Tazoe et al.
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period of 6 h. After the suspension was stirred for an addi-
tional 5 h at room temperature, it was quenched with ice
water (300 mL). The reaction mixture was extracted with
CH2Cl2 (3 × 100 mL), washed with water (200 mL), dried
with Na2SO4, and concentrated in vacuo to 15 mL. Concen-
trated HCl (15 mL) was added, and the solution was stirred
for 15 min. The organic layer was extracted again with
CH2Cl2 (3 × 100 mL), washed with water (2 × 100 mL),
dried with Na2SO4, and concentrated and condensed under
reduced pressure. The residue was chromatographed on silica
gel using CHCl3 as the eluent to give crude anti-3c as a pale
yellow solid. The anti:syn ratio was determined as 5:95 by
mp 146–148 °C. dH (CDCl3): 1.06 (9H, s, t-Bu), 1.69–1.82
(2H, m, CH2), 2.25–2.53 (6H, m, CH2), 2.88–3.12 (4H, m,
CH2), 3.47 (6H, s, OMe), 6.41–6.50 (5H, m, Ar-H). m/z:
340 (M+). Anal. calcd for C23H29FO (340.49): C 81.14, H
8.59; found: C 81.21, H 8.70.
syn-6-tert-Butyl-9,18-dimethoxy[3.3]metacyclophane (syn-
4c) was obtained as colourless prisms (hexane), mp 82–84 °C.
dH (CDCl3): 1.15 (9H, s, t-Bu), 1.81–1.89 (2H, m, CH2),
2.45–2.52 (6H, m, CH2), 3.03–3.13 (4H, m, CH2), 3.48
(3H, s, OMe), 3.49 (3H, s, OMe), 6.48–6.56 (5H, m, Ar-
H). m/z: 352 (M+). Anal. calcd for C24H32O2 (352.52): C
81.77, H 9.15; found: C 81.58, H 9.11.
1
the H NMR spectrum. The residue was chromatographed
Wolff–Kishner reduction of anti-3c
on silica gel using CHCl3 as the eluent to give crude anti-3c
and syn-3c as a pale yellow solid and a pale yellow oil, re-
spectively. Recrystallization from hexane afforded anti-3c
(96 mg, 3%). Crude syn-3c was again chromatographed on
silica gel using CHCl3 as the eluent to afford 1.62 g (50%)
of syn-3c as a pale yellow oil.
anti-6-tert-Butyl-9,18-dimethoxy[3.3]metacyclophane-2,11-
dione (anti-3c) was obtained as colourless prisms (hexane),
mp 198–199 °C. nmax (KBr, cm–1): 1685 (C=O). dH
(CDCl3): 1.32 (9H, s, t-Bu), 3.16 (6H, s, OMe), 3.23 (4H,
d, J = 14.6 Hz, CH2), 3.60 (2H, d, J = 14.6 Hz, CH2),
3.63 (2H, d, J = 14.6 Hz, CH2), 6.93–6.99 (1H, m, Ar-H),
7.17 (2H, s, Ar-H) and 7.16–7.18 (2H, m, Ar-H). m/z: 380
(M+). Anal. calcd for C24H28O4 (380.49): C 75.75, H 7.42;
found: C 75.56, H 7.54.
syn-6-tert-Butyl-9,18-dimethoxy[3.3]metacyclophane-2,11-
dione (syn-3c) was obtained as a pale yellow oil. nmax (NaCl,
cm–1): 1688 (C=O). dH (CDCl3): 1.12 (9H, s, t-Bu), 3.32
(4H, d, J = 12.7 Hz, CH2), 3.55 (3H, s, OMe), 3.56 (3H, s,
OMe), 4.30 (4H, d, J = 12.7 Hz, CH2), 6.48–6.54 (1H, m,
Ar-H), 6.66 (2H, s, Ar-H), 6.65–6.68 (2H, m, Ar-H). m/z:
380 (M+). Anal. calcd for C24H28O4 (380.49): C 75.76, H
7.42; found: C 75.62, H 7.35.
A mixture of anti-3c (1.20 g, 3.3 mmol), KOH (1.28 g,
23.0 mmol), 100% hydrazine hydrate (0.35 mL, 6.2 mmol),
and triethylene glycol (3 × 50 mL) was heated at 120 °C for
2 h and then at 220 °C for 3 h. The cooled mixture was
poured into water (50 mL), acidified with diluted HCl, ex-
tracted with CH2Cl2 (3 × 50 mL), washed with water (2 ×
20 mL), dried with Na2SO4, and concentrated under reduced
pressure. The residue was chromatographed on silica gel us-
ing hexane/benzene (1:1) as the eluent to give crude anti-4c
as a colourless solid. Recrystallization from hexane afforded
anti-6-tert-butyl-9,18-dimethoxy[3.3]metacyclophane (anti-
4c) was obtained as colourless prisms (930 mg, 80%),
mp 220–222 °C. dH (CDCl3): 1.34 (9H, s, t-Bu), 2.05–2.15
(4H, m, CH2), 2.31–2.42 (4H, m, CH2), 2.57–2.69 (4H, m,
CH2), 3.10 (3H, s, OMe), 3.15 (3H, s, OMe), 6.85–6.88 (1H,
m, Ar-H), 6.95–6.87 (4H, m, Ar-H). m/z: 352 (M+). Anal.
calcd for C24H32O2 (352.52): C 81.77, H 9.15; found: C
81.69, H 9.04.
Reaction of syn-4a with BBr3
To a solution of syn-4a (60 mg, 0.186 mmol) in CH2Cl2
(6 mL) at 0 °C was gradually added a solution of BBr3
(0.087 mL, 0.922 mmol) in CH2Cl2 (0.1 mL). After the reac-
tion mixture had been stirred at room temperature for 3 h, it
was poured into ice water (10 mL) and then extracted with
CH2Cl2 (10 mL × 3). The combined extracts were washed
with water (2 × 10 mL), dried over Na2SO4, and concen-
trated in vacuo to leave a residue. The residue was chromato-
graphed over silica gel (Wako C-300, 100 g) with hexane/
CHCl3 (4:1) as the eluent to give crude syn-5a as a colour-
less solid. Recrystallization from MeOH afforded syn-6-tert-
butyl-9-hydroxy[3.3]metacyclophane (syn-5a) was obtained
as a brown oil (46 mg, 80%). nmax (NaCl, cm–1): 3424 (OH).
dH (CDCl3): 1.03 (9H, s, t-Bu), 1.72–1.81 (2H, m, CH2),
2.25–2.32 (2H, m, CH2), 2.42–2.52 (2H, m, CH2), 2.54–2.56
(2H, m, CH2), 2.59–2.68 (2H, m, CH2), 2.81–2.90 (2H, m,
CH2), 4.61 (1H, s, OH), 6.46 (2H, s, Ar-H), 6.48 (2H, d,
J = 6.0 Hz, Ar-H), 6.72 (1H, t, J = 6.0 Hz, Ar-H). m/z: 308
(M+). Anal. calcd for C22H28O (308.46): C 85.66, H 9.15;
found: C 85.56, H 9.31.
Wolff–Kishner reduction of anti-3a
A mixture of anti-3a (1.20 g, 3.42 mmol), KOH (1.28 g,
23.0 mmol), 100% hydrazine hydrate (0.35 mL, 6.2 mmol),
and triethylene glycol (3 × 50 mL) was heated at 120 °C for
2 h and then at 220 °C for 3 h. The cooled mixture was
poured into water (50 mL), acidified with diluted HCl, ex-
tracted with CH2Cl2 (3 × 50 mL), washed with water (2 ×
20 mL), dried with Na2SO4, and concentrated under reduced
pressure. The residue was chromatographed on silica gel us-
ing hexane/benzene (1:1) as the eluent to give crude syn-4a
as a colourless solid. Recrystallization from MeOH afforded
syn-6-tert-butyl-9-methoxy[3.3]metacyclophane
(syn-4a),
which was obtained as colourless prisms (882 mg, 80%),
mp 112–114 °C. dH (CDCl3): 1.09 (9H, s, t-Bu), 1.70–1.82
(2H, m, CH2), 2.30–2.37 (2H, m, CH2), 2.47–2.76 (6H, m,
CH2), 3.00–3.09 (2H, m, CH2), 3.67 (3H, s, OMe), 6.54
(2H, d, J = 7.0 Hz, Ar-H), 6.55 (2H, s, Ar-H), 6.73 (1H, t,
J = 7.0 Hz, Ar-H), 7.18 (1H, s, Ar-H). m/z: 322 (M+). Anal.
calcd for C23H30O (322.49): C 85.66, H 9.38; found: C
85.65, H 9.39.
Compounds syn-5b and syn-5c were similarly prepared in
75% and 85% yield, respectively.
syn-6-tert-Butyl-18-furuoro-9-hydroxy[3.3]metacyclophane
(syn-5b) was obtained as a pale yellow oil. nmax (NaCl, cm–1):
3354 (OH). dH (CDCl3): 1.13 (9H, s, t-Bu), 1.80–1.92 (2H,
m, CH2), 2.33–2.43 (2H, m, CH2), 2.52–2.65 (2H, m, CH2),
2.52–2.65 (2H, m, CH2), 2.95–3.01 (4H, m, CH2), 4.81 (1H,
Compounds syn-4b and syn-4c were similarly prepared in
76% and 85% yield, respectively.
syn-6-tert-Butyl-9-furuoro-18-methoxy[3.3]metacyclophane
(syn-4b) was obtained as colourless prisms (MeOH),
Published by NRC Research Press