Supporting Information. Pd-Catalyzed Intramolecular Aminoalkylation of Unactivated. Alkenes: Access to Diverse N-Heterocycles.

Transcription

1 Supporting Information Pd-Catalyzed Intramolecular Aminoalkylation of Unactivated Alkenes: Access to Diverse N-Heterocycles Liu Ye, Kai-Yip Lo, Qiangshuai Gu and Dan Yang * Department of Chemistry, The University of Hong Kong Pokfulam Road, Hong Kong, P.R. China yangdan@hku.hk Table of Contents General Methods Preparation of Substrates Characterization Data of Substrates Representative Procedure of Pd-Catalyzed Intramolecular S2 S3 S9 S19 aminoalkylation Structures of Side Products Characterization Data of Products References 15 and 22, Scheme S1 and Figure S1 ESI-MS Analysis HPLC data for 1.2r and 2r NMR Spectra of New Compounds S20 S20 S30 S33 S34 S36 1

2 General Methods All reactions were performed in oven-dried flasks. PdCl2 and Pd(cod)2Cl2 were purchased from the Precious Metals and used as received. Pd(OAc)2 and Pd2(dba)3 were purchased from the Strem and used as received. All other commercially available chemicals were used as received. CH3CN was freshly distilled over calcium hydride or HPLC grade. The 4Å (powder) molecular sieves were activated by heating to 300 o C in oven for 6 hours and stored in a septum-sealed flask under an argon atmosphere. Reactions were monitored by thin-layer chromatography (TLC) using E. Merck silica gel 60 precoated glass plates with 0.25 mm thickness. Components were visualized by illumination with a short-wavelength ultra-violet light and/or staining in phosphomolybdic acid (PMA) solution followed by heating. Flash column chromatography were performed on E. Merck silica gel 60 ( mesh ASTM) using ethyl acetate/n-hexane as eluting solvents. 1 H and 13 C NMR spectra were recorded in deuteriochloroform (CDCl3) with tetramethylsilane (TMS) as internal standard at ambient temperature unless otherwise indicated on a Bruker Avance DPX 300 Fourier Transform Spectrometer operating at 300 MHz for 1 H and 75 MHz for 13 C, or a Bruker Avance DPX 400 Fourier Transform Spectrometer operating at 400 MHz for 1 H and 100 MHz for 13 C, a Bruker Avance DPX 500 Fourier Transform Spectrometer operating at 500 MHz for 1 H and 125 MHz for 13 C. Infrared absorption spectra were recorded as a solution in CH2Cl2 with a Bio-Rad FTS 165 Fourier Transform spectrophotometer. Mass spectra were recorded with a Finnigan MAT 95 mass spectrometer for both low resolution and high resolution mass spectra. Melting points were determined by Axiolab ZEISS microscope apparatus and were uncorrected. 1 H NMR are recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet or unresolved, br = broad singlet, coupling constant(s) in Hz, integration). 2

3 Preparation of Substrates The substituted anilines, except 1-1l and 1-1m, were prepared according to our previous reports 1, l was prepared from the following procedure The mixture of cyclohexanone (5.2 ml, 50 mmol) and pyrrolidine (7.1 ml, 85 mmol) in dry toluene (20 ml) was heated to reflux under Dean-Stark conditions for 5 h. The solvent and excess pyrrolidine were removed in vacuo. The crude residue was purified by distillation (120 C, 26 MPa) to afford 1-cyclohexenylpyrrolidine (6.01 g, 80% yield). To a solution of 1-cyclohexenylpyrrolidine (6.37 g, 42.2 mmol) in dry THF (25 ml) was added 1-fluoro-2-nitrobenzene slowly (6.25 g, 44.3 mmol) in dry THF (5 ml) at room temperature. The resulting mixture was refluxed under argon for 36 h. The mixture was cooled to room temperature and concentrated to about 20 ml. The residue was treated with 2N HCl (20 ml) and refluxed for 2 h. The mixture was cooled to room temperature, diluted with EtOAc (50 ml) and H2O (20 ml), and separated. The aqueous layer was extracted with EtOAc (30 ml 2). The combined organic phase was washed with brine (30 ml 2), dried over anhydrous Na2SO4, and then concentrated in vacuo. The residue was purified by flash column chromatography to afford 2-(2-nitrophenyl)cyclohexanone (3.23 g, 35% yield) as an oil. To a suspension of methyltriphenyl phosphonium iodide (11.2 g, 27.7 mmol) in dry THF (90 ml) was added n-buli slowly (19 ml, 1.6 M in hexane) at room temperature under argon. After refluxing for 1 h until all solid was dissolved, the mixture was cooled to room temperature and was added 2-(2-nitrophenyl)cyclohexanone (3.03 g, 13.8 mmol) in dry THF (10 ml). The resulting mixture was refluxed overnight. The mixture was cooled to room temperature and quenched with H2O (15 ml). The mixture was concentrated in vacuo to about 80 ml. The residue was extracted with EtOAc (40 ml 2). The combined organic phase was washed with brine (30 ml 2), dried over Na2SO4, and then concentrated in vacuo. The residue was purified by flash column chromatography to afford 1-(2-methylenecyclohexyl)-2-nitrobenzene (1.13 g, 38% yield) as an oil. To a solution of 1-(2-methylenecyclohexyl)-2-nitrobenzene (0.6 g, 2.76 mmol) and 5% AcOH (15 ml) in THF (15 ml) was added iron powder (1.2 g, 22.1 mmol). 3

4 The resulting mixture was stirred at room temperature overnight. The mixture was poured into the solution of EtOAc (15 ml) and H2O (10 ml) and filtered through Celite. The filtrate was separated and organic phase was subsequently washed with saturated NaHCO3 solution, and brine, then concentrated in vacuo to afford crude 1 1l, which was used directly in the next step. 1 1m was prepared in the following steps. 3 NH 2 OH a NH 2 b NH 2 OMe 1 1m Reagents and conditions: (a) H 2 SO 4,MeOH,50 C (b) allylmagnesium bromide, dry THF, 0 Ctort To a solution of (2-aminophenol)methanol (3.0 g, 24.4 mmol) in MeOH (170 ml) was added concentrated sulfuric acid (2.4 ml, 26.8 mmol) and the reaction mixture was heated at 50 C for 13 h. The resulting solution was then cooled at 0 C, added slowly with saturated NaHCO3 solution (30 ml), and concentrated in vacuo. Water (50 ml) was added and the resulting mixture was extracted with CH2Cl2 (50 ml 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and then concentrated in vacuo. The crude 2-methoxymethyl aniline was used directly after the azeotropic removal of water content by toluene. To a THF solution of allylmagnesium bromide (1 M, 75.8 ml, 75.8 mmol) was slowly added crude 2-methoxymethyl aniline at 0 C via a funnel, and the mixture was allowed to warm to room temperature with stirring for 24 h. The resulting solution was quenched with water, and the solution was extracted with CH2Cl2 (75 ml 3). The combined organic layers were washed with brine and dried over Na2SO4, then concentrated in vacuo. The crude aniline 1 1m was used directly in the next step. General procedure for the preparation of 1.1a R NH 2 R 1 1 1a n O Br Br K 2 CO 3, DCM R Br O NH R a n To the solution of 1 1a (0.267 g, 2.0 mmol) in dry DCM (8.0 ml) was added K2CO3 (0.31 g, 2.2 mmol). The mixture was stirred vigorously at room temperature under Ar for 15 min, then cooled in an ice-bath. Bromoacetyl bromide (0.21 ml, 2.4 mmol) in dry DCM (2.0 ml) was added slowly. After the addition, the resulting 4

5 mixture was stirred at room temperature for 3 h until complete consumption of 1 1a. The reaction was quenched with cold H2O (4 ml), and diluted with DCM (10.0 ml). The mixture was washed with brine (10 ml 2), dried over Na2SO4, and then concentrated in vacuo. The residue was purified by flash column chromatography to afford 1.1a (0.44 g, 90%) as a white solid. 1.1b n were synthesized following the same procedure. General procedure for the preparation of 1.1a q and 1.2s t To a solution of crude aniline 1-1a and 2-chloro-2-phenylacetic acid (0.34 g, 2.0 mmol) in dry CH2Cl2 (10 ml) was added with N,N -dicyclohexylcarbodiimide (DCC, 2.2 mmol) at room temperature. After 16 h, the reaction mixture was filtered and concentrated in vacuo. The residue was purified by flash column chromatography with ethyl acetate and hexane as eluents to give the crude 1.2s, which was further purified by recrystallization in CH2Cl2 and hexane to afford the pure product (74 % yield). 1.1b q and 1.2s t were synthesized following the same procedure. NH 2 Cl O Cl O NH Cl F K 2 CO 3, DCM F 1 1r 1.2r To the cooled solution (in an ice-bath) of 1 1r (3.0 mmol) and K2CO3 (0.46, 3.3 mmol) in dry DCM (12.0 ml) was added 2-chloropropanoyl chloride (0.32 ml, 3.3 mmol) slowly. After the addition, the resulting mixture was stirred at room temperature for 5 h until complete consumption of starting material. The reaction was quenched with cold H2O (4 ml), and diluted with DCM (10.0 ml). The mixture was washed with brine (10 ml 2), dried over Na2SO4, and then concentrated in vacuo. The residue was purified by flash column chromatography to afford 1.2r (80%) as a white solid. Preparation of substrates 1.3a g 5 5

6 In an oven-dried round-bottomed flask, diphenylacetonitrile (4.83 g, 25 mmol) was added in small portions at 0 C to a suspension of NaH (60% dispersion in oil, 1.3 g, 32.5 mmol) in dry DMF (35 ml). After stirring at room temperature for 30 min, the reaction mixture was cooled to 0 C again and allyl bromide (2.4 ml, 27.5 mmol) was slowly added. The resulting mixture was warmed to room temperature. After 12 h, the reaction mixture was quenched with water (50 ml) and extracted with CH2Cl2 (60 ml 2). The combined organic layers were washed with brine (30 ml 2), dried over anhydrous Na2SO4, filtered with a short pad of silica gel, eluted with 30% ethyl acetate in hexane, and then concentrated in vacuo to afford crude nitrile product, which was used in the next step directly without further purification. To an oven-dried round-bottomed flask charged with a solution of LiAlH4 (1.4 g, 37.4 mmol) in dry Et2O (60 ml) was added crude nitrile slowly at 0 C. After the addition, the reaction mixture was allowed to warm to room temperature. After 14 h, the reaction mixture was cooled to 0 C again and was quenched with water (3.0 ml), and 15% NaOH solution (3.0 ml). The reaction mixture was stirred for 15 min and filtered through a short pad of celite. The filtrate was dried over anhydrous MgSO4, filtered, and concentrated in vacuo to obtain crude amine 1 3a. 1 3e was prepared following the same procedure. To a cooled solution ( 78 C) of 2-phenylacetonitrile (2.35 g, 20 mmol) in dry THF (25 ml) was added LiHMDS slowly (20 ml, 1.0 M in THF) under argon atmosphere. After stirring for 30 min, allyl bromide (1.9 ml, 22 mmol) was slowly added. The resulting mixture was warmed to room temperature and stirred overnight. The reaction mixture was poured into a mixture of hexanes (50 ml) and brine (40 ml) and the resulting biphasic mixture was stirred vigorously. The organic layer was separated and washed with brine (50 ml), then dried over anhydrous Na2SO4 and concentrated. The residue was purified by flash column chromatography to afford pure nitrile product (1.98 g, 63%), which was reduced to afford crude 1.3 c following the same reduction procedure described above. 1 3b and 1 3f were prepared following the same method. 1 3d was prepared according to the following procedure. 6 6

7 A mixture of cinnamyl alcohol (6.7 g, 50 mmol), triethyl orthoacetate (10.1 ml, 55 mmol), and hexanoic acid (0.15 ml) was placed in a 50-mL round-bottomed flask equipped with a thermometer, Claisen head, and condenser. The solution was heated in an oil bath with distillation of ethanol. After 3 h, distillation of ethanol slowed down and another portion of hexanoic acid (0.1 ml) was added. Another portion of hexanoic acid (0.1 ml) was added again at 4.5 h. After 7 h, TLC analysis indicated that no cinnamyl alcohol remained. The solution was allowed to cool to room temperature, and potassium hydroxide (4.2 g, 75 mmol) in water-methanol mixture (24 ml, 1/3, v/v) was added. The mixture was heated under reflux for 2 h under argon atmosphere. The reaction mixture was then cooled to room temperature, and washed with diethyl ether and acidified with concentrated HCl. The acidic solution was extracted with diethyl ether (50 ml 3) and the organic layer was dried over MgSO4, filtered, and concentrated in vacuo to provide crude 3-phenyl-4-pentenoic acid (8.03 g, 91%). To a solution of 3-phenylpent-4-enoic acid (5.3 g, 30 mmol) in dry CH2Cl2 (40 ml) with a dry tube packed with anhydrous calcium chloride at 0 C was added oxalyl chloride (3.2 ml, 33 mmol) dropwise, followed by the addition of DMF (2 drops). After 6 h, the resulting mixture was concentrated in vacuo and the residue was taken up with dry CH2Cl2 (40 ml). In an ice water bath, aqueous ammonia solution (28%, 100 ml) was added dropwise to the above mixture through a funnel. After stirring overnight, the organic layer was separated and the aqueous layer was extracted with CH2Cl2 (60 ml 2). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography to afford the amide product (2.95 g, 56% yield). To an oven-dried round-bottomed flask charged with a suspension of LiAlH4 (0.58 g, 13 mmol) in dry Et2O (60 ml) was added the crude product amide slowly at 0 C. After addition, the reaction mixture was stirred at room temperature overnight. The reaction mixture was cooled to 0 C again and quenched with water (2.5 ml), followed by NaOH solution (15%, 2.5 ml). The reaction mixture was stirred for 15 min and filtered through a short pad of celite. The filtrate was dried over anhydrous MgSO4, filtered, and concentrated in vacuo to obtain crude amine 1 3d. 1 3g was prepared according to reference 4. General procedure for the synthesis of 1.3a g 7

8 To a mixture solution of 1 3a (0.49 g, 3 mmol) and pyridine (0.32 ml, 3.9 mmol) in dry CH2Cl2 (10 ml) was added 2-chloroacetyl chloride (0.28 ml, 3.6 mmol) in dry CH2Cl2 (2 ml) at 0 o C in argon. After addition, the reaction mixture was gradually warmed up to room temperature. After 3 h, the reaction mixture was poured into a mixture of CH2Cl2 (15 ml) and brine (10 ml) and the resulting biphasic mixture was stirred vigorously. The organic layer was separated and washed with water (10 ml), HCl (0.2 N, 10 ml), brine (10 ml) and then dried over Na2SO4, and concentrated. The residue was purified by flash column chromatography to afford 1.3a (0.59 g, 82%). 1.3b g were prepared by the same method. References: 1 Yip, K.T.; Yang, M.; Law, K. L.; Zhu, N. Y.; Yang D. J. Am. Chem. Soc. 2006, 128, He, W.; Yip, K. T.; Zhu, N. Y.; Yang, D. Org. Lett. 2009, 11, Görl, C.; Alt, H. G. J. Mol. Catal. A: Chem. 2007, 273, Julian, L. D.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, Bender, C. F.; Widenhoefer, R. A. J. Am. Chem. Soc. 2005, 127, Gonzalez, F. B.; Bartlett, P. A. Org. Syn. 1986, 64,

9 Characterization Data of Substrates 1.1a: white solid; m.p C; analytical TLC (silica gel 60), 75% DCM in n-hexane, Rf = 0.30; 1 H NMR (300 MHz, CDCl3) 8.25 (brs, 1H), 7.76 (d, J = 8.0 Hz, 1H), (m, 3H), (m, 1H), 5.15 (dd, J = 10.1, 1.4 Hz, 1H), 5.06 (dd, J = 17.2, 1.5 Hz, 1H), 3.98 (s, 2H), 3.36 (d, J = 6.0 Hz, 2H); 13 C NMR (75 MHz, CDCl3) (C), (CH), (C), (C), (CH), (CH), (CH), (CH), (CH2), 36.3 (CH2), 29.6 (CH2); IR (CH2Cl2) 3443, 2953, 2922, 2852, 1653, 1634, 1539, 1458, 1375, 754, 721 cm -1 ; LRMS (EI, 20 ev) m/z 253 (M +, 7), 255 (M +, 7), 132 (100); HRMS (EI) for C11H12ON 79 Br/ 81 Br (M + ): calcd / , found / b: white solid; m.p C; analytical TLC (silica gel 60), 75 % DCM in n-hexane, Rf = 0.40; 1 H NMR (400 MHz, CDCl3) 8.25 (br, 1H), 7.87 (d, J = 8.0 Hz, 1H), (m, 1H), (m, 2H), 4.91 (s, 1H), 4.64 (s, 1H), 4.00 (s, 2H), 3.33 (s, 2H), 1.78 (s, 3H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (C), (CH), (CH), (CH), (CH2), 40.8 (CH2), 29.6 (CH2), 22.6 (CH3); IR (CH2Cl2) 3254, 2953, 2922, 2850, 2723, 1654, 1539, 1462, 1375, 972, 721 cm -1 ; LRMS (EI, 20 ev) m/z 267 (M +, 4), 269 (M +, 4),146 (100); HRMS (EI) for C12H14ON 79 Br/ 81 Br (M + ): calcd / , found / c: white solid; m.p C; analytical TLC (silica gel 60), 10% EtOAc in n-hexane, Rf = 0.22; 1 H NMR (300 MHz, CDCl3) 8.11 (br, 1H), 7.67 (d, J = 8.1 Hz, 1H), 7.08 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), (m, 1H), (m, 2H), 4.03 (s, 2H), 3.36 (d, J = 6.3 Hz, 2H), 2.32 (s, 3H). 13 C NMR (75 MHz, CDCl3) (C), (C), (CH), (C), (C), (CH), (CH), (CH), (CH2), 36.3 (CH2), 29.6 (CH2), 20.9 (CH3); IR (CH2Cl2) 3250, 2953, 2935, 2908, 2852, 2723, 1651, 1462, 1375, 1307, 721 cm -1 ; LRMS (EI, 20 ev) m/z 267 (M +, 8), 269 (M +, 8), 146 (100); HRMS (EI) for C12H14ON 79 Br/ 81 Br (M + ): calcd / , Found: /

10 1.1d: white solid; m.p C; analytical TLC (silica gel 60), 25% EtOAc in n-hexane, Rf = 0.28; 1 H NMR (400 MHz, CDCl3) 8.17 (br, 1H), 7.76 (d, J = 8.6 Hz, 1H), 7.39 (d, J = 8.6 Hz, 1H), 7.35 (s, 1H), 5.94 (tdd, J = 17.1, 10.2, 5.9 Hz, 1H), 5.22 (d, J = 10.2 Hz, 1H), 5.11 (d, J = 17.2 Hz, 1H), 4.03 (s, 2H), 3.37 (d, J = 5.7 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (CH), (C), (CH), (C), (CH), (CH), (C), (CH2), 35.9 (CH2), 29.5 (CH2); IR (CH2Cl2) 3422, 3043, 2980, 1685, 1516, 1400, 898, 786 cm -1 ; LRMS (EI, 20 ev) m/z 331 (M +, 7), 333 (M +, 7), 131 (100); HRMS (EI) for C11H11ONBr2 (M + ): calcd / , Found: / e: white solid; m.p C; analytical TLC (silica gel 60), 25 % EtOAc in n-hexane, Rf = 0.26; 1 H NMR (300 MHz, CDCl3) 8.41 (br, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.57 (dd, J = 8.4, 1.8 Hz, 1H), 7.50 (d, J = 1.8 Hz, 1H), (m, 1H), (m, 2H), 4.06 (s, 2H), 3.44 (d, J = 6.0 Hz, 2H); 13 C NMR (75 MHz, CDCl3): (C), (C), (CH), (CH), (CH), (C), (CH), (C), (CH2), (C), 35.7 (CH2), 29.5 (CH2); IR (CH2Cl2) 3457, 2955, 2920, 2852, 2359, 1456, 1375, 1153, 993, 721, 667 cm -1 ; LRMS (EI, 20 ev) m/z 278 (M +, 5), 280 (M +, 5),157 (100); HRMS (EI) for C12H11ON2 79 Br/ 81 Br (M + ): calcd / , Found / f: white solid; m.p C; analytical TLC (silica gel 60), 10 % EtOAc in n-hexane, Rf = 0.33; 1 H NMR (300 MHz, CDCl3) 7.82 (br, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), 4.0 (s, 2H), 3.31 (d, J = 6.3 Hz, 2H), (m, 1H,), 1.19 (d, J = 6.9 Hz, 6H); 13 C NMR (75 MHz, CDCl3): (C), (C), (C), (CH), (C), (CH), (CH), (CH), (CH2), 36.8 (CH2), 29.0 (CH2), 28.6 (CH), 23.5 (CH3); IR (CH2Cl2) 3421, 2953, 2922, 2852, 2723, 1458, 1375, 1307, 721 cm -1 ; LRMS (EI, 20 ev) m/z 295 (M +, 13), 297 (M +, 13), 202 (100); HRMS (EI) for C14H18ON 79 Br/ 81 Br (M + ): calcd / , Found: /

11 1.1g: white solid; m.p C; analytical TLC (silica gel 60), 10 % EtOAc in n-hexane, Rf = 0.34; 1 H NMR (300MHz, CDCl3) 8.13 (br, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 7.04 (s, 1H), (m, 1H), (m, 2H), 4.03 (s, 2H), 3.36 (q, J = 7.2 Hz, 1H), 2.33 (s, 3H), (m, 2H), 0.92 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz, CDCl3) (C), (CH), (C), (C), (C), (CH), (CH), (CH), (CH2), 46.3 (CH), 29.7 (CH2), 26.6 (CH2), 21.2 (CH3), 12.3 (CH3); IR (CH2Cl2) 3373, 2951, 2926, 1697, 1456, 1377, 966, 721 cm -1 ; LRMS (EI, 20 ev) m/z 295 (M +, 4), 297 (M +, 4), 174 (100); HRMS (EI) for C14H18ON 79 Br/ 81 Br (M + ): calcd / , Found: / h: white solid; m.p C; analytical TLC (silica gel 60), 10 % EtOAc in n-hexane, Rf = 0.35; 1 H NMR (300 MHz, CDCl3) 8.19 (br, 1H), 7.21 (d, J = 2.4 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), (m, 1H), (m, 2H), 4.03 (s, 2H), 3.81 (s, 3H), 3.79 (s, 3H), (m, 2H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH2), (C), 99.4 (CH), 96.4 (CH), 55.8 (CH3), 55.4 (CH3), 29.7 (CH2), 27.9 (CH2). IR (CH2Cl2) 3336, 3182, 2953, 1653, 1462, 1301, 976, 831, 721 cm -1 ; LRMS (EI, 20 ev) m/z 313 (M +, 10), 315 (M +, 10), 192 (100); HRMS (EI) for C13H16O3N 79 Br/ 81 Br (M + ): calcd / , Found: / i: white solid; m.p C; analytical TLC (silica gel 60), 20 % EtOAc in n-hexane, Rf = 0.21; 1 H NMR (300 MHz, CDCl3) 7.65 (br, 1H), 6.39 (s, 2H), (m, 1H), (m, 2H), 4.01 (s, 2H), 3.77 (s, 6H), 3.28 (d, J = 6.3 Hz, 2H); 13 C NMR (75 MHz, CDCl3): (C), (C), (C), (C), (CH), (CH2), (C), (CH), 97.2 (CH), 55.8 (CH3), 55.4 (CH3), 36.5 (CH2), 29.1 (CH2); IR (CH2Cl2) 3246, 2953, 1662, 1541, 1155, 1049, 721 cm -1 ; LRMS (EI, 20 ev) m/z 313 (M +, 22), 315 (M +, 22), 192 (100); HRMS (EI) for C13H16O3N 79 Br/ 81 Br (M + ): calcd / , Found: /

12 1.1j: white solid; m.p C; analytical TLC (silica gel 60), 10 % EtOAc in n-hexane, Rf = 0.14; 1 H NMR (400 MHz, CDCl3) 7.77 (br, 1H), (m, 2H), (m, 1H), (m, 2H), 4.05 (s, 2H), (m, 2H), 2.28 (s, 3H), 2.20 (s, 3H). 13 C NMR (100 MHz, CDCl3) (C), (CH), (C), (C), (C), (C), (CH), (CH), (CH2), 32.8 (CH2), 28.9 (CH2), 19.5 (CH3), 18.2 (CH3); IR (CH2Cl2) 3441, 3244, 2953, 2922, 2852, 1654, 1531, 1462, 1375, 1307, 721 cm -1 ; LRMS (EI, 20 ev) m/z 281 (M +, 5), 283 (M +, 5), 160 (100); HRMS (EI) for C13H16ON 79 Br/ 81 Br (M + ): calcd / , Found: / k: white solid; m.p C; analytical TLC (silica gel 60), 10 % EtOAc in n-hexane, Rf = 0.23; 1 H NMR (300 MHz, acetone-d6) 9.30 (br, 1H), (m, 1H), (m, 2H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), 4.24 (s, 2H), 3.54 (d, J = 6.8 Hz, 2H); 13 C NMR (75 MHz, acetone-d6) (C), (CH), (C), (C), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH2), 36.1 (CH2), 28.8 (CH2); IR (CH2Cl2) 3419, 3244, 2953, 1654, 1528, 1462, 1155, 966, 721 cm -1 ; LRMS (EI, 20 ev) m/z 303 (M +, 14), 305 (M +, 14), 182 (100); HRMS (EI) for C15H14ON 79 Br/ 81 Br (M + ): calcd / , Found: / l: yellow oil; analytical TLC (silica gel 60), 15% EtOAc in n-hexane, Rf = 0.30; 1 H NMR (400 MHz, CDCl3) 8.31 (br, 1H), 7.82 (d, J = 8.0 Hz, 1H), (m, 3H), 4.78 (d, J = 1.3 Hz, 1H), 4.10 (d, J = 1.3 Hz, 1H), 4.04 (ABq, JAB = 14.0 Hz, 2H), 3.25 (d, J = 13.0 Hz, 1H), (m, 1H), (m, 1H), (m, 3H), (m, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl3): (C), (C), (C), (C), (CH), (CH), (CH), (CH), (CH2), 45.6 (CH), 36.5 (CH2), 32.5 (CH2), 29.8 (CH2), 28.4 (CH2), 26.8 (CH2); IR (CH2Cl2) 3373, 3180, 2953, 1693, 1523, 1462, 1155, 964, 721 cm -1 ; LRMS (EI, 20 ev) m/z 307 (M +, 5), 309 (M +, 5), 228 (100); HRMS (EI) for 12

13 C15H18ON 79 Br/ 81 Br (M + ): calcd / , Found / m: white solid; m.p C; analytical TLC (silica gel 60), 15% EtOAc in n-hexane, Rf = 0.58; 1 H NMR (400 MHz, CDCl3) 8.22 (br, 1H), 7.82 (d, J = 11.2 Hz, 1H), (m, 3H), (m, 1H), (m, 2H), 4.08 (s, 2H), 2.72 (t, J = 7.6 Hz, 2H), (m, 2H); 13 C NMR (75 MHz, CDCl3) (C), (CH), (C), (C), (CH), (CH), (CH), (CH), (CH2), 34.1 (CH2), 30.9 (CH2), 29.8 (CH2); IR (CH2Cl2) 3410, 3254, 2955, 2854, 1645, 1454, 974, 758, 721 cm -1 ; LRMS (EI, 20 ev) m/z 267 (M +, 5), 269 (M +, 5), 106 (100); HRMS (EI) for C12H14ON 79 Br/ 81 Br (M + ): calcd / , found / n: redwish oil; analytical TLC (silica gel 60), 15% EtOAc in n-hexane, Rf = 0.52; 1 H NMR (300 MHz, CDCl3) 8.92 (br, 1H), 8.32 (dd, J = 7.8, 1.5 Hz, 1H), 7.04 (dd, J = 7.8, 1.5 Hz, 1H), 6.98 (dd, J = 7.8, 1.3 Hz, 1H), 6.88 (dd, J = 7.8, 1.3 Hz, 1H), (m, 1H), (m, 2H), (m, 2H), 4.03 (s, 2H); 13 C NMR (75 MHz, CDCl3) (C), (C), (CH), (C), (CH), (CH), (CH), (CH2), (CH), 69.4 (CH2), 29.8 (CH2); IR (CH2Cl2) 3418, 2955, 1645, 1602, 1454, 1370, 1165, 684 cm -1 ; LRMS (EI, 20 ev) m/z 269 (M +, 7), 271 (M +, 7), 108 (100); HRMS (EI) for C11H12O2N 79 Br/ 81 Br (M + ): calcd / , Found: / a: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.45; 1 H NMR (400 MHz, CDCl3) 8.32 (bs, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.22 (dd, J = 7.5, 1.6 Hz, 1H), 7.16 (td, J = 7.6, 1.0 Hz, 1H), 5.97 (tdd, J = 16.1, 10.2, 5.9 Hz, 1H), 5.18 (dd, J = 10.1, 1.4 Hz, 1H), 5.09 (dd, J = 17.2, 1.6 Hz, 1H), 4.21 (s, 2H), 3.41 (d, J = 5.9 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (CH), (C), (C), (CH), (CH), (CH), (CH), (CH2), 43.1 (CH2), 36.5 (CH2); IR (CH2Cl2) 3045, 2988, 1423, 1248, 1155, 893, 677 cm -1 ; LRMS (EI, 20 ev) m/z 209 (M +, 13), 132 (100); 13

14 HRMS (EI) for C11H12ONCl (M + ): calcd , found b: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.58; 1 H NMR (400 MHz, CDCl3) 8.38 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 7.20 (dd, J = 7.5, 1.7 Hz, 1H), 7.15 (t, J = 7.3, 7.3 Hz, 1H), 4.92 (s, 1H), 4.66 (s, 1H), 4.20 (s, 2H), 3.34 (s, 2H), 1.77 (s, 3H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (C), (CH), (CH), (CH), (CH2), 43.1 (CH2), 40.9 (CH2), 22.5 (CH3); IR (CH2Cl2) 3451, 3047, 2988, 1682, 1420, 1248, 1155, 899, 687 cm -1 ; LRMS (EI, 20 ev) m/z 223 (M +, 25), 146 (100); HRMS (EI) for C12H14ONCl (M + ): calcd , found O NH Cl 1.2c: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.53; 1 H NMR (400 MHz, CDCl3) 8.24 (bs, 1H), 7.71 (d, J = 8.2 Hz, 1H), 7.09 (d, J = 8.2 Hz, 1H), 7.03 (s, 1H), 5.95 (tdd, J = 16.2, 10.2, 6.0 Hz, 1H), 5.17 (dd, J = 10.1, 1.4 Hz, 1H), 5.09 (dd, J = 17.2, 1.6 Hz, 1H), 4.20 (s, 2H), 3.36 (d, J = 5.9 Hz, 2H), 2.32 (s, 3H); 13 C NMR (100 MHz, CDCl3) (C), (C), (CH), (C), (CH), (C), (CH), (CH), (CH2), 43.0 (CH2), 36.5 (CH2), 20.9 (CH3); IR (CH2Cl2) 3436, 3049, 2988, 1420, 1248, 1155, 899, 687 cm -1 ; LRMS (EI, 20 ev) m/z 223 (M +, 22), 146 (100); HRMS (EI) for C12H14ONCl (M + ): calcd , found m: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.51; 1 H NMR (400 MHz, CDCl3) 8.30 (brs, 1H), 7.84 (d, J = 7.8 Hz, 1H), (m, 2H), 7.17 (dt, J = 7.8, 1.1 Hz, 1H), 5.86 (tdd, J = 17.0, 10.2, 6.7 Hz, 1H), (m, 2H), 4.24 (s, 2H), (m, 2H), 2.37 (dd, J = 14.6, 7.5 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (CH), (C), (C), (CH), (CH), (CH), (CH), (CH2), 43.1 (CH2), 34.0 (CH2), 31.0 (CH2); IR (CH2Cl2) 3456, 3045, 2986, 1420, 1248, 1155, 903, 681, 652 cm -1 ; LRMS (EI, 20 ev) m/z 223 (M +, 9), 182 (100); HRMS (EI) for C12H14ONCl (M + ): calcd , found

15 1.2 : white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.35; 1 H NMR (400 MHz, CDCl3) 8.15 (br, 1H), 7.64 (d, J = 8.8 Hz, 1H), 6.81 (dd, J = 8.7, 2.9 Hz, 1H), 6.76 (d, J = 2.8 Hz, 1H), 5.94 (tdd, J = 16.2, 10.2, 6.0 Hz, 1H), 5.17 (dd, J = 10.2, 1.5 Hz, 1H), 5.09 (dd, J =17.1, 1.6 Hz, 1H), 4.20 (s, 2H), 3.80 (s, 3H), 3.35 (d, J = 6.0 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (C), (CH), (C), (C), (CH), (CH2), (CH), (CH), 55.4 (CH3), 43.0 (CH2), 36.6 (CH2); IR (CH2Cl2) 3492, 3045, 2984, 1684, 685 cm -1 ; LRMS (EI, 20 ev) m/z 239 (M +, 48), 162 (100); HRMS (EI) for C12H14O2NCl (M + ): calcd , found p: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.47; 1 H NMR (400 MHz, CDCl3) 8.23 (br, 1H), 7.78 (dd, J = 8.8, 5.3 Hz, 1H), (m, 2H), 5.94 (tdd, J = 16.2, 10.3, 6.0 Hz, 1H), 5.21 (dd, J = 10.2, 1.4 Hz, 1H), 5.10 (dd, J = 17.2, 1.5 Hz, 1H), 4.21 (s, 2H), 3.37 (d, J = 6.0 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (d, 1 JC-F = 267 Hz, C), (CH), (d, 3 JC-F = 8 Hz, C), (C), (d, 3 JC-F = 9 Hz, CH), (CH2), (d, 2 JC-F = 23 Hz, CH), (d, 2 JC-F = 22 Hz, CH), 42.9 (CH2), 36.3 (CH2); 19 F NMR (376 MHz, CDCl3) 115.9; IR (CH2Cl2) 3053, 2986, 1713, 1688, 1526, 1418, 745, 706 cm -1 ; LRMS (EI, 20 ev) m/z 227 (M +, 21), 150 (100); HRMS (EI) for C11H11ONClF (M + ): calcd , found q: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf= 0.53; 1 H NMR (400 MHz, CDCl3) 8.30 (br, 1H), 7.87 (d, J = 8.6 Hz, 1H), 7.26 (dd, J = 8.6, 2.5 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 5.94 (tdd, J = 17.1, 10.2, 5.9 Hz, 1H), 5.23 (qd, J = 10.2, 1.5 Hz, 1H), 5.11 (ddd, J = 17.2, 3.2, 1.7 Hz, 1H), 4.21 (s, 2H), 3.37 (td, J = 5.9, 1.5 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (CH), (C), (C), (C), (CH), (CH), (CH), (CH2), 43.0 (CH2), 36.2 (CH2); IR (CH2Cl2) 3044, 2982, 2305, 1423, 1248, 1155, 897, 683 cm -1 ; LRMS (EI, 20 ev) m/z 243 (M +, 2), 194 (2), 166 (6), 102 (100); HRMS (EI) for C11H11ONCl2 (M + ): calcd , found

16 O NH Cl F 1.2r: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.54; 1 H NMR (400 MHz, CDCl3) 8.24 (br, 1H), 7.75 (dd, J = 5.4, 8.4 Hz, 1H), (m, 2H), (m, 1H), (m, 2H), 4.58 (q, J = 7.0 Hz, 1H), 3.35 (d, J = 5.8 Hz, 2H), 1.81 (d, J = 7.0 Hz, 3H); 13 C NMR (100 MHz, CDCl3) (C), (d, 1 JC-F = 244 Hz, C), (CH), (d, 3 JC-F = 8 Hz, C), (C), (d, 3 JC-F = 8 Hz, CH), (CH2), (d, 2 JC-F = 22 Hz, CH), (d, 2 JC-F = 22 Hz, CH), 56.3 (CH), 36.2 (CH2), 22.8 (CH3); 19 F NMR (376 MHz, CDCl3) 116.1; IR (CH2Cl2) 3248, 2923, 2856, 1662, 1542, 1459, 722 cm -1 ; LRMS (EI, 20 ev) m/z 241 (M +, 15), 150 (100); HRMS (EI) for C12H13ONClF (M + ): calcd , found r*: [α] 18 D (c 0.18, CHCl3), HPLC analysis, Chiralcel OF, i-proh/n-hexane = 90/10, flow rate 1.0 ml/min. λ = 205 nm, t(minor) = 8.15 min, t(major) = 9.0 min, 95% ee. 1.2s: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.60; 1 H NMR (400 MHz, CDCl3) 8.40 (brs, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.51 (d, J = 8.6 Hz, 2H), (m, 3H), 7.28 (d, J = 8.6 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 7.14 (t, J = 7.4 Hz, 1H), 5.94 (tdd, J = 16.1, 10.4, 5.8 Hz, 1H), 5.50 (s, 1H), 5.16 (dd, J = 10.2, 1.3 Hz, 1H), 5.04 (dd, J = 17.2, 1.4 Hz, 1H), (m, 2H); 13 C NMR (100 MHz, CDCl3) (C), (C), (CH), (C), (CH), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH2), 62.3 (CH), 36.4 (CH2); IR (CH2Cl2) 3431, 3045, 2988, 1686, 1587, 679 cm -1 ; LRMS (EI, 20 ev) m/z 285 (M +, 2), 132 (100); HRMS (EI) for C17H16ONCl (M + ): calcd , found t: white solid; m.p C; analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf = 0.40; 1 H NMR (400 MHz, CDCl3) 8.38 (s, 1H), 7.83 (d, J = 7.9 Hz, 1H), (m, 1H), 7.19 (d, J = 6.8 Hz, 1H), 7.14 (t, J = 7.2 Hz, 1H), (m, 1H), (m, 2H), 4.56 (t, J = 3.9 Hz, 1H), 3.97 (dd, J = 10.6, 4.7 Hz, 1H), 16

17 3.86 (dd, J = 10.6, 3.5 Hz, 1H), 3.44 (s, 3H), 3.38 (d, J = 5.5 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (CH), (C), (C), (CH), (CH), (CH), (CH), (CH2), 73.8 (CH2), 59.6 (CH3), 59.3 (CH), 36.3 (CH2); IR (CH2Cl2) 3390, 3064, 1685, 1525, 1454, 1122, 923, 719 cm -1 ; LRMS (EI, 20 ev) m/z 253 (M +, 12), 132 (100); HRMS (EI) for C13H16O2NCl (M + ): calcd , found a: white solid; m.p C; analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf = 0.40; 1 H NMR (300 MHz, CDCl3) (m, 4H), (m, 6H), 6,24 (brs, 1H), (m, 1H), (m, 2H), 3.97 (d, J = 6.0 Hz, 2H), 3.91 (s, 2H), 2.86 (d, J = 7.2 Hz, 2H); 13 C NMR (75 MHz, CDCl3) (C), (C), (CH), (CH), (CH), (CH), (CH2), 50.2 (C), 46.0 (CH2), 42.7 (CH2), 42.0 (CH2); IR (CH2Cl2) 3406, 2991, 2980, 1678, 1533, 759 cm -1 ; LRMS (EI, 20 ev) m/z 313 (M +, 0.3), 129 (100); HRMS (EI) for C19H20ONCl (M + ): calcd , Found b: oil; analytical TLC (silica gel 60), 25% EtOAc in n-hexane, Rf = 0.40; 1 H NMR (300 MHz, CDCl3) (m, 4H), (m, 1H), 6,34 (brs, 1H), (m, 1H), (m, 2H), 3.94 (s, 2H), 3.57 (dd, J = 13.4, 6.8 Hz, 1H), 3.48 (dd, J = 13.4, 5.3 Hz, 1H), 2.57 (dd, J = 13.9, 6.6 Hz, 1H), 2.35 (dd, J = 13.9, 7.6 Hz, 1H), 1.33 (s, 3H); 13 C NMR (75 MHz, CDCl3) (C), (C), (CH), (CH), (CH), (CH), (CH2), 49.6 (CH2), 44.4 (CH2), 42.7 (CH2), 41.8 (C), 22.6 (CH3); IR (CH2Cl2) 3419, 2980, 1676, 1533, 1244, 921, 779, 734 cm -1 ; LRMS (EI, 20 ev) m/z 251 (M +, 0.1), 145 (100); HRMS (EI) for C11H13ONCl (M + allyl): calcd , Found Ph N H O Cl 1.3c: oil; analytical TLC (silica gel 60), 33% EtOAc in n-hexane, Rf = 0.38; 1 H NMR (400 MHz, CDCl3) (m, 2H), (m, 3H), 6.53 (brs, 1H), (m, 1H), (m, 1H), (m, 1H), 3.90 (s, 2H), (m, 1H), (m, 1H), (m, 1H), (m, 2H); 13 C NMR (100 MHz, 17

18 CDCl3) (C), (C), (CH), (CH), (CH), (CH), (CH2), 45.1 (CH), 44.6 (CH2), 42.6 (CH2), 37.9 (CH2); IR (CH2Cl2) 3419, 2980, 1676, 1533, 1427, 786, 669 cm -1 ; LRMS (EI, 20 ev) m/z 237 (M +, 0.9), 144 (100); HRMS (EI) for C13H16ONCl (M + ): calcd , Found d: oil; analytical TLC (silica gel 60), 25% EtOAc in n-hexane, Rf = 0.32; 1 H NMR (400 MHz, CDCl3) (m, 2H), (m, 3H), 6.59 (brs, 1H), (m, 1H), (m, 2H), 3.97 (s, 2H), (m, 3H), (m, 2H); 13 C NMR (100 MHz, CDCl3) (C), (C), (CH), (CH), (CH), (CH), (CH2), 47.7 (CH), 42.6 (CH2), 38.3 (CH2), 34.5 (CH2); IR (CH2Cl2) 3425, 2939, 1674, 1533, 921, 769 cm -1 ; LRMS (EI, 20 ev) m/z 237 (M +, 4), 144 (100); HRMS (EI) for C13H16ONCl (M + ): calcd , Found e: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.36; 1 H NMR (300 MHz, CDCl3) (m, 10H), 6.23 (brs, 1H), 4.86 (s, 1H), 4.64 (s, 1H), 4.04 (d, J = 5.1 Hz, 2H), 3.89 (d, J = 4.2 Hz, 2H), 2.88 (s, 2H), 1.03 (s, 3H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH2), 49.7 (C), 45.7 (CH2), 45.1 (CH2), 42.7 (CH2), 24.1 (CH3); IR (CH2Cl2) 3402, 2945, 1676, 1531, 1444, 1029, 900, 615 cm 1 ; LRMS (EI, 20 ev) m/z 327 (M +, 0.1), 91 (100); HRMS (EI) for C16H15ONCl (M + 2-methylprop-1-ene): calcd , Found f: white solid; m.p C; analytical TLC (silica gel 60), 25% EtOAc in n-hexane, Rf = 0.3; 1 H NMR (300 MHz, CDCl3) 6.72 (br s, 1H), (m, 1H), (m, 2H), 4.06 (s, 2H), 3.23 (d, J = 6.3 Hz, 2H), 2.11 (d, J = 7.4 Hz, 2H), (m, 10H); 13 C NMR (75 MHz, CDCl3) (C), (CH), (CH2), 45.9 (CH2), 42.9 (CH2), 41.2 (CH2), 37.0 (C), 33.5 (CH2), 26.0 (CH2), 21.3 (CH2); IR (CH2Cl2) 3429, 2929, 1676, 1537, 921, 767, 721, 692 cm -1 ; LRMS (EI, 20 ev) m/z 229 (M +, 4), 95 (100); HRMS (EI) for C12H20ONCl (M + ): calcd , Found

19 1.3g: white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.38; 1 H NMR (400 MHz, CDCl3) (m, 4H), 6.88 (br, 1H), (m, 1H), 5.08 (dd, J = 10.0, 1.4 Hz, 1H), 4.97 (dd, J = 17.0, 1.6 Hz, 1H), 4.46 (d, J = 5.6 Hz, 2H), 4.0 (s, 2H), 3.41 (d, J = 6.0 Hz, 2H); 13 C NMR (100 MHz, CDCl3) (C), (C), (CH), (C), (CH), (CH), (CH), (CH), (CH2), 42.5 (CH2), 41.4 (CH2), 36.9 (CH2); IR (CH2Cl2) 3419, 1674, 1527, 1253, 921, 898, 732 cm -1 ; LRMS (EI, 20 ev) m/z 223 (M +, 5), 130 (100); HRMS (EI) for C12H14ONCl (M + ): calcd , Found ª: known compound, white solid; m.p C; analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf = 0.32; 1 H NMR (300 MHz, CD3CN): 8.21 (br, 1H), 7.50 (d, J = 7.8 Hz, 1H), (m, 3H), 4.01 (s, 2H), 2.25 (s, 3H). 13 C NMR (75 MHz, CDCl3): (C), (C), (CH), (C), (CH), (CH), (CH), 29.7 (CH2), 17.6 (CH3). Representative Procedure of Pd-Catalyzed Intramolecular aminoalkylation To a solution of palladium(ii) acetate (4.6 mg, 0.02 mmol) and potassium carbonate (83 mg, 0.6 mmol) in acetonitrile (2.0 ml) was added substrate 1.1a (50.6 mg, 0.2 mmol). The reaction mixture was stirred at 40 o C under argon atmosphere. After 12 h, complete conversion of starting material was indicated by TLC analysis. The reaction mixture was cooled down, filtered through the celite, eluted with ethyl acetate, and concentrated in vacuo. The residue was purified by flash column chromatography (EtOAc and n-hexane as eluents) to give 2a in 91 % yield (31.5 mg). O Pd 2 (dba) 3 (5 mol%) Ph Ph Cl LiO t Bu (1.0 equiv) Ph Ph N H Ag 2 O (0.65 equiv) t BuOH, reflux N O 1.3a 3a A mixture solution of substrate 1.3a (95 mg, 0.3 mmol), Pd2(dba)3 (13.8 mg, 5 19

20 mol %), Ag2O (45 mg, 0.65 equiv) and LiO t Bu (19 mg, 0.3 mmol) in t BuOH (3.0 ml) in a 5.0 ml oven-dried flask was refluxed under argon atmosphere. After 20 h, complete conversion of starting material was indicated by TLC analysis. The reaction mixture was cooled down, filtered through the celite and eluted with ethyl acetate, and concentrated in vacuo. The residue was purified by flash column chromatography (EtOAc and n-hexane as eluents) to give 3a in 87 % yield (72.2 mg). The structure of olefinic isomerization byproduct, dimer and O t Bu-substituted byproducts: Characterization Data of Products 2a: 91% yield (31.5 mg) from 1.1a, 83% yield (29 mg) from 1.2a; white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.19; 1 H NMR (400 MHz, CDCl3) 7.61 (d, J = 7.8 Hz, 1H), (m, 2H), 7.03 (t, J = 7.5 Hz, 1H), (m, 1H), 3.18 (dd, J = 15.6, 8.5 Hz, 1H), (m, 2H), 2.59 (dd, J = 16.6, 8.5 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), 62.8 (CH), 36.2 (CH2), 35.6 (CH2), 29.2 (CH2); IR (CH2Cl2) 3055, 2984, 1693, 1485, 683 cm -1 ; LRMS (EI, 20 ev) m/z 173 (M +, 74), 118 (100); HRMS (EI) for C11H11ON (M + ): calcd , found b: 82% yield (31 mg) from 1.1b, 88% yield (33 mg) from 1.2b; white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.33; 1 H NMR (500 MHz, CDCl3) 7.60 (d, J = 7.8 Hz, 1H), 7.23 (t, J = 7.7 Hz, 1H), 7.19 (d, J = 7.4 Hz, 1H), 7.04 (dt, J = 7.5, 1.0 Hz, 1H), 3.08 (d, J = 15.5 Hz, 1H), (m, 2H), 2.56 (ddd, J = 16.9, 6.8, 2.8 Hz, 1H), (m, 2H), 1.38 (s, 3H); 13 C NMR (125 MHz, CDCl3) (C), (C), (C), (CH), (CH), 20

21 124.2 (CH), (CH), 69.3 (C), 43.3 (CH2), 35.1 (CH2), 34.9 (CH2), 25.4 (CH3); IR (CH2Cl2) 3051, 2984, 2928, 1688, 1603, 1485, 1398, 627 cm -1 ; LRMS (EI, 20 ev) m/z 187 (M +, 52), 172 (100); HRMS (EI) for C12H13ON (M + ): calcd , found c: 88% yield (33 mg) from 1.1c, 64% yield (24 mg) from 1.2c; white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.25; 1 H NMR (300 MHz, CDCl3): 7.48 (d, J = 7.8 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H), 7.00 (s, 1H), (m, 1H), 3.12 (dd, J = 15.6, 8.4 Hz, 1H), (m, 2H), 2.58 (q, J = 8.4 Hz, 1H), (m, 1H), 2.32 (s, 3H), (m, 1H); 13 C NMR (75 MHz, CDCl3): (C), (C), (C), (C), (CH), (CH), (CH), 63.2 (CH), 36.3 (CH2), 35.8 (CH2), 39.3 (CH2), 21.1 (CH3); IR (CH2Cl2) 3047, 2988, 1423, 1248, 1155, 893, 685 cm -1 ; LRMS (EI, 20 ev) m/z 187 (M +, 44), 132 (100); HRMS (EI) for C12H13ON (M + ): calcd Found: d: 84% yield (42 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.24; 1 H NMR (400 MHz, CDCl3) 7.46 (d, J = 8.2 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.30 (s, 1H), (m, 1H), 3.16 (dd, J = 15.9, 8.5 Hz, 1H), (m, 1H), (m, 1H), 2.58 (dd, J = 16.7, 8.5 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (CH), (C), (CH), 62.9 (CH), 36.1 (CH2), 35.6 (CH2), 29.3 (CH2); IR (CH2Cl2) 2980, 1695, 1481, 775 cm -1 ; LRMS (EI, 20 ev) m/z 251 (M +, 36), 253 (M +, 36), 117 (100); HRMS (EI) for C11H10ON 79 Br/ 81 Br (M + ): calcd / , Found: / e: 76% yield (30 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.30; 1 H NMR (400 MHz, CDCl3) 7.65 (d, J = 8.0 Hz, 1H), 7.53 (dd, J = 8.0, 0.48 Hz, 1H), 7.43 (d, J = 0.48 Hz, 1H), (m, 1H), 3.26 (dd, J = 16.0, 8.8 Hz, 1H), (m, 2H), 2.62 (dd, J = 16.0, 8.8 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (CH), (C), (CH), (C), 62.7 (CH), 36.1 (CH2), 35.1 (CH2), 29.5 (CH2); IR (CH2Cl2) 2953, 2931, 2852, 2216, 1697, 1454, 1377, 721, 632 cm -1 ; LRMS (EI, 20 ev) m/z 198 (M +, 28), 143 (100); HRMS (EI) for C12H10ON2 (M + ): calcd Found:

22 2f: 84% yield (36 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.35; 1 H NMR (300 MHz, CDCl3) 7.16 (d, J = 7.5 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 7.5 Hz, 1H), (m, 1H), (m, 1H), 3.06 (dd, J = 8.1, 15.3 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H), 1.39 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.9 Hz, 3H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), (CH), 64.7 (CH), 37.6 (CH2), 35.8 (CH2), 29.9 (CH), 27.1 (CH2), 24.2 (CH3), 23.5 (CH3); IR (CH2Cl2) 3163, 2953, 2922, 2852, 1714, 1693, 1456, 846, 721 cm -1 ; LRMS (EI, 20 ev) m/z 215 (M +, 92), 118 (100); HRMS (EI) for C14H17ON (M + ): calcd , Found: g: 67% yield (29 mg); yellow solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.23; Major isomer: 1 H NMR (300 MHz, CDCl3) 7.46 (d, J = 7.5 Hz, 1H), 7.02 (d, J = 7.5 Hz, 1H), 6.96 (s, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 2.31 (s, 3H), (m, 2H), (m, 1H), 1.05 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), (CH), 69.7 (CH), 50.2 (CH), 36.3 (CH2), 29.3 (CH2), 25.2 (CH2), 21.3 (CH3), 11.8 (CH3); Minor isomer: 1 H NMR (300 MHz, CDCl3) 7.46 (d, J = 7.5 Hz, 1H), 7.02 (d, J = 7.5 Hz, 1H), 6.96 (s, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 2.31 (s, 3H), (m, 2H), (m, 1H), 0.96 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), (CH), 65.9 (CH), 43.7 (CH), 36.5 (CH2), 24.0 (CH2), 22.6 (CH2), 21.3 (CH3), 12.1 (CH3); IR (CH2Cl2) 3163, 2953, 2920, 1714, 1687, 815, 721 cm -1 ; LRMS (EI, 20 ev) m/z 215 (M +, 93), 186 (100); HRMS (EI) for C14H17ON (M + ): calcd , Found: h: 85% yield (40 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.17; 1 H NMR (300 MHz, CDCl3) 6.88 (d, J = 1.9 Hz, 1H), 6.18 (d, J = 1.9 Hz, 1H), (m, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.08 (dd, 22

23 J = 15.3, 8.7 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (C), (C), 94.9 (CH), 92.6 (CH), 63.8 (CH), 55.8 (CH3), 55.3 (CH3), 36.6 (CH2), 32.1 (CH2), 29.5 (CH2); IR (CH2Cl2) 3182, 2953, 2922, 2852, 1653, 1462, 976, 831, 721 cm -1 ; LRMS (EI, 20 ev) m/z 233 (M +, 97), 178 (100); HRMS (EI) for C13H15O3N (M + ): calcd , Found: i: 51% yield (24 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.10; 1 H NMR (400 MHz, CDCl3): 6.39 (s, 1H), 6.38 (s, 1H), (m, 1H), 3.90 (s, 3H), 3.78 (s, 3H), 3.03 (dd, J = 11.7, 6.0 Hz, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl3): (C), (C), (C), (C), (C), (CH), 99.3 (CH), 64.9 (CH), 56.6 (CH3), 55.7 (CH3), 37.9 (CH2), 35.8 (CH2), 27.4 (CH2); IR (CH2Cl2) 3163, 2953, 2852, 1697, 1600, 1456, 966, 721 cm -1 ; LRMS (EI, 20 ev) m/z 233 (M +, 69), 178 (100); HRMS (EI) for C13H15O3N (M + ): calcd , Found: j: 89% yield (35.8 mg), white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.32; 1 H NMR (400 MHz, CDCl3) 6.93 (d, J = 7.2 Hz, 1H), 6.81 (d, J = 7.2 Hz, 1H), (m, 1H), 3.02 (dd, J = 15.2, 8.0 Hz, 1H), (m, 1H), 2.71 (dd, J = 15.2, 8.0 Hz, 1H), (m, 1H), (m, 4H), 2.18 (s, 3H), (m, 1H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), (C), 64.1 (CH), 36.1 (CH2), 35.9 (CH2), 27.8 (CH2), 19.9 (CH3), 18.3 (CH3); IR (CH2Cl2) 3161, 2953, 2922, 2852, 1716, 1676, 1454, 1375, 1292, 966, 721 cm -1 ; LRMS (EI, 20 ev) m/z 201 (M +, 16), 146 (100); HRMS (EI) for C13H15ON (M + ): calcd , Found: k: 95% yield (42.5 mg); white solid; m.p C; analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf = 0.26; 1 H NMR (300 MHz, CDCl3) 8.63 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), (m, 2H), 7.27 (d, J = 8.4 Hz, 1H), (m, 1H), 3.16 (dd, J = 15.6, 8.4 Hz, 1H), (m, 2H), 2.66 (dd, J = 16.5, 8.7 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), 23

24 125.9 (CH), (2 CH), (C), (CH), 65.7 (CH), 37.4 (CH2), 36.5 (CH2), 28.2 (CH2); IR (CH2Cl2) 3163, 2951, 2933, 2908, 2854, 1681, 1454, 1377, 771, 721 cm -1 ; LRMS (EI, 20 ev) m/z 223 (M +, 88), 168 (100); HRMS (EI) for C15H13ON (M + ): calcd , Found: l: 89% yield (40.5 mg); white solid; m.p C; analytical TLC (silica gel 60), 20% EtOAc in n-hexane, Rf = 0.25; 1 H NMR (400 MHz, CDCl3) 7.55 (d, J = 8.0 Hz, 1H), (m, 1H), 7.13 (d, J = 7.3 Hz, 1H), 7.06 (dt, J = 7.4, 1.0 Hz, 1H), 3.22 (d, J = 5.6 Hz, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 2H), (m, 2H), (m, 1H), (m, 2H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), 72.0 (C), 48.2 (CH), 35.2 (CH2), 31.6 (CH2), 31.1 (CH2), 23.1 (CH2), 21.9 (CH2), 21.0 (CH2); IR (CH2Cl2) 3163, 2951, 2928, 2916, 2852, 2723, 2360, 1454, 1377, 1305, 1168, 1155, 966, 846, 759, 721 cm -1 ; LRMS (EI, 20 ev) m/z 227 (M +, 35) 184 (100); HRMS (EI) for C15H17ON (M + ): calcd , Found m: 50% yield (19 mg) from 1.1m, 57% from (21.5 mg) 1.2m; white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.29; 1 H NMR (500 MHz, CDCl3) 8.69 (d, J = 8.4 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 7.5 Hz, 1H), 7.01 (dt, J = 7.5, 0.8 Hz, 1H), 3.90 (dddd, J = 11.6, 9.2, 6.7, 2.6 Hz, 1H), (m, 1H), 2.86 (ddd, J = 16.6, 5.1, 1.4 Hz, 1H), 2.62 (ddd, J = 17.0, 11.3, 9.3 Hz, 1H), 2.50 (ddd, J = 17.0, 9.5, 2.1 Hz, 1H), (m, 1H), (m, 1H), (m, 2H); 13 C NMR (125 MHz, CDCl3) (C), (C), (CH), (CH), (C), (CH), (CH), 58.1 (CH), 32.2 (CH2), 29.4 (CH2), 27.8 (CH2), 25.5 (CH2); IR (CH2Cl2) 3045, 2984, 1684, 1491, 1421, 689 cm -1 ; LRMS (EI, 20 ev) m/z 187 (M +, 57), 132 (100); HRMS (EI) for C12H13ON (M + ): calcd , found n: 40% yield (15.2 mg); white powder; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.14; 1 H NMR (500 MHz, CDCl3) 8.51 (dd, J = 8.0, 1.7 Hz, 1H), (m, 3H), (m, 1H), 4.04 (ddt, J = 9.9, 6.9,

25 Hz, 1H), 3.76 (t, J = 3.8 Hz, 1H), 2.67 (ddd, J = 17.1, 11.2, 9.4 Hz, 1H), 2.51 (ddd, J = 17.1, 9.8, 1.9 Hz, 1H), 2.31 (dddd, J = 12.7, 9.1, 7.0, 1.9 Hz, 1H), (m, 1H); 13 C NMR (125 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), 69.5 (CH2), 54.0 (CH), 31.0 (CH2), 20.9(CH2); IR (CH2Cl2) 3047, 2986, 2253, 1497, 1421, 1252, 1157, 891, 683, 652 cm -1 ; LRMS (EI, 20 ev) m/z 189 (M +, 57), 134 (100); HRMS (EI) for C11H11O2N (M + ): calcd , found o: 80% yield (32.6 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf= 0.15; 1 H NMR (400 MHz, CDCl3) 7.50 (d, J = 8.4 Hz, 1H), (m, 2H), (m, 1H), 3.77 (s, 3H), 3.13 (dd, J = 15.7, 8.4 Hz, 1H), (m, 2H), 2.57 (dd, J = 16.6, 8.1 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (100 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), (CH), 63.3 (CH), 55.7 (CH3), 36.2 (CH2), 36.1 (CH2), 29.1 (CH2); IR (CH2Cl2) 3051, 2986, 1686, 1491, 689 cm -1 ; LRMS (EI, 20 ev) m/z 203 (M +, 74), 148 (100); HRMS (EI) for C12H13O2N (M + ): calcd , found p: 78 % yield (30 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.21; 1 H NMR (300 MHz, CDCl3) 7.53 (dd, J = 9.3, 4.7 Hz, 1H), (m, 2H), (m, 1H), 3.17 (dd, J = 15.9, 8.5 Hz, 1H), (m, 2H), 2.58 (dd, J = 16.7, 8.5 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (75 MHz, CDCl3) (C), (d, 1 JC-F = 242 Hz, C), (d, 3 JC-F = 9 Hz, C), (d, 4 JC-F = 2 Hz, C), (d, 3 JC-F = 9 Hz, CH), (d, 2 JC-F = 23 Hz, CH), (d, 2 JC-F = 24 Hz, CH), 63.3 (CH), 36.0 (CH2), 35.9 (d, 4 JC-F = 2 Hz, CH2), 29.2 (CH2); 19 F NMR (376 MHz, CDCl3) 117.9; IR (CH2Cl2) 3045, 2986, 1489, 1423, 893, 681 cm -1 ; LRMS (EI, 20 ev) m/z 191 (M +, 31), 136 (100); HRMS (EI) for C11H10ONF (M + ): calcd , found N O Cl 2q 70% yield (29 mg), white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf= 0.23; 1 H NMR (400 MHz, CDCl3) 7.51 (d, J = 8.3 Hz, 1H), (m, 2H), 4.65 (ddd, J = 18.6, 9.7, 6.2 Hz, 1H), 3.16 (dd, J = 15.9, 8.5 Hz, 1H), (m, 2H), 2.58 (dd, J = 16.7, 8.5 Hz, 1H), (m, 1H), 2.00 (ddd, J = 24.5, 12.4, 9.3 Hz, 1H); 13 C NMR (100 MHz, CDCl3) 171.7(C), (C), (C), (C), (CH), (CH), (CH), 63.0 (CH), 36.1 (CH2), 25

26 35.7 (CH2), 29.3 (CH2); IR (CH2Cl2) 3045, 2984, 1695, 1603, 1483, 1161, 899, 679 cm -1 ; LRMS (EI, 20 ev) m/z 207 (M +, 45), 152 (100); HRMS (EI) for C11H10ON35Cl (M + ): calcd , found r; 58% yield (23.8 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.23; 1 H NMR (600 MHz, CDCl3) (m, 1H), (m, 2H), (m, 1H), 3.17 (dd, J = 15.9, 8.5 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), 1.25 (d, J = 7.0 Hz, 3H); 13 C NMR (150 MHz, CDCl3) (C), (d, 1 JC-F = 241 Hz, C), (d, 3 JC-F = 8.4 Hz, C), (C), (d, 3 JC-F = 8.7 Hz, CH), (d, 2 JC-F = 23.3 Hz, CH), (d, 2 JC-F = 23.3 Hz, CH), 60.5 (CH), 41.6 (CH), 38.6 (CH2), 35.9 (CH2), 15.0 (CH3); 19 F NMR (376 MHz, CDCl3) 118.6; IR (CH2Cl2) 2922, 2724, 1691, 1457, 1375, 826, 723 cm -1 ; LRMS (EI, 20 ev) m/z 205 (M +, 37), 136 (100); HRMS (EI) for C12H12ONF (M + ): calcd , found r*: [a] 18 D 7.6 (c 0.085, CHCl3), HPLC analysis, Chiralcel β,β-gem-1 i-proh/n-hexane = 95/5, flow rate 1.0 ml/min. λ = 205 nm, t(major) = min, t(minor) = min, 93% ee. 2s: 35% yield (17.5 mg); white solid; m.p C; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.48; 1 H NMR (500 MHz, CDCl3) 7.66 (d, J = 7.8 Hz, 1H), 7.35 (t, J = 7.4 Hz, 2H), (m, 3H), (m, 2H), 7.06 (t, J = 7.5 Hz, 1H), (m, 1H), 4.12 (dd, J = 12.6, 7.1 Hz, 1H), 3.26 (dd, J = 15.7, 8.4 Hz, 1H), 2.97 (dd, J = 15.7, 9.9 Hz, 1H), (m, 1H), 2.18 (dd, J = 22.6, 12.2 Hz, 1H); 13 C NMR (125 MHz, CDCl3) (C), (C), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), (CH), 60.0 (CH), 53.3 (CH), 39.3 (CH2), 35.7 (CH2); IR (CH2Cl2) 3049, 2988, 2253, 1423, 1248, 1157, 650 cm -1 ; LRMS (EI, 20 ev) m/z 249 (M +, 100), 187 (26), 132 (49); HRMS (EI) for C17H15ON (M + ): calcd , found t: 35% yield (15.2 mg); oil; analytical TLC (silica gel 60), 30% EtOAc in n-hexane, Rf = 0.29; 1 H NMR (400 MHz, CDCl3) 7.60 (d, J = 7.8 Hz, 1H), (m, 2H), 7.03 (t, J = 7.5 Hz, 1H), (m, 1H), 3.73 (dd, J = 9.7, 3.9 Hz, 1H), 3.63 (dd, J = 9.6, 6.4 Hz, 1H), 3.37 (s, 3H), 3.19 (dd, J = 15.6, 8.5 Hz, 1H), (m, 1H), 2.90 (dd, J = 15.5, 10.0 Hz, 1H), (m, 1H), 1.98 (d, J = 11.8 Hz, 1H). 13 C 26

27 NMR (100 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), 71.2 (CH2), 60.6 (CH), 59.2 (CH3), 47.8 (CH), 35.8 (CH2), 33.4 (CH2); IR (CH2Cl2) 2927, 1693, 1604, 1485, 1409, 1192, 1103, 719, 684 cm -1 ; LRMS (EI, 20 ev) m/z 217 (M +, 48), 118 (100); HRMS (EI) for C13H15O2N (M + ): calcd , found a: 87% yield (72.2 mg); white solid; m.p C; analytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf = 0.29; 1 H NMR (500 MHz, CDCl3) (m, 4H), (m, 6H), 4.13 (d, J = 12.0 Hz, 1H), (m, 1H), 3.86 (d, J = 12.0 Hz, 1H), (m, 1H), 2.58 (dd, J = 12.0, 5.0 Hz, 1H), 2.41 (dq, J = 9.0, 1.0 Hz, 1H), (m, 2H), (m, 1H); 13 C NMR (125 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), (CH), (CH), 60.2 (CH2), 58.0 (C), 52.8 (CH2), 45.0 (CH2), 35.2 (CH2), 27.9 (CH2); IR (CH2Cl2) 3068, 2926, 1685, 1496, 1413, 1290, 680 cm 1 ; LRMS (EI, 20 ev) m/z 277 (M +, 54), 97 (100); HRMS (EI) for C19H19ON (M + ): calcd , Found b: a mixture of two isomers; 78% yield (50 mg); white solid; m.p C; analytical TLC (silica gel 60), 45% EtOAc in n-hexane, Rf = 0.25; 3b-trans (major product) 1 H NMR (600 MHz, CDCl3) (m, 2H), (m, 3H), (m, 1H), 3.83 (d, J = 11.3 Hz, 1H), 3.34 (d, J = 11.3 Hz, 1H), (m, 1H), 2.70 (dd, J = 11.8, 5.3 Hz, 1H), (m, 2H), (m, 2H), 1.46 (s, 3H); 13 C NMR (150 MHz, CDCl3) (C), (C), (CH), (CH), (CH), 60.8 (CH), 54.3 (CH2), 50.0 (C), 45.8 (CH2), 35.1 (CH2), 30.3 (CH3), 28.0 (CH2). 3b-cis (minor product): 1 H NMR (600 MHz, CDCl3) (m, 2H), (m, 3H), (m, 1H), 3.76 (d, J = 11.8 Hz, 1H), 3.46 (d, J = 11.8 Hz, 1H), (m, 1H), (m, 2H), (m, 3H), 1.41 (s, 3H); 13 C NMR (150 MHz, CDCl3) (C), (C), (CH), (CH), (CH), 60.5 (CH), 53.9 (CH2), 49.3 (C), 46.1 (CH2), 34.7 (CH2), 29.5 (CH3), 29.0 (CH2); IR (CH2Cl2) 3068, 2978, 2885, 1691, 1676, 1411, 1288, 765, 744 cm -1 ; LRMS (EI, 20 ev) m/z 215 (M +, 67), 97 (100); HRMS (EI) for C14H17ON (M + ): calcd , Found

28 3c, 67% yield (40.5 mg); 3c-trans (major product, one tertiary carbon was overlapped): analytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf = 0.28; 1 H NMR (600 MHz, CDCl3) (m, 5H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H); 13 C NMR (150 MHz, CDCl3) (C), (C), (CH), (CH), 62.5 (CH), 47.9 (CH2), 47.3 (CH), 41.4 (CH2), 35.1 (CH2), 27.0 (CH2); IR (CH2Cl2) 3068, 2980, 1693, 1602, 1404, 1242, 1170, 769, 717 cm -1. 3c-cis (minor product): analytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf = 0.30; 1 H NMR (600 MHz, CDCl3) (m, 5H), (m, 2H), (m, 1H), 3.07 (dd, J = 12.0, 7.0 Hz, 1H), (m, 1H), 2.43 (dd, J = 16.5, 9.0 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 1H); 13 C NMR (150 MHz, CDCl3) (C), (C), (CH), (CH), (CH), 60.3 (CH), 48.9 (CH2), 45.2 (CH), 39.9 (CH2), 34.7 (CH2), 28.9 (CH2); IR (CH2Cl2) 3068, 2980, 2947, 1693, 1429, 721 cm -1 ; LRMS (EI, 20 ev) m/z 201 (M +, 84), 97 (100); HRMS (EI) for C13H15ON (M + ): calcd , Found d: 70% yield (42.2 mg); a mixture of two isomers (3d-cis/3d-trans = 4/1); white solid; m.p C; analytical TLC (silica gel 60), 40% EtOAc in n-hexane, Rf = 0.29; 3d-cis (major product): 1 H NMR (600 MHz, CDCl3) (m, 5H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 2H), (m, 2H), (m, 1H); 13 C NMR (150 MHz, CDCl3) (C), (C), (CH), (CH), (CH), 67.7 (CH), 51.3 (CH), 40.9 (CH2), 35.3 (CH2), 34.8 (CH2), 25.5 (CH2). 3d-trans (minor product): 1 H NMR (600 MHz, CDCl3) (m, 3H), 6.98 (d, J = 7.2 Hz, 2H), (m, 1H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H), (m, 1H); 13 C NMR (150 MHz, CDCl3) (C), (C), (CH), (CH), (CH), 65.0 (CH), 45.5 (CH), 40.9 (CH2), 33.9 (CH2), 33.5 (CH2), 20.9 (CH2); IR (CH2Cl2) 3073, 2926, 1566, 1429, 1334, 1093, 933, 663 cm -1 ; LRMS (EI, 20 ev) m/z 201 (M +, 46), 97 (100); HRMS (EI) for C13H15ON (M + ): calcd , Found

29 3e: 88% yield (76.8 mg); white solid; m.p C; analytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf = 0.22; 1 H NMR (300 MHz, CDCl3) (m, 6H), (m, 4H), 4.93 (d, J = 12.4 Hz, 1H), 3.34 (d, J = 12.4 Hz, 1H), 2.86 (d, J = 13.2 Hz, 1H), 2.65 (d, J = 13.2 Hz, 1H), (m, 1H), 2.07 (dd, J = 13.6, 8.8 Hz, 1H), 1.82 (dd, J = 12.0, 7.8, Hz, 1H), (m, 1H), 1.30 (s, 3H); 13 C NMR (75 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), (CH), 66.6 (C), 57.9 (C), 51.3 (CH2), 51.2 (CH2), 35.4 (CH2), 32.8 (CH2), 27.4 (CH3); IR (CH2Cl2) 3068, 2991, 1683, 1400, 783, 680 cm 1 ; LRMS (EI, 20 ev) m/z 291 (M +, 24), 111 (100); HRMS (EI) for C20H21ON (M + ): calcd , Found f: 51% yield (29.5 mg); oil; analytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf = 0.27; 1 H NMR (500 MHz, CDCl3) (m, 1H), 3.36 (d, J = 11.8 Hz, 1H), 2.90 (d, J = 11.8 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 1.93 (q, J = 6.2 Hz, 1H), (m, 1H), (m, 10H), (m, 1H); 13 C NMR (125 MHz, CDCl3) (C), 60.3 (CH), 52.5 (C), 38.1 (CH2), 36.5 (CH2), 34.9 (CH2), 28.0 (CH2), 25.8 (CH2), 23.8 (CH2), 23.0 (CH2); IR (CH2Cl2) 3068, 2980, 2931, 1697, 1606, 1413, 1244, 786, 723, 673 cm -1 ; LRMS (EI, 20 ev) m/z 193 (M +, 20), 97 (100); HRMS (EI) for C12H19ON (M + ): calcd , Found g: 65% yield (36.5 mg); white solid; m.p C; analytical TLC (silica gel 60), 50% EtOAc in n-hexane, Rf = 0.24; 1 H NMR (600 MHz, CDCl3) (m, 4H), 4.96 (d, J = 17.6 Hz, 1H), 4.27 (d, J = 17.6 Hz, 1H), (m, 1H), 2.98 (dd, J = 15.5, 3.7 Hz, 1H), 2.72 (dd, J = 15.2, 11.4 Hz, 1H), (m, 3H), (m, 1H); 13 C NMR (150 MHz, CDCl3) (C), (C), (C), (CH), (CH), (CH), (CH), 53.9 (CH), 42.5 (CH2), 36.9 (CH2), 30.2 (CH2), 25.3 (CH2); IR (CH2Cl2) 3068, 1764, 1674, 1384, 1301, 1141, 725, 688 cm -1 ; LRMS (EI, 20 ev) m/z 187 (M +, 5), 157 (100); HRMS (EI) for C12H13ON (M + ): calcd , Found

30 References 15 and 22: (15) One reason for this observation is that the angular proton and the α-substituent are more stable in trans-configuration, whereas severe repulsion is found when these two groups are in cis-configuration. Another possibility is that products are in thermodynamic equalibrium under the reaction condition, thus the more stable trans-isomer is formed. (22) The fact that precipitation of Pd(0) black was observed during the course of the reaction suggests that Pd(0) is involved. However, at current stage, the Pd(II)/(IV) catalytic cycle could not be excluded, which proceeds via Pd II -mediated amidopalladation, followed by oxidative addition with α-halogen acetamide and reductive elimination to finish the catalytic cycle. For oxidative addition of alkyl halides with palladium(ii), see: (a) De Graaf, W.; Boersma, J.; Smeets, W. J. J.; Spek, A. L.; Van Koten, G.; Organometallics, 1989, 8, (b) Bayler, A.; Canty, A. J.; Skelton, B. W.; White, A. H. J. Organomet. Chem. 2000, 595, 296. (c) Campora, J.; Palma, P.; del Rio, D.; Lopez, J. A.; Valerga, P. Chem. Comm. 2004, O NH Cl Pd(OAc) 2 (6 mol %) K 2 CO 3 (3.0 equiv) N O F MeCN, 70 C, 36 h F 1.2p 2p additive yield (%) no additive 78 BHT (1.0 equiv) 55 BQ (1.0 equiv) 50 BHT = 2,6-Di-tert-butyl-4-methylphenol BQ = benzoquinone Scheme S1 Experiments with radical scavangers 30

31 CD experiment of 2r: 20 Experimental for 2r Calculated for 2r 10 0 ε(nm -1 M -1 ) nm Figure S1. Comparison of experimental and calculated ECD spectra for 2r The absolute configuration of product 2r was determined by means of chiroptical methods. Specifically, ECD spectra were calculated by the TD-DFT method, which has been proven to be useful in predicting ECD spectra and assigning the absolute configuration of organic molecules. ref1 Electronic excitation energies (nm) and rotational strengths (Δε) were calculated for 2r using the TD-DFT-B3LYP/6-31G level. ref2. As shown in Fig. S1, the simulated spectra are in good agreement with the experimental spectral data, and the 2S,9aS configuration could be reliably assigned to compound 2r. Ref. 1. For recent examples of this method to assign the absolute configurations of organic molecules, see: (a) C. Diedrich, S. Grimme, J. Phys. Chem. A, 2003, 107, 2524; (b) D. Casarini, L. Lunazzi, M. Man-cinelli, A. Mazzanti, C. Rosini, J. Org. Chem., 2007, 72, 7667; (c) O. Penon, A. Carlone, A. Mazzanti, M. Locatelli, L. Sambri, G. Bartoli, P. Melchiorre, Chem. Eur. J., 2008, 14, 4788; (d) C. Gioia, F. Fini, A. Mazzanti, L. Bernardi, A. Ricci, J. Am. Chem. Soc., 2009, 131, 9614; (e) A. Zea, A.-N. R. Alba, A. Mazzanti, A. Moyano, R. Rios, Org. Biomol. Chem., 2011, 9, 31

32 6519; (f) X.-F. Huang, Z.-M. Liu, Z.-C. Geng, S.-Y. Zhang, Y. Wang, X.-W. Wang, Org. Biomol. Chem., 2012, 10, ; For Reviews see: (g) N. Berova, L. Di Bari, G. Pescitelli, Chem. Soc. Rev., 2007, 36, 914. Ref. 2. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R.Cheeseman,; J. A. Jr. Montgomery, T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B.Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong. C. Gonzalez, J. A. Pople. Gaussian 03, Revision B.04; Gaussian, Inc.: Wallingford, CT,

33 ESI-MS Analysis of substrate 1.4a with bidentate nitrogen-ligand 33

34 HPLC-data for Racemic-1.2r and (S)-1.2r 34

35 HPLC-data for Racemic-2r and Chiral-2r 35

36 NMR Spectra of Substrates and Products 1.1a 1.1a 36

37 Current Data Parameters NAME yl -1p EXPNO 1 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM 400 av PROBHD 5 mm QNP 1H /13 PULPROG 30zg TD SOLVENT CDCl 3 NS 25 DS 0 SWH Hz FIDRES Hz AQ sec RG 80.6 DW usec DE 6.00 usec TE K D sec MCREST sec MCWRK sec 1.1b ======== CHANNEL f 1 ======== NUC 1 H 1 P1.90 usec 12 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC D NMR plot parameters CX cm CY 9.22 cm F1P ppm F Hz F2P ppm F Hz PPMCM ppm /cm HZCM Hz/cm f1 (ppm ) b 37

38 1.1c Current Data Parameters NAME yl p EXPNO 2 PROCNO F 2 - Acquisition Parameters Date_ Time INSTRUM dpx300 PROBHD DUAL 5mm PULPROG zgdc TD SOLVENT CDCl3 NS 98 DS 1 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K D sec d sec 1.1c ============ CHANNEL f 1 ============= NUC 1 C 13 P 1.00 usec 7 PL db SFO MHz ============ CHANNEL f 2 ============= CPDPRG 2 waltz16 NUC 2 H 1 PCPD usec PL db PL db SFO MHz F 2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.00 Hz GB 0 PC D NMR plot parameters CX cm F 1P ppm F Hz F 2P ppm F Hz PPMCM ppm /cm HZCM Hz /cm f1 (ppm )

39 1.1d 1.1d 39

40 1.1e 1.1e 40

41 f 1.1f

42 Current Data Parameters NAME yl p EXPNO 1 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM dpx 300 PROBHD DUAL5mm PULPROG 30zg TD SOLVENT CDCl 3 NS 37 DS 2 SWH Hz FIDRES Hz AQ sec RG 128 DW usec DE 6.00 usec TE K D sec 1.1g ============ CHANNEL f 1 ============= NUC 1 H 1 P1.00 usec 9 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) Current Data Parameters NAME yl p EXPNO 2 PROCNO 1 F 2 - Acquisition Parameters Date_ Time INSTRUM dpx300 PROBHD DUAL 5mm PULPROG zgdc TD SOLVENT CDCl3 NS 87 DS 1 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K D sec d sec 1.1g ============ CHANNEL f 1 ============= NUC 1 C 13 P 1.00 usec 7 PL db SFO MHz ============ CHANNEL f 2 ============= CPDPRG 2 waltz16 NUC 2 H 1 PCPD usec PL db PL db SFO MHz F 2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.00 Hz GB 0 PC f1 (ppm )

43 1.1h h 43

44 f1 (ppm) i 1.1i

45 j f1 (ppm) Current Data Parameters NAME yl -2p EXPNO 2 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM 400 av PROBHD 5 mm QNP 1H /13 PULPROG zgdc TD SOLVENT CDCl 3 NS 103 DS 0 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K D sec d sec MCREST sec MCWRK sec 1.1j ======== CHANNEL f 1 ======== NUC 1 C 13 P1.70 usec 12 PL db SFO MHz ======== CHANNEL f 2 ======== CPDPRG 2 waltz16 NUC 2 H 1 PCPD usec PL db PL12.90 db 12 SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.00 Hz GB 0 PC f1 (ppm )

46 f1 (ppm) k 1.1k

47 1 H NMR and 13 C NMR of 1.1l l Current Data Parameters NAME yl p EXPNO 2 PROCNO 1 F2 - Acquisition Parameters Date _ Time INSTRUM av400 QNP 1H PROBHD 5 mm /13 PULPROG zgdc TD SOLVENT CDCl3 NS 139 DS 0 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K sec D sec d11 MCREST sec MCWRK sec 1.1l ======== CHANNEL f 1 ======== NUC 1 C 13 P 1.70 usec 12 PL db SFO MHz ======== CHANNEL f 2 ======== CPDPRG 2 waltz16 NUC 2 H 1 PCPD usec PL db PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.00 Hz GB 0 PC f1 (ppm )

48 Current Data Parameters NAME yl EXPNO 1 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM 400 av QNP 1H PROBHD 5 mm /13 PULPROG 30zg TD SOLVENT CDCl 3 NS 22 DS 0 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K sec D 1 MCREST sec MCWRK sec 1.1m ======== CHANNEL f 1 ======== NUC 1 H 1 P1.90 usec 12 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) m 48

49 1 H NMR and 13 C NMR of 1.1n 1.1n 1.1n 49

50 1.2a 1.2a 50

51 1.2b 1.2b 51

52 1.2c 1.2c 52

53 1.2m 1.2m 53

54 1.2o 1.2o 54

55 1.2p 1.2p 55

56 1.2q 1.2q 56

57 Current Data Parameters NAME yl -p EXPNO 1 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM 400 av PROBHD 5 mm QNP 1H /13 PULPROG 30zg TD SOLVENT CDCl 3 NS 15 DS 0 SWH Hz FIDRES Hz AQ sec RG 90.5 DW usec DE 6.00 usec TE K D sec MCREST sec MCWRK sec 1.2r ======== CHANNEL f 1 ======== NUC 1 H 1 P1.90 usec 12 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) r 57

58 1.2s 1.2s 58

59 t 1.2t

60 Current Data Parameters NAME yl -p EXPNO 1 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM dpx 300 PROBHD DUAL5mm PULPROG 30zg TD SOLVENT CDCl 3 NS 8 DS 2 SWH Hz FIDRES Hz AQ sec RG 64 DW usec DE 6.00 usec TE K D sec 1.3a ============ CHANNEL f 1 ============= NUC 1 H 1 P1.00 usec 9 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) Current Data Parameters NAME yl p EXPNO 2 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM dpx300 PROBHD DUAL 5mm PULPROG zgdc TD SOLVENT CDCl3 NS 101 DS 1 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K D sec d sec ============ CHANNEL f 1 ============= NUC 1 C 13 P 1.00 usec 7 PL db SFO MHz 1.3a ============ CHANNEL f 2 ============= CPDPRG 2 waltz16 NUC 2 H usec PCPD db PL db PL12 SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.00 Hz 0 GB PC f1 (ppm )

61 f1 (ppm) b 1.3b

62 Current Data Parameters NAME yl -p EXPNO 1 PROCNO 1 F2 - Acquisition Parameters Date _ Time INSTRUM 400 av PROBHD 5 mm QNP 1H /13 PULPROG 30zg TD SOLVENT CDCl 3 NS 10 DS 0 SWH Hz FIDRES Hz AQ sec RG 32 DW usec DE 6.00 usec TE K D sec MCREST sec MCWRK sec 1.3c ======== CHANNEL f 1 ======== NUC 1 H 1 P1.90 usec 12 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) c 62

63 1.3d d 63

64 e 1.3e 64

65 Current Data Parameters NAME yl -p EXPNO 1 PROCNO F2 - Acquisition Parameters Date _ Time INSTRUM dpx 300 PROBHD DUAL5mm PULPROG 30zg TD SOLVENT CDCl 3 NS 6 DS 2 SWH Hz FIDRES Hz AQ sec RG 64 DW usec DE 6.00 usec TE K D sec 1.3f ============ CHANNEL f 1 ============= NUC 1 H 1 P1.00 usec 9 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) f 65

66 f1 (ppm) g 1.3g

67 2a 2a 67

68 2b 2b 68

69 2c 2c 69

70 d Current Data Parameters NAME yl p EXPNO 2 PROCNO 1 F2 - Acquisition Parameters Date _ Time INSTRUM av400 QNP 1H PROBHD 5 mm /13 PULPROG zgdc TD SOLVENT CDCl3 NS 147 DS 0 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K sec D sec d11 MCREST sec MCWRK sec 2d ======== CHANNEL f 1 ======== C NUC usec 12 P 1 PL db SFO 1 MHz CHANNEL f 2 ======== ======== CPDPRG 2 waltz16 NUC 2 H 1 PCPD usec PL db PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.00 Hz 0 GB PC f1 (ppm )

71 e 2e

72 Current Data Parameters NAME yl -1p EXPNO 1 PROCNO 1 F2 - Acquisition Parameters Date _ Time INSTRUM dpx 300 PROBHD DUAL5mm PULPROG 30zg TD SOLVENT CDCl 3 NS 12 DS 2 SWH Hz FIDRES Hz AQ sec RG 128 DW usec DE 6.00 usec TE K D sec 2f ============ CHANNEL f 1 ============= NUC 1 H 1 P1.00 usec 9 PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 0.30 Hz GB 0 PC f1 (ppm ) f 72

73 g Current Data Parameters NAME yl p EXPNO 3 PROCNO 1 F2 - Acquisition Parameters Date _ Time INSTRUM spect PROBHD BBO 5mm Z 3149 / PULPROG zgdc TD SOLVENT CDCl3 NS 101 DS 1 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K D sec d sec MCREST sec MCWRK sec 2g ======== CHANNEL f 1 ======== C NUC usec P 1 PL db SFO 1 MHz CHANNEL f 2 ======== ======== CPDPRG 2 waltz16 NUC 2 H 1 PCPD usec PL db PL db SFO MHz F2 - Processing parameters SI SF MHz WDW EM SSB 0 LB 1.20 Hz 0 GB PC f1 (ppm )

74 f1 (ppm ) f1 (ppm) 74

75 f1 (ppm) h 2h

76 f1 (ppm) i 2i

77 f1 (ppm) j 2j

78 k 2k

79 f1 (ppm) f1 (ppm) l 2l

80 f1 (ppm) f1 (ppm) 80

81 2m 2m 81

82 2n 2n 82

83 2o 2o 83

84 2p 2p 84

85 2q 2q 85

86 2r r 86

87 f1 (ppm) f1 (ppm) 87

88 2s 2s 88

89 2s 2s 89

90 Current Data Parameters NAME yl p EXPNO 1 PROCNO F2 - Acquisition Parameters Date_ Time INSTRUM spect PROBHD BBO 5mm Z3149/ PULPROG zg30 TD SOLVENT CDCl3 NS 8 DS 1 SWH Hz FIDRES Hz AQ sec RG DW usec DE 6.00 usec TE K D sec MCREST sec MCWRK sec 2t ======== CHANNEL f1 ======== NUC1 1H P usec PL db SFO MHz f1 (ppm) t 90

91 f1 (ppm ) f1 (ppm ) 91

92 a 3a

93 f2 (ppm ) H-H COSY f2 (ppm ) D NOESY

94 b 3b

95 c-cis 3c-cis

96 f1 (ppm) f1 (ppm) 96

97 c-trans 3c-trans

98 f1 (ppm) f1 (ppm) 98