3 ): δ 1.33 (3H, d, J = 6.6 Hz), 2.27 (3H, s), 3.65-3.76 (1H, m), 4.18 (3H, s), 4.68 (1H, d x d, J = 9.4, 7.7 Hz), 6.99 (2H, d, J = 8.3 Hz), 7.05-7.19 (5H, m), 7.50 (2H, d, J = 8.3 Hz), 7.64 (1H, d, J = 9.4 Hz), 11.27 (1H, br s), 12.01 (1H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 13.7, 21.4, 44.9, 60.4, 60.5, 127.0 (2C), 127.4 (2C), 127.9, 128.4 (2C), 129.2 (2C), 136.2, 137.4, 142.9, 180.1. MS (ES, pos. mode) m/z (%): 347 (M + H + - HCl, 100). Anal. Calcd for C 18 H 23 Cl 2 N 2 O 3 S: C 56.46; H 6.05; N 7.32. Found: C 56.76; H 5.98; N 6.92. (S,R)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4c. White crystals, yield 80%. [α] D + 56.1 (c 0.2, DMF). Mp 215.7-215.9 C. IR (cm -1 ): ν max 1152, 1322, 1640, 2936, 3067. 1 H NMR (300 MHz, CDCl 3 ): δ S-10

0.97 (3H, d, J = 5.0 Hz), 2.28 (3H, s), 3.65-3.80 (1H, m), 3.73 (3H, s), 4.32 (1H, d x d, J = 9.9, 9.9 Hz), 4.43 (3H, s), 6.63 (2H, d, J = 8.3 Hz), 6.97 (2H, d, J = 8.3 Hz), 7.10 (2H, d, J = 8.3 Hz), 7.40 (2H, d, J = 8.3 Hz), 8.03 (1H, d, J = 9.9 Hz), 11.58 (2H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 14.1, 21.4, 45.0, 55.2, 60.7, 61.0, 114.0 (2C), 126.9 (2C), 128.8 (2C), 128.9, 129.0 (2C), 137.7, 142.5, 159.3, 181.3. MS (ES, pos. mode) m/z (%): 377 (M + H + - HCl, 100). Anal. Calcd for C 19 H 25 ClN 2 O 4 S: C 55.26; H 6.10; N 6.78. Found: C 55.12; H 6.00; N 6.64. (R,S)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)-propanimidate hydrochloride (R,S)-anti-4c. White crystals, yield 92%. [α] D - 56.0 (c 0.2, DMF). Mp 224.0-224.4 C. IR (cm -1 ): ν max 1157, 1321, 1640, 2936, 3064. 1 H NMR (300 MHz, CDCl 3 ): δ 0.97 (3H, d, J = 5.5 Hz), 2.28 (3H, s), 3.67-3.81 (1H, m), 3.73 (3H, s), 4.30 (1H, d x d, J = 9.9, 9.9 Hz), 4.43 (3H, s), 6.63 (2H, d, J = 8.3 Hz), 6.97 (2H, d, J = 8.3 Hz), 7.10 (2H, d, J = 8.3 Hz), 7.39 (2H, d, J = 8.3 Hz), 7.91 (1H, d, J = 9.9 Hz), 11.64 (2H, br s). 13 C NMR (75 MHz, CDCl 3 ): δ 14.1, 21.5, 45.1, 55.3, 60.8, 61.4, 114.0 (2C), 127.0 (2C), 128.9 (2C), 129.0, 129.1 (2C), 137.8, 142.6, 159.4, 181.5 3. MS (ES, pos. mode) m/z (%): 377 (M + H + - HCl, 100). Anal. Calcd for C 19 H 25 ClN 2 O 4 S: C 55.26; H 6.10; N 6.78. Found: C 55.04; H 6.02; N 6.58. 3. Synthesis of chiral β-sulfonylamino amides 5 The synthesis of (S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(ptoluenesulfonylamino)propanamide (S,R)-anti-5a is representative. (S,R)-Methyl 2-methyl-3- (4-chlorophenyl)-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4a (0.57 g, 1.37 mmol) was dissolved in chloroform (20 ml). The reaction mixture was stirred for 16 hours at reflux temperature and subsequently evaporated in vacuo. Recrystallization S-11

from diethyl ether afforded 0.46 g (1.24 mmol) of pure (S,R)-methyl 2-methyl-3-(4- chlorophenyl)-3-(p-toluenesulfonylamino)propanamide (S,R)-anti-5a. (S,R)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanamide (S,R)-anti-5a. White crystals, yield 91%. [α] D + 55.3 (c 0.3, DMF). Mp 199.2-199.5 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (80%) / Ethanol (20%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-5a) = 14.88 min, t R ((S,R)-anti-5a) = 21.85 min. IR (cm -1 ): ν max 1156, 1338, 1625, 1641, 3214, 3289, 3398. 1 H NMR (300 MHz, CDCl 3 ): δ 1.02 (3H, d, J = 6.6 Hz), 2.33 (3H, s), 2.55-2.69 (1H, m), 4.45 (1H, d x d, J = 8.8, 8.8 Hz), 6.14 (1H, br s), 6.36 (1H, br s), 6.84-7.00 (6H, m), 7.20 (1H, d, J = 8.8 Hz), 7.37 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 16.0, 21.5, 46.4, 60.4, 127.0 (2C), 128.5 (2C), 128.6 (2C), 129.2 (2C), 133.3, 137.2, 137.5, 143.2, 177.0. MS (ES, pos. mode) m/z (%): 367/369 (M + H +, 100). Anal. Calcd for C 17 H 19 ClN 2 O 3 S: C 55.66; H 5.22; N 7.64. Found: C 55.61; H 4.86; N 7.49. (R,S)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanamide (R,S)-anti-5a. White crystals, yield 57%. [α] D - 57.5 (c 0.5, DMF). Mp 201.4-201.7 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (80%) / Ethanol (20%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-5a) = 14.88 min, t R ((S,R)-anti-5a) = 21.85 min. IR (cm -1 ): ν max 1156, 1338, 1641, 3216, 3288, 3398. 1 H NMR (300 MHz, CDCl 3 ): δ 1.19 (3H, d, J = 6.6 Hz), 2.34 (3H, s), 2.56 (1H, quintet, J = 6.6 Hz), 4.47 (1H, d x d, J = 8.5, 6.6 Hz), 5.44 (1H, br s), 5.59 (1H, br s), 6.93 (1H, d, J = 8.5 Hz), 6.93-7.00 (2H, m), 7.02-7.12 (4H, m), 7.45 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 16.3, 21.5, 46.3, 60.2, 126.9 (2C), 128.3 (2C), 128.5 (2C), 129.3 (2C), 133.3, 137.7, 137.8, 143.1, 176.6. MS (ES, pos. mode) m/z (%): 367/369 (M + H +, 100). Anal. Calcd for C 17 H 19 ClN 2 O 3 S: C 55.66; H 5.22; N 7.64. Found: C 55.37; H 5.12; N 7.59. S-12

(S,R)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanamide (S,R)-anti-5b. White crystals, yield 77%. [α] D + 68.9 (c 0.3, DMF). Mp 206.4-206.7 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (80%) / Ethanol (20%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-5b) = 15.80 min, t R ((S,R)-anti-5b) = 23.66 min. IR (cm -1 ): ν max 1156, 1656, 3288, 3371, 3474. 1 H NMR (300 MHz, CDCl 3 ): δ 1.12 (3H, d, J = 6.6 Hz), 2.29 (3H, s), 2.60 (1H, quintet, J = 6.6 Hz), 4.48 (1H, d x d, J = 8.8, 6.6 Hz), 5.60 (1H, br s), 5.87 (1H, br s), 6.94 (1H, d, J = 8.8 Hz), 6.95-7.09 (7H, m), 7.44 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 16.2, 21.5, 46.7, 60.8, 126.8 (2C), 127.0 (2C), 127.4, 128.4 (2C), 129.1 (2C), 137.8, 139.1, 142.8, 177.0. MS (ES, pos. mode) m/z (%): 333 (M + H +, 100). Anal. Calcd for C 17 H 20 N 2 O 3 S: C 61.42; H 6.06; N 8.43. Found: C 61.08; H 5.87; N 8.21. (R,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanamide (R,S)-anti-5b. White crystals, yield 82%. [α] D - 70.7 (c 0.5, DMF). Mp 199.2-199.4 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (80%) / Ethanol (20%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-5b) = 15.80 min, t R ((S,R)-anti-5b) = 23.66 min. IR (cm -1 ): ν max 1151, 1656, 3198, 3403. 1 H NMR (300 MHz, CDCl 3 ): δ 1.11 (3H, d, J = 7.1 Hz), 2.33 (3H, s), 2.67 (1H, quintet, J = 7.1 Hz), 4.52 (1H, d x d, 9.0, 7.1 Hz), 5.89 (1H, br s), 6.18 (1H, br s), 6.98-7.14 (8H, m), 7.46 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 16.1, 21.5, 46.7, 60.9, 127.0 (4C), 127.3, 128.4 (2C), 129.1 (2C), 137.7, 138.9, 142.7, 177.1. MS (ES, pos. mode) m/z (%): 333 (M + H +, 100). Anal. Calcd for C 17 H 20 N 2 O 3 S: C 61.42; H 6.06; N 8.43. Found: C 61.17; H 6.06; N 8.09. (S,R)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)propanamide (S,R)-anti-5c. White crystals, yield 86%. [α] D + 59.9 (c 0.5, DMF). Mp 220.5-220.7 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (80%) / Ethanol (20%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-5c) = 16.97 min, t R ((S,R)-anti-5c) = 25.81 min. IR (cm -1 ): ν max 1151, S-13

1321, 1617, 1639, 3215, 3286, 3399. 1 H NMR (300 MHz, DMSO-d 6 ): δ 0.68 (3H, d, J = 6.6 Hz), 2.25 (3H, s), 2.41-2.53 (1H, m), 3.65 (3H, s), 4.34 (1H, d x d, J = 9.4, 9.4 Hz), 6.59 (2H, d, J = 8.3 Hz), 6.93 (2H, d, J = 8.3 Hz), 7.04 (2H, d, J = 8.3 Hz), 7.30 (2H, d, J = 8.3 Hz), 7.96 (1H, d, J = 9.4 Hz). 13 C NMR (75 MHz, DMSO-d 6 ): δ 15.4, 20.7, 45.6, 54.8, 59.5, 113.0 (2C), 126.2 (2C), 128.1, 128.6 (2C), 131.4 (2C), 138.7, 141.3, 157.9, 175.5. MS (ES, pos. mode) m/z (%): 361 (M + H +, 100). Anal. Calcd for C 18 H 22 N 2 O 4 S: C 59.65; H 6.12; N 7.73. Found: C 59.40; H 5.95; N 7.52. (R,S)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)propanamide (R,S)-anti-5c. White crystals, yield 88%. [α] D - 60.4 (c 0.4, DMF). Mp 223.9-224.3 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (80%) / Ethanol (20%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-5c) = 16.97 min, t R ((S,R)-anti-5c) = 25.81 min. IR (cm -1 ): ν max 1151, 1321, 1617, 1639, 3216, 3286, 3399. 1 H NMR (300 MHz, DMSO-d 6 ): δ 0.68 (3H, d, J = 7.1 Hz), 2.25 (3H, s), 2.41-2.51 (1H, m, J = 7.1 Hz), 3.65 (3H, s), 4.34 (1H, d x d, J = 9.4, 9.4 Hz), 6.59 (2H, d, J = 8.3 Hz), 6.93 (2H, d, J = 8.3 Hz), 7.04 (2H, d, J = 8.3 Hz), 7.30 (2H, d, J = 8.3 Hz), 7.97 (1H, d, J = 9.4 Hz). 13 C NMR (75 MHz, DMSO-d 6 ): δ 15.4, 20.7, 45.6, 54.9, 59.5, 113.1 (2C), 126.2 (2C), 128.1, 128.6 (2C), 131.5 (2C), 138.7, 141.3, 158.0, 175.6. MS (ES, pos. mode) m/z (%): 361 (M + H +, 100). Anal. Calcd for C 18 H 22 N 2 O 4 S: C 59.65; H 6.12; N 7.73. Found: C 59.29; H 6.04; N 7.74. 4. Synthesis of chiral β-sulfonylamino esters 6 The synthesis of (S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(ptoluenesulfonylamino)propanoate (S,R)-anti-6a is representative. (S,R)-Methyl 2-methyl-3-(4- chlorophenyl)-3-(p-toluenesulfonylamino)propanimidate hydrochloride (S,R)-anti-4a (0.46 g, 1.11 mmol) was dissolved in H 2 O (15 ml). The reaction mixture was stirred for 7 hours at 55 S-14

C and subsequently poured in a saturated aqueous solution of NaHCO 3 (20 ml) and extracted with diethyl ether (3 x 20 ml). The combined organic phases were dried (MgSO 4 ), filtered and evaporated in vacuo. The crude product was purified by flash chromatography to yield 0.32 g of pure (S,R)-methyl 2-methyl-3-(4-chlorophenyl)-3-(ptoluenesulfonylamino)propanoate (S,R)-anti-6a. (S,R)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanoate (S,R)- anti-6a. R f = 0.39 (petroleum ether/ Et 2 O 3:7). White crystals, yield 76%. [α] D + 60.3 (c 0.4, CHCl 3 ). Mp 123.1-123.4 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (95.5%) / Ethanol (4.5%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-6a) = 28.42 min, t R ((S,R)-anti- 6a) = 31.59 min. IR (cm -1 ): ν max 1155, 1734, 3266. 1 H NMR (300 MHz, CDCl 3 ): δ 1.16 (3H, d, J = 6.6 Hz), 2.35 (3H, s), 2.79 (1H, quintet, J = 6.6 Hz), 3.56 (3H, s), 4.48 (1H, d x d, J = 8.5, 6.6 Hz), 6.00 (1H, d, J = 8.5 Hz), 6.94 (2H, d, J = 8.3 Hz), 7.09 (4H, d, J = 8.3 Hz), 7.48 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.3, 21.5, 46.0, 52.2, 59.8, 127.0 (2C), 128.2 (2C), 128.5 (2C), 129.3 (2C), 133.4, 137.4, 137.7, 143.2, 174.9. MS (ES, pos. mode) m/z (%): 380/382 (M + H +, 100). Anal. Calcd for C 18 H 20 ClNO 4 S: C 56.61; H 5.28; N 3.67. Found: C 56.49; H 5.11; N 3.57. (R,S)-Methyl 2-methyl-3-(4-chlorophenyl)-3-(p-toluenesulfonylamino)propanoate (R,S)- anti-6a. R f = 0.29 (petroleum ether/ Et 2 O 3:7). White crystals, yield 86%. [α] D - 61.1 (c 0.3, CHCl 3 ). Mp 120.5-120.7 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (95.5%) / Ethanol (4.5%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-6a) = 28.42 min, t R ((S,R)-anti- 6a) = 31.59 min. IR (cm -1 ): ν max 1156, 1734, 3266. 1 H NMR (300 MHz, CDCl 3 ): δ 1.11 (3H, d, J = 7.2 Hz), 2.34 (3H, s), 2.80 (1H, quintet, J = 7.2 Hz), 3.58 (3H, s), 4.48 (1H, d x d, J = 8.5, 7.2 Hz), 6.23 (1H, d, J = 8.5 Hz), 6.95 (2H, d, J = 8.3 Hz), 7.08 (4H, d, J = 8.3 Hz), 7.48 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.4, 21.5, 46.0, 52.2, 59.8, 127.0 (2C), S-15

128.2 (2C), 128.5 (2C), 129.3 (2C), 133.4, 137.4, 137.7, 143.2, 174.9. MS (ES, pos. mode) m/z (%): 380/382 (M + H +, 100). Anal. Calcd for C 18 H 20 ClNO 4 S: C 56.61; H 5.28; N 3.67. Found: C 56.92; H 5.14; N 3.29. (S,R)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanoate (S,R)-anti-6b. R f = 0.38 (petroleum ether/ Et 2 O 3:7). White crystals, yield 72%. [α] D + 49.6 (c 0.3, CHCl 3 ). Mp 111.3-111.5 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (95.5%) / Ethanol (4.5%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-6b) = 25.85 min, t R ((S,R)-anti-6b) = 28.29 min. IR (cm -1 ): ν max 1163, 1737, 2922, 3259. 1 H NMR (300 MHz, CDCl 3 ): δ 1.15 (3H, d, J = 7.2 Hz), 2.32 (3H, s), 2.83 (1H, quintet, J = 7.2 Hz), 3.56 (3H, s), 4.51 (1H, d x d, J = 8.8, 7.2 Hz), 5.93 (1H, d, J = 8.8 Hz), 6.96-7.03 (2H, m), 7.06 (4H, d, J = 8.3 Hz), 7.09-7.16 (3H, m), 7.49 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.6, 21.5, 46.1, 52.0, 60.3, 126.6 (2C), 127.0 (2C), 127.5, 128.4 (2C), 129.3 (2C), 137.9, 139.0, 142.9, 175.0. MS (ES, pos. mode) m/z (%): 346 (M + H +, 100). Anal. Calcd for C 18 H 21 NO 4 S: C 62.23; H 6.09; N 4.03. Found: C 62.06; H 6.03; N 3.94. (R,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanoate (R,S)-anti-6b. R f = 0.51 (petroleum ether/ Et 2 O 3:7). White crystals, yield 94%. [α] D - 48.2 (c 0.3, CHCl 3 ). Mp 115.4-115.7 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (95.5%) / Ethanol (4.5%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-6b) = 25.85 min, t R ((S,R)-anti-6b) = 28.29 min. IR (cm -1 ): ν max 1163, 1321, 1737, 2922, 3259. 1 H NMR (300 MHz, CDCl 3 ): δ 1.16 (3H, d, J = 7.2 Hz), 2.32 (3H, s), 2.83 (1H, quintet, J = 7.2 Hz), 3.56 (3H, s), 4.50 (1H, d x d, J = 8.8, 6.1 Hz), 5.91 (1H, d, J = 8.8 Hz), 6.96-7.03 (2H, m), 7.06 (4H, d, J = 8.3 Hz), 7.10-7.16 (3H, m), 7.49 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.6, 21.5, 46.1, 51.9, 60.3, 126.6 (2C), 127.0 (2C), 127.6, 128.4 (2C), 129.3 (2C), 137.9, 139.0, 143.0, 175.0. MS (ES, pos. S-16

mode) m/z (%): 346 (M + H +, 100). Anal. Calcd for C 18 H 21 NO 4 S: C 62.23; H 6.09; N 4.03. Found: C 62.08; H 5.97; N 3.95. (S,S)-Methyl 2-methyl-3-phenyl-3-(p-toluenesulfonylamino)propanoate (S,S)-syn-6b. R f = 0.42 (petroleum ether/ Et 2 O 3:7). White crystals, yield 63%. [α] D - 33.3 (c 0.3, CHCl 3 ). Mp 103.7-104.3 C. IR (cm -1 ): ν max 1161, 1735, 3256. 1 H NMR (300 MHz, CDCl 3 ): δ 1.16 (3H, d, J = 7.2 Hz), 2.32 (3H, s), 2.86 (1H, quintet, J = 7.2 Hz), 3.47 (3H, s), 4.54 (1H, d x d, J = 9.1, 7.2 Hz), 5.87 (1H, d, J = 9.1 Hz), 6.92-7.03 (2H, m), 7.04-7.17 (5H, m), 7.51 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 13.6, 21.5, 46.0, 51.9, 60.0, 127.1 (2C), 127.2 (2C), 127.6, 128.3 (2C), 129.3 (2C), 137.5, 138.3, 143.1, 173.9. MS (ES, pos. mode) m/z (%): 346 (M + H +, 100). Anal. Calcd for C 18 H 21 NO 4 S: C 62.23; H 6.09; N 4.03. Found: C 61.96; H 5.88; N 3.89. (S,R)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)propanoate (S,R)-anti-6c. R f = 0.23 (petroleum ether/ Et 2 O 3:7). White crystals, yield 82%. [α] D + 61.5 (c 0.3, CHCl 3 ). Mp 88.0-88.4 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (95.5%) / Ethanol (4.5%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-6c) = 35.24 min, t R ((S,R)-anti- 6c) = 41.98 min. IR (cm -1 ): ν max 1159, 1728, 2924, 3233. 1 H NMR (300 MHz, CDCl 3 ): δ 1.06 (3H, d, J = 7.2 Hz), 2.30 (3H, s), 2.82 (1H, quintet, J = 7.2 Hz), 3.60 (3H, s), 3.71 (3H, s), 4.47 (1H, d x d, J = 8.8, 7.2 Hz), 6.25 (1H, d, J = 8.8 Hz), 6.62 (2H, d, J = 8.3 Hz), 6.93 (2H, d, J = 8.3 Hz), 7.04 (2H, d, J = 8.3 Hz), 7.48 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.1, 21.4, 46.4, 52.0, 55.3, 60.0, 113.7 (2C), 127.1 (2C), 128.0 (2C), 129.2 (2C), 130.8, 138.0, 142.7, 159.0, 175.1. MS (ES, neg. mode) m/z (%): 376 (M - H +, 100). Anal. Calcd for C 19 H 23 NO 5 S: C 60.46; H 6.14; N 3.71. Found: C 60.22; H 6.01; N 3.57. S-17

(R,S)-Methyl 2-methyl-3-(4-methoxyphenyl)-3-(p-toluenesulfonylamino)propanoate (R,S)-anti-6c. R f = 0.24 (petroleum ether/ Et 2 O 3:7). White crystals, yield 78%. [α] D - 67.6 (c 0.3, CHCl 3 ). Mp 88.7-88.9 C. ee > 98%, HPLC Daicel Chiralcel OD-H column: Hexane (95.5%) / Ethanol (4.5%), 0.5 ml min -1, 35 C, t R ((R,S)-anti-6c) = 35.24 min, t R ((S,R)-anti- 6c) = 41.98 min. IR (cm -1 ): ν max 1159, 1251, 1728, 2936, 3235. 1 H NMR (300 MHz, CDCl 3 ): δ 1.09 (3H, d, J = 7.2 Hz), 2.32 (3H, s), 2.81 (1H, quintet, J = 7.2 Hz), 3.59 (3H, s), 3.73 (3H, s), 4.46 (1H, d x d, J = 8.8, 7.2 Hz), 6.05 (1H, d, J = 8.8 Hz), 6.64 (2H, d, J = 8.3 Hz), 6.92 (2H, d, J = 8.3 Hz), 7.06 (2H, d, J = 8.3 Hz), 7.49 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 15.3, 21.5, 46.3, 52.0, 55.3, 60.0, 113.8 (2C), 127.1 (2C), 127.9 (2C), 129.2 (2C), 131.0, 138.0, 142.8, 159.0, 175.1. MS (ES, neg. mode) m/z (%): 376 (M - H +, 100). Anal. Calcd for C 19 H 23 NO 5 S: C 60.46; H 6.14; N 3.71. Found: C 60.36; H 5.85; N 3.51. 5. Synthesis of chiral γ-sulfonylamino alcohols 7 The synthesis of γ-sulfonylamino alcohols 7 was performed according to a literature procedure starting from β-sulfonylamino esters 6. S1 The γ-sulfonylamino alcohols 7 were purified by recrystallization from diethyl ether. (R,S)-N-(3-Hydroxy-2-methyl-1-phenylpropyl)-4-methylbenzenesulfonamide (R,S)-anti- 7b. This compound is known in literature, but no spectral data are available. S2 White crystals, yield 63%. [α] D + 28.3 (c 0.1, CHCl 3 ). Mp 131.3-131.6 C. IR (cm -1 ): ν max 1158, 1322, 3243, 3498. 1 H NMR (300 MHz, CDCl 3 ): δ 0.76 (3H, d, J = 6.6 Hz), 1.90-2.02 (1H, m), 2.33 (3H, s), 2.60 (1H, m), 3.52-3.62 (1H, m), 3.88-3.98 (1H, m), 4.17 (1H, d x d, J = 7.7, 7.7 Hz), 6.14 (1H, d, J = 7.7 Hz), 6.91-6.99 (2H, m), 7.03-7.15 (5H, m), 7.48 (2H, d, J = 8.3 Hz). 13 C NMR S1 Raheem, I. T.; Jacobsen, E. N. Adv. Synth. & Cat. 2005, 347, 1701. S2 Enders, D.; Gries, J. Synthesis 2005, 20, 3508. S-18

(75 MHz, CDCl 3 ): δ 14.7, 21.5, 41.0, 61.6, 65.0, 127.0 (2C), 127.2 (2C), 127.3, 128.4 (2C), 129.3 (2C), 137.4, 140.1, 143.0. MS (ES, neg. mode) m/z (%): 318 (M - H +, 100). Anal. Calcd for C 17 H 21 NO 3 S: C 63.92; H 6.63; N 4.39. Found: C 63.78; H 6.44; N 4.23. (S,S)-N-(3-Hydroxy-2-methyl-1-phenylpropyl)-4-methylbenzenesulfonamide (S,R)-N-(3-Hydroxy-2-methyl-1-phenylpropyl)-4-methylbenzenesulfonamide (S,R)-anti- 7b. This compound is known in literature, but no spectral data are available. S2 White crystals, yield 73%. [α] D - 35.6 (c 0.1, MeOH). Mp 133.2-133.5 C. IR (cm -1 ): ν max 1088, 1158, 1322, 3246, 3499. 1 H NMR (300 MHz, CDCl 3 ): δ 0.76 (3H, d, J = 6.6 Hz), 1.90-2.02 (1H, m), 2.33 (3H, s), 2.64 (1H, m), 3.49-3.63 (1H, m), 3.87-3.98 (1H, m), 4.17 (1H, d x d, J = 7.7, 7.7 Hz), 6.18 (1H, d, J = 7.7 Hz), 6.91-6.99 (2H, m), 7.04-7.15 (5H, m), 7.45-7.52 (2H, m). 13 C NMR (75 MHz, CDCl 3 ): δ 14.7, 21.5, 41.0, 61.7, 65.0, 127.0 (2C), 127.2 (2C), 127.3, 128.3 (2C), 129.3 (2C), 137.4, 140.1, 143.0. MS (ES, neg. mode) m/z (%): 318 (M - H +, 100). Anal. Calcd for C 17 H 21 NO 3 S: C 63.92; H 6.63; N 4.39. Found: C 63.88; H 6.48; N 4.29. (S,S)-syn- 7b. White crystals, yield 87%. [α] D (1S,2S)-7b-syn -24.3 (c 0.4, MeOH) vs (1R,2R)-7b-syn +25.4 and +26,1 (c 1.0, MeOH) in Lit. S3 Mp 134.5-134.8 C vs 159.0-161.0 C in Lit. IR (cm - 1 ): ν max 1025, 1155, 3248, 3538. 1 H NMR (300 MHz, CDCl 3 ): δ 0.72 (3H, d, J = 6.6 Hz), 2.04-2.19 (1H, m), 2.28 (1H, br s), 2.31 (3H, s), 3.44-3.60 (2H, m), 4.61 (1H, d x d, J = 9.4, 4.4 Hz), 5.84 (1H, d, J = 9.4 Hz), 6.95-7.02 (2H, m), 7.05 (2H, d, J = 8.3 Hz), 7.09-7.17 (3H, m), 7.53 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 11.7, 21.5, 41.3, 59.2, 64.8, 127.0 (2C), 127.1 (3C), 128.2 (2C), 129.3 (2C), 137.5, 138.6, 143.1. MS (ES, pos. mode) m/z (%): S2 Enders, D.; Gries, J. Synthesis 2005, 20, 3508. S3 (a) Raheem, I. T.; Jacobsen, E. N. Adv. Synth. & Cat. 2005, 347, 1701. (b) Davis, F. A.; Reddy, G. V.; Liang, C. -H. Tetr. Lett. 1997, 38, 5139. S-19

320 (M + H +, 100). Anal. Calcd for C 17 H 21 NO 3 S: C 63.92; H 6.63; N 4.39. Found: C 63.76; H 6.56; N 4.32. (S,R)-N-(3-Hydroxy-2-methyl-1-(4-methoxyphenyl)propyl)-4-methylbenzenesulfonamide (S,R)-anti-7c. White crystals, yield 86%. [α] D - 29.9 (c 0.4, MeOH). Mp 160.2-160.6 C. IR (cm -1 ): ν max 1031, 1156, 2958, 3250. 1 H NMR (300 MHz, CDCl 3 ): δ 0.73 (3H, d, J = 7.2 Hz), 1.93-2.10 (1H, m), 2.31 (3H, s), 3.58 (1H, br s), 3.63-3.76 (1H, m), 3.70 (3H, s), 3.86-3.98 (1H, m), 4.10 (1H, d x d, J = 8.8, 8.8 Hz), 6.58 (2H, d, J = 8.3 Hz), 6.62 (1H, d, J = 8.8 Hz), 6.87 (2H, d, J = 8.3 Hz), 7.03 (2H, d, J = 8.3 Hz), 7.47 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 14.7, 21.5, 41.1, 55.3, 61.2, 65.2, 113.6 (2C), 127.2 (2C), 128.3 (2C), 129.2 (2C), 132.2, 137.5, 142.9, 158.7. MS (ES, neg. mode) m/z (%): 348 (M - H +, 100). Anal. Calcd for C 18 H 23 NO 4 S: C 61.87; H 6.63; N 4.01. Found: C 61.76; H 6.54; N 3.92. 6. Synthesis of chiral N-tosylazetidines 8 The synthesis of N-tosylazetidines 8 was performed according to a literature procedure starting from γ-sulfonylamino alcohols 7. S2 The N-tosylazetidines 8 were purified by flash chromatography. (R,R)-3-Methyl-2-phenyl-1-tosylazetidine (R,R)-trans-8b. R f = 0.37 (petroleum ether/ Et 2 O 7:3). White crystals, yield 89%. [α] D + 235.6 (c 0.2, CHCl 3 ) vs + 238.5 (c 1.0, CHCl 3, ee > 99%) in Lit. S2 Mp 103.4-103.7 C vs 112.0 C in Lit. ee > 98%, HPLC Daicel Chiralcel OD- H column: Hexane (99.6%) / i-propanol (0.4%), 0.5 ml min -1, 35 C, t R ((S,S)-trans-8b) = 35.39 min, t R ((R,R)-trans-8b) = 43.93 min. 1 H NMR (300 MHz, CDCl 3 ): δ 0.98 (3H, d, J = S2 Enders, D.; Gries, J. Synthesis 2005, 20, 3508. S-20

6.6 Hz), 2.41-2.54 (1H, m), 2.44 (3H, s), 3.33 (1H, t, J = 7.7 Hz), 3.91 (1H, t, J = 7.7 Hz), 4.35 (1H, d, J = 7.2 Hz), 7.24-7.40 (7H, m), 7.68 (2H, d, J = 8.3 Hz). Anal. Calcd for C 17 H 19 NO 2 S: C 67.74; H 6.35; N 4.65. Found: C 67.49; H 6.18; N 4.57. All spectroscopic data were in good agreement with reported data. S24 (S,S)-3-Methyl-2-phenyl-1-tosylazetidine (S,S)-trans-8b. R f = 0.13 (petroleum ether/ Et 2 O 8:2). White crystals, yield 94%. [α] D - 232.9 (c 0.3, CHCl 3 ) vs - 228.5 (c 1.0, CHCl 3, ee = 97%) in Lit. S2 Mp 113.5-113.8 C vs 112.0 C in Lit. ee > 98%, HPLC Daicel Chiralcel OD- H column: Hexane (99.6%) / i-propanol (0.4%), 0.5 ml min -1, 35 C, t R ((S,S)-trans-8b) = 35.39 min, t R ((R,R)-trans-8b) = 43.93 min. 1 H NMR (300 MHz, CDCl 3 ): δ 0.97 (3H, d, J = 7.2 Hz), 2.41-2.55 (1H, m), 2.44 (3H, s), 3.33 (1H, t, J = 7.7 Hz), 3.91 (1H, t, J = 7.7 Hz), 4.35 (1H, d, J = 7.2 Hz), 7.22-7.42 (7H, m), 7.68 (2H, d, J = 8.3 Hz). Anal. Calcd for C 17 H 19 NO 2 S: C 67.74; H 6.35; N 4.65. Found: C 67.62; H 6.22; N 4.47. All spectroscopic data were in good agreement with reported data. S2 (S,S)-3-Methyl-2-(4-methoxyphenyl)-1-tosylazetidine (S,S)-trans-8c. R f = 0.18 (petroleum ether/ Et 2 O 7:3). White crystals, yield 74%. [α] D - 255.9 (c 0.3, CHCl 3 ). Mp 77.3-77.5 C. IR (cm -1 ): ν max 1152, 1335, 1515, 2967. 1 H NMR (300 MHz, CDCl 3 ): δ 0.95 (3H, d, J = 6.6 Hz), 2.41-2.54 (1H, m), 2.44 (3H, s), 3.27 (1H, t, J = 7.7 Hz), 3.79 (3H, s), 3.88 (1H, t, J = 7.7 Hz), 4.27 (1H, d, J = 7.7 Hz), 6.86 (2H, d, J = 8.3 Hz), 7.28-7.36 (4H, m), 7.67 (2H, d, J = 8.3 Hz). 13 C NMR (75 MHz, CDCl 3 ): δ 17.6, 21.7, 35.3, 54.5, 55.4, 73.1, 114.0 (2C), 127.8 (2C), 128.5 (2C), 129.6 (2C), 132.2, 132.3, 143.9, 159.5. MS (ES, pos. mode) m/z (%): 332 (M + H +, 100). Anal. Calcd for C 18 H 21 NO 3 S: C 65.23; H 6.39; N 4.23. Found: C 64.94; H 6.15; N 4.11. S2 Enders, D.; Gries, J. Synthesis 2005, 20, 3508. S-21

III. Copies of 1 H NMR and 13 C NMR spectra of 3, 4, 5, 6, 7 and 8 1 H NMR (300 MHz, CDCl 3 ) N S O Cl (R S,S,R)-anti-3a S-22

13 C NMR (75 MHz, CDCl 3 ) N S O Cl (R S,S,R)-anti-3a S-23

1 H NMR (300 MHz, CDCl 3 ) S N O Cl (R S,R,S)-anti-3a S-24

13 C NMR (75 MHz, CDCl 3 ) S N O Cl (R S,R,S)-anti-3a S-25

1 H NMR (300 MHz, CDCl 3 ) N S O Cl (R S,S,S)-syn-3a S-26

13 C NMR (75 MHz, CDCl 3 ) N S O Cl (R S,S,S)-syn-3a S-27

1 H NMR (300 MHz, CDCl 3 ) S N O (R S,S,R)-anti-3b S-28

13 C NMR (75 MHz, CDCl 3 ) S N O (R S,S,R)-anti-3b S-29

1 H NMR (300 MHz, CDCl 3 ) S N O (R S,R,S)-anti-3b S-30

13 C NMR (75 MHz, CDCl 3 ) S N O (R S,R,S)-anti-3b S-31

1 H NMR (300 MHz, CDCl 3 ) S N O (R S,S,S)-syn-3b S-32

13 C NMR (75 MHz, CDCl 3 ) S N O (R S,S,S)-syn-3b S-33

1 H NMR (300 MHz, CDCl 3 ) N S O MeO (R S,S,R)-anti-3c S-34

13 C NMR (75 MHz, CDCl 3 ) N S O MeO (R S,S,R)-anti-3c S-35

1 H NMR (300 MHz, CDCl 3 ) N S O MeO (R S,R,S)-anti-3c S-36

13 C NMR (75 MHz, CDCl 3 ) N S O MeO (R S,R,S)-anti-3c S-37

1 H NMR (300 MHz, CDCl 3 ) N S O MeO (R S,S,S)-syn-3c S-38

13 C NMR (75 MHz, CDCl 3 ) N S O MeO (R S,S,S)-syn-3c S-39

1 H NMR (300 MHz, CDCl 3 ).HCl Cl (S,R)-anti-4a S-40

13 C NMR (75 MHz, CDCl 3 ).HCl Cl (S,R)-anti-4a S-41

1 H NMR (300 MHz, CDCl 3 ).HCl Cl (R,S)-anti-4a S-42

13 C NMR (75 MHz, CDCl 3 ).HCl Cl (R,S)-anti-4a S-43

1 H NMR (300 MHz, CDCl 3 ).HCl (S,R)-anti-4b S-44

13 C NMR (75 MHz, CDCl 3 ).HCl (S,R)-anti-4b S-45

1 H NMR (300 MHz, CDCl 3 ).HCl (R,S)-anti-4b S-46

13 C NMR (75 MHz, CDCl 3 ).HCl (R,S)-anti-4b S-47

1 H NMR (300 MHz, CDCl 3 ).HCl (S,S)-syn-4b S-48

13 C NMR (75 MHz, CDCl 3 ).HCl (S,S)-syn-4b S-49

1 H NMR (300 MHz, CDCl 3 ).HCl MeO (S,R)-anti-4c S-50

13 C NMR (75 MHz, CDCl 3 ).HCl MeO (S,R)-anti-4c S-51

1 H NMR (300 MHz, CDCl 3 ).HCl MeO (R,S)-anti-4c S-52

13 C NMR (75 MHz, CDCl 3 ).HCl MeO (R,S)-anti-4c S-53

1 H NMR (300 MHz, CDCl 3 ) O 2 Cl (S,R)-anti-5a S-54

13 C NMR (75 MHz, CDCl 3 ) O 2 Cl (S,R)-anti-5a S-55

1 H NMR (300 MHz, CDCl 3 ) O 2 Cl (R,S)-anti-5a S-56

13 C NMR (75 MHz, CDCl 3 ) O 2 Cl (R,S)-anti-5a S-57

1 H NMR (300 MHz, CDCl 3 ) O 2 (S,R)-anti-5b S-58

13 C NMR (75 MHz, CDCl 3 ) O 2 (S,R)-anti-5b S-59

1 H NMR (300 MHz, CDCl 3 ) O 2 (R,S)-anti-5b S-60

13 C NMR (75 MHz, CDCl 3 ) O 2 (R,S)-anti-5b S-61

1 H NMR (300 MHz, DMSO-d 6 ) O 2 MeO (S,R)-anti-5c S-62

13 C NMR (75 MHz, DMSO-d 6 ) O 2 MeO (S,R)-anti-5c S-63

1 H NMR (300 MHz, DMSO-d 6 ) O 2 MeO (R,S)-anti-5c S-64

13 C NMR (75 MHz, DMSO-d 6 ) O 2 MeO (R,S)-anti-5c S-65

1 H NMR (300 MHz, CDCl 3 ) O Cl (S,R)-anti-6a S-66

13 C NMR (75 MHz, CDCl 3 ) O Cl (S,R)-anti-6a S-67

1 H NMR (300 MHz, CDCl 3 ) O Cl (R,S)-anti-6a S-68

13 C NMR (75 MHz, CDCl 3 ) O Cl (R,S)-anti-6a S-69

1 H NMR (300 MHz, CDCl 3 ) O (S,R)-anti-6b S-70

13 C NMR (75 MHz, CDCl 3 ) O (S,R)-anti-6b S-71

1 H NMR (300 MHz, CDCl 3 ) O (R,S)-anti-6b S-72

13 C NMR (75 MHz, CDCl 3 ) O (R,S)-anti-6b S-73

1 H NMR (300 MHz, CDCl 3 ) O (S,S)-syn-6b S-74

13 C NMR (75 MHz, CDCl 3 ) O (S,S)-syn-6b S-75

1 H NMR (300 MHz, CDCl 3 ) O MeO (S,R)-anti-6c S-76

13 C NMR (75 MHz, CDCl 3 ) O MeO (S,R)-anti-6c S-77

1 H NMR (300 MHz, CDCl 3 ) O MeO (R,S)-anti-6c S-78

13 C NMR (75 MHz, CDCl 3 ) O MeO (R,S)-anti-6c S-79

1 H NMR (300 MHz, CDCl 3 ) OH (R,S)-anti-7b S-80

13 C NMR (75 MHz, CDCl 3 ) OH (R,S)-anti-7b S-81

1 H NMR (300 MHz, CDCl 3 ) OH (S,R)-anti-7b S-82

13 C NMR (75 MHz, CDCl 3 ) OH (S,R)-anti-7b S-83

1 H NMR (300 MHz, CDCl 3 ) OH (S,S)-syn-7b S-84

13 C NMR (75 MHz, CDCl 3 ) OH (S,S)-syn-7b S-85

1 H NMR (300 MHz, CDCl 3 ) OH MeO (S,R)-anti-7c S-86

13 C NMR (75 MHz, CDCl 3 ) OH MeO (S,R)-anti-7c S-87

1 H NMR (300 MHz, CDCl 3 ) N (R,R)-trans-8b S-88

1 H NMR (300 MHz, CDCl 3 ) N (S,S)-trans-8b S-89

1 H NMR (300 MHz, CDCl 3 ) N MeO (S,S)-trans-8c S-90

13 C NMR (75 MHz, CDCl 3 ) N MeO (S,S)-trans-8c S-91

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