N.P. McLaughlin et al. / Tetrahedron 66 (2010) 9681e9687
9685
the mixture was stirred for a further 30 min until a greyish white
colour was obtained. Lithium (1.99 g, 287 mmol, 4.5 equiv) was
added and the mixture was stirred for 3 h maintaining the internal
temperature at ꢀ50 ꢂC until a white suspension was observed.
Propargyl alcohol 13 (4.40 mL, 75.6 mmol, 1.2 equiv) in THF (32 mL)
was added slowly and the reaction was stirred for 2 h at ꢀ50 ꢂC.1-
Bromoheptane (10.0 mL, 63.6 mmol, 1.0 equiv) in THF (32 mL) was
added and the reaction was warmed to room temperature over
16 h. The reaction was acidified to pH 1 using a 1.0 M aqueous HCl
solution (ca. 60 mL) before extraction with DCM (2ꢃ50 mL). The
combined organic layers were washed with brine (50 mL) and dried
over MgSO4. Filtration followed by solvent evaporation under re-
duced pressure afforded the crude product. Purification by vacuum
distillation afforded the title compound (6.96 g, 71%) as a colourless
liquid.24 Rf¼0.35 (c-HexeEtOAc; 4:1); bp 59e62 ꢂC (0.1 mbar); nmax
(neat/cmꢀ1) 3370, 2919, 2857, 2289, 2261, 1466, 11,381,014; m/z (EI)
154 (Mþ, 5%), 107 (50%), 93 (100%); dH (400 MHz, CDCl3) 0.84 (3H, t,
J¼7.0 Hz, CH3), 1.22e1.36 (8H, m, CH2), 1.47 (2H, pent, J¼7.0 Hz,
CH2), 1.69 (1H, br s, OH), 2.17 (2H, tt, J¼2.0, 7.0 Hz, CH2), 4.21 (2H, t,
J¼2.0 Hz, CH2) ppm; dC (100 MHz, CDCl3) 14.3 (CH3),18.9 (CH2), 22.8
(CH2), 28.8 (CH2), 29.0 (CH2), 29.05 (CH2), 31.9 (CH2), 51.6 (CH2),
78.5 (C), 86.9 (C) ppm.
to reflux for 9 h. The reaction was cooled to room temperature and
CCl4 was removed under reduced pressure. The resulting residue
was taken up in c-Hex (20 mL) and stirred vigorously for 15 min.
Filtration followed by solvent evaporation under reduced pressure
afforded the crude product. Purification by flash column chroma-
tography (c-Hex) afforded 9b (2.18 g, 75%) as a colourless liquid.13
Rf¼0.60 (c-Hex); nmax (neat/cmꢀ1) 3027, 2899, 2851, 1652, 1466,
35
1250, 1116, 966, 765; m/z (EI) calcd for C10
H Cl 174.1175, found
19
174.1174; dH (400 MHz, CDCl3) 0.87 (3H, t, J¼6.5 Hz, CH3), 1.26e1.39
(10H, m, CH2), 2.10 (2H, q, J¼6.5 Hz, CH2), 4.07 (2H, d, J¼6.5 Hz,
CH2), 5.56e5.64 (2H, m, CH) ppm; dC (100 MHz, CDCl3) 14.3 (CH3),
22.9 (CH2), 27.3 (CH2), 29.33 (CH2), 29.37 (CH2), 29.5 (CH2), 32.0
(CH2), 39.7 (CH2), 125.3 (CH), 135.7 (CH) ppm.
4.8. ( )-Heptadeca-1,9Z-diene-4,6-diyn-3-ol 1 [( )-falcarinol 1]13
A solution of hept-1-ene-4,6-diyn-3-ol 11 (0.87 g, 8.17 mmol,
1.00 equiv) in dry DMF (10 mL) was transferred by cannula into
a suspension of anhydrous K2CO3 (1.41 g, 10.2 mmol, 1.25 equiv),
copper iodide (0.11 g, 0.59 mmol, 0.07 equiv) and Et4NCl (0.16 g,
0.98 mmol, 0.12 equiv) in dry DMF (34 mL) under N2. The mixture
was stirred for 30 min at room temperature before (Z)-1-chlorodec-
2-ene 9b (1.57 g, 8.96 mmol, 1.10 equiv) in dry DMF (10 mL) was
added. The reaction was left to stir at room temperature for 8 h. The
reaction mixture was poured into water (250 mL) and extracted
with Et2O (3ꢃ50 mL). The combined organic extracts were washed
with a saturated solution of NH4Cl (50 mL) and brine (50 mL) then
dried over MgSO4. Filtration followed by solvent evaporation under
reduced pressure afforded the crude material as a mixture of two
regioisomeric products. Purification by flash column chromatog-
raphy (c-HexeEtOAc; 98:2) afforded the title compound 1 (0.92 g,
46%), and 15 (0.38 g, 19%) as colourless liquids. Data for 1: Rf¼0.40
(c-HexeEtOAc; 4:1); nmax (neat/cmꢀ1) 3375, 3088, 3023, 2958,
4.5. (Z)-Dec-2-ene-1-ol 1424
A solution of 2-decyn-1-ol (5.36 g, 34.8 mmol, 1.00 equiv) in
EtOAc (220 mL) was treated with quinoline (0.50 mL, 4.23 mmol,
0.12 equiv) and Lindlar’s catalyst (0.54 g, 10% w/w). The mixture
was stirred under an atmosphere (ca. 1 atm) of H2 for 9 h. The re-
action mixture was then filtered through a plug of Celite. Solvent
evaporation under reduced pressure and purification by flash col-
umn chromatography (c-HexeEtOAc; 3:1) afforded the title com-
pound (5.07 g, 93%) as a colourless liquid.24 Rf¼0.30 (c-HexeEtOAc;
4:1); nmax (neat/cmꢀ1) 3370, 3016, 2922, 2855, 1655, 1466, 1033; m/
z (EI) calcd for C10H20O 156.1514, found 156.1514; dH (300 MHz,
CDCl3) 0.92 (3H, t, J¼6.5 Hz, CH3), 1.31e1.46 (10H, m, CH2), 2.10 (2H,
q, J¼6.5 Hz, CH2), 4.22 (2H, d, J¼6.0 Hz, CH2), 5.53e5.73 (2H, m, CH)
ppm; dC (75 MHz, CDCl3) 14.3 (CH3), 22.9 (CH2), 27.6 (CH2), 29.35
(CH2), 29.39 (CH2), 29.8 (CH2), 32.0 (CH2), 58.8 (CH2), 128.5 (CH),
133.4 (CH) ppm.
2929, 2854, 2256, 1642, 1466, 1285, 1118; m/z (EI) calcd for C17H24
O
244.1827, found 244.1831; dH (400 MHz, CDCl3) 0.86 (3H, t,
J¼6.5 Hz, CH3), 1.25e1.35 (10H, m CH2), 1.86 (1H, d, J¼6.5 Hz, OH),
2.01 (2H, q, J¼7.0 Hz, CH2), 3.01 (2H, d, J¼7.0 Hz, CH2), 4.89 (1H, t,
J¼5.5 Hz, CH), 5.22 (1H, d, J¼10.0 Hz, CH), 5.32e5.38 (1H, m, CH),
5.42e5.52 (2H, m, CH), 5.92 (1H, ddd, J¼5.5, 10.0, 17.0 Hz, CH) ppm;
dC (100 MHz, CDCl3) 14.3 (CH3), 17.9 (CH2), 22.9 (CH2), 27.4 (CH2),
29.37 (CH2), 29.4 (CH2), 29.5 (CH2), 32.0 (CH2), 63.8 (CH), 64.2 (C),
71.5 (C), 74.3 (C), 80.5 (C), 117.3 (CH2), 122.1 (CH), 133.3 (CH), 136.4
(CH) ppm. Data for 15: Rf¼0.42 (c-HexeEtOAc; 4:1); nmax (neat/
cmꢀ1) 3362, 3087, 3011, 2928, 2253, 1664, 1640, 1465, 1406, 1264,
1224,1118; m/z (ESþ) calcd for C17H24ONa 267.1725, found 267.1725;
dH (400 MHz, CDCl3) 0.86 (3H, t, J¼7.0 Hz, CH3), 1.26e1.56 (12H, m,
CH2), 1.89 (1H, br s, OH), 3.13 (1H, q, J¼6.5 Hz, CH), 4.91 (1H, br s,
CH), 5.08 (1H, dt, J¼10.0, 1.5 Hz, CH), 5.23 (1H, dt, J¼1.5, 10.0 Hz,
CH), 5.25 (1H, dt, J¼1.5, 17.0 Hz, CH), 5.45 (1H, dt, J¼1.5, 17.0 Hz, CH),
5.70 (1H, ddd, J¼6.5, 10.0, 17.0 Hz, CH), 5.93 (1H, ddd, J¼5.5, 10.0,
17.0 Hz, CH) ppm; dC (100 MHz, CDCl3) 14.3 (CH3), 22.9 (CH2), 27.2
(CH2), 29.4 (CH2), 29.5 (CH2), 32.0 (CH2), 35.2 (CH2), 36.2 (CH), 63.8
(CH), 67.2 (C), 71.4 (C), 75.3 (C), 82.7 (C), 116.0 (CH2), 117.3 (CH2),
136.3 (CH), 136.9 (CH) ppm.
4.6. (Z)-1-Bromodec-2-ene 9a25
At 0 ꢂC under N2, a solution of (Z)-dec-2-ene-1-ol 14 (0.80 g,
5.12 mmol, 1.00 equiv) in dry DCM (20 mL) was treated with tri-
phenylphosphine (1.71 g, 5.17 mmol, 1.01 equiv) and carbon tetra-
bromide (1.48 g, 5.64 mmol, 1.10 equiv). The reaction mixture was
warmed to room temperature and stirred for 1.5 h. Solvent evap-
oration under reduced pressure and purification by flash column
chromatography (c-Hex) afforded 9a (1.11 g, 99%) as a colourless
liquid. Rf¼0.70 (c-Hex); nmax (neat/cmꢀ1) 3026, 2909, 2842, 1648,
1465, 1204, 1145, 965, 752,658; m/z (ESþ) 231 (MNaþ, (79Br) 50%),
233 (MNaþ, (81Br) 50%); HRMS calcd for C10H1979Br 218.0670, found
218.0670; dH (400 MHz, CDCl3) 0.87 (3H, t, J¼6.5 Hz, CH3), 1.21e1.32
(8H, m, CH2), 1.38 (2H, pent, J¼7.0 Hz, CH2), 2.11 (2H, q, J¼7.0 Hz,
CH2), 3.99 (2H, d, J¼8.0 Hz, CH2), 5.55e5.61 (1H, m, CH), 5.67e5.74
(1H, m, CH) ppm; dC (100 MHz, CDCl3) 14.3 (CH3), 22.9 (CH2), 27.2
(CH2), 27.6 (CH2), 29.3 (CH2), 29.4 (CH2), 32.0 (CH2), 125.4 (CH),
136.3 (CH) ppm (Broadening of peak at 29.3 ppm observed for two
coincident CH2 carbons).
4.9. Heptadeca-1,9Z-diene-4,6-diyn-3-one 2 [falcarinone 2]
A solution of 1 (86.0 mg, 0.35 mmol, 1.00 equiv) in DCM (1.5 mL)
was treated with DesseMartin periodinane (225 mg, 0.53 mmol,
1.50 equiv). The mixture was stirred at room temperature for
30 min before being quenched with a saturated Na2S2O3 solution
(10 mL). The resulting mixture was extracted with DCM (2ꢃ10 mL).
Combined organic layers were washed with brine (15 mL) and
dried over MgSO4. Filtration followed by solvent evaporation under
reduced pressure afforded the crude product. Purification by flash
column chromatography (c-HexeEtOAc; 98:2) afforded the title
4.7. (Z)-1-Chlorodec-2-ene 9b13
A
solution of (Z)-dec-2-ene-1-ol 14 (2.58 g, 16.5 mmol,
1.00 equiv) in CCl4 (16.5 mL) was treated with triphenylphosphine
(4.59 g, 17.5 mmol, 1.06 equiv). The mixture was stirred and heated