A. M. Echavarren et al.
Yield 92% (1230 mg). 1H NMR (400 MHz, CDCl3): d = 5.06 (m, 2H),
4.05 (m, 4H), 2.25 (d, J = 2.4 Hz, 2H), 2.18 (d, J = 8.0 Hz, 2H), 2.13–
2.02 (m, 4H), 2.06 (s, 6H), 2.00 (t, J = 2.7 Hz, 1H), 1.68 (s, 3H), 1.61 (s,
3H), 1.60 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d = 170.71
(2 C), 139.57 (C) 131.64 (C) 124.07 (CH), 117.47 (CH), 71.90 (CH), 71.10
(C) 65.49 (2CH2), 40.67 (C), 40.03 (CH2), 29.70 (CH2), 26.47 (CH2),
25.67 (2CH3), 22.02 (CH2), 20.82 (CH3), 17.67 (CH3), 16.04 (CH3) ppm;
HMRS-ESI m/z calcd for C20H29O4: 333.2071; found 333.2072 [MÀ1]+.
i: Butadiene monoxide (0.946 mL, 11.75 mmol) and dimethyl propargyl-
malonate (1.78 mL, 11.75 mmol) were added to
a mixture of [Pd2-
(dba)3·dba] (338.7 mg, 0.589 mmol) and dppe (245.5 mg, 0.616 mmol) in
dry THF (10 mL). The mixture was stirred for 3 h at 238C, the volatiles
were evaporated, and the residue was dissolved in Et2O and filtered
through a plug of Celite. After chromatography (hexane/EtOAc 4:1 to
2:1), dimethyl 2-(4-hydroxybut-2-enyl)-2-(prop-2-ynyl)malonate was ob-
tained as a colorless oil (1.64 g, 58%): 1H NMR (400 MHz, CDCl3): d =
5.80 (dtt, J = 15.5, 5.6, 1.2 Hz, 1H), 5.51 (dtt, J = 15.1, 7.5, 1.5 Hz, 1H),
4.09 (d, J = 5.6 Hz, 2H), 3.74 (s, 6H), 2.82–2.80 (m, 2H), 2.79 (d, J =
2.9 Hz, 2H), 2.02 (t, J = 2.6 Hz, 1H), 1.5 (brs, 1H).
N-((E)-3,7-Dimethylocta-2,6-dien-1-yl)-N-(prop-2-ynyl)-N-(toluene-4-sul-
fonyl)amine (21)
i: A solution of toluene-4-sulfonamide (863 mg, 5.04 mmol) in DMF
(10 mL) was added at 08C to a suspension of NaH (60% in mineral oil,
202 mg, 5.04 mmol) in DMF (5 mL), followed by geranyl bromide
(1.00 mL, 5.04 mmol). The mixture was stirred for 4 h at 238C and was
then quenched with H2O. After extractive workup (EtOAc/HCl (10%))
and chromatography (hexane/EtOAc 20:1 to 10:1), N-((2E)-3,7-dimethy-
locta-2,6-dienyl)toluene-4-sulfonamide[35] was obtained as a vitreous solid
(203 mg, 13%): 1H NMR (300 MHz, CDCl3): d = 7.74 (d, J = 8.1 Hz,
2H), 7.30 (d, J = 8.3 Hz, 2H), 5.04 (m, 2H), 4.27 (t, J = 5.3 Hz, 1H),
3.55 (t, J = 6.5 Hz, 2H), 2.42 (s, 3H), 1.98–1.91 (m, 4H), 1.66 (s, 3H),
1.56 (s, 3H), 1.53 (s, 3H) ppm.
ii: A solution of the dimethyl 2-(4-hydroxybut-2-enyl)-2-(prop-2-ynyl)-
malonate (554 mg, 2.3 mmol) in DMF (2 mL) was added at 08C to a sus-
pension of NaH (101 mg, 2.5 mmol, 60% mineral oil) in DMF (3 mL).
After 30 min, neryl bromide was added and the mixture was stirred over-
night. After extractive workup (water/Et2O) and chromatography
(hexane/EtOAc 95:5), 27 (373 mg, 55%) was obtained: 1H NMR
(400 MHz, CDCl3): d = 5.70 (dt, J = 15.2, 5.9 Hz, 1H), 5.48 (dt, J =
15.2, 7.6 Hz, 1H), 4.92 (s, 1H), 4.86 (s, 1H), 3.87 (d, J = 6.5 Hz, 2H),
3.82 (s, 2H), 3.72, (s, 6H), 2.79 (d, J = 7.3 Hz, 2H), 2.77 (d, J = 2.6 Hz,
2H), 2.00 (t, J = 2.6 Hz, 1H), 1.70 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 170.10, 142.18, 132.05, 126.25, 112.02, 73.72, 71.51, 69.85,
56.87, 52.69, 35.04, 22.69, 19.40 ppm; HMRS-CI m/z calcd for C16H22O5:
295.1545; found 295.1551 [M+1]+.
ii: N-((2E)-3,7-Dimethyl-octa-2,6-dienyl)toluene-4-sulfonamide (170 mg,
0.55 mmol) was added at 08C to a suspension of NaH (60% mineral oil,
22 mg, 0.55 mmol) in DMF (10 mL). After 10 min, propargyl bromide
(80% in toluene, 82 mg, 0.55 mmol,) was added, and the resulting mix-
ture was stirred at 238C overnight. After the usual workup (EtOAc/HCl
(10%)) and chromatography (hexane/EtOAc 30:1), 21 was obtained as a
colorless oil (133 mg, 70%): 1H NMR (300 MHz, CDCl3): d = 7.42 (d, J
= 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 5.05 (m, 2H), 4.05 (d, J =
2.4 Hz, 2H), 3.82 (d, J = 7.3 Hz, 2H), 2.42 (s, 3H), 2.05–1.96 (m, 4H),
1.67 (s, 3H), 1.65 (s, 3H), 1.58 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3;
DEPT): d = 143.35 (C), 142.48 (C), 136.17 (C), 131.88 (C), 129.38 (CH),
127.80 (CH), 123.71 (CH), 117.77 (CH), 77.08 (CH), 73.29 (C), 43.84
(CH2), 39.60 (CH2), 35.22 (CH2), 26.14 (CH2), 25.67 (CH3), 21.51 (CH3),
17.65 (CH3), 16.11 (CH3) ppm; EI-MS m/z (%): 69.00 (71), 91.00 (100),
155.00 (11), 190.15 (9), 222.00 (21), 276.10 (1).
Cyclization reactions: The enyne (0.10–0.50 mmol) in CH2Cl2 (1 mL) was
added to a mixture of gold(i) complex (2 mol%) in CH2Cl2 (2 mL) and
the mixture was stirred for the time and at the temperature indicated in
Scheme 6. The resulting mixture was filtered through SiO2 and the sol-
vent was evaporated to give the corresponding product, which was puri-
fied by column chromatography (EtOAc/hexane mixtures).
Tetracycle 15: Colorless oil: 1H NMR (500 MHz, CDCl3): d = 3.43 (s,
3H), 3.34 (s, 3H), 2.87 (qd, J = 7.3, 1.8 Hz, 1H), 2.80 (dd, J = 14.5,
1.8 Hz, 1H), 2.49 (d, J = 14.5 Hz, 1H), 2.28 (dd, J = 14.5, 2.8 Hz, 1H),
1.57 (m, 2H), 1.13 (dd, J = 7.3, 2.9 Hz, 1H), 1.09 (d, J = 8.9 Hz, 1H),
1.06 (s, 3H), 1.03–0.96 (m, 4H), 0.92 (s, 3H), 0.78 (td, J = 13.0, 4.4 Hz,
1H), 0.64 (td, J = 8.6, 6.0 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): d
=
173.77, 171.67, 68.18, 52.74, 52.41, 40.14, 38.21, 34.92, 34.30, 33.07,
28.96, 28.23, 23,96, 20.24, 17.56, 16.59, 14.40 (one carbon signal over-
laps) ppm; HMRS-FAB m/z calcd for C18H26O4: 306.1813; found
306.1818. The structure of 15 was confirmed by COSY and NOESY ex-
periments.
(E)-7,11-Dimethyldodeca-6,10-dien-1-yn-3-yl 4-methoxybenzoate (23)
i: A solution of (4E)-5,9-dimethyl-4,8-deca-4,8-dienal[36] (353 mg,
1.96 mmol) in THF (5 mL) was added at 08C to a solution of propargyl-
magnesium bromide (0.5m in THF, 5.88 mL, 2.94 mmol) and the mixture
was stirred at 238C for 2 h. After extractive workup (Et2O) and chroma-
tography (hexane/EtOAc 30:1), (E)-7,11-dimethyldodeca-6,10-dien-1-yn-
3-ol was obtained as a yellow oil (218 mg, 54%): 1H NMR (300 MHz,
CDCl3): d = 5.16–5.04 (m, 2H), 4.35 (m, 1H), 2.47 (t, J = 2.0 Hz, 1H),
2.13–2.08 (m, 2H), 1.98–1.91 (m, 5H), 1.72–1.65 (m, 1H), 1.61 (s, 3H),
1.55 (s, 3H), 1.52 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3; DEPT): d =
136.33 (C), 131.38 (C), 124.17 (CH), 122.97 (CH), 84.99 (C), 72.84 (CH),
61.78 (CH), 39.63 (CH2), 37.51 (CH2), 31.83 (CH2), 26.53 (CH2), 17.59
(CH3), 15.92 (CH3) ppm; HRMS-EI m/z calcd for C14H22O: 205.1592;
found 205.1589 [MÀ1]+.
Dimethyl 3-((E)-2,6-Dimethylhepta-1,5-dienyl)cyclopent-3-ene-1,1-dicar-
boxylate (16): Yellow oil: 1H NMR (300 MHz, CDCl3): d = 5.73 (brs,
1H), 5.41 (brs, 1H), 5.09 (m, 1H), 3.74 (s, 6H), 3.20 (d, J = 1.8 Hz, 2H),
3.06 (s, 2H), 2.2–2.0 (m, 4H), 1.82 (s, 3H), 1.68 (s, 3H), 1.60 (s,
3H) ppm; 13C NMR (75 MHz, CDCl3):
d = 172.66, 139.26, 138.74,
131.74, 124.62, 123.92, 120.29, 59.29, 52.81, 43.45, 41.15, 40.39, 26.76,
25.66, 18.28, 17.67 ppm; HMRS-CI m/z calcd for C18H26O4: 306.1831;
found 306.1833.
Tetracycle 18: White solid: mp 72.5–748C; 1H NMR (500 MHz, CDCl3):
d = 8.17 (d, J = 7.3 Hz, 2H), 8.05 (d, J = 7.4 Hz, 2H), 7.73–7.68 (m,
2H), 7.63–7.57 (m, 4H), 2.85 (d, J = 16.2 Hz, 1H), 2.76 (ddd, J = 15.8,
7.3, 2.2 Hz, 1H), 2.45 (dd, J = 15.8, 2.8 Hz, 1H), 2.38 (dd, J = 16.4,
2.2 Hz, 1H), 1.73 (dt, J = 13.1, 3.2 Hz, 1H), 1.67–1.61 (m, 1H), 1.26 (dd,
J = 7.1, 2.8 Hz, 1H), 1.18 (s, 3H), 1.11 (s, 3H), 0.97 (d, J = 8.8 Hz, 1H),
0.93–0.85 (m, 1H), 0.83 (s, 3H), 0.77–0.69 (m, 2H) ppm; 13C NMR
(125 MHz, CDCl3; DEPT): d = 173.95 (C), 135.91 (C), 134.46 (CH),
134.33 (CH), 132.14 (CH), 130.84 (CH), 128.56 (CH), 128.51 (CH),
100.68 (C), 39.96 (CH), 36.78 (CH2), 36.27 (CH2), 33.24 (C), 32.74 (CH2),
31.54 (C), 27.91 (CH3), 24.69 (CH), 23.97 (CH), 20.58 (C), 17.67 (CH3),
16.16 (CH2), 13.66 (CH3) ppm; HMRS-EI m/z calcd for C26H30O4S2:
470.1586; found 470.1577. The structure of 18 was confirmed by COSY,
NOESY, HMBC, and HMQC experiments and by X-ray diffraction.
ii: A solution of (E)-7,11-dimethyldodeca-6,10-dien-1-yn-3-ol (50 mg,
0.24 mmol) in CH2Cl2 (1.5 mL) was added to a mixture of pyridine
(0.078 mL, 0.97 mmol) and p-anisoyl chloride (83 mg, 0.48 mmol) in
CH2Cl2 (2.5 mL). The mixture was stirred for 24 h at 238C and was then
heated at reflux in CH2Cl2 for 1 h. The solvent was evaporated and the
resulting oil was purified by chromatography (hexane/EtOAc 9:1) to give
1
23 as a colorless oil (75 mg, 86%): H NMR (400 MHz, CDCl3): d = 8.02
(d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 5.41 (td, J = 6.6, 2.1 Hz,
1H), 5.18–5.05 (m, 2H), 3.86 (s, 3H), 2.48 (d, J = 2.3 Hz, 1H), 2.23 (q, J
= 7.3 Hz, 2H), 2.11–1.91 (m, 6H), 1.68 (s, 3H), 1.60 (m, 3H), 1.56 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): d
= 165.19, 163.55, 136.69,
131.81, 131.47, 124.19, 122.42, 113.6, 81.64, 73.48, 63.60, 55.43, 53.20,
39.66, 34.86, 26.62, 25.66, 23.52, 17.67, 16.00ppm; HMRS-ESI m/z calcd
for C23H33O8: 437.2175; found 437.2168 [M+H]+.
1
Tetracycle 20: H NMR (400 MHz, CDCl3): d = 4.07 (s, 2H), 3.90 (dd, J
= 15.2, 11.1 Hz, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 1.75 (ddd, J = 14.4, 7.4,
1.7 Hz, 1H), 1.73–1.57 (m, 2H), 1.55 (q, J = 14.4 Hz, 2H), 1.27 (dd, J =
14.4, 2.4, Hz, 1H), 1.05–0.94 (m with a s at 1.01, 5H), 0.94 (s, 3H), 0.89–
Dimethyl 2-[(E)-4-(2-methylallyloxy)but-2-enyl]-2-(prop-2-ynyl)malonate
(27)
0.76 (m with a s at 0.87, 5H), 0.66 (td, J = 8.5, 6.2 Hz, 1H) ppm;
1700
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2006, 12, 1694 – 1702