Supporting Information. Homogeneous Gold-Catalyzed Oxidative Carboheterofunctionalization of Alkenes

Supporting Information Homogeneous Gold-Catalyzed Oxidative Intramolecular Carboheterofunctionalization of Alkenes Guozhu Zhang, Li Cui, Yanzhao Wang, and Liming Zhang Department of Chemistry and Biochemistry, University of California, Santa Barbara, California, 93106 Content Page number General 2 Preparation of Starting Materials 2 General Procedure A: Gold Catalysis 11 Deuterium-labeling Studies 22 1 H and 13 C NMR spectra 25 SI-1

General. Ethyl acetate (ACS grade), hexanes (ACS grade) and diethyl ether (ACS grade) were purchased from Fisher Scientific and used without further purification. Anhydrous dichloromethane (HPLC grade) was purified by distillation over calcium hydride. Anhydrous tetrahydrofuran in Pure-Pac from Aldrich was used directly without further purification. Anhydrous acetyl nitrile was dried over anhydrous K 2 CO 3 for 24 h, followed by further drying over 3Å molecular sieves for 24 h and then distilled. Commercially available reagents were used without further purification. Reactions were monitored by thin layer chromatography (TLC) using silicycle pre-coated silica gel plates. Flash column chromatography was performed over silicycle silica gel (230-400 mesh). 1 H NMR and 13 C NMR spectra were recorded on a Varian 500 MHz Unity plus spectrometer and a Varian 400 MHz spectrometer using residue solvent peaks as internal standards. Infrared spectra were recorded with a Perkin Elmer FT-IR spectrum 2000 spectrometer and are reported in reciprocal centimeter (cm -1 ). Mass spectra were recorded with Micromass QTOF2 Quadrupole/Time-of-Flight Tandem mass spectrometer using electrospray ionization. 2-Benzylpent-4-enoic acid (4n) 2-Benzylpent-4-en-1-ol (4a) 4n 4a n-buli (26.2 ml, 1.6 M in hexane, 42 mmol) was added dropwise to a cold (0 C) solution of i Pr 2 NH (5.9 ml, 42 mmol) in THF (30 ml), and the mixture was stirred for 30 min. Then, a solution of hydrocinnamic acid (3.0 g, 20 mmol) in THF (20 ml) was added dropwise over 20 min and stirring was continued for another 30 min at the same temperature. Allyl bromide (1.8 ml, 20.9 mmol) was added, and the stirring was continued for another 6 h. The solvent was removed under reduced pressure. The resulting residue was diluted with water (100 ml) and extracted with ether (50 ml). ph of the separated aqueous layer was adjusted to 2 by HCl (6 M) and then extracted with SI-2

ether (50 ml 3). The combined organic layers were washed with brine, dried with MgSO 4, and filtered. The solvent was evaporated, and the residue was purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate= 2:1) to give 4n (3.05 g, 11.4 mmol) in 79% yield. Lithium aluminum hydride (1 g, 25 mmol) was added to a solution of 4n (2.50 g, 13.2 mmol) in dry Et 2 O (45 ml) portion-wise at 0 C. The reaction was allowed to warm up to ambient temperature. After 1.5 h, the reaction was refluxed at 50 C for another 5 h. The reaction was cooled to room temperature and was poured into a mixture of 1M NaOH (aq) (50 ml) and ice with vigorous stirring. After the formation of a white precipitate, the suspension was filtered. The filtrate was then extracted with ether (50 ml 3). The combined organic layers were washed with 1M HCl (aq) (40 ml) and brine (40 ml), dried over MgSO 4, concentrated, and the residue was purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate= 5:1) to give 4a (2 g, 11.3 mmol) in 85% yield. 1 Compound 4n, this compound is known and the spectroscopic data match those reported: 1 H NMR (500 MHz, CDCl 3 ) 7.18 7.31 (m, 5H), 5.75 5.82 (m, 1H), 5.07 5.12 (m, 2H), 2.96 3.00 (m, 1H), 2.76 2.82 (m, 2H), 2.28 2.41(m, 2H); 13 C NMR (125 MHz, CDCl 3 ) 181.4, 138.8, 134.7, 128.9, 128.4, 126.5, 117.4, 47.0, 37.3, 35.6; IR (neat): 3422, 3029, 2926, 1707, 1624, 1496, 1418. Compound 4a: this compound is known and the spectroscopic data match those reported: 1 H NMR (400 MHz, CDCl 3 ) 7.30 7.26 (m, 2H), 7.21 5.17 (m, 3H), 5.88 5.78 (m, 1H), 5.11 5.04 (m, 2H), 3.54 (s, 2H), 2.69 2.59 (m, 2H), 2.13 (t, 2H, J = 7.2 Hz) 1.95-1.89 (m, 1H), 1.44-1.36 (bs, 1H); 13 C NMR (125 MHz, CDCl 3 ) 140.4, 136.7, 129.1, 128.2, 125.9, 116.5, 64.5, 42.3, 37.1, 35.3; IR (neat): 3346, 3074, 2921, 1639, 1454; MS (ES + ) Calculated for [C 12 H 17 O] + : - 3-Phenylpent-4-en-1-ol (4b) 1 Wang, L.; Thai, K.; Gravel, M. Org. Lett. 2009, 11, 891-893 SI-3

4b To a solution of cinnamyl alcohol (2.5 g, 18.7 mmol ) and trimethyl orthoacetate (14 mol, 107.4 mmol) in toluene (75 ml) was added catalytic amount of butyric acid. The reaction was then heated at 150 C overnight. The mixture was concentrated and purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate= 5:1) to give an oil (1 g). The resulting ester (1 g, 5.25 mmol) was then dissolved in THF (20 ml) and treated slowly with lithium aluminum hydride (0.5 g 12.5 mmol) at 0 C. The reaction was allowed to warm to ambient temperature and the stirring was continued for another 5 h. The reaction mixture was poured into a mixture of 1M NaOH (aq) (50 ml) and ice with vigorous stirring. After the formation of a white precipitate, the suspension was filtered and then extracted with ether (50 ml 3). The combined organic layers were washed with 1M HCl (aq) (40 ml), brine (40 ml), dried over MgSO 4, filtered, and concentrated. The resulting residue was purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate= 5:1) to give 4b (0.7 g, 4.6 mmol) in 88% yield. 2 1 H NMR (500 MHz, CDCl 3 ) 7.33 7.26 (m, 2H), 7.23 7.20(m, 3H), 6.03 5.94 (m, 1H), 5.12 5.05 (m, 2H), 3.66 3.59 (m, 2H), 3.48 (q, 1H, J = 7.6 Hz), 2.05 1.93 (m, 2H), 1.33 (bs, 1H); 13 C NMR (125 MHz, CDCl 3 ) 143.6, 141.8, 128.6, 127.5, 126.4, 114.4, 60.9, 46.3, 37.9; IR (neat): 3335, 3080, 2936, 2360, 1491; MS (ES + ) Calculated for [C 11 H 15 O] + : 163.1; Found: 162.9. Dec-1-en-5-ol (4c) Me HO 4c 2 Kelly, B. D.; Allen, J. M.; Tundel, R. E.; Lambert, T. H. Org. Lett. 2009, 11, 1381-1383 SI-4

The title alcohol was prepared by reacting but-3-en-1-yl magnesium bromide with hexanal in 70% yield. This compound is known and the spectroscopic data match those reported. 3 1 H NMR (500 MHz, CDCl 3 ) 5.86 5.76 (m, 1H), 5.06 4.90 (m, 2H), 3.62 3.54 (m, 1H), 2.23 2.02 (m, 2H), 1.70 1.90 (bs, 1H), 1.58 1.16 (m, 10H), 0.86 (t, 3H, J = 7.0 Hz); 13 C NMR (125 MHz, CDCl 3 ) 138.6, 114.5, 71.4, 37.4, 36.4, 31.8, 30.0, 25.2, 22.5, 13.9; IR (neat): 3348, 3078, 2956, 2930 2859, 1641, 1456. 1-But-3-enylcyclohexanol (4d) 4d Compound 4d was prepared by reaction of but-3-en-1-yl magnesium bromide and cyclohexanone in 65% yield. This compound is known and the spectroscopic data match those reported. 4 1 H NMR (500 MHz, CDCl 3 ) 5.91 5.81 (m, 1H), 5.07 4.93 (m, 2H), 2.18 2.11 (m, 2H), 1.63 1.39 (m, 12H); 13 C NMR (125 MHz, CDCl 3 ) 139.3, 114.2, 71.3, 37.4, 27.4, 25.8, 22.2; IR (neat): 3452, 2935, 2857, 2251, 1639, 1449. 4-Methyl-N-pent-4-enylbenzenesulfonamide (4f) 4f To the solution of 4-penten-1-ol (0.39 g, 4.5 mmol), N-(tert-butoxycarbonyl)-ptoluenesulfonamide (1.22 g, 4.5 mmol), triphenylphosphine (1.19 g, 4.5 mmol) in THF (10 ml) at 0 C was added dropwise diethyl azodicarboxylate (0.71 ml, 4.5 mmol). The resulting mixture was stirred at room temperature overnight. After concentration, the 3 Dupont, A. C.; Audia, V. H.; Waid, P. P.; Carter, J. P. Syn. Comm. 1990, 20, 1011-21 4 Hon, Y. S.; Liu, Y. W.; Hsieh, C. H. Tetrahedron 2004, 60, 4837-4860 SI-5

residue was purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate = 5:1) to give the desired carbamate (1.3 g, 0.38 mmol) in 84% yield. The carbamate (1.3 g, 0.38 mmol) was dissolved in MeOH (30 ml), and K 2 CO 3 (3 g) was added. The resulting mixture was heated to reflux for 3 h and cooled down to room temperature. Water (50 ml) was added and the aqueous solution was extracted with dichloromethane (30 ml 3). The combined organic layers were washed with brine, dried over MgSO 4, filtered, and concentrated. The residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate= 5:1) to give 4f (0.8 g, 0.33 mmol) in 87% yield. 1 H NMR (400 MHz, CDCl 3 ) 7.75 (d, 2H, J = 8 Hz), 7.31 (d, 2H, J = 8 Hz), 5.75 5.65 (m, 1H), 4.99 4.93 (m, 2H), 4.71 (bs, 1H), 2.94 (q, 2H, J = 6.8 Hz), 2.43 (s, 3H), 2.04 (q, 2H, J = 6.8 Hz), 1.56(quintet, 2H, J = 6.8 Hz); 13 C NMR (125 MHz, CDCl 3 ) 143.3, 137.2, 136.9, 129.7, 127.0, 115.5, 42.6, 30.6, 28.6, 21.5; IR (neat): 3273, 3076, 2920, 2865, 2255, 1920, 1642, 1428; MS (ES + ) Calculated for [C 12 H 17 NNaO 2 S] + : 362.1; Found: 362.1. N-(1-But-3-enylhexyl)-4-methylbenzenesulfonamide (4g) 4c 4g To a solution of alcohol 4c (0.312 g, 2 mmol), N-(tert-butoxycarbonyl)-ptoluenesulfonamide (0.543 g, 2 mmol), triphenylphosphine (0.525 g, 2 mmol) in dichloromethane (5 ml) at 0 C was added dropwise di-(4-chlorobenzyl)- azodicarboxylate (0.734 g, 2 mmol). The resulting mixture was stirred at room temperature overnight. After concentration, the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate= 10: 1) to give the desired carbamate (0.492 g, 1.2 mmol) in 60% yield. SI-6

The carbamate (0.492 g, 1.2 mmol) was dissolved in dichloromethane (20 ml) and treated with trifluoroacetic acid (1 ml). The resulting mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane (10 ml) and washed with saturated NaHCO 3 (aq) (10 ml) and brine (40 ml) consecutively, dried over MgSO 4, filtered, and concentrated. The resulting residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate= 10: 1) to give 4g (0.310 g, 1 mmol) in 83% yield. 1 H NMR (500 MHz, CDCl 3 ) 7.76 (d, 2H, J = 8.0 Hz), 7.27 (d, 2H, J = 8.0 Hz), 5.71 5.60 (m, 1H), 4.94 4.86 (m, 2H), 4.82 (bs, 1H), 3.26 3.14 (m, 1H), 2.40 (s, 3H), 2.05 1.86 (m, 2H), 1.54 0.96 (m, 10H), 0.78 (t, 3H, J = 7.3 Hz); 13 C NMR (125 MHz, CDCl 3 ) ; IR (neat): 3279, 3076, 2953, 2930, 2859, 1639, 1599, 1496; MS (ES + ) Calculated for [C 17 H 27 NaNO 2 S] + : 332.2; Found: 332.2. N-(1-Cyclohexylpent-4-enyl)-4-methylbenzenesulfonamide (4h) 4h To a solution of the known alcohol 5 shown above (0.336 g, 2 mmol), N-(tertbutoxycarbonyl)-p-toluenesulfonamide (1.08 g, 4 mmol), triphenylphosphine (1.04 g, 4 mmol) in THF (25 ml) at 0 C was added dropwise diethyl azodicarboxylate (0.7 g, 4 mmol). The resulting mixture was heated at 50 C overnight. After concentration, the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate= 5:1) to give desired carbamate (0.165 g, 0.4 mmol) in 20% yield. The carbamate (0.165 g, 0.4 mmol) was dissolved in dichloromethane (5 ml), TFA (1 ml) was added. The resulting mixture was stirred at room temperature for 2 h. The mixture was diluted with dichloromethane (10 ml) and washed with saturated NaHCO 3 5 Lee, A. S.-Y.; Tsao, K.-W.; Chang, Y.-T.; Chu, S.-F. J. Chin. Chem. Soc. (Taipei, Taiwan) 2007, 54, 519-524. SI-7

(aq) (10 ml) and brine (40 ml) sequentially, dried over MgSO 4, filtered, and concentrated. The resulting residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate= 5:1) to give 4h (0.1 g, 0.3 mmol) in 75% yield. 1 H NMR (500 MHz, CDCl 3 ) 7.75 (d, 2H, J = 8.5 Hz), 7.28 (d, 2H, J = 8.5 Hz), 5.66 5.58 (m, 1H), 4.90 4.85 (m, 2H), 4.49 (bs, 1H), 3.13 3.07(m, 1H), 2.42 (s, 3H), 2.42 1.80 (m, 2H), 1.69 1.60 (m, 2H), 1.59 (t, 2H, J = 12.5 Hz), 1.52 1.45 (m, 2H), 1.35 1.27 (m, 2H), 1.15 1.03 (m, 3H), 1.02 0.91 (m, 1H), 0.89 0.81 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) 143.0, 138.6, 137.8, 129.5, 127.0, 114.9, 58.4, 41.2, 31.0, 29.7, 28.7, 28.2, 26.3, 26.2, 26.16, 21.5; IR (neat): 3281, 2925, 2854, 2312, 1642, 1446; MS (ES + ) Calculated for [C 18 H 27 NNaO 2 S] + : 344.1; Found: 344.2. 4-Methyl-N-(1-phenylpent-4-enyl)benzenesulfonamide (4i) 4i At 0 C, to a solution of 3-buten-1-yl magnesium bromide in THF (20 mmol, 26 ml) was added dropwise a solution of benzonitrile (1.03 g, 10 mmol) in THF (10 ml) over 5 min; The resulting mixture was heated at 60 C overnight. The reaction was cooled down to 0 C, lithium aluminum hydride (340 mg, 10 mmol) was added slowly. The resulting mixture was heated to reflux for 3 h and then cooled to 0 C. H 2 O (0.34 ml), NaOH (15%, 0.34 ml) and H 2 O (1 ml) was added successively, and the resulting mixture was stirred for 10 min. The mixture was filtered through a pad of celite and washed with ether. The filtrate was diluted with ether (50 ml) and H 2 O (50 ml), the separated aqueous layer was extracted with ether (20 ml 3). The combined organic layers were washed with brine, dried over MgSO 4, filtered, and concentrated to afford the amine (0.53 g, 33% yield), which was used in next step without further purification. The thus-obtained amine (96 mg, 0.06 mmol) and Et 3 N (0.3 ml, 2.2 mmol) was dissolved in dichloromethane (10 ml). TsCl (114 mg, 0.06 mmol) was added in one batch. The resulting mixture was stirred at room temperature for 3 h and then washed SI-8

successively with 1M HCl (aq) (10 ml) and brine (10 ml), dried over MgSO 4, filtered, and concentrated. The resulting residue was purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate= 5:1) to give 4i (100 mg, 0.3 mmol) in 53% yield. 1 H NMR (400 MHz, CDCl 3 ) 7.54 (d, 2H, J = 8.4 Hz), 7.13 7.11 (m, 3H), 7.10 (d, 2H, J = 8 Hz), 7.01-6.99 (m, 2H), 5.74 5.64 (m, 1H), 5.37(d, 1H, J = 7.6 Hz), 4.95 4.89 (m, 2H), 4.28 (q, 1H, J = 7.2 Hz), 2.34 (s, 3H), 2.00-1.73 (m, 4H); 13 C NMR (125 MHz, CDCl 3 ) 142.9, 140.6, 137.6, 137.1, 129.2, 128.4, 127.3, 127.0, 126.5, 115.4, 57.8, 36.6, 29.9, 21.4; IR (neat): 3511, 3276, 3064, 2923, 2857, 2254, 1598; MS (ES + ) Calculated for [C 18 H 21 NNaO 2 S] + : 338.1; Found: 338.1. Isobutyronitrile (2.674 g, 40 mmol) was added to a solution of LDA (48 mmol) in THF (100 ml) at 0 ºC. After stirring 2 h at 0 ºC, allyl bromide (4.18 ml, 48 mmol) in THF (20 ml) was added. The reaction was treated with water (20 ml) after 3 h and extracted with diethyl ether (3 x 50 ml). The organic layers were combined, washed with brine and dried with MgSO 4. Evaporation of the solvent gave 4j (4.0 g, crude), which was used directly in the next step. Nitrile 4j (4.0 g, crude) in diethyl ether (80 ml) was treated with LAH (3.04 g, 80 mmol) at room temperature. The reaction was refluxed for 2 h and then cooled in an ice bath. Water (3.04 ml), 15% aqueous NaOH (3.04 ml) and water (9.12 ml) was slowly added to the reaction. The reaction mixture was stirred at room temperature for 15 minutes, and the solid was filtered off. Evaporation of the filtrate gave 4j (3.66 g, 32.4 mmol) in 81% yield (over 2 steps). SI-9

A mixture of amine 4j (1.44 g, 12.7 mmol) and triethylamine (3.48 ml, 25 mmol) in CH 2 Cl 2 (40 ml) was treated with TsCl (2.29 g, 12 mmol) at 0 ºC. The reaction was stirred at room temperature for 12 h. The mixture was washed with 10% NaHCO 3 (30 ml), brine (30 ml) and dried with MgSO 4. The solvent was evaporated and the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate= 5:1) to give 4j (3.05 g, 11.4 mmol) in 90% yield. 1 H NMR (400 MHz, CDCl 3 ) 7.72 (dd, 2H, J = 2, 6.4 Hz), 7.29 (d, 2H, J = 8.8 Hz), 5.69 5.76 (m, 1H), 4.97 5.04 (m, 2H), 4.40 (bs, 1H), 2.68 (d, 2H, J = 7.2 Hz), 2.43 (s, 3H), 1.95 (d, 2H, J = 7.6 Hz), 0.86 (s, 6H); 13 C NMR (125 MHz, CDCl 3 ) 143.2, 137.0, 134.2, 129.6,127.0, 117.8, 52.8, 44.0, 43.1, 34.1, 24.8, 21.5; IR (neat): 3286, 2963, 2872, 2373, 1598, 1419; MS (ES + ) Calculated for [C 14 H 21 NaNO 2 S] + : 290.1; Found: 290.1. N-(2-Benzylpent-4-enyl)-4-methylbenzenesulfonamide (4k) 4a 4k Following the similar procedure for preparing 4f, 4k was obtained in 75% yield from 4a. 1 H NMR (500 MHz, CDCl 3 ) 7.69 (d, 2H, J = 10.5 Hz), 7.17 7.30 (m, 5H), 7.06 (d, 2H, J = 10 Hz), 5.64 5.73 (m, 1H), 4.99 5.04 (m, 2H), 4.77 (bs, 1H), 2.82 2.90 (m, 2H), 2.55 (d, 2H, J = 9.0 Hz), 2.43 (s, 3H), 1.86 1.90 (m, 3H); 13 C NMR (125 MHz, CDCl 3 ) 143.3, 139.6, 136.8, 135.7, 129.6, 129.0, 128.4, 127.1, 126.1, 117.3, 45.7, 39.7, 37.9, 35.8, 21.5; IR (neat): 3283, 2924, 1716, 1639, 1598, 1454; MS (ES + ) Calculated for [C 19 H 23 NaNO 2 S] + : 352.1; Found: 352.2. N-Hex-5-enyl-4-methylbenzenesulfonamide (4l) SI-10

4l Following the similar procedure for preparing 4f, 4l was obtained in 70% yield from 5- hexene-1-ol. 1 H NMR (500 MHz, CDCl 3 ) 7.75 (d, 2H, J = 8.5 Hz), 7.29 (d, 2H, J = 8.5 Hz), 5.72 5.64 (m, 1H), 5.04 (bs, 1H), 4.94 4.88 (m, 2H), 2.90 (q, 2H, J = 6.5 Hz), 2.40 (s, 3H), 1.95 (td, 2H, J = 7 Hz, J = 7 Hz), 1.47-1.41(m, 2H), 1.36-1.30 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) 143.2, 138.1, 136.8, 129.6, 127.0, 114.7, 42.9, 33.0, 28.8, 25.6, 21.4; IR (neat): 3276, 2936, 2867, 1639, 1598, 1434; MS (ES + ) Calculated for [C 13 H 19 NNaO 2 S] + : 276.1; Found: 276.1. General procedure A: Ph 3 PAuCl (0.0075 mmol, 3.7 mg) was added into a solution of a substrate (0.15 mmol), Selectfluor (2 equiv) and an arylboronic acid (2 equiv) in anhydrous MeCN under N 2. The reaction mixture was heated at 60 ºC (80 C in the cases of acid substrates) and the progress of the reaction was monitored by TLC. The reaction typically took 2 h. Upon completion, the reaction mixture was cooled to room temperature and treated with water. The resulting mixture was extracted with diethyl ether (3 x 10 ml). The combined organic layers were washed with brine (10 ml), dried with MgSO 4, and filtered. The filtrate was concentrated under vacuum, and the residue was purified through silica gel flash column chromatography (eluent: hexanes/ethyl acetate). 2-Benzyltetrahydrofuran (2) SI-11

2 Compound 2 was prepared in 73% yield according to the general procedure A, and its spectroscopic data match well with those reported. 6 The reaction time was 90 minutes. 1 H NMR (400 MHz, CDCl 3 ) 7.31-7.19 (m, 5H), 4.09-4.04 (m, 1H), 3.92-3.87 (m, 1H), 3.77-3.72 (m, 1H), 2.93 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz,), 2.75 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz,), 1.95-1.82 (m, 3H), 1.59-1.54 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) 138.9, 129.2, 128.3, 126.1, 80.0, 67.9, 41.9, 30.9, 25.6; IR (neat): 3064, 2942, 2868, 2245, 1946, 1496; 2,4-Dibenzyltetrahydrofuran (5a) 5a Compound 5a was prepared in 71% yield according to the general procedure A. The reaction time was 2 h, and the diastereomeric ratio was 1.05:1. 1 H NMR (400 MHz, CDCl 3 ) 7.33 7.28 (m, 8H), 7.26 7.19 (m, 8H), 7.16 (d, 4H, J = 7.2 Hz), 4.31-4.24 (m, 1H), 4.15-4.08 (m, 1H), 3.98 (dd, 1H, J = 8.4 Hz, J = 6.4 Hz), 3.87 (dd, 1H, J = 8 Hz, J = 7.6 Hz), 3.60 (dd, 1H, J = 8 Hz, J = 7.6 Hz), 3.49 (dd, 1H, J = 8.4 Hz, J = 6.4 Hz), 3.00 (dd, 1H, J = 13.2 Hz, J = 6 Hz), 2.92 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz), 2.79 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz), 2.74 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz), 2.71-2.63 (m, 4H), 2.58-2.51(m, 2H), 2.05(m, 1H), 1.81-1.70 (m, 2H), 1.37-1.29 (m, 1Hz); 13 C NMR (125 MHz, CDCl 3 ) 140.7, 140.6, 138.8, 138.7, 129.19, 129.15, 128.6, 128.5, 128.4, 128.3, 126.17, 126.16, 126.0, 80.6, 79.4, 73.0, 72.8, 42.2, 42.1, 41.4, 40.4, 39.7, 39.3, 38.3, 36.9; IR (neat): 3061, 2925, 2854, 1875, 1603, 1583; MS (ES + ) Calculated for [C 19 H 20 NaO] + : 287.1; Found: 287.0. 2-Benzyl-3-phenyltetrahydrofuran (5b) 6 Hay, M. B.; Hardin, A. R.; Wolfe, J. R. J. Org. Chem. 2005, 70, 3099-3107 SI-12

5b Compound 5b was prepared in 61% yield according to the general procedure A. The reaction time was 2 h, and the diastereomeric ratio was 1:1. 1 H NMR (400 MHz, CDCl 3 ) 7.34 7.29 (m, 4H), 7.27 7.12 (m, 14H), 7.04 (d, 2H, J = 7.6 Hz), 4.24-4.18 (m, 2H), 4.11-3.95 (m, 3H), 3.90-3.84 (m, 1H), 3.37-3.33 (m, 1H), 2.99-2.88 (m, 2H), 2.75 (dd, 1H, J = 6 Hz, J = 14 Hz), 2.53-2.30 (m, 4H), 2.18-2.04 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) 142.1, 141.8, 139.3, 138.8, 129.3, 130.0, 128.62, 128.61, 128.24, 128.16, 128.1, 127.7, 126.6, 126.4, 126.1, 125.9, 86.5, 83.5, 67.7, 66.9, 50.4, 47.8, 39.7, 37.6, 35.5, 33.5; IR (neat): 3061, 2968, 2872, 1875, 1602, 1494; MS (ES + ) Calculated for [C 17 H 18 NaO] + : 261.1; Found: 261.1. 2-Benzyl-5-pentyltetrahydrofuran (5c) 5c Compound 5c was prepared in 62% yield according to the general procedure A. The reaction time was 2 h, and the diastereomeric ratio was 1.2:1. 1 H NMR (500 MHz, CDCl 3 ) 7.34 7.15 (m, 11.49H), 4.26 4.14 (m, 1H), 4.12 4.01 (m, 1.39H), 4.01 3.90 (m, 1.03H), 3.89 3.75 (m, 1.42H), 2.99 dd, 2.4H, J = 13.8 Hz, J = 5.8 Hz), 2.78 2.62 (m, 2.43H), 2.08 1.80 (m, 4.85H), 1.70 1.14 (m, 26.55H), 0.98 0.76 (m, 7.45H); 13 C NMR (125 MHz, CDCl 3 ) 138.90, 138.85, 129.32, 129.27, 128.19, 128.14, 126.03, 126.01, 79.82, 79.64, 79.26, 79.06, 42.42, 42.18, 36.15, 36.01, 31.94, 31.92, 31.90, 31.47, 30.87, 30.46, 25.88, 25.86, 22.58, 13.99; IR (neat): 3026, 2956, 2928, 2858, 1496, 1455,; MS (ES + ) Calculated for [C 16 H 24 NaO] + : 255.2; Found: 255.2. 2-Benzyl-1-oxaspiro[4.5]decane (5d) O Ph 5d SI-13

Compound 5d was prepared in 56% yield according to the general procedure A. The reaction time was 8 h. 1 H NMR (500 MHz, CDCl 3 ) 7.22-7.10 (m, 5H), 4.12-4.05 (m, 1H), 2.93 (dd, 1H, J = 13.2 Hz, J = 5.2 Hz,), 2.60 (dd, 1H, J = 13.2 Hz, J = 5.2 Hz,), 1.83-1.75 (m, 1H), 1.67-1.26 (m, 13H); 13 C NMR (125 MHz, CDCl 3 ) 138.9, 129.4, 128.1, 126.0, 82.8, 78.7, 42.8, 38.6, 37.7, 35.7, 30.7, 25.7, 24.1, 23.8; IR (neat): 3062, 2930, 2856, 1873, 1603, 1450; MS (ES + ) Calculated for [C 16 H 22 NaO] + : 253.1; Found: 253.2 2-Benzyltetrahydropyran (5e) 5e Compound 5e was prepared in 35% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (400 MHz, CDCl 3 ) 7.31-7.27 (m, 2H), 7.23-7.19 (m, 3H), 4.01-3.97 (m, 1H), 3.53-3.42 (m, 1H), 3.42 (td, 1H, J = 12 Hz, J = 2.4 Hz), 2.89 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz,), 2.65 (dd, 1H, J = 13.6 Hz, J = 6.4 Hz,), 1.83-1.80 (m, 1H), 1.62-1.24 (m, 5H); 13 C NMR (125 MHz, CDCl 3 ) 138.8, 129.3, 128.2, 126.0, 78.8, 68.6, 43.2, 31.4, 26.0, 23.5; IR (neat): 3063, 2935, 2842, 2739, 2360, 1878, 1603, 1498; MS (ES + ) Calculated for [C12H16NaO] + : 179.1; Found: 179.1. 2-Benzyl-1-(toluene-4-sulfonyl)pyrrolidine (5f) 5f Compound 5f was prepared in 94% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (400 MHz, CDCl 3 ) 7.76 (d, 2H, J = 8 Hz), 7.33-7.29(m, 4H), 7.26-7.20 (m, 3H), 3.85-3.79 (m, 1H),3.43-3.37 (m, 1H), 3.25 (dd, 1H, J = 13.2 Hz, J = 3.2Hz), 3.16-3.10(m, 1H), 2.76 (dd, 1H, J = 13.2 Hz, J = 9.6 Hz,), 2.42(s, 3H), 1.72-1.49 (m, 2H), 1.48-1.39 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) 143.3, 138.4, 134.6, 129.6, 129.5, 128.3, 127.4, 126.3, 61.5, 49.2, 42.6, 29.8, 23.7, 21.4; IR (neat): 3061, 2940, SI-14

2863, 1919, 1808, 1598, 1448; MS (ES + ) Calculated for [C 18 H 21 NNaO 2 S] + : 338.1; Found: 338.1. 2-Benzyl-5-pentyl-1-(toluene-4-sulfonyl)pyrrolidine (5g) 5g Compound 5g was prepared in 84% yield according to the general procedure A. The reaction time was 3 h, and the diastereomeric ratio was 1.2:1. 1 H NMR (400 MHz, CDCl 3 ) 7.77 (d, 4.33H, J = 8.0 Hz), 7.42 7.14 (m, 15.66H), 4.16 4.0 (m, 1H), 3.96 3.83 (m, 1.06H), 3.83 3.70 (m, 1.18H), 3.66 3.50 (m, 1.18H), 3.50 3.36 (m, 0.99H), 3.36 3.18 (m, 1.15H), 2.76 (d, 1.10H, J = 9.5 Hz), 2.56 2.30 (m, 7.56H), 2.04 1.02 (m, 28.34H);, 1.02 0.70 (m, 6.54H); 13 C NMR (125 MHz, CDCl 3 ) 143.2, 142.7, 139.9, 138.9, 138.4, 135.1, 129.7, 129.6, 129.5, 129.4, 128.4, 128.3, 127.5, 126.9, 126.32, 126.29, 62.8, 62.2, 62.1, 61.0, 40.1, 40.3, 28.6, 27.5, 27.2, 25.96, 25.92, 22.56, 22.55, 21.45, 21.42, 14.0, 13.9; IR (neat): 3084, 3062, 3027, 2955, 2928, 2860, 1600, 1496,; MS (ES + ) Calculated for [C 23 H 31 NaNO 2 S] + : 408.2; Found: 408.2. 2-Benzyl-5-cyclohexyl-1-(toluene-4-sulfonyl)-pyrrolidine (5h) 5h Compound 5h was prepared in 69% yield according to the general procedure A. The reaction time was 4 h, and the diastereomeric ratio was 1.04: 1. 1 H NMR (500 MHz, CDCl 3 ) 7.79 (d, 2H, J = 8Hz), 7.75 (d, 2H, J = 8 Hz), 7.31 7.28 (m, 8H), 7.23 7.20 (m, 6H), 4.15-4.11 (m, 1H), 3.81-3.79 (m, 1H), 3.74-3.69 (m, 1H), 3.52-3.43 (m, 2H), 3.30 (dd, 1H, J = 13, 3.5 Hz), 2.69 (dd, 1H, J = 13, 10.5 Hz), 2.57 (dd, 1H, J = 13, 10.5 Hz), 2.41 (2, 6H), 2.00-0.60 (m, 30H); 13 C NMR (125 MHz, CDCl 3 ) 143.2, 142.6, 139.8, 139.1, 138.5, 134.9, 129.6, 129.5, 129.4, 129.3, 128.4, 128.3, 127.6, 126.8, 126.3, 126.2, 76.7, 67.0, 64.8, 63.3, 62.9, 43.0, 41.3, 40.5, 39.8, 30.9, 30.7, 30.5, 28.8, 28.5, 28.3, SI-15

26.5, 26.4, 26.3, 26.2, 26.1, 25.7, 24.2, 21.5, 21.4; IR (neat):3026, 2926, 2852, 2255, 1598, 1451; MS (ES + ) Calculated for [C 24 H 31 NNaO 2 S] + : 420.2; Found: 420.2. 2-Benzyl-5-phenyl-1-(toluene-4-sulfonyl)pyrrolidine (5i) 5i Compound 5i was prepared in 92% yield according to the general procedure A. The reaction time was 1.5 h, and the diastereomeric ratio was 1.09: 1. 1 H NMR (500 MHz, CDCl 3 ) 7.75 (d, 2H, J = 8 Hz), 7.42-7.23 (m, 19H), 7.16-7.09 (m, 3H), 7.06 (d, 2H, J = 8 Hz), 6.99 (d, 2H, J = 8 Hz), 5.00 (d, 1H, J = 8 Hz), 4.73 (t, 1H, J = 7 Hz), 4.37 (t, 1H, J = 8 Hz), 4.03-3.98 (m, 1H), 3.58 (d, 1H, J = 13 Hz), 2.82 (dd, 1H, J = 13 Hz, J = 11 Hz ), 2.74 (dd, 1H, J = 13 Hz, J = 11 Hz ), 2.43 (s, 3H), 2.36 (s, 3H), 2.36-2.28 (m, 1H), 2.11-2.02 (m, 1H), 1.92-1.88 (m, 2H), 1.81-1.77 (m, 1H), 1.70-1.66 (m, 1H), 1.64-1.61 (m, 1H), 1.51-1.44 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) 143.4, 142.5, 142.3, 142.1, 138.8, 138.7, 138.5, 134.9, 129.6, 129.5, 129.3, 128.9, 128.5, 128.3, 128.0, 127.6, 127.0, 126.9, 126.8, 126.6, 126.4, 126.39, 126.2, 65.0, 64.0, 63.7, 62.9, 43.1, 40.8, 34.2, 32.9, 28.9, 27.3, 21.5, 21.3; IR (neat): 3062, 2935, 2871, 2253, 1850, 1807, 1599, 1494; MS (ES + ) Calculated for [C 24 H 25 NNaO 2 S] + : 414.1; Found: 414.1. 2-Benzyl-4,4-dimethyl-1-(toluene-4-sulfonyl)pyrrolidine (5j) 5j Compound 5j was prepared in 90% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (500 MHz, CDCl 3 ) 7.78 (d, 2H, J = 8.5 Hz), 7.20 7.34 (m, 7H), 3.79 (qd, 1H, J = 2.5, 1.5 Hz), 3.58 (dd, 1H, J = 13.0, 3.5 Hz), 3.12 (s, 2H), 2.77 (dd, 2H, J = 13.0, 10.0 Hz), 2.43 (s, 3H), 1.45 1.52 (m, 2H), 0.98 (m, 3H), 0.45 (m, 3H); 13 C NMR (125 MHz, CDCl 3 ) 143.2, 138.4, 135.2, 129.5, 129.4, 128.3, 127.4, SI-16

126.2, 61.6, 61.4, 45.6, 42.7, 37.1, 26.4, 25.7, 21.4; IR (neat): 3027, 2960, 2827, 1598, 1453; MS (ES + ) Calculated for [C 20 H 25 NaNO 2 S] + : 366.2; Found: 366.2. 2,4-Dibenzyl-1-(toluene-4-sulfonyl)pyrrolidine (5k) 5k Compound 5k was prepared in 87% yield according to the general procedure A. The reaction time was 2 h, and the diastereomeric ratio was 1:1. 1 H NMR (400 MHz, CDCl 3 ) 7.75 (d, 2H, J = 8.4 Hz), 7.70 (d, 2H, J = 8.4 Hz), 7.10 (d, 2H, J = 6.8 Hz), 7.16 7.34 (m, 20H), 6.94 7.00 (m, 4H), 3.90 (td, 1H, J = 11.2, 3.2 Hz), 3.70 3.77 (m, 1H), 3.41 3.53 (m, 3H), 3.20 (dd, 1H, J = 13.2, 3.2 Hz), 2.69 2.94 (m, 4H), 2.31 2.54 (m, 10H), 1.59 1.84 (m, 3H), 1.11 1.41 (m, 3H),; 13 C NMR (125 MHz, CDCl 3 ) 143.4, 143.3, 139.6, 139.5, 138.4, 138.1, 135.0, 134.5, 129.7, 129.6, 129.6, 129.5, 128.4, 128.4, 128.3, 127.5, 127.4, 126.4, 126.2, 126.2, 120.6, 115.3, 62.1, 61.4, 54.6, 54.0, 42.9, 42.8, 39.6, 38.6, 38.3, 38.2, 37.9, 35.6, 21.5, 21.5; IR (neat): 3031, 2926, 2256, 1801, 1601, 1456; MS (ES + ) Calculated for [C 25 H 27 NaNO 2 S] + : 428.2; Found: 428.2. 2-Benzyl-1-(toluene-4-sulfonyl)piperidine (5l) 5l Compound 5l was prepared in 76% yield according to the general procedure A. 7 The reaction time was 2 h. 1 H NMR (500 MHz, CDCl 3 ) 7.51 (d, 2H, J = 8.4 Hz), 7.19-7.15(m, 2H), 7.13-7.08 (m, 3H), 7.04 (d, 2H, J = 6.8 Hz), 4.21-4.16 (m, 1H), 3.69-3.65 (m, 1H), 2.98 (td, 1H, J = 13.2, 2.4 Hz), 2.98 (dd, 1H, J = 13.2, 10 Hz), 2.68 (dd, 1H, J = 13.6, 5.6 Hz), 2.29 (s, 3H), 1.62 1.42 (m, 3H), 1.39 1.25 (m, 3H); 13 C NMR (125 MHz, 7 Schlummer, B.; Hartwig, J. F. Org. Lett. 2002, 4, 1471-1474 SI-17

CDCl 3 ) 142.8, 138.6, 138.4, 129.5, 129.1, 128.5, 127.0, 126.3, 54.3, 40.8, 35.6, 25.9, 24.8, 21.4, 18.2; IR (neat): 3061, 2940, 2863, 2341, 1919, 1598, 1448; MS (ES + ) Calculated for [C19H23NaO2S] + : 352.1; Found: 352.1. 5-Benzyl-dihydrofuran-2-one (5m) 5m Compound 5m was prepared in 79% yield according to the general procedure A. The reaction time was 2 h, and the diastereomeric ratio was 1: 1. 1 H NMR (400 MHz, CDCl 3 ) 7.22 7.34 (m, 5H), 4.71 4.77 (m, 1H), 3.07 (dd, 1H, J = 14.0, 6.0 Hz), 2.93 (dd, 1H, J = 14.0, 6.0 Hz), 2.34 2.52 (m, 2H), 2.21 2.30 (m, 1H), 1.91 2.00 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) 176.9, 135.8, 129.3, 128.5, 126.8, 80.7, 41.2, 28.5, 27.0; IR (neat): 3028, 2941, 1772, 1497, 1455,; MS (ES + ) Calculated for [C 11 H 12 NaO 2 ] + : 199.1; Found: 199.1. 3,5-Dibenzyldihydrofuran-2-one (5n) 5n Compound 5n was prepared in 78% yield according to the general procedure A. The reaction time was 2 h, and the diastereomeric ratio was 1:1. 1 H NMR (500 MHz, CDCl 3 ) 7.13 7.32 (m, 20H), 4.51 4.63 (m, 2H), 3.26 (dd, 1H, J = 17.5, 5.0 Hz), 2.60 3.15 (m, 9H), 2.20 2.27 (m, 1H), 2.01 2.04 (m, 2H), 1.60 1.69 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) 1 ; IR (neat): 3027, 2926, 1771, 1496, 1454; MS (ES + ) Calculated for [C 18 H 18 NaO 2 ] + : 289.1; Found: 289.1. 2-(4-Methyl-benzyl)-1-(toluene-4-sulfonyl)pyrrolidine (5o) SI-18

5o Compound 5o was prepared in 80% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (500 MHz, CDCl 3 ) 7.76 (d, 2H, J = 8 Hz), 7.31 (d, 2H, J = 8.5 Hz), 7.15-7.10 (m, 4H), 3.82-3.78 (m, 1H), 3.42-3.38 (m, 1H), 3.21 (dd, 1H, J = 13, 3 Hz), 3.16-3.11(m, 1H), 2.71 (dd, 1H, J = 13, 9.5 Hz), 2.42 (s, 3H), 2.33 (s, 3H), 1.69 1.60 (m, 3H), 1.49 1.39 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) 143.2, 135.8, 135.3, 134.6, 129.6, 129.4, 129.0, 127.4, 76.7, 61.7, 49.2, 42.2, 29.7, 23.7, 21.5, 21.0; IR (neat): 3022, 2952, 2925, 2872, 2255, 1914, 1597, 1514, 1449; MS (ES + ) Calculated for [C 19 H 23 NNaO 2 S] + : 352.1; Found: 352.1. 2-(4-Chlorobenzyl)-1-(toluene-4-sulfonyl)pyrrolidine (5p) 5p Compound 5p was prepared in 84% yield according to the general procedure A. The reaction time was 3 h. 1 H NMR (400 MHz, CDCl 3 ) 7.74 (d, 2H, J = 8.4 Hz), 7.25 7.33 (m, 4H), 7.19 (d, 2H, J = 8.4 Hz), 3.76 3.79 (m, 1H), 3.33 3.36 (m, 1H), 3.11 3.18 (m, 2H), 2.78 (dd, 1H, J = 9.2, 13.6 Hz), 2.43 (s, 3H), 1.43 1.61 (m, 4H); 13 C NMR (125 MHz, CDCl 3 ) 143.4, 136.8, 134.5, 132.2, 131.0, 129.6, 128.4, 127.4, 61.2, 49.2, 41.8, 29.8, 23.7, 21.4; IR (neat): 3028, 2972, 2872, 1914, 1597, 1491, 1448; (ES + ) Calculated for [C 18 H 20 NaClNO 2 ] + : 372.1; Found: 372.1. SI-19

2-(2-Methylbenzyl)-1-(toluene-4-sulfonyl)pyrrolidine (5q) 5q Compound 5q was prepared in 67% yield according to the general procedure A. The reaction time was 4.5 h. 1 H NMR (400 MHz, CDCl 3 ) 7.75 (d, 2H, J = 8.4 Hz), 7.30 (d, 2H, J = 8.4 Hz), 7.10 7.18(m, 4H), 3.81 3.85 (m, 1H), 3.48 3.53 (m, 1H), 3.38 (dd, 1H, J = 13.6, 4.0 Hz), 3.14 3.20 (m, 1H), 2.66 (dd, 1H, J = 10.8, 13.6 Hz), 2.45 (s, 3H), 2.42 (s, 3H), 1.81 1.86 (m, 1H), 1.54 1.67 (m, 2H), 1.30 1.38 (m, 1H); 13 C NMR (125 MHz, CDCl 3 ) 143.3, 136.8, 136.8, 134.8, 130.42, 130.41, 129.6, 127.4, 126.6, 125.8, 60.3, 49.2, 40.1, 29.6, 23.8, 21.5, 19.6; IR (neat): 3063, 2953, 2872, 2300, 1597, 1491; MS (ES + ) Calculated for [C 19 H 23 NaNO 2 S] + : 352.1; Found: 352.1. 3-[1-(Toluene-4-sulfonyl)pyrrolidin-2-ylmethyl]benzonitrile (5r) 5r Compound 5r was prepared in 44% yield according to the general procedure A. The reaction time was 6 h. 1 H NMR (400 MHz, CDCl 3 ) 7.73 (d, 2H, J = 8 Hz), 7.55-7.50 (m, 3H), 7.42 (t, 1H, J = 8 Hz), 7.33 (d, 2H, J = 8 Hz), 3.81 3.77 (m, 1H), 3.37-3.32 (m, 1H), 3.21 (dd, 1H, J = 13.6, 3.6 Hz), 3.16 3.10 (m, 1H), 2.87 (dd, 1H, J = 13.6, 8.8 Hz), 2.43 (s, 3H), 1.60 1.43 (m, 4H); 13 C NMR (125 MHz, CDCl 3 ) 143.6, 139.8, 134.4, 134.3, 133.0, 130.2, 129.7, 129.2, 127.4, 118.8, 112.4, 60.8, 49.2, 42.0, 30.0, 23.8, 21.5; IR (neat): 3064, 2951, 2870, 2228, 1923, 1597, 1449; MS (ES + ) Calculated for [C 19 H 20 N 2 NaO 2 S] + : 363.1; Found: 363.1. SI-20

1-{4-[1-(Toluene-4-sulfonyl)pyrrolidin-2-ylmethyl]phenyl}ethanone (5s) 5s Compound 5s was prepared in 88% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (400 MHz, CDCl 3 ) 7.90 (d, 2H, J = 8.4 Hz), 7.75 (d, 2H, J = 8.4 Hz), 7.35 (d, 2H, J = 8.4 Hz), 7.32 (d, 2H, J = 8.4 Hz), 3.86-3.82 (m, 1H), 3.39-3.34 (m, 1H), 3.21 (dd, 1H, J = 13.6, 3.6 Hz), 3.16-3.10 (m, 1H), 2.88 (dd, 1H, J = 13.2, 8.8 Hz), 2.59 (s, 3H), 2.43 (s, 3H), 1.62 1.56 (m, 3H), 1.49 1.42 (m, 2H); 13 C NMR (125 MHz, CDCl 3 ) 198.1, 144.4, 143.7, 135.8, 134.7, 130.1, 130.0, 128.7, 127.7, 61.3, 49.5, 42.9, 30.2, 26.8, 24.1, 21.8; IR (neat):3030, 2931, 2870, 2253, 1681, 1605, 1449; MS (ES + ) Calculated for [C 20 H 23 NNaO 3 S] + : 380.1; Found: 380.1. Methyl 4-[1-(toluene-4-sulfonyl)pyrrolidin-2-ylmethyl]benzoate (5t) 5t Compound 5t was prepared in 81% yield according to the general procedure A. The reaction time was 3 h. 1 H NMR (400 MHz, CDCl 3 ) 7.96 (d, 2H, J = 8.0 Hz), 7.74 (d, 2H, J = 8.4 Hz), 7.31 (d, 4H, J = 8.0 Hz), 3.90 (s, 3H), 3.81 3.87 (m, 1H), 3.34 3.39 (m, 1H), 3.25 (dd, 1H, J = 3.2, 13.2 Hz), 3.11 3.15 (m, 1H), 2.86 (dd, 1H, J = 13.2, 9.2 Hz), 2.42 (s, 3H), 1.43 1.61 (m, 4H); 13 C NMR (125 MHz, CDCl 3 ) 167.0, 143.8, 143.4, 134.6, 129.7, 128.4, 127.5, 61.1, 52.0, 49.2, 42.6, 30.0, 23.8, 21.5; IR (neat):3031, 2952, 2373, 1719, 1610, 1435; MS (ES + ) Calculated for [C 20 H 23 NaNO 4 S] + : 396.1; Found: 396.1. SI-21

Deuterium-labeling Studies: A mixture of 4-pentyn-1-ol (0.84 g, 10 mmol), PPh 3 (3.14 g, 12 mmol) and BocNHTs (2.99 g, 11 mmol) in THF (20 ml) was treated with diethyl azodicarboxylate (1.89 ml, 12 mmol) at 0 ºC. The reaction mixture was slowly warmed to room temperature and stirred overnight. The solvent was evaporated under vacuum and the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate = 5:1) to gave 4f (2.66 g, 7.9 mmol) in 79% yield. To ZrCp 2 Cl 2 (0.865 g, 2.96 mmol) in THF (20 ml) at 0 ºC was added slowly a solution of LiEt 3 BH (1M in THF, 2.96 ml, 2.96 mmol) under argon. The resulting suspension was stirred for 1 h at room temperature, followed by addition of a solution of 4f (0.5 g, 1.48 mmol) in THF (5 ml). The mixture was stirred for 1 h at room temperature, followed by addition of D 2 O (1.5 ml). After stirring for 1 h, the reaction mixture was poured into 20 ml of saturated aqueous NaHCO 3 and extracted with diethyl ether (3x 30 ml). The combined organic layers were washed with brine, dried over MgSO 4, and filtered through a pad of Celite. Evaporation of the solvent and the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate = 5:1) to give compound 4f (190 mg, 0.56 mmol) in 38% yield. A mixture of compound 4f (190 mg, 0.56 mmol) and K 2 CO 3 (0.5 g, 3.6 mmol) in methanol (10 ml) was refluxed for 2 h. The reaction mixture was poured into 10 ml of water and extracted with diethyl ether (3 x 30 ml). The combined organic layers were washed with brine and dried over MgSO 4. Evaporation of the solvent and the residue was purified through silica gel flash column chromatography (eluent: hexanes : ethyl acetate = SI-22

5:1) to give compound (E)-4f-d (110 mg, 0.46 mmol) in 86% yield. 1 H NMR (500 MHz, CDCl 3 ) 7.74 (d, 2H, J = 8.0 Hz), 7.30 (d, 2H, J = 8.5 Hz), 5.68 5.72 (m, 1H), 4.95 (d, 1H, J = 17 Hz), 4.44 (s, 1H), 2.94 (dd, 2H, J = 7.0, 13.5 Hz), 2.43 (s, 3H), 2.02 2.06 (m, 2H), 1.53 1.59 (m, 3H); MS (ES + ) Calculated for [C 12 H 16 DNaNO 2 S] + : 263.1; Found: 263.1. A mixture of compound 4f (520 mg, 1.54 mmol) and K 2 CO 3 (20 mg) in D 2 O (0.5 g) and CD 3 OD (5 ml) was treated with Na (100 mg) under nitrogen. The reaction was refluxed for 4 h. The reaction mixture was poured into 10 ml of water and extracted with diethyl ether (3x 10 ml). The combined organic layers were washed with brine and dried over MgSO 4. Evaporation of the solvent and the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate = 5:1) to give compound 4f (166 mg, 0.96 mmol) in 62% yield. To ZrCp 2 Cl 2 (0.227 g, 0.778 mmol) in THF (5 ml) cooled to 0 ºC was added slowly a solution of i Bu 2 AlH (1.5 M in toluene, 0.519 ml, 0.778 mmol) under nitrogen. The resulting suspension was stirred for 1 h at room temperature, followed by addition of a solution of 4f (93 mg, 0.389 mmol) in THF (5 ml). The mixture was stirred for 1 h at room temperature, followed by addition of H 2 O (0.5 ml). After stirring for 1 h, the reaction mixture was poured into 20 ml of saturated aqueous NaHCO 3 and extracted with diethyl ether (3x 30 ml). The combined organic layer was washed with brine, dried over MgSO 4, and filtered through a pad of Celite. After concentration, the residue was purified through silica gel flash column chromatography (eluent: hexanes: ethyl acetate = 10:1) to give compound (Z)-4f-d (190 mg, 0.56 mmol) in 38% yield. 1 H NMR (500 MHz, CDCl 3 ) 7.74 (d, 2H, J = 8.4 Hz), 7.30 (d, 2H, J = 8.0 Hz), 5.67 5.71 (m, 1H), 4.93 (d, 1H, J = 10.4 Hz), 4.45 (t, 1H, J = 5.6 Hz), 2.94 (dd, 2H, J = 6.8, 13.6 Hz), 2.43 (s, 3H), 2.01 2.07 (m, 2H), 1.53 1.59 (m, 3H); MS (ES + ) Calculated for [C 12 H 16 DNaNO 2 S] + : 263.1; Found: 263.1. SI-23

6 Compound 6 was prepared in 83% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (500 MHz, CDCl 3 ) 7.76 (d, 2H, J = 8.0 Hz), 7.21 7.33 (m, 7H), 3.79 3.84 (m, 1H), 3.38 3.42 (m, 1H), 3.11 3.16 (m, 1H), 2.74 (d, 1H, J = 9.6 Hz), 2.43 (s, 3H), 1.40 1.67 (m, 4H); MS (ES + ) Calculated for [C 18 H 20 DNaNO 2 S] + : 339.1; Found: 339.2. 6 Compound 6 was prepared in 74% yield according to the general procedure A. The reaction time was 2 h. 1 H NMR (400 MHz, CDCl 3 ) 7.76 (d, 2H, J = 8.0 Hz), 7.21 7.33 (m, 7H), 3.81 3.83 (m, 1H), 3.37 3.41 (m, 1H), 3.22 (d, 1H, J = 3.2 Hz), 3.11 3.22 (m, 1H), 2.43 (s, 3H), 1.40 1.67 (m, 4H); MS (ES + ) Calculated for [C 18 H 20 DNaNO 2 S] + : 339.1; Found: 339.2. SI-24

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SI-94 3.832 3.824 3.812 3.808 3.800 3.788 3.781 3.422 3.414 3.410 3.407 3.396 3.389 3.382 3.370 3.267 3.257 3.232 3.223 3.155 3.148 3.138 3.133 3.121 3.114 3.096 2.782 2.745 2.721 2.577 2.420 2.260 1.00 1.04 1.05 0.93 0.00 0.13 0.03 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 PPM licui-3-38-1h USER: -- DATE: Oct 23 2009 F1: 399.951 F2: 399.949 SW1: 5132 OF1: 2151.2 PTS1d: 16384 EX: s2pul PW: 7.0 usec PD: 3.0 sec NA: 20 LB: 0.0 WinNuts - $licui-3-38-1h-e-deuterium-product.fid

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SI-96 3.828 3.819 3.809 3.800 3.793 3.421 3.419 3.414 3.412 3.406 3.403 3.397 3.393 3.385 3.378 3.368 3.268 3.258 3.229 3.221 3.161 3.152 3.145 3.134 3.128 3.116 3.109 3.091 2.779 2.755 2.746 2.722 1.00 1.01 0.02 0.90 1.01-0.00 0.01 0.03 4.0 3.8 3.6 3.4 3.2 3.0 2.8 PPM licui-3-45-1-1h PTS1d: 16384 LB: 0.0 F1: 399.951 F2: 399.949 SW1: 5132 OF1: 2150.4 EX: s2pul PW: 7.0 usec PD: 3.0 sec NA: 32 USER: -- DATE: Nov 3 2009 WinNuts - $licui-3-45-1-1h.fid