K. Krohn et al.
FULL PAPER
1
-{1-Hydroxy-3-[(2-methyl-1,3-dioxolan-2-yl)methyl]naphthalen-2-
yl}ethanone (24): A solution of the isocoumarin 16 (280 mg,
.01 mmol) in dry THF (2 mL) was added dropwise to a solution
of the anion of acetone [prepared under argon at 0 °C from acetone
0.30 mL, 4.04 mmol) and sodium hydride (350 mg, 8.48 mmol) in
C-2ЈЈЈ), 104.6 (d, C-7Ј), 113.7 (s, C-4Јa or C-8Јa), 121.7 (d, C-5Ј or
C-6Ј), 122.7 (d, C-4Ј), 125.4 (s, C-2Ј), 127.2 (C-6Ј or C-5Ј), 134.8
(s, C-3Ј), 135.9 (s, C-8Јa or C-4Јa), 153.0 (s, C-1Ј), 156.4 (s, C-8Ј),
205.1 (s, C-1) ppm. IR (NaCl, film): ν˜ = 3352, 2923, 1687, 1681,
1
–
1
(
1626, 1613, 1581, 1494, 1450, 1370, 1255, 1239, 1164, 1091 cm .
+
dry THF (8 mL)]. The mixture was stirred for 3 h at room temp.
After addition of dilute hydrochloric acid, the mixture was ex-
tracted with ethyl acetate, the combined organic phases were
washed with brine and dried with anhydrous sodium sulfate, and
the solvents were removed under reduced pressure. Purification by
flash chromatography (dichloromethane/diethyl ether, 100:0 to
MS (EI, 70 eV): m/z (%) = 348 (42) [M] , 279 (14), 255 (38), 230
(75), 215 (65), 167 (18), 149 (32), 119 (100), 59 (41), 43 (33).
HRMS: calcd. for C18
20 3 2
H O S 348.0854; found 348.0853.
2
-Acetyl-[(2-methyl-1,3-dithiolan-2-yl)methyl]naphthalen-1-yl (2-
Methyl-1,3-dithiolan-2-yl)acetate (28): A solution of the phenol 25
42]
(
100 mg, 0.36 mmol) was treated with the acid 27,[ DCC (111 mg,
9
5:5) afforded the acetyl-naphthol 24 (166 mg, 59%) as a yellow
1
0.54 mmol), p-toluenesulfonic acid (5 mg), and DMAP (10 mg) in
dry dichloromethane (2 mL). The mixture was stirred for 3.5 h at
room temp. and filtered, and the solvent was removed under re-
duced pressure. Purification by flash chromatography (n-hexane/
solid; m.p. 83 °C. H NMR (500 MHz, CDCl
ЈЈЈЈ-H), 2.73 (s, 3 H, 2-H), 3.30, 3.70 (2ϫm, 2ϫ2 H, 4ЈЈЈ-H, 5ЈЈЈ-
H), 3.45 (s, 2 H, 1ЈЈ-H), 7.19 (s, 1 H, 4Ј-H), 7.46 (ddd, J = 8.2, J
7.0, J = 0.8 Hz, 1 H, 7Ј-H), 7.56 (ddd, J = 8.2, J = 7.0, J =
.8 Hz, 1 H, 6Ј-H), 7.68 (d, J = 8.1 Hz, 1 H, 5Ј-H), 8.39 (m, 1 H,
3
): δ = 1.38 (s, 3 H,
1
=
ethyl acetate, 9:1 to 8:2) afforded the product 28 as a colorless oil
0
8
2
5
8
6
1
1
1
Ј-H), 13.22 (s, 1 H, OH) ppm. 1 C NMR (125 MHz, CDCl
3
(118 mg, 69%). H NMR (500 MHz, CDCl
3
): δ = 1.77 (s, 3 H,
3
): δ =
1
2
ЈЈЈЈ-H), 2.03 (s, 3 H, aЈЈЈ-H), 2.63 (s, 3 H, 2Ј-H), 3.06, 3.26 (2ϫm,
ϫ2 H, 4ЈЈЈ-H, 5ЈЈЈ-H), 3.42 (m, 4 H, dЈЈ-H, eЈЈ-H), 3.46 (s, 2 H,
5.9 (q, C-1ЈЈЈЈ), 32.5 (q, C-2), 45.8 (t, C-1ЈЈ), 60.4 (t, C-4ЈЈЈ, C-
ЈЈЈ), 109.4 (s, C-2ЈЈЈ), 117.3 (s, C-2Ј), 123.4 (d, C-4Ј), 124.2 (d, C-
Ј), 124.6 (s, C-8Јa), 125.6 (d, C-7Ј), 127.0 (d, C-5Ј), 129.5 (d, C-
Ј), 131.5 (s, C-3Ј), 135.5 (s, C-4Јa), 160.1 (s, C-1Ј), 206.2 (s, C-
) ppm. IR (KBr): ν˜ = 3447, 2985, 2953, 2923, 2883, 1618, 1570,
b-H), 3.49 (s, 2 H, 1ЈЈ-H), 7.52–7.55, 7.83–7.85 (2ϫm, 2ϫ2 H, 5-
1
3
H, 6-H, 7-H, 8-H), 7.88 (s, 1 H, 4-H) ppm. C NMR (125 MHz,
CDCl ): δ = 31.5, 31.5 (2ϫq, C-aЈЈЈ, C-1ЈЈЈЈ), 33.0 (q, C-2Ј), 40.0
3
–
1
(t, C-4ЈЈЈ, C-5ЈЈЈ), 40.2 (t, C-dЈЈ, C-eЈЈ), 46.7 (t, C-1ЈЈ), 50.4 (t, C-
b), 62.0 (q, C-bЈЈ), 66.9 (s, C-2ЈЈЈ), 122.0, 127.1, 127.6, 128.0 (4ϫd,
C-5, C-6, C-7, C-8), 125.6, 133.8 (2ϫs, C-4a, C-8a), 132.3 (s, C-3),
396, 1375, 1344, 1254, 1215, 1153, 1098, 1034, 825, 765 cm . MS
+
(
(
EI, 70 eV): m/z (%) = 286 (8) [M] , 224 (4), 163 (59), 145 (55), 87
64), 43 (100). HRMS: calcd. for C17 286.1205; found
18 4
H O
133.2 (s, C-2), 143.6 (s, C-1), 168.2 (s, C-a), 202.4 (s, C-1) ppm
2
86.1205.
(
letters refer to the acid part, numbers to the “alcohol” part). IR
1
-{1-Hydroxy-3-[(2-methyl-1,3-dithiolan-2-yl)methyl]naphthalen-2-
(
1
(
(
NaCl, film): ν˜ = 3053, 2967, 2922, 2857, 1766, 1692, 1444, 1333,
yl}ethanone (25): A solution of isocoumarin 18 (280 mg,
.01 mmol) in dry THF (2 mL) was added dropwise to a solution
–1
2 2
275, 1254, 1120, 1166 cm . UV (CH Cl ): λmax (lg ε) = 230
1
+
3.88) nm. MS (EI, 70 eV): m/z (%) = 478 (8) [M] , 414 (1), 282
of the anion of acetone [prepared under argon at 0 °C from freshly
distilled acetone (0.30 mL, 4.04 mmol) and sodium hydride
3), 360 (15), 318 (2), 279 (5), 240 (23), 224 (6), 119 (100), 98 (29),
49 (48). HRMS: calcd. for C23
26 3 4
H O S 478.0765; found 478.0765.
(240 mg, 6.06 mmol) in dry THF (8 mL)]. The mixture was stirred
2-Hydroxy-2,5-bis[(2-methyl-1,3-dithiolan-2-yl)methyl]-2,3-dihydro-
for 3 h at room temp. Workup was performed as described for 24
benzo[H]chromen-4-one (29): Lithium hydride (28 mg) was added at
0 °C under argon to a solution of the ester 28 (100 mg, 0.21 mmol)
in dry THF (21 mL). The mixture was heated under reflux for 24 h
and then cooled to 0 °C, dilute hydrochloric acid was added, the
mixture was extracted with dichloromethane, the combined organic
phases were washed with hydrochloric acid and brine and dried
over anhydrous sodium sulfate, and the solvents were removed un-
der reduced pressure. Purification by flash chromatography (dichlo-
to afford the naphthol 25 (207 mg, 64%) as a yellow solid; m.p.
1
81–82 °C. H NMR (500 MHz, CDCl
3
): δ = 1.71 (s, 3 H, 1ЈЈЈЈ-H),
2.75 (s, 3 H, 2-H), 2.92, 3.20 (2ϫm, 2ϫ2 H, 4ЈЈЈ-H, 5ЈЈЈ-H), 3.70
(s, 2 H, 1ЈЈ-H), 7.26 (s, 1 H, 4Ј-H), 7.49 (ddd, J = 8.2, J = 7.0, J =
1
6
.1 Hz, 1 H, 7Ј-H), 7.59 (ddd, J = 8.2, J = 7.0, J = 1.1 Hz, 1 H,
Ј-H), 7.71 (m, 1 H, 5Ј-H), 8.41 (m, 1 H, 8Ј-H), 13.28 (s, 1 H,
13
OH) ppm. C NMR (125 MHz, CDCl
ЈЈЈЈ), 40.3 (t, C-4ЈЈЈ, C-5ЈЈЈ), 50.6 (t, C-1ЈЈ), 67.2 (C-2ЈЈЈ), 117.1 (s,
C-2Ј), 124.0 (d, C-4Ј), 124.4 (d, C-8Ј), 124.8 (s, C-8Јa), 125.9 (d, C-
3
): δ = 33.1 (2ϫq, C-2, C-
1
romethane) afforded the hemiacetal 29 (96 mg, 96%) as a yellow
1
solid; m.p. 60–61 °C. H NMR (500 MHz, CDCl
3
): δ = 1.79 (s, 3
7
2
1
Ј), 127.1 (d, C-6Ј), 129.7 (d, C-5Ј), 132.5 (s, C-3Ј), 160.1 (s, C-1Ј),
H, 1ЈЈЈ-H), 2.14 (s, 3 H, 1sЈЈЈ-H), 2.66, 2.88 (2ϫd, J = 15.2 Hz,
2ϫ1 H, 1s-H), 3.01–3.05 (m, 2 H, 3-H), 3.10, 3.23 (2ϫm, 2ϫ2
H, 4ЈЈ-H, 5ЈЈ-H), 3.40, 3.45 (2ϫm, 2ϫ2 H, 4sЈ-H, 5sЈ-H), 3.91,
4.12 (2ϫd, J = 13.6 Hz, 2ϫ1 H, 1Ј-H), 5.75 (d, J = 1.8 Hz, 1 H,
OH), 7.42 (s, 1 H, 6-H), 7.50 (ddd, J = 8.4, J = 7.0, J = 1.5 Hz, 1
H, 9-H), 7.59 (ddd, J = 8.2, J = 7.0, J = 1.3 Hz, 1 H, 8-H), 7.75
05.5 (s, C-1) ppm. IR (KBr): ν˜ = 3431, 2959, 2921, 1612, 1569,
–1
2 2
402, 1348, 1252, 1094, 752 cm . UV (CH Cl ): λmax (lgε) = 243
(
(
4.21), 264 (4.18), 371 (3.65) nm. MS (EI, 70 eV): m/z (%) = 318
34) [M] , 279 (8), 225 (26), 182 (76), 119 (100), 57 (85), 43 (72).
+
HRMS: calcd. for C17
18 2 2
H O S 318.0748; found 318.0748.
17 18 2 2
C H O S
(318.45): calcd. C 64.12, H 5.70; found C 64.62, H
(
m, 1 H, 7-H), 8.32 (m, 1 H, 10-H) ppm (s refers to the hemiketal
5.84.
1
3
side chain). C NMR (125 MHz, CDCl
3
): δ = 32.2 (q, C-1ЈЈЈ), 33.3
3
-{1-Hydroxy-8-methoxy-3-[(2-methyl-1,3-dithiolan-2-yl)methyl]-
(
q, C-1sЈЈ), 39.2 (t, C-4sЈ, C-5sЈ), 39.8 (t, C-4ЈЈ, C-5ЈЈ), 46.0 (t, C-
naphthalen-2-yl}ethanone (26): The keto ester 22 (320 mg,
.71 mmol) was heated under reflux for 1 h in acetic acid (4 mL).
1Ј), 50.8 (t, C-3), 52.2 (t, C-1s), 63.2 (s, C-2sЈ), 68.1 (s, C-2ЈЈ), 102.7
0
(
s, C-2), 116.0 (s, C-5), 123.8 (d, C-10), 124.5 (s, C-10a), 125.5 (d,
C-6), 126.0 (d, C-9), 127.6 (d, C-7), 129.4 (d, C-8), 134.2 (s, C-4a),
35.8 (s, C-6a), 156.6 (s, C-10b), 192.8 (s, C-4) ppm (s refers to the
hemiketal side chain). IR (KBr): ν˜ = 3431, 2921, 1683, 1675, 1653,
After dilution with toluene, the solvents were removed under re-
duced pressure. Purification by flash chromatography (dichloro-
1
1
methane) afforded the ketone 26 (90 mg, 36%) as a brown oil. H
NMR (500 MHz, CDCl
3
): δ = 1.76 (s, 3 H, 1ЈЈЈЈ-H), 2.70 (s, 3 H,
–1
1
624, 1569, 1437, 668 cm . MS (EI, 70 eV): m/z (%) = 478 (10)
2-H), 3.16, 3.28 (2ϫm, 2ϫ2 H, 4ЈЈЈ-H, 5ЈЈЈ-H), 3.51 (s, 2 H, 1ЈЈ-
+
[M] , 342 (62), 276 (10), 249 (8), 224 (7), 152 (8), 119 (100), 43
3
H), 4.06 (s, 3 H, OCH ), 6.78 (dd, J = 7.0, J = 1.3 Hz, 1 H, 7Ј-H),
(
80). HRMS: calcd. for C23 478.0765; found 478.0768.
26 3 4
H O S
1
3
7.32–7.37 (m, 3 H, 4Ј-H, 5Ј-H, 6Ј-H), 9.77 (s, 1 H, OH) ppm.
C
NMR (125 MHz, CDCl
3
): δ = 32.2 (q, C-1ЈЈЈ), 33.4 (q, C-2), 39.6, Methyl 1,8-Dihydroxy-3-(4-methoxy-2,4-dioxobutyl)-2-naphthoate
9.8 (2ϫt, C-4ЈЈЈ, C-5ЈЈЈ), 46.3 (t, C-1ЈЈ), 56.3 (q, OCH ), 67.0 (s, (32b): The tert-butyl ester 32a (300 mg, 0.80 mmol) in CH Cl
3
3
3
2
2
088
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Eur. J. Org. Chem. 2010, 3080–3092