Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2009

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1 Supporting Information Copyright Wiley-VC Verlag Gmb & Co. KGaA, Weinheim, 2009

2 A Stereodivergent Strategy to Both Product Enantiomers from the Same Enantiomer of a Stereoinducing Catalyst: Agelastatin A Barry M. Trost * and Guangbin Dong Department of Chemistry, Stanford University, Stanford, California bmtrost@stanford.edu S1

3 Supporting Information General: All reactions were run under an atmosphere of nitrogen unless otherwise indicated. Anhydrous solvents were transferred via oven-dried syringe or cannula. Flasks were flame-dried under vacuum and cooled under a stream of nitrogen or argon. Tetrahydrofuran (TF), and dimethoxyethane (DME), Benzene, pyridine, diisopropylamine, triethylamine, diisopropylethylamine, and dimethylsulfoxide, acetonitrile, hexane, toluene, diethyl ether, and dichloromethane were purified with a Solv-Tek solvent purification system by passing through a column of activated alumina. Acetone was distilled from calcium sulfate. Methanol was distilled from magnesium methoxide. Where indicted, solvents are degassed via freezing in liquid nitrogen and thawing under high vacuum. The above cycle is repeated three times, unless otherwise indicated. Analytical thin layer chromatography (TLC) was carried out using 0.2 mm commercial silica gel plates (DC-Fertigplatten Krieselgel 60 F 254 ). Preparative column chromatography employing silica gel was performed according to the method of Still. Melting points were determined on a Thomas-oover melting point apparatus in open capillaries and are uncorrected. Infrared spectra were recorded on a Perkin-Elmer 1420 spectrophotometer. Absorbance frequencies are reported in reciprocal centimeters (cm -1 ). Proton nuclear magnetic resonance ( 1 MR) spectra were recorded using a Varian UI-600 (600 Mz), UI-500 (500 Mz) or Varian MERC-400 (400 Mz). Chemical shifts are reported in delta (δ) units, part per million (ppm) downfield from tetramethylsilane (TMS) or in ppm relative to the singlet at 7.26 ppm for deuterochloroform. Coupling constants are reported in ertz (z). The following abbreviations are used: s, singlet, d, doublet, t, triplet, q, quartet, m, multiplet. S2

4 Carbon-13 nuclear magnetic resonance ( 13 C MR) spectra were recorded using a Varian UI-600 (150 Mz), Varian UI-500 (125 Mz) or Varian MERC-400 (100 Mz). Chemical shifts are reported in delta (δ) units, part per million (ppm) relative to the center line of the triplet at 77.1 ppm for deuterochloroform. 13 C MR spectra were routinely run with broadband decoupling. ptical rotation data was obtained with a Jasco DIP-360 digital polarimeter at the sodium D line (589 nm) in the solvent and concentration indicated. Boc Boc 8 Compound 8: According to a procedure reported by oulihan et al., 1 to a solution of cyclopent-4-ene-1,3-diol (1 g, 10 mmol), Boc 2 (5.45 g, 25 mmol) and (n- Bu) 4 S 4 (340 mg, 1 mmol) in DCM (5 ml) was added a solution of 30% aqueous a (8 ml) at 0 o C. The mixture was stirred vigorously for 12 h at rt, before more Boc 2 (1.5 g) and a (30% aqueous solution, 3 ml) were added. The resulting mixture was stirred vigorously for another 12 hr, before brine (20 ml) was added. The mixture was extracted with C 2 Cl 2 three times and the combined organic fractions were dried over MgS 4. Compound 8 was purified by silica gel flash column chromatography (petroleum ether / diethyl ether = 25/1, then 10/1) to give a white solid (2.4 g, 80%): mp: o C; R f : 0.4 (petroleum ether / ethyl acetate = 20/1); 1 MR (CDCl 3, 500 Mz) δ 6.11 (s, 2), 6.38 (dd, J = 7.5, 4.0 z, 2), (m, 1), 1.87 (dt, J = 15, 4.0 z, 1), 1.47 (s, 18); 13 C MR (CDCl 3, 75Mz) δ 153.0,134.5, 82.2, 78.8, 37.0, 27.7; IR (film): 2981, 1738, 1459, 1395, 1370, 1339, 1272, 1253, 1159, 1087, 850 cm -1 ; ESI (C ): [M+a] +. 9 Me Compound 9: To a solution of pyrrole-2-carboxylate methyl ester (2.0 g, 16 mmol) in TF (160 ml) and Me (80 ml) was added BS (recrystalized, 0.49 g, 2.8 mmol) at S3

5 0 o C. The reaction was stirred at 0 o C for 30 min, before another portion of BS (recrystalized, 0.63 g, 3.5 mmol) was added. After 40 min, more BS (recrystalized, 0.51 g, 2.9 mmol) was added to the reaction mixture. After another 30 min, another portion of BS (recrystalized, 1.27 g, 7.1 mmol) was added. The resulting solution was then stirred for another 2 h, before the solvent was removed under vacuum. Compound 9 was purified via silica gel flash column chromatography (petroleum ether / diethyl ether = 20/1, then 8/1) to give a white floppy solid (1.63 g, 50%): mp: o C; R f : 0.35 (petroleum ether / ether = 4/1); 1 MR (CDCl 3, 400 Mz): δ 9.1 (br s, 1), 6.82 (dd, J = 3.0, 3.5 z, 1), 6.21 (dd, J = 3.0, 3.5 z, 1), 3.86 (s, 3); 13 C MR (CDCl 3, 100 Mz) δ 160.8, 123.7, 116.8, 112.7, 105.2, 51.8; IR (film): 3250, 2924, 2853, 1702, 1552, 1449, 1415, 1389, 1327, 1207 cm -1 ; RMS (C ): Calc d (M + ), Found Boc Me 10 Compound 10: (eg. Table 1, entry 5) A solution of [Pd(p-C 3 5 )Cl] 2 (18.3 mg, 0.05 mmol) and (R,R)-L ST (103.5 mg, 0.15 mmol) in C 2 Cl 2 (degassed, 15 ml) which had been stirred for 10 min at rt, was added to a mixture of compound 8 (750 mg, 2.5 mmol) compound 9 (512.5 mg, 2.5 mmol) and Cs 2 C 3 (815 mg, 2.5 mmol) under Ar. The mixture was stirred at rt for 2 to 3 h, and it was then filtered through a celite cake. After removal of the solvent under vacuum, Compound 10 was purified via silica gel flash column chromatography (petroleum ether / diethyl ether = 25/1) to give a thick yellow oil (846 mg, 88%, 87% ee by PLC D column, 98:2 heptane: i-propanol, 1 ml/min): R f : 0.5 (petroleum ether / ethyl acetate = 8/1); [α] 22 D: 2.64 (C 2 Cl 2, c 0.94); 1 MR (CDCl 3, 500 Mz) δ 6.93 (d, J = 4.0 z, 1), (m, 1), 6.19 (d, J = 4.0z, 1), 6.11 (ddd, J = 2.0, 2.0, 5.5 z, 1), 6.01 (ddd, J = 2.0, 2.5, 5.5 z, 1), (m, 1), 3.80 (s, 3), 3.10 (ddd, J = 8.0, z, 1), 2.29 (ddd, J = S4

6 6.5, 8.0, 13.5 z, 1); 13 C MR (CDCl 3, 125 Mz) δ 160.8, 153.1, 135.7, 130.8, 123.8, 119.1, 113.5, 109.7, 82.3, 79.7, 60.2, 51.3, 38.2, 27.8; IR (film): 2981, 1736, 1708, 1522, 1441, 1410, 1369, 1339, 1275, 1255, 1224, 1156, 1131, 1094 cm -1 ; RMS (C ): Calc d (M + ), Found Boc 11 Compound 11: A solution of Li (1, 4.7 ml) was added to a solution of compound 10 (605 mg, 1.57 mmol) in TF (15 ml) and 2 (0.3 ml). The resulting mixture was stirred at rt for 48 h, before it was concentrated under vacuum. The aqueous phase was diluted with water, and then acidified to p 1-2 by addition of aqueous Cl solution (3 ). Preformed white precipitate was collected and washed with water (2 ml) twice, and it was then dried under high vacuum. Compound 11 was obtained as a white powder (500 mg, 86%): mp: o C; R f : 0.5 (DCM / Me = 8/1); [α] D : (C 2 Cl 2, c 0.72); 1 MR (CDCl 3, 500 Mz): δ 7.11 (d, J = 4.4 z, 1), 6.54 (td, J = 8.0, 2.0 z, 1), 6.24 (d, J = 4.4 z, 1), (m, 1), (m, 1), 5.57 (td, J = 1.6, 8.0 z, 1), (m, 1), (m, 1); 13 C MR (CDCl 3, 125 Mz): δ 164.6, 153.2, 135.5, 131.0, 122.9, 121.2, 114.1, 111.3, 82.3, 79.6, 60.4, 38.2, 27.8; IR (film): 3200, 2981, 2926, 1736, 1670, 1523, 1448, 1403, 1276, 1254, 1162 cm -1 ; RMS (C ): Calc d (M + ), Found Boc C 3 7 S5

7 Compound 7: To a solution of compound 11 (100 mg, 0.27 mmol) in TF (2.7 ml) were added (CCl) 2 (36.8 mg, 0.29 mmol) and one drop of DMF. The resulting solution named A was then stirred for 1 h at rt. In another separate operation, water (0.3 ml) was added to a mixture of 2 Me Cl (225.5 mg, 2.7 mmol) and K 2 C 3 (372.6 mg, 2.7 mmol). The resulting mixture was stirred at rt for 0.5 h, before it was added to the above solution A. This mixture was allowed to stir for 12 h at rt before it was extracted with ethyl acetate (10 ml) three times. The combined the organic phase was washed once with brine (10 ml) and then dried over MgS 4. Compound 7 was purified by silica gel flash column chromatography (C 2 Cl 2, then C 2 Cl 2 / Me = 40/1) to give a yellow solid (87.7 mg, 85%): mp: o C; Rf: 0.6 (C 2 Cl 2 / Me = 9/1); [α] D : (C 2 Cl 2, c 0.74); 1 MR (CDCl 2, 500 Mz): δ?8.47 (br, 1) 6.50 (d, J = 4 z, 1), (m, 1), 6.13 (d, J = 4 z, 1), 6.11 (dt, J = 6, 2 z, 1), 6.00 (dt, J = 6, 2 z, 1), (m, 1), 3.81 (s, 3), (ddd, J = 13.5, 7.5 z, 1), (ddd, J = 13.5, 7.5, 6.5 z, 1), 1.47 (s, 9); 13 C MR (CDCl 2, 125 Mz): δ160.9, 153.1, 135.5, 131.2, 124.7, 113.7, 112.8, 108.4, 82.3, 79.6, 64.4, 60.5, 38.2, 27.8; IR (film): 3244, 2979, 2933, 1738, 1651, 1530, 1416, 1340, 1277, 1161, 1096, 1055 cm -1 ; RMS (C ): Calc d (M + ), Found C 3 6 Compound 6: A solution of Pd 2 (dba) 3 CCl 3 (2.29 mg, mmol) and (R,R)-L ST (5.18 mg, mmol) in C 2 Cl 2 (1 ml), which had been stirred at rt for 10 min, was added to a mixture of compound 7 (20 mg, 0.05 mmol) and Cs 2 C 3 (16.3 mg, 0.05 mmol) under Ar. The mixture was stirred at rt for 12 h, and then filtered through a celite cake. The solvent was removed under vacuum, and compound 6 was purified via silica gel flash column chromatography (petroleum ether / ether = 8/1, then C 2 Cl 2 / Me = 40/1) to give a white solid (12.9 mg, 91.5%): mp: o C; R f : 0.6 S6

8 (C 2 Cl 2 / Me = 9/1); [α] D : (C 2 Cl 2, c 0.34); 1 MR (CDCl 3, 500 Mz) δ 6.94 (dd, J = 1, 4 z, 1), 6.30 (dd, J = 1, 4 z, 1), (m, 1), (m, 1), (m, 2), 3.85 (s, 3), (m, 1), (m, 1); 13 C MR (CDCl 3, 125 Mz) δ 156.3, 135.5, 128.6, 123.7, 116.1, 106.8, 101.6, 64.1, 64.0, 57.2, 38.2; IR (film): 2927, 2853, 1668, 1545, 1418, 1358, 1334, 1310, 1027 cm -1 : RMS (C ): Calc d (M + ), Found Ts C 3 12 Compound 12: Benzene (1 ml) was added to a mixture of 4 Å molecular sieve (75 mg), compound 6 (20 mg, mmol), PhI=Ts (132 mg, mmol) and catalyst 13 (17.3 mg, mmol) under 2. The resulting mixture was stirred at rt for 4 h, before it was filtered through a silica gel cake and rinsed with ethyl acetate. The solvent was removed under vacuum, and compound 12 was purified via alumina (neutral, activity 3) flash column chromatography (petroleum ether / ethyl acetate = 8/1, 4/1, then 3/1) to give a colorless foam (16.6 mg, 52%): R f : 0.5 (petroleum ether / ethyl acetate=3/2); [α] D : (c 0.85, CCl 3 ); 1 MR (CDCl 3, 500 Mz): δ 7.86 (dd, J = 1.5, 6.5 z, 2), 7.40 (dd, J = 0.5, 8.5 z, 2), 6.94 (d, J = 4.0 z, 1), 6.26 (d, J = 4.5 z, 1), (m, 2), 3.97 (s, 3), 3.88 (d, J = 5 z, 1), 3.61 (dd, J = 2.5, 5.0 z, 1), 2.77 (dd, J = 7.0, 14 z, 1), 2.48 (s, 3), 1.93 (ddd, J = 14.5, 9.0, 2.5 z, 1); 13 C MR (CDCl 3, 125 Mz) δ 158.2, 145.5, 134.8, 130.3, 128.2, 122.8, 116.2, 114.1, 106.2, 64.5, 61.3, 53.3, 44.7, 44.1, 32.9, 22.0; IR (film): 2925, 2855, 1682, 1543, 1433, 1416, 1325, 1163 cm -1 ; RMS (C S): Calc d (M + ), Found S7

9 Ts C 3 15 Compound 15: TFA (30 µl) was added to a solution of compound 12 (18 mg, 0.04 mmol) in dioxane (0.9 ml) and water (0.6 ml) under 2. The resulting solution was heated in a microwave at 150 o C for 2.5 h. The residue was diluted with ethyl acetate, washed with saturated ac 3, then washed with brine, and finally dried over MgS 4.Compound 15 was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 4/1, then 1/1) to give a colorless foam: R f : 0.2 (petroleum ether / ethyl acetate = 1/1); [α] D : (c 0.90, C 2 Cl 2 ); 1 MR (CDCl 3, 500 Mz) δ 7.80 (d, J = 8 z, 2), 7.35 (d, J = 8 z, 2), 6.91 (d, J = 4 z, 1), 6.28 (d, J = 4 z, 1), 5.68 (d, J = 3.5 z, 1), (m, 1), 4.33 (dd, J = 7.5, 14 z, 1), 4.23 (dd, J = 3.5, 7.0 z, 1), 3.63 (dd, 1), 3.54 (br, 1), (m, 1), 2.44 (s, 3), (m, 1) ; 13 C MR (CDCl 3, 125 Mz) δ , 144.5, 135.3, 130.0, 127.4, 122.8, 115.7, 114.1, 105.8, 75.8, 65.7, 64.3, 63.0, 53.3, 38.6, 21.6; IR (film): 3435, 3238, 2828, 1652, 1540, 1415, 1338, 1160, 2093 cm -1 ; RMS (C S): Calc d (M + ), Found Ts C 3 5 Compound 5: a) From Compound 15: To a solution of compound 15 (10 mg, mmol) and ac 3 (5.4 mg, mmol) in C 2 Cl 2 (0.25 ml) was added Dess-Martin periodinane (13.5 mg, mmol). The resulting mixture was stirred at rt for 30 min before quenched with sat. aq. a 2 S 2 3. Compound 5 was purified via S8

10 silica gel flash column chromatography (petroleum ether / ethyl acetate = 3/1, then 3/2) as a white solid (ca. 7 mg 70-80%). b) From Compound 12: DMS (1 ml) was added to a mixture of compound 12 (30 mg, mmol) and In(Tf) 3 (26 mg, mmol) at rt under 2. The resulting solution was heated at 80 o C for 6 h, before diluted with ethyl acetate (30 ml). The solution was washed with brine. The aqueous phases were combined, and extracted with ethyl acetate three times. The combined the organic phase was dried over MgS 4, and compound 5 was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 3/1, then 3/2) to give a white solid (28.3 mg, 91%): mp: o C, R f : 0.3 (petroleum ether / ethyl acetate = 1/1); [α] D : (c 0.97, C 2 Cl 2 ); 1 MR (CDCl 3, 500 Mz) δ 7.82 (d, J = 8.0 z, 2), 7.37 (d, J = 8.0 z, 2), 7.03 (d, J = 4.0 z, 1), 6.35 (d, J = 4.0 z, 1), 5.63 (d, J = 7.5 z, 1), (m, 1), 5.00 (d, J = 2.5 z, 1), 4.98 (d, J = 5.5 z, 1), 4.00 (br, 1), 3.84 (s, 3), 3.02 (dd, J = 7.5, 18 z, 1), 2.68 (dd, J = 11, 18 z, 1), 2.46 (s, 3); 13 C MR (CDCl 3, 125 Mz) δ 206.3, 157.9, 144.7, 134.7, 130.0, 127.7, 122.6, 116.7, 114.3, 106.4, 64.1, 61.1, 51.9, 41.2, 29.7, 21.6; IR (film): 3252, 2924, 2854, 1768, 1652, 1548, 1416, 1338, 1162, 1093, 1025 cm -1 ; RMS (C S): Calc d (M + ), Found C Ts C 3 16 Compound 16: To a mixture of compound 5 (15 mg, mmol), Cs 2 C 3 (2.2 mg, mmol) in C 2 Cl 2 (0.5 ml), was added a solution of C 3 C (2.3 mg, in 0.85 ml benzene) via a syringe pump over 2 h at rt. The resulting mixture was stirred for another 2 h before quenched with K 2 P 4 (5 ml, 1.0 M). The mixture was extracted with CCl 3 (5 ml) twice, and then extracted with ethyl acetate (5 ml) twice. The S9

11 organic phases were combined, and dried over MgS 4. Compound 16 was purified via silica gel column chromatography (petroleum ether / ethyl acetate = 4/1, then 2/3, then 1/1) to give a foam-like colorless solid (9.0 mg, 53%): R f : 0.4 (petroleum ether / ethyl acetate = 2/3); [α] D : (c 0.73, CCl 3 ); 1 MR (CDCl 3, 500 Mz) δ 7.98 (d, J = 8.0 z, 2), 7.37 (d, J = 8.0 z, 2), 6.96 (d, J = 4.0 z, 1), 6.29 (d, J = 4.0 z, 1), 5.76 (s, 1), 5.04 (s, 1), 4.65 (m, 2), 3.95 (s, 3), 2.88 (s, 3), 2.67 (dd, J = 7.5, 13 z, 1), 2.43 (s, 3), 2.32 (dd, J = 13, 13 z, 1); 13 C MR (CDCl 3, 125 Mz) δ 156.6, 152.8, 145.6, 135.3, 130.1, 128.2, 122.6, 116.9, 114.0, 106.3, 91.6, 66.4, 65.5, 62.0, 53.4, 38.9, 25.1, 21.8; IR (film): 3290 (br), 2924, 1743, 1651, 1545, 1414, 1344, 1305, 1175, 1092, 1026 cm -1 ; RMS (C S): Calc d (M + ), Found C (+)-agelastatin A (1) (+)-Agelastatin A (1): Freshly made SmI 2 (1.6 ml, 0.1 M in TF) was added to compound 16 (10.0 mg, mmol) under argon at 0 o C. The resulting blue solution was allowed to gradually warm to rt and stirred for 2 h before another 0.5 ml SmI 2 (0.1 M in TF) was added. After the solution was stirred at rt for 15 min, TF was removed under vacuum. The residue was first purified by silica gel chromatography (10% to 15% Me in C 2 Cl 2 ). A yellow solid was obtained, which was then dissolved in 15% Me in C 2 Cl 2 and filtered through charcoal. The (+)-Agelastatin A was further purified by another silica gel chromatography (10% to 15% Me in C 2 Cl 2 ) to give an off-white solid (6.0 mg, 88%): mp: 195 o C (decomposed); R f : 0.25 (10% Me in C 2 Cl 2 ); [α] D : (c 0.13, Me); 1 MR (CD 3 D, 500 Mz): δ 6.91 (d, J = 4.0 z, 1), 6.33 (d, J = 4.0 z, 1), 4.60 (m, 1), 4.09 (d, J = 5.5 z, 1), 3.89 (s, 1), 2.81 (s, 3), 2.65 (dd, J = 6.5, 13 z, 1), 2.10 (dd, J = 13, 13 z, 1); 13 C MR (CD 3 D, 150 Mz) δ 161.4, 161.1, 124.1, 116.0, 113.8, 107.2, 95.7, S10

12 67.4, 62.2, 54.4, 40.0, 24.2; IR (film): 3346 (br), 2923, 1685, 1644, 1555, 1424, 1380 cm -1 ; ESI (C ): [M+] +, [M+a] +. Me 21 Compound 21: 2-(Trichloroacetyl)pyrrole 20 (1.08 g, 5 mmol), 2 Me Cl (625 mg, 7.5 mmol) and Et 3 (2.1 ml) were sealed in a tube. After the mixture was stirred at 80 o C overnight, Et 3 was removed under vacuum. The residue was then diluted with C 2 Cl 2. Compound 21 was purified by silica gel flash column chromatography (petroleum ether / ethyl acetate = 3/2, then 1/1) to give an off-white solid (687.5 mg, 98%): mp: o C; R f : 0.25 (petroleum ether / ethyl acetate = 1/1); 1 MR (CDCl 3, 400 Mz) δ (br, 1), 9.90 (br, 1), 6.93 (s, 1), 6.82 (s, 1), 6.19 (d, J = 2.4 z, 1), 3.80 (s, 3); 13 C MR (CDCl 3, 100 Mz) δ 161.4, 122.9, 122.4, 112.2, 110.0, 64.7; IR (film): 3240 (br), 2980, 1628, 1554, 1507, 1439, 1405, 1330, 1096, 1047 cm -1 ; RMS (C ): Calc d (M + ), Found Me 17 Compound 17: BS (225 mg, 1.26 mmol) was added to a solution of compound 21 (446 mg, 3.19 mmol) in TF (35 ml) and Me (17 ml) at 0 o C. After the mixture was stirred for 30 min, another portion of BS (314 mg, 1.76 mmol) was added. The resulting solution was allowed to warm to rt and stirred overnight. After removal of the solvent, compound 17 was purified by silica gel flash column chromatography (petroleum ether / ethyl acetate = 7/3, then 3/2) to give an off-white solid (662 mg, 95%): mp: o C; R f : 0.3 (petroleum ether / ethyl acetate = 1/1); 1 MR (CD 3 D, 400 Mz) δ 6.64 (d, J = 4.0 z, 1), 6.12 (d, J = 4.0 z, 1), 3.75 (s, 3); 13 C MR (CD 3 D, 100 Mz) δ 161.4, 125.5, 113.3, 112.5, 105.2, 64.6; IR (film): S11

13 3207 (br), 3002, 1622, 1553, 1505, 1411, 1327, 1046 cm -1 ; RMS (C ): Calc d (M + ), Found Me 19 Compound 19: (eg. Table 4, entry 11) A solution of Pd 2 (dba) 3 CCl 3 (5.2 mg, mmol) and (R,R)-L ST (10.4 mg, mmol) in degassed C 2 Cl 2 (0.5 ml), which had been stirred for 10 min at 0 o C, was added to a mixture of compound 17 (21.9 mg, 0.1 mmol), compound 8 (45 mg, 0.15 mmol) and Ac (10 µl, 1M solution in C 2 Cl 2 ) under Ar. The mixture was stirred at rt for 3.5 h, and then was added a solution of Pd 2 (dba) 3 CCl 3 (5.2 mg, mmol) and Rac-L ST (10.4 mg, mmol) in degassed C 2 Cl 2 (0.5 ml), which had been stirred for 10 min at rt. The resulting solution was stirred at rt for 3 h. Compound 19 was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 4/1, then 3/1) as a colorless solid (23.0 mg, 82%, 97.5% ee by PLC D column, 90:10 heptane: i-propanol, 0.8 ml/min): mp: o C; R f : 0.2 (petroleum ether / ethyl acetate = 4/1); [α] D : (c 1.0, C 2 Cl 2 ); 1 MR (CDCl 3, 500 Mz) δ 6.91 (d, J = 5.0 z, 1), 6.28 (d, J = 5.0 z, 1), 6.02 (m, 1), 5.95 (m, 1), 5.29 (d, J = 8.0 z, 1), 4.65 (ddd, J = 8.0, 6.5, 2.5 z, 1), 3.85 (s, 3), 2.92 (d, J = 21.5 z, 1), 2.71 (ddd, J = 21.5, 6.5, 2.5 z, 1); 13 C MR (CDCl 3, 125 Mz) δ 157.3, 132.0, 129.0, 123.8, 114.7, 113.6, 104.8, 63.0, 61.6, 60.7, 36.4; IR (film): 2925, 2854, 1667, 1545, 1417, 1320, 1028 cm -1 ; RMS (C ): Calc d (M + ), Found Ts Me 22 S12

14 Compound 22: A solution of dry pyridine (0.001 ml) in dry benzene (0.01 ml) was added to a solution of -sulfinyl-p-toluene sulfonamide (0.11 g) in dry benzene (0.19 ml) at rt. The resulting mixture was stirred at rt for 1 h, and then it was diluted with toluene (1 ml). The resulting suspension was added to compound 19 (22 mg) portionwisely at rt. The mixture was then heated at 100 o C for 40 h. The solvents were removed under vacuum. Methanol (1.5 ml) and trimethyl phosphite (0.03 ml, 0.25 mmol) were added to the residue and the resulting mixture was stirred at rt for 1 h. The solvents were removed under vacuum and the residue was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 4/1, then 3/1, then 2/1) to give compound 22 as a off-white foam (15 mg, 43%): [α] D : (c 0.90, C 2 Cl 2 ); R f : 0.2 (petroleum ether / ethyl acetate = 4/1); 1 MR (CDCl 3, 500 Mz) δ 7.79 (d, J = 8.0 z, 2), 7.33 (d, J = 8.0 z, 2), 6.89 (d, J = 4.0 z, 1), 6.29 (d, J = 4.0 z, 1), 6.02 (d, J = 5.5 z, 1), 5.85(m, 1), 5.55(d, J = 6.5 z, 1), 4.91 (d, J = 6 z, 1), 4.69 (m, 1), 4.62 (d, J = 6.5 z, 1), 3.85 (s, 3), 2.43 (s, 3); 13 C MR (CDCl 3, 125 Mz) δ 155.4, 144.4, 136.4, 134.5, 130.9, 130.1, 127.4, 123.3, 115.3, 114.0, 105.4, 64.7, 62.3, 62.0, 59.5, 21.7; IR (film): 3189, 2926, 1651, 1548, 1428, 1334, 1161, 1094 cm -1 ; RMS (C S): Calc d (M + ), Found Me Ts Me 23 Compound 23: To a mixture of compound 22 (17.6 mg, mmol) and Cs 2 C 3 (2.5 mg, mmol) in C 2 Cl 2 (0.2 ml) was added a solution of C 3 C (10 µl, in 0.1 ml DCM) dropwisely during a period of 1 h at 0 o C. The resulting solution was allowed to warm to rt. Compound 23 was purified directly via alumina (neutral, activity 3) flash column chromatography (petroleum ether / ethyl acetate = 7/3 to 3/2) to give a thick yellow oil (17.8 mg, 90%): R f : 0.3 (petroleum ether / ethyl acetate = S13

15 1/1); [α] D : (c 0.15, DCM); 1 MR (CDCl 3, 500 Mz): δ 7.81 (d, J = 8.5 z, 2), 7.34 (d, J = 8.5 z, 2), 7.20 (d, J = 5.0 z, 1), 6.89 (d, J = 4.5 z, 1), 6.28 (d, J = 4.0 z, 1), 6.11 (m, 1), 6.00 (m, 1), 5.63 (m, 2), 4.67 (d, J = 7.5 z, 1), 3.81 (s, 3), 2.81 (d, J = 4.5 z, 3), 2.44 (s, 3); 13 C MR (CDCl 3, 125 Mz) δ 156.0, 152.8, 145.4, 136.1, 134.4, 130.2, 128.9, 127.5, 122.9, 114.7, 113.9, 105.5, 68.2, 63.6, 63.1, 61.5, 27.6, 21.8; IR (film): 3409, 2926, 2855, 1694, 1681, 1538, 1417, 1348, 1159, 1028 cm -1 ; ESI (C S): ([M+a] + ). Ts Me ( )-15 Compound ( )-15: To a solution of compound 23 (10.4 mg, 0.02 mmol) in TF (1 ml) was added B 3 TF complex (0.2 ml, 1M in TF) dropwisely at 0 o C. The resulting solution was stirred at 0 o C for 1.5 h, before it was quenched with aq. a (0.5 ml, 15% w/w) and 2 2 (0.25 ml, 30% w/w). The reaction mixture was stirred at rt for 1h, before it was poured into water and extracted with ethyl acetate (3 x 10 ml). The combined organic fractions were dried over MgS 4, and compound ( )-15 was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 3/1, 1/1, then 2/3) to give a colorless foam (4.0 mg, 43%): [α] D : 35.6 (c 0.34, DCM); R f, 1 MR, 13 C MR and IR are identical to those of compound (+)-15. Me Ts Me 24 Compound 24: To a solution of compound 23 (9.3 mg, mmol) in TF (0.8 ml) was added B 3 TF complex (0.2 ml, 1M in TF) dropwisely at 0 o C. The resulting S14

16 solution was stirred at 0 o C for 1.5 h, before it was quenched with water (ca 1 ml) and ab 3 2 (54 mg, 0.18 mmol). The reaction mixture was stirred at rt for 1h, before it was poured into water and extracted with ethyl acetate (3 x 10 ml). The combined organic fractions were dried over MgS 4, and compound 24 was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 4/1, then 3/2) to give an off-white foam (4.2 mg, 44%): R f : 0.3 (petroleum ether / ethyl acetate = 3/2); [α] D : (c 0.25, CCl 3 ); 1 MR (CDCl 3, 500 Mz): δ 7.90 (d, J = 18 z, 2), 7.37 (d, J = 18 z, 2), 7.16 (d, J = 4.5 z, 1), 6.92 (d, J = 4 z, 1), 6.27 (d, J = 4.0 z, 1), 5.30 (m, 1), 4.76 (dd, J = 2.0, 6.0 z, 1), 4.66 (m, 1), 4.47 (d, J = 6.5 z, 1), 3.78 (s, 3), 2.81 (d, J = 5.0 z, 3), 2.78 (m, 1), 2.46 (s, 3), 2.41 (d, J = 4.0 z, 1), 2.08 (m, 1); 13 C MR (CDCl 3, 125 Mz) δ 158.1, 153.4, 145.6, 135.8, 130.2, 127.8, 122.9, 115.2, 113.7, 105.7, 74.1, 68.8, 66.3, 63.6, 53.5, 38.5, 27.7, 21.8; IR (film): 3404 (br), 2919, 1692, 1664, 1544, 1415, 1352, 1155, 1088, 1030 cm -1 ; RMS (C S): Calc d ([M C 3 C] + ), Found C 3 Ts Me ( )-16 Compound ( )-16: Dess-Martin periodinane (3.9 mg, mmol) was added to a solution of compound 24 (2.4 mg, mmol) and ac 3 (1.2 mg, mmol) in C 2 Cl 2 (0.2 ml) at 0 o C. The resulting mixture was stirred at rt for 2 h, before being quenched with sat. aq. a 2 S 2 3. Compound ( )-16 was purified via silica gel flash column chromatography (petroleum ether / ethyl acetate = 4/1, then 2/3, then 1/1) to give a foam-like colorless solid (2.0 mg, 84%): [α] D : 11.1 (c 0.17, CCl 3 ); R f, 1 MR, 13 C MR and IR are identical to those of compound (+)-16. Reference: S15

17 1. oulihan, F.; Bouchard, F.; Frechet, J. M. J.; Willson, C. G.; Can. J. Chem. 1985, 63, 153. S16

18 Boc Boc 8 S17

19 9 Me S18

20 Boc 10 Me S19

21 Boc 11 S20

22 Boc C 3 7 S21

23 C 3 6 S22

24 12 Ts C 3 S23

25 Ts C 3 15 S24

26 Ts C 3 5 S25

27 3 C Ts C 3 16 S26

28 3 C (+)-agelastatin A (1) S27

29 Me 21 S28

30 Me 17 S29

31 Me 19 S30

32 Ts Me 22 S31

33 Me Ts Me 23 S32

34 Me Ts Me 24 S33