highly enantioselective carbon-carbon bond …supporting information page no 1) experimental...

Highly enantioselective carbon-carbon bond formation by Cu-catalyzed asymmetric [2, 3]-sigmatropic rearrangement: Application to the syntheses of seven-membered oxacycles and six-membered carbocycles Gullapalli Kumaraswamy*a, Kadivendi Sadaiah a, Duggirala Subrahmanya Ramakrishnaa, Police Nareshb, Balasubramanian Sridharc and Bharatam Jagadeeshb

aOrganic Division-III, Telephone: + 91-40-27193154; Fax: + 91-40-27193275;

e-mail: gkswamy_iict@yahoo.co.in bNMR Division,

cLaboratory of X-ray crystallography, Indian Institute of Chemical Technology, Hyderabad, 500 007, India

Supporting Information

Page No 1) EXPERIMENTAL PROCEDURE & SPCTRAL DATA 2-18 a) Compounds generated by using (1R, 2R)-1, 2-diphenylethane-1, 2-diol 2-14 b) Compounds generated by using (R)-phenylethylene glycol 14-16 c) Cyclopropanation 16-18 2) 1H, 13C and NOESY NMR SPECTRA 19-59 a) Compounds generated by using (1R, 2R)-1, 2-diphenylethane-1, 2-diol 19-49 b) Compounds generated by using (R)-phenylethylene glycol 50-54 c) Cyclopropanation 55-59 3) SPCTRAL DATA 60-61 a) Compounds generated by using (1S, 2S)-1, 2-diphenylethane-1, 2-diol 4) 1H, 13C and NOESY NMR SPECTRA 62-69 a) Compounds generated by using (1S, 2S)-1, 2-diphenylethane-1, 2-diol 5) Chiral HPLC Analysis 70-81 6) X-ray Crystallographic analysis of 10 82

General Procedures: 1H NMR spectra were recorded at 200, 300, 400, 500 & 600 M Hz and 13C NMR 50, 75, 100, 125 & 150 M Hz, in CDCl3. IR (FT-IR) Spectrometer, measured as KBr pellets or as films between KBr plates. Mass spectral data were compiled using MS (ESI), HRMS mass spectrometers. Optical rotations recorded on HORIBA high sensitive polarimeter, 10mL cell. The diastereomeric purity of the sigmatropic rearrangement products 2, 3, 6a and 7a and cyclopropination product 10 was determined by chiral HPLC (Instrument SPD-10A SHIMADZU, Chiral ADH column and nHexane, IPA and Ethanol as mobile phase).Column chromatography carried out with silica gel, grade 60-120, 100-200 and 230-400 mesh. Starting materials: CH2Cl2 was distilled from P2O5, THF from sodium benzophenone ketyl. All other chemicals used were commercially available. All reactions were conducted under an atmosphere of nitrogen (IOLAR Grade I). Organic extracts were dried over anhydrous Na2SO4.

1) EXPERIMENTAL PROCEDURE & SPCTRAL DATA Procedure for (Z)-4-methoxy but-2-en-1-ol:

HO OMe A solution of (Z)-2-butene-1,4-diol (56 mL, 0.68 mol) in 1,4-dioxane (680 mL) was added potassium hydroxide (133 g, 2.37 mol) and H2O (20 mL). Upon heating the resulting mixture upto 70 °C, added dimethyl sulphate (65 ml, 0.68 mol) drop wise over a period of 1 h. The combined contents then stirred for 2 h at 80 °C and cooled to rt, filtered the slurry. The organic layer was separated and concentrated under vacuum. The residue was purified through column chromatography (silica gel 60-120mesh) using hexane:EtOAc (9:1) to give the product (Z)-4-methoxy but-2-en-1-ol as light yellow liquid ( 38 g. 55%). 1H NMR (200 MHz, CDCl3): δ 5.81-5.74 (m, 1H), 5.67-5.59 (m, 1H), 4.14 (d, J = 6.0 Hz, 2H), 3.97 (d, J = 6.0 Hz, 2H), 3.33 (s, 3H), 2.65 (br. s, 1H); IR (Neat): 3423, 2924, 2855, 1727, 1457, 1377, 1189, 1094 cm-1; MS (ESIMS) m/z 103 (M+H+). General Procedure A Step1: To a DCM (200 mL) solution of (Z) - 4-methoxy but-2-en-1-ol (13.34 g, 130.83 mmol) was added Et3N (20.92 mL, 150.37 mmol). To this mixture methanesulphonyl chloride (10.7 mL, 137.21 mmol) was added slowly at 0 °C. Then, the mixture was allowed over a period of 2h at 0 °C to rt. The organic layer was washed with water (2 X 100 mL) and contents were dried over anhydrous Na2SO4. The resultant solution was filtered and concentrated under reduced pressure. The crude product was used for next step without purification.

Step2: To a dry THF (500 mL) solution of 1, 2-diol (93.45 mmol) was added portion wise NaH (60% dispersion in mineral oil) (4.1 g, 102.79 mmol) at 0 °C. After 30 min, mesylate of (Z)-4-methoxy but-2-en-1-ol in THF (50 mL) was added slowly maintaining same temperature. The resulting mixture was warmed to rt and stirred overnight. The reaction mixture was quenched with water till the mixture become clear. This mixture was extracted with ethyl acetate (4 x 200 mL). The combined organic layers were washed with brine (2 X 100 mL) and dried over anhydrous Na2SO4. Filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was subjected to silicagel (100-200 mesh) column chromatography eluting with hexane:EtOAc furnished the pure product as oily compound . General Procedure B To a xylene (170 mL) solution of 2-(4-methoxybut-2-enyloxy)-phenylethanol (40.27 mmol) was added 2, 2, 6-Trimethyl-4H-1, 3-dioxine-4-one (5.85 mL, 44.29 mmol) at rt. This mixture was allowed to reflux for 30 min. Then, xylene was distilled from the reaction mixture. The crude product was subjected to silicagel (60-120mesh) column chromatography eluting with EtOAc in hexane furnished the pure product as yellow oil. General Procedure C To an acetonitrile (30 mL) solution of 3-oxobutanoate (10.86 mmol), Hunig base was added. To this mixture a predissolved solution of Tosyl azide (2.33g, 14.12 mmol) in acetonitrile (10 mL) was added. This mixture was allowed to stir at rt over a period of 3 h, then, a solution of LiOH (1.49g, 35.47 mmol) in H2O (15 mL) was added and stirred for 6 h at rt. The organic layer was separated and aqueous layer was extracted with Ethyl acetate (4 X 20 mL). To the combined organic layers brine (2 X 30 mL) wash was given, and dried over anhydrous Na2SO4. The resultant solution was filtered and concentrated under reduced pressure. The crude product was subjected to silicagel (60-120mesh) column chromatography eluting with EtOAc in hexane furnished the pure product as yellow viscous liquid. General Procedure D A solution of diazoacetate (2.73 mmol) in DCM (60 mL) was added using a syringe pump to a solution of Tetrakis (acetonitrile) copper(I) hexaflorophosphate ( 51 mg, 5 mol%) in DCM (60 mL) under reflux condition for 5 h. The reaction mixture was allowed to rt, then solvent was removed under reduced pressure. The crude product was subjected to silicagel (100-200 mesh) column chromatography eluting with EtOAc in hexane furnished the pure products syn and anti 6:4 ratio and 2-(4-methoxybut-2-enyloxy) phenylethanol (15%) also recovered.

a) Compounds generated by using (1R, 2R)-1, 2-diphenylethane-1, 2-diol Procedure for (1R, 2R, Z)-2-(4-methoxybut-2-enyloxy)-1, 2-diphenylethanol (8a):

Ph OOMe

(8a) This compound was prepared according to the general procedure A, as color less oil (Yield 68%). [α]D

24 +3.8 (c 0.110, CHCl3); 1H NMR (200 MHz, CDCl3): δ 7.19-7.10 (m, 6H), 6.98-6.93 (m, 4H), 5.81-5.62 (m, 2H), 4.60 (d, J = 8.1 Hz, 1H), 4.20 (d, J = 8.1 Hz, 1H), 3.98-3.93 (m, 2H), 3.79 (d, J = 5.1 Hz, 2H), 3.22 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 142.0, 133.5, 128.3, 128.2, 127.8, 127.2, 126.7, 86.8, 85.3, 78.4, 29.6, 27.1.IR (Neat) 3466, 3062, 3031, 2926, 2877, 1731, 1454, 1190, 701 cm-1; MS (ESIMS) m/z 299 (M+H+), 281,197, 103, 85. Procedure for (1R, 2R)-2-((Z)-4-methoxybut-2-enyloxy)-1, 2-diphenylethyl 3-oxobutanoate:

Ph OOMe

This compound was prepared according to the general procedure B. (Yield 85%). [α]D

24 -29.2 (c 0.126, CHCl3); 1H NMR (200 MHz, CDCl3): δ 7.20-7.13 (m, 6H), 7.05-7.00 (m, 4H), 5.93-5.89 (d, J = 8.0 Hz, 1H), 5.66-5.60 (m, 2H), 4.53-4.50 (d, J = 7.3 Hz, 1H), 3.91 (m, 2H), 3.76 (d, J = 5.1 Hz, 2H), 3.42 (s, 2H), 3.21 (s, 3H), 2.21(s, 3H); 13C NMR (75 MHz, CDCl3): δ 200.2, 166.0, 137.0, 129.5, 128.8, 128.0, 127.9, 127.7, 127.4, 83.2, 79.3, 67.9, 64.4, 57.8, 50.3; IR (Neat): 3453, 2925, 1717, 1360, 1201, 1151, 763, 700 cm-1 ; MS (ESIMS): m/z 405 (M+Na+), 400, 384, 180. Procedure for (1R, 2R)-2-((Z)-4-methoxybut-2-enyloxy)-1, 2-diphenylethyl 2-diazoacetate (5a):

Ph OOMeON2

(5a) This compound was prepared according to the general procedure C, as yellow oil (Yield 95%).

[α]D24 -2.4 (c 0.018, CHCl3); 1H NMR (200 MHz, CDCl3): δ 7.19-7.11 (m, 6H), 7.03-

6.98 (m, 4H), 5.94 (d, J = 7.3 Hz, 1H), 5.66-5.61 (m, 2H), 4.51 (d, J = 7.3 Hz, 1H), 3.99-3.88 (m, 2H), 3.77 (d, J = 4.4 Hz, 2H), 3.21 (s, 3H);13C NMR (75 MHz, CDCl3): δ 129.5, 127.9, 127.8, 127.3, 83.2, 78.5, 68.0, 64.5, 57.8, 46.3, 29.6, 29.0. IR (Neat): 3443, 3031, 2925, 2113, 1729, 1453, 1378, 1188, 1090.5, 702.7 cm-1; MS (ESIMS): m/z 367 (M+H+), 281, 211, 143, 85; HRMS (ESIMS): Calculated for C21H22N2O4Na, 389.1471, Found 389.1483. Procedure for (2R, 3R, 6R, 7R)-6-methoxy-2, 3-diphenyl-7-vinyl-1, 4-dioxocan-5-one (6a) and (2R, 3R, 6S, 7R)-6-methoxy-2, 3-diphenyl-7-vinyl-1, 4-dioxocan-5-one (7a): These compounds were prepared according to the general procedure D. Syn was white solid (yield 41%) and anti was a color less oil (yield 27%),(1R, 2R, Z)-2-(4-methoxybut-2-enyloxy)-1, 2- (yield 15%) also recovered.

Syn (6a) M.P 120 oC: [α]D

24 -74.0 (c 0.010, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.29-7.17(m, 6H), 7.10 (d, J = 6.5 Hz, 2H), 6.98 (d, J = 6.5 Hz, 2H), 6.13 (ddd, J1 = 17.0 Hz, J2 = 11.0 Hz, J3 = 8.7 Hz 1H), 5.94 (d, J = 9.0 Hz, 1H), 5.29-5.26 (m, 2H), 4.37 (d, J = 9.7 Hz, 1H), 4.22 (dd, J1 = 6.5, J2 = 11.6 Hz, 1H), 4.16 (d, J = 5.8 Hz, 1H), 3.93 (d, J = 10.3 Hz, 1H), 3.51 (s, 3H), 3.30-3.21 (m, 1H);13C NMR (100 MHz, CDCl3): δ 174.1, 137.0, 135.1, 133.7, 128.6, 128.2, 128.0, 127.5, 127.3, 118.4, 96.1, 86.9, 80.0, 74.0, 58.4, 50.3. IR (KBr): 3473, 3084, 2938, 2890, 1745, 1454, 1209, 1116, 986, 698 cm-1; MS (ESIMS): m/z 338. (M+H+), 321, 242, 197; HRMS (ESIMS): Calculated for C21H22O4Na, 361.1415, Found 361.1415.

Anti (7a) [α]D

24 -126.0 (c 0.091, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.25-7.24 (m, 3H), 7.22-7.20 (m, 3H), 7.13-7.11 (m, 2H), 7.00-6.99 (m, 2H), 6.02 (d, J = 9.2, 1H), 5.82 (ddd, J1 =17.4 Hz, J2 =10.4 Hz, J3 = 8.4 Hz, 1H), 5.22 (td, J = 17.3 Hz, J = 1.4, 2H), 5.18 (td, J1 = 10.4 Hz, J2 = 1.4 Hz, 1H), 4.35 (d, J = 9.2 Hz, 1H), 4.16 (t, J = 10.6 Hz, 1H), 4.05 (dd, J1

=10.7 Hz, J2= 3.01 Hz, 1H), 4.02 (d, J = 3.2 Hz, 1H), 3.48 (s, 3H), 3.18-3.13 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 175.4, 137.2, 134.1, 128.4, 128.2, 128.1, 127.5, 127.4, 117.8, 91.7, 86.7, 81.7, 73.6, 52.5; IR (Neat): 3448, 3033, 2928, 1743, 1454, 1226, 1094, 762, 699 cm-1; MS (ESIMS): m/z 339 (M+H+), 297289, 242.2, 197. HRMS (ESIMS) Calculated for C21H22O4Na, 361.1411, Found 361.1427 Procedure for (R)-2-((R)-2-(tert-butyldimethylsilyloxy)-1-methoxyethyl) but-3-en-1-ol (12):

OTBDMSMeO

(12) To a suspension of LAH (327 mg, 8.61mmol) in dry THF (40 mL), a predissolved solution of 6a in dry THF (30mL) (1.94 g, 5.74 mmol) was added slowly at 0 °C. Stirring was continued at 0oC- rt for 2 h. The reaction was quenched with 10%NaOH slowly at 0 °C and allowed to stir at rt for 45 min. Then the reaction mixture was decanted and concentrated to get the crude product which was taken for next step without any purification. To a Dry DCM (70 mL) solution of above alcohol and Imidazole (1.25 g, 18.36 mmol) TBDMSCl (922 mg, 6.11mmol) was added at 0 °C and stirred for 4 h. To the resultant mixture, water (50 mL) was added and organic layer was separated. The aqueous layer was extracted (3 X 20mL) with DCM dried over anhydrous Na2SO4. Filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was used for next step without any purification. A 250 mL two necks RB was fitted with a neck ammonia condenser with guard tube and another neck was fitted with stopper, 60-80 mL of ammonia was condensed. Then Li granules (280 mg) were added slowly. Blue colour was appeared. Then stopper was replaced by septum. To this blue solution, above silyl ether in THF (30 mL) was added slowly. After 30 min the reaction mixture was quenched with solid NH4Cl slowly. Then ammonia condenser was removed and allowed to rt to remove the excess Liquid ammonia. To this mixture water was added and extracted with Ethyl acetate (3 X 30mL). The combined organic layers were dried over anhydrous Na2SO4. Filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was subjected to silicagel (60-120mesh) column chromatography eluting with hexane:EtOAc (94:6) furnished the pure product as color less liquid (1.21 g, 81%) for three steps. [α]D

24 -2.4 (c 0.035, CHCl3); 1H NMR (300 MHz, CDCl3): δ 5.71 (ddd, J1 = 8.3 Hz, J2 = 10.6 Hz, J3 = 18.9 Hz, 1H), 5.17-5.12 (m, 2H), 3.74 (dd, J1 = 3.8 Hz, J2 = 10.6 Hz, 1H), 3.70-3.67 (m, 1H), 3.63-3.57 (m, 2H), 3.46 (s, 3H), 3.32-3.27 (m, 1H), 2.51-2.42 (m, 1H), 0.90 (s, 9H), 0.05 (s, 6H);13C NMR (75 MHz, CDCl3): δ 135.7, 118.32, 83.36, 63.81, 61.18, 57.95, 47.57, 25.81, -5.51; IR (Neat): 3426, 2928, 2857, 1465, 1253, 1092, 837, 776 cm-1; MS (ESIMS) 261 (M+H+), 243, 175; HRMS (ESIMS): Calculated for C13H28O3NaSi, 283.1699, Found 283.1701.

Procedure for (R)-2-((S)-2-(tert-butyldimethylsilyloxy)-1-methoxyethyl) but-3-en-1-ol (12’):

OTBDMSMeO

(12’) This compound was prepared according to the above procedure, starting material is 7a instead of 6a, as color less liquid yield (81%) for three steps. [α]D

24 -11.6 (c 0.036, CDCl3); 1H NMR (300 MHz, CDCl3): δ 5.72 (ddd, J1 = 9.1 Hz, J2 = 10.6 Hz, J3 = 19.6 Hz, 1H), 5.17-5.12 (m, 2H), 3.78-3.57 (m, 4H), 3.47 (s, 3H), 3.32-3.27 (m, 1H), 2.59 (br.s, 1H), 2.51-2.42 (m, 1H), 0.90 (s, 9H), 0.06 (s, 6H);13C NMR (100 MHz, CDCl3): δ 136.1, 117.6, 84.5, 64.1, 63.2, 58.5, 47.4, 25.8, 18.2, -5.5; IR (Neat): 3382, 2925, 2855, 1461, 1079, 759 cm-1; MS (ESIMS): m/z 283 (M+Na+), 261 (M+H+), 198, 182; HRMS (ESIMS): Calculated for C13H28O3NaSi, 283.1709, Found 283.1721. Procedure for ((2R, 3R)-3-(benzyloxymethyl)-2-methoxypent-4-enyloxy) (tert-butyl) dimethylsilane:

OTBDMSMeO

To a solution of 12 (2.05 g, 7.88 mmol) in Dry THF(40 mL), NaH 60%(dispersion in mineral oil) (473 mg, 11.82 mmoL) was added portions wise at 0 °C and stirred for 15 min. To the above stirred solution BnBr (1.1 mL, 10.14 mmol) was added slowly. Stirring was continued at 0oC- rt for 6 h. To this reaction mixture water (30 mL) was added then extracted with Ethyl acetate (3 X 30mL). The combined organic layers were dried over anhydrous Na2SO4, filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was subjected to silicagel (60-120 mesh) column chromatography eluting with EtOAc 5% in hexane furnished the pure product as color less liquid (2.23 g, 94 %) 1H NMR (300 MHz, CDCl3): δ 7.32-7.20 (m, 5H), 5.87-5.75 (m, 1H), 5.12-5.05 (m, 2H), 4.47 (d, J = 1.5 Hz, 2H), 3.70 (dd, J1 = 3.0 Hz, J2 = 10.6 Hz, 1H), 3.63-3.49 (m, 3H), 3.40 (s, 3H), 3.32-3.26 (m, 1H), 2.54-2.46 (m, 1H), 0.88 (s, 9H), 0.03 (s, 6H);13C NMR (75 MHz, CDCl3): δ 137.3, 128.2, 116.9, 82.0, 73.0, 70.6, 63.8, 58.8, 46.0, 25.9, 18.2, -5.4; IR (Neat): 3421, 2925, 2856, 1719, 1456, 1274, 1098, 710 cm-1; MS (ESIMS): m/z 351 (M+H+), 259, 237, 202; HRMS (ESIMS): Calculated for C20H34O3NaSi, 373.2174, found 373.2187

Procedure for ((2S, 3R)-3-(benzyloxymethyl)-2-methoxypent-4-enyloxy)(tert-butyl) dimethylsilane:

OTBDMSMeO

This compound was prepared according to the above procedure, starting material is 12’ instead of 12, as color less liquid yield (94 %). [α]D

24 +4.6 (c 0.014, CHCl3); 1H NMR (200 MHz CDCl3): δ 7.33-7.24 (m, 5H), 5.90-5.72 (m, 1H), 5.14-5.05 (m, 2H), 4.47 (s, 2H), 3.75-3.47 (m, 5H), 3.40 (s, 3H), 3.33-3.25 (m, 1H), 2.57-2.44 (m, 1H), 0.89 (s, 9H), 0.03 (s, 6H);13C NMR (75 MHz, CDCl3): δ 129.3, 128.5, 126.5, 116.9, 83.1, 73.0, 70.5, 65.6, 63.7, 57.8, 45.1, 26.8, 25.0, 17.9, -6.3; IR (Neat): 2927, 2856, 1724, 1460, 1272, 1105, 838 cm-1 ; MS (ESIMS): m/z 273 (M+Na+), 351 (M+H+), 242; HRMS (ESIMS): Calculated for C20H34O3NaSi, 373.2174, found 373.2182 Procedure for (2R, 3R)-3-(benzyloxymethyl)-2-methoxypent-4-en-1-ol (13):

(13) To the Stirred solution of silyl ether (1.63g 4.68mmol) in Methanol (35 mL), PTSA (89 mg 0.46 mmol) was added at 0 oC. Stirring was continued at 0oC- rt for 2 h, then solid NaHCO3 (50 mg) was added to the reaction mixture. After 10 min reaction mixture was filtered. Filtrate was concentrated and purified by silicagel (60-120 mesh) column chromatography eluting with EtOAc 10% in hexane, as color less oil (1.03 g, 94%) [α]D

24 -25.2 (c 0.012, CHCl3); 1H NMR (200 MHz CDCl3): δ 7.30-7.25 (m, 5H), 5.90-5.72 (m, 1H), 5.17-5.08 (m, 2H), 4.49 (s, 2H), 3.72-3.46 (m, 5H), 3.39 (s, 3H), 2.65-2.52 (m, 1H), 2.07 (br.s, 1H);13C NMR (75 MHz, CDCl3): δ 136.3, 128.3, 127.5, 117.4, 81.3, 73.2, 70.3, 61.0, 58.0, 45.7; IR (Neat): 3444, 3069, 3029, 2925, 2857, 1455, 1361, 1208, 1091, 752, 698 cm-1 ; MS (ESIMS): m/z 237 (M+H+),186, 97, 95, 91, 69; HRMS (ESIMS): Calculated for C14H20O3Na, 259.1310, Found 259.1305 Procedure for (2S, 3R)-3-(benzyloxymethyl)-2-methoxypent-4-en-1-ol (13’):

(13’)

This compound was prepared according to the above procedure, as color less oil yield (94 %). [α]D

24 +11.2 (c 0.016, CHCl3); 1H NMR (300MHz CDCl3): δ 7.32-7.20 (m, 5H), 5.86-5.74 (m, 1H), 5.15-5.07 (m, 2H), 4.48 (s, 2H), 3.70-3.42 (m, 4H), 3.40-3.22 (m, 4H), 2.62-2.54 (m, 1H);13C NMR (75 MHz, CDCl3): δ 136.3, 128.3, 127.6, 117.4, 81.3, 73.2, 70.2, 61.6, 58.0, 45.7; IR (Neat): 3446, 2925, 2858, 1456, 1362, 1093 cm-1: MS (ESIMS): m/z 259 (M+Na+), 237 (M+H+),202, 186; HRMS (ESIMS): Calculated for C14H20O3Na, 259.1310, Found 259.1316. Procedure for (((R)-2-((R)-2-(allyloxy)-1-methoxyethyl) but-3-enyloxy) methyl) benzene (14): BnO

(14) A solution of 13 (150 mg, 0.635 mmol) in Dry THF(5 mL), NaH 60% (dispersion in mineral oil)(33 mg, 0.825 mmol) was added portions wise at 0 °C and stirred for 15 min. To the above stirred solution allyl bromide (85µL, 0.98 mmol) was added slowly. Stirring was continued at 0oC- rt over a period of 6 h. The reaction was quenched with water, then extract with ethyl acetate (4 X 10mL). The combined organic layers were dried over anhydrousNa2SO4.Filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was subjected to silica gel (60-120 mesh) column chromatography eluting with EtOAc 5% in hexane furnished the pure product as color less liquid (150 mg, 86%). [α]D

24 -14.5 (c 0.020, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.33-7.20 (m, 5H), 5.92-5.73 (m, 2H), 5.28-5.06 (m, 4H), 4.48 (s, 2H), 3.94 (d J = 5.3 Hz, 2H), 3.64-3.35 (m, 8H), 2.59-2.51 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 136.9, 134.8, 128.2, 127.5, 117.1, 116.7, 80.2, 73.0, 72.2, 70.4, 58.4, 46.1; IR (Neat): 3020, 2402, 1722, 1216, 1094, 759 cm-1; MS (ESIMS): 277 (M+H+); HRMS (ESIMS): Calculated for C17H24O3Na, 299.1617, Found 299.1627. Procedure for (((R)-2-((S)-2-(allyloxy)-1-methoxyethyl) but-3-enyloxy) methyl) benzene (14’): BnO

(14’) This compound was prepared according to the above procedure, starting material is 13’ instead of 13, as color less liquid yield (86 %) [α]D

24 +8.7 (c 0.020, CHCl3); 1H NMR (300 MHz CDCl3): δ 7.32-7.20 (m, 5H), 5.92-5.75 (m, 2H), 5.26-5.06 (m, 4H), 4.48 (s, 2H), 3.95(d, J = 5.3 Hz, 2H), 3.64-3.36 (m, 8H), 2.59-2.51 (m, 1H); 13C NMR (50 MHz, CDCl3): δ 138.4, 136.8, 134.7, 128.2, 127.4, 127.3, 117.0, 116.7, 80.2, 73.0, 72.2, 70.5, 70.4, 58.4, 46.1; IR (Neat): 3021, 2404, 1721,

1216, 1094, 759 cm-1; MS (ESIMS): m/z 299 (M+Na+), 294 (M+NH4+), 277 (M+H+), 180;

HRMS (ESIMS): Calculated for C17H24O3Na, 299.1617, Found 299.1628. Procedure for oxacycles (15 & 16):

(15) To a stirred solution of 14 (170 mg, 0.98 mmol) in DCM (120 mL), Grubbs (II) catalyst (42 mg, 0.049 mmol) was added and stirred at reflux for 1 h. Then solvent was removed under reduced pressure and the crude product was dissolved in ethyl acetate (2.5 mL). In another flask, a suspension of NaIO4 (139 mg, 0.652 mmol) in H2O (0.3 mL)was treated with CeCl3.7H2O (37 mg, 0.098 mmol) and heated gently until suspension was bright yellow, at this point the suspension was diluted with MeCN (2 mL) and cooled to 0 °C. To the yellow suspension metathesis solution was added and stirred at 0 °C until oxidation was complete (10-20 min). The reaction was quenched with solid Na2SO3 and Na2SO4 and after stirring for 10 min the solution was filtered through celite (1 cm plug).Celite was washed with EtOAc (3 X 5 mL).The filtrate was concentrated under reduced pressure and the crude product was dissolved in DCM (10 mL), then CSA (23 mg, 0.1 mmol) and 2, 2 DMP (0.24 mL) was added at 0 °C and stirred for overnight at rt. Then solvent was removed under reduced pressure. The crude product was subjected to silica gel (60-120 mesh) column chromatography to afford 15 & 16 as clear oil 115 mg of 15 and 77 mg of 16, total yield 61%. [α]D

24 + 2.4 (c 0.032, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.35-7.27 (m, 5H), 7.36 (m, 4H), 7.29 (m, 1H), 4.59 (dd, J =6.7 Hz, J = 9.7 Hz, 1H), 4.55 (s, 2H), 4.24 (ddd, J1 = 6.7 Hz, J2 =10.5 Hz, J3 =4.1Hz, 1H), 4.06 (dd, J1 = 11.2 Hz, J2 =2.8 Hz, 1H), 3.90 (dd, J1 = 8.4 Hz, J2 = 2.5 Hz, 1H), 3.85 (dd, J1 =12.2 Hz, J2= 4.1 Hz, 1H), 3.70 (dd, J1 = 1.9 Hz, J2 = 8.4 Hz, 1H), 3.34 (dd, J1 =12.2 Hz, J2 =10.5 Hz, H), 3.38 (s, 3H), 3.24 (m, H), 3.21 (m, H), 1.96 (m, H), 1.39 (s, 3H), 1.35 (s, 3H);13C NMR (100 MHz, CDCl3): δ 138.8, 128.2, 127.4, 107.8, 76.3, 76.1, 75.1, 74.5, 73.1, 69.7, 67.2, 58.9, 46.8, 27.6, 24.7;IR (Neat): 2930, 2859, 1457, 1385, 1105, 758 cm-1; Mass (ESIMS): 345(M+Na+), 305, 205, 116; HRMS (ESIMS): Calculated for C18H26O5Na, 345.1677, Found 345.1663.

[α]D24 + 54.5 (c 0.026, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.35-7.27 (m, 5H), 4.76

(dd, J1= 7.9 Hz, J2 = 1.6 Hz, 1H), 4.56 (d, J = 4.0Hz, 2H), 4.17 (m, 2H), 4.01 (dd, J1 = 13.7 Hz, J2 =2.9 Hz, 1H), 3.89 (dd, J1= 9.1 Hz, J2 = 4.6, 1H), 3.84 (dd, J1 =12.2 Hz, J2 = 4.1 Hz, 1H), 3.65 (dd, J1 = 9.4 Hz, J2 = 9.1 Hz, 1H), 3.51 (m, 1H), 3.40 (dd, J1 = 13.7 Hz, J2 = 2.2 Hz, 1H) 3.34 (s, 3H), 3.19 (dd, J1 = 12.1Hz, J2 = 9.1 Hz, 1H), 2.18 (m, 1H), 1.49 (s, 3H), 1.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 138.8, 128.2, 127.4, 107.8, 76.3, 76.1, 75.1, 74.3, 73.1, 69.7, 67.2, 58.9, 46.8, 27.5, 24.7; IR (Neat): 2930, 2859, 1457, 1385, 1105, 758 cm-1; MS (ESIMS): 345 (M+Na+), 305, 205, 116; HRMS (ESIMS): Calculated for C18H26O5Na, 345.1677, Found 345.1661. Procedure for oxacycles (17 & 18):

(17) These compound were prepared according to the above procedure, starting material is 14’ instead of 14, yield (61 %) [α]D

24 -1.8 (c 0.028, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.35-7.26 (m, 5H), 4.58 (dd, J1 = 6.7 Hz, J2 = 9.7 Hz, 1H), 4.55 (s, 2H), 4.05 (dd, J1 = 11.4 Hz, J2 = 2.9 Hz, 1H), 3.90 (dd, J1 = 8.5 Hz, J2 = 2.4 Hz, 1H), 3.84 (dd, J1 = 12.2 Hz, J2 = 4.1 Hz, 1H), 3.70 (dd, J1 = 2.0 Hz, J2 = 8.5 Hz, 1H), 3.34 (dd, J1 =12.2 Hz, J2 =10.5 Hz, 1H), 3.38 (s, 3H), 3.24 (m, H), 3.21 (m, H), 1.96 (m, H), 1.39 (s, 3H), 1.35 (s, 3H);13C NMR (100 MHz, CDCl3): δ 128.2, 127.4, 127.4, 107.9, 76.3, 76.1, 75.1, 74.3, 73.1, 69.7, 67.2, 58.9, 46.8, 27.5, 24.8; IR (Neat): 2930, 2859, 1457, 1385, 1105, 758 cm-1: MS (ESIMS): 345 (M+Na+), 305, 205, 116; HRMS (ESIMS): Calculated for C18H26O5Na, 345.1675, Found 345.1684.

(18) [α]D

24 -55.2 (c 0.020, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.35-7.26 (m, 5H), 4.58 (dd, J1 = 6.7 Hz, J2=9.7 Hz, 1H), 4.55 (s, 2H), 4.05 (dd, J1 = 11.4 Hz, J2 = 2.9 Hz, 1H), 3.90 (dd, J1 = 8.5 Hz, J2 = 2.4 Hz, 1H), 3.84 (dd, J1 = 12.2 Hz, J2 = 4.1 Hz, 1H), 3.70 (dd, J1 = 2.0 Hz, J2 = 8.5 Hz, 1H), 3.34 (dd, J1 =12.2 Hz, J2 = 10.5 Hz, 1H), 3.38 (s, 3H), 3.24 (m, H), 3.21 (m, H), 1.96 (m, H), 1.39 (s, 3H), 1.35 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 138.5, 128.3, 127.5, 107.4, 77.5, 76.9, 74.2, 73.2, 73.2, 72.6, 68.9, 58.8, 45.0, 26.4, 24.3; IR (Neat): 2930, 2859, 1457, 1385, 1105, 758 cm-1; MS (ESIMS) 345(M+Na+), 305, 205, 116; HRMS (ESIMS): Calculated for C18H26O5Na, 345.1677, Found 345.1663.

CH3 CH3

Procedure for (2R, 3R)-3-(benzyloxymethyl)-2-methoxypent-4-enal (19): BnO

O (19) To the mixture of alcohol 13 (550 mg, 2.33 mmol), IBX (716 mg), dry DMSO (2 mL) dry DCM (25 mL) was added at rt. This mixture was allowed to stir at rt for 8 h. Then solvent was removed under reduced pressure. The crude product was subjected to silica gel (60-120 mesh) column chromatography to afford pure aldehyde as clear liquid (490 mg, 90%). [α]D

24 -17.6 (c 0.017, CHCl3); 1H NMR (300MHz CDCl3): δ, 9.62(s, 1H), 7.32-7.22(m, 5H), 5.84-5.72 (m, 1H), 5.19-5.12 (m, 2H), 4.44 (d J=4.5, 2H), 3.62-3.54 (m, 2H), 3.46-3.42 (m, 4H), 2.91-2.82 (m, 1H); 13C NMR (75 MHz): δ 203.4, 134.6, 128.3, 127.7, 118.0, 86.3, 73.0, 68.6, 59.2, 46.6; IR (Neat): 3433, 3066, 2925, 2861, 1727, 1642, 1454, 1364, 1172, 1101, 742, 700 cm-1.

Procedure for (2S, 3R)-3-(benzyloxymethyl)-2-methoxypent-4-enal (19’): BnO

O (19’) This compound was prepared according to the above same procedure, starting material is 13’ instead of 13, as color less oil yield (90 %) [α]D

24 -9.0 (c 0.014, CHCl3); 1H NMR (200 MHz, CDCl3): δ 9.62 (s, 1H),7.30-7.22 (m, 5H), 5.78 (ddd, J1=8.1 Hz, J2 = 10.3 Hz, J3 = 18.4 Hz, 1H), 5.21-5.11 (m, 2H), 4.44 (d, J = 2.9 Hz, 2H), 3.64-3.53 (m, 2H), 3.48-3.40 (m, 4H), 2.93-2.80 (m, 1H);13C NMR (75 MHz, CDCl3): δ 202.1, 134.8, 128.2, 127.4, 117.8, 96.2, 86.3, 73.0, 68.7, 59.1, 46.8; IR (Neat): 2925, 2858, 1731, 1455, 1197, 1097, 740 cm-1. Procedure for (5R, 6R)-6-(benzyloxymethyl)-5-methoxyocta-1, 7-dien-4-ol (20): BnO

(20) A mixture of AgOTf (0.036 mmol) and (S)-BINAP (0.036 mmol) was dissolved in dry THF (1 mL) under N2 atmosphere and exclusion of direct light, and stirred at 20 oC for 10 min. To the resulting solution was added a THF solution (1 mL) of aldehyde 19 (0.363 mmol) and then allyltributyltin (0.363 mmol) was added dropwise at -20 oC. The mixture

was stirred for 8 h at this temperature and treated with a mixture of 1 N HCl (2 mL) and solid KF (0.18 g) at ambient temperature for 30 min. The resulting precipitate was filtered and the filtrate was separated and the aqs layer was extracted with ethyl acetate (3 X 10 mL), the combined organic layers were dried over anhydrousNa2SO4, filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was subjected to silicagel (230-400 mesh) column chromatography eluting with EtOAc 5% in hexane furnished the pure product as a color less oil 61 % yield (diasteomeric ratio 49 mg and 12 mg). [α]D

24 -16.7 (c 0.010, CHCl3); 1H NMR (200 MHz, CDCl3): δ 7.36-7.21 (m, 5H), 5.96-5.75 (m, 2H), 5.16-5.06 (m, 4H), 4.52 (d, J = 2.2 Hz, 2H), 3.72-3.61 (m, 2H), 3.60-3.49 (m, 1H), 3.42 (s, 3H), 3.22 (t, J = 5.1 Hz, 1H), 2.71-2.59 (m, 2H), 2.42-2.30 (m, 1H);13C NMR (75 MHz, CDCl3): δ 137.3, 135.3, 128.4, 127.7, 117.4, 116.7, 85.0, 73.3, 71.1, 70.0, 60.1, 45.6, 37.4, 27.8, 26.8, 17.5, 13.6; MS (ESIMS): 277 (M+H+), 294(M+NH4

+), 299 (M+Na+); HRMS (ESIMS): Calculated for C17H24O3Na 299.1623, found 299.1617. Procedure for (5S, 6R)-6-(benzyloxymethyl)-5-methoxyocta-1, 7-dien-4-ol (20’): BnO

20' This compound was prepared according to the above procedure, starting material is 19’ instead of 19, as color less oil with same yield and diastereomeric ratio. [α]D

24 +15.4 (c 0.006, CHCl3); 1H NMR (200 MHz, CDCl3): δ 7.36-7.21 (m, 5H), 5.95-5.75 (m, 2H), 5.15-5.05 (m, 4H), 4.50 (d, J = 2.2 Hz, 2H), 3.73-3.18 (m, 7H), 2.70-2.58 (m, 2H), 2.34-2.29 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 137.3, 135.3, 128.4, 127.7, 117.4, 116.7, 85.0, 73.3, 73.3, 70.0, 60.1, 45.6, 37.4, 29.7, 27.8, 26.8, 17.5, 13.6; MS (ESIMS): 277(M+H+), 294(M+NH4

+), 299 (M+Na+); HRMS (ESIMS): Calculated for C17H24O3Na 299.1623, found 299.1627. Procedure for carbocycle (21): BnO

MeOOH(21)

To a stirred solution of 20 (50 mg,0.18 mmol) in DCM (20 mL) Grubbs (II) catalyst (5 mg,0.0054 mmol) was added and stirred at reflux for 45 min. The solvent was removed under reduced pressure and the crude product was purified by silicagel (60-120 mesh) column chromatography eluting with EtOAc 12% in hexane furnished the pure product 35 mg (yield 78 %) as oily liquid. [α]D

24 +77.0 (c 0.006, CHCl3); 1H NMR (500 MHz, CDCl3): δ, 7.36-7.26 (m, 5H), 5.66-5.58 (m, 2H), 4.54 (dd, J1 = 12.4 Hz, J2 =29.3 Hz, 2H), 4.15-4.13(m, 1H), 3.57-3.49 (m,

2H), 3.40 (dd, J1 =2.2 Hz, J2 =7.3 Hz, 1H), 2.62-2.58 (m, 1H), 2.35-2.27 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 138.4, 128.3, 127.6, 126.6, 124.4, 96.1, 79.4, 73.1, 70.7, 64.5, 56.9, 38.8, 31.3; MS (ESIMS): 249 (M+H+), 266 (M+NH4

+), 299; HRMS (ESIMS): Calculated for C15H20O3Na 271.1310, found 271.1324. Procedure for carbocycle (22): BnO

(22) This compound was prepared according to the above procedure, starting material is 20’ instead of 20, as oily liquid with same yield. [α]D

24 -23.3 (c , 0.002, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.36-7.27 (m, 5H), 5.64-5.54 (m, 2H), 4.55 (dd J1=12.5, J2=25.5, 2H), 3.86-3.81 (m, 1H), 3.63-3.54 (m, 2H), 3.49 (s, 3H), 3.24 (t, J = 8.3 Hz, 1H), 2.72 (br.s, 1H), 2.52-2.39 (m, 2H), 2.16-2.09 (m, 1H); MS (ESIMS): 249 (M+H+), 266 (M+NH4

+), 299; HRMS (ESIMS): Calculated for C15H20O3Na 271.1310, found 271.1332. b) Compounds generated by using (R)-phenylethylene glycol Procedure for (R, Z)-2-(4-methoxybut-2-enyloxy)-1-phenylethanol(4):

(4) This compound was prepared according to the general procedure A as color less oil(yield 53.4 %). [α]D

24 +35.0 (c 0.039, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.36-7.25 (m, 5H), 5.76-5.65 (m, 2H), 4.83 (dd, J1 = 3.0 Hz, J2 = 8.9 Hz, 1H), 4.12-4.11 (m, 2H), 3.98-3.93 (m, 2H), 3.56 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 3.39 (t, J = 9.1 Hz, 1H), 3.29 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 129.4, 129.0, 128.4, 128.2, 127.6, 126.8, 126.0, 75.7, 72.6, 66.6, 57.9; IR (Neat): 3466, 3062, 3031, 2926, 2877, 1731, 1454, 1190, 701 cm-1; MS (ESIMS): 245(M+Na+), 85. Procedure for (R, Z)-2-(4-methoxybut-2-enyloxy)-1-phenylethyl 3-oxobutanoate:

This compound was prepared according to the general procedure B, (yield 79.9 %) as yellow oil. [α]D

24 +33.0 (c 0.056, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.40-7.30 (m, 5H), 5.99 (dd, J1 =3.8 Hz, J2 =8.3 Hz, 1H),4.74-5.61 (m, 2H), 4.13-4.06 (m, 2H), 3.98-3.94 (m, 2H), 3.74 (dd, J1 = 8.3 Hz, J2 = 11.3 Hz, 1H), 3.64-3.58 (m, 1H),3.46 (s, 2H), 3.31 (s, 3H), 2.25 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 166.2, 129.5, 128.7, 128.4, 128.3, 126.8, 126.5, 78.6, 75.2, 72.4, 67.9, 66.6, 64.3, 57.825, 50.1, 29.7; IR (Neat): 3453, 2925, 1717, 1360, 1201, 1151, 763, 700 cm-1; MS (ESIMS) 329(M+Na+). Procedure for (R, Z)-2-(4-methoxybut-2-enyloxy)-1-phenylethyl 2-diazoacetate(1):

OOMeON2

(1) This compound was prepared according to the general procedure C, as light yellow oil (yield 79.1 %).[α]D

24 +13.6 (c 0.068, CHCl3); 1H NMR (300 MHz CDCl3): δ 7.37-7.26 (m, 5H), 5.98 (dd, J1 = 3.8 Hz, J2 = 8.3 Hz, 1H), 5.71-5.61 (m, 2H), 4.79 (br.s, 1H), 4.11-4.01 (m, 2H), 3.96-3.88 (m, 2H), 3.70 (dd, J1 = 7.6 Hz, J2 = 10.6 Hz, 1H), 3.61-3.56 (m, 1H),3.28 (s, 3H); 13C NMR (75 MHz, CDCl3): δ, 137.3, 129.6, 128.8, 128.4, 128.2, 126.5, 78.9, 74.6, 72.6, 68.0, 66.6, 64.3, 46.3; IR (Neat): 3443, 3031, 2925, 2113, 1729, 1453, 1378, 1188, 1090.5, 702.7 cm-1; MS (ESIMS): 313(M+Na+);HRMS (ESIMS): Calculated for C15H18N2O4Na, 313.1164, Found 313.1167. Procedure for (3R, 6R, 7R)-6-methoxy-3-phenyl-7-vinyl-1, 4-dioxocan-5-one (2) and (3R, 6S, 7R)-6-methoxy-3-phenyl-7-vinyl-1, 4-dioxocan-5-one (3): These compounds were prepared according to the general procedure D. Syn (yield 41 %) and anti (yield 27 %) as a color less oil and (R, Z)-2-(4-methoxybut-2-enyloxy)-1-phenylethanol (yield 15 %) also recovered.

Syn (2) [α]D

24 +30.0 (c 0.003, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.40-7.33 (m, 5H), 6.27 (m, 1H), 6.00-5.84 (m, 1H), 5.24-5.19 (m, 2H), 4.11-4.07 (m, 2H)3.96-3.85 (m, 1H), 3.75-3.70 (m, 1H), 3.50-3.43 (m, 4H), 3.12-3.04 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 135.2, 133.4, 128.6, 126.4, 118.4, 80.4, 58.3, 50.2, 49.8.IR (Neat) 3448, 3033, 2928, 1743, 1454, 1226, 1094, 762, 699 cm-1; MS (ESIMS) 285.5(M+Na+);HRMS (ESIMS): Calculated for C15H18O4Na, 285.1102, Found 285.1107.

Anti (3) [α]D

24 +72.50 (c 0.002, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.38-7.25 (m, 5H), 5.74 (ddd, J1 =8.5 Hz, J2 = 10.2 Hz, J3 = 17.4 Hz, 1H), 5.24-5.14 (m, 2H), 4.04-3.79 (m, 4H), 3.45 (s, 3H), 3.34 (dd, J1 = 10.39 Hz, J2 = 12.09 Hz, 1H), 3.07-2.95 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 134.2, 128.7, 126.3, 117.8, 84.6, 81.4, 79.2, 74.4, 72.8, 58.3, 53.3; IR (Neat): 3448, 3033, 2928, 1743, 1454, 1226, 1094, 762, 699 cm-1; MS (ESIMS): 285.5 (M+Na+);HRMS (ESIMS): Calculated for C15H18O4Na, 285.1102, Found 285.1099. c) Cyclopropanation Procedure for (1R, 2R)-2-(allyloxy)-1, 2-diphenylethanol (11):

OHPh (11) To a solution of (1R, 2R)-1, 2-diphenylethane-1, 2-diol diol (2.7g, 12.62 mmol) in THF (25mL) was added NaH (60 % disersion in mineral oil) (600 mg, 15.14 mmol) portions wise at 0 oC. To this stirred mixture allyl bromide (1.3mL, 15.14mmol) was added dropwise at same temparature. This mixture was allowed to stir 0 °C – rt for overnight. The reaction mixture was quenched with water till the mixture become clear. This mixture was extracted with Ethyl acetate (4 x 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered the contents and concentrated under reduced pressure yielded crude product. The crude product was subjected to silicagel (60-120 mesh) column chromatography eluting with EtOAc 8 % in hexane furnished the pure product as colorless viscous liquid (2.56g, 80%). [α]D

25 +45.2 ˚ (c 0.021, CHCl3 ); 1H NMR (300 MHz, CDCl3): δ 7.17-7.10 (m, 6H), 6.97-6.93 (m, 4H), 5.95-5.82 (m,1H), 5.26-5.14 (m, 2H), 4.62 (d, J = 8.3Hz, 1H), 4.22 (d , J = 8.3 Hz, 1H), 3.97 (dd , J1 = 5.3, J2 = 12.8 Hz, 1H), 3.80 (dd, J1 = 6.0, J2 = 12.8 Hz, 1H), 3.48 (s, 1H); 13C NMR (75 MHz, CDCl3): δ 134.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4, 127.2, 117.3, 86.7, 78.5, 69.7; IR (Neat): 3461, 2869, 1722, 1452, 1078, 763, 762, 700 cm-1; HRMS (ESIMS): calculated for C17H18O2Na, 277.1204, found 277.1202.

Procedure for (1R, 2R)-2-(allyloxy)-1, 2-diphenylethyl-3-oxobutanoate:

This compound was prepared according to the general procedure B. as yellow liquid (Yield 80 %).[α]D

25 -32.0 ˚ (c 0.012 , CHCl3 ); 1H NMR (300 MHz, CDCl3): δ 7.17-7.11 (m, 6H), 7.03-7.00 (m, 4H), 5.93(d, J = 8.3 Hz, 1H), 5.89-5.73 (m, 1H), 5.22-5.07 (m,2H), 4.53 (d, J = 7.5 Hz, 1H), 3.94 (dd, J1 = 4.5, J2 = 12.8 Hz, 1H), 3.76 (dd, J1 = 6.0, J2 = 13.6 Hz, 1H), 3.41 (s, 2H) 2.20 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 200.4, 166.0, 134.3, 128.3, 128.2, 128.1, 128.0, 127.8, 127.7, 127.6, 127.4, 127.3, 116.7, 83.2, 79.4, 69.6, 50.3, 29.8; IR (Neat): 3447, 2925, 1743, 1718, 1238, 1148, 1075, 701 cm-1; HRMS (ESIMS): calculated for C21H22O4Na, 361.1415, found 361.1412. Procedure for (1R, 2R)-2-(allyloxy)-1.2-diphenylethyl 2-diazoacetate (9):

N (9) This compound was prepared according to the general procedure C. as light yellow oil (Yield 90 %). [α]D

25 +18.0 ˚ (c 0.030, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.22-7.16 (m, 6H), 7.06-7.04 (m, 4H), 6.00 (d, J = 6.8 Hz, 1H), 5.89-5.77 (m, 1H), 5.31 -5.14 (m, 2H), 4.79 (s,1H), 4.57 (d, J = 6.8 Hz, 1H), 4.01 (dd, J1 = 4.5, J2 = 12.8 Hz, 1H), 3.79 (dd, J1 = 6.0, J2 = 13.6 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ137.3, 134.4, 128.1, 127.9, 127.7, 127.3, 127.2, 116.5, 83.0, 78.5, 69.6, 46.3; HRMS (ESIMS): calculated for C19H18N2O3Na, 345.1215, found 345.1211. Procedure for (1S, 4R, 5R, 8R)-4, 5-diphenyl-3, 6-dioxa – bicycle [6.1.0] nonan – 2 – one (10):

O (10)

A solution of diazoacetate 9 (2.73 mmol) in DCM (60 mL) was added by syringe pump to a solution of Tetrakis (acetonitrile) copper (I) hexaflorophosphate (51 mg, 5 mol %) in DCM (60 mL) under reflux condition for 5 h. The reaction mixture was allowed to rt, then solvent was removed under reduced pressure. The crude product was subjected to silicagel (100-200 mesh) column chromatography eluting with EtOAc in hexane furnished the pure product as white solid. (Yield 50 %) and the alcohol (1R, 2R)-2-(allyloxy)-1, 2-diphenylethanol (yield 15%) also recovered. Mp 118˚C; [α]D

25 -26.5 ˚ (c 0.010, CHCl3 ); 1H NMR (300 MHz, CDCl3): δ 7.25-7.21 (m, 6H), 7.05-6.99 (m, 4H), 5.89 ( d, J = 9.82 Hz, 1H), 4.79 ( d, J = 9.1 Hz, 1H), 4.29-4.26 (m, 1H), 3.75-3.69 (m, 1H), 1.98-1.89 (m, 2H), 1.78 (q, J = 5.3 Hz, 1H), 1.36-1.31 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 176.4, 138.0, 136.3, 128.3, 127.3, 127.1, 93.6, 85.0, 75.9, 24.3, 19.2, 18.0; IR (KBr): 3031, 2924, 1709, 1265, 1079, 1002, 759, 699 cm-1; HRMS (ESIMS): calculated for C19H18O3Na, 3317.1153, found 317.1159.

2) 1H, 13C and NOESY NMR SPECTRA a) Compounds generated by using (1R, 2R)-1, 2-diphenylethane-1, 2-diol

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

Ph OOMe

Compound (8a) 1H NMR 200 MHz, CDCl3.

3030404050506060707080809090100100110110120120130130140140150150160160

Ph OOMe

Compound (8a) 13C NMR 75 MHz, CDCl3.

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

Ph OOMeO

Compound 1H NMR 300 MHz, CDCl3.

20203030404050506060707080809090100100110110120120130130140140150150160160170170180180190190200200

R1 OOMe

Compound 13C NMR 75 MHz, CDCl3.

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

Ph OOMeON2

20203030404050506060707080809090100100110110120120130130

Ph OOMeON2

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

50506060707080809090100100110110120120130130140140150150160160170170

Compound (6a) NOESY

0.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

19 2010 10

2312 13

50506060707080809090100100110110120120130130140140150150160160170170

Compound (7a) 13 NMR 100 MHz, CDCl3.

Compound (7a) NOESY

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

OTBDMSMeO

Compound (12) 1H NMR 300 MHz, CDCl3.

-10-1000101020203030404050506060707080809090100100110110120120130130140140

OTBDMSMeO

Compound (12) 13C NMR 75 MHz, CDCl3.

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

13 1209

OTBDMSMeO

Compound (13’) 1H NMR 300 MHz, CDCl3.

00101020203030404050506060707080809090100100110110120120130130

OTBDMSMeO

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

OTBDMSMeO

0.600.60 0.800.80 1.001.00 1.201.20 1.401.40 1.601.60

OTBDMSMeO

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

OTBDMSMeO

-10-1000101020203030404050506060707080809090100100110110120120130130

OTBDMSMeO

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

707080809090100100110110120120130130140140150150160160

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

2.1 2.2

4.3 4.0

1.0 0.8

50506060707080809090100100110110120120130130140140

Compound (13’) 13C NMR 75 MHz, CDCl3.

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

50506060707080809090100100110110120120130130140140

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

50506060707080809090100100110110120120130130140140

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

3030404050506060707080809090100100110110120120130130140140

Compound (15) NOESY

0.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

3030404050506060707080809090100100110110120120130130140140

Compound (16) NOESY

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

1020 22

3030404050506060707080809090100100110110120120130130

Compound (17) NOESY

0.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

10 10 10 10 10

3030404050506060707080809090100100110110120120130130140140

Compound (18) NOESY

00112233445566778899

50506060707080809090100100110110120120130130140140150150160160170170180180190190200200

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.58.08.08.58.59.09.09.59.5

CHOMeO

50506060707080809090100100110110120120130130140140150150160160170170180180190190200200

CHOMeO

Compound (19’) 13C NMR 75 MHz, CDCl3.

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

20203030404050506060707080809090100100110110120120130130140140

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

20203030404050506060707080809090100100110110120120130130140140

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

20203030404050506060707080809090100100110110120120130130

Compound (21) NOESY

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

3030404050506060707080809090100100110110120120130130140140

Compound (22) NOESY

b) Compounds generated by using (R)-phenylethylene glycol

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

1018 14 10 08

6060707080809090100100110110120120130130

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

091016

20203030404050506060707080809090100100110110120120130130140140150150160160170170180180190190200200

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

111014

O OON2

50506060707080809090100100110110120120130130140140

OOMeON2

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

50506060707080809090100100110110120120130130

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

50506060707080809090100100110110120120130130140140

c) Cyclopropanation

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

707080809090100100110110120120130130140140150150

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

00252550507575100100125125150150175175200200

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.58.08.0

OPh CHN2

404050506060707080809090100100110110120120130130140140150150

OPh CHN2

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

Compound(10)1H NMR 300 MHz, CDCl3.

Compound (10) NOESY

3) SPCTRAL DATA a) Compounds generated by using (1S, 2S)-1, 2-diphenylethane-1, 2-diol

6a” Whit solid, M.P 115 oC; [α]D

24 +60.7 (c 0.008, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.25-7.14 (m, 6H), 7.08-7.04 (m, 2H), 6.95-6.92 (m, 2H), 6.13 (ddd, J1 = 17.0 Hz, J2 = 11.0 Hz, J3 = 8.7 Hz, 1H), 5.94 (d, J = 9.3 Hz,1H) 5.28 (m, 1H), 5.26 (m, 1H), 4.38 (d, J = 9.2 Hz, 1H), 4.22 (dd, J1= 11.4 Hz, J2= 5.8 Hz, 1H), 4.16 (d, J = 5.7 Hz, 1H), 3.93 (dd, J1= 11.4 Hz, J2= 1.6 Hz, 1H), 3.52 (s, 3H), 3.26 (m, 1H); 13C NMR (75 MHz): δ 174.1, 137.0, 135.2, 133.7, 128.6, 128.3, 128.0, 127.6, 127.3, 118.4, 58.4, 50.2.

7a” [α]D

24 -138.9 (c 0.004, CHCl3); 1H NMR (500 MHz, CDCl3): δ 7.25-7.21 (m, 3H), 7.18-7.16 (m, 3H), 7.10-7.07 (m, 2H), 6.95-6.92 (m, 2H), 6.02 (d ,J = 9.2 Hz, 1H), 5.82 (ddd , J1 = 17.4 Hz, J2= 10.4 Hz , J3= 8.4 Hz, 1H) 5.22 (td, J1 = 17.3 Hz, J2 = 1.4 Hz, 1H), 5.18 (td, J1 = 10.4 Hz , J2 = 1.4 Hz, 1H), 4.35 (d, J= 9.2 Hz, 1H), 4.16 (t, J = 10.6 Hz , 1H), 4.05 (dd, J1 = 10.7 Hz, J2= 3.0 Hz, 1H), 4.02 (d, J = 3.16 Hz, 1H), 3.48 (s , 3H), 3.15 (m, 1H); 13C NMR (50MHz): δ 175.4, 137.2, 135.4, 134.1, 129.1, 128.1, 127.4, 117.8, 91.7, 86.7, 81.7, 73.6, 58.3, 52.5.

15” [α]D

24 -15.0 (c 0.001, CHCl3); 1H NMR (500 MHz CDCl3): δ 7.29-7.21 (m, 5H), 4.58 (dd, J1= 6.66 Hz, J2 = 9.7 Hz, 1H), 4.55 (s, 2H), 4.24 (ddd, J1= 6.7 Hz, J2= 10.5 Hz, J3 = 4.1 Hz, 1H), 4.05 (dd, J1 = 11.4 Hz, J2 = 2.9 Hz, 1H), 3.90 (dd, J1 = 8.5 Hz, J2 = 2.4 Hz, 1H), 3.84 (dd, J1= 12.2 Hz, J2 = 4.1 Hz, 1H), 3.70 (dd, J1 = 2.0 Hz, J2 = 8.5 Hz, 1H), 3.38 (s, 3H), 3.34 (dd, J1 = 12.2 Hz, J2 = 10.5 Hz, 1H), 3.24 (m, 1H), 3.21 (m, 1H), 1.96

H H HH

CH3CH3

(m, 1H),1.39 (s, 3H), 1.35 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 138.6, 128.2, 127.4, 127.4, 107.8, 96.0, 76.0, 76.0, 75.0, 74.2, 73.0, 69.6, 67.0, 59.0, 46.6, 27.5, 24.7.

17” [α]D

24 -6.2 (c 0.004, CHCl3); 1H NMR (500 MHz,CDCl3): δ 7.36-7.29 (m, 5H), 4.59 (dd, J1= 6.7 Hz, J2 = 9.7 Hz, 1H), 4.55 (s, 2H), 4.24 (ddd, J1 = 6.7 Hz, J2 = 10.5 Hz, J3 = 4.1 Hz, 1H), 4.06 (dd, J1 = 11.2 Hz, J2 = 2.8 Hz, 1H), 3.90 (dd, J1 = 8.4 Hz, J2 = 2.5 Hz, 1H), 3.85 (dd, J1 = 12.2 Hz, J2 = 4.06 Hz, 1H), 3.70 (dd, J1 = 1.9 Hz, J2 = 8.4 Hz, 1H), 3.38 (s,3H), 3.34 (dd, J1 = 12.2 Hz, J2 = 10.5 Hz, 1H), 3.24, (m, 1H), 3.21 (m, 1H), 1.96 (m, 1H),1.40(s, 3H) ,1.35 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 138.8, 127.4, 107.9, 76.2, 74.3, 7.12, 7.72, 7.14, 59.0, 46.7, 27.5, 24.8.

CH3CH3

4) 1H, 13C and NOESY NMR SPECTRA

0.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.0

Compound (6a”) 1H NMR 500 MHz, CDCl3.

6060707080809090100100110110120120130130140140150150160160170170

Compound (6a”) NOESY

0.00.00.50.51.01.01.51.52.02.02.52.53.03.03.53.54.04.04.54.55.05.05.55.56.06.06.56.57.07.07.57.5

50506060707080809090100100110110120120130130140140150150160160170170

Compound (7a”) NOESY

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5

Compound (15”) 1H NMR 600 MHz, CDCl3.

Compound (15”) 13C NMR 150 MHz, CDCl3.

Compound (15”) NOESY

Compound(17”) 1H NMR 600 MHz, CDCl3.

Compound(17”) 13H NMR 150 MHz, CDCl3.

Compound (17”) NOESY

5) Chiral HPLC Analysis HPLC Analysis of Racemic 6a Conditions: λ=210 nm, mobile phase: 95:5 (nHex:IPA), Flow:1mL/min

HPLC Analysis of 6a Conditions: λ=210 nm, mobile phase: 95:5 (nHex:IPA), Flow:1mL/min

HPLC Analysis of 6a” Conditions: λ=210 nm, mobile phase: 95:5 (nHex:IPA), Flow:1mL/min

HPLC Analysis of Racemic 7a Conditions: λ=210 nm, mobile phase: 99:1 (nHex:IPA), Flow:0.7mL/min

HPLC Analysis of 7a Conditions: λ=210 nm, mobile phase: 99:1 (nHex:IPA), Flow:0.7mL/min

HPLC Analysis of 7a” Conditions: λ=210 nm, mobile phase: 99:1 (nHex:IPA), Flow:0.7mL/min

HPLC Analysis of racemic 2 Conditions: λ=210 nm, mobile phase: 98:2 (nHex:IPA), Flow:1mL/min

HPLC Analysis of 2 Conditions: λ=210 nm, mobile phase: 98:2 (nHex:IPA), Flow:1mL/min

HPLC Analysis of Racemic 3 Conditions: λ=210 nm, mobile phase: 98:2 (nHex:IPA), Flow:1mL/min

HPLC Analysis of 3 Conditions: λ=210 nm, mobile phase: 98:2 (nHex:IPA), Flow:1mL/min

HPLC Analysis of Racemic 10 Conditions: λ=254 nm, mobile phase: 95:5 (nHex:Ethanol), Flow:1mL/min

HPLC Analysis of 10 Conditions: λ=254 nm, mobile phase: 95:5 (nHex:Ethanol), Flow:1mL/min

6) X-ray Crystallographic analysis of 10 Crystal data for 10 C19H18O3 M = 294.33, orthorhombic, space group P212121, a = 10.1848(8) Å, b = 17.5488(14) Å, c = 8.8167(7) Å, V = 1575.8(2) Å3, ρcalc = 1.241 g m-3, λ= 0.71073Å, µ(Mo Kα ) = 0.083 mm-1, F000 = 624, T = 294(2) K. Total number of measured reflections is 15193. Rint = 0.0185. Final refinement to convergence on F2 gave R= 0.0329 (1541 obs. data only) and Rw = 0.0932 (1616 unique data), GOF = 1.042. CCDC reference number 690682.

highly enantioselective carbon-carbon bond …supporting information page no 1) experimental...

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