CDCl3): d = 13.90, 18.79, 20.80, 30.08, 32.02, 36.70, 37.96, 65.66,
74.00, 170.12; MS (ESI) m/z 312.2 (M+); Anal. Cal. for C10H17IO3
(312.022): C, 38.48; H, 5.49. Found: C, 38.40; H, 5.59%.
(3R)-[(tert-Butyldimethylsilyl)oxy]-1-propyl-pent-4-enyl
hex-
(5R)-enoate (13). To a stirred solution of 4 (0.26 g, 1.0 mmol)
in CH2Cl2 (10 mL) was added DCC (0.31 g, 1.5 mmol) followed
by a catalytic amount of DMAP at 0 ◦C. After 5 min, 5-hexenoic
acid (0.172 g, 1.5 mmol) was added and the mixture was stirred
for 17 h at room temperature. Water (10 mL) was added and the
mixture was extracted with CH2Cl2 (20 mL). The layers were
separated, the organic layer was washed successively with 10%
aqueous HCl, saturated NaHCO3 solution and brine. The organic
layer was dried (Na2SO4), the solvent was evaporated and the
residue was purified by chromatography on SiO2 (EtOAc–hexane
1 : 8) to give 0.308 g (0.87 mmol, 86%) of ester 13 as a yellow
(1R)-Acetoxy-(3R)-hydroxy-1 propyl-pent-4-ene (12). A mix-
ture of 6b (1.0 g, 3.2 mmol), iodine (36 mg, 0.28 mmol) and freshly
activated zinc (0.52 g, 8.0 mmol) in anhydrous MeOH (10 mL) was
refluxed for 8 h under a N2 atmosphere. The solution was filtered
and the residue was washed with MeOH (2 × 20 mL). The filtrates
were combined and concentrated. The residue was taken up in
ethyl acetate (30 mL) and washed with water (2 × 20 mL) and
dried (Na2SO4). The solvent was evaporated and the residue was
chromatographed on SiO2 (6% EtOAc in hexane) to give 0.452 g
oil. Ee 96%; [a]20 = +13.6 (c 1.0, CHCl3). IR (neat): 1735 cm−1;
D
(2.43 mmol, 76%) of 12 as a colorless liquid. Ee 96%; [a]20 = −5.9
1H NMR (400 MHz, CDCl3): d = 0.09 (s, 6 H), 0.86 (s, 9 H),
0.92 (t, J = 6.6 Hz, 3 H), 1.22–1.34 (m, 4 H), 1.37–1.40 (m, 2 H),
1.45–1.56 (m, 2 H), 1.85–2.01 (m, 2 H), 2.20 (t, J = 7.1 Hz, 2 H),
3.78–3.86 (m, 1 H), 4.23–4.35 (m, 1 H), 5.05 (d, J = 8.6 Hz, 2 H),
5.20 (d, J = 16.0 Hz, 2 H), 5.58–5.71 (m, 2 H); 13C NMR
(75 MHz, CDCl3): d = −4.74, −4.74, 13.90, 17.92, 18.80, 25.80,
26.95, 28.80, 33.74, 34.23, 37.10, 41.25, 70.99, 114.48, 115.45,
129.30, 138.60, 139.22, 159.00, 172.70; MS (ESI) m/z 354.61
(M+); Anal. Cal. for C20H38O3Si (354.259): C, 67.74; H, 10.80.
Found: C, 67.70; H, 11.00%.
D
(c 1.0, CHCl3). IR (neat): 3410, 1725 cm−1; 1H NMR (400 MHz,
CDCl3): d = 0.86 (t, J = 7.2 Hz, 3 H), 1.28–1.36 (m, 4 H), 1.86–2.00
(m, 2 H), 2.11 (s, 3 H), 2.21–2.29 (br s, 1 H), 4.18–4.26 (m, 1 H),
4.89–4.96 (m, 1 H), 5.02 (d, J = 8.6 Hz, 1 H), 5.18 (d, J = 15.2 Hz,
1 H), 5.58–5.71 (m, 1 H); 13C NMR (75 MHz, CDCl3): d = 13.99,
18.88, 20.85, 37.10, 41.00, 71.92, 74.27, 114.82, 141.48, 170.11;
MS (ESI) m/z 186.3 (M+); Anal. Cal. for C10H18O3 (186.125): C,
64.49; H, 9.74. Found: C, 64.30; H, 9.90%.
(1R)-Acetoxy-(3R)-[(tert-butyldimethylsilyl)oxy]-1-propyl-pent-
4-ene (4a). To a solution of 12 (0.350 g, 1.88 mmol) and
imidazole (0.253 g, 3.72 mmol) in dry DMF (4 mL) was added
TBSCl (0.283 g, 1.88 mmol) at room temperature and the mixture
was stirred for 16 h. The reaction mixture was diluted with
water (3 mL) and extracted with diethyl ether (2 × 10 mL).
The organic phase was washed with brine (1 × 5 mL), dried
(Na2SO4) and concentrated to afford the crude product. Column
chromatography (9% EtOAc in hexane) of the crude product
afforded 4a (0.53 g, 1.76 mmol, 93%) as a colorless liquid. Ee
(3R)-Hydroxy-1-propyl-pent-4-enyl hex-(5R)-enoate (14). To a
solution of 13 (0.25 g, 0.71 mmol) in THF (8 mL), TBAF (1.3 mL,
1.26 mmol, 1 M in THF) was added at 0 ◦C. After stirring for
3 h at ambient temperature, the mixture was quenched with water
(2 mL) and extracted with ethyl acetate (2 × 10 mL). The combined
organic phase was dried (Na2SO4), the solvent was evaporated and
the residue was chromatographed on SiO2 (EtOAc–hexane 1 : 6)
to give 0.119 g (0.53 mmol, 75%) of 14 as a viscous liquid. Ee 96%;
[a]20 = +6.6 (c 1.0, CHCl3). IR (neat): 3410, 1730 cm−1; 1H NMR
D
96%; [a]20 = −8.9 (c 1.0, CHCl3). IR (neat): 1735 cm−1; 1H NMR
(400 MHz, CDCl3): d = 0.90 (t, J = 7.4 Hz, 3 H), 1.23–1.37 (m,
2 H), 1.50–1.92 (m, 6 H), 2.06 (q, J = 6.8 & 12.4 Hz, 2 H), 2.28 (t,
J = 7.2, 2 H), 2.48 (br s, 1 H), 4.13 (q, J = 6.5 & 12.4 Hz, 1 H), 4.88–
5.24 (m, 5 H), 5.64–5.90 (m, 2 H); 13C NMR (75 MHz, CDCl3):
d = 13.99, 18.80, 28.80, 33.70, 34.20, 37.30, 41.00, 71.99, 74.27,
114.82, 115.48, 136.60, 141.48, 170.70; MS (ESI) m/z 226.3 (M+);
Anal. Cal. for C14H24O3 (226.157): C, 69.96; H, 10.06. Found: C,
69.52; H, 9.67%.
D
(400 MHz, CDCl3): d = 0.06 (s, 6 H), 0.88 (s, 9 H), 0.91 (t, J =
6.7 Hz, 3 H), 1.22–1.34 (m, 4 H), 1.85–2.02 (m, 2 H), 2.16 (s, 3 H),
4.03–4.12 (m, 1 H), 4.88–4.96 (m, 1 H), 5.04 (d, J = 8.5 Hz, 1 H),
5.20 (d, J = 15.4 Hz, 1 H), 5.56–5.75 (m, 1 H); 13C NMR
(75 MHz, CDCl3): d = −4.74, −4.74, 13.90, 17.92, 18.80, 20.80,
25.81, 26.90, 29.90, 37.19, 41.30, 70.92, 74.67, 115.82, 139.48,
170.31; MS (ESI) m/z 300.5 (M+); Anal. Cal. for C16H32O3Si
(300.212): C, 62.18; H, 9.69. Found: C, 62.00; H, 9.85%.
(7R,9R)-7-Hydroxy-9-propyl-5-nonen-9-olide (1). A mixture
of 14 (91 mg, 0.40 mmol) in anhydrous CH2Cl2 (10 mL) and
Grubbs second generation catalyst (15 mg, 0.003 mmol) was
degassed with N2 for 15 min, and refluxed for 16 h. The solvent
was evaporated to leave a dark brown residue. The crude product
was purified by preparative TLC (EtOAc–hexane 1 : 7) to give
analytically pure Herbarumin III (1) as a gum (46 mg, 0.22 mmol,
(3R)-[(tert-Butyldimethylsilyl)oxy]-oct-1-en-(5R)-ol (4). Com-
pound 4a (0.45 g, 1.5 mmol) was dissolved in a 0.3 M K2CO3
solution in MeOH (10 mL) and the reaction mixture was stirred
at room temperature for 6 h. After being neutralized with 0.2 M
HCl, the mixture was extracted five times with chloroform. The
organic phase was dried (Na2SO4), the solvent was evaporated and
the residue was chromatographed on SiO2 (EtOAc–hexane 1 : 5) to
55%). Ee 96%; [a]20 = +17.6 (c 0.7, EtOH). IR (neat): 3430 (br),
D
give 0.345 g (1.34 mmol, 89%) of 4 as a colorless oil. Ee 96%; [a]20 =
1726 cm−1; 1H NMR (400 MHz, CDCl3): d = 0.92 (t, J = 7.6 Hz,
3 H), 1.23–1.33 (m, 2 H), 1.42–1.53 (m, 2 H), 1.54 (dd, J = 13.8
& 8.6 Hz, 1 H), 1.67–1.77 (m, 1 H), 1.79–1.82 (m, 1 H), 1.84–1.93
(m, 1 H), 1.96–1.98 (m, 1 H), 2.00–2.04 (m, 1 H), 2.06–2.12 (m,
1 H), 2.28 (dd, J = 6.1 & 13.0 Hz, 1 H), 2.37–2.42 (m, 1 H),
4.43 (t, J = 2.5 Hz, 1 H), 5.26–5.38 (m, 1 H), 5.42–5.49 (m, 1 H),
5.68 (d, J = 16.5 Hz, 1 H); 13C NMR (75 MHz, CDCl3): d =
13.80, 18.70, 26.30, 33.90, 34.80, 37.60, 40.30, 67.55, 68.48, 124.70,
134.60, 176.70; MS (ESI) m/z 212.2 (M+); Anal. Cal. for C12H20O3
(212.112): C, 67.89; H, 9.50. Found: C, 67.62; H, 9.78%.
D
−17.9 (c 1.0, CHCl3). IR (neat): 3410 cm−1; 1H NMR (400 MHz,
CDCl3): d = 0.06 (s, 6 H), 0.78 (s, 9 H), 0.93 (t, J = 6.5 Hz, 3 H),
1.20–1.30 (m, 4 H), 1.86–2.00 (m, 2 H), 2.21–2.29 (br s, 1 H),
4.04–4.13 (m, 1 H), 4.19–4.26 (m, 1 H), 5.03 (d, J = 8.5 Hz, 1 H),
5.24 (d, J = 15.6 Hz, 1 H), 5.60–5.75 (m, 1 H); 13C NMR (75 MHz,
CDCl3): d = −4.74, −4.74, 13.98, 17.90, 19.80, 25.80, 26.95, 29.95,
40.25, 41.00, 70.09, 70.99, 115.45, 139.22; MS (ESI) m/z 258.5
(M+); Anal. Cal. for C14H30O2Si (258.202): C, 65.06; H, 11.70.
Found: C, 65.00; H, 11.66%.
3524 | Org. Biomol. Chem., 2006, 4, 3521–3525
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The Royal Society of Chemistry 2006
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