1182
H. A. I. Yoshihara et al./Bioorg. Med. Chem. 6 (1998) 1179±1183
dichromate (23.93 g, 63.60 mmol). The reaction mix-
ture was stirred for 4 h at 0 ꢀC and then ®ltered
through Celite. The ®ltrate was evaporated, and the
residue was puri®ed by ¯ash column chromatography
(silica gel, 95:5 hexane:ethyl acetate) to give 4 (6 g,
19.23 mmol, 60%); 1H NMR (CDCl3) d 1.13 (d,
J=6.9 Hz, 6H), 2.02 (s, 6H), 3.22 (heptet, J=6.9 Hz,
1H), 3.73 (s, 3H), 3.79 (s, 3H), 6.53 (s, 2H), 6.71 (d,
J=8.4 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H), 7.78 (s, 1H).
13C NMR (CDCl3) d 199.5, 161.5, 159.5, 137.7, 136.2,
133.1, 130.6, 130.4, 127.2, 113.0, 109.7, 55.7, 55.3, 27.0,
22.5, 19.9. HRMS exact mass calcd for C20H24O3:
312.1725, found: 312.1724.
J=9 Hz, 1H), 6.54 (s, 2H), 3.81 (s, 3H), 3.77 (s, 3H),
3.27 (heptet, J=6.9 Hz, 1H), 2.31 (m, 2H), 2.21 (s, 6H),
1.57 (m, 2H), 1.35 (m, 2H), 1.18 (dd, J=6.9 Hz,
6H), 0.93 (t, J=7.2 Hz, 3H). 13C NMR (CDCl3) d 157.1,
155.9, 142.1, 138.8, 136.9, 135.2, 124.2, 123.9, 115.9,
110.3, 81.9, 55.4, 55.1, 40.7, 27.3, 26.7, 25.1, 23.6, 22.9,
14.4.
4,40-Dimethoxy-60-(1-methylpropyl)-30-(1-methylethyl)-
2,6-dimethylbenzophenone (7) and 1-(4-methoxy-2,6-
dimethylphenyl)-1-[4-methoxy-3-(1-methylethyl)phenyl]-
2-methylbutanol (8). To a suspension of CeCl3 (0.515 g,
2.1 mmol) in 7 mL of dry tetrahydrofuran at 78 ꢀC was
added 1.6 mL of sec-butyllithium (1.3 M in cyclohex-
ane). After stirring for 30 min at 78 ꢀC ketone 4 (0.5 g,
1.6 mmol) in 12 mL of tetrahydrofuran was added and
the mixture was stirred for 3±4 h. Then, the reaction
mixture was treated with satd NH4Cl solution, ®ltered
through silica, and extracted with ethyl acetate. The
organic portion was dried (MgSO4), ®ltered, and eva-
porated to give the crude product, which was puri®ed by
¯ash column chromatography (silica gel, hexane:ethyl
acetate, 98:2) to give 7 (130 mg, 0.35 mmol, 22%) and 8
(100 mg, 0.27 mmol, 17%). (7) 1H NMR (CDCl3), d 7.18
(s, 1H), 6.85 (s, 1H), 6.57 (s, 2H), 3.88 (s, 3H), 3.83 (m,
1H), 3.82 (s, 3H), 3.15 (heptet, J=6.9, 1H), 2.10 (s, 6H),
1.78 (m, 1H), 1.57 (m, 1H), 1.26 (d, J=6.6 Hz, 3H),
1.04 (d, J=6.9 Hz, 6H), 0.88 (t, J=7.5 Hz, 3H); 13C
NMR (C6D6) d 201.1, 160.5, 160.3, 150.6, 137.1,
136.1, 134.5, 131.6, 131.1, 113.9, 109.2, 55.2, 55.0, 36.3,
31.9, 27.4, 23.0, 22.7, 20.7, 13.1. HRMS exact mass
4,40-Dimethoxy-60-butyl-30-(1-methylethyl)-2,6-dimethyl-
benzophenone (5). To a suspension of cerous chloride
anhydrous (CeCl3) (1.580 g, 6.41 mmol) in 20 mL of dry
tetrahydrofuran at 78 ꢀC was added 3.2 mL of butyl-
lithium (2.0 M in pentane). The reaction mixture was
stirred for 30 min at 78 ꢀC and then ketone 4 (0.2 g,
0.641 mmol) in 5 mL of tetrahydrofuran was added and
the mixture was stirred for 3±4 h. Then, the reaction
mixture was treated with satd NH4Cl solution, ®ltered
through silica, and extracted with ethyl acetate. The
organic portion was dried (MgSO4), ®ltered, and eva-
porated to give the crude product, which was puri®ed
by ¯ash column chromatography (silica gel, hexane:
ethyl acetate, 98:2) to yield 90 mg (0.24 mmol, 38%)
of addition product 5 as an oil. 1H NMR (CDCl3)
d 7.22 (s, 1H), 6.73 (s, 1H), 6.58 (s, 2H), 3.89 (s, 3H),
3.82 (s, 3H), 3.18 (heptet, J=6.9 Hz, 1H), 3.05 (t,
J=7.8 Hz, 2H), 2.09 (s, 6H), 1.62 (quintet, J=7.5,
7.8 Hz, 1H), 1.44 (sextet, J=7.2, 7.5 Hz, 2H), 1.03
(d, J=6.9 Hz, 6H), 0.96 (t, J=7.2 Hz, 3H). 13C NMR
(CDCl3, 500 MHz) d 201.1, 159.8, 159.4, 145.5, 136.4,
134.9, 134.2, 131.6, 129.5, 113.4, 113.0, 55.6, 55.3, 34.8,
33.8, 26.7, 23.3, 22.6, 20.2, 14.2. HRMS exact mass
calcd for C24H32O3: 368.2351, found: 368.2347.
1
calcd for C24H32O3: 368.2351, found: 368.2345. (8) H
NMR (CDCl3) d 7.82 (d, J=1.8 Hz, 1H), 7.46 (dd,
J=1.8, 8.1 Hz, 1H), 7.21 (d, J=8.1 Hz, 1H), 6.61 (s,
2H), 3.83 (s, 3H), 3.82 (s, 3H), 3.26 (heptet, J=6.9,
1H), 3.04 (m, 1H), 2.11 (s, 6H), 1.61 (m, 2H), 1.23 (m,
9H), 0.86 (t, J=7.2 Hz, 3H).
ꢀ-Methyl-[4,40-dimethoxy-30-(1-methylethyl)-2,6-dimethyl]
benzhydrol (9). To a suspension of CeCl3 (0.592 g,
2.4 mmol) in 7 mL of dry tetrahydrofuran at 78 ꢀC was
added 1.71 mL of methyllithium (1.4 M in diethylether).
After stirring for 30 min at 78 ꢀC ketone 4 (0.5 g,
1.6 mmol) in 10 mL of tetrahydrofuran was added and
the mixture was stirred for 3±4 h. Then, the reaction
mixture was treated with sat. NH4Cl solution, ®ltered
through silica, and extracted with ethyl acetate. The
organic portion was dried (MgSO4), ®ltered, and eva-
porated to give the crude product, which was puri®ed by
¯ash column chromatography (silica gel, 95:5 hexane/
ethyl acetate) to yield the alcohol 9 (221 mg, 0.67 mmol,
42%). 1H NMR (CDCl3) d 7.35 (d, J=2.1, 1H), 7.20
(dd, J=2.1, 7.5 Hz, 1H), 6.80 (d, J=7.5Hz, 1H), 6.64
(s, 2H), 3.89 (s, 3H), 3.85 (s, 3H), 3.35 (heptet,
J=6.9 Hz, 1H), 2.22 (s, 6H), 2.00 (s, 3H), 1.20 (dd,
J=6.9 Hz, 6H).
4,40-Dimethoxy-60-butyl-30-(1-methylethyl)-2,6-dimethyl-
benzophenone (5) and 1-(4-methoxy-2,6-dimethylphenyl)-
1-[4-methoxy-3-(1-methylethyl)phenyl] pentanol (6). To a
suspension of CeCl3 (0.205 g, 0.832 mmol) in 3 mL of
dry tetrahydrofuran at 78 ꢀC was added 0.420 mL of
butyllithium (2.0 M in pentane). After stirring for
30 min at 78 ꢀC ketone 4 (0.2 g, 0.641 mmol) in 5 mL of
tetrahydrofuran was added and the mixture was stir-
red for 3±4 h. Then, the reaction mixture was treated
with sat. NH4Cl solution, ®ltered through silica, and
extracted with ethyl acetate. The organic portion was
dried (MgSO4), ®ltered, and evaporated to give the
crude product, which was puri®ed by ¯ash column
chromatography (silica gel, hexane/ethyl acetate, 98:2)
to give 5 (64 mg, 0.173 mmol, 27%) and 6 (52 mg,
0.141 mmol, 22%). (6): 1H NMR (CDCl3) d 7.24 (d,
J=2.1 Hz, 1H), 7.08 (dd, J=2.1, 9 Hz, 1H), 6.76 (d,