SUPPORTING INFORMATION

Transcription

1 SUPPORTING INFORMATION Asymmetric Vinylogous aza-darzens Approach to Vinyl Aziridines Isaac Chogii, Pradipta Das, Michael D. Delost, Mark N. Crawford and Jon T. Njardarson* Department of Chemistry and Biochemistry, University of Arizona, 1306 E. University Blvd., Tucson, AZ 85721, USA *To whom correspondence should be addressed. Table of Contents General Experimental... S6 General Procedure A: Synthesis of various (E) tert-butanesulfinyl imines.. S7 Procedure for the synthesis of (E) tert-butanesulfinyl imine....s7 Characterization Data of various chiral imines..... S8 Compound SI S8 Scheme S4: Vinylogous Asymmetric aza-darzens Reaction Scope General Procedure B: For γ-bromo butenolide s8 Procedure for 1 mmol scale of compound S9 Characterization Data for vinyl aziridines s9-s17 Compound S9 Compound S10 Compound S10 Compound S10 Compound S11 Compound S11 Compound S12 Compound S12 Compound S13 Compound S13

2 Compound S13 Compound S14 Compound S14 Compound S15 Compound S15 Compound S16 Compound S16 Compound S16 Compound S17 Compound S17 Scheme S6: Altering Nucleophile Impacts Reaction Yields General Procedure C: For γ-bromo ester s18 Characterization Data for vinyl aziridines s18-s20 Compound S18 Compound S19 Compound S20 Scheme S7: Titanium Enolate-Mediated Mannich Reactions General Procedure D: For γ-bromo ester s20 Characterization Data for Mannich Adducts......S21 S25 Compound S21 Compound S21 Compound S22 Compound S22 Compound S22 Compound S23 Compound S23 Compound S24 Compound S24 Compound S25 S2

3 Compound S25 X-RAY Crystallographic Data Compound S26 S31 Compound S31 S36 References S37 Compounds Spectra Chiral Imines Compound SI-18 1 H-NMR S38 Compound SI C-NMR S39 Scheme S4: Vinylogous Asymmetric aza-darzens Reaction Scope Compound 13 1 H-NMR S40 Compound C-NMR S41 Compound 11 1 H-NMR S42 Compound C-NMR S43 Compound 12 1 H-NMR S44 Compound C-NMR S45 Compound 14 1 H-NMR S46 Compound C-NMR S47 Compound 15 1 H-NMR S48 Compound C-NMR S49 Compound 16 1 H-NMR S50 Compound C-NMR S51 Compound 17 1 H-NMR S52 Compound C-NMR S53 Compound 18 1 H-NMR S54 Compound C-NMR S55 S3

4 Compound 19 1 H-NMR S56 Compound C-NMR S57 Compound 20 1 H-NMR S58 Compound C-NMR S59 Compound 21 1 H-NMR S60 Compound C-NMR S61 Compound 22 1 H-NMR S62 Compound C-NMR S63 Compound 23 1 H-NMR S64 Compound C-NMR S65 Compound 24 1 H-NMR S66 Compound C-NMR S67 Compound 25 1 H-NMR S68 Compound C-NMR S69 Compound 26 1 H-NMR S70 Compound C-NMR S71 Compound 27 1 H-NMR S72 Compound C-NMR S73 Compound 28 1 H-NMR S74 Compound C-NMR S75 Compound 29 1 H-NMR S76 Compound C-NMR S77 Compound 30 1 H-NMR S78 Compound C-NMR S79 Scheme S6: Altering Nucleophile Impacts Reaction Yields Compound 32 1 H-NMR S80 Compound C-NMR S81 Compound 33 1 H-NMR S82 Compound C-NMR S83 S4

5 Compound 34 1 H-NMR S84 Compound C-NMR S85 Scheme S7: Titanium Enolate-Mediated Mannich Reactions Compound 35 1 H-NMR S86 Compound C-NMR S87 Compound 36 1 H-NMR S88 Compound C-NMR S89 Compound 37 1 H-NMR S90 Compound C-NMR S91 Compound 38 1 H-NMR S92 Compound C-NMR S93 Compound 39 1 H-NMR S94 Compound C-NMR S95 Compound 40 1 H-NMR S96 Compound C-NMR S97 Compound 41 1 H-NMR S98 Compound C-NMR S99 Compound 42 1 H-NMR S100 Compound C-NMR S101 Compound 43 1 H-NMR S102 Compound C-NMR S103 Compound 44 1 H-NMR S104 Compound C-NMR S105 Compound 45 1 H-NMR S106 Compound C-NMR S107 S5

6 General Experimental: Commercial reagents were purchased and used without further purification. All glass wares were flamedried under vacuum and all reactions were performed under a nitrogen atmosphere with dry solvents, unless otherwise stated. Dry tetrahydrofuran (THF), diethyl ether (Et2O), dichloromethane (DCM), toluene were obtained by passing previously degassed solvents through activated alumina columns. Methanol was distilled in the presence of anhydrous CaH2 and stored under nitrogen atmosphere. Reactions were monitored by thin layer chromatography (TLC) carried out on EMD 250µm silica gel 60- F254 plates. Plates were visualized using mainly potassium permanganate stain, ceric ammonium molybdate and heat. Flash Chromatography was done with SiliaFlash F60 (particle size 40-63µm). 1 H and 13 C NMR data was acquired on Bruker DRX 400, 500 or 600 and the spectra were referenced using residual solvent as internal reference for 1 H and 13 C NMR (CDCl3 : 7.26 ppm for 1 H NMR, for 13 C NMR). Signals are reported as follows: s (singlet), d (doublet), t (triplet), q (quartet), dd (doublet of doublets), dt (doublet of triplets), dq (doublet of quartets), dtt (doublet of triplets of triplets), ddq (doublet of doublets of quartets), br s (broad singlet), m (multiplet). Coupling constants are reported in hertz (Hz).Infrared spectra were obtained on a Shimadzu Prestige FT-IR. High-resolution mass spectra were acquired at the University of Arizona Mass Spectral Facility. Optical rotations were recorded on Rudolph Autopol IV polarimeter. S6

7 Experimental Procedures: General procedure A: Synthesis of various E-tert-Butanesulfinyl imines Scheme SA: Synthesis of various E-tert-Butanesulfinyl imines Procedure for the synthesis of (E) tert-butanesulfinyl imine: To a solution of the corresponding aldehyde (6.5 mmol, 1.0 equiv in THF [0.1 M overall concentration]), was added titanium(iv) isopropoxide (Ti(O i Pr)4, 13.0 mmol, 2.0 equiv) at room temp and stirred for 10 minutes after which solution of tert-butanesulfamide (6.5 mmol, 1.0 equiv in THF) was added and reaction stirred at room temp for 6 to 8 h. Reaction was quenched with brine, filtered and the filter cake washed with ethyl acetate. The filtrate was then washed with water and brine, dried over Na2SO4, concentrated and crude purified by flash column chromatography (silica gel, 5-20% EtOAc : Hexanes) [Except SI-6 was eluted with 50% EtOAc : Hexanes]. S7

8 Compounds SI-1 1, 9 2, SI-2 3, SI-3 2, SI-4 4, SI-5 5, SI-6 6, SI-7 7, SI-8 8, SI-9 9, SI-10 10, SI-11 11, SI-12 1, SI- 13 1, SI-14 1, SI-15 10, SI-16 10, SI-17 1 and SI were prepared according to the general procedure outlined above and the spectral data matched with the literature reported ones. Yellow solid, Yield = 86%. [α] 23 D = (c. 2.1, CHCl3). 1 H NMR (400 MHz, CDCl3) δ 8.46 (s, 1H), 6.97 (d, J = 2.3 Hz, 2H), 6.58 (t, J = 2.3 Hz, 1H), 3.81 (s, 6H), 1.24 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ , , , , , 57.72, 55.42, IR (NaCl film) 2964, 1587, 1415, 1380, 1208, 1159, 1074 cm -1. HRMS (ESI + ) m/z [calculated mass for C13H19NaNO3S (M+Na) ]. Scheme S4: Vinylogous Asymmetric aza-darzens Reaction Scope Scheme S4 General Procedure B: To a flame dried round bottomed flask equipped with a stir bar, tetrahydrofuran (THF, 0.1M overall concentration) and N-sulfinimine (0.4 mmol, 1.0 equiv, 1.0 M in THF) were added and the mixture cooled to -78 C. To this a solution bromo butenolide 10 in THF (0.6 mmol, 1.5 equiv, 1.0 M in THF) was added, followed by slow syringe pump addition (rate = 1mL/h) of lithium hexamethylsilyl amide (LiHMDS) (0.8 mmol, 2.0 equiv, 1.0 M in THF). The reaction mixture was stirred for additional 4-5 h at -78 C at which point TLC analysis showed complete consumption of the imine. It was then quenched with saturated ammonium chloride, warmed to room temperature and extracted using ethyl acetate (3 times). The organic fractions were combined, washed with brine, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated in vacuo. Crude material was purified by flash column chromatography (silica gel) to afford the vinyl aziridine products. S8

9 Procedure for 1 mmol scale: To a flame dried round bottomed flask equipped with a stir bar, tetrahydrofuran (THF, 5.5 ml, 0.1M overall concentration) and 4-Nitrophenylsulfinimine (250 mg, 1.0 mmol, 1.0 equiv, 1.0 ml in THF) were added and the mixture cooled to -78 C. To this a solution bromo butenolide 10 in THF (265.5 mg, 1.5 mmol, 1.5 equiv, 1.5 ml in THF) was added, followed by slow syringe pump addition (rate = 1mL/h) of lithium hexamethylsilyl amide (LiHMDS) (2.0 ml, 2.0 mmol, 2.0 equiv, 1.0 M in THF/ethylbenzene). The reaction mixture was stirred for additional 5 h at -78 C at which point TLC analysis showed complete consumption of the imine. It was then quenched with saturated ammonium chloride, warmed to room temperature and extracted using ethyl acetate (3 times). The organic fractions were combined, washed with brine, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated in vacuo. Crude material was purified by flash column chromatography (silica gel, 40-50% EtOAc/hexanes) to afford the 4-Nitrophenylvinyl aziridine product (13) in 56% yield (192.9 mg). Characterization and spectral data for the vinyl aziridine products: White solid, mg, Yield = 82%. dr = 2:1, Rf = 0.32 [40-50% EtOAc/hexanes] [α] 23 D = (c 1.8, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 8.23 (d, J = 10 Hz, 2H), 7.49 (d, J = 10 Hz, 2H), 5.99 (td, J = 1.9, 0.9 Hz, 1H), 4.43 (dd, J = 17.7, 2.0 Hz, 1H), 4.32 (ddd, J = 17.7, 1.9, 0.7 Hz, 1H), 3.89 (d, J = 7.1 Hz, 1H), 3.82 (d, J = 7.1 Hz, 1H), 1.33 (s, 9H) 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 71.52, 57.72, 41.50, 33.42, IR (NaCl film) 3094, 2961, 2868, 1734, 1522, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H18N2NaO5S (M+Na) ]. S9

10 White solid, 69.5 mg, Yield = 52%. dr = 2:1, Rf = 0.28 [20-30% EtOAc/hexanes] [α] 23 D = (c 1.0, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.48 (d, J = 10 Hz, 2H), 7.17 (d, J = 10 Hz, 2H), 5.99 (td, J = 1.9, 0.8 Hz, 1H), 4.40 (dd, J = 17.7, 1.9 Hz, 1H), 4.22 (ddd, J = 17.7, 1.9, 0.8 Hz, 1H), 3.82 (d, J = 7.0 Hz, 1H), 3.70 (d, J = 7.0 Hz, 1H), 1.30 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 71.62, 57.51, 41.61, 33.23, IR (NaCl film) 3094, 2959, 2926, 1740, 1165, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H18BrNNaO3S (M+Na) ]. White solid, 34.7 mg, Yield = 26%. dr = 1:2, Rf = 0.30 [20-30% EtOAc/hexanes] [α] 23 D = (c 0.86, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.48 (d, J = 10 Hz, 2H), 7.16 (d, J = 10 Hz, 2H), 6.02 (q, J = 1.7 Hz, 1H), 4.50 (ddd, J = 17.6, 1.9, 0.9 Hz, 1H), 4.40 (dd, J = 17.6, 2.0 Hz, 1H), 4.13 (d, J = 7.1 Hz, 1H), 3.32 (d, J = 7.0 Hz, 1H), 1.27 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 71.55, 57.55, 38.17, 36.79, IR (NaCl film) 3094, 2959, 2926, 1740, 1165, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H18BrNNaO3S (M+Na) ]. White solid, mg, Yield = 75%. dr = 2:1, Rf = 0.25 [30-40% EtOAc/hexanes] [α] 23 D = (c 2.6, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.62 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.2 Hz, 2H), 6.01 (td, J = 1.9, 0.9 Hz, 1H), 4.41 (dd, J = 17.7, 2.0 Hz, 1H), 4.24 (ddd, J = 17.8, 1.9, 0.8 Hz, 1H), 3.87 (d, J = 7.1 Hz, 1H), 3.79 (d, J = 7.0 Hz, 1H), 1.31 (s, 9H). S10

11 13 C NMR (125 MHz, CDCl3) δ , , , (q, 33 Hz), , (q, 3.7 Hz), (q, 274 Hz), , 71.57, 57.58, 41.66, 33.32, IR (NaCl film) 2964, 2930, 1749, 1324, 1066 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H18F3NNaO3S (M+Na) ]. White solid, mg, Yield = 75%. dr = 2:1, Rf = 0.3 [25-35% EtOAc/hexanes] [α] 23 D = (c 1.0, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.28 (m, 2H), 7.05 (m, 2H), 6.00 (td, J = 1.9, 0.8 Hz, 1H), 4.40 (dd, J = 17.8, 1.9 Hz, 1H), 4.19 (ddd, J = 17.7, 1.9, 0.7 Hz, 1H), 3.82 (d, J = 7.0 Hz, 1H), 3.74 (d, J = 7.0 Hz, 1H), 1.31 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , (d, Hz), , (d, 8.8 Hz), (d, 2.5 Hz), , (d, 21.3 Hz), 71.68, 57.52, 41.57, 33.32, IR (NaCl film) 3090, 2961, 2868, 1734, 1522, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H18FNNaO3S (M+Na) ]. White solid, mg, Yield = 88%. dr = 2:1, Rf = 0.25 [40-50% EtOAc/hexanes] [α] 23 D = (c 1.9, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.67 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 7.9 Hz, 2H), 5.99 (td, J = 2.0, 0.9 Hz, 1H), 4.41 (dd, J = 17.7, 2.0 Hz, 1H), 4.29 (dd, J = 17.8, 2.5 Hz, 1H), 3.87 (d, J = 7.3 Hz, 1H), 3.78 (d, J = 7.1 Hz, 1H), 1.32 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , 71.50, 57.62, 41.60, 33.38, IR (NaCl film) 2927, 2861, 2228, 1750, 1080 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H18N2NaO3S (M+Na) ]. S11

12 White solid, mg, Yield = 80%, dr = 1:1, inseparable mixture, Rf = 0.25 [45-55% EtOAc/hexanes] 1 H NMR (499 MHz, CDCl3) Cis-diastereomer 1: δ 5.78 (td, J = 2.0, 0.8 Hz, 1H), 4.81 (dd, J = 17.8, 2.0 Hz, 1H), 4.62 (dd, J = 17.7, 1.8 Hz, 1H), 3.79 (d, J = 6.0 Hz, 1H), 3.62 (d, J = 6.2 Hz, 1H), 1.32 (s, 9H). Cis-diastereomer 2: δ 5.99 (td, J = 2.0, 1.0 Hz, 1H), 4.65 (m, 2H), 4.62 (dd, J = 17.7, 1.8 Hz, 1H), 4.19 (d, J = 6.6 Hz, 1H), 3.34 (d, J = 6.8 Hz, 1H), 1.27 (s, 9H); 13 C NMR (126 MHz, CDCl3) Mixture of two diastereomers δ , , , , (m), (m), (m), (m), (m), (m), (m), (m), , , (dt, 4.3, 15.5 Hz), (dt, 4.2, 14.3 Hz), 71.70, 71.26, 57.88, 57.49, 34.96, 34.20, 31.94, 30.02, 22.31, IR (NaCl film) 2963, 2929, 2871, 1752, 1525, 1084 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H14F5NNaO3S (M+Na) ]. White solid, mg, Yield = 77%. dr = 1:1, inseparable mixture, Rf = 0.32 [80-90% EtOAc/hexanes] 1 H NMR (499 MHz, CDCl3) δ (m, 2H), 7.57 (ddt, J = 13.3, 8.0, 2.0 Hz, 1H), 7.29 (ddd, J = 7.6, 4.8, 2.5 Hz, 1H), 5.99 (td, J = 2.0, 0.9 Hz, 1H), 4.41 (dd, J = 17.1, 2.0 Hz, 1H), 4.30 (ddd, J = 17.7, 1.8, 0.7 Hz, 1H), 3.85 (d, J = 7.0 Hz, 1H), 3.76 (d, J = 6.9 Hz, 1H), 1.31 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , 71.59, 57.61, 40.07, 33.05, IR (NaCl film) 2959, 2927, 1741, 1518, 1071 cm -1. HRMS (ESI + ) m/z [calculated mass for C15H19N2O3S (M+H) ]. S12

13 White solid, 89.0 mg, Yield = 61%. dr = 3:1, Rf = 0.28 [30-40% EtOAc/hexanes] [α] 23 D = (c 0.86, CHCl3). 1 H NMR (499 MHz, CDCl3) δ (m, 5H), 6.02 (td, J = 1.9, 0.8 Hz, 1H), 4.39 (dd, J = 17.8, 1.9 Hz, 1H), 4.13 (ddd, J = 17.8, 1.9, 0.7 Hz, 1H), 3.85 (d, J = 7.1 Hz, 1H), 3.78 (d, J = 7.0 Hz, 1H), 1.31 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 71.71, 57.46, 42.19, 33.34, IR (NaCl film) 2958, 2927, 1741, 1219, 1071 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H19NNaO3S (M+Na) ]. White solid, 66.4 mg, Yield = 51%. dr = 3:1, Rf = 0.33 [35-45% EtOAc/hexanes] [α] 23 D = (c 2.0, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.42 (d, J = 8.7 Hz, 1H), 6.93 (d, J = 3.1 Hz, 1H), 6.75 (dd, J = 8.8, 3.1 Hz, 1H), 5.86 (td, J = 1.9, 0.8 Hz, 1H), 4.60 (dd, J = 17.8, 2.0 Hz, 1H), 4.34 (dd, J = 17.7, 1.9 Hz, 1H), 3.92 (d, J = 7.0 Hz, 1H), 3.79 (s, 3H), 3.74 (dt, J = 7.0, 0.6 Hz, 1H), 1.31 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , , 71.98, 57.59, 55.48, 43.59, 32.99, IR (NaCl film) 2959, 2927, 1741, 1518, 1071 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H20BrNNaO4S (M+Na) ]. White solid, 63.4 mg, Yield = 46%. dr = 3:1, Rf = 0.27 [30-40% EtOAc/hexanes] [α] 23 D = (c 1.0, CHCl3). S13

14 1 H NMR (499 MHz, CDCl3) δ 6.77 (d, J = 1.1 Hz, 2H), 6.74 (q, J = 0.9 Hz, 1H), 6.01 (td, J = 1.9, 0.8 Hz, 1H), 5.99 (q, J = 1.5 Hz, 2H), 4.44 (dd, J = 17.8, 1.9 Hz, 1H), 4.24 (ddd, J = 17.8, 2.0, 0.7 Hz, 1H), 3.78 (d, J = 6.9 Hz, 1H), 3.69 (d, J = 6.9 Hz, 1H), 1.30 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , , , 71.79, 57.44, 42.00, 33.43, IR (NaCl film) 2959, 2925, 1748, 1504, 1079 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H19NNaO5S (M+Na) ]. White solid, 83.9 mg, Yield = 58%. dr = 3:1, Rf = 0.3 [20-30% EtOAc/hexanes] [α] 23 D = (c 2.0, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.33 (dd, J = 5.0, 3.0 Hz, 1H), 7.23 (m, 1H), 6.99 (dd, J = 5.0, 1.3 Hz, 1H), 6.05 (t, J = 1.9 Hz, 1H), 4.45 (dd, J = 17.8, 1.9 Hz, 1H), 4.20 (dd, J = 17.7, 1.9 Hz, 1H), 3.79 (d, J = 6.8 Hz, 1H), 3.72 (dd, J = 6.9, 1.0 Hz, 1H), 1.29 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 77.25, 77.00, 76.74, 71.65, 57.40, 39.02, 33.20, IR (NaCl film) 2926, 1738, 1518, 1091 cm -1. HRMS (ESI + ) m/z [calculated mass for C14H17NNaO3S2 (M+Na) ]. White solid, 80.4 mg, Yield = 56%. dr = 3:1, Rf = 0.3 [20-30% EtOAc/hexanes] [α] 23 D = (c 1.1, CHCl3). 1 H NMR (499 MHz, CDCl3) δ (d, J = 3.2 Hz, 1H), 7.33 (d, J = 3.3 Hz, 1H), 6.08 (td, J = 2.0, 1.0 Hz, 1H), 4.60 (d, J = 1.9 Hz, 2H), 4.02 (d, J = 6.9 Hz, 1H), 3.88 (dd, J = 7.0, 1.1 Hz, 1H), 1.32 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , 71.75, 57.65, 40.27, 33.68, IR (NaCl film) 2959, 2923, 1738, 1518, 1071 cm -1. S14

15 HRMS (ESI + ) m/z [calculated mass for C13H17N2O3S2 (M+H) ]. White solid, 63.4 mg, Yield = 44%. dr = 3:1, Rf = 0.25 [20-30% EtOAc/hexanes] [α] 23 D = (c 2.2, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 6.00 (td, J = 1.9, 1.0 Hz, 1H), 4.86 (dd, J = 17.6, 1.9 Hz, 1H), 4.79 (dd, J = 17.7, 1.9 Hz, 1H), 3.44 (d, J = 7.0 Hz, 1H), 2.28 (dd, J = 9.1, 7.0 Hz, 1H), 1.88 (d, J =11.7 Hz, 1H), (m, 2H), 1.72 (m, 4H), (m, 1H), (m, 3H), 1.21 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.43, 57.05, 46.34, 35.91, 30.70, 30.46, 30.02, 25.93, 25.28, IR (NaCl film) 2925, 2853, 1751, 1074 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H26NO3S (M+H) ]. White solid, 75.8 mg, Yield = 52%. dr = 3:1, Rf = 0.25 [20-30% EtOAc/hexanes] [α] 23 D = (c 2.2, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 6.01 (td, J = 1.8, 0.9 Hz, 1H), 4.86 (ddd, J = 17.7, 1.9, 0.7 Hz, 1H), 4.77 (dd, J = 17.7, 1.9 Hz, 1H), 3.45 (d, J = 7.1, Hz, 1H), 2.37 (dd, J = 9.2, 7.0 Hz, 1H), (m, 1H), (m, 8H), 1.21 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.31, 57.01, 46.12, 37.67, 31.01, 30.97, 29.66, 25.30, 25.07, IR (NaCl film) 2955, 2868, 1748, 1643, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C15H23NNaO3S (M+Na) ]. S15

16 White solid, 88 mg, Yield = 58%. dr = 3:1, Rf = 0.28 [20-30% EtOAc/hexanes] [α] 23 D = (c 1.0, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 6.09 (dq, J = 2.0, 1.0 Hz, 1H), 4.91 (d, J = 17.9, 1.8 Hz, 1H), 4.81 (dd, J = 17.7, 1.9 Hz, 1H), 3.47 (d, J = 6.9 Hz, 1H), 2.19 (t, J = 6.6 Hz, 1H), 1.22 (s, 9H), 0.70 (m, 1H), 0.63 (m, 2H), 0.55 (dtd, J = 9.6, 5.0, 3.6 Hz, 1H), 0.34 (dtd, J = 10.2, 5.1, 3.6 Hz, 1H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.25, 57.18, 44.00, 31.12, 22.54, 8.01, 4.07, IR (NaCl film) 2964, 2928, 2868, 1750, 1219, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C13H19NNaO3S (M+Na) ]. White solid, 93.7 mg, Yield = 65%. dr = 3:1, Rf = 0.28 [15-25% EtOAc/hexanes] [α] 23 D = (c 0.85, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 5.99 (td, J = 1.9, 1.0 Hz, 1H), 4.85 (ddd, J = 17.7, 1.9, 0.7 Hz, 1H), 4.77 (dd, J = 17.7, 1.9 Hz, 1H), 3.43 (d, J = 7.1 Hz, 1H), 2.52 (dq, J = 7.1, 7.3 Hz, 1H), 1.44 (m, 3H), 1.20 (m, 9H), 1.27 (m, 9H), 0.87 (t, J = 7.4 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.31, 57.01, 41.32, 31.65, 30.61, 29.05, 29.01, 26.90, 26.84, 22.56, 22.51, IR (NaCl film) 2958, 2923, 1738, 1639, 1076 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H29NNaO3S (M+Na) ]. White solid, 82.3 mg, Yield = 53%. dr = 3:1, Rf = 0.3 [15-25% EtOAc/hexanes] [α] 23 D = (c 0.82, CHCl3). S16

17 1 H NMR (499 MHz, CDCl3) δ 6.00 (td, J = 1.9, 1.0 Hz, 1H), 4.86 (ddd, J = 17.7, 1.9, 0.7 Hz, 1H), 4.79 (dd, J = 17.7, 1.9 Hz, 1H), 3.47 (d, J = 7.0 Hz, 1H), 2.25 (dd, J = 9.8, 7.0 Hz, 1H), 1.37 (m, 1H), 1.21 (s, 9H), 1.11 (d, J = 6.6 Hz, 3H), 0.89 (d, J = 6.8 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.41, 57.02, 47.75, 31.15, 26.98, 22.50, 20.04, IR (NaCl film) 309, 2961, 2868, 1734, 1522, 1078 cm -1. HRMS (ESI + ) m/z [calculated mass for C13H21NNaO3S (M+Na) ]. White solid, 90.3 mg, Yield = 63%. dr = 3:1, Rf = 0.28 [15-25% EtOAc/hexanes] [α] 23 D = (c 1.6, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 5.99 (q, J = 1.6 Hz, 1H), 4.86 (dd, J = 17.5, 1.7 Hz, 1H), 4.77 (dd, J = 17.7, 1.9 Hz, 1H), 3.44 (d, J = 7.0 Hz, 1H), 2.53 (q, J = 6.6 Hz, 1H), 1.43 (m, 3H), 1.27 (m, 9H), 1.21 (s, 9H), 0.88 (t, J = 6.9 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.32, 57.02, 41.33, 31.66, 30.62, 29.05, 29.02, 26.91, 26.84, 22.57, 22.51, IR (NaCl film) 2954, 2923, 2854, 1738, 1076 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H29NNaO3S (M+Na) ]. White solid, 89.8 mg, Yield = 62%. dr = 3:1, Rf = 0.3 [15-25% EtOAc/hexanes] [α] 23 D = (c 1.0, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 5.99 (dd, J = 1.6 Hz, 1H), 4.85 (dd, J = 17.8, 1.8 Hz, 1H), 4.77 (dd, J = 17.6, 1.9 Hz, 1H), 3.43 (d, J = 7.0 Hz, 1H), 2.56 (td, J = 7.3, 5.4 Hz, 1H), (m, J = 6.8 Hz, 1H), (m, 2H), 1.21 (s, 9H), 0.97 (d, J = 6.7 Hz, 3H), 0.93 (d, J = 6.7 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ , , , 72.31, 57.01, 40.15, 35.58, 30.24, 27.01, 22.50, 22.48, S17

18 IR (NaCl film) 2956, 2927, 2868, 1739, 1639, 1076 cm -1. HRMS (ESI + ) m/z [calculated mass for C14H24NO3S (M+H) ]. Scheme S6: Altering Nucleophile Impacts Reaction Yields Scheme S6 General Procedure C: To a flame dried round bottomed flask equipped with a stir bar, tetrahydrofuran (THF, 0.1M overall concentration) and N-sulfinimine (0.2 mmol, 1.0 equiv, 1.0 M in THF) were added and the mixture cooled to -78 C. To this a solution -bromo ester (31) in THF (0.4 mmol, 2.0 equiv, 1.0 M in THF) was added, followed by slow syringe pump addition (rate = 1mL/h) of lithium hexamethylsilyl amide (LiHMDS) (0.5 mmol, 2.5 equiv, 1.0 M in THF). The reaction mixture was stirred for additional 3-5 h at -78 C at which point TLC analysis showed complete consumption of the imine. The reaction was then warmed to 0 C (ice-bath) and stirred at 0 C for 15 minutes. It was then quenched with saturated ammonium chloride, warmed to room temperature and extracted using ethyl acetate (3 times). The organic fractions were combined, washed with brine, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated in vacuo. Crude material was purified by flash column chromatography (silica gel) to afford the vinyl aziridine products. Characterization and spectral data for the vinyl aziridine products: Colorless Oil, 40.1 mg, Yield = 56%. dr = 3:1 Inseparable Mixture of diastereomers. Rf = 0.3 [30-40% EtOAc/hexanes] [α] 23 D = (c 1.6, CHCl3). 1 H NMR (499 MHz, CDCl3) Major Diastereomer δ (m, 2H), (m, 2H), 5.87 (p, J = 1.3 Hz, 1H), 3.70 (d, J = 7.5 Hz, 1H), 3.65 (d, J = 7.2 Hz, 1H), 3.64 (s, 3H), 1.95 (d, J = 1.4 Hz, 3H), 1.35 (s, 9H). S18

19 Minor Diastereomer δ (m, 2H), (m, 2H), 6.01 (t, J = 1.4 Hz, 1H), 4.11 (d, J = 7.5 Hz, 1H), 3.69 (s, 3H), 3.21 (d, J = 7.4 Hz, 1H), 1.88 (dd, J = 1.4, 0.7 Hz, 3H), 1.25 (s, 9H). 13 C NMR (126 MHz, CDCl3) Major Diastereomer δ , , , , , , , 57.40, 51.28, 42.09, 40.94, 22.60, Minor Diastereomer δ , , , , , , , 57.42, 51.24, 45.56, 37.37, 22.68, IR (NaCl film) 2955, 1751, 1556, 1432, 1326, 1238, 1188, 1084 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H22NaN2O5S (M+Na) ]. Colorless Oil, 33.3 mg, Yield = 48%. dr = 3:1 Inseparable Mixture of diastereomers. Rf = 0.3 [25-35% EtOAc/hexanes] [α] 23 D = (c 0.4, CHCl3). 1 H NMR (499 MHz, CDCl3) Major Diastereomer δ 7.42 (d, J = 8.4 Hz, 2H), (m, 2H), 5.86 (dq, J = 2.0, 1.2 Hz, 1H), 3.65 (s, 3H), 3.58 (d, J = 7.5 Hz, 1H), 3.56 (d, J = 7.4 Hz, 1H), 1.94 (d, J = 1.4 Hz, 3H), 1.32 (s, 9H). Minor Diastereomer δ 7.42 (d, J = 8.4 Hz, 2H), (m, 2H), 5.99 (q, J = 1.4 Hz, 1H), 3.98 (d, J = 7.3 Hz, 1H), 3.69 (s, 3H), 3.12 (ddd, J = 7.4, 1.4, 0.8 Hz, 1H), 1.89 (dd, J = 1.4, 0.7 Hz, 3H), 1.23 (s, 9H). 13 C NMR (126 MHz, CDCl3) Major Diastereomer δ , , , , , , , 57.18, 51.14, 41.89, 41.11, 22.62, Minor Diastereomer δ , , , , , , , 57.25, 51.17, 45.12, 37.57, 22.71, IR (NaCl film) 2962, 1734, 1456, 1241, 1196, 1101, 1055 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H22NaBrNO3S (M+Na) ]. S19

20 Colorless Oil, 27.6 mg, Yield = 36%. dr = 3:1 Inseparable Mixture of diastereomers. Rf = 0.3 [20-30% EtOAc/hexanes] [α] 23 D = (c 1.1, CHCl3). 1 H NMR (499 MHz, CDCl3) Major Diastereomer δ (m, 5H), 5.89 (p, J = 1.3 Hz, 0H), 3.64 (d, J = 7.5 Hz, 1H), 3.63 (s, 3H), 3.56 (dt, J = 7.4, 0.7 Hz, 1H), 1.94 (d, J = 1.4 Hz, 3H), 1.33 (s, 9H). Minor Diastereomer δ (m, 5H), 6.01 (p, J = 1.4 Hz, 1H), 4.04 (d, J = 7.4 Hz, 1H), 3.67 (s, 3H), 3.12 (ddd, J = 7.4, 1.5, 0.8 Hz, 1H), 1.89 (dd, J = 1.4, 0.7 Hz, 3H), 1.25 (s, 9H). 13 C NMR (126 MHz, CDCl3) Major Diastereomer δ , , , , , , , 57.09, 51.04, 41.95, 41.74, 22.64, Minor Diastereomer δ , , , , , , , 57.19, 51.07, 45.08, 38.23, 22.74, IR (NaCl film) 2984, 2953, 1720, 1652, 1436, 1321, 1214, 1167, 1083 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H24NO3S (M+H) ]. Scheme S7: Titanium Enolate-Mediated Mannich Reactions Scheme S7 General Procedure D 13 : To a flame dried round bottomed flask equipped with a stir bar, a solution of lithium hexamethylsilyl amide (LiHMDS) (1.0 mmol, 2.5 equiv) in THF (1.0 M) was added and cooled to -78 C. To this a solution of the -bromo ester (31) (0.8 mmol, 2.0 equiv) in THF (1.0 M) was added via syringe pump (2.0 ml/h) and the reaction was stirred for 30 min. Then to this solution was added ClTi(O i Pr)3 (2.0 mmol, 5.0 equiv) in THF (1.0 M in hexanes) [via syringe pump 5.0 ml/h] and the orangecolored enolate was stirred for 30 min. A solution of the N-sulfinimine (0.4 mmol, 1.0 equiv) in THF (1.0 M) was slowly added via syringe pump [0.5 ml/h] and the solution was stirred for 8-10 h at -78 C. Upon reaction completion as determined by TLC, a saturated aqueous solution of NH4Cl (10 equiv) was added S20

21 and the suspension was warmed to room temperature. The mixture was diluted with H2O and vigorously stirred to dissolve the titanium precipitate. The mixture was then decanted into a separatory funnel, and the remaining solid was diluted with equal parts of H2O and EtOAc and vigorously stirred for 1 hr. The mixture was then added to the separatory funnel and the organic layer was collected. The aqueous layer was then extracted with EtOAc (3 times). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated to give the N-sulfinyl-amino ester product. Crude material was purified by flash column chromatography (silica gel) to afford the Mannich adducts. Characterization and spectral data for the Mannich adducts: Colorless Oil, mg, Yield = 78%. dr = 15:1, Rf = 0.33 [50-60% EtOAc/hexanes] [α] 23 D = (c 1.2, CHCl3). 1 H NMR (600 MHz, CDCl3) δ (m, 2H), (m, 2H), 5.94 (q, J = 1.5 Hz, 1H), (m, 2H), (m, 1H), 3.77 (s, 3H), 1.69 (d, J = 1.6 Hz, 3H), 1.18 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , 57.58, 55.87, 54.50, 52.82, 22.50, IR (NaCl film) 3276, 2973, 1721, 1555, 1320, 1043 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H24BrN2O5S (M+H) ]. Colorless Oil, mg, Yield = 67%. dr = 15:1, Rf = 0.3 [45-55% EtOAc/hexanes] [α] 23 D = (c 2.3, CHCl3). 1 H NMR (499 MHz, CDCl3) δ (m, 2H), (m, 2H), 5.92 (q, J = 1.5 Hz, 1H), 4.83 (dd, J = 9.6, 3.7 Hz, 1H), 4.79 (d, J = 3.8 Hz, 1H), 4.28 (d, J = 9.6 Hz, 1H), 3.76 (s, 3H), 1.66 (d, J = 1.5 Hz, 3H), 1.17 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 57.71, 55.60, 54.67, 52.69, 22.55, IR (NaCl film) 3275, 2951, 1736, 1286, 1168, 1070 cm -1. S21

22 HRMS (ESI + ) m/z [calculated mass for C17H24Br2NO3S (M+H) ]. Colorless Oil, mg, Yield = 72%. dr = 12:1, Rf = 0.3 [50-60% EtOAc/hexanes] [α] 23 D = (c 2.6, CHCl3). 1 H NMR (499 MHz, CDCl3) δ (m, 2H), (m, 2H), 5.93 (q, J = 1.5 Hz, 1H), (m, 2H), 4.28 (d, J = 9.3 Hz, 1H), 3.76 (s, 3H), 1.67 (d, J = 1.6 Hz, 3H), 1.17 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , 57.85, 55.80, 54.47, 52.77, 22.50, IR (NaCl film) 3278, 2980, 2229, 1728, 1434, 1196, 1056 cm -1. HRMS (ESI + ) m/z [calculated mass for C18H24BrN2O3S (M+H) ]. Colorless Oil, mg, Yield = 65%. dr = 10:1, Rf = 0.28 [40-50% EtOAc/hexanes] [α] 23 D = (c 2.9, CHCl3). 1 H NMR (400 MHz, CDCl3) δ 7.57 (dt, J = 8.2, 0.7 Hz, 2H), 7.49 (dt, J = 8.0, 0.8 Hz, 2H), 5.93 (q, J = 1.5 Hz, 1H), (m, 2H), (m, 3H), 1.69 (d, J = 1.6 Hz, 3H), 1.28 (t, J = 7.1 Hz, 3H), 1.18 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ , , , (dd, J = 138.6, 32.5 Hz, 1C), , (q, J = 3.8 Hz, 1C), , , 61.79, 57.85, 55.69, 54.75, 22.50, 20.09, IR (NaCl film) 3275, 2982, 1733, 1325, 1161, 1125, 1067 cm -1. HRMS (ESI + ) m/z [calculated mass for C19H26F3BrNO3S (M+H) ]. Colorless Oil, 94.4 mg, Yield = 55%. dr = 8:1, Rf = 0.32 [40-50% EtOAc/hexanes] [α] 23 D = (c 1.8, CHCl3). S22

23 1 H NMR (600 MHz, CDCl3) δ 6.50 (d, J = 2.3 Hz, 2H), 6.38 (t, J = 2.3 Hz, 1H), 5.93 (q, J = 1.5 Hz, 1H), 4.80 (dd, J = 9.7, 4.1 Hz, 1H), 4.65 (d, J = 4.1 Hz, 1H), 4.31 (d, J = 9.7 Hz, 1H), 3.77 (s, 6H), 3.77 (s, 3H), 1.71 (d, J = 1.6 Hz, 3H), 1.17 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , 58.60, 55.61, 55.35, 54.88, 52.65, 29.73, 22.59, IR (NaCl film) 3247, 2925, 1725, 1607, 1597, 1292, 1204, 1151, 1064 cm -1. HRMS (ESI + ) m/z [calculated mass for C19H29BrNO5S (M+H) ]. Colorless Oil, 89.9 mg, Yield = 51%. dr = 8:1, Rf = 0.33 [30-40% EtOAc/hexanes] [α] 23 D = (c 2.5, CHCl3). 1 H NMR (499 MHz, CDCl3) δ (m, 2H), 6.72 (dd, J = 7.9, 0.5 Hz, 1H), 5.95 (q, J = 1.5 Hz, 2H), 5.91 (q, J = 1.5 Hz, 1H), 4.78 (dd, J = 9.8, 3.6 Hz, 1H), 4.74 (d, J = 3.7 Hz, 1H), 4.25 (d, J = 9.8 Hz, 1H), 3.76 (s, 3H), 1.68 (d, J = 1.5 Hz, 3H), 1.17 (s, 9H). 13 C NMR (126 MHz, CDCl3) δ , , , , , , , , , , 57.84, 55.42, 54.93, 52.60, 22.61, IR (NaCl film) 3277, 2958, 1734, 1490, 1244, 1037 cm -1. HRMS (ESI + ) m/z [calculated mass for C18H25BrNO5S (M+H) ]. Colorless Oil, mg, Yield = 59%. dr = 6:1. Inseparable mixture of diastereomers. Rf = 0.21 [100% EtOAc] [α] 23 D = (c. 1.2, CHCl3). 1 H NMR (499 MHz, CDCl3) Major Diastereomer: δ (m, 2H), 7.69 (ddd, J = 7.9, 2.4, 1.6 Hz, 1H), 7.26 (s, 1H), 5.93 (q, J = 1.5 Hz, 1H), 4.89 (d, J = 9.0 Hz, 2H), 4.33 (d, J = 9.3 Hz, 1H), 3.77 (s, 3H), 1.69 (d, J = 1.5 Hz, 3H), 1.18 (s, 9H). Minor Diastereomer: δ (m, 2H), 7.74 (dt, J = 7.9, 2.0 Hz, 1H), 7.26 (s, 1H), 6.41 (q, J = 1.5 Hz, 1H), 4.84 (dd, J = 10.5, 1.5 Hz, 2H), 4.35 (d, J = 10.5 Hz, 1H), 3.50 (s, 3H), 1.93 (d, J = 1.5 Hz, 3H), 1.15 (s, 9H). S23

24 13 C NMR (126 MHz, CDCl3) Major Diastereomer: δ , , , , , , , 56.07, 55.76, 54.62, 52.76, 22.54, Minor Diastereomer: δ , , , , , , , 56.14, 55.92, 54.23, 52.27, 22.38, IR (NaCl film) 3216, 2951, 1729, 1427, 1167, 1073 cm -1. HRMS (ESI + ) m/z [calculated mass for C16H24BrN2O3S (M+H) ]. Colorless Oil, mg, Yield = 56%. dr = 9:1, Rf = 0.33 [30-40% EtOAc/hexanes] [α] 23 D = (c 1.8, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 7.26 (s, 2H), (m, 1H), 5.95 (q, J = 1.5 Hz, 1H), 5.02 (dd, J = 9.7, 4.2 Hz, 1H), 4.66 (d, J = 4.2 Hz, 1H), 4.31 (d, J = 9.7 Hz, 1H), 3.76 (s, 3H), 1.69 (d, J = 1.5 Hz, 3H), 1.17 (s, 9H). 13 C NMR (1126 MHz, CDCl3) δ , , , , , , , 55.46, 54.84, 53.90, 52.55, 22.56, IR (NaCl film) 3275, 2952, 1734, 1433, 1288, 1190, 1064 cm -1. HRMS (ESI + ) m/z [calculated mass for C15H22NaBrNO3S2 (M+Na) ]. Colorless Oil, 71.7 mg, Yield = 38%. dr = 9:1, Rf = 0.3 [20-30% EtOAc/hexanes] [α] 23 D = (c 2.5, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 6.16 (q, J = 1.5 Hz, 1H), 4.03 (t, J = 7.9 Hz, 2H), (m, 1H), 3.72 (s, 3H), 1.81 (d, J = 1.5 Hz, 3H), (m, 3H), 1.27 (dddt, J = 14.7, 6.5, 5.0, 2.1 Hz, 10H), 1.20 (s, 9H), (m, 3H). 13 C NMR (126 MHz, CDCl3) δ , , , 56.22, 56.14, 54.33, 52.21, 33.43, 31.69, 29.03, 25.28, 22.72, 22.60, 19.89, IR (NaCl film) 3275, 2954, 2927, 2888, 1733, 1457, 1242, 1196, 1165, 1055 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H33BrNO3S (M+H) ]. S24

25 Colorless Oil, mg, Yield = 48%. dr = 6:1, Rf = 0.3 [20-30% EtOAc/hexanes] [α] 23 D = (c 2.4, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 6.11 (q, J = 1.5 Hz, 1H), 4.00 (d, J = 8.9 Hz, 1H), 3.75 (s, 4H), 3.62 (td, J = 8.8, 2.9 Hz, 1H), 1.88 (d, J = 1.5 Hz, 3H), 1.68 (pd, J = 6.8, 2.9 Hz, 1H), 1.24 (s, 9H), 0.96 (d, J = 6.8 Hz, 3H), 0.86 (d, J = 6.8 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ , , , 77.00, 61.67, 56.79, 53.20, 52.40, 31.20, 23.04, 20.67, 19.88, IR (NaCl film) 3228, 2958, 1729, 1436, 1244, 1169, 1073 cm -1. HRMS (ESI + ) m/z [calculated mass for C14H27BrNO3S (M+H) ]. White solid, 78.5 mg, Yield = 40%. dr = 6:1, Rf = 0.3 [20-30% EtOAc/hexanes] [α] 23 D = (c 2.2, CHCl3). 1 H NMR (499 MHz, CDCl3) δ 6.13 (q, J = 1.5 Hz, 1H), 4.05 (d, J = 8.5 Hz, 1H), 3.91 (d, J = 8.6 Hz, 1H), 3.76 (s, 3H), 3.58 (td, J = 8.6, 2.6 Hz, 1H), 1.89 (d, J = 1.5 Hz, 3H), (m, 2H), (m, 3H), (m, 3H), (s, 12H) (m, 2H). 13 C NMR (126 MHz, CDCl3) δ , , , 61.70, 56.79, 52.48, 52.40, 41.76, 30.89, 26.93, 26.46, 26.35, 26.04, 23.11, IR (NaCl film) 3022, 2922, 1734, 1446, 1166, 1076 cm -1. HRMS (ESI + ) m/z [calculated mass for C17H30NaBrNO3S (M+Na) ]. S25

26 X-Ray Crystallographic Data For Compound 12: 4-((2S, 3R)-3-(4-bromophenyl)-1-((S)-tert-butylsulfinyl)aziridin-2-yl)furan-2(5H)-one Table 1: Crystal data and structure refinement for compound 12 Identification Code CCDC # Formula C16H18NO3SBr Formula weight Size 0.6 x 0.04 x 0.01 mm Crystal morphology Colorless fragment Temperature K Wavelength MoKα (λ = ) Crystal system monoclinic Space group P21 Unit cell dimensions a = (13) Å α = 90 b = (3) Å β = c = (19) Å γ = 90 Volume 801.6(3) Å 3 S26

27 Z 2 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) Data collection range 4.74 to Index ranges -7 h 7, -17 k 17, -10 l 10 Reflections collected 8579 Independent reflections 2923 [Rint = , Rsigma = ] Absorption correction multi-scan Max. and min. transmission and Refinement method Full Data / restraints / parameters 2923/187/202 Goodness of fit Final R indices [I >2 σ (I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Largest diff. peak and hole 0.53 and -0.43e.Å -3 Absolute structure parameter (7) Table 2: Atomic co-ordinates ( 10 4 ) and equivalent isotropic displacement parameters (Å ) for compound 12. Ueq is defined as 1/3 of of the trace of the orthogonalised Uij tensor. Atom x y z U(eq) Br(1) (8) (4) (6) 17.13(15) S(1) 883(2) (9) (16) 11.1(3) O(2) 7959(6) -98(3) 9610(4) 14.1(9) C(9) 5263(9) -643(4) 7357(6) 9.2(11) O(1) 10951(6) -556(3) 9048(4) 15.3(9) O(3) -1306(6) -1884(3) 4548(5) 18.0(9) C(7) 5914(9) 451(4) 2640(6) 11.2(11) C(11) 8969(8) -504(4) 8665(6) 9.8(11) C(6) 4988(9) 1319(4) 2257(6) 13.5(12) C(5) 3187(9) 1593(4) 2658(7) 15.7(12) N(1) 2847(7) -1463(3) 4971(5) 10.2(10) C(13) 794(8) -2705(4) 2807(6) 11.5(11) C(10) 7255(9) -835(4) 7249(7) 11.0(12) C(8) 4976(9) -155(4) 3420(6) 13.0(12) S27

28 C(1) 3037(9) -856(4) 6305(6) 11.4(12) C(3) 3154(9) 105(4) 3836(7) 12.9(12) C(12) 5587(8) -175(4) 8874(6) 11.6(12) C(2) 2043(9) -511(4) 4648(6) 12.6(12) C(16) -971(9) -3469(4) 2432(7) 17.6(13) C(4) 2263(9) 986(4) 3439(6) 14.5(12) C(14) 93(10) -1942(4) 1619(6) 20.2(14) C(15) 3079(9) -3089(4) 2975(7) 21.8(16) Table 3: Anisotropic displacement parameters (Å ) for compound 12. The anisotropic displacement factor exponent takes the form: -2π 2 [h 2 a* 2 U11+2hka*b*U12+ ]. Atom U11 U22 U33 U23 U13 U12 Br(1) 24.2(3) 11.9(3) 16.4(3) 1.2(3) 8.3(2) -3.8(3) S(1) 11.5(6) 8.0(7) 15.2(7) -1.7(5) 6.2(5) -1.2(5) O(2) 9.6(19) 15(2) 17(2) -3.9(17) 4.1(16) -1.2(16) C(9) 14(3) 3(3) 10(3) 0(2) 5(2) -2(2) O(1) 11.7(19) 16(2) 19(2) 3.1(17) 6.4(17) 0.3(17) O(3) 13.2(19) 14(2) 29(2) -8.0(18) 10.8(18) -1.3(17) C(7) 10(3) 12(3) 10(3) -3(2) 2(2) -1(2) C(11) 10.2(15) 9.0(16) 10.2(16) 1.9(12) 3.4(12) -1.2(12) C(6) 16(3) 13(3) 11(3) 0(2) 4(2) -4(2) C(5) 22(3) 5(3) 20(3) 0(2) 7(2) 3(2) N(1) 12(2) 6(2) 12(2) -1.7(18) 3.4(19) -1.2(18) C(13) 12.4(15) 10.0(17) 11.6(15) -1.1(12) 3.4(12) -0.9(12) C(10) 11(3) 7(3) 16(3) 3(2) 7(2) 0(2) C(8) 17(3) 7(3) 15(3) -5(2) 6(2) 0(2) C(1) 14(3) 6(3) 17(3) -1(2) 8(2) 1(2) C(3) 12(3) 9(3) 17(3) -2(2) 5(2) -2(2) C(12) 8(3) 11(3) 18(3) -3(2) 7(2) 1(2) C(2) 10(3) 8(3) 18(3) -1(2) 3(2) 1(2) C(16) 19(3) 11(3) 21(3) -7(2) 4(3) -3(2) C(4) 16(3) 9(3) 18(3) -3(2) 6(2) 1(2) C(14) 29(3) 14(3) 12(3) 0(2) 0(3) -2(3) C(15) 23(3) 26(5) 20(3) -6(2) 11(2) 1(2) Table 4: Hydrogen atom co-ordinates (Å 104) and isotropic displacement parameters (Å2 103) for compound 12. S28

29 Atom x y z U(eq) H(7) H(5) H(10) H(8) H(1) H(12A) H(12B) H(2) H(16A) H(16B) H(16C) H(4) H(14A) H(14B) H(14C) H(15A) H(15B) H(15C) Table 5: Bond lengths (Å) for compound 12. Atom Atom Length/Å Atom Atom Length/Å Br(1) C(6) 1.903(5) C(11) C(10) 1.468(7) S(1) O(3) 1.487(4) C(6) C(5) 1.379(8) S(1) N(1) 1.723(5) C(5) C(4) 1.386(8) S(1) C(13) 1.836(5) N(1) C(1) 1.476(7) O(2) C(11) 1.372(6) N(1) C(2) 1.476(7) O(2) C(12) 1.442(6) C(13) C(16) 1.541(7) C(9) C(10) 1.339(8) C(13) C(14) 1.512(8) C(9) C(1) 1.459(8) C(13) C(15) 1.524(7) C(9) C(12) 1.494(8) C(8) C(3) 1.393(8) O(1) C(11) 1.199(6) C(1) C(2) 1.516(8) C(7) C(6) 1.392(8) C(3) C(2) 1.487(8) C(7) C(8) 1.390(8) C(3) C(4) 1.405(8) Table 6: Bond angles ( ) for compound 12. S29

30 Atom Atom Atom Angle/ Atom Atom Atom Angle/ O(3) S(1) N(1) 109.5(2) C(14) C(13) S(1) 111.2(4) O(3) S(1) C(13) 107.1(2) C(14) C(13) C(16) 110.7(4) N(1) S(1) C(13) 97.5(2) C(14) C(13) C(15) 112.8(5) C(11) O(2) C(12) 108.4(4) C(15) C(13) S(1) 107.3(3) C(10) C(9) C(1) 130.5(5) C(15) C(13) C(16) 111.2(5) C(10) C(9) C(12) 108.8(5) C(9) C(10) C(11) 108.4(5) C(1) C(9) C(12) 120.6(5) C(7) C(8) C(3) 120.6(5) C(8) C(7) C(6) 119.2(5) C(9) C(1) N(1) 117.6(5) O(2) C(11) C(10) 109.0(4) C(9) C(1) C(2) 125.2(5) O(1) C(11) O(2) 121.2(5) N(1) C(1) C(2) 59.1(3) O(1) C(11) C(10) 129.8(5) C(8) C(3) C(2) 123.6(5) C(7) C(6) Br(1) 119.1(4) C(8) C(3) C(4) 118.9(5) C(5) C(6) Br(1) 119.5(4) C(4) C(3) C(2) 117.5(5) C(5) C(6) C(7) 121.3(5) O(2) C(12) C(9) 105.4(4) C(6) C(5) C(4) 119.2(5) N(1) C(2) C(1) 59.1(3) C(1) N(1) S(1) 112.8(3) N(1) C(2) C(3) 118.4(5) C(2) N(1) S(1) 117.4(3) C(3) C(2) C(1) 125.9(5) C(2) N(1) C(1) 61.8(3) C(5) C(4) C(3) 120.8(5) C(16) C(13) S(1) 103.1(3) Table 7: Torsion Angles ( ) for compound 12. A B C D Angle/ A B C D Angle/ Br(1) C(6) C(5) C(4) 179.1(4) N(1) C(1) C(2) C(3) (6) S(1) N(1) C(1) C(9) 133.7(4) C(13) S(1) N(1) C(1) 168.5(4) S(1) N(1) C(1) C(2) (4) C(13) S(1) N(1) C(2) 99.6(4) S(1) N(1) C(2) C(1) 102.6(4) C(10) C(9) C(1) N(1) 7.5(9) S(1) N(1) C(2) C(3) (4) C(10) C(9) C(1) C(2) -62.6(8) O(2) C(11) C(10) C(9) -0.8(6) C(10) C(9) C(12) O(2) 1.3(6) C(9) C(1) C(2) N(1) 103.8(6) C(8) C(7) C(6) Br(1) (4) C(9) C(1) C(2) C(3) -0.8(9) C(8) C(7) C(6) C(5) 1.1(8) O(1) C(11) C(10) C(9) 178.1(6) C(8) C(3) C(2) N(1) -2.8(8) O(3) S(1) N(1) C(1) 57.4(4) C(8) C(3) C(2) C(1) 68.0(8) O(3) S(1) N(1) C(2) -11.5(4) C(8) C(3) C(4) C(5) -0.5(9) O(3) S(1) C(13) C(16) -65.9(4) C(1) C(9) C(10) C(11) (6) O(3) S(1) C(13) C(14) 52.8(4) C(1) C(9) C(12) O(2) 178.6(5) O(3) S(1) C(13) C(15) 176.6(4) C(1) N(1) C(2) C(3) 116.9(5) C(7) C(6) C(5) C(4) -0.9(9) C(12) O(2) C(11) O(1) (5) S30

31 C(7) C(8) C(3) C(2) 179.0(5) C(12) O(2) C(11) C(10) 1.6(6) C(7) C(8) C(3) C(4) 0.7(8) C(12) C(9) C(10) C(11) -0.3(6) C(11) O(2) C(12) C(9) -1.8(6) C(12) C(9) C(1) N(1) (5) C(6) C(7) C(8) C(3) -1.0(8) C(12) C(9) C(1) C(2) 120.8(6) C(6) C(5) C(4) C(3) 0.7(9) C(2) N(1) C(1) C(9) (5) N(1) S(1) C(13) C(16) (4) C(2) C(3) C(4) C(5) (5) N(1) S(1) C(13) C(14) -60.3(4) C(4) C(3) C(2) N(1) 175.5(5) N(1) S(1) C(13) C(15) 63.5(4) C(4) C(3) C(2) C(1) (6) For Compound 11: 4-((2R,3S)-3-(4-bromophenyl)-1-((S)-tert-butylsulfinyl)aziridin-2-yl)furan-2(5H)-one Table 1: Crystal data and structure refinement for compound 11. Identification code CCDC # Formula C16H18NO3SBr Formula weight Size 0.3 x 0.15 x 0.1 mm S31

32 Crystal morphology Temperature Colorless fragment K Wavelength MoKα (λ = ) Crystal system Space group Unit cell dimensions orthorhombic P a = (11) Å b = (6) Å c = (4) Å Volume Å 3 Z 4 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) Data collection range to Index ranges -10 h 9, -7 k 5, -37 l 32 Reflections collected Independent reflections 3116 [Rint = , Rsigma = ] Absorption correction multi-scan Max. and min. transmission and Refinement method Full Data / restraints / parameters 3116/0/202 Goodness of fit Table 2: Fractional Atomic Coordinates ( 10 4 ) and Equivalent Isotropic Displacement Parameters (Å ) for compound 11. Ueq is defined as 1/3 of of the trace of the orthogonalised UIJ tensor. Atom x y z U(eq) Br(1) (5) (7) (2) 31.99(14) S(1) (13) (14) (3) 18.5(2) O(3) -6827(3) (4) (8) 23.8(6) S32

33 C(4) -4632(5) (7) 143.2(11) 25.2(9) C(3) -5454(5) (6) 515.4(11) 19.7(8) C(1) -4507(5) (5) (12) 17.8(9) N(1) -6198(4) (4) (10) 16.5(8) C(2) -5517(5) (6) 862.5(12) 19.5(9) C(8) -6250(5) (6) 547.3(12) 21.0(9) C(6) -5405(5) -9381(6) (12) 23.0(9) C(5) -4595(6) (6) (13) 26.9(10) C(7) -6230(5) -8877(6) 207.4(13) 23.6(10) C(9) -3417(5) (6) (11) 18(1) C(12) -1669(4) (8) (13) 28.3(9) C(14) -5678(5) (6) (13) 23.7(10) C(13) -7326(5) (5) (12) 18.6(9) C(16) -8529(6) (7) (14) 33.1(12) O(2) -1024(3) (4) (10) 25.9(7) C(10) -3718(5) (6) (12) 19.8(9) C(11) -2233(5) -9015(6) (12) 20.6(10) O(1) -1982(3) -7251(5) (8) 26.7(7) C(15) -7801(5) (6) (13) 25.1(10) Table 3: Anisotropic Displacement Parameters (Å ) for compound 11. The Anisotropic displacement factor exponent takes the form: -2π 2 [h 2 a* 2 U11+2hka*b*U12+ ] Atom U11 U22 U33 U23 U13 U12 Br(1) 38.3(3) 36.3(2) 21.3(2) 4.6(2) -2.7(2) -2.8(3) S(1) 14.3(5) 22.1(5) 19.1(5) -3.0(4) -0.7(5) -1.6(5) O(3) 23.1(16) 18.5(13) 29.8(14) -4.5(14) 2.2(12) -0.8(14) C(4) 22(2) 29(2) 25(2) -4(2) 1.0(18) 8(3) C(3) 17(2) 25(2) 17.6(19) -5.4(16) -5.0(17) -2(2) C(1) 18(2) 15.8(18) 20(2) -0.7(16) 1(2) 2.5(19) N(1) 14.2(19) 19.9(17) 15.5(17) -1.6(12) -0.3(15) -0.1(14) C(2) 16(2) 19.2(19) 23(2) -5.0(16) -2(2) -2.8(19) C(8) 20(2) 26(2) 17(2) -5.8(17) -1.4(18) 0.4(19) C(6) 17(2) 31(2) 21(2) 0.4(17) -4(2) -7(2) C(5) 24(3) 38(2) 19(2) -2.4(18) 4(2) 4(2) C(7) 25(3) 24(2) 22(2) -5.3(18) -3(2) 0.2(19) C(9) 16(2) 26(3) 12.0(19) 4.7(16) -1.4(16) -1.0(19) C(12) 17(2) 24(2) 43(2) -1(2) -1.4(19) 1(2) C(14) 24(3) 29(2) 18(2) -0.4(17) -7.2(19) 4(2) S33

34 C(13) 16(2) 21(2) 19(2) -0.8(16) 1.3(19) -1.1(18) C(16) 34(3) 43(3) 23(2) -5(2) 8(2) -15(2) O(2) 12.4(15) 21.4(14) 43.8(19) 8.1(13) -3.2(15) -1.2(12) C(10) 19(2) 21(2) 20(2) -0.9(18) -0.6(19) 1.4(19) C(11) 22(3) 25(2) 15(2) 10.2(17) -2.2(19) -3.2(19) O(1) 29.4(18) 21.1(16) 29.5(15) 2.8(14) -5.1(12) -5.8(14) C(15) 23(2) 30(2) 22(2) -8.5(17) -0.7(19) 5.6(19) Table 4: Bond Lengths for compound 11. Atom Atom Length/Å Atom Atom Length/Å Br(1) C(6) 1.905(4) C(8) C(7) 1.381(5) S(1) O(3) 1.488(3) C(6) C(5) 1.380(6) S(1) N(1) 1.722(3) C(6) C(7) 1.381(6) S(1) C(13) 1.841(4) C(9) C(12) 1.498(5) C(4) C(3) 1.384(5) C(9) C(10) 1.333(5) C(4) C(5) 1.383(6) C(12) O(2) 1.438(5) C(3) C(2) 1.490(5) C(14) C(13) 1.519(6) C(3) C(8) 1.399(5) C(13) C(16) 1.530(5) C(1) N(1) 1.481(5) C(13) C(15) 1.533(5) C(1) C(2) 1.507(5) O(2) C(11) 1.372(5) C(1) C(9) 1.466(5) C(10) C(11) 1.460(6) N(1) C(2) 1.460(5) C(11) O(1) 1.203(5) Table 5: Bond Angles for compound 11. Atom Atom Atom Angle/ Atom Atom Atom Angle/ O(3) S(1) N(1) (16) C(7) C(6) Br(1) 119.9(3) O(3) S(1) C(13) (16) C(6) C(5) C(4) 118.8(4) N(1) S(1) C(13) 98.21(16) C(8) C(7) C(6) 119.7(4) C(5) C(4) C(3) 121.2(4) C(1) C(9) C(12) 121.8(4) C(4) C(3) C(2) 118.8(4) C(10) C(9) C(1) 129.7(4) C(4) C(3) C(8) 119.1(4) C(10) C(9) C(12) 108.5(4) C(8) C(3) C(2) 122.0(3) O(2) C(12) C(9) 104.9(4) N(1) C(1) C(2) 58.5(3) C(14) C(13) S(1) 111.3(3) C(9) C(1) N(1) 115.2(3) C(14) C(13) C(16) 110.9(3) C(9) C(1) C(2) 122.2(3) C(14) C(13) C(15) 112.1(3) S34

35 C(1) N(1) S(1) 118.4(2) C(16) C(13) S(1) 103.5(3) C(2) N(1) S(1) 114.9(2) C(16) C(13) C(15) 110.4(3) C(2) N(1) C(1) 61.6(3) C(15) C(13) S(1) 108.2(3) C(3) C(2) C(1) 124.9(3) C(11) O(2) C(12) 109.1(3) N(1) C(2) C(3) 118.9(3) C(9) C(10) C(11) 109.1(4) N(1) C(2) C(1) 59.9(2) O(2) C(11) C(10) 108.3(3) C(7) C(8) C(3) 120.0(4) O(1) C(11) O(2) 121.3(4) C(5) C(6) Br(1) 118.7(3) O(1) C(11) C(10) 130.4(4) C(5) C(6) C(7) 121.3(4) Table 6: Torsion Angles for compound 11. A B C D Angle/ A B C D Angle/ Br(1) C(6) C(5) C(4) (3) C(2) C(3) C(8) C(7) (4) Br(1) C(6) C(7) C(8) 178.6(3) C(2) C(1) N(1) S(1) 104.5(3) S(1) N(1) C(2) C(3) 134.0(3) C(2) C(1) C(9) C(12) (4) S(1) N(1) C(2) C(1) (3) C(2) C(1) C(9) C(10) 72.5(6) O(3) S(1) N(1) C(1) -24.3(3) C(8) C(3) C(2) C(1) -82.4(5) O(3) S(1) N(1) C(2) 45.6(3) C(8) C(3) C(2) N(1) -10.8(6) O(3) S(1) C(13) C(14) 48.8(3) C(5) C(4) C(3) C(2) 177.0(4) O(3) S(1) C(13) C(16) -70.3(3) C(5) C(4) C(3) C(8) -0.4(6) O(3) S(1) C(13) C(15) 172.5(3) C(5) C(6) C(7) C(8) 0.0(6) C(4) C(3) C(2) C(1) 100.2(5) C(7) C(6) C(5) C(4) 0.6(7) C(4) C(3) C(2) N(1) 171.9(4) C(9) C(1) N(1) S(1) (3) C(4) C(3) C(8) C(7) 1.0(6) C(9) C(1) N(1) C(2) 113.7(4) C(3) C(4) C(5) C(6) -0.4(7) C(9) C(1) C(2) C(3) 4.2(6) C(3) C(8) C(7) C(6) -0.8(6) C(9) C(1) C(2) N(1) (4) C(1) N(1) C(2) C(3) (4) C(9) C(12) O(2) C(11) -0.2(4) C(1) C(9) C(12) O(2) (3) C(9) C(10) C(11) O(2) 2.1(4) C(1) C(9) C(10) C(11) 177.0(4) C(9) C(10) C(11) O(1) (4) N(1) S(1) C(13) C(14) -64.3(3) C(12) C(9) C(10) C(11) -2.1(4) N(1) S(1) C(13) C(16) 176.5(3) C(12) O(2) C(11) C(10) -1.1(4) N(1) S(1) C(13) C(15) 59.3(3) C(12) O(2) C(11) O(1) 178.4(3) N(1) C(1) C(2) C(3) 106.0(4) C(13) S(1) N(1) C(1) 86.6(3) N(1) C(1) C(9) C(12) (3) C(13) S(1) N(1) C(2) 156.4(3) N(1) C(1) C(9) C(10) 5.1(6) C(10) C(9) C(12) O(2) 1.5(4) S35

36 Table 7: Hydrogen Atom Coordinates (Å 10 4 ) and Isotropic Displacement Parameters (Å ) for compound 11. Atom x y z U(eq) H(4) H(1) H(2) H(8) H(5) H(7) H(12A) H(12B) H(14A) H(14B) H(14C) H(16A) H(16B) H(16C) H(10) H(15A) H(15B) H(15C) S36