Supporting Information

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1 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 , China; Department of Chemistry, University of Science and Technology of China, Hefei , 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

2 I. General Information a. Materials All the reactions were carried out in oven-dried Schlenk tubes under argon atmosphere (purity %). 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 ( mesh). S2

3 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 (m, 2H), 7.33 (d, J = 8.0 Hz, 2H), (m, 2H), (m, 2H), (m, 1H), 3.78 (s, 3H), (m, 5H), (m, 1H), (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), (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), (m, 1H), (m, 1H), 2.44 (s, 3H), (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), (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

4 J = 12.1, 9.7, 6.1 Hz, 2H), 1.60 (ddd, J = 11.3, 7.2, 3.9 Hz, 2H), (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 (m, 2H), 7.43 (d, J = 7.7 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), (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), (m, 2H), 4.58 (p, J = 6.0 Hz, 1H), 2.44 (s, 3H), (m, 2H), (m, 2H), 1.56 (d, J = 4.4 Hz, 2H), (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, 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, 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 (m, 4H), 7.32 (t, J = 7.7 Hz, 4H), 4.94 (dt, J = 7.2, 2.4 Hz, 1H), (m, 2H), (m, 1H), 3.23 (td, J = 9.7, 7.0 Hz, 1H), 2.45 (d, J = 8.4 Hz, 6H), (m, 2H). S4

5 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 ( 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), (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 (m, 2H), (m, 2H), (m, 2H), (m, 2H), (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

6 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 (m, 2H), (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), (m, 2H), 1.80 (d, J = 6.7 Hz, 3H), 1.74 (dd, J = 10.1, 4.6 Hz, 2H), (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), (m, 2H), (m, 1H), (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 (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), (m, 2H), 1.73 (d, J = 6.7 Hz, 3H). N H + Br Br NaH/DMF 0 o C N Br S6

7 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, 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, 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 (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 (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), (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

8 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 OTs CuI TMEDA OTs CuI TMEDA - HMPA OTs CuI TMEDA LiCl HMPA OTs CuI TMEDA LiBr HMPA OTs CuI TMEDA LiI HMPA OTs CuI TMEDA LiO t Bu HMPA OTs CuI TMEDA LiOMe HMPA OTs CuI TMEDA LiOMe HMPA OTs CuI TMEDA LiOMe (81 b ) 11 OTs CuI - LiOMe OTs CuI P n Bu 3 LiOMe OTs CuI NMP LiOMe OTs CuI PhC CCH 3 LiOMe OTs CuBr TMEDA LiOMe S8

9 16 OTs CuTc TMEDA LiOMe OTs Cu(OTf) 2 TMEDA LiOMe Br CuI TMEDA LiOMe c 19 I CuI TMEDA LiOMe d 20 Cl CuI TMEDA LiOMe e 21 OMs CuI TMEDA LiOMe 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

10 concentrated, and purified by column chromatography. (3-cyclohexylbutyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (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), (m, 6H), (m, 2H), (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+): ; found: (3-cyclohexylnonyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), (m, 2H), (m, 24H), 0.93 (t, J = 6.7 Hz, 3H) ppm. 13 C NMR (101 MHz, CDCl 3 ) δ , , , , 43.12, 40.23, 34.28, 33.01, 31.97, 30.75, 29.90, 29.86, 29.75, 27.75, 27.03, 26.96, ppm. GC-MS: t =21.66, m/z 286 (M + ); HRMS calcd for C 21 H 34 (M+): ; found: (3-cyclohexyl-4-methylpentyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 5H), 2.58 (td, J = 7.7, 3.6 Hz, 2H), (m, 8H), 1.38 (tdd, J = 11.3, 5.3, 2.5 Hz, 1H), (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+): ; found: F 3 C S10

11 1-(2-cyclohexylpropyl)-3-(trifluoromethyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 4H), 2.80 (dd, J = 13.4, 5.0 Hz, 1H), 2.33 (dd, J = 13.4, 9.6 Hz, 1H), (m, 6H), (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+): ; found: 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), (m, 2H), 4.61 (s, 2H), 3.99 (t, J = 7.1 Hz, 2H), 3.87 (s, 3H), (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+): ; found: 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), (m, 7H), 1.34 (qd, J = 12.6, 4.1 Hz, 2H), (m, 4H), (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+): ; found: 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), (m, 2H), (m, 1H), (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

12 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 : ; found([m+h] + ): 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), (m, 2H), (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+): ; found: (3,4-dimethylpentyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (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), (m, 2H), (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+): ; found: 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), (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+): ; found: S12

13 (3,4-dimethylhexyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 4H), (m, 1H), (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+): ; found: 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), (m, 1H), (m, 2H), 6.51 (dd, J = 3.1, 0.4 Hz, 1H), (m, 2H), (m, 2H), (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+): ; found: (3-cyclopentylbutyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (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), (m, 3H), (m, 7H), (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+): ; found: S13

14 (3-methylnonyl)benzene. Following general procedure A, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), (m, 2H), (m, 1H), (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+): ; found: 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), (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+): ; found: 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), (m, 1H), (m, 2H), 6.49 (dd, J = 3.1, 0.6 Hz, 1H), 4.10 (t, J = 7.3 Hz, 2H), (m, 2H), (m, 13H), (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, GC-MS: t =21.90, m/z 271 (M + ); HRMS calcd for C 19 H 29 N (M+): ; found: Br O 1-bromo-2-(3-methylnonyloxy)naphthalene. Following general procedure B, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (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), (m, 1H), (m, 2H), (m, 1H), (m, 1H), 1.66 (dt, J = 14.3, 7.0 Hz, 1H), (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+): ; found: S14

15 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 (m, 2H), (m, 3H), 2.61 (t, J=7.8Hz, 2H), (m, 2H), (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+): ; found: F 3 C 1-(trifluoromethyl)-3-(2,3,3-trimethylbutyl)benzene. Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 4H), 3.01 (dd, J = 13.2, 2.5 Hz, 1H), 2.12 (dd, J = 13.2, 11.5 Hz, 1H), (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 ppm. HRMS calcd for C 14 H 19 F 3 (M+): ; found: Experimental Procedures for Examples Described in Scheme 2. S15

16 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 (m, 2H), (m, 3H), (m, 2H), (m, 2H), 3.77 (s, 3H), (m, 1H), (m, 2H), (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+): ; found: sec-butylbenzene (CAS: ). Following general procedure, colourless liquid. 1 H NMR (400 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), 2.60 (dt, J = 14.1, 7.0 Hz, 1H), (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

17 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), (m, 1H), (m, 2H), (m, 1H), (m, 7H), (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+): ; found: 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 (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), (m, 6H), (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

18 26.8, 26.7, HRMS calcd for C 16 H 23 BrO (M+): ; found: O S O NH O According to literature procedure [8]. In air, CuI (4.8 mg, 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 (m, 2H), (m, 2H), (m, 2H), 7.52 (s, 1H), (m, 4H), (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), (m, 6H), (m, 6H), 0.86 (d, J = 6.9 Hz, 3H) ppm. HRMS calcd for C 28 H 33 NO 3 S: ; found found([m+h] + ): 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

19 MHz, CDCl 3 ) δ (m, 2H), (m, 2H), 3.87 (t, J = 6.6 Hz, 2H), (m, 7H), (m, 6H), (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 ppm. GC-MS: t =17.97, m/z 236 (M + ); HRMS calcd for C 15 H 21 OF (M+): ; found: 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), (m, 8H), (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, GC-MS: t =13.14, m/z 188 (M + ); HRMS calcd for C 11 H 21 Cl (M+): ; found: 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

20 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), (m, 1H), (m, 6H), (m, 1H), (m, 4H), (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, GC-MS: t =26.02, m/z 307 (M + ); HRMS calcd for C 17 H 25 NO 2 S (M+): ; found: 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), (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), (m, 2H), (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 21.5, GC-MS: t =24.83, m/z 309 (M + ); HRMS calcd for C 17 H 27 NO 2 S (M+): ; found: 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 (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), (m, 6H), (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, GC-MS: t =18.06, m/z 232 (M + ); HRMS calcd for C 16 H 24 O (M+): ; found: 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 (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), (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, HRMS calcd for C 16 H 26 O (M+): ; found: 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

22 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), (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), (m, 1H), (m, 1H), (m, 6H), (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, HRMS calcd for C 14 H 21 BrO (M+): found: H NMR : 1 H NMR S22

23 S23 Supporting Information

24 V. References [1] D. H. Burns, J. D. Miller, H. K. Chan, and M. O. Delaney, J. Am. Chem. Soc. 1997, 119, [2] A. Corruble, J.-Y. Valnot, J. Maddaluno, and P. Duhamel, J. Org. Chem. 1998, 63, [3] P. R. Krishna, V. V. Ramana Reddy and R. Srinivas, Tetrahedron, 2007, 63, [4] S.-X. Huang, H.-Y. Li, J.-Y. Liu, C. Morisseau, B. D. Hammock, Y.-Q. Long, J. Med. Chem., 2010, 53, [5] F. González-Bobes and G. C. Fu, J. Am. Chem. Soc. 2006, 127, [6] M. A. de la Mora, E. Cuevas, J. M. Muchowski, R. Cruz-Almanzaa, Tetrahedron Lett. 2001, 42, [7] X. Yu, T. Yang, S. Wang, H. Xu, and H. Gong, Org. Lett. 2011, 8, [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

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

26 OTs S26

27 OTs S27

28 F 3 C OTs S28

29 OTs S29

30 O S N O O S O O S30

31 O OTs S31

32 Br O OTs S32

33 O O Br O S33

34 Br O Br S34

35 Br S35

36 O N Br S36

37 TsN Br S37

38 Cy S38

39 E:\yct\yct /18/ :21:03 PM RT: NL: 9.65E6 TIC MS yct Relative Abundance Time (min) yct # RT: AV: 115 SB: , NL: 3.03E5 T: + c Full ms [ ] Relative Abundance m/z S39

40 Cy S40

41 E:\yct\yct /16/2011 9:37:15 PM RT: Relative Abundance NL: 9.70E6 TIC MS yct Time (min) yct # RT: AV: 447 SB: , NL: 1.01E5 T: + c Full ms [ ] Relative Abundance m/z S41

42 Cy S42

43 E:\yct\yct /16/2011 8:54:25 PM RT: Relative Abundance NL: 9.33E6 TIC MS yct Time (min) yct # RT: AV: 802 SB: , NL: 3.54E4 T: + c Full ms [ ] Relative Abundance m/z S43

44 F 3 C Cy S44

45 E:\yct\yct /30/ :02:27 PM RT: Relative Abundance NL: 7.90E6 TIC MS yct Time (min) yct # RT: AV: 399 SB: , NL: 6.75E4 T: + c Full ms [ ] Relative Abundance m/z S45

46 HO O OMe Cy S46

47 E:\yct\yct /3/ :29:06 AM RT: NL: 2.85E5 TIC MS yct Relative Abundance Time (min) yct # RT: AV: 7 SB: , NL: 4.02E4 T: + c Full ms [ ] m/z Relative Abundance S47

48 Ts N Cy S48

49 O BuOOC Cy S49

50 E:\yct\yct /11/2012 3:06:50 AM RT: Relative Abundance NL: 5.96E6 TIC MS yct Time (min) yct # RT: AV: 95 SB: , NL: 9.99E4 T: + c Full ms [ ] Relative Abundance m/z S50

51 Cy S51

52 E:\yct\yct /11/2012 3:49:38 AM RT: Relative Abundance NL: 6.24E6 TIC MS yct Time (min) yct # RT: AV: 1354 SB: , NL: 5.76E3 T: + c Full ms [ ] m/z Relative Abundance S52

53 S53 Supporting Information

54 E:\yct\yct /8/2011 2:01:13 AM RT: Relative Abundance NL: 8.24E6 TIC MS yct Time (min) yct # RT: AV: 296 SB: , NL: 1.81E5 T: + c Full ms [ ] Relative Abundance m/z S54

55 O N S55

56 E:\yct\yct /27/2011 8:49:28 PM RT: Relative Abundance NL: 4.68E6 m/z= MS yct Time (min) yct # RT: AV: 497 SB: , NL: 1.67E5 T: + c Full ms [ ] Relative Abundance m/z S56

57 S57 Supporting Information

58 N S58

59 E:\yct\yct /27/2011 9:32:19 PM RT: Relative Abundance NL: 1.45E7 TIC MS yct Time (min) yct # RT: AV: 95 SB: , NL: 3.96E5 T: + c Full ms [ ] Relative Abundance m/z S59

60 S60 Supporting Information

61 E:\yct\yct /20/2011 5:01:47 PM RT: Relative Abundance NL: 8.69E6 TIC MS yct Time (min) yct # RT: AV: 75 SB: , NL: 5.90E5 T: + c Full ms [ ] Relative Abundance m/z S61

62 n-hexyl S62

63 E:\yct\yct /14/ :25:21 PM RT: Relative Abundance Time (min) NL: 3.07E5 TIC MS yct yct # RT: AV: 15 SB: , NL: 6.24E4 T: + c Full ms [ ] Relative Abundance m/z S63

64 n-hexyl Ts N S64

65 n-hexyl N S65

66 E:\yct\yct /29/2011 8:42:26 PM RT: Relative Abundance NL: 1.62E7 TIC MS yct Time (min) yct # RT: AV: 144 SB: , NL: 3.57E5 T: + c Full ms [ ] Relative Abundance m/z S66

67 S67 Supporting Information

68 F 3 C S68

69 S69 Supporting Information

70 S70 Supporting Information

71 MeO S71

72 Br O Cy S72

73 E:\yct\yct /12/2012 4:48:00 PM RT: Relative Abundance Time (min) NL: 7.75E4 TIC MS yct yct # RT: AV: 460 SB: , NL: 3.98E2 T: + c Full ms [ ] m/z Relative Abundance S73

74 Br O S74

75 O H N S O O Ph S75

76 O Cy F S76

77 E:\yct\yct /12/2012 6:56:30 PM RT: NL: 1.62E5 TIC MS yct Relative Abundance Time (min) yct # RT: AV: 854 SB: , NL: 2.50E3 T: + c Full ms [ ] Relative Abundance m/z S77

78 Cl Cy S78

79 E:\yct\yct /11/2012 5:58:04 AM RT: Relative Abundance NL: 4.53E6 TIC MS yct Time (min) yct # RT: AV: 856 SB: , NL: 1.69E4 T: + c Full ms [ ] Relative Abundance m/z S79

80 N Ts S80

81 E:\yct\yct /3/ :49:28 AM RT: Relative Abundance NL: 4.79E6 TIC MS yct Time (min) yct # RT: AV: 140 SB: , NL: 7.82E4 T: + c Full ms [ ] m/z Relative Abundance S81

82 n-hexyl Ts N S82

83 O S83

84 E:\yct\yct /2/ :50:42 AM RT: Relative Abundance NL: 3.05E6 TIC MS yct Time (min) yct # RT: AV: 716 SB: , NL: 1.06E4 T: + c Full ms [ ] Relative Abundance m/z S84

85 n-hexyl O S85

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

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

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

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

90 mau 700 O VWD1 A, 波长 =200 nm (LIY\ D) (race)-((2-cyclohexylpropoxy)methyl)benzene min mau O VWD1 A, 波长 =200 nm (LIY\ D) (S)-((2-cyclohexylpropoxy)methyl)benzene min S90

91 O (race)-((2-methyloctyloxy)methyl)benzene mau 250 VWD1 A, 波长 =200 nm (LIY\ D) min mau 500 O VWD1 A, 波长 =200 nm (LIY\ D) (S)-((2-methyloctyloxy)methyl)benzene min S91

92 VI. Crystallographic Data Supporting Information N Ts data_yct _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 _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

93 'C' 'C' 'International Tables Vol C Tables and ' 'N' 'N' 'International Tables Vol C Tables and ' 'O' 'O' 'International Tables Vol C Tables and ' 'S' 'S' 'International Tables Vol C Tables and ' 'H' 'H' 'International Tables Vol C Tables and ' _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 (2) _cell_length_b (7) _cell_length_c (5) _cell_angle_alpha _cell_angle_beta (4) _cell_angle_gamma _cell_volume (10) _cell_formula_units_z 4 _cell_measurement_temperature 291(2) _cell_measurement_reflns_used 2490 _cell_measurement_theta_min S93

94 _cell_measurement_theta_max _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 _exptl_crystal_density_method 'not measured' _exptl_crystal_f_ _exptl_absorpt_coefficient_mu _exptl_absorpt_correction_type 'multi-scan' _exptl_absorpt_correction_t_min _exptl_absorpt_correction_t_max _exptl_absorpt_process_details ; CrysAlisPro, Agilent Technologies, Version (release CrysAlis171.NET) (compiled Oct ,15:02:11) Empirical absorption correction using spherical harmonics, implemented in SCALE3 ABSPACK scaling algorithm. ; _exptl_special_details ;? ; _diffrn_ambient_temperature 291(2) S94

95 _diffrn_radiation_wavelength _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 _diffrn_standards_number? _diffrn_standards_interval_count? _diffrn_standards_interval_time? _diffrn_standards_decay_%? _diffrn_reflns_number 7458 _diffrn_reflns_av_r_equivalents _diffrn_reflns_av_sigmai/neti _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 _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

96 _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^ p] 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, ' _refine_ls_abs_structure_flack 0.02(7) _refine_ls_number_reflns 4651 S96

97 _refine_ls_number_parameters 381 _refine_ls_number_restraints 1 _refine_ls_r_factor_all _refine_ls_r_factor_gt _refine_ls_wr_factor_ref _refine_ls_wr_factor_gt _refine_ls_goodness_of_fit_ref _refine_ls_restrained_s_all _refine_ls_shift/su_max _refine_ls_shift/su_mean 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 (15) (5) (6) (3) Uani 1 1 d... S1 S (16) (5) (7) (3) Uani 1 1 d... O3 O (4) (15) (15) (8) Uani 1 1 d... O4 O (4) (15) (17) (7) Uani 1 1 d... O2 O (4) (17) (16) (8) Uani 1 1 d... S97

98 N2 N (5) (16) (19) (8) Uani 1 1 d... O1 O (4) (16) (17) (8) Uani 1 1 d... C15 C (6) (2) (3) (11) Uani 1 1 d... H15 H Uiso 1 1 calc R.. C11 C (6) (19) (2) (10) Uani 1 1 d... C29 C (6) (2) (3) (10) Uani 1 1 d... H29 H Uiso 1 1 calc R.. C21 C (6) (2) (3) (11) Uani 1 1 d... H21B H Uiso 1 1 calc R.. H21A H Uiso 1 1 calc R.. C22 C (5) (18) (2) (9) Uani 1 1 d... H22 H Uiso 1 1 calc R.. C5 C (5) (18) (2) (9) Uani 1 1 d... H5 H Uiso 1 1 calc R.. C20 C (6) (2) (2) (10) Uani 1 1 d... H20B H Uiso 1 1 calc R.. H20A H Uiso 1 1 calc R.. C30 C (6) (2) (3) (11) Uani 1 1 d... H30 H Uiso 1 1 calc R.. N1 N (5) (17) (2) (9) Uani 1 1 d... C16 C (6) (2) (3) (10) Uani 1 1 d... H16 H Uiso 1 1 calc R.. C6 C (6) (19) (2) (10) Uani 1 1 d... H6A H Uiso 1 1 calc R.. H6B H Uiso 1 1 calc R.. C7 C (6) (2) (2) (11) Uani 1 1 d... H7B H Uiso 1 1 calc R.. H7A H Uiso 1 1 calc R.. C27 C (6) (2) (3) (10) Uani 1 1 d... H27A H Uiso 1 1 calc R.. S98

99 H27B H Uiso 1 1 calc R.. C12 C (6) (2) (3) (11) Uani 1 1 d... H12 H Uiso 1 1 calc R.. C28 C (6) (17) (2) (10) Uani 1 1 d... C18 C (6) (2) (3) (9) Uani 1 1 d... H18B H Uiso 1 1 calc R.. H18A H Uiso 1 1 calc R.. C4 C (7) (2) (3) (10) Uani 1 1 d... H4A H Uiso 1 1 calc R.. H4B H Uiso 1 1 calc R.. C23 C (6) (19) (3) (10) Uani 1 1 d... H23A H Uiso 1 1 calc R.. H23B H Uiso 1 1 calc R.. C34 C (7) (2) (3) (13) Uani 1 1 d... H34C H Uiso 1 1 calc R.. H34B H Uiso 1 1 calc R.. H34A H Uiso 1 1 calc R.. C10 C (6) (2) (2) (10) Uani 1 1 d... H10A H Uiso 1 1 calc R.. H10B H Uiso 1 1 calc R.. C31 C (7) (2) (3) (10) Uani 1 1 d... C2 C (6) (2) (2) (11) Uani 1 1 d... H2B H Uiso 1 1 calc R.. H2A H Uiso 1 1 calc R.. C14 C (7) (2) (3) (11) Uani 1 1 d... C24 C (6) (19) (2) (10) Uani 1 1 d... H24B H Uiso 1 1 calc R.. H24A H Uiso 1 1 calc R.. C25 C (7) (2) (3) (12) Uani 1 1 d... H25A H Uiso 1 1 calc R.. S99

100 H25B H Uiso 1 1 calc R.. C8 C (6) (2) (3) (11) Uani 1 1 d... H8B H Uiso 1 1 calc R.. H8A H Uiso 1 1 calc R.. C13 C (6) (2) (3) (11) Uani 1 1 d... H13 H Uiso 1 1 calc R.. C3 C (5) (19) (2) (9) Uani 1 1 d... H3 H Uiso 1 1 calc R.. C1 C (7) (2) (2) (12) Uani 1 1 d... H1B H Uiso 1 1 calc R.. H1A H Uiso 1 1 calc R.. C33 C (6) (2) (3) (9) Uani 1 1 d... H33 H Uiso 1 1 calc R.. C19 C (5) (18) (2) (9) Uani 1 1 d... H19 H Uiso 1 1 calc R.. C9 C (6) (2) (3) (11) Uani 1 1 d... H9B H Uiso 1 1 calc R.. H9A H Uiso 1 1 calc R.. C17 C (7) (2) (3) (12) Uani 1 1 d... H17A H Uiso 1 1 calc R.. H17B H Uiso 1 1 calc R.. H17C H Uiso 1 1 calc R.. C32 C (7) (2) (3) (10) Uani 1 1 d... H32 H Uiso 1 1 calc R.. C26 C (6) (2) (3) (11) Uani 1 1 d... H26A H Uiso 1 1 calc R.. H26B H Uiso 1 1 calc R.. loop atom_site_aniso_label S100

101 _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 S (7) (6) (6) (5) (5) (5) S (7) (8) (6) (5) (6) (5) O (2) 0.092(2) (15) (14) (15) (14) O (17) (19) (18) (16) (14) (14) O (2) 0.110(2) (15) (15) (15) (16) N (2) (18) (19) (16) (16) (15) O (18) 0.104(2) (19) (16) (15) (15) C (3) 0.070(3) 0.056(3) (2) (2) 0.004(2) C (3) 0.066(2) 0.044(2) (19) (19) (18) C (3) 0.073(2) 0.052(2) (2) (19) (2) C (3) 0.078(3) 0.072(3) (2) (2) 0.002(2) C (2) (19) 0.056(2) (15) (16) (14) C (2) (19) 0.055(2) (15) (15) (15) C (2) 0.068(2) 0.066(2) (18) (17) (17) C (3) 0.073(3) 0.057(3) (2) 0.011(2) (2) N (2) 0.075(2) 0.060(2) (17) (17) (16) C (3) 0.069(2) 0.058(3) (2) 0.005(2) 0.003(2) C (2) 0.054(2) 0.073(3) (17) (18) (16) C (2) 0.067(2) 0.076(3) (19) (19) (18) C (2) 0.071(2) 0.063(2) (18) (18) (18) C (3) 0.083(3) 0.057(3) (2) (2) 0.000(2) C (2) 0.058(2) 0.050(2) (18) 0.008(2) (17) C (2) 0.056(2) 0.065(2) (17) (18) (17) C (2) 0.071(2) 0.063(2) (2) 0.004(2) (19) S101

102 C (2) 0.053(2) 0.073(2) (18) (19) (16) C (4) 0.075(3) 0.067(3) 0.000(2) 0.016(3) (2) C (2) 0.075(2) 0.068(2) (19) (18) (18) C (3) 0.060(2) 0.048(2) (19) 0.010(2) (2) C (2) 0.085(3) 0.062(2) (18) (18) (18) C (3) 0.063(2) 0.049(2) (2) 0.012(2) 0.006(2) C (2) 0.063(2) 0.070(2) (18) (18) (17) C (3) 0.074(3) 0.071(3) (2) 0.006(2) (2) C (3) 0.074(2) 0.083(3) (2) 0.010(2) 0.004(2) C (3) 0.077(3) 0.069(3) (2) 0.012(2) (2) C (2) 0.058(2) 0.052(2) (17) (16) (16) C (3) 0.090(3) 0.061(3) (2) (2) 0.008(2) C (2) 0.066(2) 0.057(2) (2) (19) (18) C (2) 0.053(2) 0.060(2) (16) (16) (15) C (3) 0.078(3) 0.077(3) (2) 0.015(2) 0.006(2) C (3) 0.084(3) 0.063(3) (2) 0.017(2) 0.000(2) C (3) 0.064(2) 0.055(3) (2) 0.003(2) 0.003(2) C (3) 0.083(3) 0.083(3) (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

103 _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 O (3).? S2 O (2).? S2 N (3).? S2 C (4).? S1 O (3).? S1 O (3).? S1 N (3).? S1 C (4).? N2 C (4).? N2 C (4).? C15 C (5).? C15 C (5).? C15 H ? C11 C (4).? C11 C (5).? C29 C (5).? C29 C (5).? C29 H ? C21 C (5).? C21 H21B ? C21 H21A ? C22 C (4).? C22 C (4).? C22 C (5).? C22 H ? S103

104 C5 C (4).? C5 C (5).? C5 C (4).? C5 H ? C20 C (4).? C20 H20B ? C20 H20A ? C30 C (5).? C30 H ? N1 C (4).? N1 C (5).? C16 H ? C6 C (4).? C6 H6A ? C6 H6B ? C7 C (5).? C7 H7B ? C7 H7A ? C27 C (4).? C27 H27A ? C27 H27B ? C12 C (5).? C12 H ? C28 C (4).? C18 C (5).? C18 H18B ? C18 H18A ? C4 C (5).? C4 H4A ? C4 H4B ? S104

105 C23 C (4).? C23 H23A ? C23 H23B ? C34 C (5).? C34 H34C ? C34 H34B ? C34 H34A ? C10 C (5).? C10 H10A ? C10 H10B ? C31 C (5).? C2 C (5).? C2 C (5).? C2 H2B ? C2 H2A ? C14 C (5).? C14 C (5).? C24 C (5).? C24 H24B ? C24 H24A ? C25 C (5).? C25 H25A ? C25 H25B ? C8 C (5).? C8 H8B ? C8 H8A ? C13 H ? C3 H ? C1 H1B ? C1 H1A ? S105

106 C33 C (5).? C33 H ? C19 H ? C9 H9B ? C9 H9A ? C17 H17A ? C17 H17B ? C17 H17C ? C32 H ? C26 H26A ? C26 H26B ? 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 O (16)..? O4 S2 N (16)..? O3 S2 N (16)..? O4 S2 C (17)..? O3 S2 C (16)..? N2 S2 C (15)..? O1 S1 O (17)..? O1 S1 N (17)..? O2 S1 N (17)..? O1 S1 C (18)..? S106

107 O2 S1 C (18)..? N1 S1 C (15)..? C21 N2 C (3)..? C21 N2 S (2)..? C18 N2 S (2)..? C14 C15 C (4)..? C14 C15 H ? C16 C15 H ? C16 C11 C (4)..? C16 C11 S (3)..? C12 C11 S (3)..? C30 C29 C (4)..? C30 C29 H ? C28 C29 H ? N2 C21 C (3)..? N2 C21 H21B ? C20 C21 H21B ? N2 C21 H21A ? C20 C21 H21A ? H21B C21 H21A ? C19 C22 C (3)..? C19 C22 C (3)..? C23 C22 C (3)..? C19 C22 H ? C23 C22 H ? C27 C22 H ? C3 C5 C (3)..? C3 C5 C (3)..? C10 C5 C (3)..? C3 C5 H ? S107

108 C10 C5 H ? C6 C5 H ? C21 C20 C (3)..? C21 C20 H20B ? C19 C20 H20B ? C21 C20 H20A ? C19 C20 H20A ? H20B C20 H20A ? C29 C30 C (4)..? C29 C30 H ? C31 C30 H ? C4 N1 C (3)..? C4 N1 S (3)..? C1 N1 S (3)..? C11 C16 C (4)..? C11 C16 H ? C15 C16 H ? C7 C6 C (3)..? C7 C6 H6A ? C5 C6 H6A ? C7 C6 H6B ? C5 C6 H6B ? H6A C6 H6B ? C6 C7 C (3)..? C6 C7 H7B ? C8 C7 H7B ? C6 C7 H7A ? C8 C7 H7A ? H7B C7 H7A ? C26 C27 C (3)..? S108

109 C26 C27 H27A ? C22 C27 H27A ? C26 C27 H27B ? C22 C27 H27B ? H27A C27 H27B ? C11 C12 C (4)..? C11 C12 H ? C13 C12 H ? C29 C28 C (4)..? C29 C28 S (3)..? C33 C28 S (3)..? N2 C18 C (3)..? N2 C18 H18B ? C19 C18 H18B ? N2 C18 H18A ? C19 C18 H18A ? H18B C18 H18A ? N1 C4 C (3)..? N1 C4 H4A ? C3 C4 H4A ? N1 C4 H4B ? C3 C4 H4B ? H4A C4 H4B ? C22 C23 C (3)..? C22 C23 H23A ? C24 C23 H23A ? C22 C23 H23B ? C24 C23 H23B ? H23A C23 H23B ? C31 C34 H34C ? S109

110 C31 C34 H34B ? H34C C34 H34B ? C31 C34 H34A ? H34C C34 H34A ? H34B C34 H34A ? C9 C10 C (3)..? C9 C10 H10A ? C5 C10 H10A ? C9 C10 H10B ? C5 C10 H10B ? H10A C10 H10B ? C30 C31 C (4)..? C30 C31 C (4)..? C32 C31 C (4)..? C1 C2 C (3)..? C1 C2 H2B ? C3 C2 H2B ? C1 C2 H2A ? C3 C2 H2A ? H2B C2 H2A ? C15 C14 C (4)..? C15 C14 C (4)..? C13 C14 C (4)..? C25 C24 C (3)..? C25 C24 H24B ? C23 C24 H24B ? C25 C24 H24A ? C23 C24 H24A ? H24B C24 H24A ? C26 C25 C (3)..? S110

111 C26 C25 H25A ? C24 C25 H25A ? C26 C25 H25B ? C24 C25 H25B ? H25A C25 H25B ? C9 C8 C (3)..? C9 C8 H8B ? C7 C8 H8B ? C9 C8 H8A ? C7 C8 H8A ? H8B C8 H8A ? C12 C13 C (4)..? C12 C13 H ? C14 C13 H ? C5 C3 C (3)..? C5 C3 C (3)..? C4 C3 C (3)..? C5 C3 H ? C4 C3 H ? C2 C3 H ? N1 C1 C (3)..? N1 C1 H1B ? C2 C1 H1B ? N1 C1 H1A ? C2 C1 H1A ? H1B C1 H1A ? C32 C33 C (4)..? C32 C33 H ? C28 C33 H ? C22 C19 C (3)..? S111

112 C22 C19 C (3)..? C20 C19 C (3)..? C22 C19 H ? C20 C19 H ? C18 C19 H ? C8 C9 C (3)..? C8 C9 H9B ? C10 C9 H9B ? C8 C9 H9A ? C10 C9 H9A ? H9B C9 H9A ? C14 C17 H17A ? C14 C17 H17B ? H17A C17 H17B ? C14 C17 H17C ? H17A C17 H17C ? H17B C17 H17C ? C33 C32 C (4)..? C33 C32 H ? C31 C32 H ? C25 C26 C (3)..? C25 C26 H26A ? C27 C26 H26A ? C25 C26 H26B ? C27 C26 H26B ? H26A C26 H26B ? loop geom_torsion_atom_site_label_1 _geom_torsion_atom_site_label_2 S112

113 _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 C (3)....? O3 S2 N2 C (3)....? C28 S2 N2 C (3)....? O4 S2 N2 C (3)....? O3 S2 N2 C (3)....? C28 S2 N2 C (3)....? O1 S1 C11 C (3)....? O2 S1 C11 C (3)....? N1 S1 C11 C (3)....? O1 S1 C11 C (3)....? O2 S1 C11 C (3)....? N1 S1 C11 C (3)....? C18 N2 C21 C (4)....? S2 N2 C21 C (2)....? N2 C21 C20 C (3)....? C28 C29 C30 C31-0.6(5)....? O1 S1 N1 C4 53.7(3)....? O2 S1 N1 C (3)....? C11 S1 N1 C4-60.1(3)....? O1 S1 N1 C (3)....? O2 S1 N1 C1-34.5(3)....? C11 S1 N1 C1 81.7(3)....? S113

114 C12 C11 C16 C15-0.1(5)....? S1 C11 C16 C (3)....? C14 C15 C16 C11-0.1(5)....? C3 C5 C6 C (3)....? C10 C5 C6 C7-53.9(4)....? C5 C6 C7 C8 56.6(4)....? C19 C22 C27 C (3)....? C23 C22 C27 C (4)....? C16 C11 C12 C13-0.3(5)....? S1 C11 C12 C (3)....? C30 C29 C28 C33 1.1(5)....? C30 C29 C28 S (2)....? O4 S2 C28 C (3)....? O3 S2 C28 C (3)....? N2 S2 C28 C (3)....? O4 S2 C28 C (3)....? O3 S2 C28 C (3)....? N2 S2 C28 C (3)....? C21 N2 C18 C (4)....? S2 N2 C18 C (3)....? C1 N1 C4 C3 16.9(4)....? S1 N1 C4 C (3)....? C19 C22 C23 C (3)....? C27 C22 C23 C (4)....? C3 C5 C10 C (3)....? C6 C5 C10 C9 52.9(4)....? C29 C30 C31 C32-0.4(5)....? C29 C30 C31 C (3)....? C16 C15 C14 C13 0.6(5)....? C16 C15 C14 C (3)....? S114

115 C22 C23 C24 C (4)....? C23 C24 C25 C (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 C (3)....? C10 C5 C3 C (3)....? C6 C5 C3 C4-55.6(4)....? C10 C5 C3 C2 61.8(4)....? C6 C5 C3 C (3)....? N1 C4 C3 C (3)....? N1 C4 C3 C2-33.2(3)....? C1 C2 C3 C (3)....? C1 C2 C3 C4 38.1(4)....? C4 N1 C1 C2 6.9(4)....? S1 N1 C1 C (3)....? C3 C2 C1 N1-28.0(4)....? C29 C28 C33 C32-0.6(5)....? S2 C28 C33 C (3)....? C23 C22 C19 C (3)....? C27 C22 C19 C (4)....? C23 C22 C19 C (4)....? C27 C22 C19 C (3)....? C21 C20 C19 C (3)....? C21 C20 C19 C (3)....? N2 C18 C19 C (3)....? N2 C18 C19 C (3)....? C7 C8 C9 C (4)....? C5 C10 C9 C8-55.5(4)....? C28 C33 C32 C31-0.4(5)....? S115

116 C30 C31 C32 C33 0.9(5)....? C34 C31 C32 C (3)....? C24 C25 C26 C (4)....? C22 C27 C26 C (4)....? _diffrn_measured_fraction_theta_max _diffrn_reflns_theta_full _diffrn_measured_fraction_theta_full _refine_diff_density_max _refine_diff_density_min _refine_diff_density_rms S116

117 O H N S O O Ph data_yct _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 _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' 'International Tables Vol C Tables and ' 'H' 'H' 'International Tables Vol C Tables and ' 'N' 'N' 'International Tables Vol C Tables and ' 'O' 'O' 'International Tables Vol C Tables and ' 'S' 'S' 'International Tables Vol C Tables and ' _symmetry_cell_setting monoclinic _symmetry_space_group_name_h-m 'P 21' loop_ S117