4
,5,6,7-Tetrahydro-5,5-dimethylbenzofuran-7-ol 18
0.95 (3 H, s, 5-Me), 0.92 [9 H, s, C(CH ) ], 0.15 (3 H, s, SiCH )
3 3 3
To a solution of ketone 5 (530 mg, 3.23 mmol) in dry ethanol (10
and 0.15 (3 H, s, SiCH ); δ 150.8 (s, C-2), 150.3 (s, C-7a), 119.4
(s, C-3a), 111.0 (d, C-3), 79.6 (d, OCH C᎐CH), 74.5 (s, OCH -
2 2
3 C
3
cm ) was added NaBH (122 mg, 3.23 mmol) at 0 ЊC. The reac-
4
tion mixture was stirred for 2 h at room temperature, then was
C᎐CH), 63.4 (d, C-7), 63.3 (t, 2-CH O), 56.6 (t, OCH C᎐CH),
᎐
2
2
quenched with saturated aq. NH Cl and extracted with diethyl
46.7 (t, C-6), 36.3 (t, C-4), 32.4 (s, C-5), 29.9 (q, 5-CH ), 27.6 (q,
4
3
ether. The combined extracts were washed with brine. After
removal of the solvent in vacuo, purification of the residue by
column chromatography [hexane–ethyl acetate (3:1)] gave com-
5-CH ), 25.9 [q, C(CH ) ], 18.3 [s, C(CH ) ], Ϫ4.6 (q, SiCH )
3
3
3
3
3
3
ϩ
and Ϫ4.8 (q, SiCH ); m/z [(ϩ)FAB] 347 ([M Ϫ H] , 74%), 293
3
(100) and 217 (92).
ϩ
pound 18 (496 mg, 93%) as an oil (Found: [M Ϫ H] , 165.0901.
Ϫ1
C H O requires m/z, 165.0916); νmax(neat)/cm 3350 (OH)
(4aSR,5RS)-5-(tert-Butyldimethylsilyloxy)-4,4a,5,6,7,8-
hexahydro-7,7-dimethylnaphtho[2,3-c]furan-4a-ol 21a and
(4aSR,5SR)-5-(tert-butyldimethylsilyloxy)-4,4a,5,6,7,8-
hexahydro-7,7-dimethylnaphtho[2,3-c]furan-4a-ol 21b
1
0
13
2
and 890 (furan); δ 7.33 (1 H, dd, J 0.7 and 2.0, 2-H), 6.18 (1 H,
H
d, J 1.7, 3-H), 4.78 (1 H, br t, J6 6.3, 7-H), 2.37 (1 H, dd, J
,7
4B,3
A
B
2
2
1
.0, J4A,4B 15.8, 4-H ), 2.19 (1 H, dt, J
1.3, J4A,4B 15.8, 4-H ),
4A,6B
.09 (1 H, br s, OH), 1.95 (1 H, ddd, J4
1.3, J6B,7 6.3, J
Compound 4 (111 mg, 0.32 mmol) was used as starting
material. By the same procedure as described for the synthesis
of compounds 14a,b and purification by flash column chrom-
atography [hexane–ethyl acetate (20:1)], compounds 21a (12.4
mg, 11%) and 21b (85.0 mg, 77%) were obtained as an oil;
A,6B
6A,6B
B
A
3.2, 6-H ), 1.63 (1 H, dd, J6 7.3, J6A,6B 13.2, 6-H ), 1.10
A,7
(
3 H, s, 5-Me) and 0.96 (3 H, s, 5-Me); δ 149.8 (s, C-7a), 142.3
C
(d, C-2), 119.0 (s, C-3a), 110.6 (d, C-3), 63.0 (d, C-7), 46.1 (t, C-
6
), 36.3 (t, C-4), 32.6 (s, C-5), 30.1 (q, 5-Me) and 27.0 (q, 5-Me);
ϩ
ϩ
m/z [(ϩ)FAB] 165 ([M Ϫ H] , 23%) and 149 (100).
the cis-naphtho[2,3-c]furanol 21a (Found: M , 348.2106.
Ϫ1
C H O Si requires M, 348.2121); νmax(neat)/cm 3550 (OH)
2
0
32
3
7
-(tert-Butyldimethylsilyloxy)-4,5,6,7-tetrahydro-5,5-dimethyl-
and 890 (furan); δ 7.26 (1 H, s, 1-H), 7.17 (1 H, d, J
2.0, 3-
H
3,4B
benzofuran 19
H), 6.33 (1 H, d, J8B,9 2.3, 9-H), 3.74 (1 H, dd, J
5.0, J5,6A
5,6B
A
The alcohol 18 (220 mg, 1.32 mmol) was used as a starting
material. By the same procedure as that described for the syn-
thesis of compound 11 and purification by column chrom-
atography [hexane–ethyl acetate (40:1)], compound 19 (340
11.5, 5-H), 3.01 (1 H, d, J
16.5, 4-H ), 2.65 (1 H, dd, J
4
A,4B
3,4B
B
2.0, J4A,4B 16.5, 4-H ), 2.61 (1 H, br s, OH), 2.50 (1 H, d, J
8A,8B
A
B
13.9, 8-H ), 1.87 (1 H, dd, J
2.3, J8A,8B 13.9, 8-H ), 1.68 (1 H,
8
B,9
A
dd, J5,6A 11.5, J6A,6B 12.9, 6-H ), 1.43 (1 H, ddd, J
2.6, J5,6B
6B,8B
Ϫ1
B
mg, 92%) was obtained as an oil; νmax(neat)/cm 880 (furan); δH
5.0, J6A,6B 12.9, 6-H ), 1.00 (3 H, s, 7-Me), 0.94 [9 H, s,
C(CH ) ], 0.87 (3 H, s, 7-Me), 0.12 (3 H, s, SiCH ) and 0.11 (3
7
.29 (1 H, dd, J 0.7 and 2.0, 2-H), 6.12 (1 H, d, J 1.7, 3-H), 4.73
3
3
3
(
1 H, br t, J6 6.3, 7-H), 2.33 (1 H, dd, J3,4B A1.7, J4A,4B 15.8, 4-
H, s, SiCH ); δ 137.6 (d, C-1), 137.0 (s, C-8a), 136.2 (d, C-3),
,7
3 C
B
H ), 2.14 (1 H, dd, J4
1.3, J4A,4B 15.8, 4-H ), 1.79 (1 H, ddd,
120.8 (s, C-9a), 118.0 (d, C-9), 117.7 (s, C-3a), 75.1 (d, C-5),
72.0 (s, C-4a), 44.5 (t, C-4 or -6), 44.0 (t, C-6 or -4), 32.0 (t, C-8),
31.8 (q, 7-Me), 31.7 (s, C-7), 25.9 [q, C(CH ) ], 25.1 (q, 7-Me),
A,6B
B
J4A,6B 1.3, J6B,7 A6.3, J6A,6B 13.2, 6-H ), 1.64 (1 H, dd, J
6.9,
6A,7
J6A,6B 13.2, 6-H ), 1.06 (3 H, s, 5-Me), 0.93 (3 H, s, 5-Me), 0.91
9 H, s, C(CH ) ], 0.14 (3 H, s, SiCH ) and 0.13 (3 H, s, SiCH );
3
3
[
18.0 [s, C(CH ) ], Ϫ4.0 (q, SiCH ) and Ϫ4.7 (q, SiCH ); m/z
3 3 3 3
ϩ
3
3
3
3
δC 150.2 (s, C-7a), 141.8 (d, C-2), 118.5 (s, C-3a), 110.4 (d, C-3),
3.5 (d, C-7), 46.9 (t, C-6), 36.4 (t, C-4), 32.6 (s, C-5), 29.9 (q, 5-
Me), 27.5 (q, 5-Me), 25.9 [q, C(CH ) ], 18.3 [s, C(CH ) ], Ϫ4.7
[(ϩ)FAB] 347 ([M Ϫ H] , 31%), 331 (98), 291 (54) and 199
ϩ
6
(100); the trans-naphtho[2,3-c]furanol 21b (Found: [M Ϫ H] ,
347.2051. C H O Si requires m/z, 347.2042); ν (CHCl )/
3
3
3
3
20 31
3
max
3
Ϫ1
(q, SiCH ) and Ϫ4.8 (q, SiCH ).
cm 3600 (OH) and 890 (furan); δ 7.26 (1 H, s, 1-H), 7.21 (1
3
3
H
H, d, J3,4B 1.7, 3-H), 6.25 (1 H, d, J 2.0, 9-H), 3.97 (1 H, dd, J
5,6B
B
7
-(tert-Butyldimethylsilyloxy)-4,5,6,7-tetrahydro-2-hydroxy-
3.3, J5,6A 8.6, 5-H), 2.88 (1 H, dd, J
1.7, J4A,4B 16.8, 4-H ),
3,4B
A
B
methyl-5,5-dimethylbenzofuran 20
2.77 (1 H, d, J4A,4B 16.8, 4-H ), 2.43 (1 H, d, J
13.5, 8-H ),
8A,8B
A
Compound 19 (3.10 g, 11.0 mmol) was used as a starting
material. By the same procedure as described for the synthesis
of compound 12 and purification by column chromatography
1.85 (1 H, d, J8A,8B 13.5, 8-H ), 1.75 (1 H, br s, OH), 1.60 (1 H,
B
dd, J5,6B 3.3, J
13.9, 6-H ), 1.33 (1 H, dd, J
8.6, J6A,6B
5,6A
6A,6B
A
13.9, 6-H ), 1.05 (3 H, s, 7-Me), 0.95 (3 H, s, 7-Me), 0.87 [9 H, s,
C(CH ) ], 0.11 (3 H, s, SiCH ) and 0.09 (3 H, s, SiCH ); δ 139.5
[
hexane–ethyl acetate (3:1)], compound 20 (2.99 g, 87%) was
3
3
3
3
C
ϩ
obtained as an oil (Found: [M Ϫ H] , 309.1891. C H O Si
requires m/z, 309.1886); νmax(neat)/cm 3350 (OH); δH 6.06 (1
(s, C-8a), 138.5 (d, C-1), 136.1 (d, C-3), 120.9 (s, C-9a), 117.9 (s,
C-3a), 116.2 (d, C-9), 75.4 (d, C-5), 74.6 (s, C-4a), 43.3 (t, C-4 or
-6), 42.8 (t, C-6 or -4), 31.5 (q, 7-Me), 31.1 (s, C-7), 29.4 (q, 7-
Me), 27.8 (t, C-8), 25.8 [q, C(CH ) ], 18.0 [s, C(CH ) ], Ϫ4.4 (q,
1
7
29
3
Ϫ1
H, s, 3-H), 4.74 (1 H, t, J6,7 6.4, 7-H), 4.54 (2 H, s, CH OH), 2.32
2
B
(
1 H, dd, J4
1.3, J4A,4B 15.8, 4-H ), 2.13 (1 H, d, J
15.8, 4-
4A,4B
B
B,6B
3
3
3 3
A
ϩ
H ), 1.81 (1 H, ddd, J4
H, br s, OH), 1.64 (1 H, dd, J6,7 6.4, J6A,6B 13.2, 6-H ), 1.08 (3 H,
s, 5-Me), 0.95 (3 H, s, 5-Me), 0.92 [9 H, s, C(CH ) ], 0.15 (6 H, s,
1.3, J6,7 6.4, J6A,6B 13.2, 6-H ), 1.77 (1
SiCH ) and Ϫ4.8 (q, SiCH ); m/z [(ϩ)FAB] 347 ([M Ϫ H] ,
B,6B
3
3
A
32%), 331 (80), 291 (64) and 199 (100).
3
3
SiCH ); δ 153.4 (s, C-2), 150.3 (s, C-7a), 119.4 (s, C-3a), 108.7
(4aSR,5SR)-4,4a,5,6,7,8-Hexahydro-7,7-dimethylnaphtho-
[2,3-c]furan-4a,5-diol 3b
3
C
(
d, C-3), 63.5 (d, C-7), 57.9 (t, CH OH), 46.8 (t, C-6), 36.3 (t,
2
C-4), 32.4 (s, C-5), 29.9 (q, 5-CH ), 27.5 (q, 5-CH ), 25.8
Compound 21b (1.84 g, 5.27 mmol) was used as starting
material. By the same procedure as described for the synthesis
of compound 15b, and purification by column chromatography
3
3
[
q, C(CH ) ], 18.3 [s, C(CH ) ], Ϫ4.6 (q, SiCH ) and Ϫ4.8 (q,
3 3 3 3 3
ϩ
SiCH ); m/z [(ϩ)FAB] 309 ([M Ϫ H] , 35%) and 293 (99).
3
[
hexane–ethyl acetate (1:1)], compound 3b (1.39 g; quant.) was
ϩ
7
-(tert-Butyldimethylsilyloxy)-4,5,6,7-tetrahydro-5,5-dimethyl-
obtained as a viscous oil (Found: M , 234.1254. C H O
14 18 3
Ϫ1
2
-(2-oxapent-4-ynyl)benzofuran 4
requires M, 234.1256); νmax(neat)/cm 3400 (OH) and 880
(furan); δH 7.30 (1 H, s, 1-H), 7.25 (1 H, s, 3-H), 6.29 (1 H, d,
Compound 20 (2.11 g, 6.81 mmol) was used as starting
material. By the same procedure as described for the synthesis
of analogue 13 and purification by column chromatography
J8B,9 2.0, 9-H), 4.06 (1 H, dd, J
d, J4A,4B 16.3, 4-H ), 2.84 (1 H, dd, J 1.8, J
3.6, J5,6A 10.2, 5-H), 2.92 (1 H,
5,6B
A
B
16.3, 4-H ), 2.44
4A,4B
B
[
hexane–ethyl acetate (20:1)], compound 4 (2.18 g, 92%) was
(1 H, dd, J8B,9 2.0, J8A,8B 13.5, 8-H ), 1.95 (2 H, br s, OH), 1.84
ϩ
A
obtained as an oil (Found: [M Ϫ H] , 347.2067. C H O Si
(1 H, d, J
H ), 1.34 (1 H, dd, J
13.5, 8-H ), 1.67 (1 H, dd, J
3.6, J6A,6B 13.5, 6-
5,6B
A
2
0
31
3
8A,8B
Ϫ1
B
requires m/z, 347.2042); νmax(neat)/cm 3300 (᎐C᎐H); δ 6.13 (1
10.2, J6A,6B 13.5, 6-H ), 1.09 (3 H, s, 7-
H
5,6A
H, s, 3-H), 4.73 (1 H, t, J6,7 6.4, 7-H), 4.50 (2 H, s, 2-CH O), 4.16
Me) and 0.96 (3 H, s, 7-Me); δ 139.3 (s, C-8a), 138.8 (d, C-1),
2
C
(
2 H, d, J 2.6, OCH C᎐CH), 2.44 (1 H, t, J 2.3, OCH C᎐CH),
136.4 (d, C-3), 120.7 (s, C-9a), 117.3 (s, C-3a), 116.6 (d, C-9),
74.6 (d, C-5), 74.5 (s, C-4a), 42.9 (t, C-4 or -6), 41.8 (t, C-6 or
-4), 31.3 (q, 7-Me), 31.0 (s, C-7), 29.5 (q, 7-Me) and 26.6 (t,
2
2
B
2
1
1
.32 (1 H, dd, J4
5.8, 4-H ), 1.80 (1 H, ddd, J4
1.7, J4A,4B 15.8, 4-H ), 2.13 (1 H, d, J
B,6B
4A,4B
B
A
1.3, J 6.4, J6A,6B 13.2, 6-H ),
B,6B
6,7
A
ϩ
.64 (1 H, dd, J6,7 6.4, J6A,6B 13.2, 6-H ), 1.07 (3 H, s, 5-Me),
C-8); m/z [(ϩ)FAB] 234 (M , 33%) and 217 (100).
1
712
J. Chem. Soc., Perkin Trans. 1, 1997