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A solution of 1-bromopentane (1.0 mL, 8.1 mmol, 1 eq) and Ph3P (2.32 g, 8.8 mmol, 1.1 eq) in anhydrous CH3CN (6 mL) under N2 was refluxed for 20 h. The reaction mixture was concentrated in vacuo and the crude product was chromatographed (SiO2, 3×20 cm, 10% EtOAc/hexanes-50% iPrOH/EtOAc, gradient elution) to afford phosphonium salt (3.27 g, 98%) as a white foam; 1H NMR (CDCl3, 400 MHz) δ 7.84-7.73 (m, 9H), 7.69-7.65 (m, 6H), 3.78-3.71 (m, 2H), 1.58-1.57 (m, 4H), 1.25 (s, 2H, J=7.2 Hz), 0.78 (t, 3H, J=7.3 Hz); 13C NMR (CDCl3, 100 MHz) δ 134.9 (3, d, J=2 Hz), 133.6 (6, d, J=10 Hz), 130.4 (6, d, J=12 Hz), 118.3 (3, d, J=86 Hz), 32.3 (d, J=15 Hz), 22.9, 22.3, 22.2 (d, J=3 Hz), 13.6; IR (film) νmax 3405, 2921, 2864, 1438, 1112, 996, 749, 723, 690 cm−1; ESI (M−Br+) 333. A solution of phosphonium salt (3.2 g, 7.74 mmol, 1.1 eq) in anhydrous THF (60 mL) under N2 at −78° C. was treated with n-BuLi (2.0M, 7.0 mL, 14.0 mmol, 2.0 eq). The reaction mixture was warmed to 25° C. and allowed to stir for 10 min. The reaction was recooled to −78° C. and treated with a solution of 2-cyanobenzaldehyde (0.9119 g, 6.95 mmol, 1 eq) in anhydrous THF (15 mL). The reaction mixture was then warmed to 25° C. and stirred for 1 h before an aqueous solution of saturated NH4Cl (100 mL) was added. The aqueous layer was extracted with EtOAc (3×100 mL) and the organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 6×20 cm, 0-5% EtOAc/hexanes, gradient elution) to afford CN-alkene (0.9796 g, 76%) as a clear oil (mixture of E/Z isomers); 1H NMR (CDCl3, 400 MHz) δ 7.64-7.22 (m, 4H), [6.72 (d, J=15.7 Hz)+6.59 (d, J=11.6 Hz)][1H], [6.41 (dt, J=15.7, 7.0 Hz)+5.90 (dt, J=11.6, 7.5 Hz)][1H], [2.27 (qd, J=7.6, 1.4 Hz)+2.21 (qd, J=7.3, 1.7 Hz)][2H], 1.50-1.20 (m, 4H), [0.91 (t, J=7.2 Hz)+0.84 (t, J=7.2 Hz)][3H]; 13C NMR (CDCl3, 100 MHz) δ 141.3, 141.2, 137.4, 136.8, 132.8, 132.7, 132.6, 132.2, 129.4, 126.8, 125.8, 125.3, 125.0, 118.1, 118.0, 112.2, 110.4, 32.8, 31.6, 31.1, 28.4, 22.2, 13.9, 13.8; IR (film) νmax 2957, 2928, 2858, 2224, 1647, 1596, 1478, 1466, 1448, 966, 759 cm−1; FABHRMS (NBA-NaI) m/z 186.1285 (C13H15N+H+ requires 186.1283). A solution of CN-alkene (0.9394 g, 5.1 mmol, 1 eq) in anhydrous toluene (10 mL) under N2 at 0° C. was treated with DIBAL (1M, 5.6 mL, 5.6 mmol, 1.1 eq). The reaction mixture was stirred for 5 min before an aqueous saturated solution of NH4Cl (60 mL) was added. The mixture was stirred at 25° C. for 15 min before the aqueous layer was extracted with EtOAc (3×60 mL). The organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 4×20 cm, 0-4% EtOAc/hexanes, gradient elution) to afford CHO-alkene (0.86 g, 91%) as a clear oil (mixture of E/Z isomers); 1H NMR (CDCl3, 400 MHz) δ [10.26+10.22][s, 1H], [7.87 (dd, J=7.8, 1.4 Hz)+7.77 (dt, J=7.6, 0.9 Hz)][1H], 7.54-7.23 (m, 3H), [7.15 (dt, J=15.6, 1.5 Hz)+6.77 (d, J=11.5 Hz)][1H], [6.13 (dt, J=15.6, 6.9 Hz) +5.90 (dt, J=11.5, 7.5 Hz)][1H], [2.26 (qd, J=7.5, 1.5 Hz)+2.03 (qd, J=7.3, 1.6 Hz)][2H], 1.50-1.18 (m, 4H), [0.91 (t, J=7.3 Hz)+0.79 (t, J=7.3 Hz)][3H]; 13C NMR (CDCl3, 100 MHz) δ 192.4, 141.0, 137.5, 136.2, 133.6, 133.5, 132.5, 130.5, 130.4, 128.4, 127.4, 127.1, 126.9, 125.6, 125.1, 33.0, 31.4, 31.2, 28.1, 22.21, 22.16, 13.9, 13.8; IR (film) νmax 2957, 2928, 2871, 1695, 1597, 1566, 1480, 1466, 1451, 1389, 1289, 1196, 968, 762 cm−1; FABHRMS (NBA-NaI) m/z 189.1280 (C13H16O+H+ requires 189.1279). A solution of 5-bromo-pentanol (0.9889 g, 5.9 mmol, 1 eq) in anhydrous CH2Cl2 (20 mL) under N2at 25° C. was treated with anhydrous Et3N (1.0 mL, 7.2 mmol, 1.2 eq), TBDPSCl (1.7 mL, 6.5 mmol, 1.1 eq) and DMAP (0.23 g, 1.9 mmol, 0.3 eq). The reaction mixture was stirred for 2 h before an aqueous solution of saturated NH4Cl (100 mL) was added. The aqueous layer was extracted with EtOAc (3×100 mL) and the organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 5×20 cm, 0-20% EtOAc/hexanes, gradient elution) to afford TBDPSOH (2.35 g, 98%) as a clear oil; 1H NMR (CDCl3, 400 MHz) δ 7.66-7.60 (m, 4H), 7.44-7.33 (m, 6H), 3.64 (t, 2H, J=6.1 Hz), 3.37 (t, 2H, J=6.9 Hz), 1.82 (p, 2H, J=7.3 Hz), 1.59-1.45 (m, 4H), 1.03 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 135.6, 129.6, 127.6, 127.5, 63.5, 33.9, 32.5, 31.6, 26.8, 24.5, 19.2; IR (film) νmax 3069, 2930, 2856, 2359, 1470, 1427, 1389, 1106, 822, 738, 700 cm−1; FABHRMS (NBA-CsI) m/z 537.0235 (C21H29OSiBr+Cs+ requires 537.0225). A solution of TBDPSOH(2.35 g, 5.8 mmol, 1 eq) and Ph3P (1.67 g, 6.4 mmol, 1.1 eq) in anhydrous CH3CN (6 mL) under N2 was refluxed for 22 h. The reaction mixture was concentrated in vacuo and the crude product was chromatographed (SiO2, 5×20 cm, 20% EtOAc/hexanes-50% iPrOH/EtOAc, gradient elution) to afford TBDPSphosphonium salt (2.82 g, 73%) as a white foam; 1H NMR (CDCl3, 400 MHz) δ 7.84-7.72 (m, 9H), 7.67-7.62 (m, 6H), 7.58-7.55 (m, 4H), 7.38-7.29 (m, 6H), 3.84 (m, 2H), 3.57 (t, 2H, J=6.3 Hz), 1.75-1.51 (m, 6H), 0.95 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 135.4 (4), 134.9 (3, d, J=3 Hz), 133.8 (2), 133.7 (6, d, J=10 Hz), 130.4 (6, d, J=13 Hz), 129.5 (2), 127.6 (4), 118.3 (3, d, J=85 Hz), 63.4, 31.9, 26.8 (3), 25.3, 23.0, 22.4 (d, J=3 Hz), 19.1; IR (film) νmax 3394, 2928, 2856, 2359, 1438, 1111, 996, 743, 703, 689 cm−1; ESI (M−Br+) 587. A solution of TBDPSphosphonium salt (2.5783 g, 3.9 mmol, 1.1 eq) in anhydrous THF (25 mL) under N2 at −78° C. was treated with n-BuLi (2.0M, 3.5 mL, 7.0 mmol, 2 eq). The reaction mixture was warmed to 25° C. and allowed to stir for 10 min. The reaction was recooled to −78° C. and treated with a solution of CHO-alkene (0.66 g, 3.5 mmol, 1 eq) in anhydrous THF (10 mL). The reaction mixture was then warmed to 25° C. and stirred for 1 h before an aqueous solution of saturated NH4Cl (60 mL) was added. The aqueous layer was extracted with EtOAc (3×60 mL) and the organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 3×20 cm, 0-20% EtOAc/hexanes, gradient elution) to afford alkene-alkene (0.57 g, 33%) as a clear oil (mixture of E/Z isomers); 1H NMR (CDCl3, 400 MHz) δ 7.67-7.57 (m, 4H), 7.45-7.33 (m, 7H), 7.24-7.09 (m, 3H), 6.63-6.35 (m, 2H), 6.14-5.61 (m, 2H), 3.70-3.58 (m, 2H), 2.21-2.06 (m, 4H), 1.64-1.23 (m, 8H), 1.04-1.01 (m, 9H), 0.94-0.80 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ 136.6, 136.5, 135.5, 134.1, 133.2, 133.0, 132.8, 129.5, 129.1, 129.0, 128.0, 127.8, 127.6, 126.8, 126.2, 125.3, 63.7, 33.0, 32.2, 32.1, 32.0, 28.19, 28.15, 26.8, 26.0, 25.9, 25.7, 22.3, 19.2, 13.9; IR (film) νmax 2929, 2857, 1473, 1428, 1111, 823, 740, 701 cm−1; FABHRMS (NBA-CsI) m/z 629.2226 (C34H44OSi+Cs+ requires 629.2216). Alkene-alkene (0.4311 g, 0.87 mmol, 1 eq) was combined with 10% Pd/C (0.33 g) under Ar. Absolute EtOH (8 mL) was added and the atmosphere was purged to H2. The reaction was stirred at 25° C. for 24 h. The crude product was filtered through Celite to afford alkane (347.3 mg, 80%) as a clear oil; 1H NMR (CDCl3, 400 MHz) δ 7.84-7.78 (m, 4H), 7.56-7.44 (m, 6H), 7.27-7.21 (m, 4H), 3.80 (t, 2H, J=6.5 Hz), 2.73 (td, 4H, J=7.9, 2.4 Hz), 1.70 (m, 6H), 1.58-1.42 (m, 10H), 1.19 (s, 9H), 1.02 (t, 3H, J=7.0 Hz); 13C NMR (CDCl3, 100 MHz) δ 140.5, 140.4, 135.6, 134.1, 129.5, 129.1, 127.6, 125.7, 63.9, 32.7, 32.6, 32.5, 31.7, 31.3, 29.50, 29.46, 26.9, 25.7, 22.6, 19.2, 14.1; IR (film) νmax 3070, 2928, 2856, 1956, 1888, 1823, 1589, 1471, 1427, 1389, 1361, 1188, 1111, 1007, 939, 910, 823, 740, 701, 614 cm−1; FABHRMS (NBA-CsI) m/z 633.2525 (C34H48OSi+Cs+ requires 633.2529). A solution of alkane (325.7 mg, 0.65 mmol, 1 eq) in anhydrous THF (6 mL) under N2 was treated with TBAF (1M in THF, 1.3 mL, 1.3 mmol, 2 eq) and stirred at 25° C. for 1.5 h. Water (30 mL) was added and the aqueous layer was extracted with EtOAc (3×30 mL). The organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 2.5×15 cm, 10-33% EtOAc/hexanes, gradient elution) to afford alcohol (142.7 mg, 84%) as a clear oil; 1H NMR (CDCl3, 400 MHz) δ 7.18-7.11 (m, 4H), 3.64 (t, 2H, J=6.6 Hz), 2.66-2.61 (m, 4H), 1.64-1.57 (m, 6H), 1.45-1.32 (m, 10H), 0.94 (t, 3H, J=6.9 Hz); 13C NMR (CDCl3, 100 MHz) δ 140.4, 140.2, 129.02, 128.98, 125.7, 125.6, 62.7, 32.6 (2), 32.5, 31.7, 31.22, 31.20, 29.5, 29.4, 25.6, 22.6, 14.0; IR (film) νmax 3340, 2928, 2856, 1489, 1463, 1055, 750 cm−1; FABHRMS (NBA-NaI) m/z 262.2308 (C18H30O+.+ requires 262.2297). A solution of alcohol (128.9 mg, 0.49 mmol, 1 eq) in anhydrous DMF (1 mL) under N2 was treated with PDC (0.91 g, 2.4 mmol, 5 eq) at 25° C. for 8 h. Water (30 mL) was added and the aqueous layer was extracted with EtOAc (3×30 mL). The organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 2.5×15 cm, 20-50% EtOAc/hexanes, gradient elution) to afford acid (88.1 mg, 65%) as a clear oil; 1H NMR (CDCl3, 400 MHz) δ 7.16-7.10 (m, 4H), 2.61 (q, 4H, J=7.2 Hz), 2.37 (t, 2H, J=7.5 Hz), 1.70 (p, 2H, J=7.7 Hz), 1.59 (septet, 4H, J=7.7 Hz), 1.48-1.30 (m, 8H), 0.90 (t, 3H, J=7.0 Hz); 13C NMR (CDCl3, 100 MHz) δ 180.3, 140.5, 140.0, 129.1, 129.0, 125.8, 125.7, 34.0, 32.7, 32.4, 31.7, 31.3, 30.9, 29.4, 29.1, 24.6, 22.6, 14.0; IR (film) νmax 2928, 2858, 2359, 1709, 1489, 1462, 1412, 1287, 1242, 941, 751 cm−1; FABHRMS (NBA-NaI) m/z 299.1976 (C18H28O2+Na+ requires 299.1987). A solution of acid (62.3 mg, 0.23 mmol, 1 eq) in anhydrous CH2Cl2 (1.2 mL) under N2at 0° C. was treated with oxalyl chloride (2M in CH2Cl2, 0.34 mL, 0.68 mmol, 3 eq). The reaction mixture was warmed to 25° C. and stirred for 3 h before the solvent was removed in vacuo. The residue was cooled to 0° C. and treated with excess concentrated NH4OH (5 mL). Water (30 mL) was added and the aqueous layer was extracted with EtOAc (3×30 mL). The organic layers were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2, 2.5×15 cm, 33-66% EtOAc/hexanes, gradient elution) to afford 6 (36.9 mg, 59%) as a white solid; mp 58-59° C.; 1H NMR (CDCl3, 400 MHz) δ 7.14-7.08 (m, 4H), 5.91 (br, 1H), 5.49 (br, 1H), 2.58 (q, 4H, J=6.4 Hz), 2.20 (t, 2H, J=7.6 Hz), 1.66 (hextet, 2H, J=7.7 Hz), 1.55 (hex, 4H, J=8.4 Hz), 1.45-1.28 (m, 8H), 0.88 (t, 3H, J=6.8 Hz); 13C NMR (CDCl3, 100 MHz) δ 175.7, 140.5, 140.0, 129.1, 129.0, 125.8, 125.7, 35.8, 32.6, 32.4, 31.7, 31.2, 30.9, 29.4, 29.2, 25.4, 22.6, 14.1; IR (film) νmax 3366, 3195, 2925, 2855, 1664, 1629, 1491, 1465, 1412, 750 cm−1; FABHRMS (NBA-NaI) m/z 276.2329 (C18H29ON+H+ requires 276.2327).
