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1 Supporting nline Material for A Powerful Chiral Counterion Strategy for Asymmetric Transition Metal Catalysis Gregory L. amilton, Eun Joo Kang, Miriam Mba, F. Dean Toste* *To whom correspondence should be addressed. fdtoste@berkeley.edu This PDF file includes Materials and Methods References Published 27 July 2007, Science 317, 496 (2007) DI: /science

2 Supporting nline Material General Information: Unless otherwise noted all commercial materials were used without further purification. Small-scale reactions were conducted in two-dram vials equipped with a magnetic stir bar, fitted with a threaded cap, and protected from ambient light. All other reactions were conducted in flame-dried glassware under an N 2 atmosphere with magnetic stirring and dried solvent. Dichloromethane, toluene, ether and tetrahydrofuran were purified by passage through an activated alumina column under nitrogen. Benzene and acetonitrile were distilled from calcium hydride. Chiral gold(i) chloride complexes were prepared according to a procedure previously described by our group (S1). ydroalkoxylation substrates (1, 8-14) were prepared according to the methods of Widenhoefer (S2). ydroamination substrates (22-25) were prepared according to the methods of Lalonde (S3). Thin-layer chromatography (TLC) analysis of reaction mixtures was performed using Merck silica gel 60 F254 TLC plates, and visualized by a combination of UV and anisaldehyde staining. Flash column chromatography was carried out on Merck 60 silica gel (32-63 µm). Nuclear magnetic resonance (NMR) spectra were recorded with Bruker DRX-500, AVB-400, AVQ-400,

3 and AV-300 spectrometers. 1 and 13 C chemical shifts are reported in ppm downfield of tetramethylsilane and referenced to residual solvent peak (CCl 3 = 7.26) unless otherwise noted. 31 P spectra are reported in ppm downfield of 85% aqueous phosphoric acid. Multiplicities are reported using the following abbreviations: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad resonance. IR spectra were recorded with a ThermoNicolet Avatar 370 FTIR spectrometer as thin films on a ZnSe plate. Enantiomeric excesses (ee s) were determined on a Shimadzu VP Series Chiral PLC or a ewlett Packard P 6850 GC equipped with a Chiraldex G-TA (30.0 m x 0.25 mm) column. Mass spectral data were obtained via the Micro-Mass/Analytical Facility operated by the College of Chemistry, University of California, Berkeley. ( 3 C) 2 C C(C 3 ) 2 C(C 3 ) 2 P Ag C(C 3 ) 2 ( 3 C) 2 C C(C 3 ) 2 Ag-(R)-6: Prepared from the corresponding phosphoric acid reported by List (S4). To a solution of (R)-3,3 -bis(2,4,6-triisopropylphenyl)-1,1 -binaphthyl-2,2 diylhydrogenphosphate (1.03 g, 1.37 mmol) in C 2 Cl 2 (10 ml) in the dark was added in one portion Ag 2 C 3 (189 mg, 0.68 mmol), followed by distilled 2 (10 ml). The resulting mixture was stirred vigorously for 1 h. After this time, the mixture was diluted

4 with C 2 Cl 2 (20 ml) and 2 (20 ml). The layers of the biphasic suspension were separated and the aqueous layer extracted with C 2 Cl 2 (2 x 30 ml). The combined organic extracts were filtered through Celite and concentrated to afford the product as a fluffy white solid (1.13 g, 96% yield). 1 NMR (400 Mz, CDCl 3 ) δ 7.87 (d, J = 8.1 z, 2) (s, 2), 7.46 (t, J = 7.3 z, 2), 7.35 (d, J = 8.4 z, 2), 7.29 (d, J = 7.4 z, 2), 7.02 (s, 2), 6.96 (s, 2), 2.82 (septet, J = 6.9 z, 2), 2.68 (septet, J = 6.6 z, 4), 1.21 (d, J = 6.9 z, 6), 1.15 (d, J = 6.7 z, 24), 0.93 (d, J = 6.8 z, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 149.0, 147.9, 147.6, 147.0, 132.3, 132.0, 131.7, 130.7, 128.4, 128.2, 127.5, 125.9, 125.2, 122.4, 120.5, 119.2, 33.8, 31.0, 31.0, 26.7, 25.1, 24.6, 24.2, 24.0, 23.7; 31 P NMR (162 Mz, CDCl 3 ) δ 13.0; IR (solid) 2965, 1225, 1085 cm -1 ; mp (dec); RMS (FAB) exact mass for [M+] + (C Ag 4 P) calcd m/z , found ; [α] D = (c = 1.0, CCl 3 ). General procedure for enantioselective hydroalkoxylation: To a 2 dram vial was added dppm(aucl) 2 (4.4 mg, 5 µmol, 2.5 mol%) and Ag-(R)-7 (8.8 mg, 10 µmol, 5 mol%). The mixture was dissolved in benzene (1 ml) and stirred for 30 mins at room temperature. After this time, allenol (0.2 mmol) was added as a solution in benzene (1 ml). The resulting mixture was stirred for the indicated amount of time (see Table 1), then filtered through a silica gel plug and concentrated. Purification by flash column chromatography afforded the desired product.

5 Allenol 1: 1 NMR (400 Mz, CDCl 3 ) δ (m, 1), 3.68 (dt, J = 8.4 z, 7.6 z, 2), (m, 6), 1.67 (quintet, J = 6.8 z, 2), (m, 6), (m, 1); 13 C NMR (100 Mz, CDCl 3 ) δ 198.3, 103.0, 87.9, 62.4, 31.8, 31.7, 27.5, 26.1, 25.5; IR (thin film) 3345, 2926, 2853, 1446, 1055, 908 cm -1 ; RMS (EI) exact mass for [M] + (C ) calcd m/z , found Allenol 8: 1 NMR (400 Mz, CDCl 3 ) δ (m, 1), 3.64 (t, J = 6.6 z, 2), 2.00 (dt, J = 7.2 z, 6.8 z, 2), 1.98 (br, 1), (m, 2), 1.65 (d, J = 3.2 z, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 201.6, 95.4, 88.1, 62.3, 31.9, 25.4, 20.6; IR (thin film) 3367, 2938, 1722, 1362, 1156, 1036, 574 cm -1 ; RMS (EI) exact mass for [M- ] + (C 8 13 ) calcd m/z , found Allenol 9: 1 NMR (400 Mz, CDCl 3 ) δ (m, 1), 3.64 (t, J = 6.4 z, 2), 2.08 (br, 1), 2.02 (dt, J = 7.6 z, 7.2 z, 2), 1.92 (dq, J = 7.2 z, 3.2 z, 4), 1.64 (quintet, J = 7.0 z, 2), 0.96 (t, J = 7.4 z, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 200.0, 108.4, 92.2, 62.3, 32.1, 25.7, 25.6, 12.3; IR (thin film) 3331, 2965, 2879, 1720,

6 1457, 1054, 963, 803 cm -1 ; RMS (EI) exact mass for [M + ] (C ) calcd m/z , found Allenol 10: 1 NMR (400 Mz, CDCl 3 ) δ (m, 1), (m, 6), (m, 8), 1.24 (s, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 198.2, 103.1, 88.9, 71.1, 42.8, 31.8, 29.4, 27.5, 26.2, 24.5; IR (thin film) 3434, 2936, 2859, 1715, 1449, 1367, 1275, 1134, 910 cm -1 ; RMS (EI) exact mass for [M] + (C ) calcd m/z , found Ph Ph Allenol 11: 1 NMR (400 Mz, CDCl 3 ) δ (m, 4), (m, 4), (m, 2), (m, 1), (m, 2), (m, 4), (m, 2), (m, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 198.1, 147.0, 128.1, 126.8, 126.0, 103.3, 88.7, 78.4, 40.9, 31.7, 27.5, 26.1, 24.0; IR (thin film) 3475, 3060, 2935, 2856, 1702, 1492, 1447, 907 cm -1 ; RMS (EI) exact mass for [M- 2 ] + (C ): calcd m/z , found

7 Allenol 12: 1 NMR (400 Mz, CDCl 3 ) δ 4.93 (tquintet, J = 8.0 z, 2.1 z, 1) (s, 2), (m, 4), 1.91 (d, J = 8.0 z, 2), (m, 6) ; 13 C NMR (100 Mz, CDCl 3 ) δ 199.8, 101.4, 84.7, 71.5, 39.4, 35.9, 31.6, 27.4, 26.2, 23.8; IR (thin film) 3365, 2925, 2854, 1964 cm -1 ; RMS (FAB) exact mass for [M-] + (C ) calcd m/z , found Allenol 13: 1 NMR (400 Mz, CDCl 3 ) δ (m, 1), 3.60 (t, J = 6.6 z, 2), 2.15 (br, 1), 1.94 (dt, J = 7.2 z, 6.8 z, 2), 1.64 (d, J = 2.8 z, 6), (m, 2), (m, 2); 13 C NMR (100 Mz, CDCl 3 ) 201.6, 94.9, 88.4, 62.6, 32.0, 28.9, 25.2, 20.6; IR (thin film) 3332, 1932, 1856, 1444, 1362, 1055, 1030, 719, 573 cm -1 ; RMS (EI) exact mass for [M-] + (C 9 16 ) calcd m/z , found Tetrahydrofuran 2: Prepared according to the general procedure on a 0.3 mmol scale. Chromatography on Si 2 (7:1 hexanes/etac) afforded the product as a colorless oil (45 mg, 90% yield). 1 NMR (400 Mz, CDCl 3 ) δ 5.17 (d, 1, J = 8.4 z), 4.54 (ddd, J = 8.4 z, 8.4 z, 6.0 z, 1), 3.90 (ddd, J = 8.0 z, 7.6 z, 7.2 z 1), 3.74

8 (ddd, J = 8.0 z, 8.0 z, 6.0 z 1), (m, 7), (m, 7); 13 C NMR (100 Mz, CDCl 3 ) δ 143.7, 122.5, 74.9, 67.7, 37.0, 32.8, 29.2, 28.3, 27.8, 26.7, 26.3; IR (thin film) 2391, 2856, 1447, 1042, 909 cm -1 ; RMS (EI) exact mass for [M] + (C ) calcd m/z , found ; [α] D = (c = 0.48, CCl 3 ). Enantiopurity was determined by PLC analysis (Regis Technologies Whelk-1 column, 99.9:0.1 hexanes/isopropanol, 1 ml/min) t r 20.0 min (major), 23.0 min (minor): 97% ee. Tetrahydrofuran 15: Prepared according to the general procedure on a 0.25 mmol scale. Chromatography on Si 2 (15:1 hexanes/etac) afforded the product as a colorless oil (29 mg, 91%). 1 NMR (400 Mz, CDCl 3 ) δ 5.19 (d, J = 8.4 z, 1), 4.49 (dt, J = 6.3 z, 8.4 z, 1), (m, 1), 3.73 (dt, J = 6.0 z, 7.8 z, 1), (m, 3), 1.72 (s, 3), 1.69 (s, 3), (m, 1); 13 C NMR (100 Mz, CDCl 3 ) δ 135.8, 125.9, 75.7, 67.7, 32.4, 26.2, 25.8, 18.1; IR (thin film) 2956, 2919, 2850, 1730, 1463, 1157 cm -1 ; RMS (EI) exact mass for [M-] + (C 8 13 ) calcd m/z , found ; [α] D = -3.7 (c = 0.27, CCl 3 ). Enantiopurity was determined by GC analysis ( ºC, 1 ºC/min) t r 14.2 min (minor), 15.8 min (major): 95% ee.

9 Tetrahydrofuran 16: Prepared according to the general procedure with Ag-(S)-7 on a 0.25 mmol scale. Chromatography on Si 2 (17:1 hexanes/etac) afforded the product as a colorless oil (34 mg, 89% yield). 1 NMR (400 Mz, CDCl 3 ) δ 5.13 (d, J = 8.4 z, 1), 4.52 (td, J = 8.4 z, 6.0 z, 1), (m, 1), 3.73 (td, J = 8.0 z, 5.6 z, 1), (m, 7), (m, 1), 1.00 (t, J = 7.2 z, 3), 0.98 (t, J = 7.4 z, 3); 13 C NMR (100 Mz, CDCl 3 ) δ 146.7, 123.6, 75.4, 67.7, 32.8, 29.0, 26.2, 23.8, 13.8, 12.3; IR (thin film) 2965, 2935, 2875, 1462, 1049, 753 cm -1 ; RMS (EI) exact mass for [M + ] (C ) calcd m/z , found ; [α] D = +9.1 (c = 0.54, CCl 3 ). Enantiopurity was determined by PLC analysis (Chiralcel D- column, 99.9:0.1 hexanes/isopropanol, 1 ml/min) t r 4.7 min (major), 5.8 min (minor): 96% ee. Tetrahydrofuran 17: Prepared according to the general procedure on a 0.3 mmol scale. Chromatography on Si 2 (8:1 hexanes/etac) afforded the product as a colorless oil (46 mg, 79% yield). 1 NMR (400 Mz, CDCl 3 ) δ 5.13 (d, J = 8.8 z, 1), (m, 1), (m, 2), (m, 2), (m, 1), (m, 9), 1.24 (s, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 142.6, 123.6, 80.3, 74.3, 39.1, 37.1, 33.6, 29.3, 29.1, 28.4, 28.2, 27.7, 26.7; IR (thin film) 2934, 2858, 1770, 1448, 1137, 909 cm -1 ;

10 RMS (EI) exact mass for [M] + (C ) calcd m/z , found ; [α] D = (c = 0.5, CCl 3 ). Enantiopurity was determined by GC analysis (70 ºC for 60 min, then ramp to 90 ºC at 1 ºC/min) t r 75.3 min (minor), 75.9 min (major): 99% ee. Ph Ph Tetrahydrofuran 18: Prepared according to the general procedure on a 0.3 mmol scale. Chromatography on Si 2 (8:1 hexanes/etac) afforded the product as a colorless oil (82 mg, 86% yield). 1 NMR (400 Mz, CDCl 3 ) δ (m, 4), (m, 5), (m, 2), 5.32 (d, J = 8.4 z, 1), (m, 1), (m, 2), (m, 2), (m, 3), (m, 7); 13 C NMR (100 Mz, CDCl 3 ) δ 147.3, 146.8, 143.0, 128.6, 128.1, 127.9, 126.6, 126.5, 125.9, 123.1, 87.9, 75.1, 39.4, 37.0, 33.1, 29.3, 28.3, 27.8, 26.7; IR (thin film) 2921, 2855, 1458, 910 cm -1. RMS (EI) exact mass for [M] + (C ) calcd m/z , found ; [α] D = (c = 0.3, CCl 3 ). Enantiopurity was determined by PLC analysis after ozonolysis to the methyl ester (Regis Technologies Whelk-1 column, 99.5:0.5 hexanes/isopropanol, 1 ml/min) t r 39.3 min (minor), 41.3 min (major): 97% ee. Tetrahydrofuran 19: Prepared according to the general procedure. Chromatography on Si 2 (3:2 C 2 Cl 2 /hexanes) afforded the product as a colorless oil

11 (36 mg, 90% yield). 1 NMR (400 Mz, CDCl 3 ) δ 5.17 (d, J = 8.6 z, 1), 4.74 (ddd, J = 8.8 z, 8.7 z, 6.8 z, 1), 3.55 (d, J = 8.0 z, 1), 3.44 (d, J = 8.0 z, 1), (m, 4), 1.80 (dd, J = 12.2 z, 6.6 z, 1), (m, 6), 1.41 (dd, J = 12.2 z, 9.0 z, 1), 1.10 (app s, 6 ); 13 C NMR (100 Mz, CDCl 3 ) δ 143.4, 123.3, 80.1, 74.9, 48.1, 40.0, 37.1, 29.2, 28.3, 27.9, 27.0, 26.8, 26.5); IR (thin film) 2954, 2925, 2851, 1446 cm -1 ; RMS (FAB) exact mass for [M] + (C ) calcd m/z , found ; [α] D = (c = 1.0, CCl 3 ). Enantiopurity was determined by GC analysis after ozonolysis to the methyl ester ( ºC, 1 ºC/min) t r 8.91 min (minor), 9.21 min (major): 90% ee. Tetrahydropyran 20: Prepared according to the general procedure on a 0.25 mmol scale. Chromatography on Si 2 (17:1 hexanes/etac) afforded the product as a colorless oil (28 mg, 81% yield). 1 NMR (400 Mz, CDCl 3 ) δ 5.16 (d, J = 8.0 z, 1), (m, 2), 3.47 (td, J = 11.4 z, 2.3 z, 1), (m, 1), 1.70 (s, 3), 1.67 (s, 3), (m, 4), (m, 1); 13 C NMR (100 Mz, CDCl 3 ) δ 135.1, 126.4, 74.8, 68.2, 32.1, 25.8, 25.7, 23.5, 18.3; IR (thin film) 2933, 2851, 1440, 1376, 1084, 1033, 900, 754 cm -1 ; RMS (EI) exact mass for [M-] (C 9 16 ) calcd m/z , found ; [α] D = (c = 1.3, CCl 3 ). Enantiopurity was determined by PLC analysis (Chiralcel D- column, 99.9:0.1 hexanes/isopropanol, 0.6 ml/min) t r 7.2 min (minor), 8.6 min (major): 90% ee.

12 Tetrahydropyran 21: This compound has been previously reported in enantioenriched form (S5). Yield was determined by GC analysis versus o-xylene internal standard. Enantiopurity was also determined by GC analysis (40-60 ºC, 1 ºC/min) t r 8.79 min (minor), 9.46 min (major): 92% ee. Determination of absolute stereochemistry: 3, Na Me 2 C C 2 Cl 2 /Me 2-78 ºC 32 To a solution of tetrahydrofuran 2 (40 mg, mmol) in C 2 Cl 2 (2.5 ml) was added a 2.5 M solution of Na in Me (0.6 ml). The resulting mixture was cooled to -78 C and through it was bubbled 3 for 15 min. The mixture was diluted with water (5 ml) and C 2 Cl 2 (5 ml) and then warmed to rt. The layers were separated and the aqueous layer was extracted with C 2 Cl 2 (3 x 5 ml). The combined organic extracts were washed with brine, dried over Na 2 S 4 and concentrated. Purification by column chromatography on Si 2 (3:1 hexanes/etac) afforded 32 as a white solid (20 mg, 64% yield). All spectral data are consistent with those previously reported (S6). [α] D = +3.2 (c = 0.3, Me) [lit. [α] D = +8.5 (c = 1.04, Me)].

13 General Procedure for the Enantioselective ydroamination: A heterogeneous suspension of Ph(C 3 ) 2 PAuCl (5 mol%) and Ag-(R)-7 (5 mol%) in benzene (0.2 M) was stirred for 30 mins at room temperature. To this mixture was added a solution of sulfonamide in benzene. The resulting mixture was stirred for 48 h. Upon reaction completion, the mixture was loaded directly onto a silica gel column. Purification by flash column chromatography afforded the desired pyrrolidine. NS 2 Mes Sulfonamide 22: 1 NMR (400 Mz, CDCl 3 ) δ 6.94 (s, 2), (m, 1), 4.71 (br, 1), 2.92 (q, J = 6.9 z, 2), 2.63 (s, 6), 2.28 (s, 3), (m, 4), 1.91 (q, J = 6.8 z, 2), (m, 8); 13 C NMR (100 Mz, CDCl 3 ) δ 198.2, 141.9, 139.0, 133.6, 131.8, 103.1, 87.2, 41.8, 31.5, 28.5, 27.3, 26.1, 26.0, 22.9, 20.8; IR (thin film) 3288, 2945, 2925, 2826, 1318, 1147, 1082, 850, 650, 535 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found NS 2 Mes Sulfonamide 23: 1 NMR (400 Mz, CDCl 3 ) δ 6.89 (s, 2), 5.19 (t, J = 6.2 z, 1), (m, 1), 2.87 (q, J = 6.8 z, 2), 2.60 (s, 6), 2.22 (s, 3), (m, 4), 1.87 (q, J = 6.8 z, 2), (m, 4), (m, 2); 13 C NMR (100

14 Mz, CDCl 3 ) δ 196.8, 141.6, 138.7, 133.5, 131.5, 103.8, 89.8, 41.6, 30.7, 28.2, 26.7, 25.9, 22.6, 20.5; IR (thin film) 3301, 2950, 2865, 1604, 1436, 1320, 1151, 851, 653 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found NS 2 Mes Sulfonamide 24: 1 NMR (400 Mz, CDCl 3 ) δ 6.95 (s, 2), (m, 1), 4.52 (t, J = 7.0 z, 1), (m, 2), 2.64 (s, 6), 2.29 (s, 3), 1.82 (d, J = 7.6 z, 2), 1.63 (s, 3), 1.62 (s, 3), 0.83 (s, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 203.3, 142.0, 138.9, 133.5, 131.9, 94.2, 84.0, 51.9, 39.9, 34.3, 24.7, 22.9, 20.9, 20.5; IR (thin film) 3313, 2975, 2956, 2847, 1450, 1327, 1149, 841, 654 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found NS 2 Mes Sulfonamide 25: 1 NMR (400 Mz, CDCl 3 ) δ 6.95 (s, 2), (m, 1), 4.46 (t, J = 7.2 z, 1), 2.75 (d, J = 7.2 z, 2), 2.65 (s, 6), 2.30 (s, 3), 1.90 (d, J = 8.0 z, 2), 1.65 (s, 3), 1.64 (s, 3), (m, 10); 13 C NMR (100 Mz, CDCl 3 ) δ 203.0, 142.0, 139.0, 133.6, 131.9, 94.4, 83.6, 48.5, 36.6, 33.2, 26.0, 23.0, 21.2, 20.9, 20.5; IR (thin film) 3310, 2977, 2921, 2848, 1324, 1157, 655 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found

15 S 2 Mes N Pyrrolidine 26: Prepared according to the general procedure on a 0.19 mmol scale. Chromatography on Si 2 (15:1 hexanes/etac) afforded the product as a colorless oil (64 mg, 97% yield). 1 NMR (400 Mz, CDCl 3 ) δ 6.88 (s, 2), 4.67 (d, J = 9.2 z, 1), (m, 1), 3.60 (dt, J = 10.0 z, 7.0 z, 1), 3.28 (dt, 1, J = 10.0 z, 6.6 z) 2.60 (s, 6), 2.26 (s, 3), (m, 1), (m, 2), (m, 2), (m, 1), (m, 1), (m, 1), (m, 6); 13 C NMR (100 Mz, CDCl 3 ) δ 141.9, 140.5, 140.1, 134.0, 131.5, 121.9, 56.3, 47.4, 36.7, 34.7, 28.7, 28.0, 27.3, 26.5, 24.4, 22.8, 20.9; IR (thin film) 2926, 2853, 1311, 1148, 1059, 671, 596 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found ; [α] D = -48 (c = 0.73, CCl 3 ). Enantiopurity was determined by PLC analysis (Chiralcel J- column, 98:2 hexanes/isopropanol, 1 ml/min) t r 7.2 min (minor), 8.9 min (major): 96% ee. S 2 Mes N Pyrrolidine 27: Prepared according to the general procedure on a 0.15 mmol scale. Chromatography on Si 2 (17:1 hexanes/etac) afforded the product as a colorless oil (44 mg, 88% yield). 1 NMR (400 Mz, CDCl 3 ) δ 6.87 (s, 2), 4.79 (d, J = 7.6 z, 1), (m, 1), 3.61 (dt, J = 9.9 z, 6.9 z, 1), 3.32 (dt, J = 9.6 z, 6.8 z,

16 1) 2.58 (s, 6), 2.25 (s, 3), (m, 2), (m, 4), (m, 1), (m, 5); 13 C NMR (100 Mz, CDCl 3 ) δ 144.7, 141.8, 140.0, 134.2, 131.4, 120.0, 58.8, 47.2, 33.8, 33.4, 28.1, 26.2, 25.8, 24.2, 22.7, 20.8; IR (thin film) 2947, 2868, 1311, 1146, 1059, 851, 671, 595 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found ; [α] D = -52 (c = 0.95, CCl 3 ). Enantiopurity was determined by PLC analysis (Chiralcel D- column, 99.5:0.5 hexanes/isopropanol, 1 ml/min) t r 13.6 min (major), 17.6 min (minor): 98% ee. S 2 Mes N Pyrrolidine 28: Prepared according to the general procedure on a 0.15 mmol scale. Chromatography on Si 2 (15:1 hexanes/etac) afforded the product as a white solid (42 mg, 84% yield). 1 NMR (400 Mz, CDCl 3 ) δ 6.86 (s, 2), (m, 2), 3.55 (dd, J = 10.0 z, 1.2 z, 1), 3.08 (d, J = 10.0 z, 1) 2.58 (s, 6), 2.25 (s, 3), (m, 1), 1.50 (s, 3), (m, 1), 1.25 (s, 3), 1.13 (s, 3), 1.09 (s, 3); 13 C NMR (100 Mz, CDCl 3 ) δ 141.7, 139.9, 134.7, 132.9, 131.3, 125.2, 60.4, 57.1, 48.3, 37.1, 26.5, 26.2, 25.3, 22.8, 20.8, 17.8; IR (thin film) 2960, 2927, 2864, 1450, 1315, 1145, 1059, 670, 592 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found ; [α] D = -22 (c = 1.0, CCl 3 ); PLC Chiralcel D- column (99:1 hexanes/isopropanol, 1 ml/min) t r 6.8 min (minor), 8.1 min (major): 99% ee.

17 S 2 Mes N Pyrrolidine 29: Prepared according to the general procedure on a 0.13 mmol scale. Chromatography on Si 2 (15:1 hexanes/etac) afforded the product as a white solid (36 mg, 73% yield). 1 NMR (400 Mz, CDCl 3 ) δ 6.86 (s, 2), (m, 2), 3.64 (d, J = 10.0 z, 1), 3.09 (d, J = 10.4 z, 1) 2.58 (s, 6), 2.26 (s, 3), 1.94 (dd, J = 12.8 z, 7.2 z, 1), (m, 11), 1.50 (s, 3), 1.25 (s, 3); 13 C NMR (100 Mz, CDCl 3 ) δ 141.7, 140.0, 134.7, 132.9, 131.3, 125.3, 57.9, 56.4, 46.0, 40.8, 36.8, 34.8, 26.0, 25.3, 23.7, 22.9, 22.7, 20.8, 17.8; IR (thin film) 2927, 2851, 1319, 1144, 671, 598 cm -1 ; RMS (FAB) exact mass for [M+] + (C N 2 S) calcd m/z , found ; [α] D = -7.1 (c = 0.91, CCl 3 ); PLC Chiralcel D- column (99:1 hexanes/isopropanol, 1 ml/min) t r 6.5 min (minor), 8.5 min (major): 98% ee. Determination of Absolute Stereochemistry: S 2 Mes N 1) 2, Pd/C, Me, 2 h N 26 96% ee 2) Na/g, Na 2 P 4, Me, reflux, 36 h 33 [!] D = + 10 (c = 0.71, CCl 3 ) A solution of pyrrolidine 26 (73 mg, 0.21 mmol) in Me (5 ml) was treated with Pd/C (5% w/w, 45 mg, 0.02 mmol) and the reaction mixture was stirred under a 2 balloon. After 2 h, the solution was filtered through a celite pad and the resulting filtrate

18 was concentrated. Purification by flash chromatography (Si 2, 10:1 hexanes:et 2 ) gave the hydrogenated pyrrolidine 26A (51 mg, 70%) as a colorless oil. 1 NMR (400 Mz, CDCl 3 ) δ 6.94 (s, 2), (m, 1), 3.48 (dt, J = 10.3 z, 7.3 z, 1), (m, 1), 2.65 (s, 6), 2.30 (s. 3), (m, 1), (m, 2), (m, 4), (m, 1), (m, 2), (m, 5), (m, 2); 13 C NMR (100 Mz, CDCl 3 ) δ 142.3, 140.1, 133.4, 131.7, 57.2, 46.8, 42.5, 34.9, 34.0, 32.3, 31.3, 26.4, 26.1, 26.0, 24.2, 22.9, 20.9; [α] D = +8.3 (c = 0.47; CCl 3 ). To a solution of pyrrolidine 26A (30 mg, mmol) in Me (5 ml) was added Na 2 P 4 (138 mg, 0.52 mmol) and Na/g amalgam (8% Na(g), 1.3 g, 4.3 mmol) and the mixture was refluxed for 36 h. An aqueous solution of N 4 (30%, 10 ml) was added and the mixture was extracted with C 2 Cl 2 (25 ml). This organic layer was washed with brine (15 ml), dried over Na 2 S 4 and concentrated to give the desired pyrrolidine 33 (14 mg, 99%) as a colorless oil. 1 NMR (400 Mz, CDCl 3 ) δ (m, 2), 2.80 (dt, J = 10.4 z, 7.6 z, 1), (m, 2), (m, 6), (m, 7), (m, 2); 13 C NMR (100 Mz, CDCl 3 ) δ 56.7, 46.5, 44.3, 35.8, 33.9, 33.4, 32.3, 26.6, 26.3, 26.3, 25.4; [α] D = +10 (c = 0.71; CCl 3 ) (for ent-33, lit. [α] D = -13 (c = 0.92; CCl 3 ), S3). Carboxylic acid 30: 1 NMR (400 Mz, CDCl 3 ) δ 11.5 (br, 1), 2.45 (t, J = 7.2 z, 2), (m, 2), 1.66 (s, 3), 1.65 (s, 3); 13 C NMR (100 Mz, CDCl 3 ) δ

19 201.5, 180.1, 97.1, 87.2, 33.0, 23.8, 20.5; IR (thin film) 2934, 2911, 1706, 1410, 1282, 1204, 909 cm -1 ; RMS (EI) exact mass for [M] + (C ) calcd m/z , found Spectral data are consistent with those previously reported (S7). Lactone 31: A flask was charged with (S)-BINAP(AuCl) 2 (9 mg, 9 µmol, 2.5 mol%) and Ag-(R)-7 (15 mg, 18 µmol, 5 mol%). The mixture was dissolved in benzene (1.8 ml) and stirred for 30 mins at room temperature. After this time, a solution of 30 (50 mg, 0.36 mmol) was added as a solution in benzene (1.8 ml). The resulting mixture was stirred for 24 h, then filtered through a silica gel plug and concentrated. Chromatography on Si 2 (2:1 hexanes/ether) afforded the product as a colorless oil. 1 NMR (400 Mz, CDCl 3 ) δ (m, 2), (m, 2), (m, 1), (m, 1), 1.78 (s, 3), 1.74 (s, 3); 13 C NMR (100 Mz, CDCl 3 ) δ 177.3, 139.9, 122.7, 29.3, 29.2, 25.7, 18.9; IR (thin film) 1766, 1175, 912 cm -1 ; RMS (EI) exact mass for [M] + (C ): calcd m/z , found ; [α] D = (c = 0.55, CCl 3 ); this optical rotation establishes the absolute stereochemistry as (S) as reported in ref. S8. Enantiopurity was determined by PLC analysis (Regis Technologies Whelk-1 column, 97:3 hexanes/isopropanol, 0.6 ml/min) t r 42.2 min (minor), 45.4 min (major): 82% ee.

20 References and Notes S1. M. J. Johansson, D. J. Gorin, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 127, (2005). S2. Z. Zhang, C. Liu, R. E. Kinder, X. an,. Qian, R. A. Widenhoefer, J. Am. Chem. Soc. 128, 9066 (2006). S3. R. L. LaLonde, B. D. Sherry, E. J. Kang, F. D. Toste, J. Am. Chem. Soc. 129, 2452 (2007). S4. J. Seayad, A. M. Seayad, B. List, J. Am. Chem. Soc. 128, 1086 (2006). S5. R. Lazzaroni, G. Uccello-Barretta, D. Pini, S. Pucci, P. Salvadori, J. Chem. Res., Synop. 11, 286 (1983). S6. R. Alajarin, J. J. Vaqueo, J. Alvarez-Builla, M. Pastor, C. Sunkel, M. F. De Casa- Juana, J. Priego, P. R. Statkow, J. Sanz-Aparicio, J. Fonseca, J. Med. Chem. 38, 2830 (1995). S7. C. Jonasson, A. orváth, J.-E. Bäckvall, J. Am. Chem. Soc. 122, 9600 (2000). S8. M. Liu, R. M. Silverstein, uaxue Xuebao 43, 467 (1985).