J. Zhang et al. / Tetrahedron 63 (2007) 6990–6995
6993
purified by column chromatography (hexanes/EtOAc, 50:1)
to give 10 (2.339 g, 98%) as a yellow oil. IR (KBr) 3073,
2850, 1660, 1244, 1112; 1H NMR (300 MHz, CDCl3)
d 1.17 (d, J¼7.2 Hz, 3H), 1.99 (s, 3H), 3.55–3.60 (m, 1H),
5.03–5.11 (m, 2H), 5.79 (ddd, J¼16.5, 10.5, 7.2 Hz, 1H),
6.46 (s, 1H), 6.55 (s, 1H); 13C NMR (75 MHz, CDCl3)
d 15.3, 18.3, 35.0, 115.4, 131.5, 133.6, 139.2, 145.2,
152.0, 186.8, 188.2; HRMS (m/z) calcd for C11H12O2,
176.0837 [M]+; found, 176.0833.
15:1) to give both (7R,10R)-13 (609 mg, 47%) and
(7S,10R)-14 (553 mg, 43%) as colorless oils. Compound
13: [a]2D5: ꢀ10 (c 0.7, CHCl3); IR (KBr) 2930, 1500, 1201,
1
1112, 839, 704 cmꢀ1; H NMR (300 MHz, CDCl3) d 0.09
(s, 3H), 0.10 (s, 3H), 0.92 (s, 9H), 1.04 (d, J¼7.8 Hz, 3H),
1.10 (s, 9H), 2.30 (s, 3H), 2.85 (dq, J¼7.6, 6.5 Hz, 1H),
3.60 (dd, J¼10.2, 5.7 Hz, 1H), 3.78 (dd, J¼10.5, 7.4 Hz,
1H), 4.31–4.33 (m, 1H), 5.34 (dd, J¼12.0, 5.6 Hz, 1H),
5.67 (ddd, J¼11.7, 6.3, 2.4 Hz, 1H), 6.08 (s, 1H), 6.83 (s,
1H), 7.32–7.43 (m, 6H), 7.67–7.73 (m, 4H); 13C NMR
(75 MHz, CDCl3) d ꢀ5.3, 16.7, 18.3, 19.6, 22.3, 25.9,
26.6, 38.2, 65.9, 80.5, 117.8, 124.3, 126.5, 126.7, 127.6,
127.7, 129.8, 133.5, 135.4, 135.5, 137.4, 150.0; HRMS
(m/z) calcd for C35H48O3Si2, 572.3142 [M]+; found,
572.3151. Compound 14: [a]2D5: +31 (c 1.1, CHCl3); IR
4.1.5. 2-(But-3-en-2-yl)-4-[(tert-butyldiphenyl)oxyl]-
5-methylphenol (4). To the quinone 10 (2.328 g,
13.23 mmol) in Et2O (50 mL) at rt was added an aqueous so-
lution of Na2S2O4 (9.22 g, 52.91 mmol, in 50 mL H2O) in
one portion with rapid stirring. After 20 min more
Na2S2O4 solution (50 mL) was added. Fifteen minutes later
the layers were separated, and the aqueous phase was
extracted with Et2O (3ꢂ50 mL). The combined organic
phases were washed with brine, dried (Na2SO4 containing
Na2S2O4), and concentrated in vacuo. The residue was puri-
fied by flash column chromatography (hexanes/EtOAc, 6:1)
to give accordingly 1,4-dihydroquinone 11 (2.284 g, 97%)
as a colorless oil. This dihydroquinone was used for the
next step immediately.
1
(KBr) 2930, 1499, 1199, 1111, 839, 704 cmꢀ1; H NMR
(300 MHz, CDCl3) d 0.09 (s, 3H), 0.10 (s, 3H), 0.80 (d,
J¼7.2 Hz, 3H), 0.94 (s, 9H), 1.12 (s, 9H), 2.32 (s, 3H),
3.59 (dq, J¼7.4, 3.2 Hz, 1H), 3.63 (dd, J¼10.4, 4.8 Hz,
1H), 3.78 (dd, J¼10.4, 7.2 Hz, 1H), 4.37 (dd, J¼4.4,
2.4 Hz, 1H), 5.25 (dd, J¼12.4, 2.4 Hz, 1H), 5.47 (ddd,
J¼12.6, 8.0, 4.0 Hz), 6.16 (s, 1H), 6.87 (s, 1H), 7.34–7.44
(m, 6H), 7.69–7.74 (m, 4H); 13C NMR (75 MHz, CDCl3)
d ꢀ5.1, 16.6, 18.4, 18.7, 19.6, 25.9, 26.7, 32.7, 40.1, 65.3,
81.1, 115.4, 124.0, 126.2, 126.6, 127.7, 129.8, 133.4,
134.8, 135.5, 138.2, 149.7; HRMS (m/z) calcd for
C35H48O3Si2, 572.3142 [M]+; found, 572.3149.
Under Ar, to a stirred solution of compound 11 (2.273 g,
12.77 mmol) in dry CH2Cl2 (50 mL) at 0 ꢁC were added
imidazole (1.04 g, 15.23 mmol) followed by TBDPSCl
(3.69 g, 13.41 mmol) and DMAP (78 mg, 0.64 mmol). After
stirring overnight at 0 ꢁC, the reaction mixture was quenched
with H2O and the layers were separated. The aqueous phase
was extracted with CH2Cl2 (3ꢂ30 mL). The combined or-
ganic phases were washed with brine, dried (Na2SO4), and
concentrated in vacuo. The residue was purified by column
chromatography (hexanes/CH2Cl2, 2:1) to give 4 (3.875 g,
73%) as a colorless oil. IR (KBr) 3398, 2931, 1507, 1410,
4.1.8. {(7R,10R)-7,10-Dihydro-5-[(tert-butyldiphenyl)-
oxyl]-4,7-dimethylbenzo[b]oxepin-2-yl}methanol (15).
To a solution of 12 (561 mg, 0.98 mmol) in 10:1 THF/H2O
(11 mL) was added TsOH$2H2O (19 mg, 0.10 mmol). The
resulting solution was stirred at rt for 24 h. Saturated
NaHCO3 was added, and the mixture was extracted with
EtOAc (4ꢂ15 mL). The combined organic extracts were
washed with brine, dried (Na2SO4), and concentrated in va-
cuo. The residue was purified by column chromatography
(hexanes/EtOAc, 10:1) to give 15 (409 mg, 91%) as a white
foam. [a]2D5: ꢀ8 (c 0.5, CHCl3); IR (KBr) 2959, 1500, 1200,
1110, 923, 705 cmꢀ1; 1H NMR (300 MHz, CDCl3) d 1.08 (d,
J¼7.2 Hz, 3H), 1.12 (s, 9H), 2.33 (s, 3H), 2.37 (br s, 1H),
2.80 (dq, J¼7.2, 6.9 Hz, 1H), 3.67–3.71 (m, 2H), 4.38–
4.42 (m, 1H), 5,22 (dd, J¼11.7, 1.1 Hz, 1H), 5.75 (ddd,
J¼11.7, 6.9, 2.4 Hz, 1H), 6.10 (s, 1H), 6.85 (s, 1H), 7.33–
7.45 (m, 6H), 7.68–7.75 (m, 4H); 13C NMR (75 MHz,
CDCl3) d 16.7, 19.6, 22.7, 26.6, 38.7, 65.6, 80.9, 118.3,
123.9, 125.2, 127.1, 127.6, 129.8, 132.8, 133.1, 134.4,
135.4, 137.1, 149.9; HRMS (m/z) calcd for C29H34O3SiNa,
481.2175 [M+Na]+; found, 481.2178.
1
1197, 1111, 910, 702 cmꢀ1; H NMR (300 MHz, CDCl3)
d 0.92 (d, J¼7.2 Hz, 3H), 1.18 (s, 9H), 2.35 (s, 3H), 3.33–
3.42 (m, 1H), 4.67 (s, 1H), 4.88–4.94 (m, 2H), 5.68 (ddd,
J¼16.4, 10.6, 6.8 Hz, 1H), 6.24 (s, 1H), 6.64 (s, 1H),
7.37–7.48 (m, 6H), 7.74–7.77 (m, 4H); 13C NMR
(75 MHz, CDCl3) d 16.6, 18.5, 19.6, 26.7, 36.8, 113.7,
117.8, 118.2, 126.9, 127.6, 127.7, 129.7, 133.3, 135.5,
142.2, 146.9, 147.7; HRMS (m/z) calcd for C27H32O2Si,
416.2172 [M]+; found, 416.2177.
4.1.6. Dialkene 3. Under Ar, to a solution of PPh3 (2.405 g,
9.16 mmol), phenol 4 (3.812 g, 9.16 mmol) and (S)-1-[(tert-
butyldimethyl)oxyl] but-3-en-2-ol 5 (1.680 g, 8.33 mmol) in
dry THF (40 mL) at 0 ꢁC was added dropwise DIAD
(1.853 g, 9.06 mmol). The reaction mixture was warmed to
rt and stirred overnight. The solvent was then evaporated
and the residue was purified by column chromatography
(hexanes/EtOAc, 100:1) to give 3 (3.546 g, 71%) as a color-
less oil. This product is a mixture of two diastereoisomers at
C-7.
4.1.9. (7R,10R)-7,10-Dihydro-5-[(tert-butyldiphenyl)-
oxyl]-4,7-dimethylbenzo[b]oxepin-carbaldehyde (16). A
mixture of alcohol 15 (376 mg, 0.82 mmol) and IBX
(1.152 g, 4.11 mmol) in THF/DMSO (9:1, 24 mL) was
stirred for 4 h at rt, diluted with hexanes, filtered through
Celite, and rinsed with hexanes/EtOAc (3:1). The filtrate
was transferred to a separated funnel and washed with brine,
dried (Na2SO4), and concentrated in vacuo to give the crude
aldehyde 16. This crude aldehyde was used directly in the
following step without further purification.
4.1.7. Compounds 13 and 14. To a solution of 3 (1.356 g,
2.26 mmol) in degassed CH2Cl2 (230 mL) at rt was added
the second-generation Grubbs catalyst 12 (192 mg,
0.226 mmol). The reaction mixture was stirred at rt for
15 h. The solvent was then evaporated and the residue was
purified by column chromatography (hexanes/CH2Cl2,
4.1.10. Compound 17. To a solution of MeMgI in Et2O
(0.5 M, 3.96 mL, 1.98 mmol) at 0 ꢁC was added a solution