G. Nemecek, R. Thomas, H. Goesmann, C. Feldmann, J. Podlech
2
s, 2 H, OCH O), 5.93 (s, 1 H, 3Ј-H), 6.49 (d, J = 2.8 Hz, 1 H, 8- 697 (m), 655 (w), 642 (w), 601 (m), 579 (w), 553 (w), 526 (w), 510
FULL PAPER
4
(
4
13
–1
+
H), 6.54 (d, J = 2.8 Hz, 1 H, 6-H) ppm. C NMR (100 MHz,
(w), 437 (w) cm . MS (EI, 120 °C): m/z (%) = 328 (23) [M] , 270
CDCl
3
): δ = 23.3 (CH
3
), 25.4 (CH
3
), 25.8 (CH
3
), 37.4 (CH
2
), 55.4 (100), 255 (29), 242 (22), 199 (20). HRMS (EI): calcd. for
1
2
1
16
(CH
3
), 55.9 (CH ), 63.3 (CH
3
2
), 89.6 (C), 96.6 (CH
2
), 101.5 (CH),
18 16 6 16 6
C H O 328.0947; found 328.0949. C18H O : calcd. C 65.85,
1
1
3
1
04.3 (C), 105.6 (C), 111.8 (CH), 119.3 (CH), 136.0 (C), 158.6 (C), H 4.91; found C 65.53, H 4.93.
59.2 (C), 164.8 (C), 170.6 (C), 171.1 (C) ppm. IR (DRIFT): ν˜ =
064 (w), 2994 (w), 2940 (w), 1754 (s), 1733 (s), 1650 (w), 1600 (s),
577 (s), 1489 (w), 1465 (w), 1420 (w), 1378 (w), 1346 (w), 1327
rac-2-[3-(7-Methoxy-2,2-dimethyl-4-oxo-4H-benzo[d][1,3]dioxin-5-
yl)-2-methyl-5-oxo-2,5-dihydrofuran-2-yl]acetaldehyde (27): Com-
pound 3 (310 mg, 794 μmol) was dissolved in TFA/H
2
O (3:1;
(m), 1243 (m), 1266 (m), 1243 (w), 1199 (m), 1167 (m), 1132 (m),
1
8 mL), and the mixture was stirred at 0 °C for 4.5 h. The reaction
1
9
105 (m), 1055 (m), 1034 (s), 1001 (w), 981 (w), 966 (w), 951 (w),
32 (w), 910 (m), 865 (m), 840 (w), 809 (w), 791 (w), 745 (w), 725
3
was quenched with NaHCO (saturated aq.; 120 mL), and the aq.
phase was extracted with EtOAc (3ϫ 50 mL). The combined or-
ganic extracts were dried (Na SO ) and concentrated. The residue
was purified by chromatography (silica gel; hexanes/EtOAc, 2:1) to
f
give aldehyde 27 (252 mg, 728 μmol, 92%) as a colorless oil. R =
(w), 709 (w), 679 (w), 639 (w), 608 (w), 575 (m), 537 (w), 508 (w),
–1
+
2
4
4
89 (w), 418 (w) cm . MS (EI, 140 °C): m/z (%) = 392 (41) [M] ,
334 (50), 304 (43), 274 (81), 246 (38), 45 (100). HRMS (EI): calcd.
12
1
16
for
20 24 8 24 8
C H O 392.1471; found 392.1471. C20H O : calcd. C
1
0
(
2
.27 (hexane/EtOAc, 1:1). H NMR (400 MHz, CDCl
s, 3 H, Me), 1.72 (s, 3 H, CMe Me ), 1.73 (s, 3 H, CMe
.84 (dd, J = 16.0, J = 1.2 Hz, 1 H, 2-H
3
): δ = 1.63
Me ),
), 2.97 (dd, J = 16.0,
a
), 3.87 (s, 3 H, OMe), 5.99 (s, 1 H, 4Ј-H),
6
1.22, H 6.16; found C 60.86, H 6.08.
rac-8-Hydroxy-6-methoxy-3a-methyl-2-oxo-2,3a-dihydronaphtho-
2,1-b]furan-9-carboxylic Acid (25): BCl (1 m in CH Cl ; 1.54 mL,
.54 mmol) was added to a solution of compound 3 (50 mg,
28 μmol) in anhydrous CH Cl (1.5 mL) at 0 °C under Ar over
min. The resulting mixture was stirred at 0 °C for 1 h, and at
a
b
a
b
2
3
2
b
[
3
2
2
3
J = 1.2 Hz, 1 H, 2-H
1
1
5
4
4
6
9
.41 (d, J = 2.4 Hz, 1 H, 8ЈЈ-H), 6.50 (d, J = 2.4 Hz, 1 H, 6ЈЈ-H),
3
3
13
2
2
.72 (dd, J = 1.2, J = 1.2 Hz, 1 H, CHO) ppm. C NMR
): δ = 24.1 (CH ), 25.5 (CH ), 25.8 (CH ), 50.6
), 88.0 (C), 101.7 (CH), 104.2 (C), 105.9 (C), 111.8
(100 MHz, CDCl
3
3
3
3
room temp. for a further 18 h. The reaction was quenched with ice-
cold water (20 mL), and the aq. phase was extracted with EtOAc
(CH ), 56.0 (CH
2
3
(
(
(
(
CH), 119.7 (CH), 135.6 (C), 159.0 (C), 159.2 (C), 164.9 (C), 170.2
C), 170.3 (C), 198.8 (CH) ppm. IR (DRIFT): ν˜ = 3439 (w), 2943
m), 2254 (w), 1731 (s), 1605 (s), 1579 (s), 1489 (m), 1457 (m), 1425
m), 1380 (m), 1284 (s), 1206 (s), 1170 (s), 1120 (m), 1072 (m), 1050
m), 985 (w), 962 (m), 913 (m), 863 (m), 792 (w), 733 (s), 678 (w),
92 (w) cm . MS (EI, 120 °C): m/z (%) = 346 (32) [M] , 288 (61),
18 (42), 204 (47), 84 (100). HRMS (EI): calcd. for
46.1053; found 346.1055.
(
5 ϫ 20 mL). The combined organic extracts were washed with
brine (40 mL), dried (Na SO ), and concentrated. The residue was
purified by chromatography (silica gel; CH Cl /MeOH/AcOH,
7:3:1Ǟ95:5:1Ǟ90:10:1) to give compound 25 (27 mg, 94 μmol,
3 %) as a yellow solid; m.p. 172–175 °C. R = 0.38 (CH Cl
OD): δ = 1.59
2
4
2
2
9
7
(
f
2
2
/
5
2
3
–1
+
1
MeOH/AcOH, 100:10:1). H NMR (400 MHz, CD
3
12
1
16
18 18 7
C H O
3
(s, 3 H, 3a-Me), 3.88 (s, 3 H, OMe), 5.97 (s, 1 H, 7-H), 6.17 (d, Jcis
3
=
10.0 Hz, 1 H, 4-H), 6.60 (s, 1 H, 1-H), 6.70 (d, Jcis = 10.0 Hz, 1
13
rac-2-Hydroxy-6-[2-(2-hydroxyethyl)-2-methyl-5-oxo-2,5-dihydro-
furan-3-yl]-4-methoxybenzoic Acid (28): BCl (1 m in CH Cl
1.5 mL, 21.5 mmol) was added at 0 °C under Ar over 5 min to a
solution of compound 24 (775 mg, 1.79 mmol) in anhydrous
CH Cl (23 mL). The resulting mixture was stirred at 0 °C for 1 h,
H, 5-H) ppm. C NMR (100 MHz, CD
3
OD): δ = 24.7 (CH
3
), 56.7
(
CH ), 90.5 (C), 102.4 (CH), 106.2 (C), 116.5 (C), 117.6 (CH),
3
3
2
2
;
2
122.2 (CH), 130.9 (C), 130.9 (CH), 161.2 (C), 164.8 (C), 172.6 (C),
173.1 (C), 174.1 (C) ppm. IR (DRIFT): ν˜ = 2930 (m), 2243 (w),
1713 (s), 1649 (s), 1613 (s), 1580 (s), 1440 (m), 1349 (m), 1200 (s),
1139 (s), 1108 (m), 1092 (m), 1059 (m), 999 (m), 965 (m), 903 (w),
876 (m), 831 (m), 776 (m), 724 (s), 669 (m), 601 (m), 538 (s), 429
2
2
and at room temp. for a further 18 h. The reaction was quenched
with ice-cold water (200 mL), and the aq. phase was extracted with
EtOAc (5ϫ 50 mL). The combined organic extracts were washed
–1
+
(
(
(
w) cm . MS (EI, 120 °C): m/z (%) = 288 (38) [M] , 277 (38), 255
with brine (80 mL), dried (Na
28 (544 mg, 1.76 mmol, 98%) was obtained virtually pure as a pale
yellow solid; m.p. 61–65 °C (decomp.). R = 0.17 (CH Cl /MeOH/
AcOH, 100:10:1). H NMR (400 MHz, CD OD): δ = 1.54 (s, 3 H,
2 4
SO ), and concentrated. Compound
37), 243 (38), 194 (23), 149 (40), 73 (42), 57 (45), 43 (100). HRMS
EI): calcd. for 12
1
16
C
15 12 6
H O 288.0634; found 288.0632.
f
2
2
rac-8a,10-Dihydro-6-methoxy-3,3,8a-trimethyl-1H-[1,3]dioxano-
4Ј,5Ј:5,6]benzo[1,2:e]benzofuran-1,10-dione (26): LiCl (44 mg,
.03 mmol) and compound 3 (80 mg, 205 μmol) were dissolved in
TFA/H O (6:1; 2 mL), and the mixture was stirred at room temp.
for 1.5 h. The reaction was quenched with NaHCO (saturated aq.;
0 mL), and the aq. phase was extracted with EtOAc (3ϫ 30 mL).
The combined organic extracts were dried (Na SO ) and concen-
1
3
[
1
CMe), 2.04 (m, 2 H, 2ЈЈ-H), 3.70 (m, 2 H, 1ЈЈ-H), 3.84 (s, 3 H,
4
OMe), 5.96 (s, 1 H, 4Ј-H), 6.37 (d, J = 2.0 Hz, 1 H, 5-H), 6.56 (d,
2
4
13
J = 2.0 Hz, 1 H, 3-H) ppm. C NMR (100 MHz, CD
3.6 (CH ), 41.4 (CH ), 56.3 (CH ), 58.5 (CH ), 91.8 (C), 102.5
CH), 106.4 (C), 109.40 (CH), 119.1 (CH), 136.4 (C), 165.0 (C),
3
OD): δ =
3
2
(
3
2
3
2
5
2
4
1
2
1
66.2 (C), 172.8 (C), 174.0 (C), 175.8 (C) ppm. IR (DRIFT): ν˜ =
962 (s), 1726 (s), 1657 (s), 1601 (s), 1442 (w), 1416 (w), 1367 (m),
250 (s), 1203 (s), 1163 (s), 1102 (m), 1014 (m), 966 (s), 848 (m),
trated. The residue was purified by chromatography (silica gel; hex-
anes/EtOAc, 5:1Ǟ3:1) to give compound 26 (43 mg, 131 μmol,
6
4 %) as orange crystals; m.p. 189–192 °C. R
f
= 0.46 (hexane/
): δ = 1.61 (s, 3 H, 8a-
Me), 1.76 (s, 3 H, 3-Me), 1.77 (s, 3 H, 3-Me), 3.91 (s, 3 H, OMe),
–1
792 (s), 709 (m), 654 (w), 620 (w), 535 (w), 503 (w) cm . MS (EI,
1
EtOAc, 1:1). H NMR (400 MHz, CDCl
3
+
1
for
50 °C): m/z (%) = 308 (19) [M] , 192 (100). HRMS (EI): calcd.
12
1
16
15 16 7
C H O 308.0896; found 308.0898.
3
6
.24 (s, 1 H, 5-H), 6.30 (d, Jcis = 10.0 Hz, 1 H, 8-H), 6.49 (s, 1 H,
1-H), 6.67 (d, 3
): δ = 24.3 (CH
), 88.0 (C), 100.9 (CH), 103.3 (C), 105.7 (C), 119.0 (CH),
19.0 (C), 120.0 (CH), 130.3 (C), 132.3 (CH), 158.5 (C), 158.9 (C), 4 mL) at 0 °C, and the mixture was stirred at this temperature for
J
cis = 10.0 Hz, 1 H, 7-H) ppm. C NMR rac-5-[2-(2-Hydroxyethyl)-2-methyl-5-oxo-2,5-dihydrofuran-3-yl]-
), 24.7 (CH ), 26.9 (CH ), 56.3 7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (29): Com-
pound 24 (208 mg, 530 μmol) was dissolved in TfOH/H O (1:1;
13
1
(
(
100 MHz, CDCl
CH
3
3
3
3
3
2
1
1
2
1
61.2 (C), 166.7 (C), 171.7 (C) ppm. IR (DRIFT): ν˜ = 3004 (w),
929 (w), 1756 (s), 1730 (s), 1619 (w), 1588 (s), 1568 (m), 1575 (m),
442 (m), 1381 (m), 1347 (m), 1277 (s), 1252 (m), 1196 (s), 1177 The combined organic extracts were dried (Na
45 min. The reaction was quenched with NaHCO
50 mL), and the aq. phase was extracted with EtOAc (3ϫ 20 mL).
SO ) and concen-
trated. The residue was purified by chromatography (silica gel; hex-
w), 914 (m), 873 (w), 855 (m), 834 (m), 816 (m), 772 (m), 727 (m), anes/EtOAc, 2:1Ǟ1:1) to give compound 29 (176 mg, 505 mmol,
3
(saturated aq.;
2
4
(
(
s), 1147 (m), 1128 (m), 1190 (m), 1053 (m), 1000 (w), 978 (w), 956
6430
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© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 6420–6432