F. Maertens, S. Toppet, F. Compernolle, G. J. Hoornaert
FULL PAPER
Methyl (2R*,4aR*,9bR*)-2-(Hydroxymethyl)-9b-phenyl-3,4,5,9b-
tetrahydroindeno[1,2-b]pyran-4a(2H)-carboxylate (15b) and Methyl
H, CH
2 2
OMs), 4.09 (dd, J ϭ 11, 6 Hz, 0.58 H, CH OMs), 4.06 (m,
2
4
0.42 H, H ), 3.94 (d, J ϭ 17 Hz, 0.42 H, H ), 3.83 (d, J ϭ 17 Hz,
0.58 H, H ), 3.22 (s, 1.74 H, OCH
4
(
2S*,4aR*,9bR*)-2-Hydroxymethyl-9b-phenyl-3,4,5,9b-tetra-
3 2 3
), 3.12 (s, 1.26 H, SO CH ), 3.10
4
hydroindeno[1,2-b]pyran-4a(2H)-carboxylate (15bЈ): IR (NaCl): ν˜ ϭ (s, 1.26 H, OCH
), 3.05 (d, J ϭ 17 Hz, 0.42 H, H ), 2.93 (s, 1.74
3
Ϫ1
4
3
3
440.8 (OH), 1724.9 (CϭO) cm . MS (EI): m/z (%) ϭ 338 (7)
H, SO
2 3
CH ), 3.03 (d, J ϭ 17 Hz, 0.58 H, H ), 2.81 (m, 1 H, H ),
·
ϩ
·ϩ
·ϩ
3
[
(
M
], 307 (12) [M Ϫ CH
3
O], 279 (100) [M Ϫ CO CH ], 275 2.01 (dd, J ϭ 13, 7 Hz, 0.42 H, H ), 1.83 (dd, J ϭ 13, 10 Hz, 0.58
2 3
17) [M· Ϫ C
ϩ
O
2
H
2
], 205 (55) [C16
H
13 ], 105 (26) [C
ϩ
H
5
CO ]; H, H ) ppm. C (100 MHz, CDCl
141.7, 141.1, 140.2, 139.5, 129.3, 129.0, 128.2, 128.0, 127.7, 127.6,
): δ ϭ 127.5, 127.4, 126.5, 126.4, 126.0, 125.6, 125.5, 125.2, 124.6, 101.9,
2
.37Ϫ7.04 (m, 9 H, H arom.), 3.81 (m, 2 H, H ϩ CH OH), 3.64 101.2, 78.6, 75.4, 70.9, 70.6, 66.2, 65.2, 51.8, 51.7, 40.9, 40.8, 40.6,
ϩ
3
13
2
6
3
): δ ϭ 173.5, 173.1, 146.0, 143.2,
exact mass calculated for C21
H
22
O
4
: 338.1518; found 338.1529.
1
Minor Isomer 15bЈ: Yield 32%. H NMR (400 MHz, CDCl
3
2
7
(
1
(
5
·ϩ
3
d, J ϭ 16 Hz, 1 H, H ), 3.35 (s, 3 H, OCH ), 2.67 (d, J ϭ 16 Hz, 38.8, 37.8, 37.6 ppm. MS (EI): m/z (%) ϭ 402 (9) [M ], 384 (20)
5
4
·ϩ
·ϩ
·ϩ
H, H ), 2.50 (s, 1 H, OH), 2.18 (m, 2 H, CH
2
OH ϩ H ), 1.65
): 288 (19) [M Ϫ H
δ ϭ 173.9, 146.5, 143.6, 139.2, 128.2, 127.7, 127.2, 126.8, 126.3, CHO], 229 (35) [C18
lated for C21 22SO
[M Ϫ H
2
O], 370 (61) [M Ϫ MeOH], 306 (2) [M Ϫ CH
3
SO
3
H],
m, 1 H H ), 1.29 (m, 2 H, H ) ppm. 13C NMR (100 MHz, CDCl
4
3
·ϩ
O Ϫ CH
SO
3
H], 264 (33) [M Ϫ CH
·ϩ
SO
CH2-
3
2
3
3
3
ϩ
ϩ
H
13 ], 205 (100) [C16H13 ]; exact mass calcu-
1
2
25.3, 124.8, 124.4, 89.4, 72.3, 66.0, 57.8, 51.5, 42.1, 29.2,
H
6
: 402.1137; found 402.1136.
1
1.2 ppm. Major Isomer 15b: Yield 61%. H NMR (400 MHz,
Methyl (2R*,4aR*,9bR*)-2-{[(Methylsulfonyl)oxy]methyl}-9b-phe-
nyl-3,4,5,9b-tetrahydroindeno[1,2-b]pyran-4a(2H)-carboxylate (15b
Mesylate) ؉ Methyl (2S*,4aR*,9bR*)-2-{[(Methylsulfonyl)-
oxy]methyl}-9b-phenyl-3,4,5,9b-tetrahydroindeno[1,2-b]pyran-
4a(2H)-carboxylate (15bЈ Mesylate): IR (KBr): ν˜ ϭ 1724.4 (CϭO),
CDCl
H, H arom.), 4.38 (m, 1 H, H ), 3.91 (d, J ϭ 17 Hz, 1 H, H ), 3.59
dd, J ϭ 12, 4 Hz, 1 H, CH OH), 3.47 (dd, J ϭ 12, 7 Hz, 1 H,
CH OH), 3.30 (s, 3 H, OCH
s, 1 H, OH), 2.18 (ddd, J ϭ 15, 6, 6 Hz, 1 H, H ), 1.93 (ddd, J ϭ
3
): δ ϭ 7.27Ϫ7.15 (m, 8 H, H arom.), 7.05 (d, J ϭ 8 Hz, 1
2
5
(
2
5
2
3
), 3.08 (d, J ϭ 17 Hz, 1 H, H ), 2.50
4
(
Ϫ1
·ϩ
4
3
3
2
1451.9 ϩ 1280.0 (SO O) cm . MS (EI): m/z (%) ϭ 416 (1) [M ],
1
5, 9, 6 Hz, 1 H, H ), 1.76 (m, 1 H, H ), 1.52 (m, 1 H, H ) ppm.
C NMR (100 MHz, CDCl ): δ ϭ 174.9, 147.0, 143.7, 139.5,
3
·
ϩ
·ϩ
1
3
384 (11) [M Ϫ MeOH], 357 (100) [M Ϫ CH
3
CO
2
], 321 (20)
M· Ϫ CH
calculated for C22
5bЈ Mesylate: Yield 32%. H NMR (300 MHz, CDCl
ϩ
SO
], 302 (9) [M Ϫ CH
·ϩ
SO
Ϫ H
O]; exact mass
[
3
3
2
3
2
1
6
28.6, 127.8, 127.4, 126.9, 126.5, 125.9, 125.0, 124.5, 89.6, 72.5,
6.2, 58.0, 42.6, 41.4, 29.5, 21.5 ppm.
24 6
H O S: 416.1294; found 416.1284. Minor Isomer
1
1
3
): δ ϭ
Methyl
(4aS*,10bR*)-2-(Hydroxymethyl)-10b-phenyl-3,4,6,10b- 7.41Ϫ6.97 (m, 9 H, H arom.), 4.52 (dd, J ϭ 11, 7 Hz, 1 H,
tetrahydro-2H-benzo[h]chromene-4a(5H)-carboxylate (21b,bЈ): Mix-
ture of diastereoisomers, de ϭ 14%; yield 70%. IR (NaCl): ν˜ ϭ
CH
2
OMs), 4.30 (dd, J ϭ 11, 3 Hz, 1 H, CH
2
OMs), 3.95 (m, 1 H,
2
5
H ), 3.62 (d, J ϭ 16 Hz, 1 H, H ), 3.35 (s, 3 H, OCH ), 3.06 (s, 3
H, SO CH ), 2.66 (d, J ϭ 16 Hz, 1 H, H ), 2.22 (m, 2 H, H ), 1.66
2 3
3
Ϫ1
1
5
4
3
342.9 (OH), 1726.0 (CϭO) cm . H NMR (400 MHz, CDCl
3
):
2
3
13
δ ϭ 7.27Ϫ7.08 (m, 9 H, H arom.), 4.32 (m, 0.43 H, H ), 3.78 (dd, (m, 2 H, H ) ppm. C NMR (75 MHz, CDCl
3
): δ ϭ 174.2, 143.7,
J ϭ 11, 7 Hz, 0.57 H, CH
CH OH), 3.59 (m, 0.57 H, H ), 3.50 (m, 0.86 H, CH
.29 H, OCH ), 3.28 (s, 1.71 H, OCH
2
OH), 3.72 (dd, J ϭ 11, 3 Hz, 0.57 H,
142.2, 139.5, 129.5, 129.2, 128.4, 128.0, 127.5, 126.5, 126.0, 125.6,
125.0, 90.3, 72.6, 69.9, 55.7, 51.9, 40.6, 38.1, 37.6, 21.9 ppm. Major
2
2
2
OH), 3.42 (s,
1
1
6
0
2
3
3
), 3.21 (ddd, J ϭ 18, 11, Isomer 15b Mesylate: Yield 63%. H NMR (300 MHz, CDCl
3
): δ ϭ
6
6
2
Hz, 0.43 H, H ), 3.02 (m, 1.14 H, H ), 2.98 (ddd, J ϭ 18, 6, 3 Hz,
7.34Ϫ7.02 (m, 9 H, H arom.), 4.63 (m, 1 H, H ), 4.20 (m, 2 H,
6
3
4
5
5
.43 H, H ), 2.63Ϫ2.19 (m, 2 H, 0.57 H ϩ 0.57 H ϩ 0.86 H ), CH
2
OMs), 3.97 (d, J ϭ 17 Hz, 1 H, H ), 3.35 (s, 3 H, OCH
3
), 3.08
), 2.20 (dt, J ϭ 14,
3
4
5
.11 (m, 1.29 H, 0.43 H ϩ 0.86 H ), 2.02 (dt, J ϭ 14, 5 Hz, 0.57 (d, J ϭ 17 Hz, 1 H, H ), 3.02 (s, 3 H, SO
H, H ), 1.87 (ddd, J ϭ 14, 5, 2 Hz, 0.57 H, H ), 1.70 (ddd, J ϭ 15,
, 3 Hz, 0.57 H, H ), 1.52Ϫ1.29 (m, 1 H, H ) ppm. C NMR
2
CH
3
5
5
4
4
3
3
6 Hz, 1 H, H ), 1.92 (m, 2 H, H ϩ H ), 1.54 (m, 1 H, H ) ppm.
4
3
13
13
6
3
C NMR (75 MHz, CDCl ): δ ϭ 175.0, 146.9, 142.3, 141.4, 130.1,
(
100 MHz, CDCl ): δ ϭ 176.4, 174.9, 145.9, 145.1, 143.8, 138.6, 129.3, 128.6, 128.1, 127.9, 126.8, 126.2, 125.7, 125.1, 90.9, 73.2,
3
1
1
4
36.8, 136.1, 129.5, 129.1, 128.8, 128.7, 128.5, 128.1, 127.8, 127.7, 70.0, 58.0, 52.2, 42.9, 38.2, 31.7, 23.6 ppm.
27.6, 127.4, 126.8, 81.0, 79.7, 75.0, 71.3, 66.9, 66.8, 52.0, 51.6,
Methyl
(3aS*,9bR*)-2-{[(Methylsulfonyl)oxy]methyl}-9b-phenyl-
8.9, 47.2, 29.7, 27.4, 26.8, 26.7, 25.8, 25.1, 23.5, 22.7 ppm. MS
ϩ
ϩ
2,3,5,9b-tetrahydronaphtho[1,2-b]furan-3a(4H)-carboxylate (21a,aЈ
Mesylate): Mixture of diastereoisomers, de ϭ 12%; yield 95%, IR
(EI): m/z (%) ϭ 353 (17) [MH ], 321 (100)[MH Ϫ MeOH], 292
·
ϩ
ϩ
ϩ
(
48)[M Ϫ CO
CH Ϫ MeOH], 105 (33) [C
exact mass calculated for C22 : 352.1675; found 352.1687.
2 3 2
CH Ϫ H ], 289 (61) MH Ϫ 2MeOH], 261 [MH
Ϫ1
1
ϩ
ϩ
(KBr): ν˜ ϭ 1721.4 (CϭO) cm . H NMR (300 MHz, CDCl
3
): δ ϭ
.27Ϫ7.03 (m, 9 H, H arom.), 5.06 (m, 0.56 H, H ), 4.83 (dd, J ϭ
1, 8 Hz, 0.44 H, CH OMs), 4.48 (dd, J ϭ 11, 4 Hz, 0.44 H,
Ϫ HCO
2
3
6 5 6 5
H CO ], 77 (34) [C H ];
2
7
1
24 4
H O
2
2
General Procedure for the Mesylation of 15a,aЈ, 15b/15bЈ, 21a,aЈ CH
and 21b,bЈ: Et N (8.5 mL, 61 mmol) was added to a solution of CH
5a,aЈ (1.98 g, 6 mmol) in CH Cl
4 mmol) and DMAP (0.15 g, 1 mmol) were then added at 0 °C. (m, 2 H, H ), 2.78 (s, 1.68 H, SO
2
OMs), 4.03 (m, 0.44 H, H ), 3.90 (dd, J ϭ 11, 4 Hz, 0.56 H,
OMs), 3.77 (dd, J ϭ 11, 6 Hz, 0.56 H, CH OMs), 3.22 (s, 1.68
), 3.20 (s, 1.32 H, SO CH ), 3.10 (s, 1.32 H, OCH ), 3.02
3
2
2
1
2
2
2
(50 mL). MsCl (1.9 mL, H, OCH
3
3
3
3
4
5
2
CH
3
), 2.52 (m, 1 H, H ), 2.48
3
3
After stirring at 0 °C for 2 h, water (50 mL) was added. The aque-
ous layer was extracted three times with CH Cl . The combined
organic phases were dried with MgSO and filtered and then the
(dd, J ϭ 13, 7 Hz, 0.57 H, H ), 2.32 (m, 0.86 H, H ), 2.08 (dd, J ϭ
3
4
13
2
2
13, 9 Hz, 0.57 H, H ), 1.99 (m, 1 H, H ) ppm. C NMR (75 MHz,
CDCl ): δ ϭ 175.0, 174.4, 144.0, 143.1, 141.5, 139.6, 136.1, 134.2,
4
3
solvents were evaporated. The residue was purified by column chro-
matrography (silica gel; heptane/ethyl acetate, 1:1).
131.1, 130.1, 128.4, 128.3, 128.1, 128.0, 127.9, 127.8, 127.5, 127.3,
127.1, 126.5, 89.2, 88.6, 76.6, 73.8, 72.3, 72.0, 58.1, 57.2, 52.1, 52.0,
3
8.1, 37.6, 34.2, 33.9, 25.0, 24.8, 24.6, 24.0 ppm. MS (EI): m/z
Methyl
,3,4,8b-tetrahydro-3aH-indeno[1,2-b]furan-3a-carboxylate (15a,aЈ
Mesylate): Mixture of diastereoisomers, de ϭ 16%; yield 78%. IR
(3aS*,8bR*)-2-{[(Methylsulfonyl)oxy]methyl}-8b-phenyl-
·ϩ
·ϩ
(%) ϭ 417 (9) [MH ], 356 (30) [M Ϫ CH
3
·ϩ
CO
2
H], 339 (16)
O], 263 (100) [MH Ϫ CH SO
], 243 (53) [M Ϫ HCO CH Ϫ CH SO H Ϫ H O]; exact
S: 416.1294; found 416.1291.
2
·ϩ
[MH Ϫ CH
3
CO
2
H Ϫ H
2
3
3
Ϫ
·ϩ
CH
3
CO
2
2
3
3
3
2
Ϫ1
1
(
KBr): ν˜ ϭ 1719.9 (CϭO), 1353.2 ϩ 1170.5 (SO
2
O) cm
): δ ϭ 7.38Ϫ7.03 (m, 9 H, H arom.), 5.01
OMs), 4.44
. H
24 6
mass calculated for C22H O
NMR (400 MHz, CDCl
3
2
(m, 0.58 H, H ), 4.58 (dd, J ϭ 11, 6 Hz, 0.42 H, CH
2
Methyl (4aS*,10bR*)-2-{[(Methylsulfonyl)oxy]methyl}-10b-phenyl-
(
dd, J ϭ 11, 4 Hz, 0.42 H, CH
2
OMs), 4.15 (dd, J ϭ 11, 4 Hz, 0.58 3,4,6,10b-tetrahydro-2H-benzo[h]chromene-4a(5H)-carboxylate
2712
2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 2707Ϫ2714