5198 J . Org. Chem., Vol. 64, No. 14, 1999
Marshall et al.
stirred solution turned clear and colorless, the organic portion
was washed with NaHCO3 and brine. The aqueous portion was
extracted with ether, and then the combined organic extracts
were dried over MgSO4, filtered, and concentrated. The crude
product was purified by flash column chromatography with
10% EtOAc-hexanes to afford 2.63 g (4.50 mmol, 94%) of
Exp er im en ta l Section
Eth yl 8-(ter t-Bu tyld ip h en ylsilyloxy)-5-isop r op en yl-6-
octyn oa te (2). To a stirred solution of 6.60 g (16.8 mmol) of
allylic alcohol 17 in 21.6 mL (118 mmol) of triethyl orthoacetate
was added 0.75 mL (1.01 mmol) of propionic acid. The solution
was heated to reflux. After 16 h, the reaction mixture was
allowed to cool to room temperature, diluted with Et2O, and
quenched with aqueous 10% HCl solution. The organic layer
was washed with 10% HCl, brine, and saturated aqueous
NaHCO3 solution. The aqueous washes were extracted with
Et2O, dried over MgSO4, filtered, and concentrated. The crude
product was purified by flash column chromatography with
10% EtOAc-hexanes as eluent to afford 6.60 g (85%) of the
1
furanyl aldehyde 6: IR (cm-1) 1720, 1690; H NMR (CDCl3) δ
9.53 (s, 1Η), 7.70 (dd, J ) 1.9, 6.7 Hz, 4H), 7.45-7.26 (m, 6H),
4.71 (s, 1H), 4.66 (s, 1H), 4.29 (t, J ) 1.9 Hz, 2H), 3.2 (dd, J )
4.8, 8.9 Hz, 1H), 3.08 (dd, J ) 7.9, 1.4 Hz, 1H), 2.80-2.72 (m,
1H), 1.65 (s, 3H), 1.62-1.53 (m, 2H), 1.55 (s, 9H), 1.05 (s, 9H)
ppm; 13C NMR (CDCl3) δ 177.7, 166.3, 162.2, 150.9, 145.1,
136.1, 130.2, 128.1, 118.9, 114.1, 85.5, 82.3, 79.2, 58.5, 46.0,
32.7, 32.0, 28.7, 27.3, 19.7, 18.5, 17.2 ppm.
1
ethyl ester 2: IR (neat) 1747; H NMR (CDCl3) δ 7.79-7.68
2-[2-Isop r op en yl-7-(ter t-bu tyld im eth ylsilyloxy)-5-h ep -
tyn yl]-3-ca r bo-ter t-bu toxy-5-(1-h yd r oxy-2-m eth yl-2-p r o-
p en yl)fu r a n (7). To a stirred suspension of 0.52 g (21.5 mol)
of Mg in 5.4 mL of THF at room temperature was added 0.76
mL (8.62 mmol) of 2-bromopropene. The resulting Grignard
reagent was added by cannula to a stirred solution of 2.52 g
(4.31 mmol) of furanyl aldehyde 6. The reaction was quenched
with saturated aqueous NH4Cl and brine. The aqueous washes
were extracted with Et2O, and then the combined organic
extracts were dried over MgSO4, filtered, and concentrated.
The crude product was purified by flash column chromatog-
raphy with 20% EtOAc-hexanes as eluent to provide 2.60 g
(96%) of allylic alcohol 7: IR 3471, 2861, 2235, 1715 cm -1; 1H
NMR (CDCl3) δ 7.73-7.69 (m, 4H), 7.45-7.26 (m, 6H), 6.45
(s, 1H), 5.14 (s, 1H), 5.03 (d, J ) 5.0 Hz, 1H), 4.99 (s, 1H),
4.69 (s, 1H), 4.64 (s, 1H), 4.29 (s, 3H), 3.13-2.94 (m, 2H), 2.70-
2.60 (m, 1H), 2.16-1.94 (m, 2H), 1.69 (s, 3H), 1.67 (s, 3H),
1.59-1.57 (m, 2H), 1.53 (s, 9H), 1.05 (s, 9H) ppm; 13C NMR
163.7, 160.5, 153.2, 145.7, 144.4, 136.1, 133.9, 130.2, 128.1,
116.6, 113.5, 112.8, 108.58, 108.55, 85.9, 81.1, 79.0, 71.7, 53.5,
46.2, 46.2, 32.4, 32.3, 32.0, 31.9, 28.8, 27.3, 19.7, 19.1, 18.5,
17.2 ppm. Anal. Calcd for C39H60O5Si: C, 74.72; H,8.04.
Found: C, 74.48; H, 8.08.
(4H, m), 7.47-7.34 (m, 6H), 4.83 (s, 1H), 4.78 (s, 1H), 4.32 (t,
J ) 2.2 Hz, 2H), 4.12 (qd, J ) 1.5, 7.3 Hz, 2H), 2.75-2.62 (m,
1H), 2.37 (d, J ) 7.4 Hz, 2H), 2.2-2.0 (m, 2H), 1.67 (s, 3H),
1.61-1.49 (m, 2H), 1.24 (td, J ) 0.8, 7.1 Hz, 3H), 1.07 (s, 9H)
ppm; 13C NMR (CDCl3) δ 172.7, 145.6, 136.2, 133.9, 130.2,
128.1, 113.4, 85.6, 79.2, 60.7, 53.5, 43.4, 39.5, 32.3, 27.3, 19.7,
19.0, 17.2, 14.8 ppm. Anal. Calcd for C29H38O3Si: C, 75.28; H,
8.28. Found: C, 75.01; H, 8.26.
ter t-Bu tyl 10-(ter t-Bu tyld ip h en ylsilyloxy)-5-isop r op e-
n yl-3-oxo-8-d ecyn oa te (3). To a stirred solution of 24.6 mL
(24.6 mmol) of 1.0 M LiN(TMS)2 in THF in 22 mL of THF at
-78 °C was added 3.18 mL (23.6 mmol) of t-BuOAc. The
solution was allowed to stir for 1 h, and then 5.20 g (11.2 mmol)
of ethyl ester 2 was added as a solution in 4.5 mL of THF.
The reaction mixture was allowed to warm gradually to room
temperature, quenched with 10% HCl solution, and diluted
with Et2O. The organic layer was washed with saturated
aqueous NH4Cl solution and brine. The aqueous portion was
extracted with Et2O, dried over MgSO4, filtered, and concen-
trated. The crude product was purified by flash column
chromatography with 10% EtOAc-hexanes as eluent to give
5.28 g (88%) of â-keto ester 3: IR (neat) 2236, 1748, 1723 cm
1
-1; H NMR (CDCl3) δ 7.72 (4H, dd, J ) 1.7, 7.5 Hz), 7.46-
2-[2-Isop r op en yl-7-(ter t-bu tyld im eth ylsilyloxy)-5-h ep -
t yn yl]-3-ca r b o-ter t-bu t oxy-5-(1-a cet oxy-2-m et h yl-2-p r o-
p en yl)fu r a n (8). To a stirred solution of 1.5 g (2.4 mmol) of
allylic alcohol 7 in 9.6 mL of pyridine at room temperature
was added 29 mg (0.24 mmol) of DMAP followed by 0.45 mL
(4.8 mmol) of acetic anhydride. After 1 h, the reaction mixture
was quenched with saturated NH4Cl solution and diluted with
ether. The organic phase was washed with brine. The aqueous
portion was extracted with ether. The combined organic
extracts were dried over MgSO4, filtered, and concentrated.
The crude product was purified by flash column chromatog-
raphy with 10% EtOAc-hexanes to afford 1.5 g (2.3 mmol,
94%) of allylic acetate 8: 1H NMR δ 7.72-7.66 (s, 4H), 7.45-
7.33 (m, 6H), 6.51 (s, 1H), 6.10 (s, 1H), 5.08 (s, 1H), 5.00 (s,
1H), 4.68 (s, 1H), 4.61 (s, 1H), 4.29 (s, 2H), 3.16-2.90 (m, 2H),
2.68-2.57 (m, 1H), 2.20-1.94 (m, 2H), 2.09 (s, 3H), 1.71 (s,
3H), 1.62 (s, 3H), 1.60-1.55 (m, 2H), 1.52 (s, 9H), 1.05 (s, 9H)
ppm.
7.36 (6H, m), 4.8 (2H, J ) 1.9 Hz), 4.3 (2H, t, J ) 1.9 Hz),
3.32 (2H, s), 2.77-2.64 (1H, m), 2.58 (2H, t, J ) 7.3 Hz), 2.9-
2.0 (2H, m), 1.65 (3H, s), 1.65-1.49 (2H, m), 1.47 (9H, s), 1.07
(9H, s) ppm; 13C NMR (CDCl3) δ 202.4, 145.7, 136.2, 130.2,
128,1, 113.3, 79.3, 58.5, 53.5, 51.4, 47.6, 41.9, 32.4, 28.5, 27.3,
19.5, 17.2 ppm. Anal. Calcd for C33H41O4Si: C, 74.39; H, 8.32.
Found: C, 74.18; H, 8.30.
2-[2-Isop r op en yl-7-(ter t-bu tyld im eth ylsilyloxy)-5-h ep -
tyn yl]-3-ca r bo-ter t-bu toxy-5-(h yd r oxym eth yl)fu r a n (5).
To 3.00 g (5.63 mmol) of â-keto ester 3 was added 1.47 g (11.26
mmol) of glyceraldehyde acetonide (4). The reaction mixture
was stirred at room temperature for 96 h. A solution of 2.82 g
(2.82 mmol) of PPTS in 5.6 mL of EtOH was added. The
reaction mixture was heated to 80 °C for 35 min, allowed to
cool to room temperature, diluted with Et2O, and quenched
with NaHCO3 solution. The organic extracts were washed with
NaHCO3 and brine. The aqueous portion was extracted with
ether, and then the combined organic extracts were dried over
MgSO4, filtered, and concentrated. The crude product was
purified by flash column chromatography with 10% EtOAc-
hexanes to afford 2.88 g (4.91 mmol, 87%) of furan 5: IR (neat),
1707; 1H NMR (CDCl3) δ 7.8-7.7 (4H, m), 7.46-7.36 (m, 6H),
6.49 (s, 1H), 4.74 (s, 1H), 4.71 (s, 1H), 4.49 (d, J ) 6.2 Hz,
2H), 4.32 (t, J ) 1.9 Hz, 2H), 3.13-2.99 (m, 2H), 2.77-2.67
(m, 1H), 2.20-2.0 (m, 2H), 1.67 (s, 3H), 1.62-1.57 (m, 2H),
1.55 (s, 9H), 1.05 (s, 9H) ppm; 13C NMR (CDCl3) δ 163.7, 160.8,
152.5, 145.9, 136.2, 133.9, 130.2, 128.2, 116.8, 113.5, 109.4,
85.9, 81.2, 79.0, 57.7, 53.5, 46.0, 32.5, 31.9, 28.8, 27.3, 19.7,
18.7, 17.2 ppm. Anal. Calcd for C36H44O5Si: C, 73.68; H, 7.90.
Found: C, 73.81; H, 8.02.
syn ,tr a n s-P r op a r gylic Alcoh ol 16a . A. Sn Cl2 Cycliza -
tion of Allylic Br om id e 13. To a stirred solution of 25 mg
(0.056 mmol) of bromo aldehyde 13 in 1.0 mL of THF and 0.3
mL of DMPU was added 13 mg (0.067 mmol) of SnCl2. After
18 h, an additional 18 mg (0.01 mmol) of SnCl2 was added,
and then after 6 h, another 18 mg (0.01 mmol) portion of SnCl2
was added. The reaction mixture was stirred for 12 h,
quenched with 10% HCl, and diluted with ether. The organic
extracts were washed with 10% HCl and brine. The aqueous
portion was extracted with ether. The combined extracts were
dried over MgSO4, filtered, and concentrated. The crude
product was purified by flash column chromatography to
provide 8.0 mg (38%) of alcohol 16a as the major component
of a mixture of diastereomers: 1H NMR (CDCl3) δ 6.51 (s, 1H),
5.2 (s, 1H), 5.1 (s, 1H), 4.9 (s, 1H), 4.75 (s, 1H), 4.59-4.52 (m,
1H), 3.56 (d, J ) 9.9 Hz, 2H), 3.45 (d, J ) 12.7, 1H), 3.39 (d,
J ) 13.0 Hz, 1H), 2.19-1.98 (m, 2H), 1.91 (s, 3H), 1.77 (s, 3H),
1.54 (s, 9H) ppm; 13C NMR (CDCl3) δ 158.9, 151.2, 148.0, 140.9,
117.5, 112.9, 110.8, 107.1, 88.5, 80.6, 78.5, 65.3, 54.3, 44.7, 32.2,
2-[2-Isop r op en yl-7-(ter t-bu tyld im eth ylsilyloxy]-5-h ep -
tyn yl]-3-ca r bo-ter t-bu toxy-5-for m ylfu r a n (6). To a stirred
solution of 2.80 g (4.77 mmol) of furanyl alcohol 5 in 78 mL of
CH2Cl2 at room temperature was added 2.40 g (5.70 mmol) of
Dess-Martin periodinane reagent.9 The reaction was allowed
to stir at room temperature for 30 min, and then 6.0 g (24
mmol) of Na2S2O3 in NaHCO3 solution was added. When the