Supporting Information

Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2010 A Highly Effective Bis(sulfonamide) Diamine Ligand: A Unique Chiral Skeleton for the Enantioselective Cu-Catalyzed Henry Reaction Wei Jin, Xincheng Li, Yongbo Huang, Fan Wu, and Boshun Wan* [a] chem_201000964_sm_miscellaneous_information.pdf

Supproting information Highly Effective Bis(sulfonamide)-Diamine Ligand: Unique Chiral Skeleton for the Enantioselective Cu-Catalyzed Henry Reaction Wei Jin, Xincheng Li, Yongbo Huang, Fan Wu, Boshun Wan* Contents 1. General information S2 2. General procedure for the preparation of ligand S2 3. The characterization of ligand S2 4. The diamines catalyze the Henry reaction S3 5. General procedure for the Henry reaction S3 6. Characterization of Nitroaldol products S3 7. General procedure for the diasteroselective Henry reaction S7 8. Synthesis of (R)-(-)-3-Methyl-1-aminobutan-2-ol (8) S7 9. The synthesis of (R)-2-phenyl-1-tosylaziridine (9) S7

1. General information. Commercially available compounds were used without further purification. Solvents were dried according to standard procedure and were distilled prior to use. All reactions were carried out under an atmosphere of argon in gas buner-dried glassware with magnetic stirring. Column chromatography was carried out using silica gel (300-400 mwsh). For TLC, silica gel GF 254 was used. The 1 H NMR spectra were recorded with 400 MHz spectrometer. Chemical shift were reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (CDCl 3, δ = 7.26). Data are reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet), coupling constants (Hz), integration, and assignment. 13 C NMR spectra were collected on a 100 MHz spectrometer with complete proton decoupling. Chemicla shifts are reported in ppm from the tetramethylsilane with the solvent resonance as internal standard (CDCl 3, δ = 77.23). The enantiomeric excesses were determined by HPLC analysis on chiralpak OD-H, chiralcel OJ-H, Chiralcel AD-H column. Optical rotation were reported as follows: [α] 25 D (c g/100ml, in solvent). HRMS data were obtained with Micromass HPLC-Q-TOF mass spectrometer. 2. General Procedure for the Preparation of 3a-3c, 4 and 5 Tosyl chloride (2.2 equiv) was added portionwise at room temperature to a stirred mixture of 1 (1.0 equiv), K 2 CO 3 (4.0 equiv) and acetonitrile. After 24 h, toluene (5 ml) was added, the solid was filtered off and the solvents evaporated, leaving the corresponding aziridine 2 as a white solid. [1] (S,S)-1,2-diamine and the corresponding aziridine 2 were dissolved in dry acetonitrile (30 ml), and the mixture was stirred under reflux for 3d. The solvent was evaporated under reduced pressure. The crude product was purified by flash column chromatography. 3. Characterization of ligand 3: 42% yield, white solid; m. p. 69-71 o C; [α] D 25 = + 51.9 (c = 0.86, CH 2 Cl 2 ); 1 H NMR (400 MHz, CD 3 COCD 3 ) 7.78-7.76 (m, 2H), 7.65-7.63 (m, 2H), 7.40-7.38 (m, 2H), 7.29-7.18 (m, 12H), 4.43 (t, J = 7.88 Hz, 1H), 3.74 (t, J = 6 Hz, 1H), 3.00-2.85 (m, 3H), 2.65 (m, 1H), 2.41 (s, 3H), 2.33 (s, 3H), 2.06-1.99 (m, 2H), 1.89-1.55 (m, 2H), 1.07-1.05 (m, 2H), 0.85-0.83 (m, 2H); 13 C NMR (100 MHz, CD 3 COCD 3 ) 144.02, 143.10, 142.78, 140.94, 138.88, 138.34, 129.76, 129.43, 128.93, 128.28, 127.37, 127.23, 127.13, 60.80, 60.51, 57.75, 52.50, 49.41, 32.56, 31.09, 25.04, 24.63, 20.67. HRMS calcd for C 36 H 44 N 4 O 4 S 2 661.2882, found: 661.2865. 4a: 58% yield, white solid; m. p. 74-76 o C; [α] D 25 = -12.9 (c = 1.06, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) 7.78-7.76 (m, 2H), 7.59-7.57 (m, 2H), 7.28-7.20 (m, 5H), 7.22-7.05 (m, 9H), 4.39 (t, J = 7.44 Hz, 1H), 3.81 3.78 (m, 1H), 3.06 3.03 (m, 1H), 2.91-2.87 (m, 2H), 2.68 (m, 1H), 2.39 (s, 1H), 2.31 (s, 3H), 2.29 (m, 1H), 1.85-1.84 (m, 2H), 1.57-1.54 (m, 2H), 0.89-0.83 (m, 4H) ; 13 C NMR (100 MHz, CDCl 3 ) 143.54, 143.11, 141.15, 139.59, 137.85, 137.21, 129.91, 129.44, 128.92, 128.54, 127.86, 127.63, 127.35, 127.24, 126.98, 126.74, 61.68, 58.37, 58.12, 57.65,52.48, 49.83, 31.95, 31.43, 24.97, 24.77, 21.70, 21.63; HRMS calcd for C 36 H 44 N 4 O 4 S 2 661.2882, found: 661.2863. 4b: 35% yield, yellow oil; [α] D 25 = -31.0 (c = 0.91, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) 7.81-7.79 (m, 4H), 7.29-7.27 (m, 4H), 3.40-3.36 (m, 2H),.75-2.71 (m, 2H), 2.40-2.36 (m, 8H), 2.10-2.08 (m, 2H), 2.04 (b, 2H), 1.84-1.80 (m, 2H), 1.63-1.61 (m, 2H), 1.12-1.09 (m, 2H), 0.99-0.91 (m, 8H); 13 C NMR (100 MHz, CDCl 3 ) 143.01, 138.45, 129.59, 127.01, 61.06, 51.69, 50.16, 31.76, 24.94, 21.48, 19.13; HRMS calcd for C 26 H 40 N 4 O 4 S 2 537.2569, found 537.2567. 4c: 44% yield, white solid; m. p. 128-129 o C; [α] D 25 = -53.9 (c = 1.06, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) 7.61-7.59 (m, 4H), 7.16-7.12 (m, 10H), 6.99-6.97 (m, 4H), 3.62 (m, 2H), 2.85-2.82 (m, 2H), 2.70-2.62 (m, 4H), 2.54-2.30 (m, 8H), 1.83 (m, 2H), 1.65 (m, 2H), 1.15-1.14 (m, 4H); 13 C NMR (100 S2

MHz, CDCl 3 ) 143.04, 138.27, 137.80, 129.75, 129.36, 128.66, 127.02, 126.53, 59.78, 56.10, 48.52, 39.53, 31.67, 25.19, 21.70; HRMS calcd for C 28 H 48 N 4 O 4 S 2 689.3195, found: 689.3178. 4d: 74% yield, white solid; m. p. 83-85 o C; [α] D 25 = +18.4 (c = 1.06, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) 7.60-7.58 (m, 2H), 7.44-7.42 (m, 2H), 7.41-7.20 (m, 10H), 7.18-7.12 (m, 3H), 7.09-7.00 (m, 5H), 6.83 (m, 4H), 6.74-6.72 (m, 2H), 5.74 (b, 1H), 5.07 (b, 1H), 4.33 (m, 1H), 3.43-3.41 (m, 1H), 3.21-3.19 (m, 2H), 2.97-2.86 (m, 2H), 2.67-2.63 (m, 1H), 2.52-2.36 (m, 1H), 2.31 (s, 3H), 2.26 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) 143.42, 143.02, 140.77, 140.37, 140.24, 139.56, 129.83, 129.47, 128.92, 128.57, 128.29, 128.15, 128.04, 127.78, 127.62, 127.35, 127.25, 127.16, 126.91, 69.20, 65.41, 58.84, 57.37, 52.56, 49.56, 21.67, 21.61; HRMS calcd for C 44 H 46 N 4 O 4 S 2 759.3039, found:759.3010. 4. The diamines catalyze the Henry reaction Table S1. All of the diamines catalyze the Henry reaction Entry Diamine Yield (%) ee(%) 1 A1 99 rac 2 A2 99 5 [a] Reactions were carried out on a 0.5 mmol hexanal using 5.0 mmol CH 3, 2.5 mol% of Cu(OAc) 2 H 2 O and 2.5 mol% of diamine in 1.0 ml of ethanol at room temperature for 12 h. [b] Enantiomeric excess was determined by HPLC on a Chiral OD-H column. The diamine (0.025 mmol) and Cu(OAc) 2 H 2 O (2.5 mg, 0.025 mmol ) were suspended in anhydrous EtOH (1.0 ml) under argon at room temperature. Nitromethane (10 mmol) and Hexanal (0.5 mmol) were added. After stirring for 12h, the volatile components were removed under reduced pressure and the crude product purified by column chromatography. 5. General Procedure for the Henry Reaction The disulfamidediamine ligand (0.025 mmol) and Cu(OAc) 2 H 2 O (2.5 mg, 0.025 mmol) were suspended in anhydrous EtOH (1.0 ml) under argon at room temperature. After 1 h, nitromethane (0.54 ml 10 mmol) and aldehyde (0.5 mmol) were added. After stirring for the amount of time indicated, the volatile components were removed under reduced pressure and the crude product purified by column chromatography. The enantiomeric excess of each product was determined by HPLC on chiral phase, the absolute configuration of the major enantiomer by comparison with its literatureknown retention time on chiral HPLC or by the sign of the optical rotation. [2] 6. Characterization of Nitroaldol Products (R)-(-)-1-Nitroheptan-2-ol (7a) 99% yield, 97% ee, colorless oil; HPLC (Chiralcel AD-H, n-hexane/i-proh, 97/3 v/v, 1.0 ml/min, 20 o C, UV 215 nm): t r (major) = 20.29 min, t r (minor) = 29.66 min; [α] D 25 = -10.4 (c = 1.11, CH 2 Cl 2, 97% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.46-4.28 (m, 3H), 2.68 (b, 1H), 1.57-1.47 (m, 3H), 1.39-1.31 (m, 5H), 0.90 (t, J = 6.72 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) 80.85, 68.89, 33.86, 31.63, 25.01, 22.63, 14.01. (R)-(-)-1-Nitrononan-2-ol (7b) 99% yield, 97% ee, colorless oil; HPLC (Chiralcel AD-H, HPLC n-hexane/i-proh, 98/2 v/v, 0.8 ml/min, 20 o C, UV 220 nm): t r (major) = 35.85 min, t r (minor) = 57.97 min; [α] D 25 = -5.3 (c = 0.99, CH 2 Cl 2, 97% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.45-4.31 (m, 3H), 2.78 (b, 1H), 1.59-1.48 (m, 3H), 1.29-1.28 (m, 9H), 0.88 (t, J = 4.4 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) 80.87, 68.89, 33.92, 31.88, 29.44, 29.26, 25.34, 22.77, 14.22. (R)-(-)-1-Nitrodecan-2-ol (7c) S3

99% yield, 97% ee, colorless oil; HPLC (Chiralcel AD-H, HPLC n-hexane/i-proh, 95/5 v/v, 1.0 ml/min, 20 o C, UV 220 nm): t r (major) = 11.02 min, t r (minor) = 16.23 min; [α] D 25 = -4.9 (c = 1.04, CH 2 Cl 2, 97% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.29-4.45 (m, 2H), 2.77 (b, 1H), 1.58-1.47 (m, 3H), 1.38-1.27 (m, 13H), 0.88 (t, J = 7 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) 80.86, 68.89, 33.91, 33.02, 29.63, 29.61, 29.48, 29.43, 25.34, 22.82, 14.25. (R)-(-)-3-Methyl-1-nitrobutan-2-ol (7d) 91% yield, 99% ee, yellow oil; HPLC (Chiralcel OD-H, n-hexane/i-proh, 98/2 v/v, 0.2 ml/min, 20 o C, UV 215 nm): t r (major) = 100.40 min, t r (minor) = 112.97 min; [α] D 25 = -30.6 (c = 0.69, CH 2 Cl 2, 99% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.50 (dd, J = 2.88 Hz and 12.72 Hz, 1H), 4.41 (dd, J = 9.36 Hz and 12.72 Hz, 1H), 4.1-4.06 (m, 1H), 3.42 (b, 1H), 1.79 (td, J = 6.72 Hz and 13.4 Hz, 1H), 0.97 (t, J = 6.72 Hz, 6H); 13 C NMR (100 MHz, CDCl 3 ) 79.39, 73.49, 31.73, 18.21, 17.34. (R)-(-)-3-Ethyl-1-nitro-2-ol (7e) 89% yield, 98% ee, colorless oil; HPLC (Chiralcel AD-H, n-hexane/i-proh, 99/1 v/v, 0.5 ml/min, 20 o C, UV 220 nm): t r (major) = 62.53 min, t r (minor) = 70.29 min; [α] D 25 = -18.4 (c = 1.01, CH 2 Cl 2, 98% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.46-4.42 (m, 2H), 4.37 (m, 1H), 2.51 (b, 1H), 1.52-1.27 (m, 5H), 0.94 (t, J = 7.2 Hz, 6H); 13 C NMR (100 MHz, CDCl 3 ) 79.67, 70.40, 44.90, 21.99, 21.48, 11.64, 11.56. (R)-(-)-3, 3-Dimethyl-1-nitrobutan-2-ol (7f) 98% yield, 98% ee, colorless oil; HPLC (Chiralcel OD-H, n-hexane/i-proh, 99/1 v/v, 1.0 ml/min, 20 o C, UV 220 nm): t r (major) = 25.32 min, t r (minor) = 30.56 min; [α] D 25 = -27.4 (c = 1.02, CH 2 Cl 2, 98% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.53 (dd, J = 1.32 Hz and 12.88 Hz, 1H), 4.37 (dd, J = 10.4 Hz and 12.88 Hz, 1H), 4.04 (dd, J = 1.32 Hz and 10.4 Hz, 1H), 2.58 (b, 1H), 0.98 (s, 9H); 13 C NMR (100 MHz, CDCl 3 ) 78.46, 76.39, 34.49, 25.77. (R)-(-)-2-Nitro-(1-cyclohexyl) ethanol (7g) 99% yield, 98% ee, colorless oil; HPLC (Chiralcel AD-H, n-hexane/i-proh, 97/3 v/v, 1.0 ml/min, 20 o C, UV 215 nm): t r (major) = 30.16 min, t r (minor) = 32.90 min; [α] D 25 = -18.3 (c = 0.56, CH 2 Cl 2, 98% ee); 1 H NMR (400 MHz, CDCl 3 ) 4.51-4.40 (m, 2H), 4.12-4.07 (m, 1H), 2.55 (b, 1H), 1.82-1.77 (m, 3H), 1.69-1.68 (m, 2H), 1.52-1.43 (m, 1H), 1.25-1.08 (m, 5H); 13 C NMR (100 MHz, CDCl 3 ) 79.51, 73.04, 41.60, 28.98, 28.13, 26.26, 26.06, 25.92. (R)-(+)-1-Nitro-4-phenylbut-2-ol (7h) 99% yield, 95% ee, off-white solid; HPLC (Chiralcel AD-H, n-hexane/i-proh, 90/10 v/v, 1.0 ml/min, 20 o C, UV 215 nm): t r (major) = 11.69 min, t r (minor) = 14.88 min; [α] D 25 = +17.86 (c = 1.13, CH 2 Cl 2, 95% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.32-7.28 (m, 2H), 7.25-7.19 (m, 3H), 4.40-4.27 (m, 3H), 2.85- S4

2.82 (m, 1H), 2.78-2.69 (m, 2H), 1.87-1.77 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) 140.79, 128.84, 128.61, 126.52, 80.74, 67.95, 35.29, 34.51. (R)-(-)-1-Nitro-4-phenyl-but-3-en-2-ol (7i) 74% yield, 94% ee, yellow solid; HPLC (Chiralcel OD-H, n-hexane/i-proh, 85/15 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 34.65 min, t r (minor) = 40.25 min; [α] D 25 = -9.5 (c = 1.01, CH 2 Cl 2, 94% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.38-7.25 (m, 5H), 6.76 (d, J = 15.88 Hz, 1H), 6.12 (dd, J = 6.28 Hz and 15.88 Hz, 1H), 5.02 (m, 1H), 4.49 (d, J = 6.08 Hz, 2H), 2.90 (d, J = 4 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) 135.68, 133.75, 128.90, 128.67, 126.89, 125.14, 80.04, 69.76. (R)-(-)-2-Nitro-1-phenylethanol (7j) 99% yield, 96% ee, yellow oil: HPLC (Chiralcel OD-H, n-hexane/i-proh, 85/15 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 13.24 min, t r (minor) = 16.33 min; [α] D 25 = -53.1 (c = 1.06, CH 2 Cl 2, 96% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.32-7.40 (m, 5H), 5.39 (dd, J = 2.86 HZ and 9.6 Hz, 1H), 4.55 (dd, J = 9.6 Hz and 13.2 Hz, 1H), 4.44 (dd, J = 2.86 Hz and 13.2 Hz, 1H), 3.20 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 138.31, 129.12, 129.06, 126.09, 81.32, 71.10. (R)-(-)-2-Nitro-1-(4-nitrophenyl) ethanol (7k) 99% yield, 92% ee, yellow solid: HPLC (Chiralcel OD-H, n-hexane/i-proh, 85/15 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 22.00 min, t r (minor) = 27.69 min; [α] D 25 = -38.2 (c = 0.99, CH 2 Cl 2, 92% ee); 1 H NMR (400 MHz, CDCl 3 ) 8.28 (dd, J = 2.4 Hz and 9.2 Hz, 2H), 7.65 (d, J = 2.4 Hz, 2H), 5.62 (dd, J = 4 Hz and 8 Hz, 1H), 4.56-4.64 (m, 2H), 3.15 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 148.39, 145.10, 127.16, 124.41, 80.78, 70.18. (R)-(-)-2-Nitro-1-(2-methoxyphenyl) ethanol (7l) 99% yield, 95% ee, colorless oil: HPLC (Chiralcel OD-H, n-hexane/i-proh, 90/10 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 15.84 min, t r (minor) = 19.20 min; [α] 25 D = -48.6 (c = 1.01, CH 2 Cl 2, 95% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.42 (dd, J = 1.6 Hz and 7.2 Hz, 1H), 7.32 (td, J = 1.6 Hz and 8 Hz, 1H), 7.02 (dd, J = 8 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 5.61 (dd, J = 3.2 Hz and 9.2 Hz, 1H), 4.63 (dd, J = 3.2 Hz and 12.8 Hz, 1H), 4.55 (dd, J = 9.2 Hz and 12.8 Hz, 1H), 3.87 (s, 3H), 3.26 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 156.15, 129.95, 127.34, 126.13, 121.29, 110.69, 80.00, 67.96, 55.56. (R)-(-)-2-Nitro-1-(4-phenylphenyl) ethanol (7m) OH Ph 76% yield, 97% ee, off white solid; HPLC (Chiralcel OD-H, n-hexane/i-proh, 85/15 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 19.62 min, t r (minor) = 23.51 min; [α] D 25 = -61.4 (c = 1.04, CH 2 Cl 2, 97% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.64-7.59 (m, 2H), 7.58 (d, J = 8 Hz, 2H), 7.48-7.39 (m, 4H), 7.38 (d, J = 6.4 Hz, 1H), 5.51 (dd, J = 3.2 Hz and 9.6 Hz, 1H), 4.65 (dd, J = 9.6 Hz and 13.2 Hz, S5

1H), 4.55 (dd, J = 3.2 Hz and 13.2 Hz, 1H), 2.83 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 142.21, 140.07, 137.16, 129.10, 127.96, 127.91, 127.32, 126.62, 81.35, 71.01. (R)-(-)-2-Nitro-1-(4-fluorophenyl) ethanol (7n) 87% yield, 96% ee, colorless oil: HPLC (Chiralcel OD-H, n-hexane/i-proh, 90/10 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 15.43 min, t r (minor) = 18.48 min; [α] D 25 = -51.2 (c = 1.04, CH 2 Cl 2, 96% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.37 (dd, J = 5.2 Hz and 8.4 Hz, 2H), 7.08 (t, J = 8.4 Hz, 2H), 5.42 (d, J = 9.2 Hz, 1H), 4.57 (dd, J = 9.2 Hz and 13.2 Hz, 1H), 4.48 (dd, J = 3.2 Hz and 13.2 Hz, 1H), 3.2 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 164.26, 161.80, 134.11, 128.01, 127.92, 116.25, 116.03, 81.29, 70.49. (R)-(-)-2-Nitro-1-(4-chlorophenyl) ethanol (7o) 99% yield, 96% ee, colorless oil: HPLC (Chiralcel OD-H, n-hexane/i-proh, 85/15 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 14.40 min, t r (minor) = 18.74 min; [α] D 25 = -49.0 (c = 1.11, CH 2 Cl 2, 96% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.37-7.30 (m, 4H), 5.41 (dd, J = 3.24 Hz and 9.36 Hz, 1H), 4.55 (dd, J = 9.36 Hz and 13.28 Hz, 1H), 4.47 (dd, J = 3.24 Hz and 13.28 Hz, 1H), 3.30 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 136.74, 134.88, 129.32, 127.51, 81.13, 70.43. (R)-(-)-2-Nitro-1-(4-bromophenyl) ethanol (7p) 88% yield, 96% ee, colorless oil: HPLC (Chiralcel OD-H, n-hexane/i-proh, 85/15 v/v, 0.8 ml/min, 20 o C, UV 215 nm): t r (major) = 14.54 min, t r (minor) = 18.97 min; [α] D 25 = -48.6 (c = 1.03, CH 2 Cl 2, 96% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.52 (d, J = 8.36 Hz, 2H), 7.26 (d, J = 8.36 Hz, 2H), 5.39 (m, 1H), 4.55 (dd, J = 9.36 Hz and 13.32 Hz, 1H), 4.47 (dd, J = 3.2 Hz and 13.32 Hz, 1H), 3.23 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 137.25, 132.30, 127.81, 123.06, 81.07, 70.48. (R)-(-)-2-Nitro-1-(2-naphthyl) ethanol (7q) 81% yield, 96% ee, yellow solid; HPLC (Chiralcel OD-H, n-hexane/i-proh, 80/20 v/v, 1.0 ml/min, 20 o C, UV 215 nm): t r (major) = 22.71 min, t r (minor) = 32.29 min; [α] D 25 = -51.1 (c = 1.06, CH 2 Cl 2, 96% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.89-7.83 (m, 4H), 7.55-7.45 (m, 3H), 5.63 (dd, J = 3.2 Hz and 9.6 Hz, 1H), 4.69 (dd, J = 9.6 Hz and 13.6 Hz, 1H), 4.59 (dd, J = 3.2 Hz and 13.6 Hz, 1H), 2.90 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 135.56, 133.63, 133.39, 129.25, 128.28, 128.01, 126.92, 125.55, 123.40, 81.39, 71.37. (R)-(-)-2-Nitro-1-(2-furyl) ethanol (7r) 95% yield, 97% ee, yellow oil; HPLC (Chiralcel OJ-H, n-hexane/i-proh, 90/10 v/v, 1.0 ml/min, 20 o C, UV 215 nm): t r (major) = 25.69 min, t r (minor) = 32.62 min; [α] D 25 = -48.5 (c = 0.58, CH 2 Cl 2, 97% ee); 1 H NMR (400 MHz, CDCl 3 ) 7.42 (s, 1H), 6.39 (m, 2H), 5.47 (d, J = 8.6 Hz, 1H), 4.79 (dd, J = 9 Hz and 13.5 Hz, 1H), 4.68 (dd, J = 3.12 Hz and 13.5 Hz, 1H), 2.83 (b, 1H); 13 C NMR (100 MHz, CDCl 3 ) 150.87, 143.40, 110.87, 108.42, 78.57, 65.05. S6

7. General Procedure for the Diasteroselective Henry Reaction The disulfamidediamine ligand 4a (16.5 mg, 0.05 mmol) and CuBr (3.6 mg, 0.05 mmol) were suspended in anhydrous MeOH (1.0 ml) under argon at room temperature. After 1 h, 1-nitropropane (0.54 ml 10 mmol) and cyclohexanecarboxaldehyde (0.5 mmol) were added. After stirring for 96h, the volatile components were removed under reduced pressure and the crude product purified by column chromatography. The diastereoselectivity was determined by 1 H-NMR analysis, and the enantiomeric excess of the adduct was determined by HPLC analysis. [3] Compound 10: 46% isolated yield as a mixture of syn:anti (97:3), 96% ee by HPLC analysis (Chiralpak OJ-H column, 0.3 ml/min, n-hexane/i-proh, 99/1 v/v, 0.3 ml/min, 20 o C, UV 220 nm): syn: t r (major) = 64.36 min, t r (minor) = 61.00 min. The absolute stereochemistry assigned based on literature data and/or other examples in the series; [α] D 25 = -4.0 (c = 0.27, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ) 4.60-4.55 (m, 0.97H) (syn), 4.54-4.50 (m, 0.03H) (anti), 3.80 (m, 0.07H) (anti), 3.62 (dd, J = 6 Hz and 12.56 Hz, 0.93H) (syn), 2.13-2.04 (m, 2H), 1.88-1.87 (m, 1H), 1.79-1.77 (m, 3H), 1.69-1.66 (m, 2H), 1.38 (m, 1H), 1.23-1.12 (m, 5H), 1.01-0.97 (t, J = 7.36 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) 92.02, 76.19, 40.50, 29.99, 29.48, 28.10, 27.09, 26.28, 26.21, 25.95, 24.25, 10.46. 8. Synthesis of (R) (-)-3-Methyl-1-aminobutan-2-ol (8). [4] β-nitroalcohol 7d in methanol (2 ml) was hydrogenated (H 2, 1 atm) in the presence of 10% Pd/C for 24 h. The solution was filtered over celite, and the methanol was removed under reduced pressure. The crude material was used without further purification. 96% Yield; yellow oil; [α] 20 D = -2.5 (c = 0.95, EtOH); 1 H NMR (400 MHz, CDCl 3 ): 3.48-3.44 (m, 1H), 3.17-3.12 (m, 1H), 2.57 (b, 2H), 2.43-2.38 (m, 1H), 1.46-1.41 (m, 1H), 0.75 (d, 8 Hz, 6H); 13 C NMR (100 MHz, CDCl 3 ): 64.40, 58.39, 30.94, 19.31, 18.35. 9. The synthesis of (R)-2-phenyl-1-tosylaziridine (9) was same as the synthesis of 2. [1] 75% yield, white solid; [α] D 25 = -6.7 (c = 1.0, CH 2 Cl 2 ); 1 H NMR (400 MHz, CDCl 3 ): 7.84-7.82 (m, 2H), 7.35-7.34 (m, 2H), 2.62-2.60 (m, 1H), 2.52-2.50 (m, 1H), 2.44 (s, 3H), 2.10 (d, J = 4.64 Hz 1H), 1.42-1.40 (m, 1H), 0.90 (dd, J = 6.84 and 1.52 Hz, 3H), 0.79 (dd, J = 6.68 and 1.48 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ): 144.58, 135.28, 129.74, 128.23, 46.42, 32.86, 30.27, 21.78, 19.69, 19.21. References [1] J. C. Mao, B. S. Wan, R. L. Wang, F. Wu, S. W. Lu, J. Org. Chem. 2004, 69, 9123-9127. [2] a) H. Maheswaran, K. L. Prasanth, G. G. Krishna, K. Ravikumar, B. Sridhar, M. L. Kantam, Chem. Commun. 2006, 4066-4068; b) B. Qin, X. Xiao, X. H. Liu, J. L. Huang, Y. H. Wen, X. M. Feng, J. Org. Chem. 2007, 72, 9323-9328; c) A. Bulut, A. Aslan, Ö. Dogan, J. Org. Chem. 2008, 73, 7373-7375; d) M. Breuning, D. Hein, M. Steiner, V. H. Gessner, C. Strohmann, Chem. Eur. J. 2009, 15, 12764-12769; e) M. Bandini, F. Piccinelli, S. Tommasi, A. Umani-Ronchi, C. Ventrici, Chem. Commun. 2007, 616-618. [3] T. Arai, M. Watanabe, A. Yanagisaka, Org. Lett. 2007, 9, 3595-3597. [4] B. T. Cho, S. H. Kang, S. H. Shin, Tetrahedron: Asymmetry 2002, 13, 1209-1217. S7

NH HN Ph Ph NH HN Ts Ts S8

NH HN Ph Ph NH HN Ts Ts S9

NH HN Ph Ph NH HN Ts Ts S10

NH HN Ph Ph NH HN Ts Ts S11

NH HN NH HN Ts Ts S12

NH HN NH HN Ts Ts S13

Ph NH HN Ph NH HN Ts Ts S14

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O 2 N OH S38

O 2 N OH S39

OMe S40

OMe S41

Ph OH NO2 S42

Ph OH NO2 S43

F OH NO2 S44

F OH NO2 S45

Cl OH S46

Cl OH S47

Br OH NO2 S48

Br OH NO2 S49

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O OH S52

O OH S53

HO NH 2 S54

HO NH 2 S55

N Ts S56

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NO2 S58

NO2 S59

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O 2 N S80

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OMe S82

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Ph S84

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F S86

F S87

Cl S88

Cl S89

Br S90

Br S91

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O S94

O S95

N Ts S96

S97