Supporting Information

Transcript

1 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2012 Bromenium-Catalysed Tandem Ring Opening/Cyclisation of Vinylcyclopropanes and Vinylcyclobutanes: A Metal-Free [3+2+1]/ACHTUGTREUG[4+2+1] Cascade for the Synthesis of Chiral Amidines and Computational Investigation Venkataraman Ganesh, [a] Devarajulu Sureshkumar, [a] Debasree Chanda, [a] and [a, b] Srinivasan Chandrasekaran* chem_ _sm_miscellaneous_information.pdf

2 Experimental Details All reactions were carried out in oven-dried apparatus using dry solvents under anhydrous conditions, unless otherwise noted. Reaction mixtures were stirred magnetically unless otherwise stated. Commercial grade solvents were distilled and dried according to literature procedures ( Purification of laboratory chemicals, 3 rd Ed., D. D. Perrin, W. L. F. Armarego, Pergamon Press,Oxford, 1988). Analytical TLC was performed on commercial plates coated with silica gel GF 254 (0.25 mm). Silica gel ( mesh) was used for column chromatography. MR spectra were recorded on 300 or 400 MHz instruments andchemical shifts are cited with respect to SiMe 4 as internal ( 1 H and 13 C). The following abbreviations explain the multiplicity s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad and dd = doublet of a doublet. IR spectra were recorded on a FT-IR spectrometer. High-resolution mass spectra (HR-MS) were recorded on a Micromass Q-TOF mass spectrometer. S1

3 Scheme 1. Synthesis of diversely functionalized VCPs; Reagents and conditions: (a) LiAlH 4, THF, 0 C, 2 h (b) ah, MeI, DMF, 0 C rt, 1 h (c) ah, BnBr, DMF, 0 C to rt, 1 h. General procedure for the reduction of cyclopropyl esters with LiAlH 4 : To a vigorously stirred suspension of LiAlH 4 (10 mmol, 1 equiv) in THF (15 ml) at 0 ºC, a solution of cyclopropyl ester (10 mmol, 1 equiv) in THF (10 ml) was added drop wise. The reaction mixture was stirred at rt for additional 1 h followed by quenching with EtOAc. The mixture was diluted with DCM (20 ml) and stirred and washed with 20% citric acid (20 ml X 2). The solvent was evaporated in vacuo and the resultant oil was further purified by column chromatography using silica to afford the desired cyclopropyl methanol. General procedure for the protection of alcohol as (benzyl/methyl) ether: To a stirred solution of cyclopropyl methanol (10 mmol, 1 equiv) in dry THF (15 ml) at 0 ºC, a suspension of 60% ah in mineral oil (10 mmol, 1 equiv) was added slowly. The reaction mixture was stirred at 0 ºC for additional 10 min followed by a drop wise addition of the respective alkyl halide (10 mmol, 1 eqiv). The reaction mixture was allowed to warm to rt and quenched with water at 0 ºC. The mixture was diluted with ether (40 ml) and stirred and S2

4 washed with water (20 ml X 2). The solvent was evaporated in vacuo and the resultant oil was further purified by column chromatography using silica to afford the desired VCP ether. Scheme 2. Synthesis of VCP and its reactivity with chloramine T; Reagents : (a) OsO 4, MMO, t BuOH/H 2 O, 18 h, reflux; (b) aio 4 /Silica gel, CH 2 Cl 2, 30 min, rt; (c) 4% w/v Aq. aoh (4 ml/mmol), 10 min, rt; (d) CeCl 3.7H 2 O (10 mol%), abh 4, MeOH, 15 C ; (e) BnBr, DMF, 0 C, 1 h. General procedure for Luche s reduction: To a stirred solution of unsaturated ketone (4 mmol, 1 equiv) in MeOH (20 ml), solid CeCl 3.7H 2 O was added (20 mol%) at 15 ºC The mixture was stirred for additional 30 min followed by slow addition of abh 4 (4 mmol, 1 equiv). The reaction mixture was warmed to room temperature and the progress of the reaction was monitored by TLC. The mixture was diluted with DCM (60 ml) and stirred and washed with 20% citric acid (20 ml X 2). The organic layer was dried over a 2 SO 4 and the solvent was evaporated in vacuo resulting in an oily crude product. The crude product was further purified by column chromatography using silica to afford the desired VCP. (S)-1- ((1S,5R)-6,6-dimethylbicyclo[3.1.0]hex-2-en-2-yl)ethanol 3ob: To a stirred solution of ketone 3oa (0.22 g, 1.46 mmol, 1 equiv) in MeOH (6 ml), solid CeCl 3.7H 2 O was added (0.084g, 0.30 mmol, 20 mol%) at 15 OH 3ob ºC The mixture was stirred for additional 30 min followed by slow addition of abh 4 (0.055g, 1.46 mmol, 1 equiv). The reaction mixture was warmed to room temperature and the S3

5 progress of the reaction was monitored by TLC. The mixture was diluted with DCM (20 ml) and stirred and washed with 20% citric acid (10 ml). The organic layer was dried over a 2 SO 4 and the solvent was evaporated in vacuo resulting in an oily crude product. The crude product was further purified by column chromatography using silica to afford 3ob. R f = 0.30 (hexanes/etoac, 3 : 1); Yield: 0.20 g, 90%; IR (neat) : 3416, 2945, 2918, 1522, 1090, 738, 667 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 5.28 (s, 1H), 4.28 (dd, J = 5.7 Hz, 12.0 Hz, 1H), 2.35 (dd, J = 7.8 Hz, 18.0 Hz, 1H), 2.13 (s, 1H), (m, 1H), (m, 1H), (m, 5H), 0.98 (s, 3H), 0.73 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): 148.2, 122.5, 67.1, 36.7, 31.5, 29.1, 27.3, 21.8, 19.2, 13.0; HR - MS m/z: calcd for C 10 H 16 ao[m+a + ]: ; found: General procedure for the synthesis of cyclic -sulfonylamidines To the stirred solution of the olefin (1 equiv) in the respective nitriles (~ 2M concentration) was added chloramine-t (1.1 equiv) and phenyltrimethylammonium bromide dibromide (PTAB) (10 mol%). The mixture was allowed to stir for 5-18 h at room temperature (25 C) and the reaction was monitored by TLC. When the reaction was found to be complete, the solvent was removed under reduced pressure. The solid residue was directly purified by flash column chromatography on silica gel. Compound 4aa: R f = 0.25 (hexanes/etoac, 7 : 3); Yield: 82%; m. p. 163 C;[ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2945, 1643, 1336, 1159, 1091, 813 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.73 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), (m, 1H), 4.63 (t, J = 5.1 Hz, 1H), 2.36 (s, 3H), 2.33 (s, 1H), (m, 4H), (m, 2H), 1.70 (s, 3H), 1.24 (s, 3H), (m, 1H), 1.09 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): 148.3, 143.7, 140.0, 138.9, 129.6, 129.5, 126.9, 126.2, 120.7, 52.8, 52.1, 42.6, 29.8, 28.7, 25.6, 24.7, 23.4, 21.4, 19.5; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: S4

6 ; found: CH Analysis for C 19 H 26 2 O 2 S: C, 65.86; H, 7.56;, 8.08; Found: C, 65.90; H, 7.47;, Procedure for Cbz deprotection in 4acB: To compound 4acB (0.089 g, 0.27 mmol), 40% KOH in methanol solution (3 ml) was added and heated to reflux for 12 h. The solvent was removed in vacuo and the mixture was extracted in Et 2 O (10 ml) and 1 HCl (10 ml) to remove the benzyl alcohol side-product by discarding the ether layer. The aqueous layer was basified with 10% aoh followed by extraction with ether. The organic layer was separated and dried over a 2 SO 4 and the solvent was removed in vacuo to obtain the amidine 7a (0.035 g, 68%). The crude product was found to be pure enough for characterization and processing. Procedure for Boc deprotection in 4aaA: To a solution 4aaA (0.120 g, 0.29 mmol) in dry CH 2 Cl 2 (1.7 ml) at 0 ºC, trifluoroacetic acid (0.3 ml) was added. The starting material was completely converted to the desired amidinium trifluoroacetate in 2 h. The solvent was removed in vacuo. The crude amindine 7b was found to be pure enough for further processing. S5

7 1 H and 13 C Spectral Data Compound 4aa: R f = 0.25 (hexanes/etoac, 7 : 3); Yield: 82%; m. p. 163 C;[ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2945, 1643, 1336, 1159, 1091, 813 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.73 (d, J = 8.4 Ts 4aa Me Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), (m, 1H), 4.63 (t, J = 5.1 Hz, 1H), 2.36 (s, 3H), 2.33 (s, 1H), (m, 4H), (m, 2H), 1.70 (s, 3H), 1.24 (s, 3H), (m, 1H), 1.09 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): 148.3, 143.7, 140.0, 138.9, 129.6, 129.5, 126.9, 126.2, 120.7, 52.8, 52.1, 42.6, 29.8, 28.7, 25.6, 24.7, 23.4, 21.4, 19.5; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: CH Analysis for C 19 H 26 2 O 2 S: C, 65.86; H, 7.56;, 8.08; Found: C, 65.90; H, 7.47;, HPLC Chromatogram for Compound 4aa Column Details :Chiralpak AD-H; 150 mm x 40mm Solvent System : n-heptane/isopropyl alcohol 80:20 isocratic flow InJection volume : 2 L in Isopropyl alcohol Flow Rate : 1.0 ml/min, 5.2 MPa, 298 K Detector Wavelength : 220 nm S6

8 Compound 4ab: R f = 0.40 (hexanes/etoac, 8 : 2); Yield: 74%; [ ] 25 D= (CHCl 3, c = 2.1) IR (neat) : 2964, 2930, 2873, 1645, 1339, 1156, 968, 680 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.80 (d, J = 8.4 Ts 4ab Pr Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 5.97 (br, 1H), 4.70 (t, J = 5.7 Hz, 1H), (m, 1H), 2.43 (s, 3H), (m, 1H), (m, 5H), 1.78 (s, 3H), (m, 3H), 1.27 (s, 3H), 1.10 (s, 3H), 0.62 (t, J = 7.2 Hz, 3H); 13 C MR (75 MHz, CDCl 3 ): 151.9, 143.6, 139.8, 138.9, 129.5, 127.1, 120.9, 52.8, 51.9, 42.9, 39.3, 29.9, 29.0, 25.5, 23.5, 21.8, 21.5, 19.4, 13.5; HR - MS m/z: calcd for C 21 H 31 2 O 2 S[M+H + ]: ; found: Compound 4ac: R f = 0.50 (hexanes/etoac, 7 : 3); Yield: 87%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2927, 1652, 1340, 1149, 1093, 813 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.82 (d, J = 8.4 Hz, Ts 4ac 2H), 7.29 (d, J = 8.4 Hz, 2H), (m, 1H), 4.66 (dd, J = 5.1 Hz, 5.1 Hz, 1H), 2.42 (s, 3H), (m, 2H), (m, 3H), 1.74 (s, 3H), 1.19 (s, 3H), (m, 1H), 1.01 (s, 3H), (m, 1H), (m, 2H), (m,1h); 13 C MR (75 MHz, CDCl 3 ): 151.6, 143.4, 139.4, 129.4, 129.4, 127.1, 121.2, 52.4, 52.3, 43.0, 29.9, 29.2, 25.5, 23.4, 21.4, 19.5, 15.7, 9.6, 9.5; HR - MS m/z: calcd for C 21 H 29 2 O 2 S[M+H + ]: ; found: Compound 4ad: R f = 0.60 (hexanes/etoac, 8 : 2); Yield: 25%; [ ] 25 D= (CHCl 3, c = 1.2); IR (neat) : 2972, 2932, 1656, 1636, 1522, 1504, 1352, 1163, 992, 674 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): Ts 4ad PFP 7.44 (d, J = 8.1 Hz, 2H), 7.19 (d, J = 8.1 Hz, 2H), 6.11 (br, 1H), 4.79 (t, J = 6 Hz, 1H), 2.40 (s, 3H), (m, 2H), 1.85 (s, 5H), (m, 1H), 1.61 (s, 1H), 1.35 (s, 3H), 1.27(s, 3H); 13 C MR (75 MHz, CDCl 3 ): 144.6, 140.9, 136.3, 130.2, 129.2, 127.2, 119.5, 55.4, 52.3, 42.9, 29.9, 28.5, 25.8, 23.6, 21.4, 19.2; 19 F MR (300MHz, CDCl 3 ): (d, J S7

9 = 30 Hz), (t, J = 24 Hz), (t, J = 27 Hz) HR - MS m/z: calcd for C 24 H 24 F 5 2 O 2 S[M+H + ]: ; found: Compound 4ae: R f = 0.40 (hexanes/etoac, 8 : 2); Yield: 62%; [ ] 25 D= (CHCl 3, c = 0.87); IR (neat) : 2985, 2916, 2832, 1652, 1466, 1118 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): (m, 9H), 6.07 (d, J Ts 4ae Ph = 3.9 Hz, 1H), 4.84 (t, J = 5.4 Hz, 1H), 2.35 (s, 3H), (m, 5H), 1.83 (s, 3H), 1.35 (s, 3H), (m, 1H), 1.20 (s, 3H); 13 C MR (75 MHz, CDCl 3 ):151.3, 143.4, 139.6, 137.3,137.0, 128.9, 128.8, 128.7, 127.7, 127.3, 120.4, 54.2, 51.5, 43.6, 29.9, 29.2, 25.1, 23.6, 21.4, 19.8; HR - MS m/z: calcd for C 24 H 29 2 O 2 S[M+H + ]: ; found: Compound 4ba: R f = 0.60 (hexanes/etoac, 8 : 2); Yield: 82%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2945, 1643, 1336, 1159, 1091, 813 cm -1 ; 1 H MR (400 MHz, CDCl 3 ): 7.79 (d, J = 6.9 Hz, 2H), 7.31 (d, J Ts 4ba = 6.9 Hz, 2H), 6.15 (dd, J = 4.2 Hz, 12 Hz, 1H), 5.96 (dd, J = 3.6 Hz, 8Hz, 1H), 4.64 (dd, J = 4.4. Hz, 4.4 Hz, 1H), 2.43 (s, 3H), 2.38 (dd, J = 4.8 Hz, 9.6 Hz, 1H), 2.07 (s, 3H), (m, 1H), 1.57 (d, J = 8.4 Hz, 1H), 1.38 (ddd, J = 3.6 Hz, 10.1 Hz, 21.2 Hz, 1H), 1.27 (s, 3H), 1.16 (s, 3H), 1.01 (d, J = 5.6 Hz, 3H) ; 13 C MR (100 MHz, CDCl 3 ): 148.7, 143.9, 138.7, 137.5, 129.6, 127.1, 125.0, 53.0, 51.3, 38.2, 28.5, 28.5, 26.3, 26.2, 24.8, 21.5, HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 4ca: R f = 0.60 (hexanes/etoac, 8 : 2); Yield: 73%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2945, 1643, 1336, 1159, 1091, 813 cm -1 ; 1 H MR (400 MHz, CDCl 3 ): 7.80 (d, J = 4.8 Hz, 2H), 7.21 (d, J Ts 4ca = 4.8 Hz, 2H), (m, 1H), 5.85 (d, J = 8 Hz, 1H), 4.67 (dd, J = 4.4 Hz, 1H), 2.43 (s, 3H), (m, 1H), 2.09 (s, 3H), (m, 2H), 1.30 (s, 3H), 1.12 (s, 3H), 1.03 (d, J S8

10 = 5.6 Hz, 3H), 0.7 (dd, J = 6 Hz, 12 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ): 148.6, 143.9, 138.8, 138.5, 129.7, 127.1, 125.4, 52.9, 51.4, 43.5, 30.9, 28.8, 28.3, 25.5, 24.9, 21.5, 21.0; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 4da: R f = 0.60 (hexanes/etoac, 1 : 1); Yield: 84%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3338, 2966, 2929, 2873, 1637, 1340, 1153, 1088, 680; 1 H-MR (400 MHz; CDCl 3 ): δ 7.75 HO Ts 4da Pr (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0Hz, 2H), 6.10 (dd, J = 1.6 Hz, 3.2 Hz, 1H), 4.64 (dd, J = 5.2 Hz, 5.2 Hz, 1H), 4.02 (s, 1H), 2.51 (ddd, J = 4.8 Hz, 10.4 Hz, 14.8 Hz, 1H), 2.34 (s, 3H), (m, 2H), 1.90 (s, 3H), 1.87 (m, 1H), (m, 4H), 1.27 (s, 3H), 1.05 (s, 3H), 0.66 (t, J = 7.2 Hz, 3H); 13 C-MR (100 MHz; CDCl 3 ): δ 152.8, 144.0, 139.0, 138.4, 129.6, 127.1, 124.5, 66.8, 60.4, 525, 51.4, 39.4, 37.0, 28.9, 28.8, 25.5, 21.8, 21.4, 21.0, 14.1, 13.5; HR - MS m/z: calcd for C 21 H 31 2 O 3 S[M+H + ]: ; found: Compound 4db: R f = 0.50 (hexanes/etoac, 7 : 3); Yield: 80%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3376, 2967, 2927, 1643, 1336, 1157, 1089, 765, 682; 1 H-MR (400 MHz; CDCl 3 ): δ HO Ts 4db 7.73 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 5.99 (dd, J = 0.8 Hz, 4 Hz, 1H), 4.72 (dd, J = 6.0 Hz, 6.0 Hz, 1H), 4.03 (s, 1H), (m, 1H), 2.43 (s, 3H), 2.17 (ddd, J = 3.0 Hz, 6.4 Hz, 13.2 Hz, 1H), 1.95 (s, 1H), 1.88 (s, 3H), 1.86 (m, 1H), 1.34 (dt, 6.4 Hz, 13.2 Hz, 1H), 1.27 (s, 3H), 1.12 (s, 3H), 1.01 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 6.4 Hz, 3H); 13 C-MR (100 MHz; CDCl 3 ): δ , 143.6, 139.1, 138.8, 129.6, 126.6, 124.4, 66.9, 52.2, 51.3, 37.2, 34.2, 29.0, 28.6, 25.4, 22.5, 21.4, 21.0, 20.2, 19.1; HR - MS m/z: calcd for C 21 H 31 2 O 3 S[M+H + ]: ; found: S9

11 Compound 4dc: R f = 0.7 (hexanes/etoac, 7 : 3); Yield: 83%; [ ] 25 D= (CHCl 3, c = 1);IR (neat) : 3392, 2957, 2925, 1624, 1156, 1037, 768; 1 H-MR (300 MHz; CDCl 3 ): δ 7.78 (d, J HO Ts 4dc = 8.4 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H), 6.06 (d, J = 4.8 Hz, 1H), 5.24 (s, 1H), 4.61 (dd, J = 5.7 Hz, 5.7 Hz, 1H), 4.02 (s, 1H), 2.11 (ddd, J = 3 Hz, 6 Hz, 13.2 Hz, 1H), 1.86 (s, 3H), (m, 2H), (m, 2H), 1.18 (s, 3H), 0.97 (s, 3H), (m, 3H), (m,1h); 13 C-MR (100 MHz; CDCl 3 ): δ 152.5, 143.7, 138.7, 138.6, 129.5, 127.1, 126.3, 124.7, 67.0, 52.1, 51.7, 37.0, 29.0, 28.8, 25.4, 21.5, 21.0, 15.6, 9.9, 9.8; HR - MS m/z: calcd for C 21 H 29 2 O 3 S[M+H + ]: ; found: Compound 4dd: R f = 0.50 (hexanes/etoac, 7 : 3); Yield: 74%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3395, 2924, 1626, 1156, 1025, 767; 1 H-MR (400 MHz; CDCl 3 ): δ (m, 3H), HO Ts 4dd Ph 7.13 (d, J = 6.8 Hz, 2H), (m, 4H), 6.17 (dd, J = 0.8 Hz, 4.4 Hz, 1H), 4.79 (dd, J = 5.2 Hz, 5.2 Hz, 1H), 3.94 (s, 1H), 2.36 (s, 3H), 2.27 (ddd, J = 2.8 Hz, 6.4 Hz, 13.6 Hz, 1H), 1.91 (s, 3H), 1.87 (dt, J = 2.4 Hz, 14.4 Hz, 1H), 1.39 (dd, J = 3.6 Hz, 14.4 Hz, 1H), 1.33 (s, 3H), 1.17 (s, 3H). 13 C-MR (100 MHz; CDCl 3 ): δ 152.2, 143.7, 136.8, 129.1, 128.6, 128.2, 127.7, 127.4, 123.9, 66.7, 50.0, 51.1, 37.6, 29.2, 29.0, 26.8, 25.2, 21.4, 21.2, 21.0, 14.1; HR - MS m/z: calcd for C 24 H 29 2 O 3 S[M+H + ]: ; found: Compound 4ea: R f = 0.50 (hexanes/etoac, 8 : 2); Yield: 87%; O [ ] 25 D= (CHCl 3, c = 1.1); IR (neat) : 2967, 2928, 2877, 1542, 1270, 1141, 1089, 711; 1 H-MR (400 MHz; CDCl 3 ): δ 7.75 Ts 4ea Pr (d, J = 7.9 Hz, 2H), (m, 3H), 5.99 (d, J = 9.7 Hz, 1H), 5.88 (dd, J = 9.5, 3.7 Hz, 1H), (m, 1H), 2.75 (t, J = 7.9 Hz, 2H), (m, 8H), 2.04 (s, 3H), 1.69 (dd, J = 15.5, 7.6 Hz, 2H), (m, 8H), 1.01 (t, J = 7.2 Hz, 3H). 13 C-MR (100 MHz; S10

12 CDCl 3 ): δ 201.1, 167.0, 141.8, 140.9, 138.2, 132.6, 131.3, 129.9, 129.6, , , 127.1, 125.9, 58.4, 40.0, 36.9, 29.8, 25.3, 24.22, 24.12, 21.3, 21.0, 20.2, 13.7; HR - MS m/z: calcd for C 23 H 33 2 O 3 S[M+a + ]: ; found: Compound 4eb: R f = 0.70 (hexanes/etoac, 8 : 2); Yield: 85%; O [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2968, 2925, 1706, 1361, 1088, 677; 1 H-MR (400 MHz; CDCl3): δ 7.79 (d, J = 8.2 Ts 4eb Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 6.17 (d, J = 3.9 Hz, 1H), 4.60 (t, J = 5.2 Hz, 1H), 3.13 (d, J = 6.5 Hz, 1H), 2.42 (s, 3H), 2.21 (s, 3H), 1.91 (d, J = 13.9 Hz, 1H), 1.81 (ddt, J = 16.3, 7.8, 3.9 Hz, 1H), 1.75 (s, 3H), 1.64 (s, 1H), 1.39 (td, J = 13.6, 6.8 Hz, 1H), 1.13 (s, 3H), 0.85 (s, 3H), 0.79 (dd, J = 4.2, 2.6 Hz, 2H), 0.68 (dd, J = 12.3, 6.6 Hz, 1H), 0.50 (td, J = 8.4, 3.4 Hz, 1H). 13 C-MR (100 MHz; CDCl 3 ): δ , , , , , , , , 52.63, 52.00, 51.74, 38.83, 29.27, 29.06, 25.23, 23.03, 22.64, 21.45, 15.56, 10.01, 9.90; HR - MS m/z: calcd for C 23 H 31 2 O 3 S[M+H + ]: ; found: Compound 4ec: R f = 0.50 (hexanes/etoac, 8 : 2); Yield: 80%; O [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2968, 2926, 2857, 1715, 1340, 1157, 1088, 768; 1 H-MR (400 MHz; CDCl3): δ 7.25 (dt, J Ts 4ec Ph = 23.1, 8.4 Hz, 5H), 7.13 (dd, J = 12.5, 7.8 Hz, 4H), 6.27 (d, J = 3.7 Hz, 1H), 4.80 (t, J = 5.2 Hz, 1H), 3.18 (d, J = 6.3 Hz, 1H), 2.38 (s, 3H), 2.24 (s, 3H), (m, 2H), 1.83 (s, 3H), (m, 3H), 1.31 (s, 3H), 1.07 (s, 3H). 13 C MR (100 MHz; CDCl 3 ): δ 208.6, 151.6, 143.8, 137.2, 136.7, 135.6, , , 128.6, 127.9, 127.5, 124.5, 53.9, 52.7, 51.1, 39.6, 29.4, 29.1, 25.0, 23.2, 23.0, 21.4; HR - MS m/z: calcd for C 26 H 31 2 O 3 S[M+H + ]: ; found: S11

13 Compound 4fa: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 80%; OH [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2968, 2926, 2857, 1715, 1340, 1157, 1088, 768; 1 H-MR (400 MHz; CDCl3): δ 7.77 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.09 (s, 1H), 4.63 (s, 1H), 4.13 (dd, J = 9.1, 4.9 Hz, 1H), 2.60 (ddd, J = 14.4, 9.4, 5.3 Hz, 1H), 2.43 (s, 3H), (m, 2H), 2.00 (dd, J = 26.4, 11.9 Hz, 3H), 1.84 (s, 3H), 1.38 (dt, J = 16.0, 8.0 Hz, 2H), (m, 8H), 0.97 (s, 3H), 0.71 (t, J = 7.3 Hz, 3H); 13 C-MR (100 MHz; CDCl 3 ): δ , , , , , , , 67.19, 53.10, 51.86, 44.57, 39.87, 39.55, 28.85, 26.09, 22.06, 21.75, 21.49, 20.57, 20.28, 13.57; HR - MS m/z: calcd for C 23 H 35 2 O 3 S[M+H + ]: ; found: fa Ts Pr Compound 4fb: R f = 0.50 (hexanes/etoac, 8 : 2); Yield: 76%; OH [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3410, 2961, 2925, 2863, 1600, 1157, 1088, 1025, 767; 1 H-MR (400 MHz; CDCl3): δ 7.76 Ts 4fb (d, J = 8.3 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 6.00 (dd, J = 2.6, 0.6 Hz, 1H), 4.70 (t, J = 4.6 Hz, 1H), 4.12 (qd, J = 6.2, 4.7 Hz, 1H), 2.89 (dt, J = 13.3, 6.6 Hz, 1H), 2.43 (s, 3H), 2.31 (ddd, J = 12.5, 7.1, 3.5 Hz, 1H), 1.99 (dd, J = 11.3, 2.9 Hz, 2H), 1.81 (s, 3H), 1.68 (s, 3H), 1.27 (s, 3H), 1.04 (s, 3H), 1.03 (d, J = 5.6 Hz, 3H), 0.91 (d, J = 6.7 Hz, 3H); 13 C-MR (100 MHz; CDCl3): δ , , , , , , , , 67.28, 52.86, 51.78, 44.68, 40.20, 34.26, 29.10, 25.88, 22.57, 22.07, 21.53, 20.56, 20.12, 19.28; HR - MS m/z: calcd for C 23 H 35 2 O 3 S[M+H + ]: ; found: Compound 4fc: R f = 0.50 (hexanes/etoac, 8 : 2); Yield: 80%; OH [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3423, 2960, 2925, 1604, 1156, 1047, 771; 1 H-MR (400 MHz; CDCl3): δ 7.81 (d, J = 8.2 Ts 4fc Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.11 (dd, J = 2.6, 0.8 Hz, 1H), 4.63 (t, J = 4.6 Hz, 1H), S12

14 (m, 1H), 2.42 (s, 3H), 2.25 (ddd, J = 12.1, 6.8, 3.4 Hz, 1H), 1.97 (dd, J = 11.5, 2.9 Hz, 2H), 1.82 (s, 3H), 1.25 (d, J = 6.4 Hz, 3H), 1.19 (s, 3H), 1.10 (dt, J = 13.1, 6.7 Hz, 1H), 0.90 (s, 3H), 0.80 (d, J = 4.8 Hz, 2H), 0.67 (ddd, J = 11.3, 8.5, 2.6 Hz, 1H), 0.49 (td, J = 7.9, 3.2 Hz, 1H). 13 C-MR (100 MHz; CDCl3): δ , , , , , , , 67.23, 52.63, 52.19, 44.63, 39.87, 28.96, 26.04, 22.03, 21.52, 20.50, 20.25, 15.70, 9.92, 9.66; HR - MS m/z: calcd for C 23 H 33 2 O 3 S[M+H + ]: ; found: Compound 4fd: R f = 0.50 (hexanes/etoac, 8 : 2); Yield: 72%; OH [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3410, 2961, 2925, 2863, 1600, 1157, 1088, 1025, 767; 1 H-MR (400 MHz; CDCl3): δ Ph Ts 4fd 7.10 (m, 9H), 6.20 (s, 1H), 4.81 (s, 1H), 4.15 (dd, J = 6.1, 3.1 Hz, 1H), (m, 5H), (m, 2H), 1.88 (d, J = 19.4 Hz, 3H), 1.36 (s, 3H), 1.26 (d, J = 6.3 Hz, 3H), 1.19 (dd, J = 18.2, 5.8 Hz, 2H), 1.11 (s, 3H). 13 C-MR (100 MHz; CDCl3): δ , , , , , , , , , , , , , 67.25, 54.60, 51.60, 44.76, 40.68, 29.11, 25.77, 22.25, 21.51, 20.67, 20.61; HR - MS m/z: calcd for C 26 H 33 2 O 3 S[M+H + ]: ; found: Compound 5a: R f = 0.20 (hexanes/etoac, 9 : 1); Yield: 35%; IR (neat) : 3296, 2967, 2921, 1632, 1435, 667 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.84 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), Br TsH Et 5.70 (s, 1H), 4.79 (dd, J = 6.6 Hz, 6.6 Hz, 1H), 2.45 (s, 3H), a 2.02 (m, 3H), 1.84 (s, 3H), 1.79 (s, 3H), 1.73 (s, 3H), (m, 1H), 1.34 (s, 3H), 1.21 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): 150.6, 143.8, 140.2, 139.0, 129.7, 126.7, 119.4, 53.6, 52.1, 46.1, 43.6, 30.0, 28.8, 25.4, 23.4, 22.1, 21.6, ; HR - MS m/z: calcd for C 20 H 31 Br 2 O 2 S[M+H + ]: ; found: S13

15 H Ph LiAlH 4,THF H Ph H COOMe 0 C, 2 h H OH 3ga 3gb 7-phenylbicyclo[4.1.0]hept-2-en-7-yl)methanol: To a vigorously stirred suspension of LiAlH 4 (0.38 g, 10 mmol, 1 equiv) in THF (15 ml) at 0 ºC,a solution of cyclopropyl ester 3ga (2.3 g,10 mmol, 1 equiv) in THF (10 ml) was added drop wise. The reaction mixture was stirred at rt for additional 1 h followed by quenching with EtOAc. The mixture was diluted with DCM (20 ml) and washed with 20% citric acid. The solvent was evaporated in vacuo and the resultant oil was further purified by column chromatography using silica to give 3gb as colorless oil. R f = 0.50 (hexanes/etoac : 8:2); Yield: 1.86 g, 93%; IR (neat) :3331, 2948, 2945, 830, 776 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): (m, 5H), (m, 1H), 5.31 (ddd, J = 1.6, 8.4, 13.2 Hz, 1H), (m, 1H), (m, 1H), 1.96 (dd, J = 11.6, 18.4 Hz, 1H), (m, 6H), (m, 1H); 13 C MR (100 MHz, CDCl 3 ): 138.1, 130.7, 128.0, 126.5, 126.0, 124.6, 72.8, 40.9, 22.6, 21.5, 19.4, 17.0; HR - MS m/z: calcd for C 14 H 16 O [M+H + ]: ; found: Compound 3g: To a solution of 3gb (0.90 g, 5 mmol,1 equiv) in dry DMF, (15 ml) cooled to -15 ºC under inert atmosphere was added H Ph ah(60% suspension in mineral oil)(0.24 g, 6 mmol, 1.2 equiv) at once H OMe 3g and stirred vigorously until all the effervescence ceased. To this MeI (2.50 g, 0.93 ml, 1.1 equiv) was added drop wise and the mixture was allowed to stir at rt for 30 min. The reaction was quenched by the addition of water drop wise and the mixture was extracted with diethyl ether. The solution was concentrated in vacuo and was purified by column chromatography using silica gel to yield compound 3g as colorless oil. R f = 0.50 (hexanes);yield: 1.50 g 98%; 1 H MR (300 MHz, CDCl 3 ): (m, 5H), (m, 1H), 5.30 (ddd, J = 1.6, 8.4, S14

16 13.2 Hz, 1H), 3.38 (d, J = 6.4 Hz, 1H), 3.24 (d, J = 6. 4 Hz, 1H), 3.21 (s, 3H), 1.96 (dd, J = 8.8, 14.0 Hz, 1H), (m, 1H), (m, 2H) (m, 1H); 13 C MR (100 MHz, CDCl 3 ): 138.8, 130.7, 127.6, 126.1, 126.0, 124.6, 82.6, 58.8, 38.6, 24.5, 21.5, 19.4, 17.0; HR - MS m/z: calcd for C 15 H 19 O [M+H + ]: ; found: Bicyclo[3.1.0]hex-2-en-6-yl methanol: R f = 0.50 (hexanes); Yield: 95%; H 1 H-MR (400 MHz; CD Cl3): δ (m, 1H), 5.42 (dd, J = 2.4 OH Hz, 2.4 Hz, 1H), (m, 1H), (m, 1H), 2.58 (dd, J = 6.4 H Hz, 17.6 Hz, 1H), 2.34 (d, J = 17.6 Hz, 1H), 2.24 (s, 1H), (m, 1H), (m, 1H), (m, 1H). 13 C-MR (100 MHz; CDCl3): δ 133.1, 128.7, 66.0, 35.5, 31.7, 29.1, 24.4; HR - MS m/z: calcd for C 14 H 16 O [M+a + ]: ; found: Compound 4ga: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 72%; IR (neat) :2948, 2945, 1643, 1340, 1156, 1091, 830, 776 cm -1 ; 1 H MR (400 MHz, CDCl 3 ): 7.44 (d, J = 8.4 Hz, 2H), (m, 5H), 7.18 (d, J = 8.4 Hz, 2H), 6.14 (dd,j = 1.5 Hz, 1H),6.02 (dd,j = 1.5 Hz, 1H), 4.10 (m, OMe Ph H H Ts 4ga 1H), 3.75 (d, J = 9.6 Hz, 1H), 3.47 (d, J = 9.2 Hz, 1H), 3.23 (s, 3H), (m, 1H), (m, 2H), 2.42 (s, 3H), (m, 2H), 2.24 (s, 3H), (m, 1H), (m, 1H); 13 C MR (100 MHz, CDCl 3 ): 150.6, 143.8, 143.2, 138.3, 132.1, 129.7, 128.4, 127.2, 126.9, 126.4, 79.2, 61.7, 59.3, 51.8, 38.3, 25.1, 24.8, 21.5, 18.7; HR - MS m/z: calcd for C 24 H 28 2 O 3 S [M+H + ]: ; found: Compound 6a: R f = 0.50 (hexanes/etoac, 7 : 3); Yield: 68%; IR H (neat) : 2942, 2940, 1341, 1056, 1090, 831, 776 cm -1 ; 1 H MR (400 MHz, CDCl 3 ): 7.80 (d, J = 8.0 Hz, 2H), (m, 7H), 4.36 (s, Ts H 6a OBn 2H), (m, 3H), (m, 1H), 2.37 (s, 3H), (m, 1H), (m, S15

17 2H), (m, 1H), (m, 1H), (m, 2H), (m, 1H); 13 C MR (100 MHz, CDCl 3 ): 144.0, 138.4, 135.7, 129.5, 128.3, 127.5, 127.4, 72.4, 72.0, 38.1, 22.1, 21.5, 20.1, 17.9, 11.6, 10.8; HR - MS m/z: calcd for C 22 H 26 O 3 S [M+H + ]: ; found: Compound 6b: R f = 0.50 (hexanes/etoac, 7 : 3); Yield: 60%; IR (neat) : 2952, 2947, 1346, 1053, 1092, 831, 770 cm -1 ; 1 H MR (400 Ts 6b OBn MHz, CDCl 3 ): 7.82 (d, J = 8.0 Hz, 2H), (m, 7 Hz), 4.43 (s, 2H) (m, 1H), (m, 1H), (m, 2H), 2.40 (s, 3H), (m, 1H), (m, 1H), (m, 1H), (m, 2H); 13 C MR (100 MHz, CDCl 3 ): 143.4, 138.0, 137.3, 129.6, 129.5, 128.4, 127.6, 127.4, 72.7, 71.3, 47.7, 36.5, 24.9, 21.54, 18.0; HR - MS m/z: calcd for C 21 H 24 O 3 S [M+H + ]: ; found: Compound 4aaA: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 86%; IR (neat) : 2948, 2945, 1643, 1340, 1156, 1091, 830, 776 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 5.79 (s, 1H), 4.27 (s, 1H), 2.24 (s, 3H), Boc 4aaA (m, 4H), 1.69 (s, 3H), 1.51 (s, 9H), 1.43 (s, 2H), (m, 4H), (m, 4H). 13 C- MR (100 MHz; CDCl 3 ): δ , , , , 81.72, 53.76, 50.63, 42.94, 29.60, 28.94, 28.30, 25.70, 24.45, 23.67, 20.39; HR - MS m/z: calcd for C 19 H 27 2 O 2 [M+H + ]: ; found: Compound 4abA: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 85%; IR (neat) : 2970, 2945, 1643, 1340, 1156, 1091, 830, 776 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 5.77 (s, 1H), 4.31 (dd, J = 1 Hz, 1Hz, 1H), 2.85 Boc 4abA Et 2.76 (m, 1H), (m, 1H), (m, 4H), 1.79 (s, 3H), 1.51 (s, 9H), 1.33 (s, 3H), 1.10 (s, 3H), 1.08 (t, J = 7.3 Hz, 3H); 13 C-MR (100 MHz; CDCl 3 ): δ , , S16

18 138.15, , 81.72, 53.76, 50.63, 42.94, 29.60, 28.94, 28.30, 25.70, 24.45, 23.67, 20.39; HR - MS m/z: calcd for C 19 H 27 2 O 2 [M+H + ]: ; found: Compound 4acA: : R f = 0.30 (hexanes/etoac, 9 : 1); Yield: 74%; IR (neat) : 2975, 2929, 1705, 1634, 1323, 1159, 891, 773 cm -1 ; 1 H- MR (400 MHz; CDCl3): δ 5.81 (s, 1H), 4.28 (s, 1H), (m, Boc 4acA 2H), (m, 2H), 1.72 (s, 3H), 1.52 (s, 9H), 1.52 (m, 1H), 1.25 (s, 3H), 1.03 (s, 3H), (m, 3H), (m, 2H), (m, 1H); 13 C-MR (100 MHz; CDCl 3 ): δ 156.4, 153.3, 137.7, 120.8, 81.2, 53.6, 50.6, 43.5, 29.6, 29.3, 28.3, 24.1, 23.6, 20.2, 17.0, 9.9, 8.0 ; HR - MS m/z: calcd for C 19 H 31 2 O 2 [M+H + ]: ; found: Compound 4aaB: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 73%; IR (neat) : 2975, 2914, 1753, 1574, 1307, 1238, 1001, 830, 776 cm -1 ; 1 H-MR (300 MHz; CDCl3): δ (m, 5H), 5.83 (s, 1H), Cbz 4aaB 5.27 (d, J = 12.6 Hz, 1H), 5.21 (d, J = 12.6 Hz, 1H), 4.36 (s, 1H), (m, 2H), (m, 2H), 1.71 (s, 3H), 1.25 (s, 3H), 1.02 (s, 3H), (m, 2H), (m, 3H); 13 C-MR (100 MHz; CDCl3): δ 156.1, 154.6, 138.2, 136.5, 129.0, 128.7, 128.4, 120.9, 68.2, 54.2, 51.5, 43.6, 30.1, 29.8, 24.7, 24.2, 20.7, 17.4, 10.4, 9.4; HR - MS m/z: calcd for C 22 H 29 2 O 2 [M+H + ]: ; found: Compound 4abB: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 69%; IR (neat) : 2975, 2914, 1750, 1544, 1313, 1238, 1004, 833, 779 cm -1 ; 1 H-MR (300 MHz; CDCl3): δ (m, 5H), 5.77 (s, 1H), 5.27 Cbz 4abB Pr (d, J = 12.3 Hz, 1H), 5.17 (d, J = 12.3 Hz, 1H), 4.39 (s, 1H), 2.83 (ddd, J = 6.9 Hz, 8.7 Hz, 15.3 Hz, 1H), (m,1h), (m, 3H), 1.70 (s, 3H), (m, 2H), 1.32 (s, 3H), (m, 1H), 1.07 (s, 3H). 13 C-MR (100 MHz; CDCl3): 156.4, 154.9, 138.9, S17

19 138.6, 129.5, 127.1, 120.9, 68.1, 52.8, 51.9, 42.9, 29.9, 29.1, 25.2, 23.5, 21.8, 21.5, 19.4, 13.5; HR - MS m/z: calcd for C 22 H 31 2 O 2 [M+H + ]: ; found: Compound 4acB: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 69%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2975, 2914, 1750, 1544,1313,1238, 1004, 833, 779 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ Cbz 4acB Ph (m, 2H), (m, 3H), (m, 3H), 6.75 (d, J = 7.1 Hz, 2H), 5.99 (s, 1H), 4.97 (d, J = 12.4 Hz, 1H), 4.89 (d, J = 12.4 Hz, 1H), 4.53 (d, J = 0.4 Hz, 1H), (m, 4H), 1.76 (s, 3H), 1.44 (s, 3H), 1.19 (s, 3H), 1.04 (qd, J = 12.6, 5.9 Hz, 1H). 13 C-MR (101 MHz; CDCl3): δ , , , , , , , , , , , , 67.74, 55.58, 51.25, 43.85, 29.61, 29.26, 23.75, 23.64, Compound 3j: 1 H-MR (400 MHz; CDCl 3 ): δ (m, 8H), 5.68 (d, J = 1.4 Hz, 1H), 4.62 (d, J = 11.9 Hz, 1H), 4.49 (d, J = 11.9 Hz, 1H), OBn 3.53 (t, J = 4.5 Hz, 1H), 2.17 (dq, J = 11.1, 4.1 Hz, 1H), (m, 4H), 1.07 (s, 4H), 0.88 (td, J = 8.5, 4.2 Hz, 1H), 0.82 (s, 3H). 13 C-MR (100 MHz; CDCl3): δ , , , , , , , , , , 73.31, 72.09, 70.35, 27.80, 24.39, 23.28, 22.66, 21.59, 17.83, 15.18; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: j Compound 4jaA: : R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 82%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2975, 2934, 1702, 1634, 1302, 1152, 776; 1 H-MR (400 MHz; CDCl3): δ BnO 4jaA Boc (m, 5H), 5.97 (d, J = 2.9 Hz, 1H), 4.62 (d, J = 11.7 Hz, 1H), 4.49 (d, J = 11.7 Hz, 1H), 3.69 (s, 1H), (m, 4H), 2.08 (d, J = 14.2 Hz, 1H), 1.79 (d, J = 20.4 Hz, 4H), (m, 10H), 1.29 (s, 3H), (m, 4H). 13 C-MR (100 MHz; CDCl 3 ): δ , , S18

20 138.57, , , , , , 82.04, 74.40, 71.89, 53.55, 50.57, 37.18, 28.83, 28.35, 25.72, 24.65, 24.49, 21.56; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 8a: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 43%; IR (neat) : 3588, 3476, 2982, 2946, 1756, 1575, 1331, 1181, 831 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ (m, 10H), 5.83 HCbz 8a HCbz 5.82 (m, 1H), 5.25 (dd, J = 12Hz, 17.2 Hz, 2H), 5.11 (s, 2H), 4.70 (m, 2H), (m, 1H), 2.30 (s, 3H), (m, 4H), 1.71 (s, 3H), 1.34 (s, 3H), 1.10 (s, 3H), (m, 1H). 13 C-MR (101 MHz; CDCl3): δ 157.4, 154.2, 152.3, 139.2, 136.7, 136.2, 129.1, 129.0, 128.8, 128.7, 128.6, 120.7, 68.4, 67.3, 54.4, 51.4, 43.1, 30.1, 29.4, 26.0, 25.0, 24.2, 20.8; HR - MS m/z: calcd for C 28 H 35 3 O 4 [M+a + ]: ; found: Traces of cyclized product was also found; HR - MS m/z: calcd for C 20 H 26 2 O 2 [M+a + ]: ; found: Compound 8b: R f = 0.30 (hexanes/etoac, 8 : 2); Yield: 45%; [ ] 25 D= (CHCl 3, c = 2.0); IR (neat) : 3576, 3480, 2967, BnO HCbz 2942, 1761, 1570, 1335, 1187, 778 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ (m, 10H), 5.97 (d, J = 3.2 Hz, 1H), b HCbz 5.19 (m, 2H), 4.62 (d, J = 11.7 Hz, 1H), 4.49 (d, J = 11.7 Hz, 1H), 4.43 (s, 1H), 3.69 (s, 1H), 2.28 (s, 3H), 2.23 (ddd, J = 13.1, 7.7, 2.9 Hz, 1H), 2.10 (d, J = 14.3 Hz, 1H), 1.76 (s, 3H), 1.30 (s, 3H), (m, 1H), 1.11 (s, 3H); 13 C-MR (100 MHz; CDCl 3 ): δ , , , , , , , , , , , , , , , , , , , , , , , , 74.26, 71.88, 68.02, 66.91, 53.64, 50.79, 36.81, 28.78, 25.50, 24.58, 24.47, 21.50; HR - MS m/z: calcd for C 35 H 41 3 O 5 [M+a + ]: ; found: S19

21 Compound 7a: Yield: 63%; IR (neat) : 3347, 2927, 1620, 1332, 1273, 772 cm -1 ; 1 H MR (400 MHz, Benzene-d 6 ): (m, 2H), 7.24 (s, 1H), (m, 3H), 5.84 (s, 1H), 4.09 (m, 1H), 1.86 (s, 3H), H 7a Ph 1.72 (s, 3H), (m, 1H), (m, 2H), 1.22 (s, 6H); 13 C MR (100 MHz, Benzene d 6 ): 149.8, 137.6, 129.2, 127.9, 127.6, 126.5, 51.2, 39.1, 30.8, 27.5, 23.3, 19.4; HR - MS m/z: calcd for C 17 H 22 2 [M+H + ]: ; found: Compound 7b: Yield: 76%; IR (neat) : 3352, 2922, 1621, 1325, 1274, 769, 699 cm -1 ; 1 H MR (400 MHz, Benzene-D 6 ): 6.99, 6.88 (s, 1H), 5.82 (d, J = 3.6 Hz, 1H), 3.93 (s, 1H), 2.00 (s, 3H), 1.88 (d, J = 4.0 Hz, 2H), 1.73 (s, 3H), 1.59 (s, 1H), 1.22 (s, 3H), 1.20 (s, 3H), (m, 1H); 13 C MR (100 MHz, Benzene d 6 ): 152.1, 136.1, 122.5, 50.7, 47.4, 38.5, 30.6, 30.5, 26.4, 23.1, 20.6, 19.1; HR - MS m/z: calcd for C 12 H 21 2 [M+H + ]: ; found: Compound 4ka: R f = 0.70 (hexanes/etoac, 7 : 3); Yield: 92%; [ ] 25 D= 79.3 (CHCl 3, c = 1.01); IR (neat) : 2964, 2930, 2873, 1649, 1343, 1156, 970, 681 cm -1 ; 1 H-MR (400 MHz; CDCl 3 ): BnO 4ka Ts δ7.76 (d, J = 8.3 Hz, 2H), 7.31 (m, J = 7.1 Hz, 7H), 5.86 (s, 1H), 4.95 (d, J = 8.7 Hz, 1H), 4.46 (d, J = 11.7 Hz, 1H), 4.33 (d, J = 11.6 Hz, 1H), 4.09 (q, J = 6.3 Hz, 1H), 2.81 (dd, J 1 =18.0, J 2 = 9.0 Hz, 1H), 2.42 (s, 3H), 2.37 (d, J = 8.6 Hz, 1H), 2.30 (d, J = 8.2 Hz, 1H), 2.27 (s, 3H), 1.26 (d, J = 9.0 Hz, 3H), 1.26 (s, 3H), 0.95 (s, 3H). 13 C MR (100 MHz, CDCl 3 ): 150.6, 150.2, 144.2, 138.2, 137.3, 129.7, 128.4, 127.7, 127.5, 127.2, 72.7, 70.2, 62.9, 52.1, 49.3, 32.0, 29.6, 25.8, 25.7, 21.5, 19.6.HR - MS m/z: calcd for C 26 H 33 2 O 3 S[M+H + ]: ; found: S20

22 Compound 4kb:R f = 0.70 (hexanes/etoac, 7 : 3); Yield: 91%; [ ] 25 D= 47.9 (CHCl 3, c = 1.11); IR (neat) : 2979, 2925, 2890, 1647, 1332, 1153, 679 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 7.81 BnO 4kb Ts (d, J = 7.9 Hz, 2H), (m, 7H), 5.79 (s, 1H), 4.98 (d, J = 8.8 Hz, 1H), 4.49 (d, J = 11.7 Hz, 1H), 4.34 (d, J = 11.7 Hz, 1H), 4.09 (q, J = 6.4 Hz, 1H), 2.80 (dd, J= 16.0, 8.0 Hz, 1H), 2.42 (s, 3H), 2.26 (dd, J = 17.8, 8.2 Hz, 2H), (m, 1H), 1.26 (d, J = 6.5 Hz, 3H), 1.18 (s, 3H), 0.88 (s, 3H), (m, 2H), (m, 1H). 13 C MR (100 MHz, CDCl 3 ): 154.2, 149.9, 143.8, 138.3, 137.7, 129.6, 128.3, 127.8, 127.6, 127.5, 127.3, 127.2, 72.8, 70.1, 63.1, 51.7, 49.5, 31.9, 29.9, 25.4, 21.5, 19.8, 15.9, 10.0, 9.0; HR - MS m/z: calcd for C 28 H 34 2 O 3 S[M+H + ]: ; found: Compound 4kc: R f = 0.70 (hexanes/etoac, 7 : 3); Yield: 81%; [ ] 25 D= 13.5 (CHCl 3, c = 1.00); IR (neat) : 2967, 2936, 2874, 1626, 1348, 1167, 681 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 7.42 BnO 4kc Ts Ph (d, J = 8.0 Hz, 2H), (m, 12H), 5.83 (s, 1H), 5.28 (d, J = 9.0 Hz, 2H), 4.45 (d, J = 11.8 Hz, 1H), 4.32 (d, J = 11.8 Hz, 1H), 4.10 (q, J = 6.3 Hz, 1H), 3.02 (dd, J 1 = 17.0, J 2 = 8.5 Hz, 1H), 2.42 (s, 1H), 2.28 (dd, J = 16.9, 8.4 Hz, 1H), 1.38 (s, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.18 (s, 3H). 13 C MR (100 MHz, CDCl 3 ): 153.8, 150.9, 143.9, 138.2, 137.9, 136.8, 129.4, 129.3, 128.4, 128.3, 127.8, 127.7, 127.4, 126.0, 73.1, 70.3, 62.8, 53.9, 50.4, 32.4, 25.1, 21.5, 20.1; HR - MS m/z: calcd for HR - MS m/z: calcd for C 31 H 35 2 O 3 S[M+H + ]: ; found: Compound 4kaA : R f = 0.40 (hexanes/etoac, 7 : 3); Yield: 81%; [ ] 25 D= (CHCl 3, c = 1.18); IR (neat) : 2972, 2925, 2871, 1725, 1648, 1162, 667 cm -1 ; 1 H-MR (400 MHz; CDCl 3 ): δ 7.37 BnO Boc 4kaA 7.26 (m, 10H), 5.81 (s, 1H), 5.27 (d, J = 12 Hz, 1H), 5.23 (d, J=12 Hz, 1H), 4.92 (d, J = 4.8 S21

23 Hz, 1H), 4.50 (d, J =12 Hz, 1H), 4.33 (d, J = 12 Hz, 1H), 4.08 (dd, J = 6.4 Hz, 12.8 Hz, 1H), 2.83 (dd, J = 8.8 Hz, 17.6 Hz, 1H), (m, 2H), (m, 2H), 1.26 (s, 3H), 1.13 (s, 3H), (m, 3H). 13 C MR (100 MHz, CDCl 3 ): 153.5, 149.6, 138.4, 135.9, 128.5, 128.3, 128.2, 127.9, 127.6, 127.5, 127.1, 73.1, 70.2, 67.8, 62.1, 52.9, 48.5, 32.2, 29.7, 24.8, 19.9, 16.5; HR - MS m/z: calcd for HR - MS m/z: calcd for C 29 H 34 2 O 3 [M+H + ]: ; found: Compound 4kbB: R f = 0.70 (hexanes/etoac, 7 : 3); Yield: 83%; [ ] 25 D= (CHCl 3, c = 1.00); IR (neat) : 2967, 2936, 2874, 1626, 1348, 1167, 681 cm -1 ; 1 H-MR (400 MHz; BnO Cbz 4kbB CDCl 3 ): δ (m, 10H), 5.81 (s, 1H), 5.27 (d, J = 12 Hz, 1H), 5.23 (d, J=12 Hz, 1H), 4.92 (d, J = 4.8 Hz, 1H), 4.50 (d, J =12 Hz, 1H), 4.33 (d, J = 12 Hz, 1H), 4.08 (dd, J = 6.4 Hz, 12.8 Hz, 1H), 2.83 (dd, J = 8.8 Hz, 17.6 Hz, 1H), (m, 2H), (m, 2H), 1.26 (s, 3H), 1.13 (s, 3H), (m, 3H). 13 C MR (100 MHz, CDCl 3 ): 153.5, 149.6, 138.4, 135.9, 128.5, 128.3, 128.2, 127.9, 127.6, 127.5, 127.1, 73.1, 70.2, 67.8, 62.1, 52.9, 48.5, 32.2, 29.7, 24.8, 19.9, 16.5; HR - MS m/z: calcd for HR - MS m/z: calcd for C 29 H 34 2 O 3 [M+H + ]: ; found: Compound 4la: R f = 0.40 (hexanes/etoac, 8 : 2); Yield: 45%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2973, 2929, 1660, 1343, 1162, 669 cm -1 ; Ts 1 H MR (300 MHz, CDCl 3 ): 7.88 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 4la Hz, 2H), 5.54 (t, J = 1.2 Hz, 1H), 4.09 (d, J = 1.8 Hz, 1H), (m, 1H), 2.45 (s, 3H), (m, 1H), (m, 2H), 1.45 (s, 3H), 1.40 (s, 3H), 1.11 (d, J = 1.85 Hz, 3H); 13 C MR (75 MHz, CDCl 3 ):147.0, 143.8, 137.2, 129.6, 128.5, 127.6, 59.9, 54.2, 34.9, 33.0, 29.7, 26.6, 26.4, 25.3, 21.51, 21.0; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: S22

24 HPLC Chromatogram for Compound 33aa Column Details : Chiralpak AD-3; 150 mm x 40mm Solvent System : n-heptane/isopropyl alcohol 80:20 isocratic flow InJection volume : 2 L in Isopropyl alcohol Flow Rate : 1.0 ml/min, 5.2 MPa, 298 K Detector Wavelength : 220 nm 4la Ts Figure 1: HPLC Chromatogram for racemic mixture of 14a S23

25 Figure 2. HPLC Chromatogram for 14a resulting from (+)-pinene From the chromatogram the enantiomeric ratio was found to be 65:35 Compound 4lb: R f = 0.45 (hexanes/etoac, 9 : 1); Yield: 43%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2976, 2927, 1658, 1342, 1162, 669 cm - 1 ; 1 H MR (300 MHz, CDCl 3 ): 7.85(d, J = 7.8 Hz, 2H), 7.34 (d, J = 7.8 Ts 4lb Et Hz, 2H), 5.41 (t, J = 1.7 Hz, 1H), 4.06 (s, 1H), (m, 2H), 2.45 (s, 3H), (m, 2H), (m, 2H), 1.45 (s, 3H), 1.13 (s, 3H), 1.00 (t, J = 7.2 Hz, 3H); 13 C MR (75 MHz, CDCl 3 ):149.8, 143.6, 137.7, 129.6, 128.9, 127.5, 59.6, 54.1, 35.0, 33.0, 31.9, 29.7, 26.5, 25.5, 21.5, 21.0, 11.6; HR - MS m/z: calcd for C 20 H 29 2 O 2 S[M+H + ]: ; found: Compound 4lc: R f = 0.6 (hexanes/etoac, 8 : 2); Yield: 35%; [ ] 25 D= (CHCl 3, c = 0.83)IR (neat) : 2977, 2925, 1653, 1340, 1163, 669 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.86 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 5.40 (s, 1H), 4.07 (s, 1H), (m, S24

26 5H), 2.45 (s, 3H), (m, 2H), (m, 1H), 1.62 (s, 3H), 1.44 (s, 3H), 1.37 (s, 3H), 1.14 (s, 3H), 0.84 (t, J = 7.5 Hz,3H); 13 C MR (75 MHz, CDCl 3 ):143.6, 137.7, 129.6, 129.2, 128.8, 127.6, 127.5, 125.4, 59.7, 54.2, 40.5,.35.0, 33.0, 29.7, 26.6, 26.1, 25.5, 21.1, 20.1, 13.5; HR - MS m/z: calcd for C 21 H 31 2 O 2 S[M+H + ]: ; found: lc Ts Pr Compound 4ld: R f = 0.50 (hexanes/etoac, 8 : 2); Yield: 37%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2973, 2929, 1660, 1343, 1162, 669 cm - 1 ; 1 H MR (300 MHz, CDCl 3 ): (m, 4H), (m, 5H), Ts 4ld Ph 5.48 (s, 1H), 4.43 (s, 1H), 2.73 (d, J = 13.5 Hz, 1H), 2.47 (s, 1H), 2.41 (s, 3H), (m, 1H), (m, 3H), 1.88 (td, J = 14.1 Hz, 4.2 Hz, 1H), 1.58 (s, 3H), 1.52 (s, 3H), 1.50 (s, 3H); 13 C MR (75 MHz, CDCl 3 ):143.6, 137.4, 129.6, 129.4, 129.3, 129.0, 128.6, 128.3, 127.8, 127.6, 127.0, 61.2, 55.5, 40.0, 36.5, 35.2, 33.1, 29.9, 26.5, 25.9, 22.0, 21.5; HR - MS m/z: calcd for C 24 H 29 2 O 2 S[M+H + ]: ; found: CH Analysis found for C 24 H 29 2 O 2 S: C, 70.55; H, 6.91;, Found: C, 70.16; H, 6.99;, Compound 4le: R f = 0.60 (hexanes/etoac, 9 : 1); Yield: 48%; [ ] 25 D= (CHCl 3, c = 0.54); IR (neat) : 2973, 1664, 1342, 1162, 669 cm - 1 ; 1 H MR (300 MHz, CDCl 3 ): 7.90 (d, J = 8.4 Hz, 2H), 7.33 (d, J = Ts 4le 8.4 Hz, 2H), 5.41 (s, 1H), 4.13 (s, 1H), (m, 1H), 2.44 (s, 3H), (m, 1H), (m, 1H), (m, 2H), (m, 1H), 1.33 (s, 3H), 1.30 (s, 3H), 1.23 (s, 3H), (m, 2H), (m, 2H), (m, 1H); 13 C MR (75 MHz, CDCl 3 ):149.3, 143.5, 138.2, 129.5, 129.4, 127.5, 127.2, 58.9, 54.3, 35.0, 33.1, 29.9, 26.6, 25.6, 21.5, 20.9, 17.6, 10.9, 9.9, 9.2; HR - MS m/z: calcd for C 21 H 29 2 O 2 S[M+H + ]: ; found: S25

27 Compound 9: R f = 0.45 (hexanes/etoac, 9 : 1); [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 3276, 2918, 2360, 1435, 1328, 1160, 665 cm -1 ; 1 H MR TsH (300 MHz, CDCl 3 ): 7.77 (d, J = 7.8 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.53 (s, 1H), 4.69 (s, 1H), 4.62 (s, 1H), 4.45(d, J = 9.9 Hz, 1H) 3.86 (br, 9 1H), 2.43 (s, 3H), (m, 6H), 1.65 (s, 3H), 1.52 (s, 3H) (m, 1H); 13 C MR (100 MHz, CDCl 3 ): 148.4, 143.2, 138.4, 132.9, 129.6, 127.0, 125.8, 109.5, 54.3, 40.1, 36.5, 30.3, 21.5, 20.8, 19.9; HR - MS m/z: calcd for C 17 H 23 ao 2 S[M+a + ]: ; found: CH Analysis found for C 17 H 23 O 2 S: C, 66.85; H, 7.59;, 4.59; Found: C, 66.67; H, 7.49;, Compound 4ma: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 48%; [ ] 25 D= (CHCl 3, c = 0.96); IR (neat) : 2974, 2927, 1662, MeO Ts 1342, 1162, 1095, 670 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.9 (d, 4ma J = 8.1 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 5.79 (t, J = 3.6 Hz, 1H), 4.52 (s, 1H), 3.20 (dd, J = 10.8 Hz, 8.7 Hz, 2H), 2.98 (s, 3H), 2.63 (d, J = 13.8 Hz, 1H), 2.45 (s, 3H), (m, 1H) (m, 1H), 2.03 (s, 3H), (m, 1H), 1.75 (td, J = 13.8 Hz, 3.3 Hz, 1H), 1.46 (s, 3H), 1.43 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): 172.3, 143.7, 137.5, 130.4, 129.6, 127.7, 73.5, 60.1, 57.6, 49.8, 35.1, 33.0, 29.6, 26.5, 25.3, 21.5; HR - MS m/z: calcd for C 20 H 29 2 O 3 S[M+H + ]: ; found: Compound 4na: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 42%; [ ] 25 D= (CHCl 3, c = 2.9); IR (neat) : 2974, 2929, 2870, 1659, BnO Ts 1598, 1343, 1162, 1093, 670 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 4na 7.82(d, J = 8.7 Hz, 2H), (m, 7H), (m, 1H), 4.39 (d, J = 12 Hz, 1H), 4.34 (d, J = 12 Hz, 1H), 4.19 (s, 1H), 3.19 (t, J = 6.6 Hz, 2H), (m, 1H), (m, 2H), 2.38 (s, 3H), 2.09 (s, 3H), (m, 2H), (m, 1H), 1.45 (s, 3H), 1.40 (s, S26

28 3H); 13 C MR (75 MHz, CDCl 3 ): 147.2, 143.9, 138.2, 137.0, 130.0, 129.6, 128.9, 127.6, 127.6, 127.4, 126.3, 72.7, 68.6, 60.0, 52.5, 35.0, 33.8, 32.9, 29.5, 26.6, 26.5, 25.3, 21.4; HR - MS m/z: calcd for C 27 H 35 2 O 3 S [M+H + ]: ; found: Compound 4nb: R f = 0.30 (hexanes/etoac, 6 : 4); Yield: 57%; IR (neat) : 3281, 2973, 2929, 2858, 1715, 1705, 1525, 1318, BnO Ts 1204, 1065, 737 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.85(d, J 4nb = 8.4 Hz, 2H), (m, 7H), 5.51 (m, 1H), 4.42 (d, J = 12 Hz, 1H), 4.34 (d, J = 12 Hz, 1H), 4.21 (s, 1H), 3.25 (dd, J = 7.2 Hz, 7.2 Hz, 2H), (m, 4H), 2.39 (s, 3H), 2.05 (dd, J = 6.9 Hz, 19.2 Hz, 1H), (m, 1H), (m, 4H), 1.41 (ddd, J = 4.8 Hz, 8.4 Hz, 12.6 Hz, 1H), 1.33 (s, 3H), 1.30 (s, 3H), (m, 1H), (m, 2H), (m, 1H); 13 C MR (75 MHz, CDCl 3 ): 149.4, 143.6, 130.8, 129.6, 128.5, 128.3, 127.6, 127.4, 127.1, 121.6, 72.7, 68.7, 58.9, 52.6, 35.2, 34.0, 33.1, 30.5, 29.8, 26.6, 25.6, 21.5, 17.8, 9.8, 9.5. Compound 4laA: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 52%; [ ] 25 D= (CHCl 3, c = 0.91); IR (neat) : 2978, 2925, 1720, 1343, 1162, 1098, 776 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 5.52 (s, 1H), 4.50 (s, 1H), 2.32 Boc 4laA (m, 2H), (m, 2H), 2.02 (s, 3H), (m, 5H), 1.48 (s, 9H), 1.47 (s, 3H), 1.43 (s, 3H), 1.11 (s, 3H). 13 C-MR (100 MHz; CDCl 3 ): δ , , , 81.10, 59.54, 34.51, 33.12, 28.74, 28.46, 28.06, 26.75, 24.57, 21.67; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 4laB: R f = 0.30 (hexanes/etoac, 6 : 4); Yield: 48%; IR (neat) : 3281, 2973, 2929, 2858, 1715, 1705, 1525, 1318, 1204, 1065, 737 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): (m, 5H), (m, 1H), 5.21 Cbz 4laB S27

29 (s, 2H), 4.58 (s, 1H), (m, 2H), (m, 1H), 2.02 (s, 3H), (m, 5H), 1.43 (s, 3H), 1.07 (s, 3H); 13 C MR (100 MHz, CDCl 3 ): 153.5, 151.2, 136.0, 129.1, 128.5, 128.1, 128.0, 127.0, 67.6, 59.6, 50.6, 34.4, 33.0, 28.7, 26.6, 24.7, 21.6; HR - MS m/z: calcd for C 20 H 27 2 O 2 [M+H + ]: ; found: (S)-1-((1S,5R)-6,6-dimethylbicyclo[3.1.0]hex-2-en-2-yl)ethanol: R f = 0.30 (hexanes/etoac, 3 : 1); Yield: 90%; IR (neat) : 3416, 2945, 2918, 1522, 1090, 738, 667 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 5.28 (s, 1H), OH 4.28 (dd, J = 5.7 Hz, 12.0 Hz, 1H), 2.35 (dd, J = 7.8 Hz, 18.0 Hz, 1H), 2.13 (s, 1H), (m, 1H), (m, 1H), (m, 5H), 0.98 (s, 3H), 0.73 (s, 3H); 13 C MR (75 MHz, CDCl 3 ): 148.2, 122.5, 67.1, 36.7, 31.5, 29.1, 27.3, 21.8, 19.2, 13.0; HR - MS m/z: calcd for C 10 H 16 ao[m+a + ]: ; found: Compound 3o: R f = 0.40 (hexanes); Yield: 98%; 1 H MR (400 MHz, CDCl 3 ): (m, 5H), 5.41 (s, 1H), 4.57 (d, J = 12.0 Hz), 4.40 (d, J = 12.0, 1H), 4.06 (dd, J = 5.8 Hz, 11.6 Hz, 1H), 2.44 (dd, J = 7.6 Hz, OBn 3o 18.0 Hz, 1H), (m, 1H), (m, 1H), (m, 9H), 1.09 (s, 3H), 0.98 (s, 3H); 13 C MR (100 MHz, CDCl 3 ): 140.3, 133.1, 122.3, 121.5, 118.5, 67.8, 63.3, 30.9, 25.9, 23.6, 20.4, 17.6, 13.5, 7.3; HR - MS m/z: calcd for C 17 H 23 ao[m+h + ]: ; found: Compound 4oa: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 90%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2974, 2929, 2870, 1659, 1598, 1343, 1162, 1093, 670 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 7.71 (d, J = 8.2 Ts OBn 4oa Hz, 1H), 7.41 (d, J = 7.3 Hz, 1H), 7.35 (t, J = 7.3 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 5.92 (s, 1H), 5.14 (d, J = 9.0 Hz, 1H), 4.56 (d, J = 11.0 Hz, 1H), 4.49 (d, J = 11.0 Hz, 1H), 4.39 (q, J S28

30 = 5.9 Hz, 1H), 2.83 (q, J = 8.5 Hz, 1H), 2.41 (s, 1H), (m, 1H), 2.34 (s, 1H), 2.21 (ddd, J = 17.3, 8.3, 2.8 Hz, 1H), 1.38 (d, J = 6.3 Hz, 1H), 1.20 (s, 1H), 0.73 (s, 1H); 13 C-MR (100 MHz; CDCl3): δ , , , , , , , , , , , 71.13, 70.46, 63.59, 52.66, 50.86, 33.20, 30.01, 26.63, 25.24, 21.55, 18.90; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 4ob: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 87%; [ ] 25 D= (CHCl 3, c = 1); 1 H-MR (300 MHz; CDCl3): δ 7.78 (d, J = 8.4 Hz, 2H), (m, 5H), 7.26 (d, J = 8.4 Hz, 2H), 5.89 (s, 1H), 5.17 (dd, J = 1.5 Hz, 9.0 Hz, 1H), 4.60 (d, J = 7.8 Hz, 1H), Ts OBn 4ob 4.49 (d, J = 7.8 Hz, 1H), 4.40 (dd, J = 7.2 Hz, 12.6 Hz, 1H), 2.79 (dd, J = 8.1 Hz, 17.1 Hz, 1H), 2.40 (s, 3H), (m, 3H), 1.41 (d, J = 6.3 Hz, 3H), 1.11 (s, 3H), (m, 5H), 0.64 (s, 3H) ; 13 C-MR (100 MHz; CDCl3): δ 158.0, 149.0, 144.0, 139.5, 138.0, 132.0, 129.0, 128.9, 128.6, 128.3, 127.9, 72.0, 71.5, 63.5, 53.5, 52.0, 34.5, 31.0, 23.5, 21.5, 19.5, 18.0, 15.0; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 4oc: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 73%; [ ] 25 D= (CHCl 3, c = 1); 1 H-MR (300 MHz; CDCl3): δ 7.48 (d, J = 7.8 Hz, 2H), (m, 10H), 7.07 (d, J = 7.8 Hz, 2H), 5.92 (s, 1H), 5.45 (dd, J = 3 Hz, 9.6 Hz, 1H), 4.63 (d, J = 11.1 Hz, 1H), 4.57 (d, J = 11.1 Hz, Ts OBn 4oc Ph 1H), (m, 1H), 2.97 (dd, J =8.4 Hz, 17.1 Hz, 1H), (m, 2H), 2.36 (s, 3H), 2.24 (dd, J = 2.1 Hz, 8.1 Hz, 1H), 1.50 (d, J = 6.6 Hz, 3H), 1.33 (s, 3H), 1.04 (s, 3H); 13 C-MR (100 MHz; CDCl3): δ 154.6, 146.3, 143.9, 139.2, 138.2, 136.4, 131.8, 129.7, 129.0, 128.8, 128.5, 128.3, 127.9, 127.8, 127.4, 127.1, 70.4, 69.5, 63.1, 54.2, 51.4, 33.3, 30.4, 25.0, 21.5, 18.2; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: S29

31 Compound 4oaA: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 90%; [ ] 25 D= (CHCl 3, c = 1.02); IR (neat) : 2974, 2929, 2870, 1720, 1649, 1347, 1159, 1086, 877, 664 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 7.34 (qd, J = 7.4, 5.6 Hz, 5H), 5.81 (s, 1H), 5.09 (dd, J = 1.9, 9.8 Hz, Boc OBn 4oaA 1H), 4.54 (d, J = 11.5 Hz, 1H), 4.40 (d, J = 11.4 Hz, 1H), 4.19 (q, J = 6.3 Hz, 1H), 2.94 (q, J = 8.5 Hz, 1H), 2.43 (dd, J = 16.8, 7.5 Hz, 1H), (m, 1H), 2.19 (s, 3H), 1.47 (s, 9H), 1.42 (s, 3H), 1.35 (s, 3H), 1.33 (s, 3H), 1.14 (s, 3H); 13 C-MR (100 MHz; CDCl3): δ , , , , , , , , , 81.57, 77.30, 76.98, 76.66, 72.37, 70.46, 61.57, 53.81, 49.96, 33.38, 29.51, 28.22, 25.37, 24.45, 20.86; HR - MS m/z: calcd for C 24 H 25 2 ao 3 [M+a + ]: ; found: Compound 4obA: R f = 0.60 (hexanes/etoac, 7 : 3); Yield: 85%; [ ] 25 D= (CHCl 3, c = 1.08); IR (neat) : 2971, 2938, 2845, 1727, 1643, 1346, 1283, 1082, 875, 660 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ 7.38 (d, J = 7.6 Hz, 2H), (m, 3H), 5.81 (s, 1H), 5.10 (dd, J = Boc OBn 4obA Et 1.6, 9.6 Hz, 1H), 4.56 (d, J = 10.8 Hz, 1H), 4.45 (d, J = 10.8 Hz, 1H), 4.16 (dd, J = 6.4 Hz, 12.8 Hz, 1H), 2.91 (dd, J = 8.8 Hz, 13.2 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), 1.48 (s, 9H), 1.35 (d, J = 6.0 Hz, 3H), 1.33 (s, 3H), 1.14 (s, 3H), 1.04 (t, J = 7.6 Hz, 3H); 13 C-MR (100 MHz; CDCl3): δ 161.1, 152.5, 146.3, 139.0, 129.7, 128.2, 127.8, 127.3, 81.4, 71.9, 70.7, 61.8, 53.5, 50.1, 33.3, 31.3, 29.6, 28.2, 24.3, 20.0, 12.1; HR - MS m/z: calcd for C 25 H 36 2 O 3 [M+H + ]: ; found: Compound 4ocA: R f = 0.60 (hexanes/etoac, 7 : 3); Yield: 83%; [ ] 25 D= (CHCl 3, c = 1.25); IR (neat) : 2975, 2931, 2865, 1707, 1365, 1342, 1163, 698 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ Boc OBn 4ocA Ph S30

32 (m, 4H), (m, 4H), (m, 2H), 5.83 (s, 1H), 5.29 (dd, J = 2.0, 9.6 Hz, 1H), 4.67 (d, J = 10.8 Hz, 1H), 4.57 (d, J = 10.8 Hz, 1H), 4.37 (dd, J = 6.4 Hz, 12.8 Hz, 1H), 3.04 (dd, J = 8.8 Hz, 16.8 Hz, 1H), (m, 1H), (m, 1H), 1.53 (d, J = 6.4 Hz, 1H), 1.44 (s, 3H), 1.26 (s, 3H), 1.06 (s, 9H); 13 C-MR (100 MHz; CDCl3): δ 156.9, 152.8, 145.8, 139.0, 130.7, 129.1, 128.2, 128.0, 127.8, 127.3, 126.8, 81.0, 71.9, 71.0, 61.3, 54.8, 50.9, 33.3, 29.7, 27.5, 24.2, 19.1; HR - MS m/z: calcd for C 29 H 37 2 O 3 [M+H + ]: ; found: Compound 4oaB: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 80%; [ ] 25 D= (CHCl 3, c = 1); IR (neat) : 2974, 2929, 2870, 1716,, 1598, 1343, 1162, 1093, 670 cm -1 ; 1 H-MR (400 MHz; CDCl3): δ (m, 10H), 5.80 (s, 1H), (m, 3H), 4.48 (d, J = 11.5 Cbz OBn 4oaB Hz, 1H), 4.37 (d, J = 11.5 Hz, 1H), 4.14 (q, J = 6.3 Hz, 1H), 2.93 (q, J = 8.5 Hz, 1H), 2.43 (dd, J = 17.1, 7.3 Hz, 1H), (m, 4H), 1.33 (s, 3H), 1.32 (d, J = 6.6 Hz, 3H), (m, 1H), 1.11 (s, 3H). 13 C-MR (100 MHz; CDCl 3 ): δ , , , , , , , , , , 72.27, 70.43, 67.95, 61.74, 53.99, 49.78, 33.43, 29.55, 25.27, 24.62, 20.19; HR - MS m/z: calcd for C 19 H 27 2 O 2 S[M+H + ]: ; found: Compound 10: R f = 0.20 (hexanes/etoac, 9 : 1); Yield: 23%; [ ] 25 D= (CHCl 3, c = 2.05); IR (neat) : 3318, 2973, 2922, Br TsH Et 1639, 1599, 1450 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.86 (d, J = Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 5.43 (s, 1H), 4.83 (dd, J = 6.6 Hz, 12.9 Hz, 1H), 3.92 (s, 1H), (m, 1H), 2.46 (s, 3H), (m, 1H), (m, 1H), 1.87 (d, J = 6.6 Hz, 3H), 1.75 (dt, J = 3.9 Hz, 15.6 Hz, 1H), 1.49 (s, 3H), 1.33 (s, 3H), 1.22 (t, 3H); 13 C MR (75 MHz, CDCl 3 ): 146.3, 144.2, , 129.9, 128.7, 127.9, 127.5, 60.7, 54.5, 47.8, S31

33 35.3, 32.6, 29.1, 26.5, 26.3, 24.9, 22.5, 21.6; HR - MS m/z: calcd for C 20 H 31 Br 2 O 2 S[M+H + ]: ; found: Compound 11: R f = 0.30 (hexanes/etoac, 7 : 3); Yield: 54%; IR (neat) : 3316, 2973, 2925, 2097, 1549, 1274, 1141, 1090, 738 cm -1 ; 1 H MR (300 MHz, CDCl 3 ): 7.78 (d, J = 9 Hz, 2H), 7.31 (d, J = 9 3 TsH 11 Hz, 2H), 5.50 (s, 1H), (d, J = 12 Hz, 1H), 3.07(br, 1H), 3.07 (s,3h) 2.43 (s, 3H), (m, 9H), 0.99 (s, 6H); 13 C MR (75 MHz, CDCl 3 ): 143.2, 138.4, 133.3, 129.5, 127.0, 125.8, 75.7, 55.0, 48.7, 41.6, 33.2, 26.4, 21.9, 21.8, 21.5, 19.7; HR - MS m/z: calcd for C 18 H 27 ao 3 S[M+a + ]: ; found: Compound 12: R f = 0.30 (hexanes/etoac, 1 : 1); Yield: 59%; IR (neat) : 3326, 3312, 2973, 2925, 1549, 1140, 1090, 738 cm -1 ; 1 H MR (400 MHz, CDCl 3 ): 7.73 (d, J = 6.4 Hz, 2H), 7.70 (d, J = TsH 12 TsH 8.0 Hz, 2H), 7.29 (d, J = 6.4 Hz, 2H), 7.24 (d, J = 6.4 Hz, 2H), 5.45 (s, 1H), (m, 1H), 4.53 (d, J = 7.6 Hz, 1H), (m, 1H), 2.41 (s, 3H), 2.40 (s, 3H), 2.28 (s, 3H), (m, 3H), (m, 2H), 1.48 (s, 3H), 1.17 (s, 3H), 1.16 (s, 3H), 1.03 (dd, J = 9.6, 18.8 Hz, 1H); 13 C MR (100 MHz, CDCl 3 ): 164.0, 143.3, 142.1, 140.7, 138.1, 133.3, 129.6, 129.2, 127.0, 126.7, 125.3, 58.2, 54.8, 38.9, 33.4, 26.2, 23.6, 23.2, 21.9, 21.5, 21.4; HR - MS m/z: calcd for C 18 H 27 ao 3 S[M+a + ]: ; found: S32

34 X Ray Crystallography Data Compound 4la: CCDC o The structure was solved by direct methods (SIR92). Refinement was by full-matrix leastsquares procedures on F 2 by using SHELXL-97. CCDC o Crystal system: Orthorhombic, space group: P , cell parameters: a = 7.320, b = , c = Å, = 90.00, = 90.00, = 90.00, V = Å 3, Z = 4, calcd = 1.26 g cm -3, F(000) = 743.9, = mm -1, = Å. Total number l.s. parameters = 222. R1 = for 3208F o 4 (F o ) and 0.09 for all data. wr2 = 0.110, GOF = 0.627, restrained GOF = for all data. S33

35 Compound 4la: CCDC o The structure was solved by direct methods (SIR92). Refinement was by full-matrix leastsquares procedures on F 2 by using SHELXL-97. CCDC o Crystal system: Monoclinic, space group: P2 1 /c, cell parameters: a = , b = 8.407, c = Å, = 90.00, = , = 90.00, V = Å 3, Z = 4, calcd = 1.25 g cm -3, F(000) = 743.9, = mm -1, = Å. Total number l.s. parameters = 222. R1 = for 3386F o 4 (F o ) and 0.09 for all data. wr2 = 0.121, GOF = 1.045, restrained GOF = for all data. S34

36 Compound 4ld: CCDC o The structure was solved by direct methods (SIR92). Refinement was by full-matrix leastsquares procedures on F 2 by using SHELXL-97. CCDC o Crystal system: Monoclinic, space group: P2 1 /c, cell parameters: a = , b = 8.641, c = Å, = 90.00, = , = 90.00, V = Å 3, Z = 4, calcd = 1.30 g cm -3, F(000) = 871.9, = mm -1, = Å. Total number l.s. parameters = 266. R1 = for 3680F o 4 (F o ) and 0.09 for all data. wr2 = 0.121, GOF = 1.078, restrained GOF = for all data. S35

37 Compound 9: CCDC o The structure was solved by direct methods (SIR92). Refinement was by full-matrix leastsquares procedures on F 2 by using SHELXL-97. CCDC o Crystal system: Orthorhombic, space group: P , cell parameters: a = 5.209, b = , c = Å, = 90.00, = 90.00, = 90.00, V = Å 3, Z = 4, calcd = 1.17 g cm -3, F(000) = 655.9, = 0.19 mm -1, = Å. Total number l.s. parameters = 193. R1 = for 3041F o 4 (F o ) and 0.04 for all data. wr2 = 0.140, GOF = 1.238, restrained GOF = for all data. S36

38 1 H, 13 C, DEPT MR Spectra Ts 4aa Me 13 C, CDCl 3, 75 MHz S37

39 Ts 4aa Me Ts 4ab Pr S38

40 Ts 4ab Pr Ts 4ac S39

41 Ts 4ac Ts 4ad PFP S40

42 Ts 4ad PFP S41

43 Ts 4ad PFP Ts 4ae Ph S42

44 Ts 4ae Ph Ts 4ba S43

45 Ts 4ba S44

46 Ts 4ca S45

47 Ts 4ca S46

48 Ts 4ca S47

49 HO Ts 4da Pr S48

50 HO Ts 4db S49

51 HO Ts 4dc S50

52 HO Ts 4dd Ph S51

53 O Ts 4ea Pr S52

54 O Ts 4eb S53

55 O Ts 4ec Ph S54

56 OH Ts 4fa Pr S55

57 OH Ts 4fb S56

58 OH Ts 4fc S57

59 OH Ts 4fd Ph S58

60 Br TsH Et 5a Br TsH Et 5a S59

61 S60

62 H Ph H OH S61

63 H Ph H 3g OMe S62

64 H OMe Ph H Ts 4ga S63

65 1 H - 1 H COSY CDCl 3, 400 MHz H OMe Ph H Ts 4ga S64

66 1 H 13 C COSY CDCl 3, 400 MHz H OMe Ph H Ts 4ga S65

67 OESY CDCl 3, 400 MHz H OMe Ph H Ts 4ga S66

68 H OH H S67

69 H Ts H 6a OBn S68

70 Ts 6b OBn S69

71 Boc 4aaA S70

72 Boc 4abA Et S71

73 Boc 4acA S72

74 Cbz 4aaB S73

75 Cbz 4abB Pr S74

76 Cbz 4acB Ph 13 C, CDCl 3, 100 MHz S75

77 OBn 3j S76

78 S77

79 S78

80 S79

81 S80

82 S81

83 S82

84 S83

85 S84

86 BnO 4ka Ts S85

87 BnO 4ka Ts BnO Ts 4kb S86

88 BnO 4kb Ts BnO 4kc Ts Ph S87

89 BnO 4kc Ts Ph BnO 4kaA Boc S88

90 BnO 4kaA Boc BnO Cbz 4kbB S89

91 BnO Cbz 4kbB 4la Ts S90

92 4la Ts S91

93 Ts Et 4lb S92

94 Ts Et 4lb Ts Pr 4lc S93

95 Ts Pr 4lc S94

96 Ts Ph 4ld S95

97 Ts 4le S96

98 TsH 9 S97

99 1 H - 1 H COSY CDCl 3, 400 MHz TsH 9 S98

100 1 H 13 C COSY CDCl 3, 400 MHz TsH 9 S99

101 MeO Ts 4ma S100

102 MeO Ts 4ma BnO Ts 4na S101

103 BnO Ts 4na BnO Ts 4nb S102

104 BnO Ts 4nb Boc 4laA S103

105 Boc 36 Cbz 4laB S104

106 Cbz 4laB S105

107 OH S106

108 OBn 3o S107

109 S108

110 Ts OBn 4ob S109

111 Ts OBn 4oc Ph S110

112 S111

113 S112

114 S113

115 S114

116 Br TsH Et 10 S115

117 Br TsH Et HTs S116

118 3 11 HTs S117

119 HTs 12 HTs HTs 12 HTs S118

120 1 H 1H COSY, 400 MHz HTs 12 HTs S119

121 1 H 13 C COSY, 400 MHz HTs 12 HTs S120

122 OESY, 400 MHz HTs 12 HTs S121

123 Computational Details References 1. Gaussian 03, Revision C.02, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, Jr., J. A.; Vreven, T.; Kudin, K..; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega,.; Petersson, G. A.; akatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; akajima, T.; Honda, Y.; Kitao, O.; akai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; anayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; and Pople, J. A.; Gaussian, Inc., Wallingford CT, Gaussian 09, Revision A.1, Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; akatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; akajima, T.; Honda, Y.; Kitao, O.; akai, H.; Vreven, T.; Montgomery, Jr., J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K..; Staroverov, V..; Kobayashi, R.; ormand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,.; Millam,. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian, Inc., Wallingford CT, S 122

124 Cartesian coordinates of Model Alkene Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of 3a S 123

125 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 124

126 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of 3k (similar in skeleton) Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6 311+G** S 125

127 Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of 3o (similar in skeleton) Standard orientation: S 126

128 Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6 311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 127

129 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of compound 3l Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= S 128

130 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Model BrCl Complex (M) Standard orientation: S 129

131 Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Intermediate Int 1a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 130

132 Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 131

133 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Int 2a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= S 132

134 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Int 3a S 133

135 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 134

136 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Int 4 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 135

137 Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= S 136

138 Cartesian coordinates of Intermediate Sol 1a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 137

139 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Intermediate Sol 2a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 138

140 Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Intermediate Sol 3a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 139

141 Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Intermediate Sol 4a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 140

142 Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Transition State TS 1a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G**//B3LYP/6 31G* S 141

143 Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Transition State TS 2a: S 142

144 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G**//B3LYP/6 31G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 143

145 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Transition State TS 3a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G**//B3LYP/6 31G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= S 144

146 Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Transition State TS 4a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 145

147 Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z S 146

148 Level: M06 2X/6 31+G* Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Transition State Sol TS 4a Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: M06 2x/6 31+G* S 147

149 Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= Cartesian coordinates of Intermediate Int 1b 1 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Sum of electronic and zero-point Energies= Sum of electronic and thermal Energies= Sum of electronic and thermal Enthalpies= Sum of electronic and thermal Free Energies= S 148

150 Cartesian coordinates of Intermediate Sol 1b 1 Standard orientation: Center Atomic Atomic Coordinates (Angstroms) umber umber Type X Y Z Level: B3LYP/6-311+G** Geometry not converged even after 500 Cycles. SCF Done: E(RB+HF-LYP) = S 149