1006 Bull. Chem. Soc. Jpn., 74, No. 6 (2001)
HEADLINE ARTICLES
1218, 1156, 1077, 1019, 967, 949, 891, 855, 824, 739, 576, 513,
416 cmꢀ1; HRMS (EI, 70 eV) m/z: calcd for C17H26O3Si, Mꢁ,
306.1652; found, 306.1644.
as a colorless amorphous solid. 41: Rf 0.46 (hexane/ethyl acetate,
6/1); [α]2D3 ꢀ14.4˚ (c 1.00, CHCl3); 1H NMR (200 MHz, CDCl3) δ
6.43 (1H, dd, J ꢃ 2.0, 0.5 Hz), 4.42 (1H, ddd, J ꢃ 8.0, 4.2, 2.0
Hz), 4.07 (1H, dd, J ꢃ 4.2, 0.5 Hz), 2.00 (1H, d, J ꢃ 8.0 Hz), 0.96
(9H, s), 0.93 (9H, s), 0.42 (3H, s), 0.29 (3H, s), 0.20 (3H, s), 0.18
(3H, s); 13C NMR (50 MHz, CDCl3) δ 144.85, 116.62, 101.68,
88.03, 84.57, 80.51, 25.85, 25.55, 18.13, 18.10, ꢀ2.85, ꢀ2.99,
ꢀ3.92, ꢀ4.85; IR (thin film) 3458, 2934, 2902, 2862, 2248, 1597,
1473, 1408, 1365, 1311, 1259, 1195, 1151, 1110, 1067, 1031,
1007, 977, 940, 839, 783 cmꢀ1; HRMS (EI, 70 eV) m/z: calcd for
C17H33INO3Si2, (M ꢀ CH3)ꢁ, 480.0886; found, 480.0882.
(4S,5R)-4-Acetoxy-5-t-butyldimethylsilyloxy-2-iodo-2-cyclo-
penten-1-one (39). To a solution of cyclopentenone (ꢀ)-7 (5.94
g, 22.0 mmol) in carbon tetrachloride (25 mL) and pyridine (25
mL) was added dropwise a solution of iodine (11.15 g, 43.9
mmol) in carbon tetrachloride (40 mL) and pyridine (40 mL) at 0
˚C. The reaction mixture was allowed to warm to room tempera-
ture and then stirred for 4 h. The mixture was diluted with ether
(200 mL) and washed with water (150 mL). The separated aque-
ous layer was extracted with ether (100 mL ꢂ 2), and the com-
bined organic extracts were washed with 1 M HCl (150 mL ꢂ 2),
water (100 mL), and saturated Na2S2O3 (60 mL), and dried over
anhydrous magnesium sulfate. After filtration and concentration,
the remaining oil was purified by flash column chromatography
(silica-gel, hexane/ethyl acetate, 10/1) to yield iodocyclopenenone
39 (8.41 g, 96.6%) as a pale yellow oil. 39: Rf 0.70 (hexane/ethyl
acetate, 3/1); [α]2D5 ꢀ143.9˚ (c 1.02, CHCl3); 1H NMR (200 MHz,
CDCl3) δ 7.79 (1H, d, J ꢃ 2.7 Hz), 5.60 (1H, dd, J ꢃ 2.8,2.2 Hz),
4.33 (1H, d, J ꢃ 2.8 Hz), 2.14 (3H, s), 0.92 (9H, s), 0.18 (3H, s),
0.14 (3H, s); 13C NMR (50 MHz, CDCl3) δ 196.56, 169.96,
160.94, 103.83, 79.84, 75.65, 25.50, 20.65, 18.21, ꢀ4.56, ꢀ5.39;
IR (thin film) 2958, 2934, 2888, 2862, 1744, 1576, 1473, 1373,
1255, 1228, 1168, 1141, 1087, 1036, 980, 888, 841, 783, 756,
698, 677, 547 cmꢀ1; HRMS (EI, 70 eV) m/z: calcd for
C9H12IO4Si, (M ꢀ C4H9)ꢁ, 338.9550; found, 338.9546.
(1R,4R,5S)-1,5-Bis(t-butyldimethylsilyloxy)-2-iodo-4-meth-
oxymethoxy-2-cyclopentene-1-carbonitrile (5). A solution of
alcohol 41 (1.10 g, 2.22 mmol) in CH2Cl2 (2.2 mL) at 0 ˚C was
treated with diisopropylethylamine (1.16 mL, 6.66 mmol) and
chloromethyl methyl ether (253 µL, 3.33 mmol), stirred at 0 ˚C for
30 min and then refluxed at 40 ˚C for 4 h. After cooling to room
temperature, the mixture was concentrated in vacuo and the resi-
due was dissolved in ether (30 mL). The solution was washed
with saturated NH4Cl (10 mL), and the aqueous layer was extract-
ed with ether (10 mL ꢂ 2). The combined organic extracts were
washed with brine (8 mL), dried over anhydrous magnesium sul-
fate, filtered, concentrated, and purified by flash column chroma-
tography (silica-gel, hexane/ethyl acetate, 50/1) to yield ether 5
(1.19 g, 99.3%). 5: Rf 0.74 (hexane/ethyl acetate, 6/1); [α]2D7 ꢀ9.8˚
(c 1.01, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.54 (1H, dd, J ꢃ
1.6, 0.4 Hz), 4.72 (1H, d, J ꢃ 6.8 Hz), 4.68 (1H, d, J ꢃ 6.8 Hz),
4.20 (1H, dd, J ꢃ 4.4, 1.6 Hz), 4.18 (1H, dd, J ꢃ 4.4, 0.4 Hz),
3.39 (3H, s), 0.96 (9H, s), 0.93 (9H, s), 0.44 (3H, s), 0.29 (3H, s),
0.17 (3H, s), 0.14 (3H, s); 13C NMR (100 MHz, CDCl3) δ 144.31,
116.64, 101.44, 97.39, 87.50, 86.16, 83.75, 55.78, 25.83, 25.59,
18.20, 18.06, ꢀ2.54, ꢀ2.88, ꢀ4.00, ꢀ4.76; IR (thin film) 2934,
2862, 1603, 1473, 1365, 1305, 1257, 1216, 1152, 1038, 1000,
940, 920, 841, 781, 712, 679 cmꢀ1; HRMS (EI, 70 eV) m/z: calcd
for C19H35INO4Si2, (M ꢀ CH3)ꢁ, 524.1148; found, 524.1160.
(1R,4R,5S)-1,5-Bis(t-butyldimethylsilyloxy)-2-{(3S,4R)-3,4-
epoxy-3-[(1R)-1,2-isopropylidenedioxyethyl]-6-triethylsilyl-
1,5-hexadiynyl}-4-methoxymethoxy-2-cyclopentene-1-carbo-
nitrile (44). A degassed solution of iodocyclopentene 5 (0.340
g, 0.572 mmol), alkyne 6 (0.316 g, 1.03 mmol) and N,N-diisopro-
pylethylamine (0.95 mL, 1.85 mmol) in DMF (0.9 mL) was added
to a suspension of bis(acetonitorile)dichloropalladium(II) (15.3
mg, 59.0 µmol) and copper(I) iodide (22.5 mg, 0.118 mmol) in
DMF (1.0 mL) at room temperature. After stirring for 1 h, the re-
action was quenched with saturated aqueous ammonium chloride,
diluted with ether, and the aqueous layer was extracted with ether.
The combined organics were washed with brine, dried over anhy-
drous magnesium sulfate, and concentrated. The residue was pu-
rified by flash column chromatography (silica-gel, hexane/ethyl
acetate, 50/1) to yield enediyne 44 (0.288 g, 72%) as a colorless
oil. 44: Rf 0.43 (hexane/ethyl acetate, 6/1); [α]2D7 ꢁ21.8˚ (c 1.05,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.34 (1H, d, J ꢃ 2.0 Hz),
4.71 (1H, d, J ꢃ 7.2 Hz), 4.67 (1H, d, J ꢃ 7.2 Hz), 4.26 (1H, dd, J
ꢃ 5.0, 2.0 Hz), 4.20 (1H, dd, J ꢃ 8.1, 6.4 Hz), 4.15 (1H, dd, J ꢃ
6.4, 6.0 Hz), 4.11 (1H, d, J ꢃ 5.0 Hz), 4.05 (1H, dd, J ꢃ 8.1, 6.0
Hz), 3.71 (1H, s), 3.10 (3H, s), 1.46 (3H, s), 1.35 (3H, s), 0.98
(9H, t, J ꢃ 7.9 Hz), 0.94 (9H, s), 0.92 (9H, s), 0.61 (6H, q, J ꢃ 7.9
Hz), 0.38 (3H, s), 0.29 (3H, s), 0.15 (3H, s), 0.12 (3H, s); 13C
NMR (100 MHz, CDCl3) δ 141.83, 126.57, 116.40, 110.99, 99.22,
97.45, 90.86, 88.65, 87.53, 84.80, 80.27, 79.93, 77.32, 75.48,
66.85, 58.27, 55.62, 49.88, 26.01, 25.73, 25.54, 25.08, 18.14,
17.97, 7.36, 7.05, ꢀ2.84, ꢀ3.09, ꢀ4.22, ꢀ4.78; IR (thin film)
(1R,4R,5S)-4-Acetoxy-1,5-bis(t-butyldimethylsilyloxy)-2-
iodo-2-cyclopentene-1-carbonitrile (40). Cyclopentenone 39
(5.15 g, 13.0 mmol) was azeotroped with toluene (10 mL ꢂ 3). A
solution of enone 39 in CH2Cl2 (26 mL) was treated with t-bu-
tyldimethylsilyl cyanide (2.87 g, 20.3 mmol) and then anhydrous
ZnI2 (1.09 g, 3.40 mmol) at room temperature and stirred for 42 h.
The mixture was diluted with ether (100 mL) and quenched with
water (10 mL). The aqueous layer was extracted with ether (10
mL ꢂ 3), and the combined organic layers were washed with
brine (8 mL), then dried over anhydrous magnesium sulfate. Puri-
fication by flash column chromatography (silica-gel, hexane/ethyl
acetate, hexane → 40/1 → 30/1) provided nitrile 40 (6.71 g,
95.9%) as a colorless oil. 40: Rf 0.68 (hexane/ethyl acetate, 6/1);
[α]2D7 ꢀ76.8˚ (c 1.05, CHCl3); 1H NMR (200 MHz, CDCl3) δ 6.46
(1H, dd, J ꢃ 2.0, 0.7 Hz), 5.22 (1H, dd, J ꢃ 4.1, 2.0 Hz), 4.29
(1H, dd, J ꢃ 4.1, 0.7 Hz), 2.09 (3H, s), 0.95 (9H, s), 0.94 (9H, s),
0.44 (3H, s), 0.30 (3H, s), 0.18 (3H, s), 0.12 (3H, s); 13C NMR (50
MHz, CDCl3) δ 169.98, 141.20, 116.32, 103.63, 84.44, 81.87,
25.72, 25.50, 20.73, 18.13, 18.02, ꢀ2.78, ꢀ3.01, ꢀ4.20, ꢀ4.82;
IR (thin film) 2960, 2934, 2900, 2862, 1750, 1473, 1392, 1365,
1255, 1228, 1143, 1081, 1027, 980, 940, 876, 841, 783, 679 cmꢀ1
;
HRMS (EI, 70 eV) m/z: calcd for C19H33INO4Si2, (M ꢀ CH3)ꢁ,
522.0992; found, 522.0994.
(1R,4R,5S)-1,5-Bis(t-butyldimethylsilyloxy)-2-cyclopentene-
1-carbonitrile (41). To a solution of acetate 40 (6.62 g, 12.32
mmol) in methanol (26 mL) was added K2CO3 (435.0 mg, 3.15
mmol) at room temperature. The reaction mixture turned black
immediately and was stirred for 2 h. The solvent was removed un-
der aspirator vacuum and the residue was dissolved in ether (50
mL) and water (10 mL). After separation of the phases, the aque-
ous layer was extracted with ether (10 mL ꢂ 2). The combined
organic extracts were washed with brine (5 mL), dried over anhy-
drous magnesium sulfate, filtered, and concentrated. The remain-
ing residue was purified by flash column chromatography (silica-
gel, hexane/ethyl acetate, 20/1) to yield alcohol 41 (5.23 g, 85.6%)