E. Negishi et al. / Tetrahedron 56 (2000) 10197±10207
10203
above except that the solvent separation was omitted. The
reaction was slower, requiring 1 h at 238C. The yield of the
desired product was 45% by NMR spectroscopy.
compound was prepared according to the representative
Procedure A in 73% yield (111 mg) using 2-methyl-1-
buten-3-yne (66 mg, 1 mmol) and the iodoenone (183 mg,
1
0.5 mmol) prepared above: H NMR (CDCl3) d 0.12 (s,
2-(3-Methyl-3-buten-1-ynyl)-2-cyclohexen-1-one. This
compound was prepared according to Representative Pro-
cedure A in 87% yield (139 mg) using 2-methyl-1-buten-3-
yne (86 mg, 1.3 mmol) and 2-iodo-2-cyclohexen-1-one
3H), 0.16 (s, 3H), 0.92 (s, 9H), 1.9±2.0 (m, 3H) 3.5±3.6
(m, 1H), 3.6±3.7 (m, 1H), 4.74 (d, J5.0 Hz, 1H), 5.30 (s,
1H), 5.40 (s, 1H), 6.65 (dd, J2.5, 4.0 Hz, 1H); 13C NMR
(CDCl3) d 24.69, 24.45, 18.11, 23.08, 25.64 (3C), 53.38,
57.98, 63.79, 81.50, 95.16, 122.30, 123.67, 126.06, 145.73,
190.02; IR (CDCl3) 2955, 2930, 2886, 1700 cm21; MS (CI,
70 eV) 305 (M111).
1
(222 mg, 1 mmol): H NMR (CDCl3) d 1.93 (t, J1.0 Hz,
3H), 2.05 (quint, J8.0 Hz, 2H), 2.4±2.6 (m, 4H), 5.2±5.3
(m, 1H), 5.3±5.4 (m, 1H), 7.28 (t, J4.5 Hz, 1H); 13C NMR
(CDCl3) d 22.42, 23.37, 26.48, 38.12, 82.78, 93.23,122.57,
125.20, 126.49, 154.08, 195.56; MS (CI, 70 eV) 161
(M111).
(4Sp,5Rp,6Rp)-5,6-Epoxy-4-hydroxy-2-(3-methyl-3-buten-
1-ynyl)-2-cyclohexen-1-one ((^)-Harveynone).23 The
TBS ether prepared above (40 mg, 0.13 mmol) was treated
with 48% HF in acetonitrile (v/v 1/50) at 238C for 2 h and
worked up as usual. Flash column chromatography (7/3
hexanes±EtOAc) gave the desired compound (20 mg) in
(1Rp,4Sp,5Rp, 6Sp)-4-(tert-Butyldimethylsilyloxy)-5,6-epoxy-
2-cyclohexen-1-ol. The title compound was prepared
according to the literature procedure16f in 5 steps (starting
from benzoquinone) in 21% overall yield: 1H NMR (CDCl3)
d 0.13 (s, 3H), 0.16 (s, 3H), 0.93 (s, 9H), 2.65 (d,
J11.0 Hz, 1H), 3.3±3.4 (m, 1H), 3.5±3.6 (m, 1H), 4.4±
4.5 (m. 1H), 4.50 (dd, J2.0, 11.0 Hz, 1H), 5.6±5.65(m,
2H); 13C NMR (CDCl3) d 24.72, 24.55, 18.15, 25.72
(3C), 54.33, 56.44, 62.88, 64.02, 126.66, 127.30; IR
(CDCl3) 3426, 2951, 2926 cm21; MS (CI, 70 eV) 243
(M111).
1
80% yield as a yellow oil: H NMR (CDCl3) d1.94 (s,
3H), 3.30 (d, J11.0 Hz, 1H), 3.57 (d, J4.0 Hz, 1H),
3.8±3.9 (m, 1H), 4.7±4.8 (m, 1H), 5.3±5.4 (m, 1H), 5.4±
5.5 (m, 1H), 6.85 (dd, J2.5, 4.0 Hz, 1H); 13C NMR
(CDCl3) d 23.02, 53.55, 57.64, 63.18, 81.18, 95.90,
122.68, 124.15, 125.91, 146.18, 191.52; IR (CDCl3) 3455,
2206, 1686 cm21; MS (CI, 70 eV) 191 (M111).
(4Rp,5Sp,6Sp)-4-(tert-Butyldimethylsilyloxy)-5,6-epoxy-2-
(7-methyl-3-methylene-6-octene-1-ynyl)-2-cyclohexen-1-
one.16f This compound was prepared according to the
Representative Procedure A in 80% yield (148 mg) using
2-(4-methyl-3-pentenyl)-1-buten-3-yne3b (134 mg, 1 mmol)
and (4Sp, 5Rp, 6Rp)-4-(tert-butyldimethylsilyloxy)-5,6-
(4Sp,5Rp,6Rp)-4-(tert-Butyldimethylsilyloxy)-5,6-epoxy-2-
cyclohexen-1-one.16f A mixture of the alcohol prepared in
the previous experiment (1.26 g, 5.2 mmol), PCC (1.68 g,
7.8 mmol) and 2 g of Celite in 50 mL of CH2Cl2 were stirred
at 238C. The reaction was monitored by TLC. After 2 h, the
reaction mixture was diluted with ether and ®ltered through
a plug of SiO2. The solvent was evaporated in vacuo. Puri-
®cation by ¯ash chromatography gave 1.1 g (88%) of the
enone as colorless oil: 1H NMR (CDCl3) d 0.16 (s, 3H), 0.19
(s, 3H), 0.95 (s, 9H), 3.4±3.5 (m, 1H), 3.6±3.7 (m, 1H), 4.66
(d, J5.0 Hz, 1H), 5.97 (dd, J1.5, 11.0 Hz, 1H), 6.5±6.6
(m, 1H); 13C NMR (CDCl3) d 24.07, 23.92, 18.67, 26.23
(3C), 53.85, 58.95, 64.19, 126.80, 144.89, 193.73; MS (CI,
70 eV) 241 (M111).
1
epoxy-2-iodo-2-cyclohexen-1-one (183 mg, 0.5 mmol): H
NMR (CDCl3) d 0.12 (s, 3H), 0.16 (s, 3H), 0.90 (s, 9H), 1.59
(s, 3H), 1.65 (s, 3H), 2.1±2.3 (m,4H), 3.5±3.6 (m, 1H), 3.6±
3.7(m, 1H), 4.71 (d, J5.5 Hz, 1H), 5.0±5.1 (m, 1H), 5.28
(d, J1.5 Hz, 1H), 5.40 (d, J1.5 Hz, 1H), 6.65 (dd, J2.5,
5.0 Hz, 1H); 13C NMR (CDCl3) d 24.70, 24.48, 17.69,
18.08, 25.62 (3C), 26.64, 37.06, 53.35, 57.95, 63.77,
82.39, 94.51, 122.35, 122.84, 123.14, 130.72, 132.27,
145.51, 189.87; IR (CDCl3) 2955, 2929, 2858,1700 cm21
;
MS (CI, 70 eV) 373 (M111).
(4Sp,5Rp,6Rp)-4-(tert-Butyldimethylsilyloxy)-5,6-epoxy-2-
iodo-2-cyclohexen-1-one.16f To a mixture of the compound
obtained above (0.6 g, 2.5 mmol) in 5 mL of pyridine and
5 mL of CCl4 mixture was added dropwise at 08C I2 (1.6 g,
6.25 mmol) dissolved in 10 mL of pyridine and CCl4 (1/1).
The mixture was stirred at 08C until TLC analysis showed
the disappearance of the starting material. It was then parti-
tioned between Et2O and 1 M HCl. The organic layer was
washed with another portion of 1 M HCl and saturated
Na2S2O3 (2£), dried over MgSO4, and concentrated in
vacuo. Puri®cation by ¯ash chromatography gave the
desired product in 94% yield (0.86 g) as a light yellow-
(4Rp,5Sp,6Sp)-5,6-Epoxy-4-hydroxy-2-(7-methyl-3-methyl-
ene-6-octene-1-ynyl)-2-cyclohexen-1-one.23 The TBS
ether obtained above (100 mg, 0.27 mmol) was treated
with 48% HF in acetonitrile (v/v 1/50) at 238C for 2 h and
worked up as usual. Flash column chromatography (7/3
hexanes±EtOAc) gave the desired compound (61 mg) in
1
88% yield as a yellow oil: H NMR (CDCl3) d 1.62 (s,
3H),1.68 (s, 3H), 2.2 (m, 4H), 3.32 (bs, 1H), 3.55 (dd,
J1.0, 3.5 Hz, 1H), 3.8±3.9 (m,1H), 4.75 (d, J5.5 Hz,
1H), 5.0±5.2 (m, 1H), 5.3±5.4 (m, 1H), 5.4±5.5 (m, 1H),
6.86 (dd, J2.5, 5.0 Hz, 1H); 13C NMR (CDCl3) d 17.78,
25.71, 26.64, 37.00, 53.51, 57.69, 63.21, 81.98, 95.34,
122.68, 123.03, 123.50, 130.52, 132.48, 146.16, 191.68;
IR (CDCl3) 3464, 2967, 2202, 1684 cm21; MS (CI, 70 eV)
259 (M111).
1
green solid: mp 72±738C; H NMR (CDCl3) d 0.16 (s,
3H), 0.19 (s, 3H), 0.92 (s, 9H), 3.6±3.7 (m, 1H), 3.7±3.8
(m, 1H), 4.60 (d, J5.0 Hz, 1H), 7.29 (dd, J2.0, 4.0 Hz,
1H); 13C NMR (CDCl3) d 24.16, 23.97, 18.63, 26.13 (3C),
52.24, 58.76, 66.65, 102.44, 153.14, 188.07; IR (CDCl3)
2954, 1696 cm21; MS (CI, 70 eV) 367 (M111).
(4Rp,5Sp,6Sp)-4-Acetoxy-5,6-epoxy-2-(7-methyl-3-methyl-
ene-6-octene-1-ynyl)-2-cyclohexen-1-one ((^)-Tricholo-
menyn A).16f The above obtained alcohol (50 mg,
0.2 mmol) was treated with DCC (0.62 g, 0.3 mmol),
(4Sp,5Rp,6Rp)-4-(tert-Butyldimethylsilyloxy)-5,6-epoxy-2-
The
(3-methyl-3-buten-1-ynyl)-2-cyclohexen-1-one.16f