Supporting Information

Supporting Information Copper-Catalyzed Cross-Coupling of Non-activated Secondary Alkyl Halides and Tosylates with Secondary Alkyl Grignard Reagents Chu-Ting Yang, Zhen-Qi Zhang, Jun Liang, Jing-Hui Liu, Xiao-Yu Lu, Huan-Huan Chen, Lei Liu* Tsinghua-Peking Center for Life Sciences, Department of Chemistry, Tsinghua University, Beijing 100084, China; Department of Chemistry, University of Science and Technology of China, Hefei 230026, China Table of Contents I. General Information S2 II. Preparation of Substrates S3-S7 III. Experimental Procedures and Spectral Data S8-S23 IV. References S24 V. NMR Spectra, GC-MS, and HPLC Analysis S25 S91 VI. Crystallographic Data S92-S130 S1

I. General Information a. Materials All the reactions were carried out in oven-dried Schlenk tubes under argon atmosphere (purity 99.999%). Copper(I) iodide was purchased from Sinopharm Chemical Reagent Co., Ltd as a off-white powder and refluxed in THF for further purification. The following chemicals were purchased and used as received: LiO t Bu (99.9%, Alfa-Aesar ), KO t Bu (Acros), NaO t Bu (Acros), LiOMe (99%, Acros), Alcohols (Alfa-Aesa or Aldrich), Grignard reagents (TCI or Aldrich),PPh 3 (Aldrich), P(n-Bu) 3 (Aldrich), P(t-Bu) 3 (Aldrich), (S)-propane-1,2-diol (Alfa-Aesa), (R)-pyrrolidin-3-ol (Alfa-Aesa), (S)-pyrrolidin-3-ol (Alfa-Aesa), (S)-4-phenylbutan-2-ol (Alfa-Aesa), N 1,N 1,N 2,N 2 -tetramethylethane-1,2-diamine(alfa-aesa). Other alkyl halides were purchased from Aldrich Chemisty or TCI AMERICA. All the other reagents and solvents mentioned in this text were purchased from commercial sources and used without purification. b. Analytical Methods 1 H-NMR, 13 C-NMR spectra were recorded on a Bruker Avance 400 spectrometer at ambient temperature in CDCl 3 unless otherwise noted; 11 B NMR signals are quoted relative to BF 3.Et 2 O. Data for 1 H-NMR are reported as follows: chemical shift (δ ppm), multiplicity, integration, and coupling constant (Hz). Data for 13 C-NMR are reported in terms of chemical shift (δ ppm), multiplicity, and coupling constant (Hz). Gas chromatographic (GC) analysis was acquired on a Shimadzu GC-2014 Series GC System equipped with a flame-ionization detector. GC-MS analysis was performed on Thermo Scientific AS 3000 Series GC-MS System. HRMS analysis was performed on Finnigan LCQ advantage Max Series MS System. HPLC analysis was performed on Waters-Breeze (2487 Dual Absorbance Detector and 1525 Binary HPLC Pump). Chiralpak IC, AD, AS, KM columns were purchased from Daicel Chemical Industries, LTD. Organic solutions were concentrated under reduced pressure on a Buchi rotary evaporator. Flash column chromatographic purification of products was accomplished using forced-flow chromatography on Silica Gel (200-300 mesh). S2

II. Preparation of Substrates a. Preparation of alkyl tosylates Alkyl tosylates were prepared according to literature procedure [1]. p-toluenesulfonyl chloride (22.8 g, 120 mmol) was added over a period of 30 min to a stirred solution of pyridine (50 ml) and alcohols (100 mmol) maintained at 0 C. The reaction mixture was allowed to stir an additional 3 h and then quenched with H 2 O (150 ml) and extracted with CH 2 Cl 2 (3 60 ml), and the combined organic layers were washed with 3 M HCl (3 80 ml) followed by 10% NaHCO 3 (1 80 ml). The organic layer was dried over Na 2 SO 4 and concentrated under vacuum and the crude product purified by silica gel chromatography (CH 2 Cl 2 ). OTs MeO 4-(4-methoxyphenyl)butan-2-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.87 7.75 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.03 6.93 (m, 2H), 6.86 6.71 (m, 2H), 4.71 4.56 (m, 1H), 3.78 (s, 3H), 2.61 2.40 (m, 5H), 1.95-1.86 (m, 1H), 1.83 1.71 (m, 1H), 1.29 (d, J = 6.3 Hz, 3H). OTs 4-methyl-1-phenylpentan-3-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.80 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.28 7.23 (m, 2H), 7.18 (t, J = 7.3 Hz, 1H), 7.07 (d, J = 7.1 Hz, 2H), 4.50 (dt, J = 7.2, 4.7 Hz, 1H), 2.65 2.55 (m, 1H), 2.54 2.46 (m, 1H), 2.44 (s, 3H), 1.91-1.8 (m, 3H), 0.87 (dd, J = 6.8, 1.7 Hz, 6H). OTs 1-phenylnonan-3-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.79 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.27 7.22 (m, 2H), 7.17 (dd, J = 8.5, 6.2 Hz, 1H), 7.07 (d, J = 7.0 Hz, 2H), 4.59 (p, J = 6.0 Hz, 1H), 2.57 (ddd, J = 16.1, 8.0, 4.5 Hz, 2H), 2.44 (s, 3H), 1.89 (ddd, S3

J = 12.1, 9.7, 6.1 Hz, 2H), 1.60 (ddd, J = 11.3, 7.2, 3.9 Hz, 2H), 1.27 1.11 (m, 8H), 0.85 (t, J = 7.0 Hz, 3H). F 3 C OTs 1-(3-(trifluoromethyl)phenyl)propan-2-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.58 7.50 (m, 2H), 7.43 (d, J = 7.7 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.26-7.24 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 4.79 4.67 (m, 1H), 2.89 (qd, J = 14.1, 6.5 Hz, 2H), 2.39 (s, 3H), 1.39 (d, J = 6.3 Hz, 3H). OTs undec-1-en-5-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.79 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 5.70 (ddt, J = 17.1, 10.5, 6.6 Hz, 1H), 5.00 4.91 (m, 2H), 4.58 (p, J = 6.0 Hz, 1H), 2.44 (s, 3H), 2.10 1.94 (m, 2H), 1.76 1.63 (m, 2H), 1.56 (d, J = 4.4 Hz, 2H), 1.27 1.13 (m, 8H), 0.86 (t, J = 7.1 Hz, 3H). O S N O O S O O According to literature procedure [2]. To a mixture of the crude (R)-3-hydroxypyrrolidine (purchased from Alfa- Aesa), pyridine (8.6 ml, 106.0 mmol, 4.8 equiv), and a catalytic amount of DMAP in CH 2 Cl 2 (50 ml) was added, at 0 C, p-tosyl chloride (21.3 g, 112.0 mmol, 5.0 equiv). After being stirred for 48 h at room temperature and under an argon atmosphere, the solvent and pyridine were evaporated and the resulting solid was at first washed by 50/50 Et 2 O/petroleum ether to remove the excessive p-tosyl chloride and then chromatographed on silica gel (eluent: 45/55 AcOEt/EP), leading to a white solid. (R)-1-tosylpyrrolidin-3-yl 4-methylbenzenesulfonate 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 7.61 (m, 4H), 7.32 (t, J = 7.7 Hz, 4H), 4.94 (dt, J = 7.2, 2.4 Hz, 1H), 3.50 3.39 (m, 2H), 3.38 3.32 (m, 1H), 3.23 (td, J = 9.7, 7.0 Hz, 1H), 2.45 (d, J = 8.4 Hz, 6H), 2.06 1.90 (m, 2H). S4

HO OH BnBr, refulx K 2 CO 3,acetone BnO OH TsCl, Py BnO OTs According to literature procedure [3]. To a stirred solution of (S)-propane-1,2-diol (12.3 mmol) in acetone (30 ml) were added K 2 CO 3 (6.8 g, 36.9 mmol), TBAI (0.02 g), and benzyl bromide (13.5 mmol). The mixture was heated to reflux for 18 h. The reaction mixture was then concentrated under reduced pressure. The crude dissolved in water (20 ml) and extracted into EtOAc (3 20 ml). The organic layer was washed with water (1 20 ml), brine (1 20 ml), dried (Na 2 SO 4 ), and concentrated under reduced pressure. The crude product was purified by column chromatography (60 120 Silica gel, 1:10 EtOAc: petroleum ether) to obtain (S)-1-(benzyloxy)propan-2-ol as a yellow syrup. Then the alkyl tosylate was prepared according to literature procedure [1]. O OTs (S)-1-(benzyloxy)propan-2-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.78 (d, J = 8.3 Hz, 2H), 7.32-7.20 (m, 7H), 4.74 (td, J = 6.2, 4.6 Hz, 1H), 4.42 (d, J = 3.5 Hz, 2H), 3.51 (dd, J = 10.7, 5.9 Hz, 1H), 3.44 (dd, J = 10.7, 4.4 Hz, 1H), 2.41 (s, 3H), 1.31 (d, J = 6.5 Hz, 3H). Br O OTs (S)-1-(4-bromobenzyloxy)propan-2-yl 4-methylbenzenesulfonate. 1 H NMR (400 MHz, CDCl 3 ) δ 7.80 7.74 (m, 2H), 7.46 7.41 (m, 2H), 7.28 7.24 (m, 2H), 7.11 7.05 (m, 2H), 4.79 4.70 (m, 1H), 4.37 (d, J = 4.3 Hz, 2H), 3.50 (dd, J = 10.7, 6.0 Hz, 1H), 3.44 (dd, J = 10.7, 4.3 Hz, 1H), 2.42 (s, 3H), 1.30 (d, J = 6.5 Hz, 3H). b. Preparation of alkyl halides. Br Br K 2 CO 3,DMF R R + Br HO rt, 12h O According to literature procedure [4]. A mixture of phenol (20 mmol) and K 2 CO 3 (3.317 g, 24 mmol) in DMF (30 ml) was stirred for 1 h at room temperature, and 1,3-dibromobutane (40 mmol) was added. After stirring overnight, the mixture was poured into water (200 ml) and extracted with CH 2 Cl 2. The organic phase was washed with 2% NaOH (3 100 ml) and water (2 100 ml), S5

dried over Na 2 SO 4, followed by usual work-up and purification on silica gel column chromatography. O O Br O butyl 4-(3-bromobutoxy)benzoate 1 H NMR (400 MHz, CDCl 3 ) δ 8.02 7.94 (m, 2H), 6.95 6.84 (m, 2H), 4.39 (ddd, J = 9.2, 6.7, 4.3 Hz, 1H), 4.29 (t, J = 6.6 Hz, 2H), 4.19 (ddd, J = 5.9, 5.1, 2.9 Hz, 2H), 2.35 2.17 (m, 2H), 1.80 (d, J = 6.7 Hz, 3H), 1.74 (dd, J = 10.1, 4.6 Hz, 2H), 1.52 1.42 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H). Br O Br 1-bromo-2-(3-bromobutoxy)naphthalene 1 H NMR (400 MHz, CDCl 3 ) δ 8.21 (dd, J = 8.5, 0.6 Hz, 1H), 7.77 (dd, J = 8.6, 5.7 Hz, 2H), 7.55 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.39 (ddd, J = 8.1, 6.9, 1.1 Hz, 1H), 7.24 (d, J = 1.9 Hz, 1H), 4.57 (ddd, J = 9.5, 6.7, 4.0 Hz, 1H), 4.35 4.27 (m, 2H), 2.44 2.31 (m, 1H), 2.30 2.15 (m, 1H), 1.83 (d, J = 6.7 Hz, 3H). OH Br 2,PPh 3,imidazole Br According to literature procedure [5]. Bromine (20 mmol) was added to a suspension of PPh 3 (20 mmol) and imidazole (20 mmol) in anhydrous CH 2 Cl 2 (100 ml) at 0 ºC. 4-phenylbutan-2-ol (15 mmol) was then added slowly by syringe. The resulting mixture was allowed to warm to room temperature. After 14 hours, the reaction mixture was concentrated under vacuum to remove the CH 2 Cl 2. The product was purified by column chromatography (eluant: petroleum ether). (3-bromobutyl)benzene, 1 H NMR (400 MHz, CDCl 3 ) δ 7.32 7.27 (m, 2H), 7.20 (dd, J = 8.7, 5.1 Hz, 3H), 4.08 (ddd, J = 8.8, 6.6, 4.5 Hz, 1H), 2.86 (ddd, J = 14.1, 8.9, 5.3 Hz, 1H), 2.75 (ddd, J = 13.8, 8.8, 7.2 Hz, 1H), 2.20 1.99 (m, 2H), 1.73 (d, J = 6.7 Hz, 3H). N H + Br Br NaH/DMF 0 o C N Br S6

1-(4-bromopentyl)-1H-indole [6] : To a solution of indole (1.17 g, 0.01 mol) in 10 ml of DMF was added sodium hydride (0.253 g, 0.011 mol, 60% in mineral oil, previously washed with hexane) under a nitrogen atmosphere and the reaction mixture was stirred for 30 min at room temperature before 1,4-dibromopentane (20 mmol) was added. After 2h of stirring the reaction mixture was quenched by drop-wise addition of water, extracted with EtOAc and washed with water and brine. The organic layer was dried over Na 2 SO 4, filtered and concentrated in vacuo and the residue purified by flash column chromatography on silica gel. GC-MS: t =34.50, m/z 265 (M + ). O Cl + HN Br Et 3 N,DMAP,DCM O N Br According to literature procedure [7]. Benzoyl chloride (10 mmol) was dissolved in DCM (5.0 ml). The resulting solution was slowly added to a mixture of 4-hydroxypiperidine (10 mmol), Et 3 N ( 20.0 mmol ) in DCM (40.0 ml) at -10 o C. The reaction mixture was warmed to room temperature. After it was stirred for 2 h, the reaction mixture was washed with HCl (1 M, 2 20.0 ml) and then brine (30.0 ml). The organic layer was dried over MgSO 4, filtered and concentrated in vacuo and the residue purified by flash column chromatography on silica gel. (4-bromopiperidin-1-yl)(phenyl)methanone, white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.46 7.33 (m, 5H), 4.43 (tt, J = 7.4, 3.8 Hz, 1H), 3.68 (br, 4H), 2.05 (br s, 4H). HN Br TsCl/Py TsN Br According to literature procedure [5].p-TsCl (30 mmol) was added to a stirred solution of 4-bromopiperidine (20 mmol) in pyridine (20 ml). The resulting orange mixture was stirred for 20 h, and then it was poured into a separation funnel that contained CH 2 Cl 2 (50 ml) and HCl (1N; 50 ml). The layers were separated, and the aqueous layer was extracted with CH 2 Cl 2 (3 30 ml). The combined organic layers were sequentially washed with HCl (1N; 75 ml) and brine (100 ml), then dried over anhydrous Na 2 SO 4, filtered, and concentrated under vacuum. The residue was purified by column chromatography, furnishing the product as a white solid (710 mg, 95%). 4-bromo-1- tosylpiperidine. 1 H NMR (400 MHz, CDCl 3 ) δ 7.70 7.58 (m, 2H), 7.34 (d, J = 7.9 Hz, 2H), 4.24 (tt, J = 7.0, 3.7 Hz, 1H), 3.21 (ddd, J = 11.6, 8.0, 3.4 Hz, 2H), 3.12 3.02 (m, 2H), 2.44 (s, 3H), 2.19 (ddt, J = 15.2, 7.7, 3.7 Hz, 2H), 2.04 (dtd, J = 13.9, 6.8, 3.5 Hz, 2H). S7

III. Copper-Catalyzed Cross-Coupling of Non-activated Secondary Alkyl Halides and Tosylates with Secondary Alkyl Grignard Reagents Experimental Procedures for Examples Described in Table 1. In air, Cu catalyst (0.05 mmol), 4-phenylbutan-2-yl 4-methylbenzenesulfonate (0.5 mmol), and the additive (0.5 mmol ) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). HMPA (50 L), ligand (0.1 mmol), and cyclohexylmagnesium bromide (1 mol/l in THF, 1mL) were added in turn under Argon atmosphere at 0 o C (if the ligand is a solid, it was added along with the Cu catalyst). The reaction mixture was stirred at the mentioned temperature for the indicated amount of time, then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ). Benzophenone (91.1mg, 0.5mmol) was added as internal standard. The product yield was determined by GC. OTs + MgBr Cu cat. 1a 1equiv 2a 2equiv 3a Entry X Catalyst (10 mol%) Additive (20 mol %) Li salt Co-solvent Temp. ( o C) Yield (%) a 1 OTs CuI - - - 25 8 2 OTs CuI TMEDA - - 25 14 3 OTs CuI TMEDA - HMPA 25 12 4 OTs CuI TMEDA LiCl HMPA 25 15 5 OTs CuI TMEDA LiBr HMPA 25 18 6 OTs CuI TMEDA LiI HMPA 25 43 7 OTs CuI TMEDA LiO t Bu HMPA 25 46 8 OTs CuI TMEDA LiOMe HMPA 25 65 9 OTs CuI TMEDA LiOMe HMPA 0 85 10 OTs CuI TMEDA LiOMe - 0 86(81 b ) 11 OTs CuI - LiOMe - 0 72 12 OTs CuI P n Bu 3 LiOMe - 0 76 13 OTs CuI NMP LiOMe - 0 75 14 OTs CuI PhC CCH 3 LiOMe - 0 83 15 OTs CuBr TMEDA LiOMe - 0 54 S8

16 OTs CuTc TMEDA LiOMe - 0 32 17 OTs Cu(OTf) 2 TMEDA LiOMe - 0 56 18 Br CuI TMEDA LiOMe - 0 84 c 19 I CuI TMEDA LiOMe - 0 43 d 20 Cl CuI TMEDA LiOMe - 0 8 e 21 OMs CuI TMEDA LiOMe - 0 21 f 22 OTs - TMEDA LiOMe - 0 Trace 23 OTs Pd(OAc) 2 TMEDA LiOMe - 0 Trace g 24 OTs NiI 2 TMEDA LiOMe - 0 Trace g a GC yields after 24 hours (average of two runs). b isolated yields. c (3-bromobutyl)benzene was used. d (3-iodobutyl)benzene was used. e (3-chlorobutyl)benzene was used. f 4-phenylbutan-2-yl methanesulfonate was used. g 2 mol% of catalyst was added.note that NiI 2 was used because it is an anhydrous salt. NiCl 2 and NiBr 2 as hydrated salts were also tested to give the same negative results. Experimental Procedures for Examples Described in Table 2. Gengeral Procedure A. In air, CuI (9.5 mg, 0.05 mmol), and LiOMe (19 mg, 0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). The alkyl 4-methylbenzenesulfonate (0.5 mmol), TMEDA (0.1 mmol) and alkyl magnesium bromide (1 mol/l in THF, 1mL) were added in turn by syringe under argon atmosphere at 0 o C (if the alkyl 4-methylbenzenesulfonate is a solid, it was added along with CuI). The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. Gengeral Procedure B. In air, CuI (9.5 mg, 0.05 mmol), and LiOMe (19 mg, 0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). The alkyl bromide (0.5 mmol), TMEDA (0.1 mmol) and alkyl magnesium bromide (1 mol/l in THF, 1mL) were added in turn by syringe under argon atmosphere at 0 o C (if the alkyl bromide is a solid, it was added along with CuI). The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), S9

concentrated, and purified by column chromatography. (3-cyclohexylbutyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 7.28 (m, 2H), 7.25 7.17 (m, 3H), 2.71 (ddd, J = 13.7, 10.8, 5.1 Hz, 1H), 2.56 (ddd, J = 13.7, 10.3, 6.1 Hz, 1H), 1.80 1.62 (m, 6H), 1.51 1.35 (m, 2H), 1.29 1.00 (m, 6H), 0.94 (d, J = 6.7 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.3, 128.3, 128.2, 125.5, 42.8, 37.8, 36.2, 34.0, 30.6, 28.7, 27.0, 26.9, 26.8, 16.1 ppm. GC-MS: t =26.66, m/z 216 (M + ); HRMS calcd for C 16 H 24 (M+): 216.1878; found: 216.1875. (3-cyclohexylnonyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.35 7.27 (m, 2H), 7.24 7.12 (m, 3H), 2.53-2.68 (m, 2H), 1.77 1.04 (m, 24H), 0.93 (t, J = 6.7 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.39, 128.34, 128.24, 125.52, 43.12, 40.23, 34.28, 33.01, 31.97, 30.75, 29.90, 29.86, 29.75, 27.75, 27.03, 26.96, 22.75 ppm. GC-MS: t =21.66, m/z 286 (M + ); HRMS calcd for C 21 H 34 (M+): 286.2661 ; found: 286.2664. (3-cyclohexyl-4-methylpentyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.29-7.17 (m, 5H), 2.58 (td, J = 7.7, 3.6 Hz, 2H), 1.85 1.50 (m, 8H), 1.38 (tdd, J = 11.3, 5.3, 2.5 Hz, 1H), 1.26 0.96 (m, 6H), 0.87 (dd, J = 12.1, 6.8 Hz, 6H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.5, 128.3, 128.3, 125.6, 49.4, 40.2, 37.1, 31.8, 30.4, 30.2, 28.9, 27.1, 27.0, 26.9, 21.5, 19.2 ppm. GC-MS: t =18.80, m/z 244 (M + ); HRMS calcd for C 18 H 28 (M+): 244.2191; found: 244.2193 F 3 C S10

1-(2-cyclohexylpropyl)-3-(trifluoromethyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.46 7.28 (m, 4H), 2.80 (dd, J = 13.4, 5.0 Hz, 1H), 2.33 (dd, J = 13.4, 9.6 Hz, 1H), 1.79 1.63 (m, 6H), 1.26 1.08 (m, 6H), 0.77 (d, J = 6.8 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.2, 132.5, 130.5(q, 2 J(C, F)=31.9 Hz), 128.5, 125.7(q, 3 J(C, F)=3.8 Hz), 124.4(q, 1 J(C, F)=272.1 Hz), 122.5(q, 3 J(C, F)=3.8 Hz), 42.6, 40.5, 30.8, 30.2, 28.7, 26.9, 26.8, 26.7, 15.6 ppm. GC-MS: t =15.63, m/z 270 (M + ); HRMS calcd for C 16 H 21 F 3 (M+): 270.1595; found: 270.1596. OMe O HO (4-(4-cyclohexylpentyloxy)-3-methoxyphenyl)methanol. Following general procedure B, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 6.92 (d, J = 1.1 Hz, 1H), 6.87 6.84 (m, 2H), 4.61 (s, 2H), 3.99 (t, J = 7.1 Hz, 2H), 3.87 (s, 3H), 1.76 1.14 (m, 17H), 0.85 (d, J = 6.7 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 149.6, 148.2, 133.6, 119.5, 113.0, 111.0, 69.6, 65.4, 56.0, 42.6, 37.9, 30.8, 30.2, 28.6, 27.2, 27.0, 26.9, 26.8, 16.1 ppm. GC-MS: t =24.81, m/z 306 (M + ); HRMS calcd for C 19 H 30 O 3 (M+): 306.2195; found: 306.2191. Ts N 4-cyclohexyl-1-tosylpiperidine. Following general procedure B, white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 3.80 (dd, J = 9.3, 2.1 Hz, 2H), 2.43 (s, 3H), 2.15 (td, J = 12.1, 2.4 Hz, 2H), 1.73 1.59 (m, 7H), 1.34 (qd, J = 12.6, 4.1 Hz, 2H), 1.23-1.03 (m, 4H), 0.98 0.82 (m, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.3, 133.2, 129.5, 127.8, 46.9, 42.2, 40.1, 30.0, 28.7, 26.6, 26.5, 21.5 ppm. HRMS calcd for C 18 H 27 NO 2 S (M+): 321.1762; found: 321.1766. O O O Butyl 4-(3-cyclohexylbutoxy)benzoate. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.98 (d, J = 8.9 Hz, 2H), 6.90 (d, J = 8.9 Hz, 2H), 4.29 (t, J = 6.6 Hz, 2H), 4.10 3.97 (m, 2H), 1.95 1.86 (m, 1H), 1.77 1.05 (m, 17H), 0.98 (t, J = 7.4 Hz, 3H), 0.90 (d, J = 6.6 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 166.5, 162.9, 131.5, 122.7, 114.1, 67.0, S11

64.5, 42.9, 35.0, 33.3, 30.9, 30.5, 28.7, 26.9, 26.8, 26.8, 19.3, 16.2, 13.8 ppm. GC-MS: t =25.65, m/z 332 (M + ); HRMS calcd for C 21 H 32 O 3 : 332.2351; found([m+h] + ): 333.2418. undec-1-en-5-ylcyclohexane. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 5.81 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 4.99 (ddd, J = 17.1, 3.6, 1.6 Hz, 1H), 4.92 (ddt, J = 10.2, 2.2, 1.1 Hz, 1H), 2.10 1.93 (m, 2H), 1.74 1.08 (m, 24H), 0.89 (t, J = 6.8 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 139.7, 113.9, 42.8, 40.2, 32.1, 32.0, 30.7, 30.2, 29.9, 29.8, 29.8, 27.8, 27.0, 27.0, 22.7, 14.1 ppm. GC-MS: t =16.30, m/z 236 (M + ); HRMS calcd for C 17 H 32 (M+): 236.2504; found: 236.2505. (3,4-dimethylpentyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.29-7.11 (m, 5H), 2.67 (ddd, J = 13.8, 10.7, 4.9 Hz, 1H), 2.52 (ddd, J = 13.7, 10.1, 6.1 Hz, 1H), 1.67-1.57 (m, 2H), 1.45-1.33 (m, 2H), 0.87 (dd, J = 6.7, 1.8 Hz, 6H), 0.82 (d, J = 6.8 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.3, 128.4, 128.3, 125.5, 38.3, 36.2, 34.0, 32.0, 20.2, 18.0, 15.3 ppm. GC-MS: t =12.11, m/z 176 (M + ); HRMS calcd for C 13 H 20 (M+): 176.1565; found: 176.1569. O N (4-isopropylpiperidin-1-yl)(phenyl)methanone. Following general procedure B, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 (m, 5H), 4.76 (br, 1H), 3.77 (br, 1H), 2.92 (br, 1H), 2.68 (br, 1H), 1.80 (br, 1H), 1.61 (br, 1H), 1.47 (dt, J = 13.2, 6.6 Hz, 1H), 1.33 1.14 (m, 3H), 0.89 (d, J = 6.8 Hz, 6H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 170.3, 136.6, 129.4, 128.4, 126.9, 48.4, 42.8, 32.4, 30.0, 29.1, 19.7 ppm. GC-MS: t =20.50, m/z 231 (M + ); HRMS calcd for C 15 H 21 NO (M+): 231.1623; found: 231.1626. S12

(3,4-dimethylhexyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 7.27 (m, 2H), 7.24 7.14 (m, 3H), 2.75-2.64 (m, 1H), 2.62 2.46 (m, 1H), 1.73 1.60 (m, 1H), 1.56 1.30 (m, 4H), 1.24 1.07 (m, 1H), 0.99 0.71 (m, 9H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.3, 143.3, 128.4, 128.3, 125.5, 39.5, 38.6, 37.0, 37.0, 36.1, 35.0, 34.1, 34.1, 27.5, 25.6, 16.5, 15.9, 14.3, 14.0, 12.2 ppm. GC-MS: t =11.37, m/z 190 (M + ); HRMS calcd for C 14 H 22 (M+): 190.1722; found: 190.1724. N 1-(4,5-dimethylheptyl)-1H-indole. Following general procedure B, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.65 (d, J = 7.9 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.25 7.20 (m, 1H), 7.15 7.07 (m, 2H), 6.51 (dd, J = 3.1, 0.4 Hz, 1H), 4.15 4.07 (m, 2H), 1.93-1.78 (m, 2H), 1.45 1.09 (m, 6H), 0.86 (ddd, J = 15.9, 10.5, 4.1 Hz, 6H), 0.76 (t, J = 7.2 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 136.0, 128.6, 127.7, 127.7, 121.3, 120.9, 119.1, 109.3, 100.8, 46.8, 46.7, 39.3, 38.4, 37.2, 36.0, 32.2, 30.3, 28.4, 28.4, 27.5, 25.4, 16.4, 16.0, 14.2, 13.9, 12.2, 12.2 ppm. GC-MS: t =19.98, m/z 243 (M + ); HRMS calcd for C 17 H 25 N (M+): 243.1987; found: 243.1989. (3-cyclopentylbutyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.31-7.27 (m, 2H), 7.22 7.15 (m, 3H), 2.72 (ddd, J = 13.7, 10.9, 4.9 Hz, 1H), 2.53 (ddd, J = 13.6, 10.3, 6.2 Hz, 1H), 1.81 1.71 (m, 3H), 1.62 1.34 (m, 7H), 1.17 1.09 (m, 2H), 0.97 (d, J = 6.5 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.3, 128.4, 128.3,125.5, 46.3, 37.9, 37.7, 33.5, 30.7, 30.2, 25.5, 17.7 ppm. GC-MS: t =16.05, m/z 202 (M + ); HRMS calcd for C 15 H 22 (M+): 202.1722; found: 202.1725. S13

(3-methylnonyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.36 7.27 (m, 2H), 7.25 7.16 (m, 3H), 2.76 2.51 (m, 2H), 1.73 1.62 (m, 1H), 1.54 1.18 (m, 12H), 0.97 (d, J = 6.3 Hz, 3H), 0.94 (t, J = 6.8 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.2, 128.4, 128.4, 125.5, 39.0, 37.0, 33.5, 32.5, 32.0, 29.7, 26.7, 22.7, 19.6, 14.1 ppm. GC-MS: t =15.80, m/z 218 (M + ); HRMS calcd for C 16 H 26 (M+): 218.2035; found: 218.2039.. Ts N 4-hexyl-1-tosylpiperidine. Following general procedure B, white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 3.75 (d, J = 11.6 Hz, 2H), 2.43 (s, 3H), 2.21 (td, J = 11.8, 2.4 Hz, 2H), 1.70 (d, J = 11.2 Hz, 2H), 1.30 1.10 (m, 13H), 0.86 (t, J = 6.9 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.3, 133.3, 129.5, 127.8, 46.6, 36.1, 35.1, 31.8, 31.6, 29.4, 26.5, 22.6, 21.5, 14.1 ppm. HRMS calcd for C 18 H 29 NO 2 S (M+): 323.1919; found: 323.1923. N 1-(4-methyldecyl)-1H-indole. Following general procedure B, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.3 Hz, 1H), 7.24 7.15 (m, 1H), 7.16 7.03 (m, 2H), 6.49 (dd, J = 3.1, 0.6 Hz, 1H), 4.10 (t, J = 7.3 Hz, 2H), 1.95 1.77 (m, 2H), 1.40 1.05 (m, 13H), 0.92 0.81 (m, 6H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 134.9, 127.6, 126.7, 120.3, 119.9, 118.1, 108.3, 99.8, 45.7, 35.9, 33.2, 31.5, 30.9, 28.6, 26.8, 25.9, 21.6, 18.5, 13.1. GC-MS: t =21.90, m/z 271 (M + ); HRMS calcd for C 19 H 29 N (M+): 271.2300; found: 271.2304. Br O 1-bromo-2-(3-methylnonyloxy)naphthalene. Following general procedure B, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 8.25 8.18 (m, 1H), 7.74 (dd, J = 12.2, 6.2 Hz, 2H), 7.53 (ddd, J = 8.4, 6.9, 1.2 Hz, 1H), 7.36 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.24 7.21 (m, 1H), 4.24 4.09 (m, 2H), 1.96 1.86 (m, 1H), 1.83 1.74 (m, 1H), 1.66 (dt, J = 14.3, 7.0 Hz, 1H), 1.38 1.20 (m, 10H), 0.96 (d, J = 6.6 Hz, 3H), 0.88 (t, J = 6.8 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 153.5, 133.3, 129.7, 128.8, 128.0, 127.6, 126.3, 124.3, 115.2, 109.5, 68.7, 37.1, 36.4, 32.0, 29.8, 29.6, 27.0, 22.7, 19.8, 14.2 ppm. HRMS calcd for C 20 H 27 BrO (M+): 362.1245; found: 362.1249. S14

Experimental Procedures for Examples Described in Scheme 1. Gengeral Procedure. In air, CuI (9.5 mg, 0.05 mmol), and LiOMe (19 mg, 0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). The alkyl 4-methylbenzenesulfonate or alkyl bromide (0.5 mmol), TMEDA (0.1 mmol) and tert-butylmagnesium chloride (2 mol/l in THF, 0.5mL) were added in turn by syringe under argon atmosphere at 0 o C. The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. (4,4-dimethylpentyl)benzene. Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.35 7.28 (m, 2H), 7.25 7.17 (m, 3H), 2.61 (t, J=7.8Hz, 2H), 1.69 1.56 (m, 2H), 1.31 1.25 (m, 2H), 0.91 (s, 9H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 142.0, 127.4, 127.2, 124.6, 42.9, 35.9, 29.3, 28.4, 25.7 ppm. GC-MS: t =11.16, m/z 176 (M + ); HRMS calcd for C 13 H 20 (M+): 176.1565; found: 176.1568. F 3 C 1-(trifluoromethyl)-3-(2,3,3-trimethylbutyl)benzene. Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.47 7.30 (m, 4H), 3.01 (dd, J = 13.2, 2.5 Hz, 1H), 2.12 (dd, J = 13.2, 11.5 Hz, 1H), 1.53-1.44 (m, 1H), 0.98 (s, 9H), 0.72 (d, J = 6.8 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 143.8, 132.6, 130.5(q, 2 J(C, F)=31.8 Hz), 128.5, 125.7(q, 3 J(C, F)=3.7 Hz), 124.3(q, 1 J(C, F)=272.2 Hz), 122.4(q, 3 J(C, F)=3.8 Hz), 45.5, 38.2, 33.2, 27.4, 13.6 ppm. 19 F NMR (377 MHz, CDCl 3 ) δ -62.5 ppm. HRMS calcd for C 14 H 19 F 3 (M+): 244.1439; found: 244.1442. Experimental Procedures for Examples Described in Scheme 2. S15

Gengeral Procedure. In air, CuI (9.5 mg, 0.05 mmol), and LiOMe (19 mg, 0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). The alkyl iodide (0.5 mmol), TMEDA (0.1 mmol) and phenylmagnesium bromide (2 mol/l in THF, 0.5mL) were added in turn by syringe under argon atmosphere at 25 o C. The resulting reaction mixture was stirred vigorously at 25 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. MeO 1-methoxy-4-(3-phenylbutyl)benzene. Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 7.26 (m, 2H), 7.21 7.15 (m, 3H), 7.08 7.00 (m, 2H), 6.84 6.76 (m, 2H), 3.77 (s, 3H), 2.76 2.65 (m, 1H), 2.53 2.38 (m, 2H), 1.94 1.81 (m, 2H), 1.26 (d, J = 7.0 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 156.6, 146.3, 133.6, 128.2, 127.4, 126.1, 124.9, 112.7, 54.2, 39.2, 38.4, 31.9, 21.5 ppm. HRMS calcd for C 17 H 20 O (M+): 240.1514; found: 240.1514. sec-butylbenzene (CAS: 135-98-8). Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.33 7.27 (m, 2H), 7.23 7.14 (m, 3H), 2.60 (dt, J = 14.1, 7.0 Hz, 1H), 1.65 1.57 (m, 2H), 1.25 (d, J = 7.0 Hz, 3H), 0.84 (t, J = 7.4 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 147.7, 128.2, 127.1, 125.8, 41.7, 31.2, 21.8, 12.2 ppm. Experimental Procedures for Examples Described in Scheme 3. In air, CuI (9.5 mg, 0.05 mmol), LiOMe (19 mg, 0.5 mmol), and 1-bromo-2-(3-bromobutoxy) -naphthalene (0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). TMEDA (0.1 mmol) and cyclohexylmagnesium bromide (1 mol/l in THF, 1mL) were added in turn by syringe under argon atmosphere at 0 o C. The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was S16

then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. Br O 1-bromo-2-(3-cyclohexylbutoxy)naphthalene, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 8.22 (d, J = 8.6 Hz, 1H), 7.78 (dd, J = 8.5, 5.9 Hz, 2H), 7.55 (ddd, J = 8.4, 6.9, 1.2 Hz, 1H), 7.38 (ddd, J = 8.0, 6.8, 1.0 Hz, 1H), 7.28 7.22 (m, 1H), 4.29 4.08 (m, 2H), 2.07 1.95 (m, 1H), 1.78 1.62 (m, 7H), 1.29 1.04 (m, 6H), 0.93 (d, J = 6.6 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 153.5, 133.2, 129.8, 128.8, 128.0, 127.6, 126.2, 124.2, 115.2, 109.4, 69.1, 42.8, 34.9, 33.6, 30.5, 28.8, 26.9, 26.8, 26.8, 16.2 ppm. GC-MS: t =26.86, m/z 360 (M + ); HRMS calcd for C 20 H 25 BrO (M+): 360.1089; found: 360.1086 Experimental Procedures for Examples Described in Scheme 4. In air, CuI (9.5 mg, 0.05 mmol), LiOMe (19 mg, 0.5 mmol), and (S)-1-(4-bromobenzyloxy) -propan-2-yl 4-methylbenzenesulfonate (0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). TMEDA (0.1 mmol) and cyclohexylmagnesium bromide (1 mol/l in THF, 1mL) were added in turn by syringe under argon atmosphere at 0 o C. The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. Br O (S)-1-bromo-4-((2-cyclohexylpropoxy)methyl)benzene. colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.49 7.42 (m, 2H), 7.20 (d, J = 8.4 Hz, 2H), 4.43 (s, 2H), 3.41 (dd, J = 9.1, 5.9 Hz, 1H), 3.25 (dd, J = 9.0, 7.0 Hz, 1H), 1.75 1.56 (m, 6H), 1.26 0.99 (m, 6H), 0.88 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 138.0, 131.4, 129.1, 121.2, 74.2, 72.2, 39.8, 38.5, 30.9, 28.8, 26.8, S17

26.8, 26.7, 13.9. HRMS calcd for C 16 H 23 BrO (M+): 310.0932; found: 310.0936 O S O NH O According to literature procedure [8]. In air, CuI (4.8 mg, 0.025 mmol), biphenyl-4-sulfonamide (0.5 mmol), and K 2 CO 3 (1.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). MeCN (1.5 ml), (S)-1-bromo-4-((2-cyclohexylpropoxy)methyl)benzene (0.6 mmol), and DMEDA (0.25 mol) were added in turn by syringe under argon atmosphere. The resulting reaction mixture was stirred vigorously at 70 ºC for 8 h. The reaction mixture was then diluted with EtOAc, filtered through silica gel with copious washings (Et 2 O or EtOAc), concentrated, and purified by column chromatograph. (S)-N-(4-((2-cyclohexylpropoxy)methyl)phenyl)biphenyl-4-sulfonamide, white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 7.79 (m, 2H), 7.65 7.62 (m, 2H), 7.58 7.55 (m, 2H), 7.52 (s, 1H), 7.48 7.36 (m, 4H), 7.31-7.26 (m, 1H), 7.07 (d, J = 8.4 Hz, 2H), 4.41 (s, 2H), 3.38 (dd, J = 9.1, 5.8 Hz, 1H), 3.22 (dd, J = 9.1, 7.1 Hz, 1H), 1.73 1.56 (m, 6H), 1.26 0.92 (m, 6H), 0.86 (d, J = 6.9 Hz, 3H) ppm. HRMS calcd for C 28 H 33 NO 3 S: 463.2181; found found([m+h] + ): 464.2254. Experimental Procedures for Examples Described in Scheme 5. O F In air, CuI (9.5 mg, 0.05 mmol), and LiOMe (19 mg, 0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). 1-(3-chloropropoxy)-4-fluorobenzene (0.5 mmol), TMEDA (0.1 mmol) and cyclohexylmagnesium bromide (1 mol/l in THF, 1mL) were added in turn by syringe under argon atmosphere at 0 o C. The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. 1-(3-cyclohexylpropoxy)-4-fluorobenzene, colourless liquid. 1 H NMR (400 S18

MHz, CDCl 3 ) δ 6.99 6.90 (m, 2H), 6.85 6.76 (m, 2H), 3.87 (t, J = 6.6 Hz, 2H), 1.80 1.61 (m, 7H), 1.34 1.12 (m, 6H), 0.95 0.84 (m, 2H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ 157.1(d, 1 J(C, F)=237.7 Hz),, 155.3(d, 4 J(C, F)=1.9 Hz), 115.7(d, 2 J(C, F)=23.1 Hz), 115.5(d, 3 J(C, F)=8.0 Hz), 69.1, 37.5, 33.7, 33.4, 26.7,26.4 ppm. 19 F NMR (377 MHz, CDCl 3 ) δ -124.5 ppm. GC-MS: t =17.97, m/z 236 (M + ); HRMS calcd for C 15 H 21 OF (M+): 236.1576; found: 236.1579. Cl In air, CuI (9.5 mg, 0.05 mmol), and LiOMe (19 mg, 0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). 5-chloropentan-2-yl 4-methylbenzenesulfonate (0.5 mmol), TMEDA (0.1 mmol) and cyclohexyl -magnesium bromide (1 mol/l in THF, 0.75 ml) were added in turn by syringe under argon atmosphere at 0 o C. The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column chromatography. (5-chloropentan-2-yl)cyclohexane, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 3.52 (t, J = 6.8 Hz, 2H), 1.83 1.49 (m, 8H), 1.30 0.95 (m, 8H), 0.83 (d, J = 6.7 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 45.6, 42.7, 37.6, 31.4, 30.8, 30.7, 28.7, 26.9, 26.9, 26.8, 16.1. GC-MS: t =13.14, m/z 188 (M + ); HRMS calcd for C 11 H 21 Cl (M+): 188.1332; found: 188.1336. Experimental Procedures for Examples Described in Table 3. Gengeral Procedure. In air, CuI (9.5 mg, 0.05 mmol), LiOMe (19 mg, 0.5 mmol), and alkyl 4-methylbenzenesulfonate (0.5 mmol) were added to a Schlenk tube equipped with a stir bar. The vessel was evacuated and filled with argon (three cycles). TMEDA (0.1 mmol) and alkyl magnesium bromide (1 mol/l in THF, 1mL) were added in turn by syringe under argon atmosphere at 0 o C. The resulting reaction mixture was stirred vigorously at 0 ºC for 24 h. The reaction mixture was then quenched with a saturated solution of NH 4 Cl (10 ml). The resulting solution mixture was then extracted with CH 2 Cl 2 (3 times, 10 ml each), dried over Mg 2 SO 4, filtered through silica gel with copious washings (CH 2 Cl 2 ), concentrated, and purified by column S19

chromatography. O N S O (R)-3-cyclohexyl-1-tosylpyrrolidine(99% ee). Following general procedure, white solid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 3.46 (dd, J = 9.6, 7.7 Hz, 1H), 3.36 (ddd, J = 9.8, 8.7, 2.4 Hz, 1H), 3.15 (td, J = 9.8, 6.8 Hz, 1H), 2.78 (t, J = 9.6 Hz, 1H), 2.44 (s, 3H), 1.96 1.87 (m, 1H), 1.56-1.76 (m, 6H), 1.32-1.41(m, 1H), 1.20 0.98 (m, 4H), 0.83-0.93 (m, 2H). 13 C NMR (101 MHz, CDCl 3 ) δ 143.2, 134.1, 129.6, 127.5, 51.9, 47.9, 45.1, 41.4, 31.9, 31.3, 29.6, 26.3, 26.0, 26.0, 21.5. GC-MS: t =26.02, m/z 307 (M + ); HRMS calcd for C 17 H 25 NO 2 S (M+): 307.1606; found: 307.1608. Enantiomeric excess was determined by chiral HPLC analysis, Chiralcel AD column, 0.5 ml/min, n-heptane/i-proh 98:2, 40 C, retention times (min.): 18.8(minor) and 20.8(major). O N S O (S)-3-cyclohexyl-1-tosylpyrrolidine(99% ee). Enantiomeric excess was determined by chiral HPLC analysis, Chiralcel AD column, 0.5 ml/min, n-heptane/i-proh 98:2, 40 C, retention times (min.): 18.8(major) and 20.8(minor). Ts N (R)-3-hexyl-1-tosylpyrrolidine(98% ee). Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.71 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 3.43 (dd, J = 9.6, 7.4 Hz, 1H), 3.30 3.35 (m, 1H), 3.19 (td, J = 9.2, 7.1 Hz, 1H), 2.77 (dd, J = 9.6, 8.0 Hz, 1H), 2.43 (s, 3H), 2.04 1.86 (m, 2H), 1.38 1.19 (m, 11H), 0.87 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 143.2, 134.1, 129.6, 127.5, 53.3, 47.6, 38.9, 33.1, 31.7, 31.6, 29.3, 28.1, 22.6, S20

21.5, 14.1. GC-MS: t =24.83, m/z 309 (M + ); HRMS calcd for C 17 H 27 NO 2 S (M+): 309.1762; found: 309.1767. Enantiomeric excess was determined by chiral HPLC analysis, Chiralcel AS column, 0.5 ml/min, n-heptane/i-proh 98:2, 40 C, retention times (min.): 37.3(minor) and 40.6 (major). (R)-(3-cyclohexylbutyl)benzene(98% ee). Following general procedure, colourless liquid. Enantiomeric excess was determined by chiral HPLC analysis, Chiralcel OJ column, 0.5 ml/min, n-heptane/i-proh 100:0, 40 C, retention times (min.): 5.6 (minor) and 5.9(major). O (S)-((2-cyclohexylpropoxy)methyl)benzene(99% ee). Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.29 7.15 (m, 5H), 4.42 (s, 2H), 3.35 (dd, J = 9.1, 5.9 Hz, 1H), 3.19 (dd, J = 9.0, 7.1 Hz, 1H), 1.67 1.50 (m, 6H), 1.28 0.89 (m, 6H), 0.82 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 137.9, 127.3, 126.5, 126.4, 73.0, 71.9, 38.7, 37.5, 29.9, 27.7, 25.8, 25.8, 25.7, 12.9. GC-MS: t =18.06, m/z 232 (M + ); HRMS calcd for C 16 H 24 O (M+): 232.1827; found: 232.1826. Enantiomeric excess was determined by chiral HPLC analysis, Chiralcel OD column, 0.8 ml/min, n-heptane/i-proh 99.8:0.2, 40 C, retention times (min.): 10.0(major) and 16.0 (minor) O (S)-((2-methyloctyloxy)methyl)benzene(98% ee). Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 7.26 (m, 5H), 4.51 (d, J = 1.3 Hz,, 2H), 3.34 (dd, J = 9.0, 6.0 Hz, 1H), 3.24 (dd, J = 9.0, 6.8 Hz, 1H), 1.77 (td, J = 13.0, 6.6 Hz, 1H), 1.44 1.11 (m, 10H), 0.94 (d, J = 6.7 Hz, 3H), 0.89 (t, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 138.9, 128.3, 127.5, 127.4, 76.1, 73.0, 33.7, 33.5, 31.9, 29.6, 26.9, 22.7, 17.2, 14.1. HRMS calcd for C 16 H 26 O (M+): 234.1984; found: 234.1986. Enantiomeric excess was determined by chiral HPLC analysis, Chiralcel OD column, 0.7 ml/min, n-heptane/i-proh 99.9:0.1, retention times (min.): S21

10.4(major) and 12.3 (minor) O Br (S)-1-bromo-4-((2,3-dimethylpentyloxy)methyl)benzene. Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ 7.46 (d, J = 8.3 Hz, 4H), 7.22 7.18 (m, 4H), 4.43 (d, J = 3.2 Hz, 4H), 3.39 (ddd, J = 15.7, 9.1, 6.1 Hz, 2H), 3.25 (ddd, J = 9.1, 7.2, 3.7 Hz, 2H), 1.88 1.79 (m, 1H), 1.77 1.71 (m, 1H), 1.52 1.10 (m, 6H), 0.91 0.84 (m, 12H), 0.81 (d, J = 6.9 Hz, 3H), 0.76 (d, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 138.0, 137.9, 131.4, 129.2, 129.1, 121.2, 121.2, 74.7, 74.0, 72.2, 72.2, 38.0, 36.7, 36.7, 35.5, 27.5, 25.5, 16.4, 14.3, 14.1, 12.0, 12.0, 11.8. HRMS calcd for C 14 H 21 BrO (M+): 284.0766 found: 284.0762. 1 H NMR : 1 H NMR S22

S23 Supporting Information

V. References [1] D. H. Burns, J. D. Miller, H. K. Chan, and M. O. Delaney, J. Am. Chem. Soc. 1997, 119, 2125-2133. [2] A. Corruble, J.-Y. Valnot, J. Maddaluno, and P. Duhamel, J. Org. Chem. 1998, 63, 8266. [3] P. R. Krishna, V. V. Ramana Reddy and R. Srinivas, Tetrahedron, 2007, 63, 9871. [4] S.-X. Huang, H.-Y. Li, J.-Y. Liu, C. Morisseau, B. D. Hammock, Y.-Q. Long, J. Med. Chem., 2010, 53, 8376 8386 [5] F. González-Bobes and G. C. Fu, J. Am. Chem. Soc. 2006, 127, 5360. [6] M. A. de la Mora, E. Cuevas, J. M. Muchowski, R. Cruz-Almanzaa, Tetrahedron Lett. 2001, 42, 5351 5353. [7] X. Yu, T. Yang, S. Wang, H. Xu, and H. Gong, Org. Lett. 2011, 8, 2138. [8] a) W. Deng, L. Liu, C. Zhang, M. Liu, Q.-X. Guo, Tetrahedron Lett. 2005, 46, 7295; b) X. Wang, A. Guram, M. Ronk, J. E. Milne, J. S. Tedrow, M. M. Faul, Tetrahedron Lett. 2012, 53, 7. S24

V. NMR Spectra, GC-MS, and HPLC Analysis OTs MeO S25

OTs S26

OTs S27

F 3 C OTs S28

OTs S29

O S N O O S O O S30

O OTs S31

Br O OTs S32

O O Br O S33

Br O Br S34

Br S35

O N Br S36

TsN Br S37

Cy S38

E:\yct\yct-111018-1 10/18/2011 12:21:03 PM RT: 21.76-33.72 100 90 80 26.66 29.50 NL: 9.65E6 TIC MS yct-111018-1 Relative Abundance 70 60 50 40 30 20 10 0 22.72 22.96 24.02 24.67 26.00 26.51 26.96 27.67 28.78 29.77 30.42 31.04 32.15 32.67 33.01 22 23 24 25 26 27 28 29 30 31 32 33 Time (min) yct-111018-1 #9621-9735 RT: 29.28-29.59 AV: 115 SB: 460 28.98-29.46, 29.53-30.34 NL: 3.03E5 T: + c Full ms [20.00-450.00] 92.00 100 Relative Abundance 90 91.00 80 70 60 50 40 30 55.04 20 123.97 39.01 65.03 10 93.05 215.92 131.03 187.09 228.97 269.01 286.04 310.69 348.97 376.11 416.64 443.90 0 50 100 150 200 250 300 350 400 450 m/z S39

Cy S40

E:\yct\yct-111216-3 12/16/2011 9:37:15 PM RT: 17.34-33.67 100 Relative Abundance 80 60 40 21.66 NL: 9.70E6 TIC MS yct-111216-3 20 0 17.83 18.87 19.84 21.24 22.18 24.21 25.13 25.99 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 Time (min) 26.50 27.60 28.56 29.72 31.17 31.97 33.05 yct-111216-3 #5171-5617 RT: 20.89-22.40 AV: 447 SB: 1316 19.91-21.52, 21.84-24.83 NL: 1.01E5 T: + c Full ms [20.00-650.00] 90.99 50 Relative Abundance 40 30 20 10 0 55.03 65.01 97.01 110.99 38.99 83.03 124.96 285.96 138.93 194.95 284.93 152.95 179.96 215.04 286.97 243.00 264.01 303.87 40 60 80 100 120 140 160 180 200 220 240 260 280 300 m/z S41

Cy S42

E:\yct\yct-111216-2 12/16/2011 8:54:25 PM RT: 0.00-37.00 100 90 80 Relative Abundance 70 60 50 40 30 20 18.80 NL: 9.33E6 TIC MS yct-111216-2 10 3.41 4.20 6.20 8.02 12.25 13.85 18.38 22.18 24.20 25.97 27.60 30.05 33.96 35.54 0 0 5 10 15 20 25 30 35 Time (min) yct-111216-2 #4169-4970 RT: 17.51-20.27 AV: 802 SB: 2730 14.81-18.53, 19.19-25.07 NL: 3.54E4 T: + c Full ms [20.00-650.00] 90.99 100 Relative Abundance 90 80 70 60 50 40 30 20 10 0 92.02 105.99 55.01 65.01 38.99 67.02 131.03 151.98 243.94 160.97 186.98 201.01 229.00 257.01 285.95 40 60 80 100 120 140 160 180 200 220 240 260 280 m/z S43

F 3 C Cy S44

E:\yct\yct-111230-4 12/30/2011 11:02:27 PM RT: 0.00-37.04 100 90 80 Relative Abundance 70 60 50 40 30 15.63 NL: 7.90E6 TIC MS yct-111230-4 20 12.10 10 15.97 17.98 28.68 3.63 4.83 7.97 11.26 14.96 22.87 23.75 27.67 29.03 34.53 0 0 5 10 15 20 25 30 35 Time (min) yct-111230-4 #3468-3866 RT: 15.06-16.39 AV: 399 SB: 695 14.73-15.58, 15.68-17.19 NL: 6.75E4 T: + c Full ms [20.00-650.00] 68.99 90 Relative Abundance 80 70 60 50 40 30 20 10 0 110.97 41.01 108.99 55.01 140.98 158.98 81.04 91.02 117.03 268.87 172.97 250.99 151.03 186.93 213.01 231.01 269.86 292.76 311.01 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 m/z S45

HO O OMe Cy S46

E:\yct\yct-120302-2 3/3/2012 11:29:06 AM RT: 23.36-27.82 100 24.81 NL: 2.85E5 TIC MS yct-120302-2 Relative Abundance 80 60 40 20 24.87 23.97 24.94 26.03 26.13 26.51 25.09 25.51 23.64 23.78 24.03 24.53 24.76 26.65 26.86 27.03 27.22 27.51 27.66 0 23.5 24.0 24.5 25.0 25.5 26.0 26.5 27.0 27.5 Time (min) yct-120302-2 #6254-6260 RT: 24.80-24.82 AV: 7 SB: 65 24.72-24.79, 24.84-24.98 NL: 4.02E4 T: + c Full ms [20.00-650.00] 152.00 100 90 80 70 60 50 40 30 55.05 97.06 20 304.03 39.03 81.06 123.06 10 305.00 163.01 207.03 235.96 298.93 0 342.04 387.10 433.04 463.11 526.00 552.03 595.29 618.20 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z Relative Abundance S47

Ts N Cy S48

O BuOOC Cy S49

E:\yct\yct-120410-2 4/11/2012 3:06:50 AM RT: 0.00-37.02 100 90 80 Relative Abundance 70 60 50 40 30 20 25.65 NL: 5.96E6 TIC MS yct-120410-2 10 24.88 28.15 3.52 4.44 5.99 7.91 9.86 12.71 13.84 16.40 19.71 24.14 31.20 33.33 35.43 0 0 5 10 15 20 25 30 35 Time (min) yct-120410-2 #6443-6537 RT: 25.48-25.79 AV: 95 SB: 765 24.87-25.58, 25.67-27.73 NL: 9.99E4 T: + c Full ms [20.00-650.00] 137.95 100 Relative Abundance 90 80 70 60 50 40 30 20 10 0 41.00 55.02 83.02 120.98 194.93 259.03 275.95 331.99 176.98 196.97 315.16 357.89 415.95 460.07 496.97 539.07 595.21 616.01 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z S50

Cy S51

E:\yct\yct-120410-3 4/11/2012 3:49:38 AM RT: 0.00-37.03 100 90 80 Relative Abundance 70 60 50 40 30 20 16.30 NL: 6.24E6 TIC MS yct-120410-3 10 18.96 23.01 3.76 5.16 7.46 10.13 12.21 13.98 15.63 19.79 26.68 29.97 31.66 32.88 35.84 0 0 5 10 15 20 25 30 35 Time (min) yct-120410-3 #3119-4472 RT: 13.85-18.51 AV: 1354 SB: 2568 12.54-16.16, 16.27-21.50 NL: 5.76E3 T: + c Full ms [20.00-650.00] 55.01 67.02 80.99 95.00 109.97 40 109.00 35 97.00 38.98 30 41.00 79.03 83.00 25 69.02 20 110.99 15 123.02 65.01 10 53.02 124.98 151.96 5 91.03 138.96 179.95 98.00 152.95 165.96 194.05 208.01 220.04 235.98 0 40 60 80 100 120 140 160 180 200 220 240 m/z Relative Abundance S52

E:\yct\yct-111207-1 12/8/2011 2:01:13 AM RT: 8.95-22.96 100 90 80 Relative Abundance 70 60 50 40 30 20 12.11 NL: 8.24E6 TIC MS yct-111207-1 10 0 9.55 10.46 11.26 12.52 14.20 15.68 16.61 17.52 18.76 20.11 21.25 22.35 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Time (min) yct-111207-1 #2487-2782 RT: 11.56-12.52 AV: 296 SB: 914 10.87-12.02, 12.23-14.19 NL: 1.81E5 T: + c Full ms [20.00-650.00] 90.96 100 90 80 Relative Abundance 70 60 50 40 30 20 10 0 91.96 64.98 175.84 38.97 104.99 42.99 57.02 77.00 84.00 174.85 26.97 98.88 115.00 132.98 148.95 176.87 161.00 40 60 80 100 120 140 160 180 m/z S54

O N S55

E:\yct\yct-111227-2 12/27/2011 8:49:28 PM RT: 0.00-37.04 100 90 80 Relative Abundance 70 60 50 40 30 20 20.56 NL: 4.68E6 m/z= 209.86-301.92 MS yct-111227-2 10 0 3.33 7.10 8.13 9.12 13.70 15.59 16.84 20.14 23.83 26.75 28.23 29.69 32.49 35.10 0 5 10 15 20 25 30 35 Time (min) yct-111227-2 #4872-5368 RT: 19.94-21.60 AV: 497 SB: 872 19.40-20.47, 20.78-22.73 NL: 1.67E5 T: + c Full ms [20.00-650.00] 230.05 100 Relative Abundance 90 80 70 60 50 40 30 20 10 0 77.00 104.96 51.00 188.04 160.03 212.07 271.96 308.11 335.99 373.87 430.84 460.91 516.54 572.26 596.02 646.03 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z S56

E:\yct\yct-111227-3 12/27/2011 9:32:19 PM RT: 0.00-37.04 100 90 80 Relative Abundance 70 60 50 40 30 19.98 NL: 1.45E7 TIC MS yct-111227-3 20 10 19.13 3.49 4.84 7.95 11.38 12.86 15.58 16.39 20.42 22.87 26.76 28.85 29.79 32.92 36.18 0 0 5 10 15 20 25 30 35 Time (min) yct-111227-3 #4805-4899 RT: 19.68-20.00 AV: 95 SB: 353 19.29-19.94, 20.05-20.58 NL: 3.96E5 T: + c Full ms [20.00-650.00] 130.01 100 Relative Abundance 90 80 70 60 50 40 30 20 10 0 132.02 158.01 243.05 117.04 77.02 186.07 41.00 228.12 298.07 346.14 372.95 398.07 440.02 499.16 534.66 599.39 642.43 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z S59

E:\yct\yct-111220-3 12/20/2011 5:01:47 PM RT: 9.60-25.01 100 90 80 Relative Abundance 70 60 50 40 30 20 16.05 NL: 8.69E6 TIC MS yct-111220-3 10 0 10.82 11.26 12.79 13.61 14.25 15.58 16.43 17.31 18.76 19.68 20.50 21.27 22.36 23.39 24.36 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Time (min) yct-111220-3 #3723-3797 RT: 15.95-16.18 AV: 75 SB: 180 15.78-16.01, 16.09-16.44 NL: 5.90E5 T: + c Full ms [20.00-650.00] 90.99 80 Relative Abundance 70 60 50 40 30 20 10 0 92.01 201.92 65.01 39.00 109.99 200.93 55.04 77.03 202.96 118.98 26.98 133.00 146.03 173.06 187.06 215.99 243.03 257.87 40 60 80 100 120 140 160 180 200 220 240 260 m/z S61

n-hexyl S62

E:\yct\yct-111014-3 10/14/2011 10:25:21 PM RT: 14.70-19.03 Relative Abundance 100 90 80 70 60 50 40 30 20 10 0 14.91 15.14 15.40 15.80 16.26 16.38 16.45 15.91 16.54 16.69 17.56 18.05 15.67 17.31 17.59 18.09 18.59 18.77 15.0 15.5 16.0 16.5 17.0 17.5 18.0 18.5 19.0 Time (min) NL: 3.07E5 TIC MS yct-111014-3 yct-111014-3 #3820-3834 RT: 16.28-16.32 AV: 15 SB: 290 15.95-16.22, 16.43-17.15 NL: 6.24E4 T: + c Full ms [20.00-650.00] 91.00 35 30 Relative Abundance 25 20 15 10 5 0 65.03 41.01 105.04 43.01 77.04 115.06 125.93 57.03 71.03 85.03 217.94 133.02 147.02 160.97 186.02 207.04 231.14 249.05 40 60 80 100 120 140 160 180 200 220 240 m/z S63

n-hexyl Ts N S64

n-hexyl N S65

E:\yct\yct-111229-3 12/29/2011 8:42:26 PM RT: 0.00-37.02 100 90 80 Relative Abundance 70 60 50 40 30 21.90 NL: 1.62E7 TIC MS yct-111229-3 20 21.53 10 0 3.49 4.53 6.81 8.28 11.76 13.71 16.55 19.51 25.75 27.68 29.69 31.05 34.55 36.97 0 5 10 15 20 25 30 35 Time (min) yct-111229-3 #5390-5533 RT: 21.73-22.19 AV: 144 SB: 417 21.33-21.88, 21.97-22.81 NL: 3.57E5 T: + c Full ms [20.00-650.00] 130.01 100 Relative Abundance 90 132.02 80 70 60 50 271.09 158.01 40 30 20 117.05 186.07 10 77.03 39.01 200.10 228.10 334.13 374.20 400.91 450.09 519.82 544.70 600.18 638.03 0 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z S66

F 3 C S68

MeO S71

Br O Cy S72

E:\yct\yct-120412-3 4/12/2012 4:48:00 PM RT: 0.00-37.02 Relative Abundance 100 90 80 70 60 50 40 30 20 10 24.31 23.41 21.65 3.25 3.12 5.59 7.30 8.42 9.84 11.82 14.71 17.64 19.91 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Time (min) 26.43 25.89 25.22 26.86 35.76 33.77 32.14 30.10 36.01 NL: 7.75E4 TIC MS yct-120412-3 yct-120412-3 #6535-6994 RT: 25.75-27.40 AV: 460 SB: 1203 24.20-26.58, 27.14-29.05 NL: 3.98E2 T: + c Full ms [20.00-650.00] 221.97 100 90 80 70 60 50 40 115.03 30 55.03 20 126.04 359.93 39.00 67.04 144.06 10 195.03 251.97 277.03 317.00 354.95 373.97 431.96 454.04 510.01 554.99 612.05 636.29 0 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z Relative Abundance S73

Br O S74

O H N S O O Ph S75

O Cy F S76

E:\yct\yct-120412-6 4/12/2012 6:56:30 PM RT: 0.00-37.03 100 90 80 17.97 NL: 1.62E5 TIC MS yct-120412-6 Relative Abundance 70 60 50 40 30 27.24 26.61 20 25.85 10 24.60 23.20 3.12 5.38 7.08 8.65 9.76 11.77 14.02 17.58 18.83 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Time (min) 33.71 34.67 35.64 29.85 31.95 28.38 yct-120412-6 #3967-4820 RT: 16.81-19.75 AV: 854 SB: 2348 14.63-17.79, 18.52-23.53 NL: 2.50E3 T: + c Full ms [20.00-650.00] 111.97 100 90 80 Relative Abundance 70 60 50 40 30 20 10 0 67.03 81.98 39.00 123.97 235.96 125.98 167.00 233.99 258.99 292.20 351.00 371.98 427.96 464.02 509.88 549.00 623.99 640.95 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z S77

Cl Cy S78

E:\yct\yct-120410-6 4/11/2012 5:58:04 AM RT: 0.00-37.04 100 90 80 Relative Abundance 70 60 50 40 30 20 13.14 NL: 4.53E6 TIC MS yct-120410-6 10 3.18 4.14 6.72 8.23 9.71 11.99 15.52 16.67 19.05 22.63 24.47 26.39 28.69 30.19 32.75 34.00 36.83 0 0 5 10 15 20 25 30 35 Time (min) yct-120410-6 #2609-3464 RT: 12.08-15.01 AV: 856 SB: 2553 9.43-12.94, 13.23-18.58 NL: 1.69E4 T: + c Full ms [20.00-650.00] 55.01 100 Relative Abundance 90 66.99 80 70 60 69.00 50 38.99 83.00 104.90 40 30 20 151.03 10 130.88 186.93 0 230.12 267.89 325.99 347.21 414.96 441.79 494.54 518.82 546.86 577.30 630.29 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z S79

N Ts S80

E:\yct\yct-120302-1 3/3/2012 10:49:28 AM RT: 0.00-37.03 100 90 80 Relative Abundance 70 60 50 40 30 20 26.12 NL: 4.79E6 TIC MS yct-120302-1 10 3.73 4.49 7.87 9.57 12.08 15.82 17.46 18.66 20.57 22.00 24.00 27.63 0 28.53 30.89 32.51 36.99 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Time (min) yct-120302-1 #6545-6684 RT: 25.89-26.36 AV: 140 SB: 459 25.31-26.04, 26.25-27.20 NL: 7.82E4 T: + c Full ms [20.00-650.00] 100 152.07 90 80 70 60 50 91.03 40 154.90 30 44.02 136.05 183.90 20 65.04 93.05 10 184.93 264.00 306.11 0 354.97 398.19 428.95 464.10 502.95 565.90 586.79 637.07 50 100 150 200 250 300 350 400 450 500 550 600 650 m/z Relative Abundance S81

n-hexyl Ts N S82

E:\yct\yct-120301-2 3/2/2012 10:50:42 AM RT: 0.00-37.04 100 90 80 Relative Abundance 70 60 50 40 30 20 18.06 NL: 3.05E6 TIC MS yct-120301-2 10 3.08 3.91 7.17 8.83 11.27 12.10 15.56 17.59 20.00 22.28 24.27 26.04 28.06 29.77 30.95 33.36 34.48 36.20 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 Time (min) yct-120301-2 #3999-4714 RT: 16.92-19.39 AV: 716 SB: 2915 13.14-17.92, 18.28-23.65 NL: 1.06E4 T: + c Full ms [20.00-650.00] 67.07 81.03 91.02 20 79.04 124.01 Relative Abundance 15 10 5 0 39.03 41.03 55.06 95.08 109.07 140.97 51.04 111.02 105.05 125.01 181.07 230.95 187.14 206.08 214.96 245.04 40 60 80 100 120 140 160 180 200 220 240 m/z S84

n-hexyl O S85

O N S O race-3-cyclohexyl-1-tosylpyrrolidine O N S O (R)-3-cyclohexyl-1-tosylpyrrolidine S86

O N S O (S)-3-cyclohexyl-1-tosylpyrrolidine S87

Ts N (race)-3-hexyl-1-tosylpyrrolidine Ts N (R)-3-hexyl-1-tosylpyrrolidine. S88

(race)-(3-cyclohexylbutyl)benzene (R)-(3-cyclohexylbutyl)benzene S89

mau 700 O VWD1 A, 波长 =200 nm (LIY\20120228000004.D) (race)-((2-cyclohexylpropoxy)methyl)benzene 10.066 600 500 400 15.812 300 200 100 0 0 2 4 6 8 10 12 14 16 min mau O VWD1 A, 波长 =200 nm (LIY\20120228000003.D) (S)-((2-cyclohexylpropoxy)methyl)benzene 10.018 800 600 400 200 0 16.035 0 2 4 6 8 10 12 14 16 min S90

O (race)-((2-methyloctyloxy)methyl)benzene mau 250 VWD1 A, 波长 =200 nm (LIY\20120329000007.D) 10.612 12.219 200 150 100 50 0 0 2 4 6 8 10 12 14 min mau 500 O VWD1 A, 波长 =200 nm (LIY\20120329000003.D) (S)-((2-methyloctyloxy)methyl)benzene 10.396 400 300 200 100 0 12.273 0 2 4 6 8 10 12 min S91

VI. Crystallographic Data Supporting Information N Ts data_yct-120228 _audit_creation_method SHELXL-97 _chemical_name_systematic ;? ; _chemical_name_common? _chemical_melting_point? _chemical_formula_moiety? _chemical_formula_sum 'C17 H25 N O2 S' _chemical_formula_weight 307.44 _chemical_absolute_configuration 'ad' loop atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source S92

'C' 'C' 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'N' 'N' 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'O' 'O' 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'S' 'S' 0.1246 0.1234 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'H' 'H' 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting monoclinic _symmetry_space_group_name_h-m 'P 21' loop symmetry_equiv_pos_as_xyz 'x, y, z' '-x, y+1/2, -z' _cell_length_a 6.3826(2) _cell_length_b 17.8095(7) _cell_length_c 14.7575(5) _cell_angle_alpha 90.00 _cell_angle_beta 99.669(4) _cell_angle_gamma 90.00 _cell_volume 1653.67(10) _cell_formula_units_z 4 _cell_measurement_temperature 291(2) _cell_measurement_reflns_used 2490 _cell_measurement_theta_min 3.2312 S93

_cell_measurement_theta_max 29.0667 _exptl_crystal_description? _exptl_crystal_colour? _exptl_crystal_size_max 0.45 _exptl_crystal_size_mid 0.36 _exptl_crystal_size_min 0.32 _exptl_crystal_density_meas? _exptl_crystal_density_diffrn 1.235 _exptl_crystal_density_method 'not measured' _exptl_crystal_f_000 664 _exptl_absorpt_coefficient_mu 0.200 _exptl_absorpt_correction_type 'multi-scan' _exptl_absorpt_correction_t_min 0.9153 _exptl_absorpt_correction_t_max 0.9387 _exptl_absorpt_process_details ; CrysAlisPro, Agilent Technologies, Version 1.171.35.19 (release 27-10-2011 CrysAlis171.NET) (compiled Oct 27 2011,15:02:11) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. ; _exptl_special_details ;? ; _diffrn_ambient_temperature 291(2) S94

_diffrn_radiation_wavelength 0.71073 _diffrn_radiation_type _diffrn_radiation_source _diffrn_radiation_monochromator _diffrn_measurement_device_type _diffrn_measurement_method MoK\a 'Enhance (Mo) X-ray Source' graphite 'Gemini S Ultra, Oxford Diffraction' '\w scans' _diffrn_detector_area_resol_mean 15.9149 _diffrn_standards_number? _diffrn_standards_interval_count? _diffrn_standards_interval_time? _diffrn_standards_decay_%? _diffrn_reflns_number 7458 _diffrn_reflns_av_r_equivalents 0.0217 _diffrn_reflns_av_sigmai/neti 0.0400 _diffrn_reflns_limit_h_min -7 _diffrn_reflns_limit_h_max 7 _diffrn_reflns_limit_k_min -20 _diffrn_reflns_limit_k_max 18 _diffrn_reflns_limit_l_min -16 _diffrn_reflns_limit_l_max 16 _diffrn_reflns_theta_min 3.24 _diffrn_reflns_theta_max 24.10 _reflns_number_total 4651 _reflns_number_gt 3800 _reflns_threshold_expression >2sigma(I) _computing_data_collection _computing_cell_refinement _computing_data_reduction _computing_structure_solution 'CrysAlisPro (Oxford Diffraction Ltd.)' 'CrysAlisPro (Oxford Diffraction Ltd.)' 'CrysAlisPro (Oxford Diffraction Ltd.)' 'SHELXS-97 (Sheldrick, 1997)' S95

_computing_structure_refinement _computing_molecular_graphics _computing_publication_material 'SHELXL-97 (Sheldrick, 1997)' 'Ortep-3 (L. J. Farrugia, 2001)' SHELXL-97 _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wr and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type _refine_ls_weighting_scheme full calc _refine_ls_weighting_details 'calc w=1/[\s^2^(fo^2^)+(0.0387p)^2^+0.0212p] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary _atom_sites_solution_secondary _atom_sites_solution_hydrogens _refine_ls_hydrogen_treatment _refine_ls_extinction_method direct difmap geom constr none _refine_ls_extinction_coef? _refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881' _refine_ls_abs_structure_flack 0.02(7) _refine_ls_number_reflns 4651 S96

_refine_ls_number_parameters 381 _refine_ls_number_restraints 1 _refine_ls_r_factor_all 0.0545 _refine_ls_r_factor_gt 0.0407 _refine_ls_wr_factor_ref 0.0912 _refine_ls_wr_factor_gt 0.0831 _refine_ls_goodness_of_fit_ref 1.053 _refine_ls_restrained_s_all 1.053 _refine_ls_shift/su_max 0.000 _refine_ls_shift/su_mean 0.000 loop atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_u_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_symmetry_multiplicity _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group S2 S 0.50185(15) 0.35032(5) 0.87724(6) 0.0552(3) Uani 1 1 d... S1 S -0.00415(16) 0.60715(5) 1.62021(7) 0.0620(3) Uani 1 1 d... O3 O 0.3761(4) 0.33010(15) 0.79092(15) 0.0701(8) Uani 1 1 d... O4 O 0.7272(4) 0.35753(15) 0.88543(17) 0.0686(7) Uani 1 1 d... O2 O 0.1189(4) 0.62511(17) 1.70770(16) 0.0778(8) Uani 1 1 d... S97

N2 N 0.4113(5) 0.43069(16) 0.90566(19) 0.0552(8) Uani 1 1 d... O1 O -0.2299(4) 0.60078(16) 1.61017(17) 0.0742(8) Uani 1 1 d... C15 C -0.0742(6) 0.7472(2) 1.4031(3) 0.0609(11) Uani 1 1 d... H15 H -0.1840 0.7605 1.3561 0.073 Uiso 1 1 calc R.. C11 C 0.0476(6) 0.67529(19) 1.5396(2) 0.0507(10) Uani 1 1 d... C29 C 0.2570(6) 0.2511(2) 0.9565(3) 0.0571(10) Uani 1 1 d... H29 H 0.1473 0.2631 0.9088 0.069 Uiso 1 1 calc R.. C21 C 0.1803(6) 0.4449(2) 0.8863(3) 0.0694(11) Uani 1 1 d... H21B H 0.1008 0.4005 0.8977 0.083 Uiso 1 1 calc R.. H21A H 0.1353 0.4609 0.8232 0.083 Uiso 1 1 calc R.. C22 C 0.3743(5) 0.55888(18) 1.1016(2) 0.0484(9) Uani 1 1 d... H22 H 0.4090 0.6018 1.0653 0.058 Uiso 1 1 calc R.. C5 C 0.1411(5) 0.41927(18) 1.3773(2) 0.0486(9) Uani 1 1 d... H5 H 0.1749 0.4648 1.3453 0.058 Uiso 1 1 calc R.. C20 C 0.1512(6) 0.5074(2) 0.9532(2) 0.0610(10) Uani 1 1 d... H20B H 0.0107 0.5052 0.9699 0.073 Uiso 1 1 calc R.. H20A H 0.1702 0.5562 0.9265 0.073 Uiso 1 1 calc R.. C30 C 0.2220(6) 0.2009(2) 1.0239(3) 0.0601(11) Uani 1 1 d... H30 H 0.0878 0.1798 1.0212 0.072 Uiso 1 1 calc R.. N1 N 0.0829(5) 0.52806(17) 1.5887(2) 0.0602(9) Uani 1 1 d... C16 C -0.1121(6) 0.6962(2) 1.4693(3) 0.0583(10) Uani 1 1 d... H16 H -0.2472 0.6757 1.4663 0.070 Uiso 1 1 calc R.. C6 C -0.0790(6) 0.39349(19) 1.3317(2) 0.0567(10) Uani 1 1 d... H6A H -0.1201 0.3502 1.3646 0.068 Uiso 1 1 calc R.. H6B H -0.1804 0.4333 1.3363 0.068 Uiso 1 1 calc R.. C7 C -0.0892(6) 0.3728(2) 1.2312(2) 0.0687(11) Uani 1 1 d... H7B H -0.0618 0.4171 1.1967 0.082 Uiso 1 1 calc R.. H7A H -0.2306 0.3548 1.2064 0.082 Uiso 1 1 calc R.. C27 C 0.1847(6) 0.5815(2) 1.1469(3) 0.0599(10) Uani 1 1 d... H27A H 0.0652 0.5936 1.0994 0.072 Uiso 1 1 calc R.. S98

H27B H 0.1440 0.5391 1.1815 0.072 Uiso 1 1 calc R.. C12 C 0.2473(6) 0.7058(2) 1.5435(3) 0.0624(11) Uani 1 1 d... H12 H 0.3566 0.6924 1.5907 0.075 Uiso 1 1 calc R.. C28 C 0.4558(6) 0.28377(17) 0.9600(2) 0.0499(10) Uani 1 1 d... C18 C 0.5100(6) 0.4669(2) 0.9925(3) 0.0553(9) Uani 1 1 d... H18B H 0.5975 0.5091 0.9806 0.066 Uiso 1 1 calc R.. H18A H 0.5973 0.4314 1.0320 0.066 Uiso 1 1 calc R.. C4 C -0.0074(7) 0.4981(2) 1.4976(3) 0.0621(10) Uani 1 1 d... H4A H -0.0226 0.5375 1.4516 0.075 Uiso 1 1 calc R.. H4B H -0.1455 0.4756 1.4984 0.075 Uiso 1 1 calc R.. C23 C 0.5666(6) 0.54405(19) 1.1763(3) 0.0598(10) Uani 1 1 d... H23A H 0.6894 0.5333 1.1477 0.072 Uiso 1 1 calc R.. H23B H 0.5391 0.5002 1.2115 0.072 Uiso 1 1 calc R.. C34 C 0.3429(7) 0.1274(2) 1.1692(3) 0.0800(13) Uani 1 1 d... H34C H 0.3601 0.1531 1.2271 0.120 Uiso 1 1 calc R.. H34B H 0.4426 0.0867 1.1729 0.120 Uiso 1 1 calc R.. H34A H 0.2008 0.1080 1.1546 0.120 Uiso 1 1 calc R.. C10 C 0.3042(6) 0.3599(2) 1.3632(2) 0.0621(10) Uani 1 1 d... H10A H 0.4454 0.3788 1.3868 0.075 Uiso 1 1 calc R.. H10B H 0.2813 0.3155 1.3984 0.075 Uiso 1 1 calc R.. C31 C 0.3823(7) 0.1813(2) 1.0952(3) 0.0565(10) Uani 1 1 d... C2 C 0.3614(6) 0.4729(2) 1.5253(2) 0.0659(11) Uani 1 1 d... H2B H 0.4689 0.4342 1.5394 0.079 Uiso 1 1 calc R.. H2A H 0.4121 0.5104 1.4865 0.079 Uiso 1 1 calc R.. C14 C 0.1251(7) 0.7785(2) 1.4062(3) 0.0586(11) Uani 1 1 d... C24 C 0.6163(6) 0.61124(19) 1.2413(2) 0.0636(10) Uani 1 1 d... H24B H 0.7331 0.5985 1.2899 0.076 Uiso 1 1 calc R.. H24A H 0.6600 0.6536 1.2076 0.076 Uiso 1 1 calc R.. C25 C 0.4233(7) 0.6333(2) 1.2836(3) 0.0749(12) Uani 1 1 d... H25A H 0.3908 0.5933 1.3236 0.090 Uiso 1 1 calc R.. S99

H25B H 0.4561 0.6781 1.3207 0.090 Uiso 1 1 calc R.. C8 C 0.0742(6) 0.3121(2) 1.2200(3) 0.0704(11) Uani 1 1 d... H8B H 0.0394 0.2661 1.2494 0.084 Uiso 1 1 calc R.. H8A H 0.0710 0.3018 1.1553 0.084 Uiso 1 1 calc R.. C13 C 0.2844(6) 0.7563(2) 1.4772(3) 0.0645(11) Uani 1 1 d... H13 H 0.4202 0.7760 1.4800 0.077 Uiso 1 1 calc R.. C3 C 0.1520(5) 0.43926(19) 1.4779(2) 0.0524(9) Uani 1 1 d... H3 H 0.1263 0.3933 1.5109 0.063 Uiso 1 1 calc R.. C1 C 0.3121(7) 0.5080(2) 1.6120(2) 0.0720(12) Uani 1 1 d... H1B H 0.3366 0.4727 1.6627 0.086 Uiso 1 1 calc R.. H1A H 0.3986 0.5523 1.6283 0.086 Uiso 1 1 calc R.. C33 C 0.6178(6) 0.2639(2) 1.0311(3) 0.0535(9) Uani 1 1 d... H33 H 0.7522 0.2849 1.0342 0.064 Uiso 1 1 calc R.. C19 C 0.3222(5) 0.49321(18) 1.0366(2) 0.0510(9) Uani 1 1 d... H19 H 0.2763 0.4511 1.0714 0.061 Uiso 1 1 calc R.. C9 C 0.2935(6) 0.3381(2) 1.2630(3) 0.0726(11) Uani 1 1 d... H9B H 0.3333 0.3809 1.2290 0.087 Uiso 1 1 calc R.. H9A H 0.3947 0.2981 1.2588 0.087 Uiso 1 1 calc R.. C17 C 0.1659(7) 0.8345(2) 1.3352(3) 0.0769(12) Uani 1 1 d... H17A H 0.0477 0.8350 1.2855 0.115 Uiso 1 1 calc R.. H17B H 0.2926 0.8207 1.3122 0.115 Uiso 1 1 calc R.. H17C H 0.1836 0.8835 1.3624 0.115 Uiso 1 1 calc R.. C32 C 0.5808(7) 0.2138(2) 1.0965(3) 0.0595(10) Uani 1 1 d... H32 H 0.6916 0.2010 1.1433 0.071 Uiso 1 1 calc R.. C26 C 0.2315(6) 0.6481(2) 1.2108(3) 0.0733(11) Uani 1 1 d... H26A H 0.2572 0.6921 1.1756 0.088 Uiso 1 1 calc R.. H26B H 0.1092 0.6582 1.2401 0.088 Uiso 1 1 calc R.. loop atom_site_aniso_label S100

_atom_site_aniso_u_11 _atom_site_aniso_u_22 _atom_site_aniso_u_33 _atom_site_aniso_u_23 _atom_site_aniso_u_13 _atom_site_aniso_u_12 S2 0.0476(7) 0.0707(6) 0.0490(6) -0.0093(5) 0.0133(5) -0.0049(5) S1 0.0523(7) 0.0857(8) 0.0495(6) -0.0122(5) 0.0127(6) -0.0011(5) O3 0.073(2) 0.092(2) 0.0464(15) -0.0156(14) 0.0114(15) -0.0042(14) O4 0.0457(17) 0.0931(19) 0.0727(18) -0.0110(16) 0.0258(14) -0.0063(14) O2 0.077(2) 0.110(2) 0.0427(15) -0.0156(15) 0.0022(15) -0.0011(16) N2 0.050(2) 0.0602(18) 0.0537(19) -0.0064(16) 0.0026(16) 0.0005(15) O1 0.0500(18) 0.104(2) 0.0733(19) -0.0092(16) 0.0241(15) -0.0055(15) C15 0.051(3) 0.070(3) 0.056(3) -0.016(2) -0.008(2) 0.004(2) C11 0.042(3) 0.066(2) 0.044(2) -0.0157(19) 0.0086(19) 0.0024(18) C29 0.046(3) 0.073(2) 0.052(2) -0.008(2) 0.0063(19) -0.004(2) C21 0.053(3) 0.078(3) 0.072(3) -0.006(2) -0.003(2) 0.002(2) C22 0.043(2) 0.0461(19) 0.056(2) 0.0034(15) 0.0071(16) -0.0043(14) C5 0.042(2) 0.0477(19) 0.055(2) 0.0045(15) 0.0061(15) -0.0017(15) C20 0.045(2) 0.068(2) 0.066(2) -0.0030(18) 0.0006(17) 0.0079(17) C30 0.051(3) 0.073(3) 0.057(3) -0.013(2) 0.011(2) -0.013(2) N1 0.045(2) 0.075(2) 0.060(2) -0.0064(17) 0.0078(17) -0.0010(16) C16 0.046(3) 0.069(2) 0.058(3) -0.015(2) 0.005(2) 0.003(2) C6 0.042(2) 0.054(2) 0.073(3) -0.0080(17) 0.0055(18) 0.0019(16) C7 0.058(2) 0.067(2) 0.076(3) -0.0196(19) -0.0030(19) 0.0000(18) C27 0.045(2) 0.071(2) 0.063(2) -0.0014(18) 0.0075(18) 0.0010(18) C12 0.043(3) 0.083(3) 0.057(3) -0.014(2) -0.003(2) 0.000(2) C28 0.041(2) 0.058(2) 0.050(2) -0.0157(18) 0.008(2) -0.0031(17) C18 0.042(2) 0.056(2) 0.065(2) -0.0096(17) 0.0022(18) -0.0046(17) C4 0.050(2) 0.071(2) 0.063(2) -0.015(2) 0.004(2) -0.0042(19) S101

C23 0.050(2) 0.053(2) 0.073(2) -0.0020(18) 0.0015(19) 0.0027(16) C34 0.098(4) 0.075(3) 0.067(3) 0.000(2) 0.016(3) -0.017(2) C10 0.041(2) 0.075(2) 0.068(2) 0.0012(19) 0.0058(18) 0.0028(18) C31 0.061(3) 0.060(2) 0.048(2) -0.0151(19) 0.010(2) -0.007(2) C2 0.047(2) 0.085(3) 0.062(2) -0.0054(18) 0.0003(18) 0.0087(18) C14 0.065(3) 0.063(2) 0.049(2) -0.019(2) 0.012(2) 0.006(2) C24 0.054(2) 0.063(2) 0.070(2) -0.0094(18) -0.0004(18) -0.0021(17) C25 0.077(3) 0.074(3) 0.071(3) -0.018(2) 0.006(2) -0.007(2) C8 0.054(3) 0.074(2) 0.083(3) -0.019(2) 0.010(2) 0.004(2) C13 0.048(3) 0.077(3) 0.069(3) -0.015(2) 0.012(2) -0.008(2) C3 0.048(2) 0.058(2) 0.052(2) 0.0052(17) 0.0078(16) -0.0034(16) C1 0.059(3) 0.090(3) 0.061(3) -0.007(2) -0.008(2) 0.008(2) C33 0.036(2) 0.066(2) 0.057(2) -0.011(2) 0.0023(19) -0.0068(18) C19 0.039(2) 0.053(2) 0.060(2) 0.0045(16) 0.0060(16) -0.0027(15) C9 0.064(3) 0.078(3) 0.077(3) -0.015(2) 0.015(2) 0.006(2) C17 0.086(3) 0.084(3) 0.063(3) -0.005(2) 0.017(2) 0.000(2) C32 0.058(3) 0.064(2) 0.055(3) -0.007(2) 0.003(2) 0.003(2) C26 0.058(3) 0.083(3) 0.083(3) -0.020(2) 0.021(2) 0.004(2) _geom_special_details ; All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. ; loop_ S102

_geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag S2 O4 1.429(3).? S2 O3 1.433(2).? S2 N2 1.625(3).? S2 C28 1.762(4).? S1 O1 1.428(3).? S1 O2 1.430(3).? S1 N1 1.611(3).? S1 C11 1.769(4).? N2 C21 1.476(4).? N2 C18 1.478(4).? C15 C14 1.383(5).? C15 C16 1.385(5).? C15 H15 0.9300.? C11 C16 1.377(4).? C11 C12 1.378(5).? C29 C30 1.384(5).? C29 C28 1.388(5).? C29 H29 0.9300.? C21 C20 1.519(5).? C21 H21B 0.9700.? C21 H21A 0.9700.? C22 C19 1.513(4).? C22 C23 1.529(4).? C22 C27 1.532(5).? C22 H22 0.9800.? S103

C5 C3 1.518(4).? C5 C10 1.521(5).? C5 C6 1.523(4).? C5 H5 0.9800.? C20 C19 1.523(4).? C20 H20B 0.9700.? C20 H20A 0.9700.? C30 C31 1.384(5).? C30 H30 0.9300.? N1 C4 1.471(4).? N1 C1 1.489(5).? C16 H16 0.9300.? C6 C7 1.520(4).? C6 H6A 0.9700.? C6 H6B 0.9700.? C7 C8 1.531(5).? C7 H7B 0.9700.? C7 H7A 0.9700.? C27 C26 1.514(4).? C27 H27A 0.9700.? C27 H27B 0.9700.? C12 C13 1.379(5).? C12 H12 0.9300.? C28 C33 1.390(4).? C18 C19 1.530(5).? C18 H18B 0.9700.? C18 H18A 0.9700.? C4 C3 1.522(5).? C4 H4A 0.9700.? C4 H4B 0.9700.? S104

C23 C24 1.533(4).? C23 H23A 0.9700.? C23 H23B 0.9700.? C34 C31 1.506(5).? C34 H34C 0.9600.? C34 H34B 0.9600.? C34 H34A 0.9600.? C10 C9 1.520(5).? C10 H10A 0.9700.? C10 H10B 0.9700.? C31 C32 1.390(5).? C2 C1 1.504(5).? C2 C3 1.524(5).? C2 H2B 0.9700.? C2 H2A 0.9700.? C14 C13 1.390(5).? C14 C17 1.500(5).? C24 C25 1.523(5).? C24 H24B 0.9700.? C24 H24A 0.9700.? C25 C26 1.510(5).? C25 H25A 0.9700.? C25 H25B 0.9700.? C8 C9 1.509(5).? C8 H8B 0.9700.? C8 H8A 0.9700.? C13 H13 0.9300.? C3 H3 0.9800.? C1 H1B 0.9700.? C1 H1A 0.9700.? S105

C33 C32 1.363(5).? C33 H33 0.9300.? C19 H19 0.9800.? C9 H9B 0.9700.? C9 H9A 0.9700.? C17 H17A 0.9600.? C17 H17B 0.9600.? C17 H17C 0.9600.? C32 H32 0.9300.? C26 H26A 0.9700.? C26 H26B 0.9700.? loop geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag O4 S2 O3 120.21(16)..? O4 S2 N2 107.21(16)..? O3 S2 N2 106.29(16)..? O4 S2 C28 106.54(17)..? O3 S2 C28 108.28(16)..? N2 S2 C28 107.78(15)..? O1 S1 O2 120.20(17)..? O1 S1 N1 106.94(17)..? O2 S1 N1 107.00(17)..? O1 S1 C11 106.48(18)..? S106

O2 S1 C11 108.53(18)..? N1 S1 C11 107.05(15)..? C21 N2 C18 111.0(3)..? C21 N2 S2 119.3(2)..? C18 N2 S2 119.3(2)..? C14 C15 C16 120.7(4)..? C14 C15 H15 119.7..? C16 C15 H15 119.7..? C16 C11 C12 119.2(4)..? C16 C11 S1 119.6(3)..? C12 C11 S1 121.2(3)..? C30 C29 C28 120.1(4)..? C30 C29 H29 120.0..? C28 C29 H29 120.0..? N2 C21 C20 103.2(3)..? N2 C21 H21B 111.1..? C20 C21 H21B 111.1..? N2 C21 H21A 111.1..? C20 C21 H21A 111.1..? H21B C21 H21A 109.1..? C19 C22 C23 112.8(3)..? C19 C22 C27 112.0(3)..? C23 C22 C27 109.1(3)..? C19 C22 H22 107.6..? C23 C22 H22 107.6..? C27 C22 H22 107.6..? C3 C5 C10 112.1(3)..? C3 C5 C6 112.9(3)..? C10 C5 C6 109.4(3)..? C3 C5 H5 107.4..? S107

C10 C5 H5 107.4..? C6 C5 H5 107.4..? C21 C20 C19 104.7(3)..? C21 C20 H20B 110.8..? C19 C20 H20B 110.8..? C21 C20 H20A 110.8..? C19 C20 H20A 110.8..? H20B C20 H20A 108.9..? C29 C30 C31 121.4(4)..? C29 C30 H30 119.3..? C31 C30 H30 119.3..? C4 N1 C1 110.0(3)..? C4 N1 S1 118.6(3)..? C1 N1 S1 121.1(3)..? C11 C16 C15 120.9(4)..? C11 C16 H16 119.6..? C15 C16 H16 119.6..? C7 C6 C5 112.9(3)..? C7 C6 H6A 109.0..? C5 C6 H6A 109.0..? C7 C6 H6B 109.0..? C5 C6 H6B 109.0..? H6A C6 H6B 107.8..? C6 C7 C8 111.0(3)..? C6 C7 H7B 109.4..? C8 C7 H7B 109.4..? C6 C7 H7A 109.4..? C8 C7 H7A 109.4..? H7B C7 H7A 108.0..? C26 C27 C22 113.0(3)..? S108

C26 C27 H27A 109.0..? C22 C27 H27A 109.0..? C26 C27 H27B 109.0..? C22 C27 H27B 109.0..? H27A C27 H27B 107.8..? C11 C12 C13 119.6(4)..? C11 C12 H12 120.2..? C13 C12 H12 120.2..? C29 C28 C33 118.8(4)..? C29 C28 S2 120.9(3)..? C33 C28 S2 120.3(3)..? N2 C18 C19 104.6(3)..? N2 C18 H18B 110.8..? C19 C18 H18B 110.8..? N2 C18 H18A 110.8..? C19 C18 H18A 110.8..? H18B C18 H18A 108.9..? N1 C4 C3 104.6(3)..? N1 C4 H4A 110.8..? C3 C4 H4A 110.8..? N1 C4 H4B 110.8..? C3 C4 H4B 110.8..? H4A C4 H4B 108.9..? C22 C23 C24 111.9(3)..? C22 C23 H23A 109.2..? C24 C23 H23A 109.2..? C22 C23 H23B 109.2..? C24 C23 H23B 109.2..? H23A C23 H23B 107.9..? C31 C34 H34C 109.5..? S109

C31 C34 H34B 109.5..? H34C C34 H34B 109.5..? C31 C34 H34A 109.5..? H34C C34 H34A 109.5..? H34B C34 H34A 109.5..? C9 C10 C5 113.0(3)..? C9 C10 H10A 109.0..? C5 C10 H10A 109.0..? C9 C10 H10B 109.0..? C5 C10 H10B 109.0..? H10A C10 H10B 107.8..? C30 C31 C32 117.5(4)..? C30 C31 C34 121.3(4)..? C32 C31 C34 121.2(4)..? C1 C2 C3 105.1(3)..? C1 C2 H2B 110.7..? C3 C2 H2B 110.7..? C1 C2 H2A 110.7..? C3 C2 H2A 110.7..? H2B C2 H2A 108.8..? C15 C14 C13 117.5(4)..? C15 C14 C17 120.8(4)..? C13 C14 C17 121.7(4)..? C25 C24 C23 111.2(3)..? C25 C24 H24B 109.4..? C23 C24 H24B 109.4..? C25 C24 H24A 109.4..? C23 C24 H24A 109.4..? H24B C24 H24A 108.0..? C26 C25 C24 111.6(3)..? S110

C26 C25 H25A 109.3..? C24 C25 H25A 109.3..? C26 C25 H25B 109.3..? C24 C25 H25B 109.3..? H25A C25 H25B 108.0..? C9 C8 C7 109.8(3)..? C9 C8 H8B 109.7..? C7 C8 H8B 109.7..? C9 C8 H8A 109.7..? C7 C8 H8A 109.7..? H8B C8 H8A 108.2..? C12 C13 C14 122.0(4)..? C12 C13 H13 119.0..? C14 C13 H13 119.0..? C5 C3 C4 115.2(3)..? C5 C3 C2 115.7(3)..? C4 C3 C2 101.8(3)..? C5 C3 H3 107.9..? C4 C3 H3 107.9..? C2 C3 H3 107.9..? N1 C1 C2 104.0(3)..? N1 C1 H1B 111.0..? C2 C1 H1B 111.0..? N1 C1 H1A 111.0..? C2 C1 H1A 111.0..? H1B C1 H1A 109.0..? C32 C33 C28 120.4(4)..? C32 C33 H33 119.8..? C28 C33 H33 119.8..? C22 C19 C20 115.8(3)..? S111

C22 C19 C18 113.7(3)..? C20 C19 C18 102.3(3)..? C22 C19 H19 108.2..? C20 C19 H19 108.2..? C18 C19 H19 108.2..? C8 C9 C10 112.0(3)..? C8 C9 H9B 109.2..? C10 C9 H9B 109.2..? C8 C9 H9A 109.2..? C10 C9 H9A 109.2..? H9B C9 H9A 107.9..? C14 C17 H17A 109.5..? C14 C17 H17B 109.5..? H17A C17 H17B 109.5..? C14 C17 H17C 109.5..? H17A C17 H17C 109.5..? H17B C17 H17C 109.5..? C33 C32 C31 121.9(4)..? C33 C32 H32 119.0..? C31 C32 H32 119.0..? C25 C26 C27 111.0(3)..? C25 C26 H26A 109.4..? C27 C26 H26A 109.4..? C25 C26 H26B 109.4..? C27 C26 H26B 109.4..? H26A C26 H26B 108.0..? loop geom_torsion_atom_site_label_1 _geom_torsion_atom_site_label_2 S112

_geom_torsion_atom_site_label_3 _geom_torsion_atom_site_label_4 _geom_torsion _geom_torsion_site_symmetry_1 _geom_torsion_site_symmetry_2 _geom_torsion_site_symmetry_3 _geom_torsion_site_symmetry_4 _geom_torsion_publ_flag O4 S2 N2 C21 168.0(3)....? O3 S2 N2 C21 38.2(3)....? C28 S2 N2 C21-77.7(3)....? O4 S2 N2 C18-50.1(3)....? O3 S2 N2 C18-179.9(3)....? C28 S2 N2 C18 64.2(3)....? O1 S1 C11 C16-15.7(3)....? O2 S1 C11 C16-146.4(3)....? N1 S1 C11 C16 98.4(3)....? O1 S1 C11 C12 166.9(3)....? O2 S1 C11 C12 36.2(3)....? N1 S1 C11 C12-79.0(3)....? C18 N2 C21 C20 13.5(4)....? S2 N2 C21 C20 158.3(2)....? N2 C21 C20 C19-31.9(3)....? C28 C29 C30 C31-0.6(5)....? O1 S1 N1 C4 53.7(3)....? O2 S1 N1 C4-176.3(3)....? C11 S1 N1 C4-60.1(3)....? O1 S1 N1 C1-164.5(3)....? O2 S1 N1 C1-34.5(3)....? C11 S1 N1 C1 81.7(3)....? S113

C12 C11 C16 C15-0.1(5)....? S1 C11 C16 C15-177.5(3)....? C14 C15 C16 C11-0.1(5)....? C3 C5 C6 C7-179.5(3)....? C10 C5 C6 C7-53.9(4)....? C5 C6 C7 C8 56.6(4)....? C19 C22 C27 C26-178.8(3)....? C23 C22 C27 C26 55.5(4)....? C16 C11 C12 C13-0.3(5)....? S1 C11 C12 C13 177.1(3)....? C30 C29 C28 C33 1.1(5)....? C30 C29 C28 S2-177.8(2)....? O4 S2 C28 C29-165.1(3)....? O3 S2 C28 C29-34.5(3)....? N2 S2 C28 C29 80.1(3)....? O4 S2 C28 C33 15.9(3)....? O3 S2 C28 C33 146.5(3)....? N2 S2 C28 C33-98.9(3)....? C21 N2 C18 C19 10.0(4)....? S2 N2 C18 C19-134.8(3)....? C1 N1 C4 C3 16.9(4)....? S1 N1 C4 C3 162.5(3)....? C19 C22 C23 C24-179.9(3)....? C27 C22 C23 C24-54.8(4)....? C3 C5 C10 C9 179.0(3)....? C6 C5 C10 C9 52.9(4)....? C29 C30 C31 C32-0.4(5)....? C29 C30 C31 C34 179.2(3)....? C16 C15 C14 C13 0.6(5)....? C16 C15 C14 C17-179.3(3)....? S114

C22 C23 C24 C25 55.4(4)....? C23 C24 C25 C26-54.8(4)....? C6 C7 C8 C9-56.1(4)....? C11 C12 C13 C14 0.8(5)....? C15 C14 C13 C12-1.0(5)....? C17 C14 C13 C12 178.9(3)....? C10 C5 C3 C4-179.7(3)....? C6 C5 C3 C4-55.6(4)....? C10 C5 C3 C2 61.8(4)....? C6 C5 C3 C2-174.1(3)....? N1 C4 C3 C5-159.2(3)....? N1 C4 C3 C2-33.2(3)....? C1 C2 C3 C5 163.8(3)....? C1 C2 C3 C4 38.1(4)....? C4 N1 C1 C2 6.9(4)....? S1 N1 C1 C2-137.8(3)....? C3 C2 C1 N1-28.0(4)....? C29 C28 C33 C32-0.6(5)....? S2 C28 C33 C32 178.4(3)....? C23 C22 C19 C20-172.3(3)....? C27 C22 C19 C20 64.1(4)....? C23 C22 C19 C18-54.2(4)....? C27 C22 C19 C18-177.8(3)....? C21 C20 C19 C22 162.2(3)....? C21 C20 C19 C18 38.0(3)....? N2 C18 C19 C22-154.8(3)....? N2 C18 C19 C20-29.1(3)....? C7 C8 C9 C10 55.7(4)....? C5 C10 C9 C8-55.5(4)....? C28 C33 C32 C31-0.4(5)....? S115

C30 C31 C32 C33 0.9(5)....? C34 C31 C32 C33-178.6(3)....? C24 C25 C26 C27 54.8(4)....? C22 C27 C26 C25-56.0(4)....? _diffrn_measured_fraction_theta_max 0.997 _diffrn_reflns_theta_full 24.10 _diffrn_measured_fraction_theta_full 0.997 _refine_diff_density_max 0.124 _refine_diff_density_min -0.244 _refine_diff_density_rms 0.040 S116

O H N S O O Ph data_yct120411 _audit_creation_method SHELXL-97 _chemical_name_systematic ;? ; _chemical_name_common? _chemical_melting_point? _chemical_formula_moiety? _chemical_formula_sum 'C28 H33 N O3 S' _chemical_formula_weight 463.61 _chemical_absolute_configuration 'ad' loop atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source 'C' 'C' 0.0181 0.0091 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'H' 'H' 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'N' 'N' 0.0311 0.0180 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'O' 'O' 0.0492 0.0322 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' 'S' 'S' 0.3331 0.5567 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting monoclinic _symmetry_space_group_name_h-m 'P 21' loop_ S117