Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to. Vinyl Sulfone: An Organocatalytic Access to Chiral. 3-Fluoro-3-Substituted Oxindoles

Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to Vinyl Sulfone: An Organocatalytic Access to Chiral 3-Fluoro-3-Substituted Oxindoles Xiaowei Dou and Yixin Lu * Department of Chemistry & Medicinal Chemistry Program, Life Sciences Institute National University of Singapore, 3 Science Drive 3, Singapore, 117543; Email: chmlyx@nus.edu.sg Supporting Information A. General Information S2 B. Preparation of the 3-F-Oxindole Substrates S2 C. Representative Procedure for the Conjugate Addition Reactions S7 D. Analytical Data and HPLC Chromatogram of the Products S7 E. X-Ray Crystallographic Analysis and Determination of the Absolute Configurations of the Products S24 F. NMR Spectra of the Substrates and the Products S26 S1

A. General Information All the starting materials were obtained from commercial sources and used without further purification unless otherwise stated. 1 H and 13 C NMR spectra were recorded on a Bruker ACF3 or AMX5 (5 MHz) spectrometer. Chemical shifts were reported in parts per million, and the residual solvent peak was used as an internal reference: proton (chloroform δ 7.26), carbon (chloroform δ 7). Multiplicity was indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet of doublet), br s (broad singlet). Coupling constants were reported in Hertz (Hz). Low resolution mass spectra were obtained on a Finnigan/MAT LCQ spectrometer in ESI mode, and a Finnigan/MAT 95XL- T mass spectrometer in FAB mode. All high resolution mass spectra were obtained on a Finnigan/MAT 95XL- T spectrometer. For thin layer chromatography (TLC), Merck pre-coated TLC plates (Merck F254) were used, and compounds were visualized with a UV light at 254 nm. Further visualization was achieved by staining with iodine, or ceric ammonium molybdate followed by heating on a hot plate. Flash chromatographic separations were performed on Merck (.-.63 mm) mesh silica gel. The enantiomeric excesses of products were determined by chiral-phase HPLC analysis. B. Preparation of the 3-F-Oxindole Substrates Boc-protected oxindole (1 mmol) was dissolved in dry THF (5 ml) under N 2 protection and the solution was cooled to o C. NaH (1 mmol) was added and the mixture was stirred at o C for 3 min. NFSI (1 mmol) was added to the mixture in one portion and the resulting mixture was stirred at o C to room temperature for 15 min. The reaction mixture was quenched by addition of water (1 ml) and the mixture was extracted with CH 2 Cl 2 (15 ml 3). The combined organic phase was dried over MgSO 4, filtered and concentrated in S2

vacuo, which was purified by flash column chromatography (ethyl acetate/hexane = 1:7) to afford the desired monofluorinated product (38-46% yield), the bisfluorinated side product (8-13% yield) and the recovered Boc-protected oxindole ( 23-41% recovered). tert-butyl 3-fluoro-2-oxoindoline-1-carboxylate 1a A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.63 (s, 9H), 5.7 (d, J = 51.1 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 7.9 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 8 (d, J = 187.7 Hz), 85.1, 115.6, 121.8 (d, J = 16.4 Hz), 12 (d, J = 2.7 Hz), 125.9, 131.7 (d, J = 2.7 Hz), 1.9 (d, J = 4.6 Hz), 148.7, 169. (d, J = 17.3 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -111.1 (d, J = 51.6 Hz); HRMS (ESI) m/z calcd for C 13 H 14 FNO 3 Na [M+Na] + = 2785, found = 278. tert-butyl 5-chloro-3-fluoro-2-oxoindoline-1-carboxylate 1b A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.63 (s, 9H), 5.68 (d, J = 5.9 Hz, 1H), 7.-7.44 (m, 1H), 7.48 (s, 1H), 7.85 (dd, J = 1.3 Hz, 8.7 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 84.6 (d, J = 19.4 Hz), 85.4, 11, 123.3 (d, J = 16.4 Hz), 126.1, 13.6 (d, J = 2.7 Hz), 131.7 (d, J = 2.7 Hz), 139.4 (d, J = 4.6 Hz), 148.5, 168.1 (d, J = 18.2 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -112.2 (d, J = 52.6 Hz); HRMS (ESI) m/z calcd for C 13 H 13 FClNO 3 Na [M+Na] + = 38.4, found = 38.452. tert-butyl 6-chloro-3-fluoro-2-oxoindoline-1-carboxylate 1c S3

A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.64 (s, 9H), 5.68 (d, J = 51.1 Hz, 1H), 7.21-7.24 (m, 1H), 7.43 (dd, J = 1.1 Hz, 7.9 Hz, 1H), 7.97 (s, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 84.4 (d, J = 189.5 Hz), 85.6, 116.5, 1. (d, J = 16.4 Hz), 125.2 (d, J = 2.7 Hz), 126.8, 137.8 (d, J = 3.7 Hz), 141.9 (d, J = 4.6 Hz), 148.4, 168.4 (d, J = 18.2 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -11.8 (d, J = 51.6 Hz); HRMS (ESI) m/z calcd for C 13 H 13 FClNO 3 Na [M+Na] + = 38.4, found = 38.452. tert-butyl 5-bromo-3-fluoro-2-oxoindoline-1-carboxylate 1d A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.63 (s, 9H), 5.69 (d, J = 5.9 Hz, 1H), 7.55-7.59 (m, 1H), 7.63 (s, 1H), 7.76-7.82 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 84.4 (d, J = 19.4 Hz), 85.5, 117.1, 117.3, 123.6 (d, J = 16.4 Hz), 128.9 (d, J = 34.6 Hz), 134.7 (d, J = 3.7 Hz), 139.9, 148.5, 168.1 (d, J = 21. Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -112.1 (dd, J= 2.1 Hz, 27.3 Hz); HRMS (ESI) m/z calcd for C 13 H 13 F 79 BrNO 3 Na [M+Na] + = 351.9951, found = 351.9926, C 13 H 13 F 81 BrNO 3 Na [M+Na] + = 353.9937, found = 353.9918. tert-butyl 3,7-difluoro-2-oxoindoline-1-carboxylate 1e S4

A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.61 (s, 9H), 5.75 (d, J = 5.8 Hz, 1H), 7.17-7.24 (m, 2H), 7.31-7.34 (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 27.6, 76.5, 84.6 (d, J = 1.4 Hz), 86.1 (d, J = 2.2 Hz), 119.8 (d, J = 3.3 Hz), 1.1 (d, J = 2.7 Hz), 121.8 (d, J = 3.3 Hz), 124.7 (d, J = 15.3 Hz), 126.2 (d, J = 2.7 Hz), 126.3, 146.7 (d, J = 14.2 Hz), 15.2, 168.4 (d, J = 18.5 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -111. (d, J = 5.5 Hz), (-42.2) (t, J =7.2 Hz); HRMS (ESI) m/z calcd for C 13 H 13 F 2 NO 3 Na [M+Na] + = 292.761, found = 292.753. tert-butyl 7-chloro-3-fluoro-2-oxoindoline-1-carboxylate 1f A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.63 (s, 9H), 5.74 (d, J = 5.8 Hz, 1H), 7.15-7.21 (m, 1H), 7.41-7.44 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 27.7, 85.1 (d, J = 191.3 Hz), 86.3, 119.5, 124.5, 12 (d, J = 21.9 Hz), 125.8, 133.3, 138.2, 147.1, 169.2 (d, J =. Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -112.5 (d, J = 5.5 Hz); HRMS (ESI) m/z calcd for C 13 H 13 FClNO 3 Na [M+Na] + = 38.4, found = 38.452. tert-butyl 3-fluoro-5-methyl-2-oxoindoline-1-carboxylate 1g A colorless oil; 1 H NMR (3 MHz, CDCl 3 ) δ 1.63 (s, 9H), 2.37 (s,3h), 5.68 (d, J = 51.3 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.31 (s, 1H), 7.74 (d, J = 8.4 Hz, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ.8, 28., 84.8, 85.1 (d, J = 187.6 Hz), 115.3 (d, J = 1.6 Hz), 121.6 (d, J = 16.4 Hz), 126.3, 132.1 (d, J = 3.3 Hz), 134.8 (d, J = 2.7 Hz), 138.4 (d, J = 5.5 Hz), 148.6, 169. (d, J = 17.5 Hz); 19 F NMR S5

(282.38 MHz, CDCl 3 ) δ -11.8 (d, J = 51.6 Hz); HRMS (ESI) m/z calcd for C 14 H 16 FNO 3 Na [M+Na] + = 288.16, found = 288.1. tert-butyl 3-fluoro-5-methoxy-2-oxoindoline-1-carboxylate 1h A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.63 (s, 9H), 3.83 (s,3h), 5.69 (d, J = 51.1 Hz, 1H), 6.95-6.98 (m, 1H), 6 (s, 1H), 7.79 (dd, J = 1.3 Hz, 8.8 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28.1, 55.8, 84.9, 85.2 (d, J = 188.6 Hz), 111.4, 116.7, 11 (d, J = 3.6 Hz), 122.8 (d, J = 16.4 Hz), 134.1 (d, J = 3.6 Hz), 148.7, 157.2 (d, J = 3.7 Hz), 169. (d, J = 19.1 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -111.4 (t, J = 25.8 Hz); HRMS (ESI) m/z calcd for C 14 H 16 FNO 4 Na [M+Na] + = 3956, found = 3965. tert-butyl 3-fluoro-5,7-dimethyl-2-oxoindoline-1-carboxylate 1i A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.62 (s, 9H), 2.19 (s, 3H), 2.32 (s, 3H), 5.67 (d, J = 51.3 Hz, 1H), 5 (s, 1H), 7.14 (s, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 19.3,.7, 27.7, 85.1, 85.6 (d, J = 188.7 Hz), 123. (d, J = 16.4 Hz), 12, 124.2 (d, J = 1.6 Hz), 134.7 (d, J = 3.3 Hz), 13 (d, J = 3.3 Hz), 136.8 (d, J = 4.9 Hz), 148.5, 17.1 (d, J = 17.5 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -11.6 (d, J = 51.6 Hz); HRMS (ESI) m/z calcd for C 15 H 17 FNO 3 [M-H] - = 278.81, found = 278.818. S6

C. Representative procedure Asymmetric Conjugate Addition of 3-F-Oxindoles to Vinylsulfone Oxindole 1 (.5 mmol) was at room temperature added to a mixture of vinylsulfone 2 (.5 mmol), catalyst 6 (1.5 mg,.25 mmol) and 4 Å molecular sieves (1 mg) in CHCl 3 (1. ml) in a sample vial, and the resulting mixture was sealed and stirred at room temperature for the time specified in Table 2. At the end of the reaction, the reaction mixture was filtered and concentrated in vacuo to yield the crude product, which was purified by flash column chromatography (ethyl acetate/hexane = 1:3) to afford the desired adducts 3. The enantiomeric excessess of 3 were determined by chiral HPLC analysis. D. Analytical data and HPLC chromatogram of the conjugate addition adducts (S)-tert-Butyl 3-(2,2-bis(phenylsulfonyl)ethyl)-3-fluoro-2-oxoindoline-1-carboxylate 3a A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.62 (s, 9H), 3.-3.8 (m, 1H), 3.1-3.23 (m, 1H), 5.38 (t, J = 4.4 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.51-7.58 (m, 4H), 7.65-7.71 (m, 2H), 7.86 (d, J = 7.6 Hz, 2H), 7.93 (d, J = 8.2 Hz, 1H), 8.1-8.3 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 31.2 (d, J = 31. Hz), 76.8, 8, 89.2 (d, J = 189.5 Hz), 116.1, 123.7 (d, J = 18.2 Hz), 12, 125.2, 129.1 (d, J = 23.7 Hz), 129.7 (d, J S7

= 1.8 Hz), 132.2 (d, J = 2.7 Hz), 134.6 (d, J = 3.1 Hz), 13, 138.3, 1. (d, J = 4.6 Hz), 148.3, 17.1 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -75.6 (dd, J = 11.3 Hz, 32. Hz); The ee value was 93%, t R (minor) = 17.52 min, t R (major) =.4 min (Chiralcel AD-H, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 27 H 26 FNO 7 S 2 Na [M+Na] + = 582.127, found = 582.125; [ ] 27 D = +21.2 (c =.95, CHCl 3 ). (racemic 3a) (enantiomerically enriched 3a) S8

(S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-5-chloro-3-fluoro-2-oxoindoline-1-carboxylat e 3b A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.62 (s, 9H), 2.98-3.9 (m, 1H), 3.13-3.19 (m, 1H), 5.32 (t, J = 4.4 Hz, 1H), 7.3 (t, J = 1.9 Hz, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.54-7.59 (m, 4H), 7.68-7.72 (m, 2H), 7.88-7.92 (m, 3H), 8.2 (d, J = 8.2 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 31.3 (d, J = 31. Hz), 85.4, 88.9 (d, J = 192.3 Hz), 117.6, 124.2, 125.3 (d, J = 18.2 Hz), 129.2 (d, J = 23.7 Hz), 129.7 (d, J = 1.9 Hz), 13.8 (d, J = 2.7 Hz), 132.2 (d, J = 1.8 Hz), 134.7 (d, J = 31.9 Hz), 136.8, 138.3, 138.5 (d, J = 4.6 Hz), 148.2, 169.5 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -76.5 (dd, J = 11.9 Hz, 31.4 Hz); The ee value was 93%, t R (minor) = 14.51 min, t R (major) = 15.43 min (Chiralcel AD-H, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 27 H 25 FClNO 7 S 2 Na [M+Na] + = 61637, found = 61613; [ ] 27 D = +23.4 (c = 1., CHCl 3 ). (racemic 3b) S9

(enantiomerically enriched 3b) (S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-6-chloro-3-fluoro-2-oxoindoline-1-carboxylat e 3c A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.62 (s, 9H), 2.94-3.23 (m, 2H), 5.33 (t, J = 4.5 Hz, 1H), 7.22-7.32 (m, 2H), 7.51-7.59 (m, 4H), 7.65-7.73 (m, 2H), 7.84-7.87 (m, 2H), 7.99-8.3 (m, 3H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 31.3 (d, J = 31.9 Hz), 76.8, 85.6, 89. (d, J = 19.4 Hz), 11, 122.1 (d, J = 19.1 Hz), 12, 125.4 (d, J = 2.7 Hz), 129.2 (d, J = 23.7 Hz), 129.7 (d, J = 2.7 Hz), 134.7 (d, J = 28.2 Hz), 137.1, 138.3, 138.4 (d, J = 3.7 Hz), 141. (d, J = 4.6 Hz), 148.2, 169.7 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -75.2 (dd, J = 11.4 Hz, 32. Hz); The ee value was 91%, t R (minor) = 17. min, t R (major) =.55 min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 27 H 25 FClNO 7 S 2 Na [M+Na] + = 61637, found = 61613; [ ] 27 D = +1 (c =., CHCl 3 ). S1

(racemic 3c) (enantiomerically enriched 3c) S11

(S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-5-bromo-3-fluoro-2-oxoindoline-1-carboxylat e 3d A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.62 (s, 9H), 2.99-3.19 (m, 2H), 5.3 (t, J = 4.7 Hz, 1H), 7.44 (t, J = 1.9 Hz, 1H), 7.55-7.62 (m, 5H), 7.68-7.73 (m, 2H), 7.85-7.9 (m, 3H), 8.1-8.3 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 31.3 (d, J = 31. Hz), 85.5, 88.9 (d, J = 191.3 Hz), 117.9, 118.1 (d, J = 2.7 Hz), 125.7 (d, J = 17.3 Hz), 12, 129.2 (d, J = 22.8 Hz), 129.7 (d, J = 14.6 Hz), 134.8 (d, J = 32.8 Hz), 135.2, 136.8, 138.3, 139.1 (d, J = 5.5 Hz), 148.2, 169.4 (d, J = 21.9 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -76.2 (dd, J = 12.4 Hz, 32. Hz); The ee value was 93%, t R (minor) = 15.53 min, t R (major) = 17.34 min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 27 H 25 F 79 BrNO 7 S 2 Na [M+Na] + = 6.132, found = 6.19, C 27 H 25 F 81 BrNO 7 S 2 Na [M+Na] + = 662.112, found = 662.91; [ ] 27 D = +15.5 (c =.75, CHCl 3 ). (racemic 3d) S12

(enantiomerically enriched 3d) (S)-tert-Butyl 3-(2,2-bis(phenylsulfonyl)ethyl)-3,7-difluoro-2-oxoindoline-1-carboxylate 3e A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.59 (s, 9H), 3.2-3.13 (m, 1H), 3.19-3.25 (m, 1H), 5.36 (t, J = 4.4 Hz, 1H), 7.18 (t, J = 3.2 Hz, 1H), 7.25 (d, J = 6.9 Hz, 2H), 7.52-7.59 (m, 4H), 7.65-7.72 (m, 2H), 7.86 (d, J = 7.6 Hz, 2H), 8. (d, J = 8.2 Hz, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 27.6, 31.3 (d, J = 31.9 Hz), 77.2, 85.7, 89.6 (d, J = 19 Hz), 119.9 (d, J = 3.7 Hz), 1.5, 1.7 (d, J = 2.7 Hz), 126.7 (d, J = 4.6 Hz), 126.9 (d, J = 1. Hz), 12, 129.1 (d, J = 18.2 Hz), 129.7 (d, J = 9.1 Hz), 134.7 (d, J = 23.7 Hz), 137.1, 138.1, 146.3, 148., 15.6, 169.7 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -75.1 (dd, J = 12.1 Hz, 32. Hz), -.1 (t, J = 7.7 Hz); The ee value was 89%, t R (minor) = 26.71 min, t R (major) = 31. min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 27 H 25 F 2 NO 7 S 2 Na [M+Na] + =.933, found =.943; [ ] 27 D = +15.8 (c =.84, CHCl 3 ). S13

(racemic 3e) (enantiomerically enriched 3e) (S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-7-chloro-3-fluoro-2-oxoindoline-1-carboxylat e 3f S14

A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1. (s, 9H), 3.1-3.12 (m, 1H), 3.19-3.25 (m, 1H), 5. (t, J = 4.4 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.51-7.58 (m, 4H), 7.65-7.72 (m, 2H), 7.86 (dd, J = 1.3 Hz, 8.2 Hz, 2H), 8. (t, J = 4.1 Hz, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 27.6, 31.4 (d, J = 31. Hz), 76.7, 86.1, 89.7 (d, J = 193.1 Hz), 1.6, 122.6, 126.2, 127.2 (d, J = 19.1 Hz), 129.2 (d, J = 22.8 Hz), 129.7 (d, J = 17.3 Hz), 133.9 (d, J = 2.7 Hz), 134.7 (d, J = 23.7 Hz), 137.3, 138.2, 146.5, 17.3 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -76.7 (dd, J = 11.3 Hz, 33. Hz); The ee value was 87%, t R (minor) = 27.51 min, t R (major) = 31 min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 27 H 25 FClNO 7 S 2 Na [M+Na] + = 61637, found = 61613; [ ] 27 D = +12.4 (c = 1.1, CHCl 3 ). (racemic 3f) S15

(enantiomerically enriched 3f) (S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-3-fluoro-5-methyl-2-oxoindoline-1-carboxylat e 3g A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1.62 (s, 9H), 2.38 (s, 3H), 2.98-3.23 (m, 2H), 5.39 (t, J = 4.4 Hz, 1H), 7.14 (s, 1H), 7.28 (s, 1H), 7.52-7.58 (m, 4H), 7.65-7.71 (m, 2H), 7.79 (d, J = 8.2 Hz, 1H), 7.86-7.88 (m, 2H), 8.1-8.3 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 21., 28., 31.3 (d, J = 31. Hz), 76.9, 84.9, 89.4 (d, J = 19.4 Hz), 11, 123.7 (d, J = 18.2 Hz), 124.4, 129.1 (d, J = 22.8 Hz), 129.7 (d, J = 2.7 Hz), 132.7 (d, J = 1.8 Hz), 134.6 (d, J = 29.2 Hz), 135.2 (d, J = 2.7 Hz), 137.3, 137.7 (d, J = 4.6 Hz), 138.5, 148.5, 17.3 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -75.3 (dd, J = 1.3 Hz, 32. Hz); The ee value was 89%, t R (minor) = 19.79 min, t R (major) = 22.86 min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 28 H 28 FNO 7 S 2 Na [M+Na] + = 596.1183, found = 596.1175; [ ] 27 D = +17.3 (c =.98, CHCl 3 ). S16

(racemic 3g) (enantiomerically enriched 3g) S17

(S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-3-fluoro-5-methoxy-2-oxoindoline-1-carboxyl ate 3h A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.62 (s, 9H), 2.96-3.25 (m, 2H), 3.85 (s, 3H), 5.41 (t, J = 4.4 Hz, 1H), 6.92-1 (m, 2H), 7.5-7.58 (m, 4H), 7.61-7.73 (m, 2H), 7.83-7.92 (m, 3H), 7.95-8.2 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 31.3 (d, J = 31. Hz), 55.9, 76.9, 84.9, 89.4 (d, J = 191.3 Hz), 19.8, 117.3 (d, J = 3.6 Hz), 124.9 (d, J = 17.3 Hz), 129.1 (d, J = 23.7 Hz), 129.7 (d, J = 1.8 Hz), 133.1 (d, J = 4.6 Hz), 134.6 (d, J = 31.9 Hz), 137.2, 138.4, 148.5, 157.4 (d, J = 2.7 Hz), 17.2 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -76.2 (dd, J = 11.3 Hz, 31.9 Hz); The ee value was 9%, t R (minor) = 26.12 min, t R (major) = 32.68 min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 28 H 28 FNO 8 S 2 Na [M+Na] + = 612.1133, found = 611.1127; [ ] 27 D = +24.8 (c =.85, CHCl 3 ). (racemic 3h) S18

(enantiomerically enriched 3h) (S)-tert-Butyl-3-(2,2-bis(phenylsulfonyl)ethyl)-3-fluoro-5,7-dimethyl-2-oxoindoline-1-carbox ylate 3i A white solid; 1 H NMR (5 MHz, CDCl 3 ) δ 1. (s, 9H), 2.22 (s, 3H), 2.33 (s, 3H), 2.98-3.22 (m, 2H), 5.39 (t, J = 4.4 Hz, 1H), 6.96 (s, 1H), 8 (s, 1H), 7.51-7.58 (m, 4H), 7.64-7.71 (m, 2H), 7.87 (d, J = 7.6 Hz, 2H), 8.2 (d, J = 7.6 Hz, 2H); 13 C NMR (125 MHz, CDCl 3 ) δ 19.8,.8, 27.8, 31.5 (d, J = 31.9 Hz), 85.1, 9.1 (d, J = 189.5 Hz), 121.9, 125.1 (d, J = 17.3 Hz), 125.5, 129.1 (d, J = 23.7 Hz), 129.7 (d, J = 9.1 Hz), 134.6 (d, J = 26.4 Hz), 135.3 (d, J = 2.7 Hz), 135.7 (d, J = 2.7 Hz), 136.1 (d, J = 5.5 Hz), 137.4, 138.5, 148.1, 171.3 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -75.2 (dd, J = 11.4 Hz, 21.7 Hz); The ee value was 89%, t R (minor) = 17.12 min, t R (major) = 19.55 min (Chiralcel IA, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 29 H 3 FNO 7 S 2 Na [M+Na] + = 61.13, found = 61.1346; [ ] 27 D = +16.8 (c =.78, CHCl 3 ). S19

(racemic 3i) (enantiomerically enriched 3i) (3S)-tert-Butyl-fluoro-2-oxo-3-(1-phenyl-2,2-bis(phenylsulfonyl)ethyl)indoline-1-carboxylat e 3j S

A white solid; 1 H NMR (3 MHz, CDCl 3 ) δ 1.62 (s, 9H), 4.66 (dd, J = 2.5 Hz, 31.5 Hz, 1H), 6.39 (d, J = 1.9 Hz, 1H), 6.77 (d, J = 7.6 Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 6.9 Hz, 3H), 7.35-7.41 (m, 4H), 7.43-7.49 (m, 3H), 7.55-7.61 (m, 3H), 7.85 (d, J = 7.6 Hz, 2H), 7.93 (d, J = 8.2 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) δ 28., 48. (d, J = 26.4 Hz), 77.2,.6, 85.1, 92.4 (d, J = 199.5 Hz), 115.6, 123.5 (d, J = 19.1 Hz), 124.5 (d, J = 1.8 Hz), 126.3, 128., 128.5, 128.9 (d, J = 3.1 Hz), 129.3 (d, J = 31. Hz), 129.9, 131.8 (d, J = 7.3 Hz), 133.3 (d, J = 2.7 Hz), 133.8, 134.1, 138.3, 139.7, 1. (d, J = 18.3 Hz), 148.4, 17.7 (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) δ -.4 (d, J =.6 Hz); The ee value was 98%, t R (minor) = 3.69 min, 52.43 min t R (major) = 27.33 min, 33.48 min (Chiralcel AD-H, λ = 254 nm, 1% iproh/hexanes, flow rate = 1. ml/min); HRMS (ESI) m/z calcd for C 33 H 3 FNO 7 S 2 Na [M+Na] + = 658.13, found = 658.1348. (racemic 3j) S21

(enantiomerically enriched 3j) tert-butyl- 3-fluoro-3-(2-nitro-1-phenylethyl)-2-oxoindoline-1-carboxylate 3k A colorless oil; 1 H NMR (5 MHz, CDCl 3 ) The major isomer: δ 1.59 (s, 9H), 4.12-4.19 (m, 1H), 6 (dd, J = 1.4 Hz, 13.6 Hz, 1H), 5.55 (dd, J = 4.7 Hz, 13.6 Hz, 1H), 6.69 (d, J = 7.6 Hz, 1H), -7.14 (m, 3H), 7.22-7.31 (m, 3H), 7. (t, J = 15.8 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H); 13 C NMR (125 MHz, CDCl 3 ) The major isomer: δ 28., 49.4 (d, J = 24.6 Hz), 73.9 (d, J = 3.6 Hz), 85.2, 92.9 (d, J = 198.6 Hz), 115.4 (d, J = 16.4 Hz), 124.6, 125.1 (d, J = 2.7 Hz), 125.6, 128.7 (d, J = 9.1 Hz), 129.2 (d, J = 39.2 Hz), 131.7 (d, J = 3.7 Hz), 132. (d, J = 2.7 Hz), 1.1, 148., 17. (d, J = 22.8 Hz); 19 F NMR (282.38 MHz, CDCl 3 ) The major isomer: δ -85.5 (d, J = 19.6 Hz); The ee value was 46%, 28%, t R (minor) = 1.26 min, 11.78 min t R (major) = 15.26 min, 17.9 min (Chiralcel ID, λ = 254 nm, 3% iproh/hexanes, flow rate = 1. ml/min); MS (ESI) m/z calcd for C 21 H 21 FN 2 O 5 Na [M+Na] + = 423, found = 423.1. S22

(racemic 3k) (enantiomerically enriched 3k) S23

E. X-Ray Crystallographic Analysis and Determination of the Absolute Configurations of the Products X-Ray Crystallographic Analysis of 3e The absolute configuration of the product 3e was assigned based on the X-ray crystallographic analysis of a single crystal of 3e (Figure S1). The configurations of other products 3 were assigned by analogy. Figure S1. X-ray structure of 3e Table 1. Crystal data and structure refinement for C9. Identification code c9 Empirical formula C27 H25 F2 N O7 S2 Formula weight 577. Temperature 1(2) K Wavelength.7173 Å Crystal system Orthorhombic Space group P2(1)2(1)2(1) Unit cell dimensions a = 8.2718(7) Å = 9. S24

b = 13.6799(13) Å = 9. c = 23.831(2) Å = 9. Volume 2696.7(4) Å 3 Z 4 Density (calculated) 1.423 Mg/m 3 Absorption coefficient.258 mm -1 F() 1 Crystal size. x. x.8 mm 3 Theta range for data collection 1.71 to 27.5. Index ranges -1<=h<=1, -17<=k<=14, -28<=l<=3 Reflections collected 19152 Independent reflections 6196 [R(int) =.465] Completeness to theta = 27.5 99.9 % Absorption correction Semi-empirical from equivalents Max. and min. transmission.7457 and.6628 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 6196 / / 355 Goodness-of-fit on F 2 1.28 Final R indices [I>2sigma(I)] R1 =.2, wr2 =.883 R indices (all data) R1 =.458, wr2 =.91 Absolute structure parameter.12(6) Largest diff. peak and hole.472 and -.2 e.å -3 S25

169.341 168.8957 148.6514 1.9267 1.893 131.7374 131.7155 125.9439 12184 124.9965 121.8411 121.799 115.5886 85.795 8617 84.2893 77.2934 7456 76.796 28.381 Integral.9838 1.5 1.615 1.869 9.3118 7.87 7.8597 7.53 7.4852 7.4537 7.4386 7.4222 7.28 7.2394 7.2242 7.91 5.753 5.659 1.6329 F. NMR Spectra of the Substrates and Products 1H AMX5 dxw119-3 Ph sub 9. 8. 3. 2. 1.. 13C AMX5 dxw119-4 Ph sub 2 1 1 1 1 1 S26

Integral 2.241.9932 2.39 2.147 4.1378 1.31 1.519 1.1446 1.193 1.55 9.3478 2.241.9932 2.39 2.147 4.1378 1.31 1.519 1.1446 1.193 1.55 7.5443 7.5279 7.5128 7.4951 7. 7.4636 7.3691 7.3539 7.26 7.24 7.2329 5.3897 5.39 5.3721 3.2326 3.2225 3.99 3.1986 3.1885 3.1759 3.1671 3.113 3.115 3.763 3.675 3.448 3.359 3.17 3.19 8.297 8.146 8.1 7.92 7.9238 7.8671 7.8519 7.717 7.6969 7.6817 7.6754 7.63 7.6452 7.5771 7.57 7.5443 7.5279 7.5128 7.4951 7. 7.4636 7.3691 7.3539 7.26 7.24 7.2329 5.3897 5.39 5.3721 3.2326 3.2225 3.99 3.1986 3.1885 3.1759 3.1671 3.113 3.115 3.763 3.675 3.448 3.359 3.17 3.19 1.6227-111.454-111.22 F19(no decoupled) nv1dxw-4 Phsub -5 - -7 - -9-1 -11-1 -13-1 1H AMX5 dxw613-1 PhH 8. 7.6 7.2 6.8 6.4 5.6 5.2 4.8 4.4 3.6 3.2 11. 1. 9. 8. 3. 2. 1.. S27

-75.523-75.5424-75.6155-75.6556 17.237 17.486 148.3613 1.173 139.99 138.3193 13368 134.7412 134.58 132.2271 132.52 129.6765 129.66 129.1883 128.9988 125.2167 123.975 123.7883 123.6426 116.12 9.41 88.4883 8414 77.2585 734 76.66 76.7483 31.37 31.93 27.9594 13C AMX5 dxw613-2 PhC 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) nv1dxw-3 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S28

168.34 168.576 148.4765 139.3891 139.3527 131.7374 131.7155 13.6297 13.78 126.1261 123.3277 123.1966 116.94 85.44 85.2294 83.763 77.2715 7165 76.7614 28.162 Integral 1.19.938 1.544 9.1388 7.8673 7.8629 7.8383 7.8339 7.4833 7.4378 7.4312 7.4258 7.88 7.22 7.3951 7.23 5.77 5.42 1.6273 1H normal range AC3 nv9dxw-2 1222 5-Cl sub 9. 8. 3. 2. 1.. 13C AMX5 dxw119-5 5-Cl sub 2 1 1 1 1 1 S29

Integral 1.9581 2.943 2.379 1.9762.9461 1.23 1.263 9.3512 1.9581 2.943 2.379 1.9762.9461 1.23 1.263 7.5557 7.55 7.4573 7.49 7.2997 7.2959 7.2922 7.26 5.3254 5.3166 5.378 3.1935 3.1847 3.1696 3.1595 3.157 3.1355 3.1267 3.914 3.813 3.574 3.473 3.259 3.17 2.9918 2.983 8.39 8.146 7.9175 7.8973 7.89 7.7246 7.795 7.6956 7.6842 7.6691 7.5922 7.5771 7.57 7.57 7.5557 7.55 7.4573 7.49 7.2997 7.2959 7.2922 7.26 5.3254 5.3166 5.378 3.1935 3.1847 3.1696 3.1595 3.157 3.1355 3.1267 3.914 3.813 3.574 3.473 3.259 3.17 2.9918 2.983 1.6164-112.1152-112.314 F19(no decoupled) nv1dxw-5 5Cl sub - - - - -1-1 1H AMX5 dxw613-3 5-Cl H 7.5 6.5 5.5 4.5 3.5 11. 1. 9. 8. 3. 2. 1.. S3

-76.4114-76.4516-76.59-76.5647 169.56 169.3858 148.15 138.5 138.4655 138.296 136.8332 134.8656 134.615 132.22 132.1984 13.7846 13.7628 129.7498 129.6624 129.2761 129.867 125.4138 125.2681 124.1531 117.5653 89.713 88.1754 85.4426 77.2589 738 76.7488 76.65 31.67 31.159 27.9525 13C AMX5 dxw613-4 5-Cl C 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) nv1dxw-2 1123F - - - - -1-1 S31

168.4366 168.298 148.4182 141.8814 141.845 137.7786 137.7494 126.8475 125.1933 125.1714 1.167 119.9755 116.4557 85.6156 85.2 83.6844 77.2643 792 76.7541 28.16 Integral.9185.9959.9899 9.852 7.9665 7.4438 7.4 7.4175 7.4137 7.23 7.2378 7.2351 7.2324 7.2115 7.83 7.55 5.763 5.5926 1.6355 1H normal range AC3 nv9dxw-3 12 6-Cl sub 9. 8. 3. 2. 1.. 13C AMX5 dxw111-3 6-Cl sub 2 1 1 1 1 1 S32

Integral 2.8754 1.9625 1.9956 3.9525 2.8147 2.366 9. 2.8754 1.9625 1.9956 3.9525 2.8147 2.366 7.5162 7.517 7.3168 7.3113 7.2894 7.2845 7.23 7.255 7.2291 7.2236 5.3357 5.321 5.356 3.2342 3.2188 3.1953 3.1772 3.1619 3.1389 3.1235 3.1148 3.994 3.578 3.424 3.85 2.9931 2.9515 2.9362 8.279 8.136 7.9895 7.9852 7.8652 7.8411 7.8367 7.731 7.757 7.6992 7.6811 7.67 7.6526 7.6488 7.5912 7.5639 7.5354 7.5162 7.517 7.3168 7.3113 7.2894 7.2845 7.23 7.255 7.2291 7.2236 5.3357 5.321 5.356 3.2342 3.2188 3.1953 3.1772 3.1619 3.1389 3.1235 3.1148 3.994 3.578 3.424 3.85 2.9931 2.9515 2.9362 1.6224-7751 -75.1153-75.1883-75.2285 F19(no decoupled) nv1dxw-6 6-Cl product - - - - -1-1 1H normal range AC3 nv9dxw-4 1221 8. 7.5 6.5 5.5 4.5 3.5 3. 1. 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. S33

-11.7314-11.91 169.7483 169.5661 148.68 141.652 141.288 138.3689 138.3397 138.2741 13717 134.8272 134.13 129.7333 129.7115 129.2669 129.775 125.46 125.3828 124.9965 122.21 122.67 1123 89.7475 88.2245 85.632 77.2788 7238 76.877 76.7687 31.393 31.1352 29.6923 27.9798 13C AMX5 dxw1111-2 1221 6-Cl product 2 1 1 1 1 1 F19(no decoupled) nv1dxw-7 6-Cl sub - - - - -1-1 S34

168.1524 167.9848 148.4619 139.8555 134.6815 134.6523 128.9973 128.74 123.6411 123.599 117.3375 11897 85.563 85.1419 83.6188 77.2788 7238 76.77 28.235 Integral 1.1477.969 1.623 9.2859 7.8158 7.819 7.7868 7.7818 7.7594 7.7555 7.6312 7.5923 7.5873 7.5824 7.5627 7.5583 7.5517 7.23 5.7783 5.85 1.6278 AC3 nv23dxw-1 1127 5-Br-Substrate 9. 8. 3. 2. 1.. 13C AMX5 dxw1123-1 1237 5-Br substrate 2 1 1 1 1 1 S35

Integral 2.166 2.94 1.996.9866 1.965 9.227 2.166 2.94 1.996.9866 1.965 7.59 7.5783 7.5657 7.56 7.5468 7.44 7.4422 7.4384 7.26 5.3 5.2952 5.2851 3.1872 3.1784 3.1645 3.1532 3.1444 3.135 3.1217 3.965 3.876 3.624 3.536 3.322 3.233 2.9981 2.9893 8.297 8.146 8.1 7.911 7.88 7.8834 7.8633 7.8456 7.7271 7.7132 7.744 7.6981 7.6893 7.6754 7.6187 7.6149 7.6111 7.5973 7.59 7.5783 7.5657 7.56 7.5468 7.44 7.4422 7.4384 7.26 5.3 5.2952 5.2851 3.1872 3.1784 3.1645 3.1532 3.1444 3.135 3.1217 3.965 3.876 3.624 3.536 3.322 3.233 2.9981 2.9893 1.6176-112.312-112.385-112.458-112.2174 F19(no decoupled) nv23dxw-6 1127 5-Br sub - - - - -1-1 1H AMX5 dxw613-5 5-Br H 8. 7.5 6.5 5.5 4.5 3.5 11. 1. 9. 8. 3. 2. 1.. S36

-76.111-76.1449-76.2142-76.2581 169.4658 169.299 148.86 139.775 139.411 138.3123 136.8257 135.1569 134.8873 134.6249 129.7 129.6841 129.296 129.184 12388 125.7343 125.5959 118.972 118.753 117.9368 89.756 88.1752 85.4935 77.2514 737 76.7486 31.3993 31.1515 27.9669 13C AMX5 dxw613-6 5-Br C 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) nv25dxw-4 11C 5-Br product - - - - -1-1 S37

169.851 168.9321 157.1776 157.1484 148.7169 13839 13548 122.8395 122.783 11314 1123 116.7254 111.4275 85.9872 84.865 84.4788 55.7592 29.769 28.672.35 Integral.9786.9826 1.447 3.731 9.311 7.45 7. 7.7869 7.7844 7.2637 557 6.9775 6.9737 6.9687 6.9599 6.9561 6.951 5.7369 5.6348 3.8269 1.6333.6 1H AMX5 dxw1128-1 1239 5-OMe sub 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. 13C AMX5 dxw1128-2 1239 5-OMe sub 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 S38

Integral 2.233 3.459 2.1683 4.1 1.9893 2.99 2.283 9.255 2.233 3.459 2.1683 4.1 1.9893 2.99 2.283 7.5551 7.5288 7.542 7.2642 149 62 1 6.9848 6.97 6.976 6.9371 6.936 6.9229 5.4218 5.7 5.3922 3.8484 3.251 3.2353 3.2118 3.1937 3.1783 3.1548 3.1383 3.1219 3.797 3.649 3.293 3.145 2.9723 2.9576 8.2 7.9956 7.997 7.8822 7.8575 7.8526 7.8351 7.8318 7.7162 7.691 7.6658 7.66 7.5787 7.5551 7.5288 7.542 7.2642 149 62 1 6.9848 6.97 6.976 6.9371 6.936 6.9229 5.4218 5.7 5.3922 3.8484 3.251 3.2353 3.2118 3.1937 3.1783 3.1548 3.1383 3.1219 3.797 3.649 3.293 3.145 2.9723 2.9576 1.6175-111.332-111.3375-111.5128 F19(no decoupled) nv28dxw-1 1239 5-OMe sub 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 AC3 nv3dxw-3 5-OMe product 8. 7.5 6.5 5.5 4.5 3.5 3. 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. S39

-7938-76.1339-76.69-76.2471 17.394 17.1272 157.3671 157.3452 148.556 138.4345 137.2175 134.7471 134.49 133.1657 133.1293 129.7261 129.7115 129.2232 129.338 124.9237 124.7852 117.3375 117.384 19.7587 9.2139 88.6836 84.8577 77.2861 77.2351 7384 76.877 76.7833 55.894 31.48 31.1571 28.381 13C AMX5 dxw113-1 1243 5-OMe product 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) nv3dxw-1 5-OMe product F 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S

169.14 168.977 148.88 138.4411 138.3684 134.7828 134.7464 132.99 132.554 126.3461 121.75 121.523 115.2984 115.2766 86.3373 84.7736 83.8354 77.3697 76.9478 76.52 27.9569.3 Integral 1.71.9726 1.1863 3.1333 9.889 7.7513 7.7234 7.381 7.2665 7.2528 7.2248 5.7582 5.5873 2.3665 1.63.3 de2dxw-3 5-Me-substrate 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. 13C Standard AC3 de2dxw-5 5-Me substrate 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 S41

Integral 2.799 2.356 1.158 2.1485 55 1.8865.9542 1.239 1.4 3.89 9.456 2.799 2.356 1.158 2.1485 55 1.8865.9542 1.239 1.4 7.5624 7.5498 7.5461 7.5347 7.5183 7. 7.2624 7.1489 5.41 5.3953 5.3864 3.2293 3.25 3.79 3.1991 3.1953 3.1865 3.1738 3.165 3.919 3.831 3.579 3.49 3.263 3.175 2.9923 2.9835 8.32 8.138 8.113 7.8751 7.8 7.8575 7.45 7.7881 7.7112 7.6961 7.681 7.6784 7.6633 7.6482 7.5776 7.5624 7.5498 7.5461 7.5347 7.5183 7. 7.2624 7.1489 5.41 5.3953 5.3864 3.2293 3.25 3.79 3.1991 3.1953 3.1865 3.1738 3.165 3.919 3.831 3.579 3.49 3.263 3.175 2.9923 2.9835 2.38 1.6181-11.795-11.8921 F19(no decoupled) de2dxw-4 5-Me subs 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 1H AMX5 dxw12-3 1247 5-Me product 7.5 6.5 5.5 4.5 3.5 3. 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. S42

-75.1919-75.2285-75.351-75.3416 17.4187 17.2366 148.4837 138.5 137.6911 137.6547 137.2612 135.1843 135.1624 134.7398 134.566 132.7357 132.7212 129.7333 129.7115 129.2232 129.41 124.4281 123.81 123.672 115.9675 9.1556 88.6326 84.914 77.2934 7384 76.9363 76.7833 31.4267 31.1789 28.381.9766 13C AMX5 dxw12-1 1247 5-Me 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) de2dx2-2-2 1247 5-Me product 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S43

168.4786 168.2313 15.88 146.85 146.6669 126.325 126.2661 126.79 124.42 124.6 121.8296 121.7859 1.1495 1.1131 119.84 119.8368 86.1264 8973 85.69 83.5881 83.5517 77.3697 77.1515 76.9478 76.5187 29.6 27.58 Integral.95 1.9845 9.522 7.39 7.3316 7.3245 7.3217 7.3124 7.358 7.24 7.2439 7.2362 7.2193 7.1968 7.1722 5.8316 5.6623 1.54 1H normal range AC3 de21dxw-2 1271H 9. 8. 3. 2. 1.. 13C Standard AC3 de21dxw 1271C 2 1 1 1 1 1 S44

Integral 1.9448 1.9616 2.75 868 2.9885 1.17 1.458 1.3 9.1529 1.9448 1.9616 2.75 868 2.9885 1.17 1.458 1.3 7.547 7.536 7.5154 7.26 7.2557 7.2419 7.1889 7.1814 7.1763 5.3722 5.3634 5.3546 3.2542 3.2454 3.2315 3.2214 3.2113 3.1974 3.1886 3.1319 3.1231 3.979 3.89 3.663 3.575 3.323 3.235 8.19 7.9945 7.8647 7.8495 7.79 7.746 7.697 7.6819 7.6667 7.6516 7.5886 7.5722 7.5571 7.547 7.536 7.5154 7.26 7.2557 7.2419 7.1889 7.1814 7.1763 5.3722 5.3634 5.3546 3.2542 3.2454 3.2315 3.2214 3.2113 3.1974 3.1886 3.1319 3.1231 3.979 3.89 3.663 3.575 3.323 3.235 1.59-42.17-42.1826-42.2118-111.3886-111.5675 F19(no decoupled) de21dxw-1 1271F - - - - -1-1 1H AMX5 dxw617-5 1271H 7.5 6.5 5.5 4.5 3.5 3. 1.5 1. 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. S45

-.13 -.358 -.65-74.9838-7276 -797-75.18 169.7431 169.561 149.9944 147.9758 146.35 138.941 13811 134.7929 134.34 129.79 129.64 129.2399 129.942 12464 126.9736 126.8934 126.7477 126.7112 1.7356 1.7137 1.5461 119.9194 119.892 9.3545 88.23 85.696 77.2518 77.81 741 76.749 31.4726 31.2175 29.6726 27.6467 13C AMX5 dxw617-6 1271C 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) de27dxw-6 1271-2 7-F product 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S46

169.2382 169.779 147.1429 138.245 133.3479 125.8273 125.1131 124.9382 124.583 119. 86.2569 85.876 84.33 77.2788 7238 76.77 29.769 27.6591 Integral 1.9119 1.12 9.12 7.4397 7.4359 7.4326 7.4145 7.2611 7.58 7.36 7.1789 7.1537 5.8252 5.6559 1.6319 de27dxw-8 1272-2 7-Cl sub 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. 13C AMX5 dxw1229-2 1272-2 7-Cl substrate 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 S47

Integral 1.9126 1.947 2.492 3.9636.9675.9774.9879 1.312 1.162 9.2289 1.9126 1.947 2.492 3.9636.9675.9774.9879 1.312 1.162 7.5153 7.4813 7.4649 7.335 7.2884 7.26 7.2266 7.212 7.1951 5.74 5.3985 5.3897 3.25 3.2452 3.231 3.2 3.2112 3.19 3.1872 3.14 3.1116 3.864 3.775 3.548 3.448 3.195 3.17 8.83 8.57 7.9919 7.8696 7.8671 7.8532 7.857 7.717 7.719 7.68 7.6792 7.6653 7.652 7.5846 7.5683 7.5531 7.5468 7.534 7.5153 7.4813 7.4649 7.335 7.2884 7.26 7.2266 7.212 7.1951 5.74 5.3985 5.3897 3.25 3.2452 3.231 3.2 3.2112 3.19 3.1872 3.14 3.1116 3.864 3.775 3.548 3.448 3.195 3.17 1.25-112.3671-112.54 F19(no decoupled) de27dxw-9 1272-2 7-Cl sub 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 1H AMX5 dxw614-1 7-Cl H 7.5 6.5 5.5 4.5 3.5 11.5 11. 1.5 1. 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. -.5 S48

-76.6341-76.6743-76.751-76.7911 17.3532 17.171 146.516 138.13 137.2831 134.7981 134.86 133.99 133.8871 129.7698 129.6313 129.2815 129.993 127.272 127.1172 126.2354 122.5699 1.595 9.554 88.95 86.1184 77.2861 7311 76.77 76.6594 31.4996 31.2518 27.6664 13C AMX5 dxw614-2 7-Cl C 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) de3dxw-1 1275C 7-ClPF 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S49

17.15 169.9477 148.5215 136.8338 136.7683 13591 13155 134.7828 134.7391 124.2296 124.78 123.9751 123.196 122.8914 86.89 85.1372 84.3445 77.3915 76.9624 76.56 27.6951.6693 19.3457 Integral.99.993 3.838 3.81 9.1247 7.26 7.1422 469 5.7485 5.5776 2.3195 2.198 1.6199 de27dxw-2 1273-2 5,7-Me sub 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. 13C de27dxw-4 1273-2 5,7-Me sub 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 S5

Integral 2.45 2.137 2.995 4.1859 1.93 1.86 1.269 1.383 3.1121 3.1434 9.379 2.45 2.137 2.995 4.1859 1.93 1.86 1.269 1.383 7.5658 7.5494 7.5456 7.535 7.5141 7.27 829 6.9594 5.3986 5.3898 5.39 3.2163 3.74 3.1948 3.1822 3.1734 3.18 3.15 3.914 3.826 3.574 3.486 3.259 3.171 2.9919 2.983 8.285 8.133 7.8797 7.8646 7.71 7.6969 7.6818 7.6717 7.6565 7.6414 7.59 7.5658 7.5494 7.5456 7.535 7.5141 7.27 829 6.9594 5.3986 5.3898 5.39 3.2163 3.74 3.1948 3.1822 3.1734 3.18 3.15 3.914 3.826 3.574 3.486 3.259 3.171 2.9919 2.983 2.3338 2.2215 1.5975-11.587-11.6913 F19(no decoupled) de27dxw-3 1273-2 5,7-Me sub 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 1H AMX5 dxw1229-3 1274C 5,7-Me product 7.5 6.5 5.5 4.5 3.5 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. S51

-7678-75.143-75.181-75.2212 171.3952 171.2131 148.829 138.573 137.375 136.1389 13952 135.717 135.6798 135.2936 135.2717 134.716 134.4993 129.7698 129.6969 129.2232 129.338 125.4994 125.1423 138 121.9431 9.8916 89.3759 8763 77.37 7456 76.796 31.6162 31.3611 27.8122.8454 19.7523 13C AMX5 dxw1229-4 1274C 5,7-Me product 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) de29dxw-1 1274F 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S52

17.77 17.5958 148.57 1.617 1.252 139.6827 138.3419 134.1225 133.7654 133.39 133.299 131.7759 131.7614 129.8521 129.3 129.1525 129.723 128.8318 128.5185 127.9646 126.27 124.5542 124.5396 123.5412 123.3882 115.53 93.1747 91.5788 85.1222.6113 77.2591 77.81 741 76.749 48.196 47.8983 28.183 Integral.95 1.9244 3.1777 2.6516 4.3178 3.2426 1.788.9778.9699 8.8623.95 1.9244 3.1777 2.6516 4.3178 3.2426 1.788.9778.9699 7.4259 7.95 7.3944 7.3818 7.3793 7.3692 7.3541 7.291 7.2772 7.28 6.9632 6.9481 6.933 6.783 6.7678 6.3984 6.3947 4.6939 4.6889 4.639 4.6259 7.9353 7.9189 7.8571 7.84 7.6138 7.5987 7.5785 7.5634 7.5482 7.4928 7.4776 7.471 7.4549 7.4259 7.95 7.3944 7.3818 7.3793 7.3692 7.3541 7.291 7.2772 7.28 6.9632 6.9481 6.933 6.783 6.7678 6.3984 6.3947 4.6939 4.6889 4.639 4.6259 1.6783 1.63 1H AMX5 dxw617-3 1824H 7.5 6.5 5.5 4.5 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. -.5 13C AMX5 dxw617-4 1824C 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 S53

Integral.9293.5736 1.56 1.2428 2.75 1.8438 1.9296.5741.95.5562 1.34.2674 1.88 2.6351 9.264.9293.5736 1.56 1.2428 2.75 1.8438 1.9296.5741.95.5562 1.34.2674 1.88 7.1259 7.1133 969 83 755 3 452 162 11 6.9645 6.956 6.6972 6.6821 5.5714 5.5626 5.5449 5.5348 5.4214 5.41 5.3924 5.3823 5.3634 5.3546 5.3356 873 671 8 394 4.4985 4.4872 4.4784 4.4683 4.4582 4.199 4.1821 4.1695 4.16 4.156 4.1417 4.1291 4.13 7.7789 7.7625 7.5835 7.5684 7.55 7.5356 7.4133 7.3982 7.3818 7.3137 7.2986 7.2847 7.28 7.2469 7.2318 7.2167 7.1397 7.1259 7.1133 969 83 755 3 452 162 11 6.9645 6.956 6.6972 6.6821 5.5714 5.5626 5.5449 5.5348 5.4214 5.41 5.3924 5.3823 5.3634 5.3546 5.3356 873 671 8 394 4.4985 4.4872 4.4784 4.4683 4.4582 4.199 4.1821 4.1695 4.16 4.156 4.1417 4.1291 4.13 1.5825 1.5686 -.3138 -.3869 F19(no decoupled) ja6dxw-2 1284F 45 35 3 25 15 1 5-5 -1-15 - -25-3 -35 - -45-5 -55 - -65-7 1H AMX5 dxw617-1 1866H 7.5 6.5 5.5 4.5 1.5 1. 9.5 9. 8.5 8. 7.5 6.5 5.5 4.5 3.5 3. 2.5 2. 1.5 1..5. -.5 S54

-76.8276-76.8459-85.4843-85.5537 17.779 17.124 169.8958 169.8447 148.118 147.8223 1.1123 1.685 132.87 131.9723 131.954 131.7464 131.7172 129.3561 129.428 128.693 128.61 125.6323 1293 12711 124.47 124.592 124.2841 123.234 122.8776 122.1781 122.25 115.4154 115.2842 93.6844 93.5387 92.958 91.9646 85.2165 85.1291 77.2514 736 76.7486 73.9356 73.965 73.4984 73.4693 5.695 49.8655 49.3918 49.195 27.9523 27.913 13C AMX5 dxw617-2 1866C 2 21 19 1 17 1 15 1 13 1 11 1 9 7 5 3 1-1 F19(no decoupled) ju17dxw-1 1866F 9 7 5 3 1-1 - -3 - -5 - -7 - -9-1 -11-1 -13 S55