Stereoselective synthesis of conjugated trienols from allylic alcohols and 1-iodo-1,3-dienes

Transcription

1 Stereoselective synthesis of conjugated trienols from allylic alcohols and 1-iodo-1,3-dienes Damien Brandt, Véronique Bellosta, and Janine Cossy* Laboratoire de Chimie rganique, ESPCI, CNRS, 10 rue Vauquelin, Paris Cedex 05, France Table of contents I. General Experimental Methods S2 II. Experimental and Spectral data S3-S33 III. Copies of 1 H NMR & 13 C NMR S34-S91 S1

2 General experimental methods Infrared (IR) spectra were recorded on a Bruker TENSRTM 27 (IRFT) on an ATR plate, wavenumbers are indicated in cm -1. NMR was performed on a Bruker Avance instrument. 1 H NMR spectra were recorded at 400 MHz in CDCl 3 or deuterated benzene (C 6 D 6 ) and data are reported as follows: chemical shift in ppm from tetramethylsilane as an internal standard, multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, quint = quintuplet, m = multiplet or overlap of non-equivalent resonances, br = broad), integration. 13 C NMR spectra were recorded at 100 MHz in CDCl 3 or deuterated benzene (C 6 D 6 ) and data are reported as follows: chemical shift in ppm from tetramethylsilane with the solvent as an internal indicator (CDCl 3 : ppm or C 6 D 6 : ppm), multiplicity, with respect to proton (deduced from DEPT experiment, s = quaternary, d = CH, t = CH 2, q = CH 3 ). In some cases, chemical shift of the carbon substituted by a boron atom could not be determined due to the carbon-boron coupling. High resolution mass spectra (HRMS) were performed by the Groupe de Spectrométrie de Masse de l Université Pierre et Marie Curie (Paris-France). ptical rotations were measured with a Perkin Elmer model 343 polarimeter with a 1 dm path length. TLC was performed on Merck 60F254 silica gel plates with UV and p-anisaldehyde stain visualization. Flash chromatography was performed on silica gel ( mesh). CH 2 Cl 2 was distillated from CaH 2, Et 2 and THF were distillated from Na/benzophenone. S2

3 (Hex-5-yn-1-yloxy)methylbenzene (4a) 4a C 13 H 16 Mol. Wt.: Sodium hydride (224 mg, 60%wt in mineral oil, 5.60 mmol, 1.1 equiv) was washed with pentane and then suspended in THF (10 ml) at rt and a solution of hex-5-yn-1-ol (500 mg, 5.10 mmol, 1.0 equiv) in THF (1 ml) was added via cannula. After 2 h stirring at rt, a solution of benzyl bromide (636 L, 5.35 mmol, 1.05 equiv) in THF (3 ml) was added via cannula. After 17 h at rt the reaction mixture was filtered through a pad of silica gel and the filtrate was evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 99/1) to afford benzyl ether 4a (795 mg, 4.23 mmol, 83%) as a colorless oil. Spectroscopic and physical data matched the ones reported in the literature. 1 IR (pur): 3297, 3031, 2939, 2860, 1496, 1454, 1361, 1205, 1105, 1028, 917, 735, 697, 630 cm H NMR (400 MHz, CDCl 3 ): (m, 5H), 4.50 (s, 2H), 3.49 (t, 2H, 3 J = 6.2 Hz), 2.21 (td, 2H, 3 J = 7.0, 4 J = 2.6 Hz), 1.94 (t, 1H, 4 J = 2.7 Hz), 1.73 (m, 2H), 1.63 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): (s), (d, 2CH), (d, 2CH), (d), 84.4 (s), 72.9 (t), 69.8 (t), 68.4 (d), 28.8 (t), 25.3 (t), 14.2 (t). MS (EI, 70 ev) m/z (abundance): 188 (M +, 2), 187 (10), 105 (14), 92 (14), 91 (100), 79 (13), 67 (12), 65 (15). tert-butyl-(hex-5-yn-1-yloxy)-diphenylsilane (4b) 4b C 22 H 28 Mol. Wt.: To a solution of hex-5-yn-1-ol (1.0 g, mmol, 1.0 equiv) in dichloromethane (20 ml) at 0 C was added imidazole (1.387 g, mmol, 2.0 equiv). After 10 min stirring at 0 C, tert-butyldiphenylsilyl chloride (3.361 g, mmol, 1.2 equiv) was added. After 17 h from 0 C to rt, the reaction was quenched with water (50 ml). The layers were separated and the aqueous phase was extracted with CH 2 Cl 2 (3 50 ml). The combined organic extracts were 1 Altman, R. A.; Nilsson, B. L.; verman, L. E.; Read de Alaniz, J.; Rohde, J. M.; Taupin, V. J. rg. Chem. 2010, 75, S3

4 washed with brine (100 ml), dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 99/1) to afford silyl ether 4b (3.39 g, mmol, 99%) as a colorless oil. Spectroscopic and physical data matched the ones reported in the literature. 2 IR (pur): 3307, 3071, 2932, 2858, 1472, 1428, 1389, 1361, 1188, 1107, 1008, 975, 823, 740, 700, 687, 613 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), (m, 6H), 3.72 (t, 2H, 3 J = 5.9 Hz), 2.22 (td, 2H, 3 J = 6.7, 4 J = 2.6 Hz), 1.96 (t, 1H, 4 J = 2.6 Hz), (m, 4H), 1.09 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (d, 4CH), (s, 2C), (d, 2CH), (d, 4CH), 84.6 (s), 68.3 (d), 63.3 (t), 31.6 (t), 26.9 (q, 3Me), 25.0 (t), 19.3 (s), 18.2 (t). MS (EI, 70 ev) m/z (abundance): 279 ((M-t-Bu) +, 12), 237 (5), 201 (16), 200 (17), 199 (100), 105 (9), 77 (14). 1-[(Hex-5-yn-1-yloxy)methyl]-4-methoxybenzene (4c) 4c C 14 H 18 2 Mol. Wt.: Sodium hydride (224 mg, 60%wt in mineral oil, 5.60 mmol, 1.1 equiv) was washed with pentane and then suspended in THF (10 ml) at rt and a solution of hex-5-yn-1-ol (500 mg, 5.10 mmol, 1.0 equiv) in THF (1 ml) was added via cannula. After 20 min stirring at rt, a solution of 4-methoxybenzyl bromide (1.332 g, 6.62 mmol, 1.3 equiv) in THF (1 ml) was added via cannula. After 17 h at rt the reaction mixture was quenched with glacial acetic acid (2 ml) and water (50 ml). The layers were separated and the aqueous phase was extracted with EtAc (3 50 ml). The combined organic extracts were dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 98/2) to afford 4c (1.00 g, 4.59 mmol, 90%) as a colorless oil. Spectroscopic and physical data matched the ones reported in the literature. 3 IR (pur): 3292, 2937, 2860, 1612, 1512, 1456, 1361, 1301, 1244, 1173, 1094, 1034, 819, 635 cm Baldwin, J. E.; Romeril, S. P.; Lee, V.; Claridge, T. D. W. rg. Lett. 2001, 3, Lee, D.; Danishefsky, S. J. J. Am. Chem. Soc. 2010, 132, S4

5 1 H NMR (400 MHz, CDCl 3 ): 7.26 (m, 2H), 6.87 (m, 2H), 4.43 (s, 2H), 3.80 (s, 3H), 3.46 (t, 2H, 3 J = 6.3 Hz), 2.20 (td, 2H, 3 J = 7.0, 4 J = 2.7 Hz), 1.94 (t, 1H, 4 J = 2.7 Hz), 1.72 (m, 2H), 1.62 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): (s), (s), (d, 2CH), (d, 2CH), 84.4 (s), 72.6 (t), 69.4 (t), 68.4 (d), 55.3 (q), 28.8 (t), 25.3 (t), 18.2 (t). MS (EI, 70 ev) m/z (abundance): 218 (M +, 5), 135 (23), 122 (11), 121 (100), 78 (11), 77 (16). (E)-(6-Iodohex-5-en-1-yloxy)methylbenzene (5a) 5a I C 13 H 17 I Mol. Wt.: To a suspension of bis(cyclopentadienyl)zirconium(iv) dichloride, Cp 2 ZrCl 2, (932 mg, 3.19 mmol, 1.5 equiv) in dry THF (11 ml) at 0 C was added DIBAL-H dropwise (3.19 ml, 1M in hexanes, 3.19 mmol, 1.5 equiv). After 30 min at 0 C, a solution of alkyne 4a (400 mg, 2.13 mmol, 1.0 equiv) in dry THF (5 ml) was added via cannula at 0 C and the mixture was stirred at rt for 2 h. The reaction mixture was cooled to -78 C and a solution of N- iodosuccinimide (1.55 g, 6.37 mmol, 3.0 equiv) in dry THF (7 ml) was added via cannula. The mixture was stirred at -78 C for 30 min and quenched by the addition of aqueous HCl (1 M, 25 ml). The layers were separated and the aqueous phase was extracted with Et 2 (3 25 ml). The combined organic extracts were washed with a saturated aqueous solution of NaHC 3 (30 ml), a saturated aqueous solution of Na 2 S 2 3 (30 ml) and brine (30 ml) and dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 99/1) to afford vinyl iodide 5a (636 mg, 2.01 mmol, 95%) as a colorless oil. IR (pur): 3029, 2934, 2855, 1604, 1495, 1453, 1361, 1203, 1101, 1027, 948, 733, 696, 659, 611 cm H NMR (400 MHz, CDCl 3 ): (m, 5H), 6.50 (dt, 1H, 3 J = 14.4, 3 J = 7.2 Hz), 5.98 (dt, 1H, 3 J = 14.4, 4 J = 1.5 Hz), 4.49 (s, 2H), 3.46 (t, 2H, 3 J = 6.3 Hz), 2.07 (tdd, 2H, 3 J = 7.3, 3 J = 7.3, 4 J = 1.4 Hz), 1.61 (m, 2H), 1.49 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): (d), (s), (d, 2CH), (d, 2CH), (d), 74.8 (d), 73.0 (t), 70.0 (t), 35.8 (t), 29.1 (t), 25.1 (t). MS (EI, 70 ev) m/z (abundance): 287 (1), 92 (12), 91 (100), 80 (13), 79 (11), 65 (10). HRMS calculated for (M+Na + ): Found: S5

6 (E)-tert-Butyl(6-iodohex-5-en-1-yloxy)diphenylsilane (5b) 5b I C 22 H 29 I Mol. Wt.: To a suspension of bis(cyclopentadienyl)zirconium(iv) dichloride, Cp 2 ZrCl 2, (1.56 g, 5.35 mmol, 1.5 equiv) in dry THF (17 ml) at 0 C was added DIBAL-H dropwise (5.35 ml, 1M in hexanes, 5.35 mmol, 1.5 equiv). After 30 min at 0 C, a solution of alcyne 4b (1.200 g, 3.57 mmol, 1.0 equiv) in dry THF (10 ml) was added via cannula at 0 C and the mixture was stirred at rt for 2 h. The reaction mixture was cooled to -78 C and a solution of N- iodosuccinimide (2.60 g, mmol, 3.0 equiv) in dry THF (12 ml) was added via cannula. The mixture was stirred at -78 C for 30 min and quenched by the addition of aqueous HCl (1 M, 30 ml). The layers were separated and the aqueous phase was extracted with Et 2 (3 50 ml). The combined organic extracts were washed with a saturated aqueous solution of NaHC 3 (60 ml), a saturated aqueous solution of Na 2 S 2 3 (60 ml) and brine (60 ml) and dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 99/1) to afford vinyl iodide 5b (1.59 g, 3.43 mmol, 96%) as a colorless oil. Spectroscopic and physical data matched the ones reported in the literature. 4 IR (pur): 2930, 2857, 1472, 1427, 1389, 1107, 998, 942, 908, 823, 733, 700, 613 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), (m, 6H), 6.48 (dt, 1H, 3 J = 14.3, 3 J = 7.1 Hz), 5.94 (dt, 1H, 3 J = 14.4, 4 J = 1.4 Hz), 3.65 (t, 2H, 3 J = 6.1 Hz), 2.03 (tdd, 2H, 3 J = 7.2, 3 J = 7.2, 4 J = 1.4 Hz), (m, 4H), 1.05 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (d), (d, 4CH), (s, 2C), (d, 2CH), (d, 4CH), 74.5 (d), 63.5 (t), 35.7 (t), 31.7 (t), 26.9 (q, 3Me), 24.6 (t), 19.2 (s). MS (EI, 70 ev) m/z (abundance): 408 (11), 407 ((M-t-Bu) +, 46), 310 (17), 309 (91), 249 (19), 199 (34), 183 (13), 181 (15), 123 (12), 105 (15), 81 (100), 79 (11), 77 (21). (E)-1-(6-Iodohex-5-en-1-yloxy)methyl-4-methoxybenzene (5c) 5c I C 14 H 19 I 2 Mol. Wt.: Lauzon, S.; Tremblay, F.; Gagnon, - Spino, C. J. rg. Chem. 2008, 73, S6

7 To a suspension of bis(cyclopentadienyl)zirconium(iv) dichloride, Cp 2 ZrCl 2, (1.00 g, 3.44 mmol, 1.5 equiv) in dry THF (12 ml) at 0 C was added DIBAL-H dropwise (3.44 ml, 1M in hexanes, 3.44 mmol, 1.5 equiv). After 30 min at 0 C, a solution of alkyne 4c (500 mg, 2.29 mmol, 1.0 equiv) in dry THF (6 ml) was added via cannula at 0 C and the mixture was stirred at rt for 2 h. The reaction mixture was cooled to -78 C and a solution of N- iodosuccinimide (1.67 g, 6.87 mmol, 3.0 equiv) in dry THF (7 ml) was added via cannula. The mixture was stirred at -78 C for 30 min and quenched by the addition of aqueous HCl (1 M, 25 ml). The layers were separated and the aqueous phase was extracted with Et 2 (3 25 ml). The combined organic extracts were washed with a saturated aqueous solution of NaHC 3 (30 ml), a saturated aqueous solution of Na 2 S 2 3 (30 ml) and brine (30 ml) and dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 99/1) to afford 562 mg (71%) of vinyl iodide 5c as a slightly yellow oil. Spectroscopic and physical data matched the ones reported in the literature. 5 IR (pur): 3000, 2933, 2855, 1611, 1586, 1511, 1461, 1360, 1301, 1245, 1172, 1095, 1035, 949, 819, 755, 658 cm H NMR (400 MHz, CDCl 3 ): 7.25 (m, 2H), 6.88 (m, 2H), 6.49 (dt, 1H, 3 J = 14.3, 3 J = 7.2 Hz), 5.97 (dt, 1H, 3 J = 14.3, 4 J = 1.4 Hz), 4.42 (s, 2H), 3.80 (s, 3H), 3.43 (t, 2H, 3 J = 6.3 Hz), 2.06 (tdd, 2H, 3 J = 7.3, 3 J = 7.3, 4 J = 1.3 Hz), 1.59 (m, 2H), 1.47 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (s), (d, 2CH), (d, 2CH), 74.7 (d), 72.6 (t), 69.7 (t), 55.3 (q), 35.8 (t), 29.1 (t), 25.1 (t). MS (EI, 70 ev) m/z (abundance): 346 (1), 122 (10), 121 (100). 2-[(1E,3E)-8-(Benzyloxy)octa-1,3-dien-1-yl]-4,4,6-trimethyl-1,3,2-dioxaborinane (7a) 7a B C 21 H 31 B 3 Mol. Wt.: To a solution of vinyl iodide 5a (617 mg, 1.95 mmol, 1.0 equiv) in acetonitrile (10 ml) was added silver acetate (423 mg, 2.55 mmol, 1.3 equiv), tri-(o-tolyl)phosphine (59 mg, mmol, 10 mol %) and palladium acetate (22 mg, mmol, 5 mol %). The mixture was degased using freeze-pump-thaw method (2 cycles), vinylboronic acid 2-methyl-2,4- pentanediol ester 6 (440 L, 2.54 mmol, 1.3 equiv) was added, the mixture was degased twice 5 Grisé; Tessier, G.; Barriault, L. rg. Lett. 2007, 9, S7

8 more and heated to 50 C for 60 h. The mixture was diluted with Et 2 (50 ml), filtered through a pad of Celite and the filtrate was washed with aqueous 5 %wt HCl (2 25 ml), water (50 ml) and brine (50 ml), dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac gradient: 99/1 to 98/2) to afford boronate 7a (429 mg, 1.25 mmol, 64%) as a yellow oil. IR (pur): 2973, 2934, 2857, 1643, 1603, 1454, 1415, 1388, 1302, 1251, 1206, 1163, 1102, 1008, 768, 734, 697, 636 cm H NMR (400 MHz, CDCl 3 ): (m, 5H), 6.89 (dd, 1H, 3 J = 17.5, 3 J = 10.4 Hz), 6.10 (br dd, 1H, 3 J = 15.2, 3 J = 10.4 Hz), 5.82 (dt, 1H, 3 J = 15.2, 3 J = 7.0 Hz), 5.36 (d, 1H, 3 J = 17.5 Hz), 4.49 (s, 2H), 4.21 (dqd, 1H, 3 J = 11.6, 3 J = 6.2, 3 J = 2.9 Hz), 3.46 (t, 2H, 3 J = 6.5 Hz), 2.11 (br q app, 2H, 3 J = 7.2 Hz), 1.77 (dd systab, 1H, 2 J = 13.9, 3 J = 2.9 Hz), 1.62 (m, 2H), (m, 3H), 1.30 (s, 3H), 1.29 (s, 3H), 1.27 (d, 3H, 3 J = 6.4 Hz). 13 C NMR (100 MHz, CDCl 3 ): (d), (s), (d), (s), (d, 2CH), (d, 2CH), (d), (d), 72.9 (t), 70.7 (s), 70.2 (t), 64.7 (d), 46.0 (t), 32.4 (t), 31.3 (q), 29.2 (t), 28.1 (q), 25.7 (t), 23.2 (q). MS (EI, 70 ev) m/z (abundance): 342 (M +, 1), 151 (14), 107 (56), 105 (17), 93 (11), 92 (13), 91 (100), 83 (32), 79 (81), 67 (12), 55 (32). HRMS calculated for (M+Na + ): Found: tert-butyldiphenyl-[(5e,7e)-8-(4,4,6-trimethyl-1,3,2-dioxaborinan-2-yl)octa-5,7-dien-1- yloxy]silane (7b) 7b B C 30 H 43 B 3 Mol. Wt.: To a solution of vinyl iodide 5b (1.95 g, 4.20 mmol, 1.0 equiv) in acetonitrile (21 ml) was added silver acetate (911 mg, 5.46 mmol, 1.3 equiv), tri-(o-tolyl)phosphine (128 mg, mmol, 10 mol %) and palladium acetate (47 mg, mmol, 5 mol %). The mixture was degased using freeze-pump-thaw method (2 cycles), vinylboronic acid 2-methyl-2,4- pentanediol ester 6 (941 L, 5.46 mmol, 1.3 equiv) was added, the mixture was degased twice more and heated to 50 C for 17 h. The mixture was diluted with Et 2 (100 ml), filtered through a pad of Celite and the filtrate was washed with aqueous 5 %wt HCl (2 50 ml), water (100 ml) and brine (100 ml), dried over MgS 4, filtered and concentrated under S8

9 reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac gradient: 99/1 to 98/2) to afford boronate 7b (1.65 g, 3.36 mmol, 80%) as a colorless oil. IR (pur): 2972, 2932, 2858, 1643, 1603, 1428, 1388, 1302, 1252, 1207, 1164, 1108, 1008, 909, 823, 768, 733, 701, 613 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), (m, 6H), 6.90 (dd, 1H, 3 J = 17.4, 3 J = 10.4 Hz), 6.08 (br dd, 1H, 3 J = 15.2, 3 J = 10.6 Hz), 5.80 (dt, 1H, 3 J = 15.0, 3 J = 7.0 Hz), 5.37 (d, 1H, 3 J = 17.4 Hz), 4.22 (dqd, 1H, 3 J = 11.5, 3 J = 6.0, 3 J = 3.0 Hz), 3.64 (t, 2H, 3 J = 6.4 Hz), 2.07 (br q app, 2H, 3 J = 7.1 Hz), 1.77 (dd systab, 1H, 2 J = 13.8, 3 J = 3.0 Hz), (m, 5H), (m, 6H), 1.27 (d, 3H, 3 J = 6.3 Hz), 1.04 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (d), (d), (d, 4CH), (s, 2C), (d), (d, 2CH), (d, 4CH), (C 8 ), 70.6 (s), 64.7 (d), 63.7 (t), 46.0 (t), 32.4 (t), 32.0 (t), 31.3 (q), 28.1 (q), 26.9 (q, 3Me), 25.4 (t), (s), (s). MS (EI, 70 ev) m/z (abundance): 475 (M-Me +, 1), 433 (M-t-Bu +, 7), 334 (13), 333 (44), 332 (11), 273 (10), 255 (15), 229 (18), 227 (24), 226 (10), 225 (28), 209 (10), 199 (40), 183 (12), 181 (11), 151 (10), 149 (10), 135 (48), 123 (18), 109 (11), 107 (11), 105 (25), 93 (13), 91 (10), 84 (10), 83 (100), 79 (14), 77 (121), 67 (15), 55 (33). HRMS 6 calculated for the dimethylboronic acid ester (M+Na + ): Found: [(1E,3E)-8-(4-Methoxybenzyloxy)octa-1,3-dien-1-yl]-4,4,6-trimethyl-1,3,2-dioxaborinane (7c) 7 7c B C 22 H 33 B 4 Mol. Wt.: To a solution of vinyl iodide 5c (380 mg, 1.10 mmol, 1.0 equiv) in acetonitrile (5.5 ml) was added silver acetate (232 mg, 1.43 mmol, 1.3 equiv), tri(o-tolyl)phosphine (33 mg, mmol, 10 mol %) and palladium acetate (12 mg, mmol, 5 mol %). The mixture was degased using freeze-pump-thaw method (2 cycles), vinylboronic acid 2-methyl-2,4- pentanediol ester 6 (246 L, 1.43 mmol, 1.3 equiv) was added, the mixture was degased twice more and heated to 50 C for 17 h. The mixture was diluted with Et 2 (30 ml), filtered 6 7b reacted with the methanol used as HRMS sample solvent and only the transesterification product (dimethylboronic acid ester) was observed. 7 It was impossible to obtain the HRMS but 7c was successfully transformed to 1c, for which we were able to obtain the HRMS. S9

10 through a pad of Celite and the filtrate was washed with aqueous 5 %wt HCl (2 15 ml), water (30 ml) and brine (30 ml), dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac gradient: 99/1 to 98/2) to afford boronate 7c (235 mg, mmol, 58%) as a colorless oil. IR (pur): 2972, 2935, 2857, 1643, 1605, 1512, 1456, 1415, 1388, 1301, 1246, 1207, 1165, 1096, 1036, 1008, 817, 767, 636 cm H NMR (400 MHz, CDCl 3 ): 7.25 (m, 2H), (m, 3H), 6.09 (br dd, 1H, 3 J = 15.2, 3 J = 10.5 Hz), 5.81 (dt, 1H, 3 J = 15.2, 3 J = 7.0 Hz), 5.36 (d, 1H, 3 J = 17.6 Hz), 4.42 (s, 2H), 4.21 (dqd, 1H, 3 J = 11.7, 3 J = 6.1, 3 J = 2.9 Hz), 3.80 (s, 3H), 3.43 (t, 2H, 3 J = 6.4 Hz), 2.10 (br td, 2H, 3 J = 7.1, 3 J = 7.1 Hz), 1.77 (dd systab, 1H, 2 J = 13.8, 3 J = 2.9 Hz), 1.60 (m, 2H), (m, 3H), 1.30 (s, 3H), 1.29 (s, 3H), 1.27 (d, 3H, 3 J = 6.2 Hz). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (d), (d), (s), (d, 2CH), (d, 2CH), 72.6 (t), 70.7 (s), 69.9 (t), 64.7 (d), 55.3 (q), 46.0 (t), 32.4 (t), 31.3 (q), 29.3 (t), 28.1 (q), 25.8 (t), 23.2 (q). MS (EI, 70 ev) m/z (abundance): 372 (M +, 1), 122 (10), 121 (100), 79 (9). (5E,7E)-8-(4,4,6-Trimethyl-1,3,2-dioxaborinan-2-yl)octa-5,7-dien-1-ol (7e) H 7e C 14 H 25 B 3 Mol. Wt.: B To a solution of silyl ether 7b (258 mg, mmol, 1.0 equiv) in THF (3.5 ml) was added TBAF (0.790 ml, 1.0 M in THF, mmol, 1.5 equiv). After 3 h at rt the mixture was diluted with Et 2 (30 ml), washed with a saturated aqueous solution of NaHC 3 (30 ml) and dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac gradient: 90/10 to 80/20) to afford alcohol 7e (91 mg, 0.36 mmol, 68%) as a yellow oil. IR (pur): 3372, 2973, 2933, 1692, 1643, 1603, 1415, 1388, 1302, 1251, 1207, 1163, 1056, 1008, 767, 665, 636 cm H NMR (400 MHz, CDCl 3 ): 6.90 (dd, 1H, 3 J = 17.6, 3 J = 10.3 Hz), 6.11 (br dd, 1H, 3 J = 15.1, 3 J = 10.5 Hz), 5.82 (dt, 1H, 3 J = 15.1, 3 J = 7.2 Hz), 5.37 (d, 1H, 3 J = 17.5 Hz), 4.21 (dqd, 1H, 3 J = 11.6, 3 J = 6.2, 3 J = 2.9 Hz), 3.64 (t, 2H, 3 J = 6.5 Hz), 2.13 (br td, 2H, 3 J = 7.2, 3 J = S10

11 7.2 Hz), 1.78 (dd systab, 1H, 2 J = 13.8, 3 J = 3.0 Hz), (m, 5H), 1.30 (s, 3H), 1.29 (s, 3H), 1.27 (d, 3H, 3 J = 6.1 Hz). 13 C NMR (100 MHz, CDCl 3 ): (d), (d), (d), 70.7 (s), 64.7 (d), 62.8 (t), 46.0 (t), 32.4 (t), 32.2 (t), 31.3 (q), 28.1 (q), 25.2 (t), 23.2 (q). MS (EI, 70 ev) m/z (abundance): 252 (1), 237 (3), 152 (56), 151 (19), 134 (11), 124 (22), 123 (44), 122 (12), 119 (11), 111 (13), 110 (17), 109 (25), 108 (56), 107 (18), 106 (23), 105 (24), 98 (15), 96 (24), 95 (13), 94 (18), 93 (100), 92 (13), 91 (30), 85 (14), 84 (41), 83 (97), 82 (12), 81 (23), 80 (81), 79 (88), 78 (18), 77 (14), 71 (24), 69 (27), 68 (10), 67 (56), 66 (30), 59 (34), 57 (15), 56 (18), 55 (98), 54 (10), 53 (13). HRMS calculated for (M+Na + ): Found: tert-butyl N-tosyl-[(5E,7E)-8-(4,4,6-trimethyl-1,3,2-dioxaborinan-2-yl)octa-5,7-dien-1-yl]- carbamate (7d) N S B C 26 H 40 BN 6 S Mol. Wt.: d To a solution of alcohol 7e (65 mg, mmol, 1.0 equiv) in THF (650 L) was added triphenylphosphine (68 mg, mmol, 1.0 equiv), N-(tert-butoxycarbonyl)-ptoluenesulfonamide (70 mg, mmol, 1.0 equiv) and the mixture was cooled to 0 C. DIAD (51 ml, mmol, 1.0 equiv) was added dropwise and after 5 min at 0 C the mixture was warmed to rt and stirred for 17 h. The mixture was then concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 95/5) to afford protected amine 7d (80 mg, mmol, 62%) as a white solid. IR (pur): 2975, 2933, 1725, 1643, 1602, 1456, 1389, 1353, 1302, 1254, 1208, 1154, 1088, 1009, 911, 848, 813, 768, 729, 672 cm H NMR (400 MHz, CDCl 3 ): 7.77 (m, 2H), 7.29 (m, 2H), 6.90 (dd, 1H, 3 J = 17.4, 3 J = 10.5 Hz), 6.12 (br dd, 1H, 3 J = 15.1, 3 J = 10.4 Hz), 5.82 (dt, 1H, 3 J = 15.1, 3 J = 7.1 Hz), 5.38 (d, 1H, 3 J = 17.5 Hz), 4.22 (dqd, 1H, 3 J = 11.6, 3 J = 6.2, 3 J = 2.9 Hz), 3.81 (t, 2H, 3 J = 7.5 Hz), 2.43 (s, 3H), 2.15 (td, 2H, 3 J = 7.1, 3 J = 7.1 Hz), (m, 3H), (m, 3H), 1.33 (s, 9H), 1.30 (s, 3H), 1.29 (s, 3H), 1.27 (d, 3H, 3 J = 6.2 Hz). S11

12 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (s), (s), (d), (d), (d, 2CH), (d, 2CH), 84.1 (s), 70.7 (s), 64.7 (d), 47.0 (t), 46.0 (t), 32.2 (t), 31.3 (q), 29.7 (t), 28.1 (q), 27.9 (q, 3Me), 26.2 (t), 23.2 (q), 21.6 (q). MS (EI, 70 ev) m/z (abundance): 250 (43), 156 (11), 155 (33), 150 (65), 149 (23), 133 (34), 132 (36), 129 (17), 124 (10), 108 (27), 107 (40), 106 (12), 105 (35), 93 (29), 92 (22), 91 (100), 83 (65), 79 (41), 67 (35), 35 (30), 56 (30), 55 (54). HRMS calculated for (M+Na + ): Found: [(5E,7E)-8-Iodo-octa-5,7-dien-1-yloxymethyl]benzene (1a) 1a I C 15 H 19 I Mol. Wt.: To a solution of vinyl boronate 7a (400 mg, 1.17 mmol, 1.0 equiv) in THF (8 ml) at -78 C was added sodium methoxide (3.50 ml, 0.5 M in MeH, 1.75 mmol, 1.5 equiv) and the mixture was stirred at -78 C for 30 min. A solution of iodine monochloride (1.20 ml, 1.0 M in CH 2 Cl 2, 1.20 mmol, 1.03 equiv) was added dropwise and the resulting mixture was stirred for another hour at -78 C and was then warmed to rt and diluted with Et 2 (50 ml). The organic phase was washed with a saturated aqueous solution of Na 2 S 2 5 (50 ml), an aqueous solution of NaH 1M (3 50 ml), water (50 ml), brine (50 ml) and dried over MgS 4, filtered and concentrated under reduced pressure to afford iodide 1b (342 mg, 1.00 mmol, 85%) as a colorless oil. IR (pur): 3027, 2932, 2855, 1639, 1568, 1495, 1453, 1361, 1269, 1200, 1100, 1027, 979, 908, 732, 696 cm H NMR (400 MHz, CDCl 3 ): (m, 5H), 6.97 (dd, 1H, 3 J = 14.3, 3 J = 10.5 Hz), 6.15 (d, 1H, 3 J = 14.4 Hz), 5.96 (br dd, 1H, 3 J = 15.1, 3 J = 10.5 Hz), 5.71 (dt, 1H, 3 J = 15.2, 3 J = 7.0 Hz), 4.50 (s, 2H), 3.46 (t, 2H, 3 J = 6.4 Hz), 2.06 (br q app, 2H, 3 J = 7.2 Hz), 1.62 (m, 2H), 1.48 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): (d), (s), (d), (d), (d, 2CH), (d, 2CH), (d), 79.6 (d), 72.9 (t), 70.1 (t), 32.2 (t), 29.3 (t), 25.5 (t). MS (EI, 70 ev) m/z (abundance): 342 (M +, 1), 251 (M-Bn +, 2), 123 (10), 106 (19), 91 (100), 80 (15), 79 (22), 66 (15), 65 (13). HRMS calculated for (M+Na + ): Found: S12

13 tert-butyldiphenyl-[(5e,7e)-8-iodo-octa-5,7-dien-1-yloxy]silane (1b) 1b I C 24 H 31 I Mol. Wt.: To a solution of vinyl boronate 7b (89 mg, mmol, 1.0 equiv) in THF (1.2 ml) at -78 C was added sodium methoxide (544 L, 0.5 M in MeH, mmol, 1.5 equiv) and the mixture was stirred at -78 C for 30 min. A solution of iodine monochloride (187 L, 1.0 M in CH 2 Cl 2, mmol, 1.03 equiv) was added dropwise and the resulting mixture was stirred for another hour at -78 C and was then warmed to rt and diluted with Et 2 (10 ml). The organic phase was washed with a saturated aqueous solution of Na 2 S 2 5 (10 ml), an aqueous solution of NaH 1M (3 10 ml), water (10 ml), brine (10 ml) and dried over MgS 4, filtered and concentrated under reduced pressure to afford iodide 1b (82 mg, mmol, 92%) as a colorless oil. IR (pur): 2930, 2857, 1589, 1568, 1472, 1427, 1389, 1361, 1107, 979, 822, 739, 700, 613 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), (m, 6H), 6.97 (dd, 1H, 3 J = 14.4, 3 J = 10.6 Hz), 6.14 (d, 1H, 3 J = 14.3 Hz), 5.94 (br dd, 1H, 3 J = 15.1, 3 J = 10.6 Hz), 5.69 (dt, 1H, 3 J = 15.3, 3 J = 6.9 Hz), 3.65 (t, 2H, 3 J = 6.2 Hz), 2.02 (td, 2H, 3 J = 7.1, 3 J = 7.1 Hz), (m, 4H), 1.04 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (d), (d), (d, 4CH), (s, 2C), (d), (d, 2CH), (d, 4CH), 79.4 (d), 63.7 (t), 32.7 (t), 32.1 (t), 26.9 (q, 3Me), 25.2 (t), 19.2 (s). MS (EI, 70 ev) m/z (abundance): 436 (1), 434 (26), 433 (M-tBu +, 100), 355 (23), 310 (11), 309 (59), 305 (13), 249 (64), 228 (10), 227 (45), 216 (13), 201 (11), 200 (19), 199 (99), 197 (18), 184 (11), 183 (61), 182 (10), 181 (43), 155 (17), 153 (25), 141 (16), 135 (31), 129 (10), 123 (22), 121 (19), 117 (28), 107 (53), 106 (42), 105 (46), 91 (61), 79 (75), 78 (21), 77 (47), 67 (12), 66 (43), 65 (10). HRMS calculated for (M+Na + ): Found: [(5E,7E)-8-Iodo-octa-5,7-dien-1-yloxymethyl]-4-methoxybenzene (1c) 1c I C 16 H 21 I 2 Mol. Wt.: S13

14 To a solution of vinyl boronate 7c (51 mg, mmol, 1.0 equiv) in THF (1 ml) at -78 C was added sodium methoxide (410 L, 0.5 M in MeH, mmol, 1.5 equiv) and the mixture was stirred at -78 C for 30 min. A solution of iodine monochloride (0.140 ml, 1.0 M in CH 2 Cl 2, mmol, 1.03 equiv) was added dropwise and the resulting mixture was stirred for another hour at -78 C and was then warmed to rt and diluted with Et 2 (10 ml). The organic phase was washed with a saturated aqueous solution of Na 2 S 2 5 (10 ml), an aqueous solution of NaH 1M (3 10 ml), water (10 ml) and brine (10 ml) and dried over MgS 4, filtered and concentrated under reduced pressure to afford iodide 1c (46 mg, mmol, 90%) as a yellow oil. IR (pur): 2933, 2855, 1612, 1586, 1511, 1456, 1361, 1301, 1245, 1172, 1096, 1035, 980, 819, 755, 683 cm H NMR (400 MHz, CDCl 3 ): 7.25 (m, 2H), 6.97 (dd, 1H, 3 J = 14.3, 3 J = 10.5 Hz), 6.87 (m, 2H), 6.15 (d, 1H, 3 J = 14.3 Hz), 5.95 (dd, 1H, 3 J = 15.1, 3 J = 10.5 Hz), 5.70 (dt, 1H, 3 J = 15.2, 3 J = 7.0 Hz), 4.42 (s, 2H), 3.80 (s, 3H), 3.43 (t, 2H, 3 J = 6.5 Hz), 2.04 (td, 2H, 3 J = 7.2, 3 J = 7.1 Hz), 1.60 (m, 2H), 1.47 (m, 2H). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (d), (s), (d), (s, 2CH), (d, 2CH), 76.4 (d), 72.6 (t), 69.8 (t), 55.3 (q), 32.2 (t), 29.3 (t), 25.5 (t). MS (EI, 70 ev) m/z (abundance): 372 (M +, 1), 245 (M-I +, 2), 121 (100). HRMS calculated for (M+Na + ): Found: tert-butyl N-tosyl-[(5E,7E)-8-iodoocta-5,7-dien-1-yl]-carbamate (1d) N S I 1d C 20 H 28 IN 4 S Mol. Wt.: To a solution of vinyl boronate 7d (50 mg, 98.9 mol, 1.0 equiv) in THF (700 L) at -78 C was added sodium methoxide (300 L, 0.5 M in MeH, mmol, 1.5 equiv) and the mixture was stirred at -78 C for 30 min. A solution of iodine monochloride (0.102 ml, 1.0 M in CH 2 Cl 2, mmol, 1.03 equiv) was added dropwise and the resulting mixture was stirred for another hour at -78 C and was then warmed to rt and diluted with Et 2 (10 ml). The organic phase was washed with a saturated aqueous solution of Na 2 S 2 5 (10 ml), an aqueous solution of NaH 1M (3 10 ml), water (10 ml) and brine (10 ml) and dried over MgS 4, S14

15 filtered and concentrated under reduced pressure to afford iodide 1d (35 mg, 69.3 mol, 70%) as a colorless oil. IR (pur): 2930, 1723, 1598, 1455, 1352, 1286, 1256, 1152, 1087, 981, 847, 812, 770, 720, 672 cm H NMR (400 MHz, CDCl 3 ): (m, 2H), (m, 2H), 6.98 (dd, 1H, 3 J = 14.4, 3 J = 10.5 Hz), 6.17 (d, 1H, 3 J = 14.3 Hz), 5.99 (br dd, 1H, 3 J = 15.2, 3 J = 10.6 Hz), 5.71 (dt, 1H, 3 J = 15.1, 3 J = 7.0 Hz), 3.81 (t, 2H, 3 J = 7.6 Hz), 2.43 (s, 3H), 2.10 (q app, 2H, 3 J = 7.1 Hz), 1.75 (m, 2H), 1.45 (m, 2H), 1.32 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (s), (s), (d), (d), (d, 2CH), (d, 2CH), 84.2 (s), 76.6 (d), 46.9 (t), 31.9 (t), 29.6 (t), 27.9 (q, 3Me), 25.9 (t), 21.6 (q). MS (EI, 70 ev) m/z (abundance): 235 (13), 234 (8), 233 (41), 232 (16), 231 (60), 204 (44), 203 (15), 202 (39), 184 (11), 177 (11), 175 (34), 173 (93), 155 (78), 147 (17), 145 (32), 111 (11), 92 (15), 91 (100), 65 (28), 64 (14), 50 (16). HRMS calculated for (M+Na + ): Found: tert-butyldiphenyl-[(5e,7e)-8-bromo-octa-5,7-dien-1-yloxy]silane (8) 8 Br C 24 H 31 Br Mol. Wt.: To a solution of vinyl boronate 7b (100 mg, mmol, 1.0 equiv) in THF (1.5 ml) at -78 C was added sodium methoxide (612 L, 0.5 M in MeH, mmol, 1.5 equiv) and the mixture was stirred at -78 C for 30 min. N-bromosuccinimide (37 mg, mmol, 1.03 equiv) was added and the resulting mixture was stirred 1 h at -78 C and was then warmed to rt, stirred for 2 h at rt and diluted with Et 2 (10 ml). The organic phase was washed with a saturated aqueous solution of Na 2 S 2 5 (10 ml), an aqueous solution of NaH 1M (3 10 ml), water (10 ml) and brine (10 ml), dried over MgS 4, filtered and concentrated under reduced pressure to afford bromide 8 (80 mg, mmol, 88%) as a slightly yellow oil. IR (pur): 2931, 2857, 1587, 1472, 1427, 1389, 1107, 977, 822, 738, 700, 613 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), (m, 6H), 6.66 (dd, 1H, 3 J = 13.5, 3 J = 10.7 Hz), 6.16 (d, 1H, 3 J = 13.4 Hz), 5.92 (dd, 1H, 3 J = 15.2, 3 J = 10.6 Hz), 5.69 (dt, 1H, 3 J = 15.3, 3 J = 6.9 Hz), 3.65 (t, 2H, 3 J = 6.2 Hz), 2.04 (td, 2H, 3 J = 7.1, 3 J = 7.1 Hz), (m, 4H), 1.04 (s, 9H). S15

16 13 C NMR (100 MHz, CDCl 3 ): (d), (d), (d, 4CH), (s, 2C), (d, 2CH), (d), (d, 4CH), (d), 63.7 (t), 32.3 (t), 32.0 (t), 26.9 (q, 3Me), 25.2 (t), 19.3 (s). MS (EI, 70 ev) m/z (abundance): 388 (10), 387 (M 81 Br-tBu +, 35), 386 (9), 385 (M 79 Br-tBu +, 35), 263 (32), 261 (32), 227 (16), 203 (32), 201 (37), 199 (72), 197 (15), 185 (11), 184 (10), 183 (53), 181 (36), 155 (17), 153 (30), 141 (17), 135 (24), 129 (11), 123 (13), 121 (19), 117 (28), 107 (54), 106 (16), 105 (51), 91 (69), 81 (16), 79 (100), 78 (15), 77 (42), 67 (11), 66 (23), 65 (24). HRMS calculated for (M+Na + ): Found: Phenylprop-2-en-1-ol (2e) H 2e C 9 H 10 Mol. Wt.: A solution of benzaldehyde (200 mg, 1.88 mmol, 1.0 equiv) in THF (2.5 ml) was added to a solution of vinylmagnesium bromide (2.25 ml, 1.0 M in THF, 2.25 mmol, 1.2 equiv) at 0 C and the mixture was stirred at this temperature for 30 min and at rt for 1 h. The reaction was quenched by the addition of a saturated aqueous solution of NH 4 Cl (5 ml). The phases were separated, the aqueous phase was extracted with Et 2 (3 5 ml) and the combined organic phases were dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 90/10) to afford alcohol 2e (232 mg, 1.73 mmol, 92%) as a slightly yellow oil. Spectroscopic and physical data matched the ones reported in the literature. 8 IR (pur): 3345, 3063, 3030, 2872, 1642, 1602, 1493, 1452, 1408, 1247, 1195, 1115, 1074, 1023, 988, 925, 833, 760, 698 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), 7.27 (m, 1H), 6.02 (ddd, 1H, 3 J = 17.1, 3 J = 10.3 Hz, 3 J = 6.1 Hz), 5.32 (dt, 1H, 3 J = 17.1, 4 J = 1.4 Hz), 5.17 (dt, 1H, 3 J = 10.3, 4 J = 1.3 Hz), 5.15 (br s, 1H), 2.28 (br s, 1H). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (d, 2CH), (d), (d, 2CH), (t), 75.3 (d). MS (EI, 70 ev) m/z (abundance): 135 (5), 134 (M +, 53), 133 (100), 117 (10), 116 (14), 115 (37), 107 (19), 105 (84), 103 (12), 92 (86), 91 (41), 79 (80), 78 (45), 77 (90), 63 (10), 57 (11), 56 (14), 55 (51), 52 (10), 51 (42), 50 (14). 8 Hanessian, S.; Focken, T.; za, R. Tetrahedron 2011, 67, S16

17 1-Cyclohexylprop-2-en-1-ol (2f) H 2f C 9 H 16 Mol. Wt.: A solution of cyclohexanecarboxaldehyde (500 mg, 4.46 mmol, 1.0 equiv) in THF (6 ml) was added to a solution of vinylmagnesium bromide (5.35 ml, 1.0 M in THF, 5.35 mmol, 1.2 equiv) at 0 C and the mixture was stirred at this temperature for 30 min and at rt for 1 h. The reaction was quenched by the addition of a saturated aqueous solution of NH 4 Cl (10 ml). The phases were separated, the aqueous phase was extracted with Et 2 (3 10 ml) and the combined organic phases were dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (petroleum ether/etac 90/10) to afford alcohol 2f (609 mg, 4.34 mmol, 97%) as a colorless oil. Spectroscopic and physical data matched the ones reported in the literature. 9 IR (pur): 3356, 2922, 2852, 1644, 1449, 1424, 1307, 1259, 1082, 1018, 991, 919, 892 cm H NMR (400 MHz, CDCl 3 ): 5.86 (ddd, 1H, 3 J = 17.2, 3 J = 10.4 Hz, 3 J = 6.7 Hz), 5.20 (dt, 1H, 3 J = 17.2, 4 J = 1.5 Hz), 5.14 (dt, 1H, 3 J = 10.4, 4 J = 1.4 Hz), 3.84 (t, 1H, 3 J = 6.4 Hz), 1.85 (m, 1H), (m, 5H), 1.64 (br s, 1H), 1.40 (m, 1H), (m, 4H). 13 C NMR (100 MHz, CDCl 3 ): (d), (t), 77.8 (d), 43.5 (d), 28.7 (t), 28.4 (t), 26.5 (t), 26.1 (t), 26.0 (t). MS (EI, 70 ev) m/z (abundance): 140 (M +, 1), 122 (M-H 2 +, 3), 96 (11), 83 (48), 82 (18), 81 (11), 67 (22), 58 (56), 57 (32), 55 (100). 4-Methylpent-1-en-3-ol (2g) H 2g C 6 H 12 Mol. Wt.: A solution of 2-methylpropanal (500 mg, 6.93 mmol, 1.0 equiv) in THF (10 ml) was added dropwise to a solution of vinylmagnesium bromide (8.32 ml, 1.0 M in THF, 8.32 mmol, 1.2 equiv) at 0 C and the mixture was stirred at rt for 2 h. The reaction was quenched by the addition of a saturated aqueous solution of NH 4 Cl (10 ml). The phases were separated, the aqueous phase was extracted with Et 2 (3 10 ml) and the combined organic phases were dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (pentane/et 2 90/10) to afford alcohol 2g (371 9 Fuchter, M. J.; Levy, J.-N. rg. Lett. 2008, 10, S17

18 mg, 3.70 mmol, 53%) as a slightly yellow oil. Spectroscopic and physical data matched the ones reported in the literature. 10 IR (pur): 3375, 2960, 2875, 1469, 1426, 1384, 1368, 1256, 1149, 1095, 1020, 991, 920 cm H NMR (400 MHz, CDCl 3 ): 5.86 (ddd, 1H, 3 J = 17.1, 3 J = 10.4 Hz, 3 J = 6.4 Hz), 5.22 (ddd, 1H, 3 J = 17.2, 2 J = 1.5 Hz, 4 J = 1.5 Hz), 5.16 (ddd, 1H, 3 J = 10.4, 2 J = 1.6 Hz, 4 J = 1.2 Hz), 3.86 (m, 1H), 1.74 (m, 1H), 1.68 (br s, 1H), 0.94 (d, 3H, 3 J = 6.8 Hz), 0.91 (d, 3H, 3 J = 6.8 Hz). 13 C NMR (100 MHz, CDCl 3 ): (d), (t), 78.3 (d), 33.6 (d), 18.1 (q), 17.8 (q). 4,4-Dimethylpent-1-en-3-ol (2h) H 2h C 7 H 14 Mol. Wt.: A solution of 2,2-dimethylpropanal (500 mg, 5.81 mmol, 1.0 equiv) in THF (9 ml) was added dropwise to a solution of vinylmagnesium bromide (6.97 ml, 1.0 M in THF, 6.97 mmol, 1.2 equiv) at 0 C and the mixture was stirred at rt for 2 h. The reaction was quenched by the addition of a saturated aqueous solution of NH 4 Cl (10 ml). The phases were separated, the aqueous phase was extracted with Et 2 (3 10 ml) and the combined organic phases were dried over MgS 4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (pentane/et 2 90/10) to afford alcohol 2h (142 mg, 1.24 mmol, 21%) as a slightly yellow oil. Spectroscopic and physical data matched the ones reported in the literature. 11 IR (pur): 3421, 2956, 2907, 2871, 1479, 1465, 1425, 1394, 1364, 1122, 1050, 991, 960, 921 cm H NMR (400 MHz, CDCl 3 ): 5.93 (ddd, 1H, 3 J = 17.2, 3 J = 10.4 Hz, 3 J = 6.8 Hz), 5.23 (ddd, 1H, 3 J = 17.1, 2 J = 1.8 Hz, 4 J = 1.2 Hz), 5.18 (ddd, 1H, 3 J = 10.4, 2 J = 1.8 Hz, 4 J = 1.1 Hz), 3.75 (br d, 1H, 3 J = 6.8 Hz), 1.70 (br s, 1H), 0.91 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (d), (t), 81.2 (d), 34.7 (s), 25.6 (q, 3Me). 10 Grünanger, C. U.; Breit, B. Angew. Chem. Int. Ed. 2010, 49, Craig, D.; Pennington, M. W.; Warner, P. Tetrahedron 1999, 55, S18

19 2-Methylpent-1-en-3-ol (2k) H 2k C 6 H 12 Mol. Wt.: To a solution of methacrolein (5.5 g, mmol, 1.0 equiv) in Et 2 (30 ml) at -20 C was added dropwise a solution of ethylmagnesium bromide (26.15 ml, 3.0 M in Et 2, mmol, 1.0 equiv). The reaction was quenched by the addition of a saturated aqueous solution of NH 4 Cl (30 ml). The phases were separated, the aqueous phase was extracted with Et 2 (3 40 ml) and the combined organic phases were dried over MgS 4, filtered and concentrated by distillation under atmospheric pressure. The crude alcohol was then purified by distillation under reduced pressure (24-25 mmhg, 34 C) to afford alcohol 2h (2.75 g, mmol, 35%) as a colorless oil. Spectroscopic and physical data matched the ones reported in the literature. 12 IR (pur): 3355, 2965, 2936, 2877, 1651, 1455, 1374, 1326, 1236, 1094, 1051, 1016, 980, 962, 897, 831, 626 cm H NMR (400 MHz, CDCl 3 ): 4.93 (m, 1H), 4.85 (m, 1H), 3.99 (t, 1H, 3 J = 6.5 Hz), 1.72 (t, 3H, 3 J = 1.3 Hz), 1.68 (m, 1H), (m, 2H), 0.89 (t, 3H, 3 J = 7.5 Hz). 13 C NMR (100 MHz, CDCl 3 ): (s), (t), 77.3 (d), 27.7 (t), 17.4 (q), 9.8 (q). General procedure for the coupling reaction: To a solution of 1-iodo-1,3-diene (1.0 equiv) in degased DMF (0.4 M) was added the allylic alcohol (2.0 equiv), silver acetate (1.1 equiv) and palladium acetate (5 mol %). The resulting mixture was then heated at 45 C for 17 h. After confirmation of the complete conversion of 1-iodo-1,3-diene by TLC or GCMS, the mixture was cooled to rt, diluted with Et 2, filtered through a pad of Celite, washed with water ( 3). The organic phase was dried over MgS 4, filtered and concentrated under reduced pressure. Purification of the residue by flash chromatography on silica gel afforded the corresponding conjugated trienol derivative. (3E,5E,7E)-12-Benzyloxy-dodeca-3,5,7-trien-2-ol (3a) H 3a C 19 H 26 2 Mol. Wt.: Paterson, I.; Perkins, M. V. Tetrahedron 1996, 52, S19

20 The general procedure for the coupling reaction with 1-iodo-1,3-diene 1a (50 mg, mmol, 1.0 equiv) was applied to commercially available alcohol 2a (21 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3a (29 mg, mmol, 69%) as a colorless oil. IR (pur): 3402, 2928, 2857, 1721, 1683, 1638, 1496, 1454, 1364, 1205, 1100, 995, 735, 698, 612 cm H NMR (400 MHz, CDCl 3 ): (m, 5H), (m, 4H), (m, 2H), 4.50 (s, 2H), 4.35 (quint app, 1H, 3 J = 6.4 Hz), 3.47 (t, 2H, 3 J = 6.5 Hz), 2.12 (br q app, 2H, 3 J = 7.2 Hz), (m, 3H), (m, 2H), 1.29 (d, 3H, 3 J = 6.5 Hz). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (d), (d), (d), (d), (d), (d, 2CH), (d, 2CH), (d), 72.9 (t), 70.2 (t), 68.7 (d), 32.6 (t), 29.3 (t), 25.9 (t), 23.3 (q). MS (EI, 70 ev) m/z (abundance): 268 (M-H 2 +, 2), 133 (10), 131 (10), 119 (11), 117 (14), 105 (16), 93 (23), 92 (13), 91 (100), 81 (13), 80 (16), 79 (24), 77 (13), 71 (10), 67 (16), 65 (13), 55 (14). HRMS calculated for (M+Na + ): Found: (3E,5E,7E)-12-(tert-Butyldiphenylsilanyloxy)dodeca-3,5,7-trien-2-ol (3b) 3b H C 28 H 38 2 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1b (40 mg, 81.6 mol, 1.0 equiv) was applied to commercially available alcohol 2a (12 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3b (19 mg, 43.7 mol, 54%) as a colorless oil. IR (pur): 3402, 2928, 2857, 1721, 1683, 1638, 1496, 1454, 1364, 1205, 1100, 995, 735, 698, 612 cm H NMR (400 MHz, CDCl 3 ): 7.66 (m, 4H), (m, 6H), (m, 4H), (m, 2H), 4.36 (m, 1H), 3.65 (t, 2H, 3 J = 6.3 Hz), 2.09 (br q app, 2H, 3 J = 7.1 Hz), (m, 5H), 1.29 (d, 3H, 3 J = 6.5 Hz), 1.04 (s, 9H). 13 C NMR (100 MHz, CDCl 3 ): (d), (d), (d, 4CH), (s, 2C), (d), (d), (d), (d), (d, 2CH), (d, 4CH), 68.7 (d), 63.7 (t), 32.5 (t), 32.0 (t), 26.9 (q, 3Me), 25.5 (t), 23.3 (q), 19.2 (s). S20

21 MS (EI, 70 ev) m/z (abundance): 416 (M-H 2 +, 4), 360 (10), 359 (28), 281 (20), 200 (20), 199 (100), 197 (13), 183 (30), 181 (14), 161 (11), 160 (13), 159 (14), 135 (22), 131 (16), 123 (15), 121 (10), 119 (11), 117 (24), 93 (17), 92 (11), 91 (41), 81 (36), 80 (11), 79 (20), 78 (10), 77 (22), 67 (15), 55 (12). HRMS calculated for (M+Na + ): Found: (3E,5E,7E)-12-(4-Methoxy-benzyloxy)dodeca-3,5,7-trien-2-ol (3c) 3c H C 20 H 28 3 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1c (42 mg, mmol, 1.0 equiv) was applied to commercially available alcohol 2a (16 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3c (21 mg, 66.4 mol, 59%) as a colorless oil. IR (pur): 3413, 2931, 2856, 1737, 1612, 1512, 1456, 1370, 1301, 1244, 1173, 1096, 1036, 996, 940, 819 cm H NMR (400 MHz, CDCl 3 ): 7.26 (m, 2H), 6.88 (m, 2H), (m, 4H), (m, 2H), 4.42 (s, 2H), 4.31 (m, 1H), 3.80 (s, 3H), 3.44 (t, 2H, 3 J = 6.5 Hz), 2.11 (q app, 2H, 3 J = 7.3 Hz), (m, 3H), 1.47 (m, 2H), 1.28 (d, 3H, 3 J = 6.3 Hz). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (d), (d), (s), (d), (d), (d), (d, 2CH), (d, 2CH), 72.5 (t), 69.9 (t), 68.7 (d), 55.3 (q), 32.6 (t), 29.3 (t), 25.9 (t), 23.3 (q). MS (EI, 70 ev) m/z (abundance): 298 (M-H 2 +, 1), 177 (6), 122 (13), 121 (100), 91 (15), 77 (10). HRMS calculated for (M+Na + ): Found: tert-butyl N-[(5E,7E,9E)-11-hydroxydodeca-5,7,9-trien-1-yl]-N-tosyl carbamate (3d) H N S C 24 H 35 N 5 S 3d Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1d (23 mg, 45.5 mol, 1.0 equiv) was applied to commercially available alcohol 2a (6.5 mg, 91.3 mol, 2.0 equiv). S21

22 Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3d (12 mg, 26.6 mol, 58%) as a colorless oil. IR (pur): 3522, 2980, 2931, 1728, 1456, 1370, 1355, 1242, 1154, 1088, 1045, 998, 847, 813, 735, 672 cm H NMR (400 MHz, C 6 D 6 ): 7.85 (br d, 2H, 3 J = 8.2 Hz), 6.75 (br d, 2H, 3 J = 8.5 Hz), (m, 4H), (m, 2H), 4.08 (m, 1H), 3.93 (t, 2H, 3 J = 7.4 Hz), 2.00 (q app, 2H, 3 J = 7.2 Hz), 1.86 (s, 3H), (m, 5H), 1.19 (s, 9H), 1.12 (d, 3H, 3 J = 6.3 Hz). 13 C NMR (100 MHz, C 6 D 6 ): (s), (s), (s), (d), (d), (d), (d), (d), (d), (d, 2CH), (d, 2CH), 83.4 (s), 68.3 (d), 47.2 (t), 32.6 (t), 30.1 (t), 27.8 (q, 3Me), 26.6 (t), 23.6 (q), 21.1 (q). HRMS calculated for (M+Na + ): Found: (2E,4E,6E)-11-(tert-Butyldiphenylsilanyloxy)undeca-2,4,6-trien-1-ol (3e) 3e H C 27 H 36 2 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1b (40 mg, mmol, 1.0 equiv) was applied to commercially available alcohol 2b (12 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3e (16 mg, 38.0 mol, 37%) as a colorless oil. IR (pur): 3393, 2930, 2857, 1472, 1428, 1389, 1286, 1109, 995, 823, 740, 701, 613 cm H NMR (400 MHz, C 6 D 6 ): (m, 4H), (m, 6H), (m, 4H), (m, 2H), 3.86 (br d, 2H, 3 J = 5.6 Hz), 3.65 (t, 2H, 3 J = 6.3 Hz), 1.97 (q app, 2H, 3 J = 7.1 Hz), 1.54 (m, 2H), 1.43 (m, 2H), 1.19 (s, 9H). 13 C NMR (100 MHz, C 6 D 6 ): (d, 4CH), (d), (s, 2C), (d), (d), (d), (d), (d), (d, 2CH), (d, 4CH), 64.0 (t), 63.2 (t), 32.8 (t), 32.4 (t), 27.1 (q, 3Me), 25.8 (t), 19.5 (s). MS (EI, 70 ev) m/z (abundance): 285 (1), 283 (20), 205 (17), 200 (18), 199 (100), 181 (13), 165 (12), 145 (12), 143 (12), 139 (52), 123 (10), 105 (12), 91 (21), 77 (20). HRMS calculated for (M+Na + ): Found: S22

23 (4E,6E,8E)-13-(tert-Butyldiphenylsilanyloxy)trideca-4,6,8-trien-3-ol (3f) 3f H C 29 H 40 2 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1b (40 mg, 81.6 mol, 1.0 equiv) was applied to commercially available alcohol 2c (14 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3f (23 mg, 51.3 mol, 62%) as a slightly yellow oil. IR (pur): 3361, 2930, 2857, 1472, 1428, 1389, 1361, 1107, 996, 823, 739, 700, 613 cm H NMR (400 MHz, CDCl 3 ): (m, 4H), (m, 6H), (m, 4H), (m, 2H), 4.07 (q app, 1H, 3 J = 6.6 Hz), 3.65 (t, 2H, 3 J = 6.2 Hz), 2.09 (q app, 2H, 3 J = 7.1 Hz), (m, 7H), 1.05 (s, 9H), 0.91 (t, 3H, 3 J = 7.4 Hz). 13 C NMR (100 MHz, CDCl 3 ): (d), (d, 4CH), (d), (s, 2C), (d), (d), (d), (d), (d, 2CH), (d, 4CH), 74.2 (d), 63.7 (t), 32.5 (t), 32.1 (t), 30.2 (t), 26.9 (q, 3Me), 25.5 (t), 19.2 (s), 9.7 (q). MS (EI, 70 ev) m/z (abundance): 415 (1), 412 (5), 410 (7), 257 (15), 255 (23), 177 (11), 175 (64), 173 (100), 147 (10), 145 (16), 91 (25), 81 (11). HRMS calculated for (M+Na + ): Found: (7E,9E,11E)-16-Benzyloxyhexadeca-7,9,11-trien-6-ol (3g) 3g H C 23 H 34 2 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1a (50 mg, mmol, 1.0 equiv) was applied to commercially available alcohol 2d (37 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac 95/5) afforded the trienol 3g (32 mg, 93.4 mol, 64%) as a colorless oil. IR (pur): 3391, 2927, 2857, 1719, 1454, 1275, 1074, 1027, 975, 736, 698 cm H NMR (400 MHz, C 6 D 6 ): (m, 2H), (m, 2H), 7.11 (m, 1H), (m, 4H), (m, 2H), 4.34 (s, 2H), 3.96 (q app, 1H, 3 J = 6.2 Hz), 3.29 (t, 2H, 3 J = 6.3 Hz), 2.01 (q app, 2H, 3 J = 7.2 Hz), (m, 13H), 0.87 (t, 3H, 3 J = 7.0 Hz). S23

24 13 C NMR (100 MHz, C 6 D 6 ): (s), (d), (d), (d), (d), (d), (d), (d, 2CH), (d, 2CH), (d), 73.0 (t), 72.6 (d), 70.2 (t), 37.8 (t), 32.9 (t), 32.2 (t), 29.7 (t), 26.3 (t), 25.5 (t), 23.0 (t), 14.3 (q). MS (EI, 70 ev) m/z (abundance): 324 (M-H 2 +, 1), 233 (4), 218 (6), 145 (11), 136 (25), 131 (11), 117 (17), 105 (16), 93 (19), 92 (11), 91 (100), 81 (16), 80 (11), 79 (29), 77 (11), 71 (18), 67 (22), 65 (13), 57 (11), 55 (26). HRMS calculated for (M+Na + ): Found: (2E,4E,6E)-11-Benzyloxy-1-phenylundeca-2,4,6-trien-1-ol (3h) 3h H C 24 H 28 2 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1a (35 mg, mmol, 1.0 equiv) was applied to alcohol 2e (27 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3h (18 mg, 51.7 mol, 51%) as a colorless oil. IR (pur): 3341, 3027, 2936, 2857, 1601, 1493, 1452, 1358, 1098, 993, 967, 745, 697 cm H NMR (400 MHz, C 6 D 6 ): (m, 4H), (m, 4H), (m, 2H), 6.27 (ddd, 1H, 3 J = 15.1, 3 J = 10.4, 2 J = 1.2 Hz), (m, 3H), 5.73 (dd, 1H, 3 J = 15.2, 3 J = 6.4 Hz), 5.58 (dt, 1H, 3 J = 15.2, 3 J = 7.2 Hz), 5.01 (d, 1H, 3 J = 6.4 Hz), 4.33 (s, 2H), 3.28 (t, 2H, 3 J = 6.3 Hz), 1.99 (q app, 2H, 3 J = 7.3 Hz), 1.61 (br s, 1H), (m, 2H), (m, 2H). 13 C NMR (100 MHz, C 6 D 6 ): (s), (s), (d), (d), (d), (d), (d), (d), (d), (d, 2CH), (d, 2CH), (d, 2CH), (d), (d, 2CH), 74.8 (d), 73.0 (t), 70.2 (t), 32.9 (t), 29.7 (t), 26.3 (t). MS (EI, 70 ev) m/z (abundance): 239 (13), 222 (44), 221 (17), 220 (19), 219 (54), 204 (12), 193 (30), 191 (42), 180 (10), 179 (26), 178 (40), 167 (18), 166 (16), 165 (43), 155 (16), 128 (10), 115 (14), 105 (18), 92 (14), 91 (100), 85 (13), 77 (10), 65 (12). HRMS calculated for (M+Na + ): Found: (2E,4E,6E)-11-Benzyloxy-1-cyclohexylundeca-2,4,6-trien-1-ol (3i) 3i H C 24 H 34 2 Mol. Wt.: S24

25 The general procedure for the coupling reaction with 1-iodo-1,3-diene 1a (35 mg, mmol, 1.0 equiv) was applied to alcohol 2f (29 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3i (22 mg, 62.1 mol, 61%) as a colorless oil. IR (pur): 3424, 2924, 2852, 1721, 1685, 1451, 1363, 1266, 1099, 990, 734, 697 cm H NMR (400 MHz, CDCl 3 ): (m, 5H), (m, 4H), (m, 2H), 4.50 (s, 2H), 3.87 (t app, 1H, 3 J = 6.9 Hz), 3.47 (t, 2H, 3 J = 6.5 Hz), 2.12 (q app, 2H, 3 J = 7.3 Hz), (m, 16H). 13 C NMR (100 MHz, CDCl 3 ): (s), (d), (d), (d), (d), (d), (d), (d, 2CH), (d, 2CH), (d), 77.4 (d), 72.9 (t), 70.2 (t), 43.9 (d), 32.6 (t), 29.3 (t), 28.8 (t), 28.6 (t), 26.5 (t), 26.1 (t), 26.1 (t), 25.9 (t). MS (EI, 70 ev) m/z (abundance): 192 (1), 108 (12), 107 (40), 92 (21), 91 (100), 65 (14), 57 (15), 55 (10). HRMS calculated for (M+Na + ): Found: (4E,6E,8E)-13-(tert-Butyldiphenylsilanyloxy)-2-methyltrideca-4,6,8-trien-3-ol (3j) 3j H C 30 H 42 2 Mol. Wt.: The general procedure for the coupling reaction with 1-iodo-1,3-diene 1b (50 mg, mmol, 1.0 equiv) was applied to alcohol 2g (20 mg, mmol, 2.0 equiv). Purification by flash chromatography on silica gel (petroleum ether/etac gradient: 98/2 to 95/5) afforded the trienol 3j (23 mg, 49.7 mol, 49%) as a colorless oil. IR (pur): 3427, 2931, 2858, 1687, 1471, 1428, 1388, 1107, 996, 822, 740, 701, 613 cm H NMR (400 MHz, C 6 D 6 ): (m, 4H), (m, 6H), (m, 4H), (m, 2H), 3.70 (t app, 1H, 3 J = 6.3 Hz), 3.65 (t, 2H, 3 J = 6.2 Hz), 1.98 (q app, 2H, 3 J = 7.2 Hz), (m, 6H), 1.19 (s, 9H), 0.94 (d, 3H, 3 J = 6.8 Hz), 0.88 (d, 3H, 3 J = 6.9 Hz). 13 C NMR (100 MHz, C 6 D 6 ): (d, 4CH), (d), (d), (s, 2C), (d), (d), (d), (d), (d, 2CH), (d, 4CH), 77.6 (d), 64.0 (t), 34.4 (d), 32.8 (t), 32.4 (t), 27.1 (q, 3Me), 25.9 (t), 19.5 (s), 18.5 (q), 18.1 (q). MS (EI, 70 ev) m/z (abundance): 285 (2), 284 (5), 283 (21), 205 (18), 200 (20), 199 (100), 181 (13), 165 (12), 145 (12), 143 (11), 139 (54), 135 (10), 123 (11), 105 (12), 91 (22), 77 (20). S25